Nevin Manimala

J Health Care Chaplain. 2022 Jun 11:1-19. doi: 10.1080/08854726.2022.2077555. Online ahead of print.

ABSTRACT

Health is holistic, but health services are often not. Primary care is the first point of contact for patients in the UK, and at least two in every three present with complex bio-psycho-socio-economic issues. In Scotland, the Community Chaplaincy Listening (CCL) service was created to see if chaplains could help. CCL involves specially trained chaplains listening to patients referred to them by general practitioners (GP) for spiritual support. Between 2018 and 2019, 143 people used CCL and completed baseline and post-discharge outcome measures. Mean Scottish PROM scores rose from 7.94 (± 3.4) at baseline to 12 (± 3.5) post discharge, a statistically and clinically significant rise of 4.06 (95% CI, 3-5.12), t(50) = 7.7, p < 0.0001, d = 1.08. The improvement was seen whether patients self-described as religious, spiritual, both, or neither. Health-related quality of life outcomes were mixed but patients referred to the service scored some of the lowest baseline EQ-5D-3L scores ever seen in the literature. Together these results suggest that CCL worked in primary care, especially for patients historically considered “difficult to treat.” Limitations of the study are considered alongside implications for commissioners and service developers.

PMID:35695021 | DOI:10.1080/08854726.2022.2077555

J Ultrasound Med. 2022 Jun 13. doi: 10.1002/jum.16040. Online ahead of print.

ABSTRACT

OBJECTIVES: This is a prospective study to evaluate the clinical value of high-frequency ultrasound (HFUS), superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) in differentiation of pigmented villonodular synovitis (PVNS) and highly active rheumatoid arthritis (RA).

METHODS: Twenty PVNS patients and 24 active RA patients were selected to undergo HFUS, SMI, and CEUS examinations. The characteristics of HFUS, SMI, and CEUS in PVNS and RA were compared, and the differential diagnosis performances of HFUS, SMI, and CEUS in PVNS and RA were evaluated by receiver operating characteristic (ROC) analysis.

RESULTS: There were statistically significant in joint effusion, synovial thickness, synovial morphology, synovial echo, synovial vessel shape, synovial enhanced direction, and enhanced pattern between PVNS and RA (P < .05). However, no statistically significant were found in bone erosion, synovial boundary, blood signal grading of synovium, synovial enhanced strength, and CEUS quantitative parameters (including PI, TTP, S, MTT, and AUC) (P > .05). The AUC of HFUS, SMI, and CEUS for differential diagnosis PVNS and RA were 0.832, 0.675, and 0.817, respectively. The AUC of HFUS + SMI, HFUS + CEUS, SMI + CEUS, HFUS + SMI + CEUS were 0.923, 0.940, 0.817, and 0.940, respectively. The AUC of HFUS + SMI and HFUS + CEUS was higher than that of each alone (P < .05).

CONCLUSIONS: HFUS, SMI, and CEUS can be used as supplementary methods for diagnosis and differential diagnosis in PVNS and active RA. What is more, the combination of HFUS + SMI and HFUS + CEUS was suggested.

PMID:35695018 | DOI:10.1002/jum.16040

Stroke. 2022 Jun 13:STROKEAHA121037006. doi: 10.1161/STROKEAHA.121.037006. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with symptomatic internal carotid artery (ICA) stenosis are at high risk of recurrent ischemic stroke and require early interventional treatment and antiplatelet therapy. Increased bleeding rates might counterbalance the periprocedural efficacy of intensified platelet inhibition. We aim to investigate, whether Revacept, a competitive antagonist of glycoprotein VI, adjunct to standard antiplatelet therapy reduces the occurrence of ischemic lesions in patients with symptomatic ICA stenosis.

METHODS: International, multicenter (16 sites), 3-arm, randomized (1:1:1), double-blind, and placebo-controlled study with parallel groups, including patients with symptomatic ICA stenosis. A single infusion over 20 minutes of either placebo, 40 mg or 120 mg Revacept in addition to guideline-conform antiplatelet therapy was evaluated with regard to the exploratory efficacy end point: Number of new ischemic lesions on diffusion-weighted magnetic resonance imaging after treatment initiation. Main clinical outcome was the combined safety and efficacy end point including any stroke or death, transient ischemic attack, myocardial infarction, coronary intervention, and bleeding complications during follow-up.

RESULTS: Out of 160 randomized patients, 158 patients (68±10.1 years, 24% female) received study medication (51 patients placebo, 54 patients 40 mg Revacept and 53 patients 120 mg Revacept) and were followed for 11.2±2.3 months. A total of 1.16 (95% CI, 0.88-1.53)/1.05 (95% CI, 0.78-1.42; P=0.629)/0.63 (95% CI, 0.43-0.93) new diffusion-weighted magnetic resonance imaging lesions per patient were detected in the placebo/40 mg/120 mg Revacept groups, without statistical evidence of a difference. A reduction of the combined safety and efficacy end point during the study period was observed in patients who received 120 mg (HR, 0.46 [95% CI, 0.21-0.99]; P=0.047), but not 40 mg Revacept compared with placebo (HR, 0.72 [95% CI, 0.37-1.42]; P=0.343).

CONCLUSIONS: Revacept 120 mg reduced the combined safety and efficacy end point in patients with symptomatic ICA stenosis.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique Identifier: NCT01645306.

PMID:35695006 | DOI:10.1161/STROKEAHA.121.037006

J Gastrointestin Liver Dis. 2022 Jun 12;31(2):191-197. doi: 10.15403/jgld-4187.

ABSTRACT

BACKGROUND AND AIMS: Celiac disease is characterized by an inappropriate T-cell-mediated response to gluten in small bowel in genetically predisposed individuals, carriers of the DQ2 and/or DQ8 haplotypes of the human leukocyte antigen. The aim of our study was to asses HLA typing in adult patients with celiac disease, in their first degree relatives and in a healthy control group.

METHODS: We conducted a prospective observational study on three cohorts: 117 patients diagnosed with celiac disease, 41 first-degree relatives of celiac patients and 57 asymptomatic healthy volunteers. Low resolution HLA typing for DQ alleles was performed in all study subjects with DNA extracted from peripheral blood, using SSP HLA-DQB1 kit (Innotrain Diagnostik GmbH, Germany). Next Generation Sequencing (NGS) was used only in 18 patients for typing confirmation of DQB1 and DQA1 loci and whole gene sequencing.

RESULTS: Prevalence of HLA-DQ2 was significantly higher in the CD group compared to the healthy subjects group (95.6% vs 29.8%, p <0.001), with no statistically significant differences in HLA-DQ8 and combined HLA-DQ2/DQ8 prevalences.Several HLA DQA1 and DQB1 alleles (HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02) and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our group: OR 4.28, 4.28, 4.67 and 5.43 and 4.28 respectively. Predominantly, patients presented with typical symptoms and iron deficiency anemia. 95.5% of them had histological Marsh type modifications ≥3a. A relatively poor response to gluten-free diet was observed and 9.4% developed complications (refractory celiac disease, enteropathy-associated T cell lymphoma, intestinal adenocarcinoma), with a death rate of 6.8%. 23% associated other autoimmune diseases.Screening adherence for 1st degree relatives was very low: only 16%. Familial screening diagnosed 4 cases of asymptomatic celiac disease. 32 relatives (78%) had HLA-DQ2 haplotype, 5 carried HLA-DQ8, 4 didn’t carry any risk haplotype.

CONCLUSIONS: This study demonstrated a higher prevalence of the HLA-DQ2 genotype in patients with celiac disease compared to the healthy population but not of HLA-DQ8 or combined HLA-DQ2/DQ8. Alleles HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02 and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our cohort.

PMID:35694992 | DOI:10.15403/jgld-4187

Environ Toxicol Chem. 2022 Jun 13. doi: 10.1002/etc.5396. Online ahead of print.

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are structurally diverse organic chemicals that can have adverse effects on the health of fishes through activation of the aryl hydrocarbon receptor 2 (AhR2). PAHs are ubiquitous in the environment, but alkyl PAHs are more abundant in some environmental matrices. However, relatively little is known regarding the effects of alkylation on the toxicity of PAHs to fishes in vivo and how this relates to potency for activation of the AhR2 in vitro. Therefore, objectives of this study were to determine the toxicity of benz[a]anthracene (BAA) and three alkylated homologues representing various alkylation positions to early life-stages of zebrafish (Danio rerio), and to assess the potency of each for activation of the zebrafish AhR2 in a standardized in vitro AhR transactivation assay. Exposure of embryos to each of the PAHs caused a dose-dependent increase in mortality and malformations characteristic of AhR2 activation. Each alkyl homolog had in vivo toxicities and in vitro AhR2 activation potencies different than the parent PAH in a position-dependant manner. However, there was no statistically significant linear relationship between responses measured in these assays. Results suggest a need for further investigation into the effect of alkylation on the toxicity of PAHs to fishes and greater consideration of the contribution of alkylated homologues in ecological risk assessments. This article is protected by copyright. All rights reserved.© 2022 SETAC.

PMID:35694968 | DOI:10.1002/etc.5396

Work. 2022 Jun 10. doi: 10.3233/WOR-211272. Online ahead of print.

ABSTRACT

BACKGROUND: The Bioservo Ironhand ® is a commercially available active hand exoskeleton for reducing grip-induced stress.

OBJECTIVES: The study aimed at quantifying the effect of the Ironhand ® exoskeleton on the myoelectric muscle activity of forearm flexor and extensor muscles in three relevant assembly grip tasks: 2-Finger-grip (2Finger), 5-Finger-grip (5Finger) and Full grip (FullGrip).

METHODS: Twenty-two subjects were tested in three different exoskeleton conditions for each grip task (overall 3×3×10 = 90 repetitions in randomized order): Exoskeleton off (Off), Exoskeleton on, “locking tendency” 0% (On_LT0), and Exoskeleton on, “locking tendency” 85% (On_LT85). Muscle activity was measured at 25% of the participant’s maximum grip force using two EMG sensors at the M. flexor digitorum superficialis (M.FDS) and one at the M. extensor digitorum (M.ED).

RESULTS: The effect of the Ironhand ® exoskeleton varied depending on the grip task and the participant’s sex. A statistically significant reduction in muscle activity of the M.FDS was found only for male subjects in the FullGrip condition. No reduction of muscular activity in the M.FDS was found for the other grip tasks (2Finger, 5Finger). For the females in the 2Finger condition, mean muscle activity of M.FDS even increased significantly in On_LT0 compared to Off. Besides differences between grip tasks and sex, the current study revealed substantial individual differences.

CONCLUSIONS: In addition to testing for statistical significance, a detailed exploratory analysis of exoskeleton effects at subject level should be performed to evaluate these from a safety and regulatory perspective.

PMID:35694945 | DOI:10.3233/WOR-211272

J Parkinsons Dis. 2022 Jun 6. doi: 10.3233/JPD-223274. Online ahead of print.

ABSTRACT

BACKGROUND: The Parkinson’s Disease Patient Report of Problems (PD-PROP) captures the problems and functional impact that patients report verbatim. Online research participation and advances in language analysis have enabled longitudinal collection and classification of symptoms as trial outcomes.

OBJECTIVE: Analyze verbatim reports longitudinally to examine postural-instability symptoms as 1) precursors of subsequent falling and 2) newly occurring symptoms that could serve as outcome measures in randomized controlled trials.

METHODS: Problems reported by >25,000 PD patients in their own words were collected online in the Fox Insight observational study and classified into symptoms by natural language processing, clinical curation, and machine learning. Symptoms of gait, balance, falling, and freezing and associated reports of having fallen in the last month were analyzed over three years of longitudinal observation by a Cox regression model in a cohort of 8,287 participants. New onset of gait, balance, falling, and freezing symptoms was analyzed by Kaplan-Meier survival techniques in 4,119 participants who had not previously reported these symptoms.

RESULTS: Classified verbatim symptoms of postural instability were significant precursors of subsequent falling among participants who were older, female, and had longer PD duration. New onset of symptoms steadily increased and informed sample size estimates for clinical trials to reduce the onset of these symptoms.

CONCLUSION: The tools to analyze symptoms reported by PD patients in their own words and capacity to enroll large numbers of research participants online support the feasibility and statistical power for conducting randomized clinical trials to detect effects of therapeutic interventions.

PMID:35694935 | DOI:10.3233/JPD-223274

J Parkinsons Dis. 2022 Jun 4. doi: 10.3233/JPD-213126. Online ahead of print.

ABSTRACT

BACKGROUND: PRESENCE was a Phase 2 trial assessing mevidalen for symptomatic treatment of Lewy body dementia (LBD). Participants received daily doses (10, 30, or 75 mg) of mevidalen (LY3154207) or placebo for 12 weeks.

OBJECTIVE: To evaluate if frequent cognitive and motor tests using an iPad app and wrist-worn actigraphy to track activity and sleep could detect mevidalen treatment effects in LBD.

METHODS: Of 340 participants enrolled in PRESENCE, 238 wore actigraphy for three 2-week periods: pre-, during, and post-intervention. A subset of participants (n = 160) enrolled in a sub-study using an iPad trial app with 3 tests: digital symbol substitution (DSST), spatial working memory (SWM), and finger-tapping. Compliance was defined as daily test completion or watch-wearing ≥23 h/day. Change from baseline to week 12 (app) or week 8 (actigraphy) was used to assess treatment effects using Mixed Model Repeated Measures analysis. Pearson correlations between sensor-derived features and clinical endpoints were assessed.

RESULTS: Actigraphy and trial app compliance was > 90% and > 60%, respectively. At baseline, daytime sleep positively correlated with Epworth Sleepiness Scale score (p < 0.01). Physical activity correlated with improvement on Movement Disorder Society -Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II (p < 0.001). Better scores of DSST and SWM correlated with lower Alzheimer Disease Assessment Scale -Cognitive 13-Item Scale (ADAS-Cog13) (p < 0.001). Mevidalen treatment (30 mg) improved SWM (p < 0.01), while dose-dependent decreases in daytime sleep (10 mg: p < 0.01, 30 mg: p < 0.05, 75 mg: p < 0.001), and an increase in walking minutes (75 mg dose: p < 0.001) were observed, returning to baseline post-intervention.

CONCLUSION: Devices used in the LBD population achieved adequate compliance and digital metrics detected statistically significant treatment effects.

PMID:35694933 | DOI:10.3233/JPD-213126

J Alzheimers Dis. 2022 Jun 6. doi: 10.3233/JAD-215630. Online ahead of print.

ABSTRACT

BACKGROUND: Depression is a common manifestation in Alzheimer’s disease (AD). In clinical practice, antidepressant medication is often used for depression in AD.

OBJECTIVE: We explore the effectiveness of the atypical antidepressant tianeptine compared with other conventional antidepressants in AD patients with depression in a real-life setting.

METHODS: We retrospectively identified 126 AD patients who had received antidepressant treatment for 12 months with tianeptine or other antidepressants. Subjects were divided into two groups according to the treatment they had received: tianeptine group (n = 38) or other antidepressant group (n = 88). Drug effects on depression, cognition, behavior, and functional performance were evaluated at baseline, 6, and 12 months. A Mixed Effects Model Analysis was carried out to evaluate changes in performance scores.

RESULTS: Both tianeptine and other antidepressants showed an antidepressant effect after 12 months with significant improvement on the Cornell Scale for Depression in Dementia, the Hamilton Depression Rating Scale, and the Neuropsychiatric Inventory-Depression subscale. A statistically significant improvement at 12 months was shown in the tianeptine group versus the other antidepressants group on most of the cognitive measures such as the Mini-Mental State Examination, the Letter and Category Fluency Test, the Rey Auditory Verbal Learning Test, and the Boston Naming Test.

CONCLUSION: Our results suggest that tianeptine reduces depressive symptoms and improve cognition in AD patients. This could be considered clinically relevant and should inspire the design of future long-term randomized controlled trials that contribute to supporting the use of tianeptine for improving cognitive function in AD patients.

PMID:35694919 | DOI:10.3233/JAD-215630

J Oral Rehabil. 2022 Jun 13. doi: 10.1111/joor.13348. Online ahead of print.

ABSTRACT

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a hereditary disorder that affects the connective tissue and collagen structures in the body characterized by joint hypermobility, skin hyperextensibility and tissue fragility.

OBJECTIVE: The aim was to investigate temporomandibular disorders (TMD), bite force, teeth in occlusal contact and osseous changes of the temporomandibular joints (TMJs) in 26 patients with hypermobile EDS (hEDS), differentiated by a genetic test, compared to 39 healthy controls.

METHODS: Clinical examination according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), radiological examinations of the TMJs by cone-beam computed tomographic (CBCT) scans, registration of bite force and teeth in occlusal contact was performed. Statistical analyses included Fisher’s Exact Test, multiple logistic and linear regression models adjusted for age, gender and Body Mass Index (BMI).

RESULTS: Single symptoms and signs of TMD occurred significantly more often in hEDS (p=0.002; p=0.001; p=0.003; p=<0.0001; p=0.012) and maximum mouth opening was significantly smaller in hEDS compared to controls (p=<0.0001). The DC/TMD diagnosis myalgia, myofascial pain with referral, arthralgia, headache attributed to TMD, disc displacement disorders and degenerative joint disease occurred significantly more often in hEDS compared to controls (p=0.000; p=0.008; p=0.003; p=0.000; p=<0.0001; p=0.010, respectively). No significant differences were found in bite force and in teeth in occlusal contact between the groups (p>0.05). On CBCT of the TMJs, subcortical sclerosis occurred significantly more often in hEDS compared to controls (p=0.005).

CONCLUSION: Symptoms and signs of TMD and osseous changes of the TMJs occurred significantly more often in hEDS. Bite force and teeth in occlusal contact were comparable to controls.

PMID:35694904 | DOI:10.1111/joor.13348