Ceft-to-Ceft Study: Real-Life Experience with Ceftaroline and Ceftobiprole in Treatment of the Principal Infectious Syndromes in a Spanish Multicenter Hospital Cohort.

BACKGROUND: To compare the real-life effectiveness and safety of ceftaroline fosamil (ceftaroline-F) and ceftobiprole medocaril (ceftobiprole-M) for infections in hospitalized patients. METHODS: This comparative, observational, retrospective, and multicenter Spanish study included patients receiving outpatient parenteral antimicrobial therapy (OPAT) and hospitalized patients treated for at least 48 h with ceftaroline-F or ceftobiprole-M between their first incorporation in the clinical protocol of each hospital and 31 July 2022. RESULTS: Ceftaroline-F was administered to 227 patients and ceftobiprole-M to 212. In comparison to the latter, ceftaroline-F-treated participants were younger (63.02 vs. 66.40 years, OR 1.1; 95%CI: 1.001-1.05) and had higher rates of septic shock (OR 0.27; 95%CI: 0.09-0.81) and higher frequencies of targeted (57.7 vs. 29.7%; OR: 0.35; 95%CI: 0.18-0.69) and combined (89.0 vs. 45.8%, OR: 0.13; 95%CI: 0.06-0.28) therapies that were second line or more (82.4% vs. 64.6%%; OR 0.35; 95%CI: 0.18-0.69), and higher rates of infections due to Gram-positive cocci (92.7 vs. 64.7%, p = 0.001), bacteremia (51.9 vs. 21.7%, p = 0.001), infective endocarditis (24.2 vs. 2.4%, p = 0.0001), and mechanical ventilation-associated pneumonia (8.8 vs. 2.4%, p = 0.0001). Ceftobiprole-M was more frequently administered against polymicrobial infections (38.1 vs. 14.0%, p = 0.001), those produced by Gram-negative bacilli (19.7 vs. 6.0%, p = 0.0001), nosocomial pneumonia (33 vs. 10.6%, p = 0.0001), and skin and soft-tissue infections (25.4 vs. 10.1%, p = 0.0001). Patients treated with ceftaroline-F had a longer hospital stay (36 (IQR: 19-60) vs. 19.50 (IQR: 12-30.75, p = 0.0001) days), with no difference in infection-related mortality at 14 (13.2 vs. 8.0%, p = 0.078) or 28 (4.8 vs. 3.3%, p = 0.415) days or in dropout rate for adverse effects (2.2 vs. 0.9%; p = 1). CONCLUSIONS: The fifth-generation cephalosporins, ceftaroline-F and ceftobiprole-M, are safe and effective in real life, with no difference between them in health outcomes.

Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study.

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI. Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed. Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines' recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16-3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28-6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35-0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16-0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13-0.38), p < 0.001) were identified as protective factors against i-EAT. Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.

Immunoregulatory and/or Anti-inflammatory Agents for the Management of Core and Associated Symptoms in Individuals with Autism Spectrum Disorder: A Narrative Review of Randomized, Placebo-Controlled Trials.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a so far poorly understood underlying pathogenesis, and few effective therapies for core symptoms. Accumulating evidence supports an association between ASD and immune/inflammatory processes, arising as a possible pathway for new drug intervention. However, current literature on the efficacy of immunoregulatory/anti-inflammatory interventions on ASD symptoms is still limited. The aim of this narrative review was to summarize and discuss the latest evidence on the use of immunoregulatory and/or anti-inflammatory agents for the management of this condition. During the last 10 years, several randomized, placebo-controlled trials on the effectiveness of (add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, N-acetylcysteine (NAC), sulforaphane (SFN), and/or omega-3 fatty acids have been performed. Overall, a beneficial effect of prednisolone, pregnenolone, celecoxib, and/or omega-3 fatty acids on several core symptoms, such as stereotyped behavior, was found. (Add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, NAC, SFN, and/or omega-3 fatty acids was also associated with a significantly higher improvement in other symptoms, such as irritability, hyperactivity, and/or lethargy when compared with placebo. The mechanisms by which these agents exert their action and improve symptoms of ASD are not fully understood. Interestingly, studies have suggested that all these agents may suppress microglial/monocyte proinflammatory activation and also restore several immune cell imbalances (e.g., T regulatory/T helper-17 cell imbalances), decreasing the levels of proinflammatory cytokines, such as interleukin (IL)-6 and/or IL-17A, both in the blood and in the brain of individuals with ASD. Although encouraging, the performance of larger randomized placebo-controlled trials, including more homogeneous populations, dosages, and longer periods of follow-up, are urgently needed in order to confirm the findings and to provide stronger evidence.

Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and/or medical conditions are urgently needed to confirm the findings.

Short versus long course therapy in the treatment of febrile urinary tract infections in men based on serum PSA values.

BACKGROUND: Febrile urinary tract infections (fUTI) in men are frequently complicated with subclinical prostatic involvement, measured by a transient increase in serum prostate-specific-antigen (sPSA). The aim of this study was to evaluate recurrence rates in a 6-month follow-up period of 2-week versus 4-week antibiotic treatment in men with fUTI, based on prostatic involvement. Clinical and microbiological cure rates at the end-of-therapy (EoT) were also assessed. METHODS: Open label, not-controlled, prospective study. Consecutive men diagnosed of fUTI were included. Duration of therapy was 2 weeks for patients with a sPSA level <5mg/L (short duration therapy, SDT) or 4 weeks for PSA >5 mg/L (long duration therapy, LDT). RESULTS: Ninety-one patients were included; 19 (20%) received SDT. Median age was 56.9 years (range 23-88). Bacteremia was present in 9.8% of patients (Escherichia coli was isolated in 91%). Both groups had similar demographic, clinical characteristics and laboratory findings. Median PSA levels were 2.3 mg/L in the SDT group vs 23.4 mg/L in the LDT group. In the 6-month visit, 26% of patients had achieved complete follow-up. Nonsignificant differences between groups were found neither in recurrence rates after 6 months (9% in SDT vs 10% in LDT) nor in clinical or microbiological cure rates at EoT (100% in SDT vs 95% in LDT and 95% in SDT vs 93% in LDT respectively). CONCLUSIONS: One fifth of men with fUTI did not present apparent prostatic involvement. A 2-week regimen seems adequate in terms of clinical, microbiological cure and recurrence rates for those patients without PSA elevation.

The Benefits of Dog-Assisted Therapy as Complementary Treatment in a Children's Mental Health Day Hospital.

Dog-assisted therapy (DAT) has shown benefits in people with mental health disorders. A child psychiatric day hospital would be a suitable setting to implement DAT and evaluate the benefits in a pediatric population. METHODS: Mixed methods research in a naturalistic setting was considered in this pre-post quantitative study including 23 children under 13 treated in a day hospital over 2 years. Quantitative analysis included the number of emotional and behavioral outbursts and attendance rate and self-control and social impairment questionnaires completed by family members and therapists. In the qualitative study, the experiences of 12 mental health professionals involved in DAT were documented through semi-structured interviews. RESULTS: On DAT days, there were fewer emotional and behavioral outbursts and higher attendance. Significant differences were obtained between pre- and post-test scores on the SCRS and the SRS-2 completed by the therapists, while no significant differences were obtained on the questionnaires completed by the parents. Observations based on the qualitative study were as follows: (1) DAT improves emotional self-regulation; (2) DAT could facilitate the work of therapists in day hospitals; (3) health professionals displayed uncertainty due to a lack of familiarity with DAT. CONCLUSIONS: DAT improved emotional self-regulation, attendance rate and self-control and social response in children with mental disorders attending a day hospital.

Effects of the COVID-19 Pandemic on Physical Activity in Chronic Diseases: A Systematic Review and Meta-Analysis.

The management of chronic diseases (CD) includes physical activity (PA). It is necessary to determine the effects of COVID-19 restrictions in CD. The aim was to review the research related to PA levels before and during the COVID-19 pandemic in people with CD. This review was designed according to PRISMA guidelines and registered in PROSPERO: CRD42020218825. The search was performed in CINAHL, Medline, Scopus, and Web of Science up to January 2021. The PICOS recommendations were applied. The search was conducted by two reviewers, who completed the data extraction of included articles. Methodological quality was assessed using the STROBE checklist, and a meta-analysis was conducted. The literature search strategy identified 227 articles. Five studies remained and were included. Only three studies were included in the meta-analysis. Two articles used accelerometers to objectively compare PA levels before and during the pandemic. Three studies made this comparison using an online survey. All articles showed a decrease in PA levels during the COVID-19 pandemic. The meta-analysis showed a significant reduction in PA levels during pandemic. PA levels during the COVID-19 pandemic have been reduced with respect to previous levels of PA in patients with CD.

Sleep in adults with autism spectrum disorder and attention deficit/hyperactivity disorder: A systematic review and meta-analysis.

Sleep-related problems have been frequently reported in neurodevelopmental disorders, with special emphasis in Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD). The aim of the present study is to conduct a systematic review and meta-analysis on sleep disturbances in adults with ASD and/or ADHD (PROSPERO's CRD42019132916). PubMed and PsycINFO were searched for studies reporting data on sleep objective/subjective measures, as well as prevalence data of sleep disorders, in adults with ASD and/or ADHD. A manual search was conducted throughout reference lists of eligible studies. A total of 1126 studies and 66 references were identified by electronic and manual searches, respectively. Of these, 42 studies were included in the meta-analysis. Results showed that both disorders share a similar sleep-impaired profile with higher sleep onset latency, poorer sleep efficiency, greater number of awakenings during sleep, and a general lower self-perceived sleep quality compared with healthy controls. A higher proportion of N1 sleep was found in ASD participants, while a greater Periodic Limb Movements in Sleep is specific in ADHD adults. More studies are needed, especially those directly comparing ASD and ADHD participants. Controlling for medication, intellectual disability, and concurrent psychiatric disorders is mandatory.

Genome-wide analysis of emotional lability in adult attention deficit hyperactivity disorder (ADHD).

Emotional lability is strongly associated with Attention Deficit Hyperactivity Disorder (ADHD), represents a major source of impairment and predicts poor clinical outcome in ADHD. Given that no specific genes with a role in the co-occurrence of both conditions have been described, we conducted a GWAS of emotional lability in 563 adults with ADHD. Despite not reaching genome-wide significance, the results highlighted genes related with neurotransmission, cognitive function and a wide range of psychiatric disorders that have emotional lability as common clinical feature. By constructing polygenic risk scores on mood instability in the UK Biobank sample and assessing their association with emotional lability in our clinical dataset, we found suggestive evidence of common genetic variation contributing to emotional lability in general population and in clinically diagnosed ADHD. Although not conclusive, these tentative results are in agreement with previous studies that suggest emotion dysregulation as a transdiagnostic construct and highlight the need for further investigation to disentangle the genetic basis of mood instability in ADHD and co-occurring psychiatric disorders.

The Relationship Between Neuropsychological Deficits and Emotional Lability in Adults With ADHD.

Objective: The objective of this study was to investigate the extent to which neuropsychological performance parameters implicated in ADHD might mediate the relationship between emotional lability (EL) and this disorder. Method: Eight hundred twelve adult patients with ADHD were examined. EL was assessed using the EL subscale of Conners' Adult ADHD Rating Scales (CAARS). To assess cognitive and executive functions, a battery of neuropsychological tests was performed in 262 patients with ADHD and high EL symptomatology and 550 patients with ADHD and low EL symptomatology. Results: Several differences between groups were found regarding neuropsychological performance; however, nearly all significant differences disappeared when the effect of gender, inattention, and hyperactive symptoms and psychiatric comorbidities were taken into account. Conclusion: Our results do not support the hypothesis that neuropsychological deficits are associated with EL in adults with ADHD.

The Impact of Emotional Lability Symptoms During Childhood in Adults With ADHD.

OBJECTIVE: To determine whether emotional lability (EL) in adult ADHD patients can already be identified during their childhood and the extent to which this childhood symptomatology can predict EL in adulthood. METHOD: Seven hundred eighteen adults with ADHD were examined. EL in adulthood was assessed using the Conners' Adult ADHD Rating Scales (CAARS). According to Conners' definition of EL, seven items from the Wender Utah Rating Scale (WURS) were used to determine this symptomatology in childhood. RESULTS: EL was identified in 31.1% of the participants, and 29.6% of this subgroup reported EL symptoms in childhood. Childhood EL was the strongest predictor of these symptoms in adulthood (odds ratio [OR] = 6.18). ADHD subtype, female sex, family history of ADHD, psychiatric comorbidities, and physical abuse were also related to EL development/persistence. CONCLUSION: Screening for EL symptoms in children with ADHD is important, as they are the strongest predictor of this symptomatology in adulthood.