Health service and psychotropic medication use for mental health conditions among healthcare workers active during the Spain Covid-19 Pandemic - A prospective cohort study using web-based surveys.

Little is known about healthcare workers' (HCW) use of healthcare services for mental disorders. This study presents data from a 16-month prospective cohort study of Spanish HCW (n = 4,809), recruited shortly after the COVID-19 pandemic onset, and assessed at four timepoints using web-based surveys. Use of health services among HCW with mental health conditions (i.e., those having a positive screen for mental disorders and/or suicidal thoughts and behaviours [STB]) was initially low (i.e., 18.2 %) but increased to 29.6 % at 16-month follow-up. Service use was positively associated with pre-pandemic mental health treatment (OR=1.99), a positive screen for major depressive disorder (OR=1.50), panic attacks (OR=1.74), suicidal thoughts and behaviours (OR=1.22), and experiencing severe role impairment (OR=1.33), and negatively associated with being female (OR = 0.69) and a higher daily number of work hours (OR=0.95). Around 30 % of HCW with mental health conditions used anxiolytics (benzodiazepines), especially medical doctors. Four out of ten HCW (39.0 %) with mental health conditions indicated a need for (additional) help, with most important barriers for service use being too ashamed, long waiting lists, and professional treatment not being available. Our findings delineate a clear mental health treatment gap among Spanish HCW.

Traumatic stress symptoms among Spanish healthcare workers during the COVID-19 pandemic: a prospective study.

AIM: To investigate the occurrence of traumatic stress symptoms (TSS) among healthcare workers active during the COVID-19 pandemic and to obtain insight as to which pandemic-related stressful experiences are associated with onset and persistence of traumatic stress. METHODS: This is a multicenter prospective cohort study. Spanish healthcare workers (N = 4,809) participated at an initial assessment (i.e., just after the first wave of the Spain COVID-19 pandemic) and at a 4-month follow-up assessment using web-based surveys. Logistic regression investigated associations of 19 pandemic-related stressful experiences across four domains (infection-related, work-related, health-related and financial) with TSS prevalence, incidence and persistence, including simulations of population attributable risk proportions (PARP). RESULTS: Thirty-day TSS prevalence at T1 was 22.1%. Four-month incidence and persistence were 11.6% and 54.2%, respectively. Auxiliary nurses had highest rates of TSS prevalence (35.1%) and incidence (16.1%). All 19 pandemic-related stressful experiences under study were associated with TSS prevalence or incidence, especially experiences from the domains of health-related (PARP range 88.4-95.6%) and work-related stressful experiences (PARP range 76.8-86.5%). Nine stressful experiences were also associated with TSS persistence, of which having patient(s) in care who died from COVID-19 had the strongest association. This association remained significant after adjusting for co-occurring depression and anxiety. CONCLUSIONS: TSSs among Spanish healthcare workers active during the COVID-19 pandemic are common and associated with various pandemic-related stressful experiences. Future research should investigate if these stressful experiences represent truly traumatic experiences and carry risk for the development of post-traumatic stress disorder.

Mental health impact of the first wave of COVID-19 pandemic on Spanish healthcare workers: A large cross-sectional survey.

INTRODUCTION: Healthcare workers are vulnerable to adverse mental health impacts of the COVID-19 pandemic. We assessed prevalence of mental disorders and associated factors during the first wave of the pandemic among healthcare professionals in Spain. METHODS: All workers in 18 healthcare institutions (6 AACC) in Spain were invited to web-based surveys assessing individual characteristics, COVID-19 infection status and exposure, and mental health status (May 5 - September 7, 2020). We report: probable current mental disorders (Major Depressive Disorder-MDD- [PHQ-8≥10], Generalized Anxiety Disorder-GAD- [GAD-7≥10], Panic attacks, Posttraumatic Stress Disorder -PTSD- [PCL-5≥7]; and Substance Use Disorder -SUD-[CAGE-AID≥2]. Severe disability assessed by the Sheehan Disability Scale was used to identify probable "disabling" current mental disorders. RESULTS: 9,138 healthcare workers participated. Prevalence of screen-positive disorder: 28.1% MDD; 22.5% GAD, 24.0% Panic; 22.2% PTSD; and 6.2% SUD. Overall 45.7% presented any current and 14.5% any disabling current mental disorder. Workers with pre-pandemic lifetime mental disorders had almost twice the prevalence than those without. Adjusting for all other variables, odds of any disabling mental disorder were: prior lifetime disorders (TUS: OR=5.74; 95%CI 2.53-13.03; Mood: OR=3.23; 95%CI:2.27-4.60; Anxiety: OR=3.03; 95%CI:2.53-3.62); age category 18-29 years (OR=1.36; 95%CI:1.02-1.82), caring "all of the time" for COVID-19 patients (OR=5.19; 95%CI: 3.61-7.46), female gender (OR=1.58; 95%CI: 1.27-1.96) and having being in quarantine or isolated (OR= 1.60; 95CI:1.31-1.95). CONCLUSIONS: One in seven Spanish healthcare workers screened positive for a disabling mental disorder during the first wave of the COVID-19 pandemic. Workers reporting pre-pandemic lifetime mental disorders, those frequently exposed to COVID-19 patients, infected or quarantined/isolated, female workers, and auxiliary nurses should be considered groups in need of mental health monitoring and support.

Thirty-day suicidal thoughts and behaviors among hospital workers during the first wave of the Spain COVID-19 outbreak.

BACKGROUND: Healthcare workers are a key occupational group at risk for suicidal thoughts and behaviors (STB). We investigated the prevalence and correlates of STB among hospital workers during the first wave of the Spain COVID-19 outbreak (March-July 2020). METHODS: Data come from the baseline assessment of a cohort of Spanish hospital workers (n = 5450), recruited from 10 hospitals just after the height of the coronavirus disease 2019 (COVID-19) outbreak (May 5-July 23, 2020). Web-based self-report surveys assessed 30-day STB, individual characteristics, and potentially modifiable contextual factors related to hospital workers' work and financial situation. RESULTS: Thirty-day STB prevalence was estimated at 8.4% (4.9% passive ideation only, 3.5% active ideation with or without a plan or attempt). A total of n = 6 professionals attempted suicide in the past 30 days. In adjusted models, 30-day STB remained significantly associated with pre-pandemic lifetime mood (odds ratio [OR] = 2.92) and anxiety disorder (OR = 1.90). Significant modifiable factors included a perceived lack of coordination, communication, personnel, or supervision at work (population-attributable risk proportion [PARP] = 50.5%), and financial stress (PARP = 44.1%). CONCLUSIONS AND RELEVANCE: Thirty-day STB among hospital workers during the first wave of the Spain COVID-19 outbreak was high. Hospital preparedness for virus outbreaks should be increased, and strong governmental policy response is needed to increase financial security among hospital workers.

Mental health impact of the first wave of COVID-19 pandemic on Spanish healthcare workers: A large cross-sectional survey.

INTRODUCTION: Healthcare workers are vulnerable to adverse mental health impacts of the COVID-19 pandemic. We assessed prevalence of mental disorders and associated factors during the first wave of the pandemic among healthcare professionals in Spain. METHODS: All workers in 18 healthcare institutions (6 AACC) in Spain were invited to web-based surveys assessing individual characteristics, COVID-19 infection status and exposure, and mental health status (May 5 - September 7, 2020). We report: probable current mental disorders (Major Depressive Disorder-MDD- [PHQ-8≥10], Generalized Anxiety Disorder-GAD- [GAD-7≥10], Panic attacks, Posttraumatic Stress Disorder -PTSD- [PCL-5≥7]; and Substance Use Disorder -SUD-[CAGE-AID≥2]. Severe disability assessed by the Sheehan Disability Scale was used to identify probable "disabling" current mental disorders. RESULTS: 9,138 healthcare workers participated. Prevalence of screen-positive disorder: 28.1% MDD; 22.5% GAD, 24.0% Panic; 22.2% PTSD; and 6.2% SUD. Overall 45.7% presented any current and 14.5% any disabling current mental disorder. Workers with pre-pandemic lifetime mental disorders had almost twice the prevalence than those without. Adjusting for all other variables, odds of any disabling mental disorder were: prior lifetime disorders (TUS: OR=5.74; 95%CI 2.53-13.03; Mood: OR=3.23; 95%CI:2.27-4.60; Anxiety: OR=3.03; 95%CI:2.53-3.62); age category 18-29 years (OR=1.36; 95%CI:1.02-1.82), caring "all of the time" for COVID-19 patients (OR=5.19; 95%CI: 3.61-7.46), female gender (OR=1.58; 95%CI: 1.27-1.96) and having being in quarantine or isolated (OR= 1.60; 95CI:1.31-1.95). CONCLUSIONS: One in seven Spanish healthcare workers screened positive for a disabling mental disorder during the first wave of the COVID-19 pandemic. Workers reporting pre-pandemic lifetime mental disorders, those frequently exposed to COVID-19 patients, infected or quarantined/isolated, female workers, and auxiliary nurses should be considered groups in need of mental health monitoring and support.

Malignant infarction of the middle cerebral artery in a porcine model. A pilot study.

BACKGROUND AND PURPOSE: Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4). METHODS: A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression. RESULTS: PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 µM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels. CONCLUSIONS: The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies.

Combining statins with tissue plasminogen activator treatment after experimental and human stroke: a safety study on hemorrhagic transformation.

AIMS: Statins may afford neuroprotection against ischemic injury, but it remains controversial whether combined treatment with tissue plasminogen activator (tPA) after stroke increases the risk of hemorrhagic transformation (HT), the major tPA-related complication. We evaluated the safety of combining statin with tPA administration during the acute phase of both experimental and human stroke. METHODS: The occurrence and severity of HT, infarct volume, and neurological outcome were evaluated in spontaneous hypertensive rats (SHR) subjected to embolic middle cerebral arterial occlusion (MCAO), which received vehicle or simvastatin (20 mg/kg), 15 min after ischemia and tPA (9 mg/kg) 3 h after ischemia. Additionally, HT rate was evaluated in stroke patients who were treated with tPA (0.9 mg/kg) within 3 h after symptom onset, considering whether or not were under statins treatment when the stroke occurred. RESULTS: In the experimental study, no differences in HT rates and severity were found between treatment groups, neither regarding mortality, neurological deficit, infarct volume, or metalloproteinases (MMPs) brain content. In the clinical study, HT rates and hemorrhage type were similar in stroke patients who were or not under statins treatment. CONCLUSION: This study consistently confirms that the use of statins does not increase HT rates and severity when is combined with tPA administration.

Citicoline in pre-clinical animal models of stroke: a meta-analysis shows the optimal neuroprotective profile and the missing steps for jumping into a stroke clinical trial.

The neuroprotective actions of citicoline have been documented for experimental stroke therapy. We used a systematic review and meta-analysis to assess this evidence. From 64 identified studies using citicoline in stroke animal models, only those describing ischemic occlusive stroke and reporting data on infarct volume and/or neurological outcome were included (14 studies, 522 animals). Overall, the quality of the studies was modest (5, 4-6), while the absence of studies involving animals with co-morbidities, females, old animals or strain differences indicated that studies did not fulfill the STAIR recommendations. Weighted mean difference meta-analysis showed citicoline to reduce infarct volume by 27.8% [(19.9%, 35.6%); p < 0.001]. In the stratified analysis, citicoline effect on reducing infarct volume was higher in proximal occlusive models of middle cerebral artery (MCA) compared with distal occlusion. Moreover, the efficacy was superior using multiple doses than single dose and when a co-treatment was administered compared with citicoline monotherapy, the only independent factor identified in the meta-regression. Citicoline improved neurological deficit by 20.2% [(6.8%, 33.7%); p = 0.015], but only four studies including 176 animals reported these data. In conclusion, this meta-analysis provides evidence of citicoline efficacy in stroke animal models and shows the optimal neuroprotective profile and the missing experimental requirements before jumping into clinical trials.

[Advances in the pathophysiology and management of infections in the acute phase of stroke]. / Avances en la fisiopatología y el tratamiento de las infecciones en la fase aguda del ictus.

Infection in the acute phase of stroke has been identified as an independent predictor of poor outcome, both in the short and intermediate term. Various factors raising the risk of developing an infection (exposure to multiple pathogens, disruption of the protective function of the mucous membranes and a state of relative immunosuppression) coexist during the acute phase of stroke. Several risk factors have been identified for their development (especially increasing age and stroke severity). It has been proposed that infection contributes to a worse prognosis through different mechanisms, notably the development of an inflammatory response to brain tissue (with a potential to add secondary damage to that caused by the ischemic insult). Clinical trials evaluating the prophylactic and early administration of antibiotics to reduce the incidence of infection in the acute phase of stroke have yielded inconsistent results. Immunomodulating strategies, which may provide therapeutic alternatives in the future, are currently being evaluated.

Evidence for the efficacy of statins in animal stroke models: a meta-analysis.

Protective effects of statins have been well documented for stroke therapy. Here, we used a systematic review and meta-analysis to assess these evidences. We identified 190 studies using statin treatment in stroke animal models by electronic searching. From those, only studies describing ischemic occlusive stroke and reporting data on infarct volume and/or neurological outcome were included in the analysis (41 publications, 1882 animals). The global estimate effect was assessed by Weighted Mean Difference meta-analysis. Statins reduced infarct volume by 25.12% (20.66%-29.58%, P < 0.001) and consistently, induced an improvement on neurological outcome (20.36% (14.17%-26.56%), P < 0.001). Stratified analysis showed that simvastatin had the greatest effect on infarct volume reduction (38.18%) and neurological improvement (22.94%), whereas bigger infarct reduction was observed giving the statin as a pre-treatment (33.5%) compared with post-treatment (16.02%). The use of pentobarbital sodium, the timing of statin administration, the statement of conflict of interest and the type of statin studied were found to be independent factors in the meta-regression, indicating their influence on the results of studies examining statin treatment. In conclusion, this meta-analysis provides further evidences of the efficacy of statins, supporting their potential use for human stroke therapy.

Effects of acute post-treatment with dipyridamole in a rat model of focal cerebral ischemia.

Dipyridamole (DP) is a platelet inhibitor with known antithrombotic benefits in stroke prevention. In addition to its anti-aggregant properties, recent studies have reported that DP promotes anti-inflammatory, anti-oxidative and neuroprotective effects. We aimed to test whether post-treatment with DP may exert protection after ischemic cerebral injury in the rat. For this purpose, rats were subjected to 120 min or 90 min of middle cerebral artery occlusion (MCAO) followed by 24 or 48 h of reperfusion, respectively. Either DP (100mg/kg) or vehicle was administered i.v. at the onset of reperfusion; rats subjected to 90 min MCAO also received additional doses of DP orally (60 mg/kg) at 24 and 36 h after ischemia. Matrix metalloproteinases, extravasated hemoglobin content and IL-6, MIP-1α and MCP-1 cytokine level were examined in brain tissue by zymography, western blot and multiple ELISA, respectively. DP post-treatment led to a neurological improvement in both models (p < 0.05) and a significant reduction in the infarct volume of rats subjected to 90 min of ischemia, as compared to vehicle group (7.9% vs. 24.4%, p = 0.03). This neuroprotection was accompanied by a modest increase in expression of MMP-9 pro-form and a significant attenuation of MIP-1α levels in the infarcted hemisphere. These results provide support for the development of novel therapies based on DP for acute treatment of stroke. In selected animals, intravenous administration of high dose DP induced an adverse hypotensive effect leading to rapid death. Thus, alternative ways of acute administration must be examined in order to avoid this unfavorable effect.

Plasma VAP-1/SSAO activity predicts intracranial hemorrhages and adverse neurological outcome after tissue plasminogen activator treatment in stroke.

BACKGROUND AND PURPOSE: Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme involved in recruitment of lymphocytes and neutrophils through its semicarbazide-sensitive amine oxidase (SSAO) activity. We aimed to study plasma VAP-1/SSAO activity in relation to the risk for intracranial bleeding complications in patients with stroke treated with tissue plasminogen activator (tPA), the greatest safety concern with this treatment. METHODS: In 141 patients with ischemic stroke, we measured VAP-1/SSAO activity in plasma taken before tPA administration. Hemorrhagic events were classified according to brain CT criteria and functional outcomes evaluated using the National Institutes of Health Stroke Scale. We also assessed the potential therapeutic effect of blocking VAP-1/SSAO activity in a rat embolic stroke model treated with tPA. RESULTS: We saw significantly higher levels of plasma VAP-1/SSAO activity in patients who subsequently experienced hemorrhagic transformation. Elevated plasma VAP-1/SSAO activity also predicted worse neurological outcome in these patients. In the rat model, we confirmed that use of the inhibitor semicarbazide prevented adverse effects caused by delayed tPA administration, leading to a smaller infarct volume. CONCLUSIONS: Our data demonstrate that baseline VAP-1/SSAO activity predicts parenchymal hemorrhage after tPA, suggesting the safety of thrombolytic agents could be improved by considering VAP-1/SSAO activity. Furthermore, anti-VAP-1/SSAO drugs given with tPA may prevent neurological worsening in patients with ischemic stroke.