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Cognition and Memory after Covid-19 in a Large Community Sample

N Engl J Med. 2024 Feb 29;390(9):806-818. doi: 10.1056/NEJMoa2311330.

ABSTRACT

BACKGROUND: Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

METHODS: We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (“brain fog”).

RESULTS: Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

CONCLUSIONS: Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).

PMID:38416429 | DOI:10.1056/NEJMoa2311330

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Evaluation of the Status of Patients with Autoimmune Bullous Diseases (Pemphigus and Bullous Pemphigoids) in Dermatology Clinics of Mashhad University of Medical Sciences During the COVID-19 Pandemic Using Telemedicine

Telemed J E Health. 2024 Feb 27. doi: 10.1089/tmj.2023.0395. Online ahead of print.

ABSTRACT

Background: The COVID-19 pandemic impacted the growth of telemedicine. The challenge was in the way of dermatologists, who needed a comprehensive examination of the lesions. Here, we tried a tele-management of patients with autoimmune bullous diseases. Methods: This cross-sectional study was conducted on confirmed bullous disorder cases. Demographic data and the status of COVID-19 infection were assessed in the patients. Some of the cases were provided online, and some with office visits. Drug and treatment plan changes were compared between these two groups. All statistical analysis was conducted using SPSS version 20. Result: Totally, 100 patients, including 46 males (46.0%) and 54 females (54.0%), 48.15 ± 11.11 years old, were studied. Among them, 73 were pemphigus vulgaris (73.0%), 11 were bullous pemphigoid (11.0%), 10 were pemphigus foliaceus (10.0%), and the other 6 (6.0%) were categorized as other autoimmune bullous diseases. During the pandemic, 38 cases (38.0%) had COVID-19 infection. 72 patients had office and 28 had online visits. Treatment plans after visits during the pandemic (p = 0.588) and drug dose change (p = 0.297) showed no significant difference between office and online visits. Conclusion: Our patients tended to plan office visits more than online; however, we found no differences regarding the plan or treatment changes. Online visit has good efficacy, but further investigation in case of provision of a suitable platform and getting the attention of the patients is needed.

PMID:38416427 | DOI:10.1089/tmj.2023.0395

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New autophagy-modulating lanostane-type triterpenoids from a hallucinogenic poisonous mushroom Gymnopilus orientispectabilis

Arch Pharm Res. 2024 Feb 28. doi: 10.1007/s12272-024-01486-1. Online ahead of print.

ABSTRACT

Gymnopilus orientispectabilis, also known as “big laughter mushroom,” is a hallucinogenic poisonous mushroom that causes excessive laughter upon ingestion. From the fruiting bodies of G. orientispectabilis, eight lanostane-type triterpenoids (1-8), including seven novel compounds: gymnojunols A-G (2-8), were isolated. The chemical structures of these new compounds (2-8) were determined by analyzing their 1D and 2D NMR spectra and HR-EISMS, and their absolute configurations were unambiguously assigned by quantum chemical ECD calculations and a computational method coupled with a statistical procedure (DP4+). Upon evaluating autophagic activity, compounds 2, 6, and 7 increased LC3B-II levels in HeLa cells to a similar extent as bafilomycin, an autophagy inhibitor. In contrast, compound 8 decreased the levels of both LC3B-I and LC3B-II, and a similar effect was observed following treatment with rapamycin, an autophagy inducer. Our findings provide experimental evidence for new potential autophagy modulators in the hallucinogenic poisonous mushroom G. orientispectabilis.

PMID:38416389 | DOI:10.1007/s12272-024-01486-1

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Comparison of Adverse Events Between PARP Inhibitors in Patients with Epithelial Ovarian Cancer: A Nationwide Propensity Score Matched Cohort Study

Target Oncol. 2024 Feb 28. doi: 10.1007/s11523-024-01037-0. Online ahead of print.

ABSTRACT

BACKGROUND: Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce.

OBJECTIVE: This study aimed to compare the safety of different PARPi in patients with EOC.

PATIENTS AND METHODS: Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence.

RESULTS: In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26-0.98] and 0.09 [0.01-0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots.

CONCLUSIONS: No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.

PMID:38416378 | DOI:10.1007/s11523-024-01037-0

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Brain identification of IBS patients based on GBDT and multiple imaging techniques

Phys Eng Sci Med. 2024 Feb 28. doi: 10.1007/s13246-024-01394-0. Online ahead of print.

ABSTRACT

The brain biomarker of irritable bowel syndrome (IBS) patients is still lacking. The study aims to explore a new technology studying the brain alterations of IBS patients based on multi-source brain data. In the study, a decision-level fusion method based on gradient boosting decision tree (GBDT) was proposed. Next, 100 healthy subjects were used to validate the effectiveness of the method. Finally, the identification of brain alterations and the pain evaluation in IBS patients were carried out by the fusion method based on the resting-state fMRI and DWI for 46 patients and 46 controls selected randomly from 100 healthy subjects. The results showed that the method can achieve good classification between IBS patients and controls (accuracy = 95%) and pain evaluation of IBS patients (mean absolute error = 0.1977). Moreover, both the gain-based and the permutation-based evaluation instead of statistical analysis showed that left cingulum bundle contributed most significantly to the classification, and right precuneus contributed most significantly to the evaluation of abdominal pain intensity in the IBS patients. The differences seem to suggest a probable but unexplored separation about the central regions between the identification and progression of IBS. This finding may provide one new thought and technology for brain alteration related to IBS.

PMID:38416373 | DOI:10.1007/s13246-024-01394-0

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ACROMORFO study: gait analysis in a cohort of acromegalic patients

J Endocrinol Invest. 2024 Feb 28. doi: 10.1007/s40618-024-02340-3. Online ahead of print.

ABSTRACT

PURPOSE: In acromegaly, skeletal complications resulted to be associated with low quality of life (QoL) and high risk of falls. The aim of the present study was to perform a quantitative assessment of movement through gait analysis technique in patients with acromegaly.

STUDY POPULATION: Thirty-three acromegalic patients [9 with active disease (AD), 14 with controlled disease (CD) and 10 with disease remission (RD)] and 20 healthy subjects were enrolled for the study.

MEASUREMENTS: Kinetic and kinematic data were collected with 3D-gait analysis. Kinematic data were processed to compute the Gait Profile Score (GPS), a parameter that summarizes the overall deviation of kinematic gait data relative to unaffected population.

RESULTS: The acromegalic group showed longer stance phase duration (p < 0.0001) compared to controls. The GPS and several gait variable scores resulted to be statistically higher in the acromegalic group compared to healthy controls. GPS values were significantly higher in AD compared to CD (p < 0.05) and RD groups (p = 0.001). The AD group presented significantly higher values in terms of hip rotation and ankle dorsiflexion compared to CD and RD groups and with regard to the foot progression compared to RD. Interestingly, patients with RD exhibited a more physiological gait pattern.

CONCLUSION: Acromegalic patients showed quantitative alterations of gait pattern, suggesting instability and increased risk of falls. Arthropathy, along with its associated abnormal joint loading, proprioceptive impairment and hyperkyphosis could be contributing factors. Disease control and remission appear to improve postural balance. A better knowledge on walking performance in acromegaly would help to develop specific rehabilitation programmes to reduce falls’ risk and improve QoL.

PMID:38416368 | DOI:10.1007/s40618-024-02340-3

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Diagnostic performance of blue laser imaging for early detection of gastric cancer: A systematic review and meta-analysis

Indian J Gastroenterol. 2024 Feb 28. doi: 10.1007/s12664-023-01495-w. Online ahead of print.

ABSTRACT

BACKGROUND: Gastric cancer (GC) is associated with a significant global health burden and high mortality rates when diagnosed at later stages. The diagnosis often occurs at advanced stages when treatment options are limited and less effective. Early detection strategies are crucial to improving survival rates and outcomes for patients. Blue laser imaging (BLI) is an image-enhanced endoscopy technique that utilizes white light and narrow-band light to detect pathological changes in the mucosal architecture. This study aims at investigating the diagnostic performance of BLI for the detection of GC.

METHODS: A comprehensive search was conducted across multiple databases from inception until March 2023. Studies assessing the diagnostic efficacy of BLI for GC detection were included. The sensitivity, specificity and accuracy of BLI were calculated using pooled proportions and 95% confidence intervals (CI) with a random-effects model. Heterogeneity among the included studies was assessed using the I2 statistic.

RESULTS: Six studies were included in the pooled analysis. There were 708 patients with 380 GC lesions. Most of the lesions involved the lower two-thirds of the stomach. The pooled performance metrics of BLI for GC detection were as follows: sensitivity of 91.9% (95% CI 83.3-96.3%; I2 = 82.3%), specificity of 93.4% (95% CI 82.0-97.8%; I2 = 87.9%) and accuracy of 95.4% (95% CI 72.6-99.8%; I2 = 73.6%).

CONCLUSION: BLI demonstrates high diagnostic efficacy for the detection of GC. BLI can be a valuable tool in clinical practice. However, large-scale, randomized controlled studies are needed to further establish the role of BLI in routine clinical practice for GC detection.

PMID:38416344 | DOI:10.1007/s12664-023-01495-w

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Spatial Cluster Change of Schistosoma japonicum Transmission Foci in Indonesia During the Schistosomiasis Elimination Program

Acta Parasitol. 2024 Feb 28. doi: 10.1007/s11686-024-00802-5. Online ahead of print.

ABSTRACT

PURPOSE: The Government of Indonesia committed to eliminating schistosomiasis by 2025. Collaboratively snail control became one of the crucial strategies to ensure that the prevalence of Schistosoma japonicum in Oncomelania hupensis lindoensis reaches zero by the end of the program. This research investigated the spatial cluster change of S. japonicum transmission foci in Indonesia between 2017 and 2021.

METHODS: We mapped the snail foci, collected the snails, and calculated the snail density. We also conducted laboratory tests to detect the existence of cercariae in the snails. Identified infected snails were used to calculate the infection rate (IR) or snails’ prevalence of schistosome cercariae among freshwater snails. We then analysed the spatial cluster using the Getis-Ord Gi* statistic to identify the hot and cold spots.

RESULTS: The 5-year schistosomiasis elimination program successfully declined 18.84% of the snail foci and reduced 40.37% of the infected snail foci. Local spatial autocorrelation of snail density and infection rate identified that in 2017 and 2021, the number of cold spots decreased by 53.91% and 0%, while hot spots increased by 2.63% and 56.1%. The presence of more hot spots suggests a rise in the number of foci with high snail density and infection rates. The implementation of snail control was not optimal, and the parasite transmission through domestic animals still existed, causing the spatial cluster of hot spots to change during this period. Most hotspots have been observed near settlements, primarily in cocoa plantations, developed and deserted rice fields, grassland, and bush wetlands.

CONCLUSION: During the schistosomiasis elimination program, the number of hot spots increased while cold spots decreased, and there were notable changes in the geographical distribution of hot spots, indicating a shift in the clustering pattern of schistosomiasis cases. The findings become essential for policymakers, particularly in selecting priority areas for intervention. In the Discussion section, we demonstrated the selection process based on the existence of hot and cold spots. Furthermore, we proposed that enhancing cross-sector integration is crucial, particularly in connection with the management of S. japonicum transmission through domestic animals.

PMID:38416327 | DOI:10.1007/s11686-024-00802-5

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Evaluation of Effectiveness of the Unplugged Program on Gambling Behaviours among Adolescents: Study Protocol of the Experimental Controlled Study “GAPUnplugged”

J Prev (2022). 2024 Feb 28. doi: 10.1007/s10935-024-00772-4. Online ahead of print.

ABSTRACT

Gambling risk behaviour is an emerging problem among adolescents. “Unplugged” is an effective Social Influence curriculum for preventing substance use among students. This study aims to develop and test a new component focused on gambling added to the Unplugged program. Schools of Piedmont region and Rome city were invited to participate in the study. A self-completed anonymous questionnaire including questions on socio-demographic characteristics, addictive behaviours, beliefs, attitudes and risk perceptions about gambling, normative perceptions, parental practices, school climate, refusal skills, impulsiveness, self-esteem, antisocial behaviours and sensation seeking was prepared for baseline and follow-up surveys. The protocol of the study was submitted and approved by the Novara Ethical Committee and registered in ClinicalTrials.gov (NCT05630157, Protocol ID: 080.742, 11/17/2022). Twenty-nine schools accepted to participate in the study. Sixty-three classes (1325 students) satisfied the eligibility criteria for intervention and were allocated to the intervention arm, and the other 61 (1269 students) were allocated to the control arm. Because of drop-out, absentees, refusals, and invalid questionnaires, data on 1874 students (998 in the intervention and 876 in the control arm), were available for the analysis at baseline. Data management of follow-up questionnaires is in progress. Results of the present study will be useful to clarify the effectiveness of prevention interventions in reducing gambling behaviours among adolescents. Moreover, this will be the first experience of evaluating a new component focused on a different risk behaviour, added to a curriculum previously shown as effective on other risk behaviours.

PMID:38416313 | DOI:10.1007/s10935-024-00772-4

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Recent Advances in Clinical Trials in Multiple System Atrophy

Curr Neurol Neurosci Rep. 2024 Feb 28. doi: 10.1007/s11910-024-01335-0. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by parkinsonism, cerebellar, and autonomic dysfunction. It also describes the preclinical therapeutic pipeline and provides some considerations relevant to successfully conducting clinical trials in MSA, i.e., diagnosis, endpoints, and trial design.

RECENT FINDINGS: Over 30 compounds have been tested in clinical trials in MSA. While this illustrates a strong treatment pipeline, only two have reached their primary endpoint. Ongoing clinical trials primarily focus on targeting α-synuclein, the neuropathological hallmark of MSA being α-synuclein-bearing glial cytoplasmic inclusions. The mostly negative trial outcomes highlight the importance of better understanding underlying disease mechanisms and improving preclinical models. Together with efforts to refine clinical measurement tools, innovative statistical methods, and developments in biomarker research, this will enhance the design of future neuroprotection trials in MSA and the likelihood of positive outcomes.

PMID:38416311 | DOI:10.1007/s11910-024-01335-0