Likelihood‐based dynamic factor analysis for measurement and forecasting

We present new results for the likelihood‐based analysis of the dynamic factor model. The latent factors are modelled by linear dynamic stochastic processes. The idiosyncratic disturbance series are specified as autoregressive processes with mutually correlated innovations. The new results lead to computationally efficient procedures for the estimation of the factors and for the parameter estimation by maximum likelihood methods. We also present the implications of our results for models with regression effects, for Bayesian analysis, for signal extraction, and for forecasting. An empirical illustration is provided for the analysis of a large panel of macroeconomic time series.     

Drug repurposing and emerging adjunctive treatments for schizophrenia

Introduction: Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial. Nevertheless, the understanding of the pathophysiology of this syndrome, concise diagnostic methods and more effective and tolerable treatments are still lacking. Thus, innovative approaches and the exploration of new territories are required.

Areas covered: An overview of repurposed drugs and emerging treatments for schizophrenia is presented, focusing on randomized, controlled trials and meta-analyses.

Expert opinion: Despite many years of drug research, several needs in the treatment of schizophrenia including the safety and tolerability, stage-dependent and personalized approaches, as well as drug delivery and sustainability have not been addressed sufficiently. Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs (e.g., acetylsalicylic acid, celecoxib and minocycline), as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones (e.g., estrogen, raloxifene and oxytocin), glutamatergic (e.g., glycine and d-serine) and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoidmodulator, represent promising agents in this field.     

COVID19 infection in a patient with paroxysmal nocturnal hemoglobinuria: A case report

Introduction:Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hemopoietic stem cell disorder characterized by the triad of hemolytic anemia, thrombosis, and impaired bone marrow function. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state.Patient concerns:A 27-year-old Caucasian man with PNH presented to the Emergency Department of our hospital with acute onset shortness of breath, cough and blood in urine.Diagnosis:The patient was diagnosed with acute hemolytic exacerbation of PNH complicated with moderate COVID19 pneumonia.Outcomes:The patient was initiated with an anticoagulant unfractionated heparin, dexamethasone, and cefuroxime injection. His symptoms quickly resolved, and he was discharged after 5 days.Conclusion:The complement system activation is a critical component in the sequalae of COVID19 infection. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. Notably, C5a concentration was noted to be higher in patients with COVID19 infection. The use of complement inhibitors to attenuate immune mediated damage in COVID19 nevertheless represents a very interesting theoretical approach. However, careful consideration as to which patients may benefit will be required and the outcome of clinical trials needed.     

Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report

Rationale:Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene.Patient concerns:We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband''s older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms.Diagnoses:The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband''s genome that absented in any other analyzed family member, suggesting its de novo origin.Interventions and outcomes:The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus.Lessons:We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available.     

Childhood urinary tract infection in primary care: a prospective observational study of prevalence,diagnosis, treatment,and recovery

BackgroundThe prevalence of targeted and serendipitous treatment for, and associated recovery from, urinary tract infection (UTI) in pre-school children is unknown.AimTo determine the frequency and suspicion of UTI in children who are acutely ill, along with details of antibiotic prescribing, its appropriateness, and whether that appropriateness impacted on symptom improvement and recovery.MethodSystematic urine sampling from children aged <5years presenting in primary care with acute illness with culture in NHS laboratories.ResultsOf 6079 children’s urine samples, 339 (5.6%) met laboratory criteria for UTI and 162 (47.9%) were prescribed antibiotics at the initial consultation. In total, 576/7101 (8.1%) children were suspected of having a UTI prior to urine sampling, including 107 of the 338 with a UTI (clinician sensitivity 31.7%). Children with a laboratory-diagnosed UTI were more likely to be prescribed antibiotics when UTI was clinically suspected than when it was not (86.0% versus 30.3%, P<0.001). Of 231 children with unsuspected UTI, 70 (30.3%) received serendipitous antibiotics (that is, antibiotics prescribed for a different reason). Overall, 176 (52.1%) children with confirmed UTI did not receive any initial antibiotic. Organism sensitivity to the prescribed antibiotic was higher when UTI was suspected than when treated serendipitously (77.1% versus 26.0%; P<0.001). Children with UTI prescribed appropriate antibiotics at the initial consultation improved a little sooner than those with a UTI who were not prescribed appropriate antibiotics initially (3.5 days versus 4.0 days; P = 0.005).ConclusionOver half of children with UTI on culture were not prescribed antibiotics at first presentation. Serendipitous UTI treatment was relatively common, but often inappropriate to the organism’s sensitivity. Methods for improved targeting of antibiotic treatment in children who are acutely unwell are urgently needed.