SARS-CoV-2 infection: use and effectiveness of antigenic swab for the health surveillance of healthcare workers.

BACKGROUND:  The gold standard to identify SARS-CoV-2 infections is the Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on rhino-pharyngeal swabs, but faster and cheaper methods such as antigenic swabs have been developed. A retrospective observational study on antigenic swabs included in the extraordinary health surveillance protocol of a large Hospital in Turin was aimed to assess their performance validity. Methods: From 30 October 2020 to 4 May 2021, 4000 antigenic swabs were carried out in three groups of healthcare workers (HCWs), respectively (i) asymptomatic, (ii) cohabiting with a positive case, and (iii) not recently exposed to the virus.  Results: Overall sensitivity and specificity associated with a prevalence of 1.30% were 26.9%, 97.2%, respectively, the corresponding positive (PPV) and negative predictive value (NPV) being 11.29% and 99.02% [95% IC (99.00 - 99.04)] respectively; a prevalence of 0.29% was observed in the asymptomatic group, among whom sensitivity and specificity were 25.0% and 98.9%, respectively, the corresponding PPV and NPV being 6.25% and 99.78% [95% IC (99.76 - 99.81)], respectively; the cohabitant group showed a prevalence of 21.11%, sensitivity and specificity were 47.4%, 81.7%, respectively, giving rise to a PPV of 40.91% and NPV of 85.29% [95% IC (85.18 - 85.41)] respectively. The prevalence in the not exposed group was 0.77%, sensitivity and specificity were 29.2%, 97.4%, respectively, and PPV and NPV 8.05% and 99.44% [95% IC (99.42 - 99.46)] respectively. Conclusions: Antigenic swabs reduced costs and provided reliable diagnostic results. In the cohabitant group, the higher-prevalence groups showed poor test performances, likely because of the high prevalence of pre-symptomatic illness in this group. Owing to the relatively low NPV, a negative result would still require confirmation with a molecular test to be acceptable for a surveillance program that effectively reduces the virus's intra-hospital spread.

SARS-CoV-2 infection: efficacy of extensive vaccination of the healthcare workforce in a large Italian hospital.

BACKGROUND: A prospective observational study involved 13,787 Health Care Workers (HCWs) of a large hospital to assess the effectiveness of a SARS-CoV-2 mRNA vaccine. METHODS: The daily incidence of infections was estimated from 1st October 2020 to 30th April 2021 and compared with that of the province of Turin (2.26 million). In the middle of this period, a mass vaccination began among HCW, and its effect was assessed. RESULTS: In the first half-period, 1,163 positive HCWs were observed, the average daily incidence rate per 100,000 being 79.58 (± 15.58; 95% CI) compared to 38.54 (± 5.96; 95% CI) in the general population (p<0.001). The vaccination campaign immunized 9,843 HCWs; among them, the average daily incidence was 14.23 (± 2.73; 95% CI) compared to 34.2 (± 2.95; 95% CI) in the province (p<0.001). Among fully vaccinated HCW, 59 cases were observed, giving rise to an incidence of 6.3 (± 2.66; 95% CI) much lower than in the province (p<0.001). In the second half of the observation period, the RR for HCWs compared to the province dropped from 2.07 (1.96 - 2.18; 95% CI; p<0.001) to 0.5 (0.42 - 0.58; 95% CI; p<0.001) and to 0.17 (0.13 - 0.22; 95% CI; p<0.001) for unvaccinated and vaccinated HCWs, respectively. The RR of vaccinate HCW was 0.43 (0.31 - 0.58; 95% CI; p<0.001) compared to unvaccinated. In the second half of the observation period, unvaccinated HCWs had a RR of 0.21 (0.18 - 0.25; 95% CI; p<0.001) as compared to the first one. A linear regression model (R2 = 0.87) showed that every percent increase in vaccinated HCWs lowered daily incidence by 0.94 (0.86 - 1.02; IC 95%; p<0.001). Vaccinated HCWs had a RR of 0.09 (0.07 - 0.12; 95% CI; p<0.001) compared to unvaccinated HCWs, which led to estimated effectiveness of the two-dose vaccine of 91 % (± 3 %; CI 95%) similar to that reported by the manufacturer.

COVID-19 infection and diffusion among the healthcare workforce in a large university-hospital in northwest Italy.

Backgroud: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, healthcare workers (HCWs) have been the workers most likely to contract the disease. Intensive focus is therefore needed on hospital strategies that minimize exposure and diffusion, confer protection and facilitate early detection and isolation of infected personnel. METHODS: To evaluate the early impact of a structured risk-management for exposed COVID-19 HCWs and describe how their characteristics contributed to infection and diffusion. Socio-demographic and clinical data, aspects of the event-exposure (date, place, length and distance of exposure, use of PPE) and details of the contact person were collected. RESULTS: The 2411 HCWs reported 2924 COVID-19 contacts. Among 830 HCWs who were at 'high or medium risk', 80 tested positive (9.6%). Physicians (OR=2.03), and non-medical services -resulted in an increased risk (OR=4.23). Patient care did not increase the risk but sharing the work environment did (OR=2.63). There was a significant time reduction between exposure and warning, exposure and test, and warning and test since protocol implementation. HCWs with management postitions were the main source of infection due to the high number of interactions. DISCUSSION: A proactive system that includes prompt detection of contagious staff and identification of sources of exposure helps to lower the intra-hospital spread of infection. A speedier return to work of staff who would otherwise have had to self-isolate as a precautionary measure improves staff morale and patient care by reducing the stress imposed by excessive workloads arising from staff shortages.

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.

Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.

Postictal MRI abnormalities and seizure-induced brain injury: notions to be challenged.

OBJECTIVE: This was a bibliographic search to address the quality of evidence in clinical reports supporting the assertion that brain MRI signal abnormalities are a direct consequence of seizures. METHODS: The search on PubMed was performed by applying the following inclusion criteria: a) original case reports, b) in humans, c) as single case reports or series of patients, d) of visually detected acute MRI signal abnormalities, e) attributable directly to seizures, and f) published in English. Bibliographic references of initially selected publications were reviewed for additional articles. Full texts of selected publications were read for information regarding clinical, EEG, and MRI features. Moreover, claimed evidence supporting seizure-induced excitotoxicity was assessed. RESULTS: The search resulted in 91 publications corresponding to 413 cases. There was a wide range of clinical features and EEG and MRI abnormalities. Premorbid or comorbid conditions were present in many cases, and some of them are potential causes of MRI changes. Claimed evidence for MRI signal abnormalities as a direct consequence of ictal activity was mostly based on the similarity with previous reports, animal models, reversibility, congruent EEG, MRI changes not respecting vascular territories, and ruling out other etiologies. CONCLUSIONS: Evidence supporting the notion of seizure-induced excitotoxicity is questionable in the studied reports of postictal MRI abnormalities.

Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations.

In the large group of genetically undetermined infantile-onset mitochondrial encephalopathies, multiple defects of mitochondrial DNA-related respiratory-chain complexes constitute a frequent biochemical signature. In order to identify responsible genes, we used exome-next-generation sequencing in a selected cohort of patients with this biochemical signature. In an isolated patient, we found two mutant alleles for EARS2, the gene encoding mitochondrial glutamyl-tRNA synthetase. The brain magnetic resonance imaging of this patient was hallmarked by extensive symmetrical cerebral white matter abnormalities sparing the periventricular rim and symmetrical signal abnormalities of the thalami, midbrain, pons, medulla oblongata and cerebellar white matter. Proton magnetic resonance spectroscopy showed increased lactate. We matched this magnetic resonance imaging pattern with that of a cohort of 11 previously selected unrelated cases. We found mutations in the EARS2 gene in all. Subsequent detailed clinical and magnetic resonance imaging based phenotyping revealed two distinct groups: mild and severe. All 12 patients shared an infantile onset and rapidly progressive disease with severe magnetic resonance imaging abnormalities and increased lactate in body fluids and proton magnetic resonance spectroscopy. Patients in the 'mild' group partially recovered and regained milestones in the following years with striking magnetic resonance imaging improvement and declining lactate levels, whereas those of the 'severe' group were characterized by clinical stagnation, brain atrophy on magnetic resonance imaging and persistent lactate increases. This new neurological disease, early-onset leukoencephalopathy with thalamus and brainstem involvement and high lactate, is hallmarked by unique magnetic resonance imaging features, defined by a peculiar biphasic clinical course and caused by mutations in a single gene, EARS2, expanding the list of medically relevant defects of mitochondrial DNA translation.

Epstein-Barr virus acute encephalomyelitis in a 13-year-old boy.

The association of acute myelopathy and encephalopathy is reported in a 13-year-old boy. Signs and symptoms of infectious mononucleosis, presence of heterophile antibodies, anticapsid antibodies and Epstein-Barr virus DNA detected in cerebrospinal fluid, disclosed a primary or reactivated infection by Epstein-Barr virus. Outcome was rapid and benign with complete clinical recovery in 1 month, after pulse therapy with methylprednisolone. Epstein-Barr virus is a known agent related to acute disseminated encephalomyelitis, by immune mediated mechanisms. However, in this case, cortical involvement in magnetic resonance imaging, short time between infectious mononucleosis and central nervous system manifestations, and the presence of viral DNA in cerebrospinal fluid, raised the possibility of a direct action of the virus in central nervous system. Acute myelopathy associated to Epstein-Barr virus encephalitis has been rarely reported in children.

SADE3: an effective system for automated detection of epileptiform events in long-term EEG based on context information.

Interictal spike detection is a time-consuming, low-efficiency task, but is important to epilepsy diagnosis. Automated systems reported to date usually have their practical efficacy compromised by elevated rates of false-positive detections per minute, which are caused mainly by the influence of artifacts (such as noise activity and ocular movements) and by the adoption of single or simple approaches. This work describes the development of a hybrid system for automatic detection of spikes in long-term electroencephalogram (EEG), named System for Automatic Detection of Epileptiform Events in EEG (SADE(3)), which uses wavelet transform, neural networks and artificial intelligence procedures to recognize epileptic and to reject non-epileptic activity. The system's pre-processing stage filters the EEG epochs with the Coiflet wavelet function, which showed the closest correlation to epileptogenic (EPG) activity, in opposition to some other wavelet functions that did not correlate with these events. In contrast to current attempts using continuous wavelet transform, we chose to work with fast wavelet transform to reduce processing time and data volume. Detail components at appropriate decomposition levels were used to accentuate spikes, sharp waves, high-frequency noise activity and ocular artifacts. These four detailed components were used to train four specialized neural networks, designed to detect and classify the EPG and non-EPG events. An expert module analyzes the networks' outputs, together with multichannel and context information and concludes the detection. The system was evaluated with 126,000 EEG epochs, obtained from seven different patients during long-term monitoring, under diverse behavior and mental states. More than 6,721 spikes and sharp waves were previously identified by three experienced human electroencephalographers. In these tests, the SADE(3) system simultaneously achieved 70.9% sensitivity, 99.9% specificity and a rate of 0.13 false-positives per minute, indicating its usefulness and low vulnerability to artifact influence. After tests, the SADE(3) system showed itself to be able to process bipolar cortical EEG records, from long-term monitoring, up to 32 channels, without any data preparation or event positioning. At the same time, SADE(3) revealed a high capacity to reject non-epileptic paroxysms, robustness in relation to a variety of spike morphologies, flexibility in adjustment of performance rates and the capacity to actually save time during EEG reading. Furthermore, it can be adapted to other applications for pattern recognition, with simple adjustments.

Rapidly progressive spinal muscular atrophy in an ambulatory 2-year-old male.

A 2-year 9-month-old male was referred for gait disturbances. Main complaints were abnormal gait with frequent falls observed as soon as he began to walk unaided, at 18 months of age. The first neurologic examination revealed symmetric and proximal weakness in the lower limbs with difficulty running and walking upstairs. Deep tendon reflexes were decreased, and generalized hypotonia was observed. Three months later, at 3 years of age, he had lost independent gait, and 1 month later he could not stand unaided. DNA analysis revealed homozygous deletion in exons 7 and 8 of SMN1 gene, confirming the diagnosis of spinal muscular atrophy. According to the current classification, this patient would be classified as spinal muscular atrophy type III. The distinctive feature of this case was the short time elapsed (18 months) between onset of spinal muscular atrophy and the age at which he lost ambulation. This patient reinforces the notion that late onset of symptoms in spinal muscular atrophy and acquisition of independent gait do not exclude a rapidly progressive motor deterioration, which is important when talking with families about outcome. In those rapidly progressive cases, when promptly available, testing for SMN1 gene will prevent unnecessary, invasive, or uncomfortable procedures such as lumbar puncture, electromyography, or spinal cord magnetic resonance imaging.

Detection of organic acidemias in Brazil.

BACKGROUND: Organic acidurias or organic acidemias are inherited metabolic disorders in which organic acids (carboxylic acids) accumulate in tissues and physiologic fluids of affected individuals. They are considered the most frequent metabolic disorders among severely ill children. Patients frequently present acute symptoms in early life. Metabolic acidosis and neurologic symptoms are the most common signs. METHODS: Urine specimens obtained from 1,926 children from January 1994 to July 2001 were used in analyses. Venous blood specimens were also collected from some patients. Samples were initially submitted to screening tests for detection of inborn errors of metabolism. Identification and semi-quantitation of organic acids in urine were performed by gas chromatography or gas chromatography coupled to mass spectrometry using capillary column (DB-5) and flame ionization detection. RESULTS: Ninety three (4.8%) cases of organic acidemias were diagnosed among 1,926 patients investigated from January 1994 to July 2001. Prompt therapy was instituted after diagnosis in a considerable number of patients and resulted in rapid improvement in their symptomatology, distinct from our previous cases diagnosed abroad where patients representing index cases died before any measure could be taken. CONCLUSIONS: Results demonstrate the importance of diagnosing organic acidurias in loco in developing countries despite implied extra costs.

[Early manifestations of behavioral disorders in children and adolescents]. / Manifestações precoces dos transtornos do comportamento na criança e no adolescente.

OBJECTIVE: To discuss the early diagnosis of behavioral disorders in childhood and adolescence and to provide the pediatrician with practical knowledge about the first symptoms of the main behavioral disorders at this age. SOURCES OF DATA: PubMed (emphasis on the past decade). SUMMARY OF THE FINDINGS: Pediatricians should be prepared to detect behavioral disorders as early as possible. Early detection could improve outcome and/or lead to etiologic diagnosis of mendelian inheritance disorders, allowing genetic counseling. Early symptoms of pervasive developmental disorders, attention deficit/hyperactivity disorder, separation anxiety disorder, generalized anxiety disorder, depression, schizophrenia, the main eating disorders (anorexia nervosa and bulimia nervosa) and substance use and abuse are discussed. CONCLUSIONS: The early symptoms of the main behavioral disorders in children and adolescents may appear before the age in which these conditions are currently diagnosed. Detection of early symptoms leads to early intervention, proper orientation about prognosis and, in some cases, to genetic counseling. The comorbidity among these disorders is frequent, and the symptoms of one disorder could be the first clue to allow the diagnosis of other conditions.