bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes After Transcutaneous Bone-Conduction Implantation in Adults and Children
Authors: Harris Micah K. , Kaul Vivian F. , Bergman Maxwell , Dodson Edward E. , Ren Yin , Adunka Oliver F.
Published: January 2023

Objective

To evaluate clinical and audiometric outcomes of adult and pediatric patients implanted with a semi-implantable transcutaneous active bone-conduction implant.

Study Design

Retrospective chart review.

Setting

Two tertiary referral centers.

Patients

Subjects implanted with the semi-implantable transcutaneous active bone-conduction implant called BoneBridge.

Intervention

Implantation of the BoneBridge and audiometric evaluations.

Main Outcome Measures

Audiometric, clinical, and surgical outcomes as well as complications.

Results

Forty-two adults and 20 children were implanted for conductive or mixed hearing loss as well as single-sided deafness. Implantation significantly improved mean air-conduction pure-tone average from 72.8 ± 22.3 to 35 ± 9 dB in adults and from 65.7 ± 24.3 to 19.6 ± 8.2 dB in children (both p < 0.001). Word recognition score improved from 63.7 ± 38.8% to 85.6 ± 10.6% in adults and 57.8 ± 38% to 89.3 ± 10.1% in children (both p < 0.05). The rate of revision surgery was 11.3%, with four patients (6.5%) undergoing removal for device-related complications, two (3.2%) for complications associated with implantation, and one (1.6%) for device failure secondary to external trauma.

Conclusions

In a large retrospective series consisting of both pediatric and adult patients, implantation with a transcutaneous active bone-conduction implant was found to be a reliable aural rehabilitation option for a variety of hearing loss etiologies.
Comparing the Use of High-Dose to Standard-Dose Corticosteroids for the Treatment of Bell’s Palsy in Adults—A Systematic Review and Meta-analysis
Authors: Gupta Keshav Kumar , Balai Edward , Tang Ho Tsun , Ahmed Abiya Amna , Doshi Jayesh R.
Published: January 2023

Objective

Bell’s palsy is typically treated with oral corticosteroids (40–60 mg daily). Concomitant antivirals are currently not recommended. The objective of this systematic review and meta-analysis was to examine the effect of high-dose versus standard-dose corticosteroids, without antivirals, in the management of Bell’s palsy.

Databases Reviewed

Embase, MEDLINE, PubMed, CINAHL, Cochrane Library.

Methods

A systematic review and meta-analysis was performed according to PRISMA guidelines. Studies comparing high-dose (≥80 mg) or standard-dose (40–60 mg) corticosteroid therapy for Bell’s palsy were included. Exclusion criteria were coexisting antiviral treatment, nonoral drug delivery, and facial palsy due to other causes. Risk of bias was assessed using ROBINS-I. A weighted estimate of treatment effects across trials as odds ratios (OR) using a Mantel–Haenzel random-effects model was calculated.

Results

Three articles were included in the analysis, representing 485 patients. There was a significant decrease in nonrecovery with high-dose, compared with standard-dose, corticosteroids at 6 months follow-up (OR = 0.17, 95% confidence interval = 0.05–0.56, p = 0.004). Overall adverse events were 5.8% (n = 28), all reported in one study in the high-dose group (transient elevated liver enzymes and fecal occult blood).

Conclusions

Our analysis shows a favorable effect of high-dose corticosteroid in the treatment of Bell’s palsy. It is the first to evaluate this effect without the use of antivirals in keeping with current treatment recommendations. As all included studies had a serious risk of bias, future research should focus on larger trials with more robust methodology. This will allow for more up-to-date and large-scale analyses where more valid conclusions can be drawn that may potentially influence treatment protocols.
What does quantitative HBsAg level mean in chronic hepatitis D infection?
Authors: Ebik Berat , Cangul M. Sadik , Yalçin Kendal
Published: January 2023

Objective

In hepatitis delta virus (HDV) infection, which is an important etiological cause of chronic liver disease, the relationship between serum quantitative HBsAg level and fibrosis and histological activity was investigated.

Methods

Between 2014 and 2020, 98 patients with chronic HDV infection (53 noncirrhotic, 45 cirrhotic) participated in this prospectively designed study. Quantitative HBsAg levels of the patients were measured and their relationship with the stage of chronic liver disease was compared with histological activity index (HAI), fibrosis score and HDV RNA, model for end-stage liver disease score and other biochemical parameters.

Results

All patients were infected with genotype 1 (100%). HBeAg was positive in 8 (8.1%) of the patients. A correlation was found between quantitative HBsAg level and HDV RNA level in patients with both cirrhotic (r = 0.568; P < 0.001) and noncirrhotic (r = 0.644; P < 0.001) HDV infection. Alanine transaminase (P = 0.001; r = 0.495) and aspartate transaminase (P = 0.001; r = 0.511) levels correlated with quantitative HBsAg levels, more prominently in noncirrhotic patients. There was a correlation between quantitative HBsAg level and histological activity index (HAI) in patients with noncirrhotic HDV infection (P < 0.001; r = 0.664). In receiver operating characteristic analysis, both quantitative HBsAg (for cutoff: 1000; sensitivity 76%; specificity 17%; P = 0.335) and HDV RNA (for cutoff: 100000; sensitivity 2%; specificity 98%; P = 0.096) were not predictive markers for cirrhosis.

Conclusion

Quantitative HBsAg level can be evaluated as an indicator of viral replication and histological activity in patients with chronic delta hepatitis without cirrhosis. We think that quantitative HBsAg level will be useful in the management of chronic HDV infection, especially in noncirrhotic patients.
Contrast-enhanced ultrasound pattern of hepatocellular carcinoma in noncirrhotic liver – results from the prospective multicentre DEGUM CEUS HCC study
Authors: Schellhaas Barbara , Jesper Daniel , Strobel Deike ,   DEGUM CEUS HCC Study Group.
Published: January 2023

Objectives

Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. However, as HCC in noncirrhosis becomes an emerging clinical concern, our study aimed to assess the diagnostic value of CEUS and the CEUS algorithms CEUS LI-RADS and ESCULAP in noncirrhotic liver in a prospective multicentre real-life setting.

Methods

High-risk patients for HCC with focal liver lesions upon B-mode ultrasound were recruited prospectively in a multicentre real-life approach to undergo standardized CEUS. Diagnostic accuracies of CEUS and the CEUS algorithms were assessed for the sub-collective of noncirrhotic patients. Histology, MRI and CT served as the reference standard.

Results

In total 47/517 patients were noncirrhotic. The reference standard of the lesions showed 30 HCCs (63.8%), four intrahepatic cholangiocellular carcinomas (iCCAs), two other malignancies and 11 benign lesions. HCCs in noncirrhosis showed a tendency towards larger tumor size and better differentiation. A typical CEUS pattern of arterial phase hyperenhancement and late-onset (>60 s), mild washout occurred in 22/30 HCCs (73.3%). Very late onset of washout > 4–6 min was not seen in noncirrhotic liver. The CEUS algorithm ESCULAP showed a perfect sensitivity (100 vs. 68% with CEUS LI-RADS), whereas CEUS LI-RADS had a superior specificity (83 vs. 53%). The positive predictive value was high with both algorithms.

Conclusion

The CEUS patterns of HCCs in noncirrhotic liver resembled those in cirrhosis. Our findings suggest that although designed for the application in cirrhosis only, the diagnostic accuracies of the CEUS algorithms in noncirrhotic liver seem comparable to the findings in cirrhosis.
Nomogram model for predicting esophsagogastric varices in hepatocellular carcinoma with cirrhosis
Authors: Zhang Daoming , Deng Junjian , Guo Xufeng , Zheng Yongfa , Xu Ximing
Published: January 2023

Background/aims

The prognosis for hepatocellular carcinoma (HCC) with cirrhosis is poor. The risk of death also increases in patients with esophagogastric varices (EGV). Based on routine clinical features and related noninvasive parameters, a nomogram prediction model was developed in this study to facilitate the early identification of EGV in HCC patients.

Methods

A retrospective cohort analysis of patients with HCC in the Renmin Hospital of Wuhan University from 2020 to 2021 was performed. Clinical and noninvasive parameters closely related to EGV risk were screened by univariate and multivariate logistic regression analysis and integrated into a nomogram. The nomogram was validated internally and externally by calibration, receiver operating characteristic curve and decision curve analysis (DCA).

Results

A total of 165 patients with HCC-related cirrhosis were recruited. In the raining cohort, multivariate logistic regression analysis identified platelet (PLT) [odds ratio (OR), 0.950; 95% confidence interval (CI), 0.925–0.977; P < 0.001], D-dimer (OR. 3.341; 95% CI, 1.751–6.376, P < 0.001), spleen diameter (SD) (OR, 2.585; 95% CI, 1.547–4.318; P < 0.001) as independent indicators for EGV. The nomogram for predicting EGV risk was well calibrated with a favorable discriminative ability and an area under curve of 0.961. In addition, the nomogram showed better net benefits in the DCA. The results were validated in the validation cohort.

Conclusions

The proposed nomogram model based on three indicators (PLT, D-dimer and SD) showed an excellent predictive effect, leading to the avoidance of unnecessary esophagogastroduodenoscopy.
Impact of metformin on the incidence of human cholangiocarcinoma in diabetic patients: a systematic review and meta-analysis
Authors: Laffusa Alice , Ciaccio Antonio , Elvevi Alessandra , Gallo Camilla , Ratti Laura , Invernizzi Pietro , Massironi Sara
Published: January 2023

Cholangiocarcinoma (CCA) is the second most common liver cancer. Diabetes is a well-known risk factor; however, treatment with metformin has been reported to be protective for several cancers, but data on CCA are still sparse and heterogeneous. We performed this meta-analysis to investigate the role of metformin as a potential protective factor for CCA. In this systematic review and meta-analysis, we searched PubMed/MEDLINE and EMBASE databases, from the date of inception to November 2022, for studies analyzing CCA rate in patients taking metformin. Twenty-nine articles were initially identified, of which four were eligible and included in our systematic review and meta-analysis, from which we estimated the relative risk (RR). The rate of CCA was lower for diabetic patients taking metformin than diabetic patients without metformin intake when comparing two highest quality studies [RR, 0.38; 95% confidence interval (CI), 0.290–0.508; P < 0.001], and three studies with similar inclusion criteria (RR, 0.34; 95% CI, 0.51–0.35; P < 0.001) without significant statistical heterogeneity among them (I
2 = 29.83%, P = 0,2326 and I
2 = 35.08%; P = 0.2143, respectively). Our study demonstrated a significant impact of metformin in reducing the risk of CCA by nearly 62–66% in diabetic patients taking metformin.
Infectious mononucleosis is associated with an increased incidence of Crohn’s disease: results from a cohort study of 31 862 outpatients in Germany
Authors: Loosen Sven H. , Kostev Karel , Schöler David , Orth Hans-Martin , Freise Noemi F. , Jensen Björn-Erik Ole , May Petra , Bode Johannes G. , Roderburg Christoph , Luedde Tom
Published: January 2023

Objective

The pathogenesis of inflammatory bowel disease (IBD) has not been fully uncovered to date. Epstein-Barr-Virus (EBV) infection has recently been associated with the pathogenesis of multiple sclerosis, suggesting a general link between EBV and autoimmune diseases. However, data on an association between EBV and IBD have remained inconclusive. This study aims at evaluating an association between EBV and the development of IBD.

Methods

This retrospective cohort study included 15 931 patients with and 15 931 matched patients without infectious mononucleosis from the Disease Analyzer database (IQVIA) between 2000 and 2018. Incidences of Crohn’s disease and ulcerative colitis were evaluated using Cox regression models.

Results

Within 5 years of the index date, the cumulative incidence of IBD was 124 and 90 cases per 100 000 person-years among patients with and without infectious mononucleosis, respectively (P = 0.040). In regression analyses, infectious mononucleosis was significantly associated with IBD [hazard ratios (HR), 1.35; 95% confidence interval (CI), 1.01–1.81]. Subgroup analyses revealed an association between infectious mononucleosis and Crohn’s disease (HR, 1.93; 95% CI, 1.22–3.05) but not ulcerative colitis (HR, 1.03; 95% CI, 0.70–1.51). This association was strongest in patients between 14 and 20 years (HR, 4.50; 95% CI, 1.55–13.13) and was only observed in females (HR, 2.51; 95% CI, 1.39–4.53).

Conclusion

Infectious mononucleosis is significantly associated with an increased incidence of Crohn’s disease but not ulcerative colitis, especially in young female patients. Our data support the hypothesis of a pathophysiological involvement of EBV in the development of Crohn’s disease and should trigger molecular research to further dissect the pathophysiology of IBD.
Outcomes of immunomodulator and advanced therapies for primary sclerosing cholangitis-associated inflammatory bowel disease
Authors: Sayed Amr , Assis David N. , Silveira Marina G. , Deng Yanhong , Ciarleglio Maria , Gaidos Jill K.J. , Proctor Deborah D. , Al-Bawardy Badr
Published: January 2023

Background

Inflammatory bowel disease (IBD) coexists in up to 80% of patients with primary sclerosing cholangitis (PSC). The aim of this study is to investigate the outcomes of immunomodulator (IMM)/advanced therapies for the treatment of PSC-IBD.

Methods

This was a single-center, retrospective study of patients with PSC from 1 January 2012 to 1 April 2021. Adult patients (age ≥ 18 years) with PSC-IBD were included. Primary outcomes were rates and predictors of IMM/advanced therapies to treat PSC-IBD. Secondary outcomes included rates of cholangitis, PSC-IBD clinical remission, and endoscopic healing.

Results

A total of 106 patients with PSC were reviewed and 72 (68%) with confirmed PSC-IBD were included in the study. The median age was 48 years (IQR, 33–59.5) and 69.4% were male. Overall, 28 patients (38.9%) required IMM/advanced therapies to treat PSC-IBD (22 biologic/small molecule therapy and six thiopurine monotherapy). Patients in the IMM/advanced therapies group were more likely to have small bowel involvement (32.1% vs. 4.6%; P = 0.002). In the IMM/advanced therapies group, clinical remission was achieved in 78.6% but endoscopic healing in only 50%. The rate of acute ascending cholangitis was 42.9% in the IMM/advanced therapies group compared with 31.8% in the non-IMM/advanced therapies group (P = 0.34).

Conclusion

In our cohort, up to a third of patients with PSC-IBD required IMM/advanced therapies with only 50% of these patients achieving endoscopic healing. The use of IMM/advanced therapies was not associated with a higher risk of cholangitis, but larger studies are needed to investigate the risk with different classes of advanced therapies.
Clinical characteristics and quality of life in patients with inflammatory bowel disease-associated anemia in Southeast China
Authors: Xue Mengli , Chen Jintong , Zheng Weiwei , Liu Yijuan , Lin Yijuan , Wang Chengdang
Published: January 2023

Background/aims

Clinical characteristics of inflammatory bowel disease (IBD) with anemia have not been fully elucidated. This study aimed to investigate the frequency of, risk factors for, and management of anemia in IBD patients and to evaluate the quality of life (QOL) in IBD patients with anemia.

Methods

We included two patient cohorts. In cohort 1, clinical data from 697 IBD patients were retrospectively collected. In cohort 2, the Short Form-36 Health Survey (SF-36) and Fatigue Scale-14 (FS-14) questionnaires for IBD patients were completed to evaluate the QOL.

Results

Anemia was present in 35.6% of IBD patients [38.2% of Crohn’s disease (CD) patients vs. 29.3% of ulcerative colitis (UC) patients, P = 0.025]. Elevated platelet (PLT) count (CD: OR, 1.004; 95% CI, 1.001–1.007; P = 0.007; UC: OR, 1.010; 95% CI, 1.004–1.016; P = 0.001), elevated erythrocyte sedimentation rate (ESR) (CD: OR, 1.024; 95% CI, 1.012–1.036; P < 0.001; UC: OR, 1.025; 95% CI, 1.001–1.051; P = 0.044), and lower albumin levels (CD: OR, 0.801; 95% CI, 0.749–0.857; P < 0.001; UC: OR, 0.789; 95% CI, 0.720–0.864; P < 0.001) were associated with anemia. Among the IBD patients with anemia, only 25.8% received treatment for anemia. IBD patients with anemia had significantly lower SF-36 scores (P = 0.011) and higher FS-14 scores (P = 0.026) than those without anemia.

Conclusion

Anemia is common in IBD patients. Elevated PLT count and ESR are risk factors for anemia in IBD patients. Anemia may negatively impact IBD patients’ QOL, but few anemia patients receive treatment for anemia.
Successful Retransplantation With Killer Cell Immunoglobulin-like Receptor Ligand-mismatched Cord Blood in Infant Acute Lymphoblastic Leukemia That Relapsed After Transplantation
Authors: Mizuki Kazuyoshi , Honda Yuko , Asai Hiroshi , Higuchi Naoko , Morita Hiromi , Yabe Hiromasa , Kusuhara Koichi
Published: January 2023

The prognosis of children with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) remains dismal. This report describes the successful retransplantation of a patient with infant ALL who relapsed both bone marrow and central nervous system. The patient received HLA-matched cord blood transplantation (CBT) and relapsed 18 months later. After achieving the second remission, the patient received a killer cell immunoglobulin-like receptor ligand-mismatched CBT with a reduced-intensity conditioning regimen and has been in remission for 52 months. Thus, killer cell immunoglobulin-like receptor ligand-mismatched CBT with reduced-intensity conditioning might be a treatment option for patients with KMT2A-r ALL who relapsed after transplantation, even with extramedullary relapse.
Ovarian Clear Cell Carcinoma and Markers of Epithelial-Mesenchymal Transition (EMT): Immunohistochemical Characterization of Tumor Budding
Authors: Lin Lawrence Hsu , Zamuco Ronaldo DeLeon , Shukla Pratibha S.
Published: January 2023

Tumor budding, largely considered a manifestation of epithelial-mesenchymal transition (EMT) is an established prognostic marker for several cancers. In a recent study, tumor budding was associated with poor clinical outcomes in early-stage ovarian clear cell carcinoma. Here, we evaluated the immune expression of 3 proteins shown to be associated with EMT (E-cadherin, β-catenin, and glypican-3) in 72 primary tumors of ovarian clear cell carcinoma with median follow-up of 39.47 mo. E-cadherin and β-catenin expression was further evaluated in tumor buds in 29 (40%) cases. In the tumor mass, diffuse membranous expression of E-cadherin and β-catenin was seen in 83% (60/72) and 81% (58/72) cases, respectively. Nuclear accumulation of E-cadherin was seen in 7 (10%) cases, while none of the cases showed nuclear β-catenin expression. Glypican-3 expression was diffuse in 33.3% (24/72), patchy in 29.2% (21/72), and absent in 37.5% (27/72) cases. Evaluation of tumor buds showed aberrant patterns of expression (complete loss/cytoplasmic accumulation/diminished, discontinuous incomplete membranous staining) of E-cadherin in 29/29 (100%) and of β-catenin in 26/29 (90%) cases. E-cadherin, β-catenin, and glypican-3 expression in the main tumor mass had no association with stage, lymph node status, recurrent/progressive disease, status at last follow-up, survival and histopathologic features (P>0.05). Our finding of aberrant expression of both E-cadherin and β-catenin in tumor buds indicates involvement of Wnt signaling pathway/EMT in tumor budding and outlines its significance as a prognostic marker especially for early-stage ovarian clear cell carcinoma.
Equitable Healthy Aging in Community Health Improvement Practice
Authors: Black Kathy , Levine Marissa , Veal Britney
Published: January 2023

The Equitable Healthy Aging in Public Health Toolkit provides local health departments with guidance on advancing equitable healthy aging in community health improvement practice. The toolkit includes modules on foundational principles such as social justice, social determinants of health and intersectionality across the life course, age-friendly public health frameworks, and evidence-based actions to advance equitable healthy aging in community health improvement infrastructure, assessment, implementation planning, and practice. The toolkit is based on contemporaneous public health knowledge and practice on healthy aging and health equity along with advisory input from the Trust for America's Health and the National Association of City and County Health Officials. The toolkit was informed by Florida Department of Health practitioners (n = 79) and further vetted and well received with a statewide master class of public health leaders (n = 29). The toolkit is publicly available and free of charge.
Educational Interventions for Newly Diagnosed Patients With Inflammatory Bowel Disease
Authors: Navarro-Correal Ester , Ibarz Arantxa , Basagaña-Farres Míriam , Feijoo-Cid María , Espart Anna , Selva Laia
Published: January 2023

The latest consensus standards for patients with inflammatory bowel disease published by the European Crohn's and Colitis Organisation conclude that optimizing quality of care in inflammatory bowel disease involves information and education after diagnosis. A scoping review was performed to identify educational interventions in newly diagnosed inflammatory bowel disease patients. A systematic literature search was conducted using five databases and gray literature. Inclusion criteria were studies with at least one group of patients whom were less than 2 years from their initial inflammatory bowel disease diagnosis. The review process initially identified 447 articles, resulting in four relevant studies: three randomized controlled trials and one pre-/post-test. Only one study exclusively included newly diagnosed inflammatory bowel disease patients. All studies included a multidisciplinary assessment and three were based on a group intervention, but none of them was described in enough detail to be replicated. The content was the same for all patients regardless of the time elapsed since diagnosis. Education of newly diagnosed patients does not seem to be a priority given the lack of publications meeting our criteria despite the evidence of their need. Interventions and outcomes are heterogeneous. Interventions did not consider patient needs and suggest that they centered more on the professional than on the patient. More evidence is clearly needed about this topic.
Comparing the Effect of Incentive Spirometry and Deep Breathing Exercises on the Level of Shoulder Pain and Nausea Following Laparoscopic Cholecystectomy Surgery
Authors: Bastamizad Nasrin , Abbasi Parvin , Salari Nader , Jalali Rostam
Published: January 2023

Cholecystitis treated by laparoscopy results in patients experiencing shoulder pain and nausea. Thus, the aim of the present study was to compare the effect of incentive spirometry and deep breathing exercises on the level of shoulder pain and nausea following laparoscopy. In this clinical trial, 105 patients were enrolled into three groups: use of incentive spirometry, deep breathing exercises, and control. Data were collected using a checklist and a visual analog scale and analyzed through the χ2, the Kruskal–Wallis, the Friedman, and the paired t test by SPSS Version 25. In the deep breathing exercise, incentive spirometry, and control groups, mean pain scores immediately after surgery but within 24 hours following the intervention were 3.8, 2.6, and 4.4, respectively. The mean score of severity of nausea for patients in the deep breathing exercise and incentive spirometry groups showed a significant difference immediately after the procedure, as well as at 12 and 24 hours post-intervention. Breathing exercises and incentive spirometry can be effective in reducing pain and nausea in patients undergoing cholecystectomy through laparoscopy. Because of the effectiveness of the two methods, nurses can use incentive spirometery and deep breathing exercises to diminish patients' pain post-cholecystectomy.
The Reparative Roles of IL-33
Authors: Bou Saba Johnny , Turnquist Hēth R.
Published: January 2023

When discovered in the early 2000s, interleukin-33 (IL-33) was characterized as a potent driver of type 2 immunity and implicated in parasite clearance, as well as asthma, allergy, and lung fibrosis. Yet research in other models has since revealed that IL-33 is a highly pleiotropic molecule with diverse functions. These activities are supported by elusive release mechanisms and diverse expression of the IL-33 receptor, STimulation 2 (ST2), on both immune and stromal cells. Interestingly, IL-33 also supports type 1 immune responses during viral and tumor immunity and after allogeneic hematopoietic stem cell transplantation. Yet the IL-33–ST2 axis is also critical to the establishment of systemic homeostasis and tissue repair and regeneration. Despite these recent findings, the mechanisms by which IL-33 governs the balance between immunity and homeostasis or can support both effective repair and pathogenic fibrosis are poorly understood. As such, ongoing research is trying to understand the potential reparative and regulatory versus pro-inflammatory and pro-fibrotic roles for IL-33 in transplantation. This review provides an overview of the emerging regenerative role of IL-33 in organ homeostasis and tissue repair as it relates to transplantation immunology. It also outlines the known impacts of IL-33 in commonly transplanted solid organs and covers the envisioned roles for IL-33 in ischemia-reperfusion injury, rejection, and tolerance. Finally, we give a comprehensive summary of its effects on different cell populations involved in these processes, including ST2+ regulatory T cells, innate lymphoid cell type 2, as well as significant myeloid cell populations.
Anticholinergic Drug Burden and Risk of Incident MCI and Dementia
Authors: Gildengers Ariel , Stoehr Gary P. , Ran Xinhui , Jacobsen Erin , Teverovsky Esther , Chang Chung-Chou H. , Ganguli Mary
Published: January 2023

Objective:

We investigated whether anticholinergic drug use was related to developing mild cognitive impairment (MCI) or dementia in older adults at the population level.

Methods:

We used an Anticholinergic Rating (ACR) scale, Clinical Dementia Rating, APOE genotype, and number of prescription medications. We examined time to incident MCI and incident dementia in a population-based cohort (n=1959). We assessed whether developing MCI or dementia was associated with (1) any anticholinergic drug use, (2) total ACR score, or (3) number of anticholinergic drugs taken.

Results:

Taking any anticholinergic drug was significantly associated with higher risk of developing MCI; however, higher ACR score or higher number of anticholinergic drugs, compared with lower, were not associated with greater risk of developing MCI. We found no significant relationship between anticholinergic use and developing dementia. The relationship between anticholinergic use and cognitive outcome was not affected by APOE genotype.

Conclusions:

Among cognitively normal older adults in a population-based sample, anticholinergic drug use is independently associated with subsequently developing MCI, but not dementia. Thus, anticholinergic drug use may influence risk of MCI that is nonprogressive to dementia and potentially be a modifiable risk factor for MCI.
Potential cost-effectiveness of individualized medicine in prodromal Alzheimer’s disease by demographic, clinical and cerebrospinal fluid proteomics factors
Authors: Handels Ron , Wesenhagen Kirsten , Tijms Betty , Teunissen Charlotte , Visser Pieter Jelle , Jönsson Linus
Published: January 2023

INTRODUCTION

Three distinct pathophysiological subtypes of Alzheimer’s disease (AD) have been identified based on CSF proteomics. We aim to estimate the potential incremental cost-effectiveness ratio of individualized hypothetical AD pharmacological treatment through stratification by these subtypes.

METHODS

In a model-based health-economic evaluation usual care was compared to A) hypothetical treatment to in all subtypes and B) hypothetical treatment to those categorized as subtype 1 (high levels of BACE1) based on CSF proteomics; in a population of persons with MCI and positive amyloid and assuming hypothetical treatment efficacy in this subtype 1 only.

RESULTS

The potential incremental cost-effectiveness ratio (ICER) was k€36 per quality-adjusted life year (QALY) for strategy A (no subtyping test, hypothetical treatment in all subtypes) as compared to usual care, and k€22 for strategy B (subtyping and hypothetical treatment for subtype 1 only) as compared to usual care. Compared to strategy A, strategy B was dominant, in terms of no difference in QALY and mean cost savings of k€6 per person.

DISCUSSION

Given the assumptions in this study, individualized hypothetical AD pharmacological treatment of specific subgroups of AD patients, here based on a proteomics biomarker profile, has the potential to gain health-economic benefits. Future research should focus on retrospective analysis of trial data to generate empirical evidence on treatment effect between CSF proteomics subgroups.
Longitudinal home self-collection of capillary blood usinghomeRNA correlates interferon and innate viral defense pathways with SARS-CoV-2 viral clearance
Authors: Lim Fang Yun , Kim Soo-Young , Kulkarni Karisma N. , Blazevic Rachel L. , Kimball Louise E. , Lea Hannah G. , Haack Amanda J. , Gower Maia. S. , Stevens-Ayers Terry , Starita Lea M. , Boeckh Michael , Schiffer Joshua T. , Hyrien Ollivier , Theberge Ashleigh B. , Waghmare Alpana
Published: January 2023

Blood transcriptional profiling is a powerful tool to evaluate immune responses to infection; however, blood collection via traditional phlebotomy remains a barrier to precise characterization of the immune response in dynamic infections (e.g., respiratory viruses). Here we present an at-home self-collection methodology,homeRNA, to study the host transcriptional response during acute SARS-CoV-2 infections. This method uniquely enables high frequency measurement of the host immune kinetics in non-hospitalized adults during the acute and most dynamic stage of their infection. COVID-19+ and healthy participants self-collected blood every other day for two weeks with daily nasal swabs and symptom surveys to track viral load kinetics and symptom burden, respectively. While healthy uninfected participants showed remarkably stable immune kinetics with no significant dynamic genes, COVID-19+ participants, on the contrary, depicted a robust response with over 418 dynamic genes associated with interferon and innate viral defense pathways. When stratified by vaccination status, we detected distinct response signatures between unvaccinated and breakthrough (vaccinated) infection subgroups; unvaccinated individuals portrayed a response repertoire characterized by higher innate antiviral responses, interferon signaling, and cytotoxic lymphocyte responses while breakthrough infections portrayed lower levels of interferon signaling and enhanced early cell-mediated response. Leveraging cross-platform longitudinal sampling (nasal swabs and blood), we observed thatIFI27, a key viral response gene, tracked closely with SARS-CoV-2 viral clearance in individual participants. Taken together, these results demonstrate that at-home sampling can capture key host antiviral responses and facilitate frequent longitudinal sampling to detect transient host immune kinetics during dynamic immune states.

One Sentence Summary

Self-blood collection usinghomeRNA captures temporal dynamics in host transcriptional immune response during acute SARS-CoV-2 infection.
Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) Cancer Prevention Recommendations with Stages of Colorectal Carcinogenesis
Authors: Kværner Ane Sørlie , Andersen Astrid Riseth , Henriksen Hege Berg , Knudsen Markus , Wetting Johansen Anne Marte , Hjartåker Anette , Bøhn Siv Kjølsrud , Paur Ingvild , Wiedswang Gro , Smeland Sigbjørn , Rounge Trine B. , Blomhoff Rune , Berstad Paula
Published: January 2023

While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with colorectal carcinogenesis in a cross-sectional setting. Baseline data from two studies was combined to measure adherence to the seven-point 2018 WCRF/AICR Score in screening participants with a positive faecal immunochemical test and CRC patients in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected colorectal lesions and CRC. Of 1,914 participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advances lesions and 493 had CRC (63 screen-detected and 430 recruited from the intervention study). Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced colorectal lesions; OR 0.82 (95% CI 0.71, 0.94,ptrend0.005) per score point, but not CRC. Adherence to the alcohol recommendation was the single factor most strongly inversely associated with CRC development, being significantly associated with advanced colorectal lesions and CRC. Adherence to the 2018 WCRF/AICR cancer prevention recommendations was associated with lower probability of screen-detected advanced colorectal lesions, but not CRC. Taking a holistic approach to cancer prevention is important to prevent the occurrence of precancerous colorectal lesions.

What’s new?

While several studies have documented an association between adherence to cancer prevention recommendations and risk colorectal cancer, data is sparse when it comes to the precancerous lesions. In this study, including participants representing the entire spectrum of colorectal carcinogenesis, strong inverse associations were observed between adherence to the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) and the two main precursor lesion types (advanced adenoma and advanced serrated lesion), highlighting the importance of adopting a healthy lifestyle early on to prevent the development of colorectal cancer.

Trial Registration

ClinicalTrials.govIdentifier:NCT01538550(Bowel Cancer Screening in Norway (BCSN) trial) andNCT01570010(CRC-NORDIET).
Exploring the Transmission Dynamics of the COVID-19 Outbreaks after Dec. 2022 in Shaanxi Province, China: Analysis of Baseline Data from A Large Scale Cohort
Authors: Zhang Tianxiao , Mi Baibing , Shen Mingwang , Nian Yunpeng , Cao Suixia , Liu Jingchun , Huang Hao , Wei Zhongxi , Liu Lixi , Wu Qian , Zhang Yi , Zhang Shaobai
Published: January 2023

Backgrounds

The goal of this study is to explore the transmission dynamics for recent large-scale COVID-19 outbreaks in Shaanxi Province on the Chinese mainland. Furthermore, the potential effects of the Spring Festival travel rush on the ongoing COVID-19 pandemic were depicted.

Methods

This study uses baseline data from a large cohort to investigate the characteristics of the recent COVID-19 epidemic in Shaanxi province. A cluster sampling method was used to recruit the study participants during the COVID-19 pandemic in Shaanxi province since Dec. 1st, 2022. A total of 44 sampling cluster (11 village in rural areas and 33 residences in urban areas) were chosen for enrollment of study participants. A self-developed questionnaire was applied to data collection of socio-demographic and COVID-19 pandemic related information.

Results

A total of 14,744 study participants were enrolled in the baseline survey and 12,111 completed survey data were extracted for analysis. The cumulative infection attack rate (IAR) of COVID-19 among the study participants was 84.7%. The cumulative IAR in urban and rural areas were 85.6% and 83.7%, respectively. A peak of COVID-19 self-reported diagnosis could be observed from Dec. 15th, 2022 to Jan. 1st, 2023 in the provincial level. Beside this major peak of the recent epidemic (around Dec.20th, 2022), a small but steep rise could also be identified between Jan 13thto 14th, 2023. Individuals who escaped the first wave of COVID-19 outbreaks may face danger of infection from returnees during the 2023 Spring Festival.

Conclusion

According to the COVID-19 cumulative IAR data, the herd community was primarily achieved in Shaanxi province’s urban and rural areas. The epidemic in Shaanxi province has been exacerbated by mass population movement during the Spring Festival travel rush in both urban and rural areas. Further surveillance should be performed to monitor the spread of SARS-CoV-2 infections.
Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals
Authors: Zhou Hang , Kember Rachel L. , Deak Joseph D. , Xu Heng , Toikumo Sylvanus , Yuan Kai , Lind Penelope A. , Farajzadeh Leila , Wang Lu , Hatoum Alexander S. , Johnson Jessica , Lee Hyunjoon , Mallard Travis T. , Xu Jiayi , Johnston Keira J.A. , Johnson Emma C. , Galimberti Marco , Dao Cecilia , Levey Daniel F. , Overstreet Cassie , Byrne Enda M. , Gillespie Nathan A. , Gordon Scott , Hickie Ian B. , Whitfield John B. , Xu Ke , Zhao Hongyu , Huckins Laura M. , Davis Lea K. , Sanchez-Roige Sandra , Madden Pamela A. F. , Heath Andrew C. , Medland Sarah E. , Martin Nicholas G. , Ge Tian , Smoller Jordan W. , Hougaard David M. , Børglum Anders D. , Demontis Ditte , Krystal John H. , Gaziano J. Michael , Edenberg Howard J. , Agrawal Arpana ,   Million Veteran Program, Justice Amy C. , Stein Murray B. , Kranzler Henry R. , Gelernter Joel
Published: January 2023

Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.
Integrating NHANES and Toxicity Forecaster Data to Compare Pesticide Exposure and Bioactivity by Farmwork History and US Citizenship
Authors: Forté Chanese A. , Millar Jess A. , Colacino Justin
Published: January 2023

Introduction

Farmworkers in the United States, especially migrant workers, face unique barriers to healthcare and have documented disparities in health outcomes. Exposure to pesticides, especially those persistent in the environment, may contribute to these health disparities.

Methods

We queried the National Health and Nutrition Examination Study (NHANES) from 1999-2014 for pesticide exposure biomarker concentrations among farmworkers and non-farmworkers by citizenship status. We combined this with toxicity assay data from the US Environmental Protection Agency’s (EPA’s) Toxicity Forecast Dashboard (ToxCast). We estimated adverse biological effects that occur across a range of human population-relevant pesticide doses.

Results

In total, there were 1,137 people with any farmwork history and 20,205 non-farmworkers. Of the 14 commonly detectable pesticide biomarkers in NHANES, 2,4-dichlorophenol (OR= 4.32, p= 2.01×10−7) was significantly higher in farmworkers than non-farmworkers. Farmworkers were 1.37 times more likely to have a bioactive pesticide biomarker measurement in comparison to non-farmworkers (adjusted OR=1.37, 95% CI: 1.10, 1.71). Within farmworkers only, those without U.S. citizenships were 1.31 times more likely to have bioactive pesticide biomarker concentrations compared those with U.S. citizenship (adjusted OR 1.31, 95% CI: 0.75, 2.30). Additionally, non-citizen farmworkers were significantly more exposed to bioactive levels ofβ-hexachlorocyclohexane (BHC) (OR= 8.50, p= 1.23×10−9), p,p-DDE (OR= 2.98, p= 3.11×10−3), and p,p’-DDT (OR= 10.78, p= 8.70×10−4).

Discussion

These results highlight pesticide exposure disparities in farmworkers, particularly those without U.S. citizenship. Many of these exposures are occurring at doses which are bioactive in toxicological assays.
Progression and management of diabetes in Indian settings with universal access to health care: Protocol and plans for CHIPS cohort study
Authors: Kulkarni Anjali , Dilip TR , Shejul Yogesh K , Bhandarkar Prashant , Goswami Puja , Sharma Palak , Patil Priti , James KS
Published: January 2023

There is a demand for more comprehensive studies related to diabetes management in Indian settings covering; incidence, multimorbidity and complications in diabetes patients, clinical progression, medication, and treatment-seeking patterns. CHIPS study aims to bridge this research gap through a systematic analysis of the medical records maintained under an employees contributory health services scheme (CHSS). The CHSS based in an urban metropolitan area has 89,204 beneficiaries. The hospital information management system (HIMS) has records of lab reports, clinical summaries, prescriptions, and drugs and other medical consumables, supplied for every interaction with CHSS. Firstly, a cohort of 835 patients newly diagnosed as diabetic in the year 2011-2012 was identified from the HIMS. Their 10-year (2011-2021) medical history after getting diagnosed as a diabetic patient was elicited from the HIMS in a retrospective manner. For comparison needs another cohort of 1670 age-sex matched non-diabetic beneficiaries was created and similar 10-year medical history was created. A total of 144,511 lab records and 247,473 drug records from the HIMS for the period 2010-2012 were scrutinized to identify newly diabetic patients and their non-diabetic counterparts. The reconstructed 10-year medical history of these two groups will be used to investigate the burden of diabetes in the community, transitions from a non-diabetic and pre-diabetic to a diabetic, excess morbidity in diabetic patients, seasonal variation in glycaemic levels, association between glycaemic control and frequency of health care utilization, and COVID-19-induced temporal changes in glycaemic control.
Wearable technology to capture arm use of stroke survivors in home and community settings: feasibility and early insights on motor performance
Authors: Demers Marika , Bishop Lauri , Cain Amelia , Saba Joseph , Rowe Justin , Zondervan Daniel , Winstein Carolee
Published: January 2023

Objective

To establish short-term feasibility and usability of wrist-worn wearable sensors to capture arm/hand activity of stroke survivors and to explorethe association betweenfactors related to use of the paretic arm/hand.

Methods

30 chronic stroke survivors were monitored with wrist-worn wearable sensors during 12h/day for a 7-day period. Participants also completed standardized assessments to capture stroke severity, arm motor impairments, self-perceived arm use and self-efficacy. Usability of the wearable sensors was assessed using the adapted System Usability Scale and an exit interview. Associations between motor performance and capacity (arm/hand impairments and activity limitations) were assessed using Spearman’s correlations.

Results

Minimal technical issues or lack of adherence to the wearing schedule occurred, with 87.6% of days procuring valid data from both sensors. Average sensor wear time was 12.6 (standard deviation: 0.2) h/day. Three participants experienced discomfort with one of the wristbands and three other participants had unrelated adverse events. There were positive self-reported usability scores (mean: 85.4/100) and high user satisfaction. Significant correlations were observed for measures of motor capacity and self-efficacy with paretic arm use in the home and the community (Spearman’s correlation ρs: 0.44-0.71).

Conclusions

This work demonstrates the feasibility and usability of a consumer-grade wearable sensor to capture paretic arm activity outside the laboratory. It provides early insight into stroke survivors’ everyday arm use and related factors such as motor capacity and self-efficacy.

Impact

The integration of wearable technologies into clinical practice offers new possibilities to complement in-person clinical assessments and to better understand how each person is moving outside of therapy and throughout the recovery and reintegration phase. Insights gained from monitoring stroke survivors arm/hand use in the home and community is the first step towards informing future research with an emphasis on causal mechanisms with clinical relevance.
Parental Risk Perception: Influence of Disease Perceived Controllability, Experience and Severity
Authors: Sylvestre Philippe , Enok Bonong Pascal Roland , Perez Tamara , Drouin Olivier
Published: January 2023

Optimistic health bias is widespread in adults, impacting responsiveness to information regarding health risks. Comparatively little is known about parents’ perception of their child’s likelihood of developing disease, despite the frequency with which parents make decisions about their child’s health. We hypothesized that parental optimism about their child’s likelihood of developing disease would be greater for diseases perceived as more controllable and those with which parents do not have experience.

Parents of children <18 years complete an online survey. Primary outcome was participants’ perceived comparative likelihood of their child developing appendicitis, dental caries, head lice, leukemia, food allergies, pneumonia, asthma and obesity. Optimism was defined as the belief that one’s child was less likely than average to develop a given disease. Logistic regression models were used to examine the relationship between parental optimism and four independent variables: perceived disease controllability; knowing someone with the disease; child’s history of the disease; perceived disease severity.

Among 374 participants, the proportion of optimistic parents ranged from 35.3% (appendicitis) to 65.0% (obesity). Perceived controllability increased the odds of parental optimism (adjusted odds ratio [ aOR] range: 1.57 for asthma to 4.48 for head lice). Odds of optimism were lower if participants knew somebody with the disease (aOR range: 0.42 for head lice to 0.81 for leukemia) or if the child had a history of the disease (aOR range: 0.27 for dental caries to 0.47 for head lice).

These findings are important to enhance parental counseling effectiveness regarding child health behaviors.