Tag: nevin manimala

Rev Esc Enferm USP. 2023 Sep 4;57:e20230122. doi: 10.1590/1980-220X-REEUSP-2023-0122en. eCollection 2023.

ABSTRACT

OBJECTIVE: To assess the intensity and frequency of moral distress in mental health nurses in Brazil.

METHOD: Cross-sectional study with 173 nurses from the Psychosocial Care Network in Brazil. The Brazilian Scale of Moral Distress in Nurses, adapted for the context of mental health, was used. For data processing, descriptive and inferential statistical analysis was used.

RESULTS: Mostly moderate levels of intensity and frequency of moral distress (medians between 2.25 – 3.73 and 2.00 – 3.22, respectively) were observed, with emphasis on the factors working conditions and social conflicts.

CONCLUSION: The level of moral distress evidenced in mental health nurses in Brazil reflects the dimension and amplitude of the phenomenon in different points of the Psychosocial Care Network. The relevance of discussions on coping strategies for moral distress is highlighted, articulating elements such as sensitivity, resilience, and moral courage, so that ethical deliberation is applied in care and management settings.

PMID:37695606 | DOI:10.1590/1980-220X-REEUSP-2023-0122en

Invest Ophthalmol Vis Sci. 2023 Sep 1;64(12):17. doi: 10.1167/iovs.64.12.17.

ABSTRACT

PURPOSE: Retinal detachment (RD) is a sight-threatening ocular disease caused by separation of the neurosensory retina from the underlying retinal pigment epithelium layer. Its genetic basis is unclear because of a limited amount of data. In this study, we aimed to identify genetic risk loci associated with RD in participants without diabetes mellitus and to construct a polygenic risk score (PRS) to predict the risk of RD.

METHODS: A genome-wide association study was conducted using data from the Taiwan Biobank to identify RD risk loci. A total of 1533 RD cases and 106,270 controls were recruited, all of whom were Han Chinese. Replication studies were performed using data from the UK Biobank and Biobank Japan. To construct the PRS, a traditional clumping and thresholding method was performed and validated by fivefold cross-validation.

RESULTS: Two novel loci with significant associations were identified. These two genes were TMEM132D (lead single nucleotide polymorphism [SNP]: rs264498, adjusted-P = 7.18 × 10-9) and VIPR2 (lead SNP: rs3812305, adjusted-P = 8.38 × 10-9). The developed PRS was effective in discriminating individuals at high risk of RD with a dose-response relationship. The quartile with the highest risk had an odds ratio of 1244.748 compared to the lowest risk group (95% confidence interval, 175.174-8844.892).

CONCLUSIONS: TMEM132D and VIPR2 polymorphisms are genetic candidates linked to RD in Han Chinese populations. Our proposed PRS was effective at discriminating high-risk from low-risk individuals.

PMID:37695605 | DOI:10.1167/iovs.64.12.17

JAMA Pediatr. 2023 Sep 11. doi: 10.1001/jamapediatrics.2023.3566. Online ahead of print.

ABSTRACT

IMPORTANCE: Currently, the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) for short stature cohorts is uncertain. Despite previous studies reporting the widespread use of ES and CMA, a definitive diagnostic yield has not been established.

OBJECTIVE: To investigate the diagnostic yield of ES and CMA in short stature.

DATA SOURCES: A systematic literature search was conducted using relevant keywords in 3 databases (PubMed, Embase, and Web of Science) in February 2023.

STUDY SELECTION: Eligible studies for meta-analysis were those that had at least 10 participants with short stature who were diagnosed using either ES or CMA and the number of diagnosed patients was reported. Of 5222 identified studies, 20 were eventually included in the study.

DATA EXTRACTION AND SYNTHESIS: Two independent investigators extracted relevant information from each study, which was then synthesized using proportional meta-analysis to obtain the overall diagnostic yield of ES and CMA.

MAIN OUTCOMES AND MEASURES: The primary outcome measure was to determine the overall diagnostic yield of ES and CMA. A subgroup meta-analysis was also performed to assess if the diagnostic yield varied depending on whether ES was used as a first-tier or last-resort test. Additionally, a meta-regression was carried out to investigate how the diagnostic yield varied over time.

RESULTS: Twenty studies were included, comprising 1350 patients with short stature who underwent ES and 1070 patients who completed CMA. The overall diagnostic yield of ES among the cohorts and CMA among the cohorts was found to be 27.1% (95% CI, 18.1%-37.2%) and 13.6% (95% CI, 9.2%-18.7%), respectively. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time.

CONCLUSION AND RELEVANCE: This systematic review and meta-analysis provides high-level evidence supporting the diagnostic efficacy of ES and CMA in patients with short stature. The findings serve as a solid reference for clinicians when making informed decisions about recommending these genetic tests.

PMID:37695591 | DOI:10.1001/jamapediatrics.2023.3566

J Neurovirol. 2023 Sep 11. doi: 10.1007/s13365-023-01169-5. Online ahead of print.

ABSTRACT

Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genotyping was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for developing HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.

PMID:37695541 | DOI:10.1007/s13365-023-01169-5

Phys Eng Sci Med. 2023 Sep 11. doi: 10.1007/s13246-023-01317-5. Online ahead of print.

ABSTRACT

In fluoroscopy-guided interventions (FGIs), obtaining large quantities of labelled data for deep learning (DL) can be difficult. Synthetic labelled data can serve as an alternative, generated via pseudo 2D projections of CT volumetric data. However, contrasted vessels have low visibility in simple 2D projections of contrasted CT data. To overcome this, we propose an alternative method to generate fluoroscopy-like radiographs from contrasted head CT Angiography (CTA) volumetric data. The technique involves segmentation of brain tissue, bone, and contrasted vessels from CTA volumetric data, followed by an algorithm to adjust HU values, and finally, a standard ray-based projection is applied to generate the 2D image. The resulting synthetic images were compared to clinical fluoroscopy images for perceptual similarity and subject contrast measurements. Good perceptual similarity was demonstrated on vessel-enhanced synthetic images as compared to the clinical fluoroscopic images. Statistical tests of equivalence show that enhanced synthetic and clinical images have statistically equivalent mean subject contrast within 25% bounds. Furthermore, validation experiments confirmed that the proposed method for generating synthetic images improved the performance of DL models in certain regression tasks, such as localizing anatomical landmarks in clinical fluoroscopy images. Through enhanced pseudo 2D projection of CTA volume data, synthetic images with similar features to real clinical fluoroscopic images can be generated. The use of synthetic images as an alternative source for DL datasets represents a potential solution to the application of DL in FGIs procedures.

PMID:37695509 | DOI:10.1007/s13246-023-01317-5

Am J Clin Dermatol. 2023 Sep 11. doi: 10.1007/s40257-023-00809-0. Online ahead of print.

ABSTRACT

Atopic dermatitis (AD) is a chronic inflammatory disease requiring efficacious and safe long-term therapy. Several new systemic treatments have recently been approved for use in patients with moderate to severe AD. However, head-to-head comparisons have not been conducted for all the currently available treatments for AD. Multiple network meta-analyses have compared efficacy of these different therapies during the initial 16-week treatment period, but not beyond week 16. Therefore, understanding the differences in key trial design and statistical methods is essential for evaluating long-term efficacy, making cross-trial comparisons, and informing treatment decisions. This focused narrative review provides an overview of data and trial methodology to guide clinicians in evaluating longer-term efficacy and safety of currently approved systemic treatments for patients with AD. We discuss important elements of longer-term trial designs and statistical analysis strategies that should be considered based on our experience as clinical trialists. In addition, a summary of key efficacy results of published, longer-term, phase III clinical trials of US Food and Drug Administration-approved, novel systemic treatments (i.e., dupilumab, tralokinumab, abrocitinib, and upadacitinib) is provided, including the design and data handling methods used. Long-term safety considerations and differences in the time-effect and safety profiles of various medications are also noted to help inform clinical decisions for individual patients. Overall, the findings of these trials support efficacy in long-term treatment with novel systemic agents for patients with AD.

PMID:37695504 | DOI:10.1007/s40257-023-00809-0

Clin Transl Oncol. 2023 Sep 11. doi: 10.1007/s12094-023-03317-z. Online ahead of print.

ABSTRACT

PURPOSE: This study investigated the prognostic potential of baseline C-reactive protein (CRP) levels and early CRP kinetics in a real-world cohort of patients with metastatic renal cell carcinoma (mRCC) under first-line (1L) therapy with immune checkpoint inhibitors (CPI).

METHODS/PATIENTS: Analyses were performed retrospectively in a cohort of 61 mRCC patients under CPI-based 1L therapy. Patients were stratified based on baseline CRP (< 10 vs ≥ 10 mg/l) and CRP change within the initial three months of CPI therapy (normal: baseline < 10 mg/l, normalized: baseline ≥ 10 mg/l and nadir < 10 mg/l, non-normalized: baseline and nadir ≥ 10 mg/l). Finally, the association of baseline CRP and CRP change with progression-free (PFS) and overall survival (OS) was evaluated.

RESULTS: Baseline CRP was not significantly associated with both PFS (p = 0.666) and OS (p = 0.143). Following stratification according to early CRP kinetics, 23, 25 and 13 patients exhibited normal, normalized and non-normalized CRP levels, respectively. Patients with normal and normalized CRP had a markedly prolonged PFS (p = 0.091) and OS (p = 0.008) compared to patients with non-normalized CRP. Consequently, significantly better PFS (p = 0.031) and OS (p = 0.002) were observed for the combined normal-normalized group. In multivariate analysis including ECOG and IMDC risk, normalized CRP kinetics alone or in combination with the normal group was identified as significant independent risk factor for OS, whereas a statistical trend was observed for PFS.

CONCLUSIONS: The present study emphasizes the prognostic potential of early CRP kinetics in CPI-treated mRCC. As a standard laboratory parameter, CRP can be easily implemented into clinical routine to facilitate therapy monitoring.

PMID:37695463 | DOI:10.1007/s12094-023-03317-z

J Endocrinol Invest. 2023 Sep 11. doi: 10.1007/s40618-023-02190-5. Online ahead of print.

ABSTRACT

AIMS: SIRT1 deficiency has been associated with diabetes, and a variant of the SIRT1 gene has been found to be involved in human autoimmune diabetes; however, it is unclear whether this genetic variation exists in Han Chinese with type 1 diabetes (T1D) and whether it contributes to development of T1D. Therefore, we aimed to explore the association of the SIRT1 gene single-nucleotide polymorphisms (SNPs) rs10997866 and rs3818292 in a Han Chinese population with T1D.

METHODS: This study recruited 2653 unrelated Han Chinese individuals, of whom 1289 had T1D and 1364 were healthy controls. Allelic and genotypic distributions of SIRT1 polymorphisms (rs10997866 and rs3818292) were determined by MassARRAY. Basic characteristics, genotype and allele frequencies of selected SNPs were compared between the T1D patients and healthy controls. Further genotype-phenotype association analysis of the SNPs was performed on the T1D patients divided into three groups according to genotype. Statistical analyses included the chi-square test, Mann‒Whitney U test, Kruskal‒Wallis H test and logistic regression.

RESULTS: The allelic (G vs. A) and genotypic (GA vs. AA) distributions of SIRT1 rs10997866 were significantly different in T1D patients and healthy controls (P = 0.039, P = 0.027), and rs10997866 was associated with T1D susceptibility under dominant, overdominant and additive models (P = 0.026, P = 0.030 and P = 0.027, respectively). Moreover, genotype-phenotype association analysis showed the GG genotype of rs10997866 and the GG genotype of rs3818292 to be associated with higher titers of IA-2A (P = 0.013 and P = 0.038, respectively).

CONCLUSION: SIRT1 rs10997866 is significantly associated with T1D susceptibility, with the minor allele G conferring a higher risk of T1D. Moreover, SIRT1 gene rs10997866 and rs3818292 correlate with the titer of IA-2A in Han Chinese individuals with T1D.

PMID:37695462 | DOI:10.1007/s40618-023-02190-5

J Endocrinol Invest. 2023 Sep 11. doi: 10.1007/s40618-023-02186-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the impact of pasireotide (PAS) therapy on hormonal and glycometabolic outcome in patients with acromegaly previously treated with combination medical therapies or unconventional dosages of first-generation somatostatin receptor ligands (fg-SRLs).

METHODS: Retrospective study carried out in two referral centers for pituitary diseases. Twenty-one acromegalic patients were switched to PAS (12 had biochemical control, 9 were uncontrolled). Data were collected after 3- and 6-months PAS treatment, and at the last available visit (median 35 months).

RESULTS: After switching to PAS therapy, a significant reduction in IGF-1 values was observed [median 39%; 0.79 xULN (IQR 0.5-1.01) vs 1.29 xULN (IQR 1.06-1.83); p = 0.009]. IGF-1 reduction was statistically significant in the 9 patients previously uncontrolled (61%, p = 0.016), and in the 12 controlled subjects (33%, p = 0.037). At last follow-up, the number of patients reaching an acceptable biochemical control (IGF-1 < 1.3 xULN) raised from 57 to 90% (p = 0.032). Mean HbA1c levels increased from 5.7% (5.5-5.9) to 6.0% (5.9-7) (p = 0.002), and the percentage of diabetic patients raised from 14% (3/21) to 67% (14/21) (p = 0.004). At the last evaluation HbA1c was ≥ 7.0% in 5 patients (24%). Antidiabetic drugs were initiated in 9 new patients, and in 7 out of 9 metformin alone was effective. Younger age and male sex were predictors for the maintenance of glucose homeostasis.

CONCLUSION: PAS monotherapy can be effective in acromegalic patients previously treated with combination medical therapies or unconventional dosages of fg-SRLs. Glucose imbalance can be managed in the vast majority of cases by use of lifestyle interventions and metformin.

PMID:37695461 | DOI:10.1007/s40618-023-02186-1

Int Endod J. 2023 Sep 11. doi: 10.1111/iej.13973. Online ahead of print.

ABSTRACT

AIM: To evaluate two- and three-dimensionally the effect of resorbable collagen-based bone-filling material on periapical healing of endodontic lesions with four-wall defects following endodontic microsurgery (EMS).

METHODOLOGY: This parallel, randomized controlled superiority clinical trial involved 86 lesions with the strictly endodontic origin and four-wall defect morphology. EMS procedures were performed by calibrated postgraduate residents. Before flap closure, osteotomies were randomized to the control or treatment group. In the control group, the flap was repositioned with no material added. In the treatment group, a collagen-based bone-filling augmentation material was placed into the osteotomy. Clinical and radiographic examinations were completed after 12 months. Periapical healing was evaluated by blinded evaluators using periapical (PA) radiographs according to Molven’s criteria and cone beam computed tomography (CBCT) scans according to PENN’s 3D criteria. Cortical plate healing was scored according to the RAC/B index. The data were analysed using Fisher’s exact test, Logistic regression models and Chi-squared test. The significance level was predetermined at p < .05.

RESULTS: Sixty-six cases were evaluated at the 12-month follow-up, with 30 and 36 cases in the control and treatment groups, respectively. Only the asymptomatic cases (control = 26, treatment = 32) were included in the radiographic evaluation. Twenty-three cases (88.5%) in the control and 28 (87.5%) cases in the treatment group demonstrated complete healing on PA radiographs (p = 1.000). On CBCT, 10 (38.4%) and 21 (65.6%) cases had completely healed in the control and treatment groups, respectively (p = .095). The re-establishment of the buccal cortical plate was detected in 12 (46.2%) and 22 (68.8%) cases in the control and treatment groups, respectively (p = .243).

CONCLUSION: Within the limitations of the present study, the use of collagen-based bone-filling material had no statistically significant effect on the periapical healing of endodontic lesions with four-wall defect following EMS at the 12-month follow-up when evaluated by PA radiographs or CBCT scans. However, the observed higher percentage of a re-established cortical plate in the treatment group could suggest a clinical benefit that is of interest after surgical endodontic treatment.

PMID:37695450 | DOI:10.1111/iej.13973