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Teduglutide in short bowel syndrome patients – A way back to normal life?

JPEN J Parenter Enteral Nutr. 2021 Oct 6. doi: 10.1002/jpen.2272. Online ahead of print.

ABSTRACT

BACKGROUND: The glucagon-like peptide 2 (GLP-2) analogue teduglutide is an effective drug for the treatment of patients suffering from short bowel syndrome with intestinal failure (SBS-IF). This intestinotrophic peptide improves intestinal capacity for fluid and nutrient absorption through induction of mucosal growth and reduction of gastrointestinal motility. Clinical trials demonstrated the efficacy of teduglutide in reducing the need for parenteral support. This study describes an SBS-IF patient population receiving teduglutide therapy in a specialized medical care setting.

METHOD: A retrospective analysis was performed using data of patients suffering from non-malignant SBS-IF. They were treated with teduglutide in a multidisciplinary SBS-IF program at a single university medical center between June 2016 and June 2020.

RESULTS: Thirteen patients were treated with teduglutide and included into the final analysis. Mean small bowel length was 82±31cm with 77% of patients having their colon in continuity. Over a median follow-up period of 107 weeks, all patients (13/13, 100%) responded to the therapy with a clinically significant reduction of parenteral support volume. Mean parenteral support reduction increased with therapy duration and ranged from -82.5% at week 24 (n = 13) to -100% in patients (n = 5) who were treated for 144 weeks. Enteral autonomy was achieved in 12/13 (92%). Teduglutide therapy also improved stool frequency and consistency, changed dietary habits and reduced disease-associated sleep disruptions.

CONCLUSION: Integrating SBS-IF patients treated with teduglutide in a pro-active and tight-meshed patient care program significantly improves the clinical outcome leading to an increased proportion of patients who reach enteral autonomy. This article is protected by copyright. All rights reserved.

PMID:34614239 | DOI:10.1002/jpen.2272

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Periapical lesions in two inbred strains of rats differing in immunological reactivity

Int Endod J. 2021 Oct 6. doi: 10.1111/iej.13638. Online ahead of print.

ABSTRACT

AIM: To investigate the influence of strain differences in immune responses on the pathogenesis of experimental periapical lesions in Dark Agouti (DA) and Albino Oxford (AO) inbred strains of rats.

METHODOLOGY: Periapical lesions were induced in male DA and AO rats by pulp exposure of the first mandibular right molars to the oral environment. Animals were sacrificed 21 days after pulp exposure. The mandibular jaws were retrieved and prepared for radiographic, pathohistological, immunohistochemical analysis, real-time PCR, and flow cytometry. Blood samples and the supernatant of periapical lesions were collected for measurement of cytokines and oxidative stress marker levels. Statistical analysis was performed the Kruskal-Wallis H and Mann-Whitney U non-parametric tests or parametric One-Way ANOVA and Independent Samples T-test to determine the differences between groups depending on the normality of the data. A significant difference was considered when p values were < .05.

RESULTS: DA rats developed significantly larger (p˂.05) periapical lesions compared to AO rats as confirmed by radiographic and pathohistological analysis. The immunohistochemical staining intensity for CD3 was significantly higher in periapical lesions of DA rats compared to AO rats (p˂.05). In DA rats, periapical lesions had a significantly higher (p˂.05) percentage of CD3+ cells compared to AO rats. Also, the percentage of INF-γ, IL-17, and IL-10 CD3+CD4+ cells was significantly higher in DA rats (p˂.05). DA rats had a significantly higher Th17/Th10 ratio. RT-PCR expression of IL-1β, INF-γ, and IL-17 genes was significantly higher in periapical lesions of DA compared to AO rats (p˂.05). The receptor activator of nuclear factor kappa-Β ligand/osteoprotegerin ratio was higher in DA compared to AO rats with periapical lesions (p˂.05). Systemic levels of TNF-α and IL-6 were significantly higher in DA compared to AO rats (p˂.05). Levels of lipid peroxidation measured as thiobarbituric acid reactive substances and reduced glutathione were significantly higher (p˂.05) in the supernatant in the periapical lesions of DA rats.

CONCLUSION: After pulp exposure, Dark Agouti rats developed much larger periapical lesions compared to Albino Oxford rats. Genetically determined differences in immunopathology have been demonstrated to be a significant element defining the severity of periapical lesions.

PMID:34614243 | DOI:10.1111/iej.13638

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Household caregivers’ knowledge and control of helminthiasis in preschool children in a rural community of Enugu state, Nigeria

J Community Psychol. 2021 Oct 6. doi: 10.1002/jcop.22727. Online ahead of print.

ABSTRACT

Helminthiasis causes iron deficiency anemia, pica, growth, and mental retardation in children. Deworming exercises are being included as part of various interventional programs to reduce the disease burden. However, the success or failure of such activities in terms of household caregivers’ knowledge and practice of deworming is not usually adequately evaluated, thus this study. This was a cross-sectional descriptive study carried out in the rural community of Enugu State, Nigeria. Pretested semi-structured interviewer-administered questionnaire was used. Inferential statistics, χ2 test, and t-test were also used in the analysis for categorical and continuous variables, respectively. A total of 294 preschool children and 250 caregivers were studied. Among the caregivers, 212 (71.9%) had good knowledge and 149 (50.5%) had good practice of deworming. There was a statistically significant association between the age of respondents and knowledge score (χ2 = 6.471, p = 0.039) and between the educational level of respondents and practice score (χ2 = 30.632, p < 0.001). Most respondents in the rural community had a good knowledge of worm infestation and only half had good practice of deworming. Also, there was a significant difference between the age of respondents and knowledge of helminthiasis and between the educational level of respondents and deworming activities of respondents.

PMID:34614217 | DOI:10.1002/jcop.22727

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Impact of COVID-19 on public health nursing student learning outcomes

Public Health Nurs. 2021 Oct 6. doi: 10.1111/phn.12978. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has highlighted the importance of a strong, effective public health nursing workforce while also requiring public health nursing faculty to adapt teaching strategies as courses transitioned online. It is essential to understand how the pandemic-enforced transition from face-to-face to remote learning impacts student outcomes. The purpose of this paper is to compare student learning outcomes in a pre-licensure public health nursing course before, during, and after the transition to remote learning.

METHODS: Descriptive statistics were computed for assignments, exams, and final course grades for three terms (Fall 2019, Spring 2020 and Fall 2020).

RESULTS: Analysis showed statistically significant differences between terms for assignments and exams but not the final course grade. However, these differences were driven by small standard deviations rather than differences between mean scores demonstrating that there was actual little difference in student learning outcomes across terms.

CONCLUSIONS: Authors suggest strategies to support consistent academic outcomes and future research needed understand student learning outcomes during the pandemic; ultimately building the public health nursing workforce necessary to address the current and future public health crises.

PMID:34614222 | DOI:10.1111/phn.12978

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Agreement between local and central reading of endoscopic disease activity in ulcerative colitis: results from the tofacitinib OCTAVE trials

Aliment Pharmacol Ther. 2021 Oct 6. doi: 10.1111/apt.16626. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopy is routine in trials of ulcerative colitis therapies.

AIM: To investigate agreement between central and local Mayo endoscopic subscore (MES) reads in the OCTAVE programme METHODS: Flexible sigmoidoscopy was performed in tofacitinib induction (OCTAVE Induction 1&2, NCT01465763 and NCT01458951), maintenance (OCTAVE Sustain, NCT01458574) and open-label, long-term extension (OCTAVE Open, NCT01470612) studies. Kappa statistics and Bowker’s tests evaluated agreement/disagreement between centrally and locally read MES, with potential determinants of differences analysed by logistic regression.

RESULTS: Moderate-to-substantial agreement was observed between central and local reads at screening (77.1% agreement; kappa 0.62 [95% confidence interval 0.59-0.66]), OCTAVE Induction 1&2 week (Wk) 8 (63.8%; 0.62 [0.59-0.66]), OCTAVE Sustain Wk 52 (55.6%; 0.56 [0.50-0.62]) and for induction non-responders at OCTAVE Open month 2 (59.9%; 0.54 [0.48-0.60]). Where disagreements occurred, local reads were systematically lower than central reads at OCTAVE Induction 1&2 Wk 8, OCTAVE Sustain Wk 52 and OCTAVE Open month 2 (Bowker’s P < 0.0001); this difference was not observed at screening (P = 0.0852). Using multivariable logistic regression, geographical region, C-reactive protein (Wk 8), partial Mayo score (Wk 8) and prior tumour necrosis factor antagonist failure were associated with disparity at OCTAVE Induction 1&2 Wk 8 (P < 0.05). In OCTAVE Induction 1&2 and OCTAVE Sustain, significantly higher proportions of patients endoscopic improvement, remission and endoscopic remission with tofacitinib vs placebo, using either central or local reads.

CONCLUSION: Moderate-to-substantial agreement was observed between central and local endoscopic reads. Where disagreements occurred, local reads were systematically lower than central reads at most timepoints, suggesting potential bias. ClinicalTrials.gov identifier: NCT01465763, NCT01458951, NCT01458574, NCT01470612.

PMID:34614208 | DOI:10.1111/apt.16626

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Fatigue and endocrine symptoms among women with early breast cancer randomized to endocrine versus chemoendocrine therapy: Results from the TAILORx patient-reported outcomes substudy

Cancer. 2021 Oct 6. doi: 10.1002/cncr.33939. Online ahead of print.

ABSTRACT

BACKGROUND: TAILORx (Trial Assigning Individualized Options for Treatment) prospectively assessed fatigue and endocrine symptoms among women with early-stage hormone receptor-positive breast cancer and a midrange risk of recurrence who were randomized to endocrine therapy (E) or chemotherapy followed by endocrine therapy (CT+E).

METHODS: Participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue, the Patient-Reported Outcomes Measurement Information System-Fatigue Short Form, and the Functional Assessment of Cancer Therapy-Endocrine Symptoms at the baseline and at 3, 6, 12, 24, and 36 months. Linear regression was used to model outcomes on baseline symptoms, treatment, and other factors.

RESULTS: Participants (n = 458) in both treatment arms reported greater fatigue and endocrine symptoms at early follow-up in comparison with the baseline. The magnitude of change in fatigue was significantly greater for the CT+E arm than the E arm at 3 and 6 months but not at 12, 24, or 36 months. The CT+E arm reported significantly greater changes in endocrine symptoms from the baseline to 3 months in comparison with the E arm; change scores were not significantly different at later time points. Endocrine symptom trajectories by treatment differed by menopausal status, with the effect larger and increasing for postmenopausal patients.

CONCLUSIONS: Adjuvant CT+E was associated with greater increases in fatigue and endocrine symptoms at early time points in comparison with E. These differences lessened over time, and this demonstrated early chemotherapy effects more than long-term ones. Treatment arm differences in endocrine symptoms were more evident in postmenopausal patients.

LAY SUMMARY: Participants in TAILORx (Trial Assigning Individualized Options for Treatment) with early-stage hormone receptor-positive breast cancer and an intermediate risk of recurrence were randomly assigned to endocrine or chemoendocrine therapy. Four hundred fifty-eight women reported fatigue and endocrine symptoms at the baseline and at 3, 6, 12, 24, and 36 months. Both groups reported greater symptoms at early follow-up versus the baseline. Increases in fatigue were greater for the chemoendocrine group than the endocrine group at 3 and 6 months but not later. The chemoendocrine group reported greater changes in endocrine symptoms in comparison with the endocrine group at 3 months but not later.

PMID:34614209 | DOI:10.1002/cncr.33939

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A randomized controlled trial of the effect of ramosetron on postoperative restoration of bowel motility after gynecologic laparoscopic surgery

Int J Gynaecol Obstet. 2021 Oct 6. doi: 10.1002/ijgo.13969. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effect of ramosetron after gynecological laparoscopic surgery on the recovery of bowel function.

METHODS: A prospective randomized controlled trial conducted at Kyung Hee University hospital, South Korea, from August 2016 to September 2017. Patients were randomized to receive either 10 mg dexamethasone before induction of anesthesia (control group C), followed by intravenous administration of patient-controlled analgesia (IV-PCA) or 2 mL normal saline before induction of anesthesia and 0.6 mg ramosetron (study group R) administered with IV-PCA.

RESULTS: A total of 88 patients were enrolled. Times to first flatus (group C 23.98 ± 6.31 vs group R 27.14 ± 9.56 hours; P = 0.148) and first defecation (group C 36.16 ± 16.04 vs group R 43.41 ± 20.01 hours; P = 0.138) showed no statistically significant differences. No significant differences were observed in the frequency of postoperative nausea and vomiting (PONV) and demand for additional analgesics. Multiple linear regression for analysis of factors affecting time to first flatus revealed no significant results.

CONCLUSION: Ramosetron did not delay bowel movement recovery after gynecologic laparoscopic surgery and was as effective as dexamethasone in regulating PONV. Ramosetron can be used with IV-PCA without concerns about delay in recovery of bowel function.

PMID:34614204 | DOI:10.1002/ijgo.13969

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Impaired Muscle Mitochondrial Function in Familial Partial Lipodystrophy

J Clin Endocrinol Metab. 2021 Oct 6:dgab725. doi: 10.1210/clinem/dgab725. Online ahead of print.

ABSTRACT

BACKGROUND: Familial Partial Lipodystrophy (FPL), Dunnigan variety is characterized by skeletal muscle hypertrophy and insulin resistance besides fat loss from the extremities. The cause for the muscle hypertrophy, and its functional consequences is not known.

OBJECTIVE: To compare muscle strength and endurance, besides muscle protein synthesis rate between subjects with FPL and matched controls (n = 6 in each group). In addition, we studied skeletal muscle mitochondrial function and gene expression pattern to help understand the mechanisms for the observed differences.

METHODS: Body composition by DEXA, insulin sensitivity by minimal modelling, assessment of peak muscle strength and fatigue, skeletal muscle biopsy and calculation of muscle protein synthesis rate, mitochondrial respirometry, skeletal muscle transcriptome, proteome and gene set enrichment analysis.

RESULTS: Despite increased muscularity, FPL subjects did not demonstrate increased muscle strength but had earlier fatigue on chest press exercise. Decreased mitochondrial state 3 respiration in the presence of fatty acid substrate was noted, concurrent to elevated muscle lactate and decreased long-chain acylcarnitine. Based on gene transcriptome, there was significant down regulation of many critical metabolic pathways involved in mitochondrial biogenesis and function. Moreover, the overall pattern of gene expression was indicative of accelerated aging in FPL subjects. A lower muscle protein synthesis and down regulation of gene transcripts involved in muscle protein catabolism was observed.

CONCLUSION: Increased muscularity in FPL is not due to increased muscle protein synthesis and is likely due to reduced muscle protein degradation. Impaired mitochondrial function and altered gene expression likely explain the metabolic abnormalities and skeletal muscle dysfunction in FPL subjects.

PMID:34614176 | DOI:10.1210/clinem/dgab725

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Circulating Biomarkers of Inflammation and Endothelial Activation in Diabetic Retinopathy

Transl Vis Sci Technol. 2021 Oct 4;10(12):8. doi: 10.1167/tvst.10.12.8.

ABSTRACT

Inflammation and endothelial activation play a pivotal role in development and progression of diabetic retinopathy (DR), a vision-threatening complication of diabetes mellitus (DM) and the leading cause of blindness in the working age population. Easily accessible and validated biomarkers for DR early diagnosis and progression are required for use in clinical trials: here, we reviewed the available literature to understand the association of circulating levels of selected markers of inflammation and endothelial activation with the presence of nonproliferative and proliferative DR (NPDR and PDR) and investigate the relationship between their systemic and ocular levels. We additionally provide data synthesis and perform statistical analysis for interpretation of the collected evidence. CRP, IL-1β, IL-6, TNFα, sICAM1, and sVCAM1 circulating levels were increased in subjects with DM compared to healthy individuals. Moreover, TNFα and sVCAM1 showed increasing systemic levels with DR presence and severity; circulating CRP increased with the transition from no DR to NPDR, whereas IL-6 was increased in PDR compared to NDPR stages. The relationship between ocular and systemic concentrations of these proteins remained unclear due to the low number of studies with matched sampling. In conclusion, the available data supports the use of systemic biomarkers of inflammation and endothelial activation to identify DM status and DR severity. These systemic biomarkers are likely reflecting an overall state of inflammation and vascular activation in different tissues of the body, including the eyes. Prospective, longitudinal datasets are required to validate these biomarkers as predictors of early DR presence, of DR progression, or for disease monitoring.

PMID:34614163 | DOI:10.1167/tvst.10.12.8

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A Mediterranean lifestyle and frailty incidence in older adults: the Seniors-ENRICA-1 cohort

J Gerontol A Biol Sci Med Sci. 2021 Oct 6:glab292. doi: 10.1093/gerona/glab292. Online ahead of print.

ABSTRACT

BACKGROUND: Frailty is a geriatric syndrome that entails high risk of hospitalization, disability, and death. While adherence to Mediterranean diet has been associated with lower risk of frailty, the joint effect of diet and lifestyle is uncertain. This study examined the association between a Mediterranean lifestyle (diet, customs, and traditions) and frailty incidence in older adults.

METHODS: We analyzed data from 1,880 individuals aged ≥ 60 from the prospective Seniors-ENRICA-1 cohort. Adherence to the Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (higher scores representing better adherence), divided into three blocks: 1) “Mediterranean food consumption”, 2) “Mediterranean dietary habits” (practices around meals)” and 3) “Physical activity, rest, social habits and conviviality”. Frailty was ascertained as the presence of ≥ 3 of the 5 Fried criteria: a) Exhaustion; b) Muscle weakness; c) Low physical activity; d) Slow walking speed; e) Unintentional weight loss. Main statistical analyses were performed using logistic regression models, adjusting for the main confounders.

RESULTS: After a 3.3-y follow-up, 136 incident frailty cases were ascertained. Compared with participants in the lowest tertile of the MEDLIFE score, the OR (95% CI) for frailty was 0.88 (0.58-1.34) for the second tertile, and 0.38 (0.21-0.69) for the third tertile (p-trend = 0.003). Blocks 1 and 3 of the MEDLIFE score were independently associated with lower frailty risk. Most items within these blocks showed a tendency to reduced frailty.

CONCLUSIONS: Higher adherence to a Mediterranean lifestyle was associated with lower risk of frailty.

PMID:34614144 | DOI:10.1093/gerona/glab292