Αρχειοθήκη ιστολογίου

Τρίτη 18 Οκτωβρίου 2022

Brief Report: Urine Tenofovir Levels Strongly Correlate with Virologic Suppression in Patients with HIV on Tenofovir Alafenamide-Based Antiretroviral Therapy

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Abstract
We found that urine tenofovir (TFV) levels >1500 ng/ml strongly predict virologic suppression among patients with HIV taking tenofovir alafenamide (TAF, OR 5.66; 95% CI 1.59-20.14; p = 0.007). This suggests an existing point-of-care assay developed for tenofovir disoproxil fumarate (TDF) will support adherence monitoring for patients on all TFV-based antiretrovirals.
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The paradox of technology: Negativity bias in consumer adoption of innovative technologies

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Innovative technologies often feature inherently conflicting properties. This poses a challenge for marketers because negative properties not only weigh heavily on consumers' technology adoption decisions but potentially do more so than positive ones. To shed light on the paradox of technology and its underlying processes, the present research develops a conceptual model drawing on technology adoption and valence perception theories about the prevalence of negativity bias in consumers' technology adoption decisions with its unique effect through the serial chain of consumers' perceptions of risk and trust regarding the technology. Results of three studies (N = 1309) demonstrate that the effect of negative valence consistently outperforms that of positive valence in consumers' technology adoption intentions (Studies 1–2) and decisions (Study 3). Furthermore, results show that the disproportionate effect of negative (vs. positive) valence can be expl ained by the proposed serial causal chain through consumers' perception of risk of the technology and trust in the technology (Studies 2–3) while ruling out company trust and consumer knowledge as alternative drivers of the effects (Study 3). These findings contribute to the pertinent literature on consumer psychology in decisions to adopt novel technologies in that they quantify and explain the potential outcome stemming from the ambiguous properties of novel technology. Moreover, this study finds negativity bias to be an often overlooked consumer bias with implications for marketing practice and useful for understanding and lowering resistance towards artificial intelligence technology.

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Adoption of adjuvant chemotherapy in high‐risk salivary gland malignancies

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Abstract

Background

The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies.

Methods

The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004–2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan–Meier and Cox proportional hazards analyses.

Results

Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan–Meier analysis (HR: 0.98; 95% CI: 0.86–1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78–1.09; p = 0.34).

Conclusions

Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

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Tamoxifen Alters TGF‐β1/Smad Signaling in Vocal Fold Injury

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Tamoxifen Alters TGF-β1/Smad Signaling in Vocal Fold Injury

This study investigated the effects of tamoxifen on acute vocal fold injury in a preclinical model. The antifibrotic actions of tamoxifen appear to be mediated by transforming growth factor beta 1/Smad signaling providing a novel target for intervention.


Objectives

Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF-β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis.

Methods

In vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF-β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real-time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre-injury day 5 to post-injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture.

Results

TAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF-β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF-β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment.

Conclusions

TAM has antifibrotic potential via the regulation of TGF-β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis.

Level of Evidence

NA Laryngoscope, 2022

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Monkeypox treatment: current evidence and future perspectives

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Abstract

As of 11 September 2022, 57,669 reports of monkeypox infection raised global concern. Previous vaccinia virus vaccination can protect from monkeypox. However, after smallpox eradication, immunization against that was stopped. Indeed, therapeutic options following the disease onset are of great value. This study aimed to review the available evidence on virology and treatment approaches for monkeypox and provide guidance for patient care and future studies.

Since no randomized clinical trials were ever performed, we reviewed monkeypox animal model studies and clinical trials on the safety and pharmacokinetics of available medications. Brincidofovir and tecovirimat were the most studied medications that got approval for smallpox treatment according to the Animal Rule. Due to the conserved virology among orthopoxviruses, available medications might also be effective against monkeypox. However, tecovirimat has the strongest evidence to be effective and saf e for monkeypox treatment, and if there is a choice between the two drugs, tecovirimat has shown more promise so far. The risk of resistance should be considered in patients who failed to respond to tecovirimat. Hence, the target-based design of novel antivirals will enhance the availability and spectrum of effective anti-orthopoxvirus agents.

This article is protected by copyright. All rights reserved.

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Hypermethylation of RASSF1A gene in pediatric rhabdoid tumor of the kidney and clear cell sarcoma of the kidney

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Abstract

Background

Among pediatric renal tumors, rhabdoid tumor of the kidney (RTK) and clear cell sarcoma of the kidney (CCSK) are rare and associated with an unfavorable prognosis, while congenital mesoblastic nephroma (CMN) is associated with a good prognosis. Methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) promoter has been reported to correlate with a poor prognosis in patients with Wilms tumors, while its methylation status is unclear in other types of pediatric renal tumors.

Method

DNA methylation of the RASSF1A promoter in several pediatric renal tumors was analyzed with pyrosequencing. In order to clarify the correlation between expression of RASSF1A and DNA methylation of its promoter, the RTK cell line was treated with 5-Aza-2′-deoxycytidine (5-Aza-dC). RASSF1A was overexpressed in the RTK cell line to evaluate its functional effects.

Results

Quantitative methylation analysis demonstrated hypermethylation in the RASSF1A promoter region in RTK and CCSK, but not CMN. The 5-Aza-dC treatment induced demethylation of the RASSF1A promoter as well as increased RASSF1A mRNA expression. The transduction of RASSF1A has an effect on the suppression of viability and proliferation of RTK cells.

Conclusion

DNA methylation-mediated deficiency of RASSF1A might be involved in the development and aggressiveness of some pediatric renal tumors and correlated with a poor prognosis.

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Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham)

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.

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Posterior nasal neurectomy for intractable rhinitis: a systematic review of the literature

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Abstract

Background

Rhinitis affects up to 40% of the population worldwide and can significantly reduce quality of life. Some patients remain symptomatic despite maximal medical therapy. In refractory cases, posterior nasal neurectomy (PNN - the endoscopic division of the intranasal nerve branches containing postganglionic parasympathetic fibres) is postulated to reduce symptom burden.

Objectives of review

To establish whether PNN is effective and safe in the management of allergic and non-allergic rhinitis.

Type of review

Systematic review

Methods

A comprehensive literature search was undertaken using PubMed, EMBASE, MEDLINE, and Cochrane. The inclusion criteria were: studies published in English, studies where PNN was performed either with or without additional procedures, and where measures of objective/subjective outcomes and/or complications were reported. Extracted data included study type, sample size, surgical technique, study population characteristics, follow-up period, outcome measures, complications of surgery, and symptom outcomes.

Results

Twenty-three articles satisfied the inclusion criteria studying in total 2282 patients. Sample size ranged from 8-1056. There were three randomised controlled trials, three case control studies, and the remaining seventeen were case series using both objective and subjective outcome measures. All but one study found improved patient reported outcomes following PNN. Complications were reported in 14 studies - epistaxis was the most common complication and was observed in 30 patients (1.5% of subjects).

Conclusions

Posterior nasal neurectomy had a low rate of complications. Although most studies reported significant symptomatic improvement, their heterogeneity, level of evidence, study design, and/or quality was not sufficient to draw any firm conclusions on the effectiveness of the procedure. Larger, well designed studies are needed to clarify its role in the management of difficult-to-treat rhinitis.

This article is protected by copyright. All rights reserved.

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The Role of Pelvic Floor Muscle Training on Low Anterior Resection Syndrome: A Multicenter Randomized Controlled Trial

alexandrossfakianakis shared this article with you from Inoreader
imageBackground and Objective: Total mesorectal excision (TME) for rectal cancer (RC) often results in significant bowel symptoms, commonly known as low anterior resection syndrome (LARS). Although pelvic floor muscle training (PFMT) is recommended in noncancer populations for treating bowel symptoms, this has been scarcely investigated in RC patients. The objective was to investigate PFMT effectiveness on LARS in patients after TME for RC. Methods: A multicenter, single-blind prospective randomized controlled trial comparing PFMT (intervention; n=50) versus no PFMT (control; n=54) 1 month following TME/stoma closure was performed. The primary endpoint was the proportion of participants with an improvement in the LARS category at 4 months. Secondary outcomes were: continuous LARS scores, ColoRectal Functioning Outcome scores, Numeric Rating Scale scores, stool diary items, and Short Form 12 scores; all assessed at 1, 4, 6, and 12 months. Results: The proportion of participants with an improvement in LARS category was statistically higher after PFMT compared with controls at 4 months (38.3% vs 19.6%; P=0.0415) and 6 months (47.8% vs 21.3%; P=0.0091), but no longer at 12 months (40.0% vs 34.9%; P=0.3897). Following secondary outcomes were significantly lower at 4 months: LARS scores (continuous, P=0.0496), ColoRectal Functioning Outcome scores (P=0.0369) and frequency of bowel movements (P=0.0277), solid stool leakage (day, P=0.0241; night, P=0.0496) and the number of clusters (P=0.0369), derived from the stool diary. No significant differences were found for the Numeric Rating Scale/quality of life scores. Conclusions: PFMT for bowel symptoms after TME resulted in lower proportions and faster recovery of bowel symptoms up to 6 months after surgery/stoma closure, justifying PFMT as an early, first-line treatment option for bowel symptoms after RC.
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Mobile Health Application and Hypertension Management in Rural, Middle-Aged Adults: A Quality Improvement Project

alexandrossfakianakis shared this article with you from Inoreader
imageOver 29% of the adult population in the United States are diagnosed with hypertension, and rates are significantly higher in those adults who live in rural areas. Hypertension is recognized as the most prevalent comorbidity and modifiable risk factor leading to premature death. The purpose of this quality improvement project was to determine if using a mobile phone–based health application called Medisafe could enhance medication adherence and improve blood pressure control in rural-dwelling adults. A small group (N = 14) of middle-aged (45-64 years old) patients with hypertension were recruited to download the free Medisafe phone-based health application. Patients utilized the Medisafe application between their initial visit and a 4- to 6-week follow-up. At the follow-up visit, 64% (n = 9) of participants improved their level of hypertension control by blood pressure classification and improved their scores on the medication adherence questionnaire. The findings from this quality improvement project suggest the Medisafe application is useful to enhance medication adherence and blood pressure control. Future research and quality improvement initiatives are necessary to determine the broader efficacy of phone-based health applications in the rural adult population.
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