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1.
Exp Neurol ; : 113713, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798562

RESUMO

Current hypotheses on the therapeutic action of non-invasive brain stimulation (NIBS) in psychiatric disorders build on the abundant data from neuroimaging studies. This makes NIBS a very promising tool for developing personalized interventions within a precision medicine framework. NIBS methods fundamentally vary in their neurophysiological properties. They comprise repetitive transcranial magnetic stimulation (rTMS) and its variants (e.g. theta burst stimulation - TBS) as well as different types of transcranial electrical stimulation (tES), with the largest body of evidence for transcranial direct current stimulation (tDCS). In the last two decades, significant conceptual progress has been made in terms of NIBS targets, i.e. from single brain regions to neural circuits and to functional connectivity as well as their states, recently leading to brain state modulating closed-loop approaches. Regarding structural and functional brain anatomy, NIBS meets an individually unique constellation, which varies across normal and pathophysiological states. Thus, individual constitutions and signatures of disorders may be indistinguishable at a given time point, but can theoretically be parsed along course- and treatment-related trajectories. We address precision interventions on three levels: 1) the NIBS intervention, 2) the constitutional factors of a single patient, and 3) the phenotypes and pathophysiology of illness. With examples from research on depressive disorders, we propose solutions and discuss future perspectives, e.g. individual MRI-based electrical field strength as a proxy for NIBS dosage, and also symptoms, their clusters, or biotypes instead of disorder focused NIBS. In conclusion, we propose interleaved research on these three levels along a general track of reverse and forward translation including both clinically directed research in preclinical model systems, and biomarker guided controlled clinical trials. Besides driving the development of safe and efficacious interventions, this framework could also deepen our understanding of psychiatric disorders at their neurophysiological underpinnings.

3.
Schizophr Res ; 228: 425-434, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33561620

RESUMO

BACKGROUND: Clinical guidelines can facilitate the transfer of scientific evidence into clinical practice, yet their implementation still faces difficulties. The aim of this study was to examine the implementation status of the current German evidence- and consensus-based guidelines for schizophrenia (2019) and psychosocial therapies (2019) and to identify barriers as well as facilitators in guideline adherence. METHODS: We used a quantitative approach by developing an online questionnaire, focusing on the current implementation status as well as barriers and facilitators in guideline adherence. The questionnaire was sent to 100 hospitals for psychiatry and psychosomatics and 52 professional associations in mental healthcare in Germany (investigation period: 10/2019-01/2020). RESULTS: In total, 657 mental healthcare professionals (MHCP, e.g. medical doctors, psychologists, psychosocial therapists, caregivers) provided sufficient responses for analyses. Less than half (47%) of our participants were aware of the existence of the guideline for psychosocial therapies, while 74% exhibited awareness of the schizophrenia guideline. A minority reported to adhere to the current guidelines for schizophrenia (41%) and psychosocial interventions (18%). Profession-related differences in the implementation-status were detected. Specifically, medical doctors exhibited higher awareness rates than psychosocial therapists and caregivers and additionally higher adherence rates than psychologists and caregivers. Medical doctors were less exposed to knowledge-related barriers (e.g. lack of guideline familiarity), while no differences across professions were found in external/behavior-related barriers (e.g. long versions). DISCUSSION AND CONCLUSION: Our findings indicate that the implementation of guidelines as well as related barriers vary between professions. To prevent a growing gap in guideline adherence between MHCP, target-specific implementation strategies should be considered.

4.
Schizophr Res ; 228: 218-226, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33454644

RESUMO

OBJECTIVE: The aim of this systematic review and meta-analysis was to characterize ultra-treatment-resistant Schizophrenia also known as clozapine-resistant schizophrenia (CRS) patients across clozapine combination and augmentation trials through demographic and clinical baseline data. Furthermore, we investigated the variability and consistency in CRS definitions between studies. METHODS: Systematic searches of articles indexed in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO were conducted in March 2020. 1541 randomized and non-randomized clinical trials investigating pharmacological and non-pharmacological clozapine add-on strategies were screened and a total of 71 studies were included. The primary outcome was the overall symptom score at baseline, measured with Positive and Negative Syndrome Scale (PANSS) total or Brief Psychiatric Rating Scale (BPRS) total scores. RESULTS: Data from 2731 patients were extracted. Patients were overall moderately ill with a mean PANSS total score at baseline of 79.16 (±7.52), a mean duration of illness of 14.64 (±4.14) years with a mean clozapine dose of 436.94 (±87.47) mg/day. Illness severity data were relatively homogenous among patients independently of the augmentation strategy involved, although stark geographical differences were found. Overall, studies showed a large heterogeneity of CRS definitions and insufficient guidelines implementation. CONCLUSIONS: This first meta-analysis characterizing CRS patients and comparing CRS definitions revealed a lack of consistent implementation of a CRS definition from guidelines into clinical trials, compromising the replicability of the results and their applicability in clinical practice. We offer a new score modeled on a best practice definition to help future trials increase their reliability.

5.
Nervenarzt ; 2021 Jan 25.
Artigo em Alemão | MEDLINE | ID: mdl-33492411

RESUMO

In recent years noninvasive brain stimulation (NIBS) applications have emerged as a third and novel treatment option alongside psychopharmacology and psychotherapy in the treatment of mental diseases. It is assumed that NIBS could represent a supplement or (in some indications) even replacement to established therapeutic strategies, e.g. in disorders with high resistance to current treatment regimens, such as negative symptoms or cognitive impairments in schizophrenia. Although positive symptoms in schizophrenia can be treated sufficiently with antipsychotic drugs, patients with negative symptoms frequently suffer from persistent lack of impetus, cognitive decline, social withdrawal and loss of global functioning in the activities of daily life; however, in these cases, current treatment strategies exert only moderate effects, and new treatment options are urgently needed. This review article provides a summary of the clinical effects of new electrical NIBS methods, e.g. transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) for the treatment of negative symptoms in schizophrenia. These new NIBS methods could help restore the disrupted neuronal networks and improve disturbed connectivity, especially of the left dorsolateral prefrontal cortex and left temporoparietal junction. Promising results are reported for the treatment of negative symptoms with tDCS, tACS and tRNS and could thus represent new therapeutic options in the treatment of schizophrenia.

8.
Front Psychiatry ; 11: 569912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132934

RESUMO

Objective: Avoiding withdrawal symptoms following antipsychotic discontinuation is an important factor when planning a safe therapy. We performed a systematic review and meta-analysis concerning occurrence of withdrawal symptoms after discontinuation of antipsychotics. Data Sources: We searched the databases CENTRAL, Pubmed, and EMBASE with no restriction to the beginning of the searched time period and until October 1, 2019 (PROSPERO registration no. CRD42019119148). Study Selection: Of the 18,043 screened studies, controlled and cohort trials that assessed withdrawal symptoms after discontinuation of oral antipsychotics were included in the random-effects model. Studies that did not implement placebo substitution were excluded from analyses. The primary outcome was the proportion of individuals with withdrawal symptoms after antipsychotic discontinuation. We compared a control group with continued antipsychotic treatment in the assessment of odds ratio and number needed to harm (NNH). Data Extraction: We followed guidelines by the Cochrane Collaboration, PRISMA, and MOOSE. Results: Five studies with a total of 261 individuals were included. The primary outcome, proportion of individuals with withdrawal symptoms after antipsychotic discontinuation, was 0.53 (95% CI, 0.37-0.70; I2 = 82.98%, P < 0.01). An odds ratio of 7.97 (95% CI, 2.39-26.58; I2 = 82.7%, P = 0.003) and NNH of 3 was calculated for the occurrence of withdrawal symptoms after antipsychotic discontinuation. Conclusion: Withdrawal symptoms appear to occur frequently after abrupt discontinuation of an oral antipsychotic. The lack of randomized controlled trials with low risk of bias on antipsychotic withdrawal symptoms highlights the need for further research.

9.
BMC Psychiatry ; 20(1): 503, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046040

RESUMO

BACKGROUND: Information regarding the distribution of evidence grades in psychiatry and psychotherapy guidelines is lacking. Based on the German evidence- and consensus- based (S3) psychiatry and psychotherapy and the Scottish Intercollegiate Guidelines Network (SIGN) treatment guidelines, we aimed to specify how guideline recommendations are composed and to what extent recommendations are evidence-based. METHODS: Data was collected from all published evidence- and consensus-based S3-classified psychiatry and psychotherapy guidelines. As control conditions, data from German neurology S3-classified guidelines as well as data from recent SIGN guidelines of mental health were extracted. Two investigators reviewed the selected guidelines independently, extracted and analysed the numbers and levels of recommendations. RESULTS: On average, 45.1% of all recommendations are not based on strong scientific evidence in German guidelines of psychiatry and psychotherapy. A related pattern can be confirmed for SIGN guidelines, where the mean average of recommendations with lacking evidence is 33.9%. By contrast, in the German guidelines of neurology the average of such recommendations is 16.5%. A total of 24.5% of all recommendations in the guidelines of psychiatry and psychotherapy are classified as level A recommendations, compared to 31.6% in the field of neurology and 31.1% in the SIGN guidelines. Related patterns were observed for B and 0 level recommendations. CONCLUSION: Guidelines should be practical tools to simplify the decision-making process based on scientific evidence. Up to 45% of all recommendations in the investigated guidelines of psychiatry and psychotherapy are not based on strong scientific evidence. The reasons for this high number remain unclear. Possibly, only a limited number of studies answer clinically relevant questions. Our findings thereby question whether guidelines should include non-evidence-based recommendations to be methodologically stringent and whether specific processes to develop expert-opinion statements must be implemented.

10.
Physiol Rep ; 8(19): e14595, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32996722

RESUMO

BACKGROUND: In this study, we investigate the capacity of two different non-invasive brain stimulation (NIBS) techniques (anodal transcranial direct current stimulation (anodal tDCS) and high-frequency transcranial random noise stimulation (hf-tRNS)) regarding the relationship between stimulation duration and their efficacy in inducing long-lasting changes in motor cortical excitability. METHODS: Fifteen healthy subjects attended six experimental sessions (90 experiments in total) and underwent both anodal tDCS of 7, 13, and 20 min duration, as well as high-frequency 1mA-tRNS of 7, 13, and 20 min stimulation duration. Sessions were performed in a randomized order and subjects were blinded to the applied methods. RESULTS: For anodal tDCS, no significant stable increases of motor cortical excitability were observed for either stimulation duration. In contrast, for hf -tRNS a stimulation duration of 7 min resulted in a significant increase of motor cortical excitability lasting from 20 to 60 min poststimulation. While an intermediate duration of 13 min hf-tRNS failed to induce lasting changes in motor cortical excitability, a longer stimulation duration of 20 min hf-tRNS led only to significant increases at 50 min poststimulation which did not outlast until 60 min poststimulation. CONCLUSION: Hf-tRNS for a duration of 7 min induced robust increases of motor cortical excitability, suggesting an indirect proportional relationship between stimulation duration and efficacy. While hf-tRNS appeared superior to anodal tDCS in this study, further systematic and randomized experiments are necessary to evaluate the generalizability of our observations and to address current intensity as a further modifiable contributor to the variability of transcranial brain stimulation.

11.
PLoS Comput Biol ; 16(9): e1008162, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32997653

RESUMO

Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderline personality disorder (N = 31) as well as healthy controls (N = 34) performed a probabilistic reward learning task in which participants could learn from social and non-social information. Patients with schizophrenia and borderline personality disorder performed more poorly on the task than healthy controls and patients with major depressive disorder. Broken down by domain, borderline personality disorder patients performed better in the social compared to the non-social domain. In contrast, controls and major depressive disorder patients showed the opposite pattern and schizophrenia patients showed no difference between domains. In effect, borderline personality disorder patients gave up a possible overall performance advantage by concentrating their learning in the social at the expense of the non-social domain. We used computational modeling to assess learning and decision-making parameters estimated for each participant from their behavior. This enabled additional insights into the underlying learning and decision-making mechanisms. Patients with borderline personality disorder showed slower learning from social and non-social information and an exaggerated sensitivity to changes in environmental volatility, both in the non-social and the social domain, but more so in the latter. Regarding decision-making the modeling revealed that compared to controls and major depression patients, patients with borderline personality disorder and schizophrenia showed a stronger reliance on social relative to non-social information when making choices. Depressed patients did not differ significantly from controls in this respect. Overall, our results are consistent with the notion of a general interpersonal hypersensitivity in borderline personality disorder and schizophrenia based on a shared computational mechanism characterized by an over-reliance on beliefs about others in making decisions and by an exaggerated need to make sense of others during learning specifically in borderline personality disorder.

12.
Dtsch Arztebl Int ; 117(24): 412-419, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32865492

RESUMO

BACKGROUND: The lifetime prevalence of schizophrenia is 1%. Schizophrenia is among the most severe mental illnesses and gives rise to the highest treatment costs per patient of any disease. It is characterized by frequent relapses, marked impairment of quality of life, and reduced social and work participation. METHODS: The group entrusted with the creation of the German clinical practice guideline was chosen to be representative and pluralistic in its composition. It carried out a systematic review of the relevant literature up to March 2018 and identified a total of 13 389 publications, five source guidelines, three other relevant German clinical practice guidelines, and four reference guidelines. RESULTS: As the available antipsychotic drugs do not differ to any great extent in efficacy, it is recommended that acute antipsychotic drug therapy should be sideeffect- driven, with a number needed to treat (NNT) of 5 to 8. The choice of treatment should take motor, metabolic, sexual, cardiac, and hematopoietic considerations into account. Ongoing antipsychotic treatment is recommended to prevent relapses (NNT: 3) and should be re-evaluated on a regular basis in every case. It is also recommended, with recommendation grades ranging from strong to intermediate, that disorder- and manifestation-driven forms of psychotherapy and psychosocial therapy, such as cognitive behavioral therapy for positive or negative manifestations (effect sizes ranging from d = 0.372 to d = 0.437) or psycho-education to prevent relapses (NNT: 9), should be used in combination with antipsychotic drug treatment. Further aspects include rehabilitation, the management of special treatment situations, care coordination, and quality management. A large body of evidence is available to provide a basis for guideline recommendations, particularly in the areas of pharmacotherapy and cognitive behavioral therapy. CONCLUSION: The evidence-based diagnosis and treatment of persons with schizophrenia should be carried out in a multiprofessional process, with close involvement of the affected persons and the people closest to them.


Assuntos
Antipsicóticos , Terapia Cognitivo-Comportamental , Psicoterapia , Esquizofrenia , Antipsicóticos/uso terapêutico , Humanos , Qualidade de Vida , Esquizofrenia/terapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-32815019

RESUMO

Healthcare workers (HCW) face tremendous challenges during the COVID-19 pandemic. Little is known about the subjective burden, views, and COVID-19 infection status of HCWs. The aim of this work was to evaluate the subjective burden, the perception of the information policies, and the agreement on structural measures in a large cohort of German HCW during the COVID-19 pandemic. This country-wide anonymous online survey was carried out from April 15th until May 1st, 2020. 25 content-related questions regarding the subjective burden and other dimensions were evaluated. We evaluated different dimensions of subjective burden, stress, and perspectives using 5-point Likert-scale questions. Moreover, the individual COVID-19 infection status, the amount of people infected in circle of friends and acquaintances and the hours working overtime were assessed. A total of 3669 HCWs provided sufficient responses for analyses. 2.8% of HCWs reported to have been tested positive for COVID-19. Nurses reported in principle higher ratings on all questions of subjective burden and stress than doctors and other hospital staff. Doctors (3.6%) and nurses (3.1%) were more likely to be tested positive for COVID-19 than other hospital staff (0.6%, Chi(2)2 = 17.39, p < 0.0005). HCWs who worked in a COVID-19 environment reported higher levels of subjective burden and stress compared to all other participants. Working in a COVID-19 environment increased the likelihood to be tested positive for COVID-19 (4.8% vs. 2.3%, Chi(1)2 = 12.62, p < 0.0005) and the severity of the subjective burden. During the COVID-19 pandemic, nurses experience more stress than doctors. Overall, German HCWs showed high scores of agreement with the measures taken by the hospitals.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32748261

RESUMO

Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients' health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40-50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients' mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

15.
Pharmacopsychiatry ; 53(6): 273-283, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32757178

RESUMO

BACKGROUND: Even though clozapine is the recommended last-resort antipsychotic, many patients fail to respond and show treatment-refractory psychotic symptoms. Smoking has been suggested as a possible risk factor for poor clozapine response, hampering remission and negatively impacting somatic outcomes. METHODS: Our aim was to test whether smoking status is associated with remission rates and other symptomatic and somatic outcomes. We therefore assessed remission rates according to The Remission in Schizophrenia Working Group (RSWG) criteria, and metabolic and cognitive outcomes among patients with schizophrenia-spectrum disorders treated with clozapine for at least 6 months. For analyses, we grouped our cohort into 3 groups according to clozapine treatment duration (6 months, 2 years, 5 years). RESULTS: One hundred five patients were included in our analyses and grouped according to their clozapine treatment duration. In the 6-months analyses, patients who smoked were significantly more likely to be younger of age (p=0.002) despite on average shorter duration of clozapine treatment (p=0.041) and significantly more likely to be treated with mood-stabilizing co-medication (p=0.030) compared to nonsmokers. Remission rates (p=0.490), as well as a set of metabolic and cognitive variables did not differ between the 2 groups. A related pattern could be observed for the 2- and 5-years analyses. CONCLUSIONS: Smoking behavior among clozapine-treated schizophrenia patients might delineate a cohort with an earlier onset of the disease. Nevertheless, most findings comparing disease-specific and clinical outcomes among smokers and nonsmokers were negative. Further research is needed to identify strategies to overcome insufficient remission rates in this patient group.

16.
Neurophysiol Clin ; 50(4): 301-304, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32631667

RESUMO

Non-invasive transcranial brain stimulation therapies, such as transcranial direct current stimulation, have been found to improve negative symptoms in schizophrenia. Another new technique is transcranial alternating current stimulation (tACS). Here we report a series of three patient treated with twice-daily 10min prefrontal 40Hz tACS stimulation over ten days. Patients showed an improvement in the Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and subjective well-being. Furthermore, there was an improvement in the Trail Making Test and word fluency. ytACS merits further investigation in the treatment of schizophrenia symptoms.

17.
Schizophr Res ; 222: 73-78, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600779

RESUMO

BACKGROUND: Catatonia is a potentially life threatening syndrome in various psychiatric disorders. As first line treatment, benzodiazepines and electroconvulsive therapy (ECT) are recommended. In some cases, benzodiazepines are ineffective and ECT is not available or contraindicated. Therefore, the search for new and alternative treatment strategies is of great importance. OBJECTIVE: To review the evidence for alternative neurostimulation treatment strategies (rTMS and tDCS) for catatonia according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. METHOD: We performed a systematic literature search in several electronic databases. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov database to detect registered studies. RESULTS: We identified nine publications on rTMS treatment and four publications on tDCS in catatonia. Most of the publications reported clinically relevant improvement of catatonic symptoms. Only two publications reported insufficient improvement. The available Bush-Francis Catatonia Rating Scale scores showed statistical significant improvement following rTMS and tDCS. We could not identify any finished clinical studies or case series, dedicated to this topic. We also could not identify any publications that compared first line treatment options with rTMS or tDCS. CONCLUSIONS: Based on the case report literature, rTMS and tDCS might be promising alternative treatment strategies for patients who do not respond to benzodiazepines or in case ECT is not available or contraindicated. There are even hints that rTMS or tDCS might be an option in patients who respond to ECT but need long-term treatment to control catatonic symptoms. Further clinical trials are needed to allow for an evidence-based evaluation of potential risks and benefits of rTMS and tDCS for catatonia.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32594235

RESUMO

Nicotine intake and cortical activity are closely related, as they can influence each other. Nicotine is implicated in the induction and modification of cortical plasticity and excitability, whereas a change on cortical plasticity and excitability can also lead to a modification of the smoking behaviour of an individual. The aim of this systematic review was, on the one hand, to evaluate the effects of nicotinergic modulation on cortical excitability and plasticity, and, on the other hand, to assess if modifying the brain's excitability and plasticity could influence one's smoking behaviour. Two systematic literature searches in the PubMed/MEDLINE and PsycINFO databases were conducted. Studies focusing either on the impact of nicotinergic modulation on cortical activity or the treatment effect of non-invasive brain stimulation techniques (NIBS) on smoking behaviour were included. A total of 22 studies for the first systematic search and 35 studies for the second one were included after full-text screening. Nicotine's effect on cortical activity appeared to depend on smoking status of the individual. While deprived smokers seem to generally profit from nicotine consumption in terms of cortical excitability and plasticity, the contrary was true for non-smokers. Regarding the questions of how changes in cortical excitability can influence smoking behaviour, a trend points towards NIBS being a potential intervention technique for smoking cessation.

20.
Neurocase ; 26(4): 241-247, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32529897

RESUMO

Transcranial direct current stimulation (tDCS) has been explored for treatment of several neuropsychiatric disorders. For tDCS use in structural brain lesions there is some evidence from motor stroke rehabilitation and post-stroke depression. Here we report the application of tDCS in a woman previously diagnosed with schizophrenia presenting refractory auditory verbal hallucinations and left prefrontal tissue lesion. Treatment with 20 left fronto-temporal tDCS had no effect on psychiatric symptoms and neuropsychological evaluation. An ex-post electric field simulation and calculation of dorsolateral prefrontal cortex activation showed lower activation in this patient compared to a matched non-lesioned schizophrenia, and healthy control brain.

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