A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy.

Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP ( https://www.ncbi.nlm.nih.gov/snp/ ), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein-protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene-miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein-Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, L-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein-Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information.

Attention Deficits in Healthcare Workers with Non-Clinical Burnout: An Exploratory Investigation.

Burnout syndrome is characterized by exhaustion, cynicism, and reduced effectiveness. Workers with high burnout scores who continue their professional activities are identified as experiencing non-clinical burnout (NCB), which includes early stages where burnout symptoms (BNS) are present but not yet severe enough to necessitate work leave. This study aimed to investigate the impact of BNS on attention performance among healthcare workers (HCWs) at a COVID-19 reference hospital during the pandemic. The Maslach Burnout Inventory (MBI) was applied to assess the three burnout dimensions. The Continuous Visual Attention Test (CVAT) evaluated four different attention subdomains. Participants were divided into two groups based on their scores on the MBI: controls and NCB. Thirteen controls were matched with 13 NCB subjects based on age, sex, and HCW category. This sample (n = 26, 65% male) consisted of 11 physicians and 15 nursing professionals with a mean age of 35.3 years (standard deviation = 5.47). NCB subjects had higher impulsivity than controls. There were not any significant group differences in the other attention subdomains. We found significant correlations between impulsivity and all burnout dimensions: higher absolute scores in BNS are associated with higher impulsivity. We concluded that NCB leads to executive attention deficits.

General low alertness in people with obstructive sleep apnea.

STUDY OBJECTIVES: In patients with obstructive sleep apnea (OSA), a previous study using a Go/No-Go task reported an average attention deficit. However, the temporal dynamics of such a deficit are unknown. Here, we investigated whether attention deficits in different subdomains increased as the test progressed. We also investigated the effect of target frequency and speed of stimulus presentation on performance. METHODS: Twenty-seven untreated people with OSA and 27 age- and sex-matched controls underwent a 15-minute Go/No-Go task, divided into 6 blocks. Each block was subdivided into 3 different interstimulus intervals (1, 2, and 4 seconds). Three blocks had a low and three had a high target probability (20% and 80%, respectively). Reaction time (alertness), variability of reaction time (sustained attention), commission errors (response inhibition), and omission errors (focused attention) were measured. RESULTS: Alertness was lower in the group with OSA compared with controls, as evidenced by a significantly higher average reaction time. This effect was seen from the start of the task and continued until the end but did not increase in test progression. The temporal pattern of intrinsic alertness deficits in patients with OSA was found to be independent of target frequency or interstimulus interval. CONCLUSIONS: The primary attention problem in OSA is on the alertness subdomain irrespective of the number of required responses or speed of stimulus presentation. The present results support the notion that OSA is distinct from other neurological and psychiatric conditions, such as depression or chronic pain. The results also suggest significant concerns regarding daily life activities (eg, driving). CITATION: de Souza Bezerra ML, van Duinkerken E, Simões E, Schmidt SL. General low alertness in people with obstructive sleep apnea. J Clin Sleep Med. 2024;20(5):689-698.

Cognitive Performance in Asymptomatic Elderly People with Hepatitis C: The Role of Education.

BACKGROUND: Neurotropism of the hepatitis C virus (HCV) can be the source of subtle neuropsychological symptoms in non-cirrhotic patients. Age is a risk factor for cognitive impairment (CI). Thus, asymptomatic elderly people who carry HCV might be at a greater risk of CI. Education can influence test performance. OBJECTIVES: (1) To verify whether elderly people with HCV performed poorer than controls on cognitive tests. (2) To analyze how education affects performance. (3) To verify whether the extent of the effect of education on performance depends on the group (HCV vs. controls) and the type of cognitive test. METHODS: Asymptomatic HCV carriers older than 60 years (n = 41) were matched with 41 corresponding controls. All participants performed the following tests: Mini-Cog, Mini Mental State Examination, clock drawing test (CDT), and verbal fluency. RESULTS: (1) There were no significant differences in cognitive performance between the two groups. (2) Higher education was always associated with better performance. (3) There was a significant group difference in the slopes of the regression lines between years of education and CDT performance. No differences were found for the other three tests. CONCLUSION: Considering the scores on the CDT, the rate of improvement in performance when schooling increases is higher in HCV carriers.

Hepatitis C Virus (HCV) Infection and Neurocognitive Impairment in Subjects with Mild Liver Disease.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma, and liver-related deaths. It is estimated that 40-74% of patients with hepatitis C will experience at least one extrahepatic manifestation within their lifetime. The finding of HCV-RNA sequences in post-mortem brain tissue raises the possibility that HCV infection may affect the central nervous system and be the source of subtle neuropsychological symptoms, even in non-cirrhotic. Our investigation aimed to evaluate whether asymptomatic, HCV-infected subjects showed cognitive dysfunctions. Twenty-eight untreated asymptomatic HCV subjects and 18 healthy controls were tested using three neuropsychological instruments in a random sequence: Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association Test (COWAT), and Continuous Visual Attention Test (CVAT). We performed depression screening, liver fibrosis assessment, blood tests, genotyping, and HCV-RNA viral load. A MANCOVA and univariate ANCOVAS were performed to examine group differences (HCV vs. healthy controls) in four scores of the CVAT (omission errors, commission errors, reaction time-RT, and variability of RT-VRT), and the scores derived from the SDMT, and the COWAT. A discriminant analysis was performed to identify which test variables effectively discriminate HCV-infected subjects from healthy controls. There were no group differences in the scores of the COWAT, SDMT, and in two variables of the CVAT (omission and commission errors). In contrast, the performance of the HCV group was poorer than the controls in RT (p = 0.047) and VRT (p = 0.046). The discriminant analysis further indicated that the RT was the most reliable variable to discriminate the two groups with an accuracy of 71.7%. The higher RT exhibited by the HCV group may reflect deficits in the intrinsic-alertness attention subdomain. As the RT variable was found to be the best discriminator between HCV patients and controls, we suggest that intrinsic-alertness deficits in HCV patients may affect the stability of response times increasing VRT and leading to significant lapses in attention. In conclusion, HCV subjects with mild disease showed deficits in RT and intraindividual VRT as compared to healthy controls.

Comparing online and face-to-face administration of a neuropsychological computerized attention test: Assessment modality does not influence performance.

Background: The cognitive impairment associated with the COVID-19 pandemic highlighted the need for teleneuropsychology (1). Moreover, neurologic diseases associated with mental deterioration usually require the use of the same neuropsychological instrument to assess cognitive changes across time. Therefore, in such cases, a learning effect upon retesting is not desired. Attention and its subdomains can be measured using Go/no-go tests, such as, the Continuous Visual Attention Test (CVAT). Here, we administered the CVAT to investigate the effect of modality (online vs. face-to-face) on attentional performance. The variables of the CVAT measures four attention domains: focused-attention, behavioral-inhibition, intrinsic-alertness (reaction time, RT), and sustained-attention (intra-individual variability of RTs, VRT). Methods: The CVAT was applied face-to face and online in 130 adult Americans and 50 adult Brazilians. Three different study designs were used: (1) Between-subjects design: healthy Americans were tested face-to-face (n = 88) or online (n = 42). We verified if there were any differences between the two modalities. (2) Within-subjects design: Brazilians participants (n = 50) were tested twice (online and face-to-face). For each CVAT variable, repeated measures ANCOVAs were performed to verify whether modality or first vs. second tests differ. Agreement was analyzed using Kappa, intraclass correlation coefficients, and Bland-Altman plots. (3) Paired comparisons: we compared Americans vs. Brazilians, pairing subjects by age, sex, and level of education, grouping by modality. Results: Assessment modality did not influence performance using two independent samples (between-subjects design) or the same individual tested twice (within-subjects design). The second test and the first test did not differ. Data indicated significant agreements for the VRT variable. Based on paired samples, Americans did not differ from Brazilians and a significant agreement was found for the VRT variable. Conclusion: The CVAT can be administered online or face-to-face without learning upon retesting. The data on agreement (online vs. face-to-face, test vs. retest, Americans vs. Brazilians) indicate that VRT is the most reliable variable. Limitations: High educational level of the participants and absence of a perfect balanced within-subjects design.

COVID-19 Patients with Early Gastrointestinal Symptoms Show Persistent Deficits in Specific Attention Subdomains.

Previous studies have shown that COVID-19 inpatients exhibited significant attentional deficits on the day of discharge. However, the presence of gastrointestinal symptoms (GIS) has not been evaluated. Here, we aimed to verify: (1) whether COVID-19 patients with GIS exhibited specific attention deficits; (2) which attention subdomain deficits discriminated patients with GIS and without gastrointestinal symptoms (NGIS) from healthy controls. On admission, the presence of GIS was recorded. Seventy-four physically functional COVID-19 inpatients at discharge and sixty-eight controls underwent a Go/No-go computerized visual attentional test (CVAT). A Multivariate Analysis of Covariance (MANCOVA) was performed to examine group differences in attentional performance. To discriminate which attention subdomain deficits discriminated GIS and NGIS COVID-19 patients from healthy controls, a discriminant analysis was applied using the CVAT variables. The MANCOVA showed a significant overall effect of COVID-19 with GIS on attention performance. The discriminant analysis indicated that the GIS group could be differentiated from the controls by variability of reaction time and omissions errors. The NGIS group could be differentiated from controls by reaction time. Late attention deficits in COVID-19 patients with GIS may reflect a primary problem in the sustained and focused attention subsystems, whereas in NGIS patients the attention problems are related to the intrinsic-alertness subsystem.

Association between attention performance and the different dimensions of DSM-5 depression symptoms.

Objective: Depressive symptoms can be assessed with self-reported questionnaires, such as the Patient Health Questionary-9 (PHQ-9). Previous studies have suggested that the PHQ-9 items can be grouped into somatic and non-somatic clusters. However, the classification of the PHQ-9 item "concentration difficulties" into somatic or non-somatic is still controversial. This controversy may be explained by difficulties experienced by subjects in accurately evaluating their attention problems. The primary objective of this study was to determine the correlation between objective attentional performance and the two clusters of depressive symptoms in hospital employees working in stressful conditions. Methods: The participants filled out the PHQ-9 to identify their depressive symptoms. Based on the PHQ-9, the somatic or non-somatic symptoms were measured without considering the question about subjective concentration difficulties. Then, a brief version of the Continuous Visual Attention Test (CVAT) was applied to assess four attentional subdomains. The CVAT is a Go/No-go task that measures number of correct responses (focused attention), number of incorrect responses (behavior-inhibition), average reaction time of correct responses (RT-alertness), and variability of reaction time (VRT-sustained attention). The entire task lasted 90 s. Correlation analyses assessed the relationships between attentional performance and the two dimensions of depressive symptoms. Results: After applying the inclusion/exclusion criteria, 359 individuals were selected. Their age ranged from 20 to 70 years (mean = 40.5, SD = 10.37), and the majority was female (67.6%). A predominance in somatic depressive symptoms was present in 231 (64%) participants, whereas 59 (16%) showed a predominance of non-somatic symptoms. Sixty-nine participants (20%) did not show any predominance. Higher somatic scores were associated with higher RTs, whereas higher non-somatic scores were related to an increase in the number of incorrect responses. Conclusion: The predominance of the somatic cluster was related to lower alertness, whereas the predominance of non-somatic cluster was associated with impulsivity/hyperactivity. This result may explain the difficulties associated with correctly classifying the item concentration difficulties. A brief attentional task can be used as an auxiliary tool to correctly identify the different dimensions of attention that are associated with different clusters of depressive symptoms.

Attention deficits in Brazilian health care workers with chronic pain.

The impact of COVID-19 on chronic pain (CP) in non-infected vulnerable South American subjects is unknown. Healthcare workers (HCWs) are at increased risk for CP. During the pandemic, many HCWs with CP kept working. Knowing how cognition is affected by CP in these subjects is an important subject for work safety. The attention domain has a pivotal role in cognition. Previously, the Continuous Visual Attention Test (CVAT) was applied to detect specific attention deficits in fibromyalgia patients. The present investigation described CP prevalence in non-infected Brazilian HCWs during the pandemic and assessed HCWs' attentional performance with the aid of the CVAT. This study was carried out at a reference University Hospital in Rio de Janeiro, Brazil. HCWs of both sexes, aged 20 or older, were interviewed from August to December 2020. A 90-second version of the CVAT was performed. The average reaction time to correct responses and the respective intraindividual reaction time variability for correct responses to target (VRT) was determined. Omission and commission errors were also calculated. Then, for each participant we calculated the Z-scores of the CVAT variables based on the distribution of CVAT performance of 211 healthy subjects (reference-comparison group). HCWs with Z-scores > 1.64 were classified as significantly impaired. From the 154 selected HCWs, 72 reported CP during the pandemic (prevalence = 47%). Post hoc ANCOVAs showed that the average correct VRT was significantly higher in the CP group than in the non-CP group (F = 4.99, df = 1/150, p = 0.027, η2 = 0.032). The percentage of participants with impaired VRT performance was 30% (n = 21) in the CP group and 16% (n = 13) in the non-CP group. The difference between these two propositions reached significance (χ2 = 3.96, df = 1, p = 0.047). As VRT is associated with the sustained-attention subdomain, our data suggest that this subdomain is disrupted in the CP group.

Incidence of Postoperative Cognitive Dysfunction Following Inhalational vs Total Intravenous General Anesthesia: A Systematic Review and Meta-Analysis.

Postoperative cognitive dysfunction (POCD) has been increasingly recognized as a contributor to postoperative complications. A consensus-working group recommended that POCD should be distinguished between delayed cognitive recovery, ie, evaluations up to 30 days postoperative, and neurocognitive disorder, ie, assessments performed between 30 days and 12 months after surgery. Additionally, the choice of the anesthetic, either inhalational or total intravenous anesthesia (TIVA) and its effect on the incidence of POCD, has become a focus of research. Our primary objective was to search the literature and conduct a meta-analysis to verify whether the choice of general anesthesia may impact the incidence of POCD in the first 30 days postoperatively. As a secondary objective, a systematic review of the literature was conducted to estimate the effects of the anesthetic on POCD between 30 days and 12 months postoperative. For the primary objective, an initial review of 1913 articles yielded ten studies with a total of 3390 individuals. For the secondary objective, four studies with a total of 480 patients were selected. In the first 30 days postoperative, the odds-ratio for POCD in TIVA group was 0.46 (95% CI = 0.26-0.81; p = 0.01), compared to the inhalational group. TIVA was associated with a lower incidence of POCD in the first 30 days postoperatively. Regarding the secondary objective, due to the small number of selected articles and its high heterogeneity, a metanalysis was not conducted. Given the heterogeneity of criteria for POCD, future prospective studies with more robust designs should be performed to fully address this question.

Spirituality as a protective factor for chronic and acute anxiety in Brazilian healthcare workers during the COVID-19 outbreak.

BACKGROUND: Anxiety symptoms (AS) are exacerbated in healthcare workers (HCWs) during the COVID-19 pandemic. Spirituality is known to protect against AS in the general population and it is a construct that differs from religion. It can be assessed using structured questionnaires. A validated questionnaire disclosed three spirituality dimensions: peace, meaning, and faith. In HCWs we investigated the predictors of chronic anxiety (pre-COVID-19 and during the pandemic) and acute anxiety (only during the pandemic), including spirituality in the model. Then, we verified which spirituality dimensions predicted chronic and acute anxiety. Lastly, we studied group differences between the mean scores of these spirituality dimensions. MATERIAL AND METHODS: The study was carried out in a Brazilian Hospital. HCWs (n = 118) were assessed for spirituality at a single time-point. They were also asked about AS that had started pre-COVID-19 and persisted during the pandemic (chronic anxiety), and AS that had started only during the pandemic (acute anxiety). The subjects without chronic anxiety were subdivided into two other groups: acute anxiety and without chronic and acute anxiety. Forward stepwise logistic regressions were used to find the significant AS predictors. First, the model considered sex, age, religious affiliation, and spirituality. Then, the analysis were performed considering only the three spirituality dimensions. Group means differences in the spirituality dimensions were compared using univariate ANCOVAS followed by T-tests. RESULTS: Spirituality was the most realible predictor of chronic (OR = 0.818; 95%CI:0.752-0.890; p<0.001) and acute anxiety (OR = 0.727; 95%CI:0.601-0.881; p = 0.001). Peace alone predicted chronic anxiety (OR = 0.619; 95%CI:0.516-0.744; p<0.001) while for acute anxiety both peace (OR:0.517; 95%CI:0.340-0.787; p = 0.002), and faith (OR:0.674; 95%CI:0.509-0.892; p = 0.006) significantly contributed to the model. Faith was significantly higher in subjects without AS. CONCLUSION: Higher spirituality protected against chronic and acute anxiety. Faith and peace spirituality dimensions conferred protection against acute anxiety during the pandemic.

Post-COVID-19 olfactory dysfunction: carbamazepine as a treatment option in a series of cases.

Olfactory dysfunction is reported frequently in patients with coronavirus disease 2019. However, an effective treatment for this dysfunction is unknown. The present study evaluated carbamazepine as a treatment option for olfactory dysfunction based on its use in cases of neuralgia, especially of the V cranial nerve. The study included 10 patients with coronavirus disease with olfactory complaints who were part of a cohort of 172 coronavirus disease patients monitored for late neurological manifestations. Carbamazepine was administered for 11 weeks. The adverse effects reported were drowsiness (9/10) and dizziness (2/10); 9 of the 10 patients reported improved olfactory function after carbamazepine treatment. While the role of carbamazepine in the control of post-coronavirus disease olfactory dysfunction could not be confirmed in this study, the satisfactory response observed in most patients in this series suggests that further studies are warranted.

Attention profile of physically recovered COVID-19 inpatients on the day of discharge.

Few studies have reported specific attention deficits in post-COVID-19 patients. Attention consists of different subdomains. Disruptions to specific attention subdomains might impair a wide range of everyday tasks, including road safety. As there are millions of COVID-19 patients with different socio-economic backgrounds, screening of attentional performance less dependent on education is needed. Here, we verified if physically recovered COVID-19 inpatients showed specific attention decrements at discharge. The Continuous Visual Attention Test (CVAT) is a Go/No-go task which is independent of participants' schooling. It detects visuomotor reaction time (RT = intrinsic alertness), variability of reaction time (VRT = sustained attention), omission (focused-attention), and commission errors (response-inhibition). Thirty physically functional COVID-19 inpatients at discharge and 30 non-infected controls underwent the CVAT. A MANCOVA was performed to examine differences between controls and patients, followed by post-hoc ANCOVAs. Then, we identified the percentile score for each patient within the distribution of the CVAT performance of 211 subjects mentally capable of driving (reference group). COVID-19 patients at discharge showed greater RT and VRT, and more omission errors than controls. Twenty-two patients (73%) had performance below the 5th percentile of the reference group in one or more subdomains. As slow visuomotor RT, deficits in focusing and difficulties in keeping visual attention are associated with traffic accidents, we concluded that most COVID-19 patients at discharge had deficits that may increase the risk of road injuries. As these deficits will probably affect other daily activities, a routine assessment with the CVAT could provide useful information on whom to send to post-COVID centers.

Allopurinol for fibromyalgia pain in adults: A randomized controlled trial.

BACKGROUND: Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used in the treatment of hyperuricemia and gout. Because it is well known that purines exert multiple affects on pain transmission, we hypothesized that the inhibition of xanthine oxidase by allopurinol could be a valid strategy to treat pain in humans. This study aimed to compare the analgesic efficacy of oral allopurinol versus placebo as an adjuvant therapy in patients displaying fibromyalgia. METHODS: This randomized, double-blinded, placebo-controlled study included 60 women with the diagnosis of fibromyalgia. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 31) or placebo (n = 29) twice daily during 30 days. The patients were submitted to evaluation for pain sensitivity, anxiety, depression, and functional status before treatment, and 15 and 30 days thereafter. RESULTS: Oral administration of allopurinol 300 mg twice daily was ineffective in improving pain scores measured by several tools up to 30 days of treatment (P > 0.05). Additionally, no significant effects of allopurinol over anxiety, depressive symptoms, and functional status of fibromyalgia patients were observed in the present study. CONCLUSIONS: Although previous findings indicated that allopurinol could present intrinsic analgesic effects in both animals and humans, this study showed no benefit of the use of oral allopurinol as an adjuvant strategy during 30 days in women displaying fibromyalgia. However, considering previous promising results, new prospective studies are still valid to further investigate allopurinol and more selective purine derivatives in the management of pain syndromes.

Cerebellar Symptoms in Gluten Sensitivity: a Systematic Review of the Effect of a Gluten-Free Diet on Brain Imaging.

Cerebellar manifestations have been described in patients with gluten sensitivity (GS)-related disorders. A better understanding of the neurological manifestations of GS requires the use of neuroimaging techniques. We performed a systematic review on neuroimaging findings in GS patients with cerebellar symptoms. We also included a specific search on neuroimaging findings in GS patients with cerebellar manifestations on a gluten-free diet (GFD). PubMed, Embase, and Bireme were systematically searched to identify studies assessing neuroimaging features of adults with cerebellar manifestations and GS with or without enteropathy on a GFD. Ten studies with a total of 222 adult-GS patients were included. Magnetic resonance imaging was used in 100% of the studies. Cerebellar atrophy was evaluated in 7 studies and observed in 63% of the patients. White matter abnormalities were described in 2 studies. Single-photon emission computed tomography was used in 2 studies, and decreased cerebellar perfusion was detected in 92% of the included patients. No study employed nuclear medicine after the start of GFD. Magnetic resonance spectroscopy (MRS) was performed in 2 studies before and after GFD. An increase in the Naa/Cr ratio in cerebellar vermis was seen in 98% of the cases on a strict GFD. Cerebellar atrophy was found to be a prevalent condition in GS patients. MRS demonstrated to be useful in the follow-up of GS patients with cerebellar manifestations on a GFD. Prospective studies using nuclear medicine imaging are needed to study brain changes in GS patients on a GFD.

Allopurinol attenuates postoperative pain and modulates the purinergic system in patients undergoing abdominal hysterectomy: a randomized controlled trial.

PURPOSE: Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used primarily in the treatment of hyperuricemia and gout. The aim of this study was to compare the analgesic efficacy of preanesthetic allopurinol versus placebo on postoperative pain and anxiety in patients undergoing abdominal hysterectomy. METHODS: This is a prospective, double-blinded, placebo-controlled, randomized clinical trial. We investigated 54 patients scheduled to undergo elective abdominal hysterectomy. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 27) or placebo (n = 27) the night before and 1 h before surgery. Patients were submitted to evaluation of pain and anxiety before the treatment, for 24 h postoperatively, 30 and 90 days after surgery. Cerebrospinal fluid was collected at the time of the spinal anesthesia to perform the measurement of the central levels of purines. RESULTS: Preoperative administration of allopurinol was effective in reducing postoperative pain 2 h after surgery. Allopurinol caused a reduction of approximately 40% in pain scores measured by the visual analogue pain scale after surgery (p < 0.05). No differences were found between groups in anxiety scores after surgery. There was a significant change in the cerebrospinal fluid concentrations of xanthine and uric acid before surgery (p < 0.01). CONCLUSION: This study showed a short-term benefit of the use of allopurinol as a preanesthetic medication since it was related to a reduction on pain scores 2 h after surgery. The purinergic system is a potential target for new analgesic drugs. New studies investigating more selective purine derivatives in the management of pain should be performed. TRIAL NUMBER REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC #RBR-9pw58p.

Assessment of Attentional Functioning in Health Professionals of a Brazilian Tertiary Referral Hospital for COVID-19.

This study is aimed at assessing differences in basic attentional functioning between substantial and minimal work-related exposure to COVID-19 patients in professionals working in a tertiary referral hospital in Rio de Janeiro, Brazil. Therefore, hospital employees performed a Continuous Visual Attention Test. This test consisted of a 90-second Go/No-Go task with 72 (80%) targets and 18 (20%) nontargets. For each participant, reaction time and intraindividual variability of reaction times of all correct target responses, as well as the number of omission and commission errors, were evaluated. Participants were divided into 2 groups based on their exposure to COVID-19 patients (substantial versus minimal exposure). The substantial exposure group consisted of participants with 24 hours/week or more direct contact with COVID-19 patients. This cut-off was based on the clear division between professionals working and not working with COVID-19 patients and considered that 12-hour and 24-hour daily shifts are common for hospital employees in Brazil. A MANCOVA was performed to examine between-group differences, using age, sleep quality, sex, education level, previous COVID-19 infection, and profession as covariates. Of 124 participants, 80 had substantial exposure and 44 had minimal exposure to COVID-19. The overall MANCOVA reached statistical significance (P = 0.048). Post hoc ANCOVA analysis showed that the substantial exposure group had a statistically significantly higher intraindividual variability of reaction time of all correct target responses (P = 0.017, Cohen's δ = -0.55). This result remained after removing those with a previous COVID-19 infection (P = 0.010, Cohen's δ = -0.64) and after matching groups for sample size (P = 0.004, Cohen's δ = -0.81). No other variables reached statistical significance. Concluding, hospital professionals with a substantial level of exposure to patients with COVID-19 show a significant attention decrement and, thus, may be at a higher risk of accidental SARS-CoV-2 infection.

The role of the purinergic system in the acupuncture-induced analgesia / O papel do sistema purinérgico na analgesia induzida pela acupuntura

ABSTRACT BACKGROUND AND OBJECTIVES: Musculoskeletal disorders and acute and chronic pain are the main causes of disability. Acupuncture is a safe and well-tolerated treatment, and the understanding of the physiological basis of its effectiveness in the management of acute and chronic painful conditions is growing. The objective of this study was to describe the main components of the purinergic system involved in the acupuncture-mediated analgesia. CONTENTS: Review the literature relevant to the terms "acupuncture", "purinergic system", "purines", "pain" and "analgesia" found on the Pubmed platform. CONCLUSION: Several previous studies have shown relevant roles of purines and their derivatives on acupuncture-mediated analgesia, displaying promising results in the knowledge of the potential biological benefits of acupuncture. New experimental and clinical studies are warranted to further investigate the purinergic mechanisms involved in the acupuncture-mediated analgesia, addressing potential therapeutic benefits of acupuncture in different clinical settings.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os distúrbios musculoesqueléticos e a dor aguda e crônica são as principais causas de incapacidade. A acupuntura é um tratamento seguro e bem tolerado, e o entendimento sobre a base fisiológica de sua eficácia para o tratamento de quadros dolorosos agudos e crônicos está crescendo. O objetivo deste estudo foi descrever os principais componentes do sistema purinérgico envolvidos na analgesia mediada pela acupuntura. CONTEÚDO: Revisar a literatura pertinente aos temas "acupuntura", "sistema purinérgico", "purinas", "dor" e "analgesia" encontrados na plataforma Pubmed. CONCLUSÃO: Diversos estudos prévios têm evidenciado efeitos relevantes das purinas e seus derivados na analgesia mediada pela acupuntura, demonstrando resultados promissores no conhecimento dos potenciais benefícios biológicos da acupuntura. A ampliação da investigação dos mecanismos purinérgicos envolvidos na acupuntura deverá ser garantida por meio de novos estudos experimentais e clínicos, abordando potenciais benefícios terapêuticos da acupuntura em diversos cenários clínicos.