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Management of cerebral venous thrombosis due to adenoviral COVID-19 vaccination

Ann Neurol. 2022 Jun 10. doi: 10.1002/ana.26431. Online ahead of print.

ABSTRACT

OBJECTIVE: Cerebral venous thrombosis caused by vaccine-induced immune thrombotic thrombocytopenia (VITT-CVT) is a rare adverse effect of adenovirus-based SARS-CoV-2 vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.

METHODS: We used data from an international prospective registry of patients with CVT after adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable or definite VITT-CVT cases included until 18 January 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.

RESULTS: 99 VITT-CVT patients from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11/24 (46%), and 28/37 (76%) of patients diagnosed in March, April, and from May onwards, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 (32%) vs 29/55 (52%), adjusted OR 0.43 (95%CI 0.16-1.19)). However, patients who received immunomodulation had lower mortality (19/65 (29%) vs 24/34 (70%), adjusted OR 0.19 (95%CI 0.06-0.58)). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 (33%) vs 13/35 (37%), adjusted OR 0.70 (95%CI 0.24-2.04)). Mortality was also not significantly influenced by platelet transfusion (17/27 (63%) vs 26/72 (36%), adjusted OR 2.19 (95%CI 0.74-6.54)).

CONCLUSIONS: In VITT-CVT patients, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. This article is protected by copyright. All rights reserved.

PMID:35689346 | DOI:10.1002/ana.26431

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Letter: non-selective beta-blockers in cirrhosis-effect beyond portal hypertension. Authors’ reply

Aliment Pharmacol Ther. 2022 Jul;56(1):186-187. doi: 10.1111/apt.16982.

NO ABSTRACT

PMID:35689317 | DOI:10.1111/apt.16982

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Ileus in patients treated with immune checkpoint inhibitors: a retrospective, pharmacovigilance study using Food and Drug Administration Adverse Event Reporting System (FAERS) database

Pharmacoepidemiol Drug Saf. 2022 Jun 10. doi: 10.1002/pds.5493. Online ahead of print.

ABSTRACT

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have been widely used in cancer treatment; however, some case reports suggested that ICIs treatment might result in ileus. This study aims to comprehensively reveal the relationship between ileus and ICIs treatment in real-world cases from Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

METHODS: Reports from January 1, 2011 to December 31, 2020 were extracted from the FAERS. ICIs-related adverse events in patients were defined as related to use of anti-programmed cell death protein 1 antibodies (PD-1, nivolumab and pembrolizumab), anti-programmed cell death-ligand 1 inhibitors (PD-L1, atezolizumab, durvalumab, avelumab, and cemiplimab), and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, ipilimumab and tremelimumab). ICIs-related ileus cases were identified to characterize their clinical features. Reporting odds ratios (ROR) and information component (IC) were used to assess the relationship between ICIs and ileus.

RESULTS: Among the 105001 cases related to ICIs, 245 were reported with ICI-related ileus. The affected patients were mainly elderly (median age, 64.5 years) and male (58%, n=143). The median onset for all cases was 36 (range 0-880) days, and no statistical difference was observed between monotherapy and combination therapy (PD-1 or PD-L1 plus CTLA-4) (p = 0.21). Most patients required drug withdrawal treatment (n=113, 74%) and can achieve a recovered-resolved state (n=72, 46%). All ICIs were significantly associated with ileus (ROR=4.27, 95%Cl: 3.75-4.85; IC=2.04, 95%Cl: 1.79-2.31). Ileus events were most commonly reported in PD-1 treatment (n=164, ROR=3.83, 95%Cl: 3.28-4.48; IC=1.90, 95%Cl: 1.62-2.21).

CONCLUSION: This pharmacovigilance database analysis suggested that ICIs are related to ileus. However, combination therapy may not speed up the onset of ileus. This article is protected by copyright. All rights reserved.

PMID:35689298 | DOI:10.1002/pds.5493

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Knowledge and willingness of parents towards child girl HPV vaccination in Debre Tabor Town, Ethiopia: a community-based cross-sectional study

Reprod Health. 2022 Jun 10;19(1):136. doi: 10.1186/s12978-022-01444-4.

ABSTRACT

BACKGROUND: Cervical cancer is currently the second-leading cause of cancer death among women in Ethiopia. Vaccination against the human papillomavirus (HPV) is an effective primary prevention strategy for HPV-related illnesses. The knowledge and willingness of parents toward the HPV vaccine are crucial to increasing the uptake of the vaccine. The vaccine’s acceptance by children and young adolescents is dependent on parental consent. Therefore, this study aimed to assess knowledge, willingness, and associated factors of the human papillomavirus vaccine among parents of girls aged 9-14 years at Debre Tabor Town.

METHOD: A community-based cross-sectional study was conducted among participants from December 10, 2020, to January 15, 2021. A simple random sample technique was used to include 638 participants. A structured face-to-face interviewer-administered questionnaire was used to collect data. The data were entered and analyzed using Epi-Data and SPSS software, respectively. Bivariate and multivariable analyses were used to examine the association. The Odds Ratio (OR), 95% CI, and p-values less than 0.05 were used to determine the statistical association.

RESULTS: Thirty-five percent (35.4%, 95% CI = 31.4%, 38.8%) and 44.8% (95% CI = 40.40%, 48.67%) of participants were knowledgeable about HPV vaccination and willing to get it, respectively. Being government employees (AOR = 5.46, 95% CI = 2.42, 9.34), and having a family history of sexually transmitted diseases (STD) (AOR = 1.76, 95% CI = 1.14, 2.72) were significantly associated with knowledge of the human papilloma virus (HPV) vaccine. Participants’ age (AOR = 1.43, 95% CI = 1.16, 2.87), secondary education and above (AOR = 1.70, 95% CI = 1.05, 2.74), fear of HPV infection (AOR = 2.29, 95% CI = 1.21, 4.32), and having good knowledge of the HPV vaccine (AOR = 3.30, 95% CI = 2.21, 4.93) were significantly associated with willingness to receive the HPV vaccine.

CONCLUSION AND RECOMMENDATION: The knowledge and willingness of parents toward the HPV vaccine were low. Then, health officials should boost HPV vaccination promotion through public media. In schools, churches, mosques, and health facilities, health extension workers and health professionals provide information about the HPV vaccine for the parents. Mixed quantitative and qualitative studies are preferable for future research to address “why” issues.

PMID:35689288 | DOI:10.1186/s12978-022-01444-4

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Tissue catabolism and donor-specific dexamethasone response in a human osteochondral model of post-traumatic osteoarthritis

Arthritis Res Ther. 2022 Jun 10;24(1):137. doi: 10.1186/s13075-022-02828-4.

ABSTRACT

BACKGROUND: Post-traumatic osteoarthritis (PTOA) does not currently have clinical prognostic biomarkers or disease-modifying drugs, though promising candidates such as dexamethasone (Dex) exist. Many challenges in studying and treating this disease stem from tissue interactions that complicate understanding of drug effects. We present an ex vivo human osteochondral model of PTOA to investigate disease effects on cartilage and bone homeostasis and discover biomarkers for disease progression and drug efficacy.

METHODS: Human osteochondral explants were harvested from normal (Collins grade 0-1) ankle talocrural joints of human donors (2 female, 5 male, ages 23-70). After pre-equilibration, osteochondral explants were treated with a single-impact mechanical injury and TNF-α, IL-6, and sIL-6R ± 100 nM Dex for 21 days and media collected every 2-3 days. Chondrocyte viability, tissue DNA content, and glycosaminoglycan (sGAG) percent loss to the media were assayed and compared to untreated controls using a linear mixed effects model. Mass spectrometry analysis was performed for both cartilage tissue and pooled culture medium, and the statistical significance of protein abundance changes was determined with the R package limma and empirical Bayes statistics. Partial least squares regression analyses of sGAG loss and Dex attenuation of sGAG loss against proteomic data were performed.

RESULTS: Injury and cytokine treatment caused an increase in the release of matrix components, proteases, pro-inflammatory factors, and intracellular proteins, while tissue lost intracellular metabolic proteins, which was mitigated with the addition of Dex. Dex maintained chondrocyte viability and reduced sGAG loss caused by injury and cytokine treatment by 2/3 overall, with donor-specific differences in the sGAG attenuation effect. Biomarkers of bone metabolism had mixed effects, and collagen II synthesis was suppressed with both disease and Dex treatment by 2- to 5-fold. Semitryptic peptides associated with increased sGAG loss were identified. Pro-inflammatory humoral proteins and apolipoproteins were associated with lower Dex responses.

CONCLUSIONS: Catabolic effects on cartilage tissue caused by injury and cytokine treatment were reduced with the addition of Dex in this osteochondral PTOA model. This study presents potential peptide biomarkers of early PTOA progression and Dex efficacy that can help identify and treat patients at risk of PTOA.

PMID:35689293 | DOI:10.1186/s13075-022-02828-4

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Immediate and six-week effects of wearing a knee sleeve following anterior cruciate ligament reconstruction on knee kinematics and kinetics: a cross-over laboratory and randomised clinical trial

BMC Musculoskelet Disord. 2022 Jun 10;23(1):560. doi: 10.1186/s12891-022-05488-2.

ABSTRACT

BACKGROUND: Elastic knee sleeves are often worn following anterior cruciate ligament reconstruction (ACLR) but their effects on movement patterns are unclear.

AIM: To determine the immediate and six-week effects of wearing a knee sleeve on biomechanics of the knee during a step-down hop task.

METHODS: Using a cross-over design, we estimated sagittal plane knee kinematics and kinetics and stance duration during a step-down hop for 31 participants (age 26.0 [SD 6.6] years, 15 women) after ACLR (median 16 months post-surgery) with and without wearing a knee sleeve. In a subsequent randomised clinical trial, participants in the ‘Sleeve Group’ (n = 9) then wore the sleeve for 6 weeks at least 1 h daily, while a ‘Control Group’ (n = 9) did not wear the sleeve. We used statistical parametric mapping to compare (1) knee flexion/extension angle and external flexion/extension moment trajectories between three conditions at baseline (uninjured side, unsleeved injured side and sleeved injured side); (2) within-participant changes for knee flexion angles and external flexion/extension moment trajectories from baseline to follow-up between groups. We compared discrete flexion angles and moments, and stance duration between conditions and between groups.

RESULTS: Without sleeves, knee flexion was lower for the injured than the uninjured sides during mid-stance phase. When wearing the sleeve on the injured side, knee flexion increased during the loading phase of the stance phase. Discrete initial and peak knee flexion angles increased by (mean difference, 95% CIs) 2.7° (1.3, 4.1) and 3.0° (1.2, 4.9), respectively, when wearing the knee sleeve. Knee external flexion moments for the unsleeved injured sides were lower than the uninjured sides for 80% of stance phase, with no change when sleeved. The groups differenced for within-group changes in knee flexion trajectories at follow-up. Knee flexion angles increased for the Control group only. Stance duration decreased by 22% for the Sleeve group from baseline to follow-up (-89 ms; -153, -24) but not for the Controls.

CONCLUSIONS: Application of knee sleeves following ACLR is associated with improved knee flexion angles during hop landing training. Longer term (daily) knee sleeve application may help improve hop stance duration, potentially indicating improved hop performance.

TRIAL REGISTRATION: The trial was prospectively registered with the Australia New Zealand Clinical Trials Registry No: ACTRN12618001083280, 28/06/2018. ANZCTR.

PMID:35689284 | DOI:10.1186/s12891-022-05488-2

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Biomechanical comparison of the femoral neck system versus InterTan nail and three cannulated screws for unstable Pauwels type III femoral neck fracture

Biomed Eng Online. 2022 Jun 10;21(1):34. doi: 10.1186/s12938-022-01006-6.

ABSTRACT

BACKGROUND: There are a variety of internal fixation methods for unstable femoral neck fractures (FNFs), but the best method is still unclear. Femoral neck system (FNS) is a dynamic angular stabilization system with cross screws, and is a new internal fixation implant designed for minimally invasive fixation of FNFs. In this study, we conducted a biomechanical comparison of FNS, InterTan nail and three cannulated screws for the treatment of Pauwels III FNFs and investigate the biomechanical properties of FNS.

METHODS: A total of 18 left artificial femurs were selected and randomly divide into Group A (fixation with FNS), Group B (fixation with InterTan nail) and Group C (fixation with three cannulated screws), with 6 specimens in each group. After creating Pauwels type III FNF models, the specimens in each were tested with non-destructive quasi-static tests, including torsion, A-P bending and axial compression tests. The average slope of the linear load-deformation curve obtained from quasi-static tests defines the initial torsional stiffness, A-P bending stiffness, and axial compression stiffness. After cyclic loading test was applied, the overall deformation of models and local deformation of implant holes in each group were assessed. The overall deformation was estimated as the displacement recorded by the software of the mechanical testing apparatus. Local deformation was defined as interfragmental displacement. Data were analyzed by one-way analysis of variance (ANOVA) followed by Bonferroni post hoc test using the SPSS software (version 24.0, IBM, New York, NY, USA). Correlation analysis was performed using Pearson’s correlation analysis.

RESULTS: Group B exhibited significantly higher axial stiffness and A-P bending stiffness than the other two groups (P < 0.01), while Group A had significantly higher axial stiffness and A-P bending stiffness than Group C (P < 0.01). Groups A and B exhibited significantly higher torsional stiffness than Group C (P < 0.01), no statistical significance was observed between Groups A and B (P > 0.05). Group B exhibited significantly lower overall and local deformations than the other two groups (P < 0.01), while Group A had significantly lower overall and local deformations than Group C (P < 0.01). Correlation analysis revealed positive correlation between axial stiffness and A-P bending stiffness (r = 0.925, P < 0.01), torsional stiffness (r = 0.727, P < 0.01), between torsional stiffness and A-P bending stiffness; negative correlation between overall, local deformations and axial stiffness (r = – 0.889, – 0.901, respectively, both P < 0.01), and positive correlation between the two deformations (r = – 0.978, P < 0.01).

CONCLUSION: For fixation of unstable FNFs, InterTan nail showed the highest axial stiffness and A-P bending stiffness, followed by FNS, and then three cannulated screws. Torsional stiffness of FNS was comparable to that of the InterTan nail. FNS, as a novel minimally invasive implant, can create good mechanical environment for the healing of unstable FNFs. Clinical studies are needed to confirm the potential advantages of FNS observed in this biomechanical study.

PMID:35689282 | DOI:10.1186/s12938-022-01006-6

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Burden and pattern of acute diarrhea in Thai children under 5 years of age: a 5-year descriptive analysis based on Thailand National Health Coverage (NHC) data

BMC Public Health. 2022 Jun 10;22(1):1161. doi: 10.1186/s12889-022-13598-8.

ABSTRACT

BACKGROUND: The incidence of acute diarrhea in Thai children under five years of age has increased over the last three decades. Even though mortality has significantly declined, the burden and cost of medical treatment are still high. Our objectives are to describe the burden and pattern of acute diarrhea cases that required admissions by Thai children under five years of age from 2015 to 2019.

METHODS: Data regarding the admission of acute diarrhea cases of Thai children with Thailand National Health Coverage (NHC) under five years of age from 2015 to 2019, recorded as International Statistical Classification of Diseases and Related Health Problems, tenth Revision, Thai Modification (ICD-10-TM), were analyzed.

RESULTS: The incidence trend of yearly acute diarrhea in children 0-5 years of age slightly increased from 33.36 cases per 1,000 population in 2010 to an average of 33.79 cases per 1,000 population/ year from 2015 to 2019 or approximately 0.43 cases per 1,000 population over the last decade while diarrhea-related mortality had a low, constant rate of 0.71 to 1.16 per 100,000 population per year. Two thirds of the mortality rate was observed in children under 1 year of age or 4.1 cases per 100,000 person-years in 5-year period (P < 0.01). The high cost of performing the medical treatment of approximately four hundred million baht per year. Seasonal variations demonstrated consistency with similar patterns during the cold and rainy seasons throughout the 5-year period. Regional distribution of the causative agent was also observed in Cholera, Typhoid, and Amoebiasis cases. A08: viral and other specified intestinal infections and A09: other gastroenteritis and colitis of infectious and unspecified origin were the two most common causes of diarrheal diseases.

CONCLUSIONS: The incidence rate of acute diarrhea in Thai children under five years of age was higher while the mortality rate of acute diarrhea was lower than those in the past decade. A similar seasonal outbreak of acute diarrhea was seen during each examined year. The causative agent was not significant and was mainly unspecific.

TRIAL REGISTRATION: Number TCTR20220117002, date of registration: 17/01/2022, site: Thai Clinical Trials Registry, URL http://www.thaiclinicaltrials.org/show/TCTR20220117002.

PMID:35689279 | DOI:10.1186/s12889-022-13598-8

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Compliance with the World Health Organization’s surgical safety checklist and related postoperative outcomes: a nationwide survey among 172 health facilities in Ethiopia

Patient Saf Surg. 2022 Jun 10;16(1):20. doi: 10.1186/s13037-022-00329-6.

ABSTRACT

BACKGROUND: Ministry of Health (MOH) of Ethiopia adopted World Health Organization’s evidence-proven surgical safety checklist (SSC) to reduce the occurrence of surgical complications, i.e., death, disability and prolong hospitalization. MOH commissioned this evaluation to learn about SSC completeness and compliance, and its effect on magnitude of surgical complications.

METHODS: Health institution-based cross-sectional study with retrospective surgical chart audit was used to evaluate SSC utilization in 172 public and private health facilities in Ethiopia, December 2020-May 2021. A total of 1720 major emergency and elective surgeries in 172 (140 public and 32 private) facilities were recruited for chart review by an experienced team of surgical clinicians. A pre-tested tool was used to abstract data from patient charts and national database. Analyzed descriptive, univariable and bivariable data using Stata version-15 statistical software.

RESULTS: In 172 public and private health facilities across Ethiopia, 1603 of 1720 (93.2%) patient charts were audited; representations of public and private facilities were 81.4% (n = 140) and 18.6% (n = 32), respectively. Of surgeries that utilized SSC (67.6%, 1083 of 1603), the proportion of SSC that were filled completely and correctly were 60.8% (659 of 1083). Surgeries compliant to SSC guide achieved a statistically significant reduction in perioperative mortality (P = 0.002) and anesthesia adverse events (P = 0.005), but not in Surgical Site Infection (P = 0.086). Non-compliant surgeries neither utilized SSC nor completed the SSC correctly, 58.9% (944 of 1603).

CONCLUSIONS: Surgeries that adhered to the SSC achieved a statistically significant reduction in perioperative complications, including mortality. Disappointingly, a significant number of surgeries (58.9%) failed to adhere to SSC, a missed opportunity for reducing complications.

PMID:35689263 | DOI:10.1186/s13037-022-00329-6

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Parental care and depressive symptoms among Chinese medical students: roles of empathy and gender

BMC Med Educ. 2022 Jun 11;22(1):451. doi: 10.1186/s12909-022-03524-2.

ABSTRACT

BACKGROUND: Medical students in China who face the dual pressure of study and employment tend to experience subclinical depressive symptoms. Parental care plays an important direct and indirect role in the psychological development of medical students, and the extent and mechanism of this role urgently need to be studied and discussed.

METHODS: After simple random sampling and screening of valid questionnaires, data from a total of 924 people were used. The participants completed the parental bonding instrument, self-rating depression scale, Chinese version of the Jefferson empathy scale-medical student edition and self-rating anxiety scale to evaluate parental care, empathy, depressive symptoms and anxiety. The data were statistically processed using a descriptive analysis, correlation analysis and test of moderated mediation.

RESULTS: Maternal care had a significant negative predictive effect on depressive symptoms among medical students. Strong maternal care can reduce the occurrence of depressive symptoms in medical students. Empathy played a positive mediating role such that both types of empathy could alleviate the effect of weak maternal care on the depressive symptoms of medical students. However, neither cognitive empathy nor affective empathy played a mediating role in the relationship between paternal care and depressive symptoms. Nevertheless, the relationship between maternal care and empathy was moderated by the medical students’ gender.

CONCLUSIONS: The effect of this relationship on female medical students deserves special attention. The results of this study provide a reference and basis for the adjustment of medical education. This study could also help in the design of effective psychological intervention measures to reduce the degree of depressive symptoms and enhance personal empathy.

PMID:35689260 | DOI:10.1186/s12909-022-03524-2