Background: Problematic social media use (PSMU) has been increasingly conceptualized as a form of behavioral addiction, characterized by loss of control and continued engagement despite negative consequences. Adolescents with psychiatric disorders may represent a particularly vulnerable group, yet clinical evidence remains limited. This study examined the prevalence of PSMU in help-seeking adolescents and investigated how psychological vulnerabilities influence social media (SM) engagement, platform selection, and content preferences. Methods: A cross-sectional study was conducted on 265 adolescents (12–18 years) undergoing psychiatric evaluation. Participants completed validated measures of PSMU (Social Media Disorder Scale-9) and perceived stress, along with items assessing screen time, platform usage, engagement style (active vs. passive), and content preferences. Diagnostic data were retrieved from clinical assessments. Results: PSMU prevalence was 14.4%, rising to 19.2% among adolescents with internalizing disorders. Female and gender-diverse adolescents showed significantly higher PSMU scores. PSMU was associated with greater screen time (OR = 2.41) and nearly threefold higher odds of intensive TikTok use. Overall, SM engagement was predominantly passive, particularly among adolescents with depressive disorders, while those with neurodevelopmental disorders more frequently engaged actively. Higher stress levels were linked to greater SM use, especially on TikTok and Instagram. Conclusions: PSMU appeared to be relatively prevalent among adolescents receiving psychiatric care, particularly those with mood and anxiety disorders and high stress levels. Findings highlight the importance of assessing PSMU in these groups of adolescents and analyzing qualitative patterns of SM engagement to identify at-risk youth and inform targeted clinical interventions.

[This corrects the article DOI: 10.3389/fpsyg.2025.1669090.].

Developmental dyscalculia (DD) is a neurodevelopmental disorder characterized by both functional and structural brain modifications. Individuals with DD exhibit impairments in higher-order cognitive processes. Timely intervention is crucial, as difficulties in mathematical learning can impact academic achievement, contribute to behavioral problems, and increase the risk of school dropout. This study aims to explore whether targeting higher-order cognitive processes could partially remediate developmental dyscalculia, with pre-registered primary outcomes including numerical facts, mental calculation speed, and mental calculation accuracy (ISRCTN, ISRCTN15190285). We conducted a single-center, two-arm, randomized controlled trial. Seventy adolescents aged 13–17 years, who had recently received a first diagnosis of developmental dyscalculia, were randomly assigned to either the intervention or waitlist group. The intervention leveraged the synergy between an initial stimulation phase—utilizing prismatic adaptation, a bottom-up visuomotor rehabilitation technique, to activate neural activity in brain regions involved in cognitive processing—followed by a targeted (top-down) cognitive training phase designed to strengthen the specific skills underlying mathematical deficits. Group differences over time were examined using a general linear model with two groups (treatment vs. control) and two-time points (pre- and post-treatment) for each outcome variable. Significant increases were observed in the working memory index (between group change = 16.51 (CI = 13.59–19.44); p < 0.001, η2 = 0.66), processing speed index (between group change = 12.40 (CI = 9.73–15.70); p < 0.001, η2 = 0.58), mental calculation speed (between group change = 0.74 (CI = 0.55–0.93); p < 0.001, η2 = 0.46), mental calculation accuracy (between group change = 0.43 (CI = 0.14–0.71); p < 0.001, η2 = 0.17), and numerical fact retrieval (between group change = 14.07 (CI = 8.58–19.56); p < 0.001, η2 = 0.31). These findings suggest that combining neurostimulation via prismatic adaptation with targeted cognitive training using serious games enhances both mathematical accuracy and response speed, as well as executive functions, attention, inhibition, and cognitive processing. Prismatic adaptation appears to enhance activity in brain regions that are subsequently reinforced by cognitive training. This innovative approach could have important implications for the early remediation of core neuropsychological deficits in dyscalculia.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by symptoms that emerge in childhood and often improve or even disappear in adulthood, providing a model for understanding how altered brain development shapes neural structure and function. We investigate brain structural alterations in TS and Chronic Tic Disorders (TS/CTD) across development, presenting the largest structural neuroimaging analysis for TS/CTD to date (1,803 individuals from the ENIGMA-TS Working Group), and integrating with large-scale genomewide association studies. Nonlinear age effects were observed in cortical thickness across development and in thalamic volume in children, indicating altered trajectories of brain maturation. Pediatric and adult TS/CTD showed distinct structural patterns, with widespread alterations in childhood and more focal changes in adulthood. Children also showed the most prominent effects highlighting the involvement of orbitofrontal cortex and putamen, alongside additional regions such as frontal and paralimbic areas. Genetic pleiotropy analyses identified overlap between TS/CTD-associated genetic effects on brain structure and neuroanatomical differences. Cross-disorder comparisons revealed correlations with ADHD and OCD and age-related patterns. These findings demonstrate altered neurodevelopmental trajectories in TS/CTD and implicate systems underlying inhibitory control and urge regulation.

Since 2010, there has been a significant increase in mental health issues among children and adolescents, which coincides with the widespread use of social media (SM). While the exact relationship between SM use and psychiatric health remains unclear, growing evidence suggests that excessive screen time is linked to psychosocial symptoms. This article examines the importance of systematically assessing SM use as part of a comprehensive psychiatric evaluation for young individuals. Key factors to consider include the type, content, and purpose of SM use, as well as daily usage patterns and overall screen time. For instance, nighttime SM use can disrupt sleep and contribute to mental health issues. Additionally, while exposure to inappropriate content on SM may negatively affect mental health, positive online interactions can provide support and educational opportunities. Clinicians should also distinguish between different types of SM users—active creators, interactive participants, and passive consumers—since these engagement levels may influence mental health outcomes. Standardized tools for assessing SM use are recommended, though challenges arise due to the rapidly evolving digital landscape. Lastly, fostering open and non-judgmental communication with young patients about their digital habits is essential for understanding the role of SM in their lives and promoting healthier behaviors.

BackgroundChildren and adolescents with autism spectrum disorder (ASD) frequently experience functional somatic symptoms (FSS), although the underlying causes often remain unclear. Various biological and psychological factors, both individual and within families, such as alexithymia or health anxiety, can intensify these symptoms, sometimes resulting in excessive and unnecessary medical interventions.MethodsA narrative review of the literature was conducted, alongside the presentation of a case report involving a 13-year-old boy with ASD. The case illustrates how personal and familial factors can influence the presentation of FSS and the risks of inappropriate treatment.DiscussionThe findings suggest that psychological and familial factors play a significant role in the manifestation of FSS in ASD. These factors can increase the risk of unnecessary medicalization, as they often lead to misinterpretation of symptoms by caregivers and healthcare providers. The case report further underscores how the interaction of personal and familial dynamics can complicate the management of FSS. A comprehensive biopsychosocial approach that addresses both the individual and the family is crucial for managing FSS in ASD. Future research should focus on developing targeted interventions that address these psychological and familial influences to enhance the quality of care and reduce unnecessary and potentially harmful healthcare utilization in ASD.

Amidst rising concerns about mental health in adolescents, the role of social media (SM), particularly highly visual platforms such as TikTok, has become a growing focus of investigation. In the extant literature, conclusive evidence is limited by the aggregate analysis of very heterogeneous SM platforms. This systematic scoping review examines the relationship between TikTok and mental health in adolescents. Additionally, it aims to highlight potential interactions between typical developmental processes and the unique aspects of TikTok, exploring their relevance to mental health within this demographic. Following PRISMA guidelines, a systematic search across PubMed, Scopus, Web of Knowledge, and PsychINFO yielded 20 studies that met the inclusion criteria, encompassing a total of 17,336 subjects from 10 countries. The retrieved studies analyzed four main topics related to TikTok use, i.e., the overall impact on adolescents’ mental health, risk of problematic use and behavioral addiction, consequences on body image and self-esteem, and possible spreading of mental illness behaviors. While TikTok offers creative opportunities for self-expression and peer connection, the literature raises concerns about its potential negative effects on teens, such as lower life satisfaction, increased risk of “contagion” of certain psychiatric symptoms, and problematic usage patterns. Significant variations in study methodologies and outcome measures were observed. In the current era of evolving SM landscapes, a comprehensive approach informed by developmentally grounded research is critically needed to further understand the interplay between SM and adolescent mental health, providing insights for health authorities and policymakers. TikTok has become a prominent platform for teens to discuss and display mental health issues. Reviewed articles indicate an overall negative impact of TikTok on youth mental health, although robust evidence is lacking. Research mainly focused on the risk of addictive use, spreading of mental illness behavior, and decreased self-esteem. Type of TikTok use and psychological characteristics of users may influence positive or negative mental health outcomes.

Background: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. Methods: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6–16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. Results: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. Conclusions: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.

Despite intense and costly treatments, developmental dyslexia (DD) often persists into adulthood. Several brain skills unrelated to speech sound processing (i.e., phonology), including the spatial distribution of visual attention, are abnormal in DD and may represent possible treatment targets. This study explores the efficacy in DD of rightward prismatic adaptation (rPA), a visuomotor adaptation technique that enables visuo-attentive recalibration through shifts in the visual field induced by prismatic goggles. A digital intervention of rPA plus cognitive training was delivered weekly over 10 weeks to adolescents with DD (aged 13–17) assigned either to treatment (N = 35) or waitlist (N = 35) group. Efficacy was evaluated by repeated measures MANOVA assessing changes in working memory index (WMI), processing speed index (PSI), text reading speed, and words/pseudowords reading accuracy. rPA treatment was significantly more effective than waitlist (p ≤ 0.001; ηp2 = 0.815). WMI, PSI, and reading speed increased in the intervention group only (p ≤ 0.001, ηp2 = 0.67; p ≤ 0.001, ηp2 = 0.58; p ≤ 0.001, ηp2 = 0.29, respectively). Although modest change was detected for words and pseudowords accuracy in the waitlist group only (words: p ≤ 0.001, d = 0.17, pseudowords: p = 0.028; d = 0.27), between-group differences were non-significant. rPA-coupled cognitive training enhances cognitive and reading abilities in adolescents with DD. This innovative approach could have implications for early remedial treatment.

BACKGROUND:Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. METHODS:We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. RESULTS:257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78). CONCLUSIONS:UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

Tourette syndrome (TS) and early-onset obsessive-compulsive disorder (OCD) are frequently associated and conceptualized as distinct phenotypes of a common disease spectrum. However, the nature of their relationship is still largely unknown on a pathophysiological level. In this study, early structural white matter (WM) changes investigated through diffusion tensor imaging (DTI) were compared across four groups of drug-naïve children: TS-pure (n = 16), TS+OCD (n = 14), OCD (n = 10), and 11 age-matched controls. We analyzed five WM tracts of interest, i.e., cortico-spinal tract (CST), anterior thalamic radiations (ATR), inferior longitudinal fasciculus (ILF), corpus callosum (CC), and cingulum and evaluated correlations of DTI changes to symptom severity. Compared to controls, TS-pure and TS+OCD showed a comparable pattern of increased fractional anisotropy (FA) in CST, ATR, ILF and CC, with FA changes displaying negative correlation to tic severity. Conversely, in OCD, FA decreased in all WM tracts (except for the cingulum) compared to controls and negatively correlated to symptoms. We demonstrate different early WM microstructural alterations in children with TS-pure/TS+OCD as opposed to OCD. Our findings support the conceptualization of TS+OCD as a subtype of TS while suggesting that OCD is characterized by independent pathophysiological mechanisms affecting WM development.

The COVID-19 pandemic has deeply affected the psychophysical wellbeing of children worldwide. Alexithymia, a personality trait involving difficulties in identifying and expressing feelings represents a vulnerability factor for stress-related disorders. Under pandemic stress exposure, we aimed to investigate the role of parents’ and children’s alexithymia in the psychophysical symptomatology shown by children and to evaluate possible differences according to age, gender and history of COVID-19 infections. The perception of parents and children about the impact of the pandemic on children’s emotional, social and physiological wellbeing was also explored. Sixty-five familial triads were surveyed in the period from March to May 2022: children (n = 33 males; mean age = 9.53, sd = 1.55), mothers (mean age = 44.12; sd = 6.10) and fathers (mean age = 47.10; sd = 7.8). Both parental and children’s alexithymia scores were significantly associated with somatic and externalizing symptomatology in children. Self-reported anger and externally oriented thinking scores were higher in younger children (age 8–9.9 years) than in older ones (10–12 years). Girls scored higher than boys in somatic complaints, as reported by parents. No difference emerged between children affected/not affected by COVID-19. Notably, children reported a greater negative impact of the pandemic on their emotional and psychosocial well-being than their parents. The findings emphasize the role of alexithymia in the occurrence of psychophysical symptoms in children during the COVID-19 pandemic. The reduced parental awareness of the emotional burden imposed by the pandemic on children indicates the need to better consider how epidemics affect children’s mental health and to develop adequate preventive strategies to support them in these exceptional times.

AIM:Daydreaming is a cognitive phenomenon characterized by the redirection of attention from the external world to inner representations. Although serving several adaptive functions, excessive daydreaming has been related to emotional problems and poor psychosocial adjustment. During adolescence, this phenomenon has been scarcely explored as potential psychopathological correlate. This study aims to explore daydreaming frequency and association with psychopathological symptoms in a non-referred population.METHODS:Participants were adolescents from a community sample (N = 251). Daydreaming was assessed through the Daydreaming Frequency Scale (DDFS). Youth Self-Report (YSR) and Strength and Difficulties Questionnaire (SDQ) were used as self-reports to evaluate psychopathological problems and adaptive functioning.RESULTS:Excessive daydreaming was present in 12.7% of participants. DDFS scores were significantly elevated in respondents with clinical scores for internalizing, depressive, obsessive-compulsive, and post-traumatic stress problems. Symptom severity correlated positively with the DDFS. Higher daydreaming was also associated with emotional symptoms, conduct problems and total difficulties on the SDQ.CONCLUSIONS:Adolescents who daydream show increased depressive, obsessive-compulsive, and post-traumatic stress symptoms. Possible cognitive processes at play in the relationship between daydreaming and psychopathology are discussed. Daydreaming may represent a silent psychopathological index that deserves better recognition in the clinical practice and in mental health initiatives for adolescents.

Tourette syndrome (TS) and obsessive–compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involvement in the pathophysiology of TS and OCD, we explored cerebellar structural and functional abnormalities in drug-naive children with TSpure, TS + OCD, and OCD and assessed possible correlations with severity scores. We examined 53 drug-naive children, classified as TSpure ( n = 16), TS + OCD ( n = 14), OCD ( n = 11), or controls ( n = 12). All subjects underwent a multimodal 3T magnetic resonance imaging examination. Cerebellar lobular volumes and quantitative diffusion tensor imaging parameters of cerebellar peduncles were used as measures of structural integrity. The dentate nucleus was selected as a region of interest to examine cerebello-cerebral functional connectivity alterations. Structural analysis revealed that both TSpure and TS + OCD patients had higher fractional anisotropy in cerebellar peduncles than controls. Conversely, OCD patients were characterized by lower fractional anisotropy than both controls and TSpure and TS + OCD patients. Lastly, cerebellar functional connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical circuit in TSpure, TS + OCD, and OCD patients. Early cerebellar structural and functional changes in drug-naive pediatric TSpure, TS + OCD, and OCD patients support a primary role of the cerebellum in the pathophysiology of these disorders.

Because tics are the defining clinical feature of Tourette syndrome, it is conceptualized predominantly as a motor disorder. There is some evidence though suggesting that the neural basis of Tourette syndrome is related to perception–action processing and binding between perception and action. However, binding processes have not been examined in the motor domain in these patients. If it is particularly perception–action binding but not binding processes within the motor system, this would further corroborate that Tourette syndrome it is not predominantly, or solely, a motor disorder.Here, we studied N = 22 Tourette patients and N = 24 healthy controls using an established action coding paradigm derived from the Theory of Event Coding framework and concomitant EEG-recording addressing binding between a planned but postponed, and an interleaved immediate reaction with different levels of overlap of action elements. Behavioral performance during interleaved action coding was normal in Tourette syndrome. Response locked lateralized readiness potentials reflecting processes related to motor execution were larger in Tourette syndrome, but only in simple conditions. However, pre-motor processes including response preparation and configuration reflected by stimulus-locked lateralized readiness potentials were normal. This was supported by a Bayesian data analysis providing evidence for the null hypothesis. The finding that processes integrating different action-related elements prior to motor execution are normal in Tourette syndrome suggests that Tourette it is not solely a motor disorder. Considering other recent evidence, the data show that changes in “binding” in Tourette syndrome are specific for perception–action integration but not for action coding.

Coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic infection to critical illness and death. In COVID-19 disease coagulopathy is frequently reported, being more prevalent in critically ills patients; indeed, SARS-CoV-2 may predispose patients to thrombotic disease, both in the venous and arterial circulation, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Increased prevalence of antiphospholipid antibodies was also reported. Elevated D-dimer values correlate with a poor prognosis, with the development of acute respiratory distress syndrome (ARDS), and with the risk for admission to intensive care unit. The increase in the value of D-dimer is the most sensitive change in coagulation parameters in COVID-19 and indicate a greater risk for the development of thrombosis; nevertheless, D-dimer is a marker of fibrinolysis, and only a proxy for ongoing thrombosis, and it is already known that its specificity for venous thromboembolism is low. Moreover, since the Ddimer is known to be a mixture of fragments of different weight, and tests may report results in terms of weight for units of volume or as fibrinogen equivalent units (FEU). So, it may be not correct to compare results between different tests. In arterial thromboembolism D-dimer has a marginal role, if any. Therefore, the use of heparin in the treatment of COVID-19 disease, should play a fundamental role, and prophylactic doses of low molecular weight heparin (LMWH) or unfractionated heparin (UFH) were associated with a reduced 28-day mortality in more severe COVID-19 patients. Consequently, the International Society of Thrombosis and Haemostasis (ISTH) recommended systematic pharmacological thromboprophylaxis in all patients who require hospital admission for COVID-19 disease. Also in a position paper from Italian Society on Thrombosis and Haemostasis (SISET), the use of LMWH, UFH, or fondaparinux at doses indicated for prophylaxis of venous thromboembolism (VTE) was strongly advised in all COVID-19 hospitalized patients. However, these reccomendations are largely derived on the experience from trials in medical patients without COVID-19. Moreover, it is not known if antithrombotic prophylaxis in COVID-19 patients should be guided by risk assessment models (the standard practice in nonsurgical admitted patients before the current pandemic), or by D-dimer levels, or instead by clinical judgement alone. In a retrospective cohort study conducted in 2 French centers, consecutive patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were enrolled and subjected to systematic low limb venous duplex ultrasonography. D-dimers at baseline were significantly higher in patients with deep venous thrombosis (DVT) (P < 0.001). The negative predictive value of a baseline D-dimer level <1.0 mg/ml was 90% for VTE and 98% for pulmonary embolism (PE). The positive predictive value for VTE was 44% and 67% for D-dimer level 1.0 mg/ml and 3 mg/ml, respectively. Increased D-dimer concentrations of more than 1.0 mg/ml predict the risk of VTE. In an other prospective study, 165 consecutive patients hospitalized in non-intensive care units with diagnosis of COVID19 pneumonia and D-dimer >1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound. All but 3 patients were received standard doses of thromboprophylaxis. Twenty-three patients were diagnosed with DVT (of whom only 1 had proximal DVT, and 7 patients had bilateral distal DVT). In these kind of patients the D-dimer

Coronavirus disease 2019 (COVID-19) emerged as a potentially life-threatening disease characterized by multiorgan involvement, high rate of venous thromboembolism (VTE), primarily among hospitalized patients, and substantial fatality particularly among the elderly [1Lodigiani C. Iapichino G. Carenzo L. Cecconi M. Ferrazzi P. Sebastian T. Kucher N. Studt J.D. Sacco C. Bertuzzi A. Sandri M.T. Barco S. Humanitas C.-T.F. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.Thromb. Res. 2020; 191: 9-14Abstract Full Text Full Text PDF PubMed Scopus (1507) Google Scholar, 2Roncon L. Zuin M. Barco S. Valerio L. Zuliani G. Zonzin P. Konstantinides S.V. Incidence of acute pulmonary embolism in COVID-19 patients: systematic review and meta-analysis.Eur. J. Intern. Med. 2020; 82: 29-37Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 3Bompard F. Monnier H. Saab I. Tordjman M. Abdoul H. Fournier L. Sanchez O. Lorut C. Chassagnon G. Revel M.P. Pulmonary embolism in patients with COVID-19 pneumonia.Eur. Respir. J. 2020; : 56(1)Google Scholar]. Unanswered questions include whether an early thromboprophylaxis, as for example in the outpatient setting, may reduce these risks [4Barco S. Bingisser R. Colucci G. Frenk A. Gerber B. Held U. Mach F. Mazzolai L. Righini M. Rosemann T. Sebastian T. Spescha R. Stortecky S. Windecker S. Kucher N. Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial.Trials. 2020; 21: 770Crossref PubMed Scopus (27) Google Scholar], if selected hospitalized patients may benefit from therapeutic-dosed anticoagulation (against the use of a standard thromboprophylaxis) [5Tritschler T. Mathieu M.E. Skeith L. Rodger M. Middeldorp S. Brighton T. Sandset P.M. Kahn S.R. Angus D.C. Blondon M. Bonten M.J. Cattaneo M. Cushman M. Derde L.P.G. DeSancho M.T. Diehl J.L. Goligher E. Jilma B. Juni P. Lawler P.R. Marietta M. Marshall J.C. McArthur C. Miranda C.H. Mirault T. Morici N. Perepu U. Schorgenhofer C. Sholzberg M. Spyropoulos A.C. Webb S.A. Zarychanski R. Zuily S. Le Gal G. International Network of VTCRNI-VTE Anticoagulant interventions in hospitalized patients with COVID-19: a scoping review of randomized controlled trials and call for international collaboration.J. Thromb. Haemost. 2020; 18: 2958-2967Crossref PubMed Scopus (81) Google Scholar]; and if post-discharge VTE prevention is necessary [6Rashidi F, Barco S, Kamangar F, Heresi GA, Emadi A, Kaymaz C, Jansa P, Reis A, Rashidi A, Taghizadieh A, Rezaeifar P, Moghimi M, Ghodrati S, Mozafari A, Foumani AA, Tahamtan O, Rafiee E, Abbaspour Z, Khodadadi K, Alamdari G, Boodaghi Y, Rezaei M, Muhammadi MJ, Abbasi M, Movaseghi F, Koohi A, Shakourzad L, Ebrahimi F, Radvar S, Amoozadeh M, Fereidooni F, Naseari H, Movalled K, Ghorbani O, Ansarin K. Incidence of symptomatic venous thromboembolism following hospitalization for coronavirus disease 2019: prospective results from a multi-center study. Thromb. Res. 2020: 198: 135–138.Google Scholar]. In the absence of firm evidence from phase 3 trials, international guidance and expert consensus vary widely, particularly concerning the timing and dosage of in-hospital thromboprophylaxis [7Fontana P. Casini A. Robert-Ebadi H. Glauser F. Righini M. Blondon M. Venous thromboembolism in COVID-19: systematic review of reported risks and current guidelines.Swiss Med. Wkly. 2020; 150: w20301PubMed Google Scholar]. Data comparing the first and the second COVID-19 wave are still sparse and likely influenced by the change in our medical approach to disease management and prevention of thromboembolic complications [8Kaptein F. Stals M. Grootenboers M. Klok F. Huisman M. Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.Thromb. Res. 2021; 199: 143-148Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar]. In this study, we described the characteristics and course of patients admitted to the Internal Medicine Ward of the Magenta Hospital (Italy), where an institutional COVID-19 clinical protocol was implemented in March 2020 to guide decisions of the medical personnel concerning the use of specific medications and respiratory support. In particular, the suggestion to opt for standard thromboprophylaxis regimen in all medical patients (not requiring admission to an intensive care unit) remained unchanged during the first and in the second COVID-19 waves, based on lacking evidence from interventional studies. The scheme for thromboprophylaxis consisted of enoxaparin 40 mg once daily, reduced to 20 mg once daily in case of patients with severe renal insufficiency (estimated glomerular filtration rate < 30 ml/min) and increased to 60 mg once daily in obese patients (Body Mass Index >30 kg/m2). The diagnosis of SARS-CoV-2 infection was confirmed by reverse-transcriptase–polymerase-chain-reaction assays performed on nasopharyngeal swab specimens. Patients aged 17 years or younger, on therapeutic-dose antithrombotic therapy upon admission, with a previous VTE, or still hospitalized at the time of data analysis were excluded from this study. By doing so, we included patients who were hospitalized up to 4 December 2020, allowing a two-week follow-up until the updated data collection. The end of follow-up was the date of discharge, transferral to another hospital, or death. In this retrospective analysis, we focused on the in-hospital incidence of VTE (acute deep vein thrombosis, DVT, and pulmonary embolism, PE), as well as on in-hospital death. The diagnostic pathway of VTE, including compression ultrasound followed by computed tomography pulmonary angiography, was left to the attending physician. While no systematic imaging screening was performed, the suspicion of VTE was raised in the presence of signs or symptoms or in patients with an otherwise unexplainable clinical worsening or in the presence of a significant increase of D-dimer levels, e.g. more than two folds from admission. Electronic medical charts were accessed to retrieve clinical information into a pseudo-anonymized database. The ethical approval for this study and the need for written informed consent were not required due to local regulations in light of the retrospective nature of the study. In-hospital incidences were accompanied by the corresponding 95% confidence interval (95% CI). The first and the second waves were compared by fitting univariate and multivariable logistic regression models: conditioning variables were chosen based on their clinical relevance and lack of collinearity. In line with current literature and recommendations, no inferential analysis was performed to compare the groups with respect to baseline characteristics and biomarkers levels. JASP served for statistical analysis. A total of 476 patients have been admitted: 316 between 21 February 2020 and 5 April 2020 (first wave) and 160 between 15 October 2020 and 4 December 2020 (second wave). The demographic and baseline characteristics are summarized in Table 1. No clinically relevant differences were observed concerning age, sex, and prevalence of cardiovascular risk factors. The distribution of commonly tested biomarkers also appeared comparable over time. The use of metilprednisolone 1 mg/kg/day was routinely used in all patients requiring Continuous Positive Airway Pressure: 130 (41.1%) in the first wave and 98 (61.3%) in the second wave. Other specific medications intended to mitigate the course of COVID-19 were differently used in the first and in the second wave. In particular, remdesevir was used in only 7 (4.4%) patients from the second wave, whereas tocilizumab was used in only 7 (2.2%) patients from the first wave. The routine use of plaquenil and ritonativ/lopinavir was abandoned in the second wave.Table 1Baseline characteristics and in-hospital incidence of events in COVID-19 patients during the first and second 2020 wave.First wave (n = 316)MissingSecond wave (n = 160)MissingDemographic and baseline characteristicsAge, median (Q1–Q3)72 (63–80)072 (62–81)0Women, n (%)99 (31.3)053 (33.1)0Chronic heart failure, n (%)56 (17.7)027 (16.9)0Chronic obstructive pulmonary disease, n (%)44 (13.9)122 (13.8)1Diabetes mellitus, n (%)71 (22.5)1436 (22.5)1Arterial hypertension, n (%)184 (58.2)1487 (54.4)1Prior stroke, n (%)17 (5.4)08 (5.0)1Body mass index >30 kg/m2, n (%)40 (12.7)022 (13.8)1Active cancer, n (%)16 (5.1)07 (4.4)1Pneumonia upon admission, n (%)247 (78.2)0114 (71.3)2Acute respiratory distress syndrome, n (%)92 (29.1)074 (46.3)3Days on continuous positive airway pressure, median (Q1–Q3)6 (3.8–4.9)011 (7–17)0Days of hospitalization, median (Q1–Q3)10 (7–17)017 (8–27)0Biomarkers levels measured upon admissionCreatinine (mg/dL), median (Q1–Q3)0.89 (0.74–1.15)410.98 (0.81–1.20)1D-dimer (μg/l), median (Q1–Q3)526 (339–1563)78414 (244–1031)20Hemoglobin (g/dL), median (Q1–Q3)12.9 (11.9–14.1)2413.9 (12.5–14.8)1White blood cells (per 109/L), median (Q1–Q3)6.9 (5.2–9.6)248.0 (5.5–10.2)1Platelet count (per 109/L), median (Q1–Q3)215 (159–284)24198 (150–262)1C-reactive protein (mg/L), median (Q1–Q3)9.8 (5.3–13.7)1658.0 (3.3–13.3)3 Open table in a new tab During the second wave, a higher proportion of patients presented with acute respiratory distress syndrome (ARDS; 46.3% vs. 29.1%) and the median length of hospitalization was longer (17 days; [Q1–Q3 8–27] vs. 10 days [Q1–Q3 7–17]). Twelve (3.8%) patients in the first wave and 14 (8.8%) patients during the second wave underwent computed tomography pulmonary angiography. Of these, 5 (1.6%) and 7 (4.4%) were diagnosed with PE, respectively; Table 1. Eleven of 12 patients with PE had a concomitant upper- or lower-extremity DVT. A total of 316 compression ultrasounds were performed: 143 (45% of total) during the first wave and 114 (71%) during the second wave after a median of 5 (Q1–Q3 4–7) days and 7 (Q1–Q3 5–12) days, respectively. Of these patients, 121 (84.6% of ultrasounds) and 102 (89.5%) had no typical signs or symptoms of DVT and the exam was performed based on other clinical reasons. The in-hospital incidence of lower-extremity DVT was 8.5% and 13.1% in the two waves with a similar percentage of positive ultrasonography tests (16% of tests), but with a lower proportion of isolated distal DVT vs. proximal DVT being diagnosed in the first wave (3 distal DVT; 24 proximal DVT) than in the second wave (11 distal DVT; 10 proximal DVT); Table 2. Upper-extremity DVT was diagnosed in 5.7% of patients during the first wave and 10.0% of patients during the second wave, corresponding to a rate of positive ultrasound examinations of 12.6% and 14.0%, respectively. Overall, a total of 44 (13.9%; 95%CI 10.5%–18.2%) patients during the first wave and 29 (18.1%; 95%CI 12.9%–24.8%) patients during the second wave were diagnosed with DVT or PE.Table 2Clinical events during hospitalization.First wave (n = 316)Second wave (n = 160)Lower-extremity DVT, n (% of patients)27 (8.5)21 (13.1) (Iliaco)-femoro-popliteal, n158 Popliteal, n92 Isolated distal, n311Upper-extremity DVT, n (% of patients)18 (5.7)16 (10.0) Axillary vein (bilateral), n54 Axillary vein (unilateral), n610 Subclavian vein (unilateral), n12 Subclavian vein (bilateral), n00 Catheter-related, n81PE, n (% of total; % of CT pulmonary angiogram)5 (1.6; 41.7)7 (4.4; 50.0) Central or lobar, n22 Segmental, n34 Subsegmental, n01Any VTE (DVT or PE), n (; 95% CI)44 (13.9; 10.5–18.2)29 (18.1; 12.9–24.8)Death, n (%; 95% CI)78 (24.7; 20.3–28.9)40 (25.0; 18.9–32.2)PE, pulmonary embolism; DVT, deep vein thrombosis; VTE, venous thromboembolism; 95% CI, 95% confidence interval. Open table in a new tab PE, pulmonary embolism; DVT, deep vein thrombosis; VTE, venous thromboembolism; 95% CI, 95% confidence interval. In-hospital fatality was 24.7% during the first wave (n = 78) and 25.0% (n = 40) during the second wave for an OR of 1.02 (95%CI 0.67–1.58); Table 2. In a multivariable model conditioning for sex, chronic obstructive pulmonary disease, prior chronic heart failure, cancer, and time distribution the covariates "age" (OR 1.11 per year increase; 95%CI 1.10–1.15) and "ARDS diagnosis" (OR 3.05; 95%CI 1.84–5.04) correlated with the risk of in-hospital death. This could not been shown for time distribution (adjusted OR for the second vs. first wave 0.81; 95%CI 0.49–1.33). Our results are in line with data from two Italian provinces indicating a stable trend in COVID-19-related fatality [9Flacco M.E. Acuti Martellucci C. Bravi F. Parruti G. Mascitelli A. Mantovani L. Boccia S. Manzoli L. Severe acute respiratory syndrome coronavirus 2 lethality did not change over time in two Italian provinces.Open Forum Infect Dis. 2020; 7 (ofaa556)Crossref PubMed Scopus (6) Google Scholar]. These appear in contrast with a more recent analysis of data from eight Dutch hospitals, which showed a 50%-reduced risk for overall fatality and a similar incidence of VTE [8Kaptein F. Stals M. Grootenboers M. Klok F. Huisman M. Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.Thromb. Res. 2021; 199: 143-148Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar]. In our cohort, the demographic and baseline characteristics of patients admitted in spring and autumns appeared surprisingly similar and characterized by older patients with a median age of 72 years. However, the proportion of patients requiring Continuous Positive Airway Pressure increased from 41% in the first wave to 61% in the second wave, consistently with that of Acute Respiratory Distress Syndrome (29% to 46%, respectively). This may partly explain why no apparent improvement in patient survival could be observed. The rate of VTE events in our study is similar to what reported in other cohorts of COVID-19 patients [2Roncon L. Zuin M. Barco S. Valerio L. Zuliani G. Zonzin P. Konstantinides S.V. Incidence of acute pulmonary embolism in COVID-19 patients: systematic review and meta-analysis.Eur. J. Intern. Med. 2020; 82: 29-37Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar] and, considering the routine use of thromboprophylaxis, much higher than what observed in patients with medical illnesses without COVID-19 [10Spyropoulos A.C. Anderson Jr., F.A. FitzGerald G. Decousus H. Pini M. Chong B.H. Zotz R.B. Bergmann J.F. Tapson V. Froehlich J.B. Monreal M. Merli G.J. Pavanello R. Turpie A.G.G. Nakamura M. Piovella F. Kakkar A.K. Spencer F.A. Investigators I. Predictive and associative models to identify hospitalized medical patients at risk for VTE.Chest. 2011; 140: 706-714Abstract Full Text Full Text PDF PubMed Scopus (400) Google Scholar]. Nonetheless, this likely represents an underestimation of the actual rate, which remains unknown and largely depends on the number of imaging tests been performed. For instance, in the Dutch study 21% of patients in the first wave and in 38% in the second wave underwent computed tomography pulmonary angiography, which represent much higher values compared to what observed (3.8% and 8.8%, respectively) in this cohort. A more frequent use of imaging testing was associated with more subsegmental PE events been diagnosed. In the Dutch cohort, 24% of patients with PE in the first wave and 38% in the second wave were diagnosed with a subsegmental PE event. In this cohort, the percentage was overall much lower with only one subsegmental PE event (8%) been diagnose. It remains unclear in whom an acute PE should be excluded, how accurate computed tomography pulmonary angiography is for the detection of small emboli and whether their detection has clinical relevance in this setting. Moreover, the strategy of performing a compression ultrasound as a first-line imaging test if a PE is suspected may be useful in other settings to reduce the number of computed tomography pulmonary angiography, but not efficient if the pathophysiological mechanism of disease accounts for pulmonary thrombosis secondary to local inflammation and pneumonia. It is clear that the available risk assessment models fall short to identify patients for whom an anticoagulant prophylaxis is indicated. A number of randomized controlled studies overcoming the intrinsic limitations of observational studies are ongoing to study the impact of non-standard thromboprophylaxis regimens in this setting [5Tritschler T. Mathieu M.E. Skeith L. Rodger M. Middeldorp S. Brighton T. Sandset P.M. Kahn S.R. Angus D.C. Blondon M. Bonten M.J. Cattaneo M. Cushman M. Derde L.P.G. DeSancho M.T. Diehl J.L. Goligher E. Jilma B. Juni P. Lawler P.R. Marietta M. Marshall J.C. McArthur C. Miranda C.H. Mirault T. Morici N. Perepu U. Schorgenhofer C. Sholzberg M. Spyropoulos A.C. Webb S.A. Zarychanski R. Zuily S. Le Gal G. International Network of VTCRNI-VTE Anticoagulant interventions in hospitalized patients with COVID-19: a scoping review of randomized controlled trials and call for international collaboration.J. Thromb. Haemost. 2020; 18: 2958-2967Crossref PubMed Scopus (81) Google Scholar]. At the same time, the so far unsatisfactory results of available trials showed that only corticosteroids appear to improve survival among COVID-19 patients [11Horby P. Lim W.S. Emberson J.R. Mafham M. Bell J.L. Linsell L. Staplin N. Brightling C. Ustianowski A. Elmahi E. Prudon B. Green C. Felton T. Chadwick D. Rege K. Fegan C. Chappell L.C. Faust S.N. Jaki T. Jeffery K. Montgomery A. Rowan K. Juszczak E. Baillie J.K. Haynes R. Landray M.J. Dexamethasone in hospitalized patients with Covid-19 - preliminary report.N. Engl. J. Med. 2021; 384: 693-704Crossref PubMed Scopus (7056) Google Scholar,12Edalatifard M. Akhtari M. Salehi M. Naderi Z. Jamshidi A. Mostafaei S. Najafizadeh S.R. Farhadi E. Jalili N. Esfahani M. Rahimi B. Kazemzadeh H. Mahmoodi Aliabadi M. Ghazanfari T. Sattarian M. Ebrahimi Louyeh H. Raeeskarami S.R. Jamalimoghadamsiahkali S. Khajavirad N. Mahmoudi M. Rostamian A. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial.Eur. Respir. J. 2020; : 56(6)Google Scholar], leaving vaccination as the sole hope to prevent deaths globally and minimize the burden of disease. In conclusion, in this retrospective study we observed no major clinical differences between the first and the second COVID-19 wave in terms of baseline characteristics, biomarker levels upon admission, parameters of severity, and fatality among patients admitted to the same institution and receiving standard-dose thromboprophylaxis. We ascribe the higher incidence of VTE observed during the second wave to longer length of in-hospital stay and more diagnostic tests been performed, the latter as the result of a greater awareness [13Roncon L. Zuin M. Barco S. Zuliani G. Konstantinides S.V. Increased interest in acute pulmonary embolism in Italy during the COVID-19 pandemic: a google trends-based analysis.J. Thromb. Thrombolysis. 2020; https://doi.org/10.1007/s11239-020-02336-9Crossref Scopus (4) Google Scholar] for thromboembolic complications. The present work was conducted at Department of Internal Medicine, Magenta Hospital, Ospedale "Fornaroli" and was not funded.