Nevin Manimala

Urology. 2023 Sep 9:S0090-4295(23)00778-1. doi: 10.1016/j.urology.2023.08.031. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the risk of persistent opioid use following various urologic procedures in adolescents and young adults.

MATERIALS AND METHODS: The TriNetX LLC Diamond Network was queried for patients aged 13 to 21 years who underwent pyeloplasty, hypospadias repair, inguinal hernia repair, inguinal orchiopexy, hydrocelectomy, or circumcision. Cohorts of patients prescribed and not prescribed postoperative opioids were created and propensity-matched for age, race/ethnicity, psychiatric diagnoses, and preoperative pain diagnoses. The primary outcome was new persistent opioid use, defined as new opioid use 3-9 months after index procedure without another surgery requiring anesthesia during the post-operative timeframe.

RESULTS: Of 32,789 patients identified, 66.0% received a postoperative opioid prescription. After propensity score matching for each procedure, 18,416 patients were included: 197 for pyeloplasty, 469 for hypospadias repair, 1,818 for inguinal hernia repair, 2,664 for inguinal orchiectomy, 534 for hydrocelectomy, and 3,526 for circumcision. Overall, 0.41% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 1.69% of patients who received postoperative opioids developed new persistent opioid use (p<0.05). Patients prescribed postoperative opioids had statistically higher odds of developing new persistent opioid use for hypospadias repair (RR: 17.0; 95% CI: 2.27-127.2), inguinal orchiectomy (RR: 3.46; 95% CI: 1.87-6.4), inguinal hernia repair (RR: 2.18; 95% CI: 1.07-4.44), and circumcision (RR: 4.83; 95% CI: 2.60-8.98).

CONCLUSIONS: The use of postoperative opioids after urological procedures in adolescents and young adults is associated with a significant risk of developing new persistent opioid use.

PMID:37696308 | DOI:10.1016/j.urology.2023.08.031

JMIR Pediatr Parent. 2023 Sep 11;6:e47035. doi: 10.2196/47035.

ABSTRACT

BACKGROUND: The Structured E-Parenting Support (STEPS) app provides support for parents of children with elevated hyperactivity, impulsivity, inattention, and conduct problems who are awaiting clinical assessment. STEPS will be evaluated in a randomized controlled trial (RCT) within the Online Parent Training for the Initial Management of ADHD Referrals (OPTIMA) research program in the United Kingdom. Phase 1 of the OPTIMA tested the feasibility of participants’ recruitment and the app’s usability.

OBJECTIVE: This study aimed to adapt a digital routine clinical monitoring system, myHealthE, for research purposes to facilitate waitlist recruitment; test using remote methods to screen and identify participants quickly and systematically; pilot the acceptability of the recruitment and assessment protocol; and explore the usability of STEPS.

METHODS: myHealthE was adapted to screen patients’ data. Parents’ and clinicians’ feedback on myHealthE was collected, and information governance reviews were conducted in clinical services planning to host the RCT. Potential participants for the observational feasibility study were identified from new referrals using myHealthE and non-myHealthE methods. Descriptive statistics were used to summarize the demographic and outcome variables. We estimated whether the recruitment rate would meet the planned RCT sample size requirement (n=352). In addition to the feasibility study participants, another group of parents was recruited to assess the STEPS usability. They completed the adapted System Usability Scale and responded to open-ended questions about the app, which were coded using the Enlight quality construct template.

RESULTS: Overall, 124 potential participants were identified as eligible: 121 (97.6%) via myHealthE and 3 (2.4%) via non-myHealthE methods. In total, 107 parents were contacted, and 48 (44.9%) consented and were asked if, hypothetically, they would be willing to participate in the OPTIMA RCT. Of the 28 feasibility study participants who provided demographic data, 21 (75%) identified as White. Their children had an average age of 8.4 (SD 1.7) years and 65% (31/48) were male. During the primary recruitment period (June to July 2021) when 45 participants had consented, 38 (84%) participants agreed hypothetically to take part in the RCT (rate of 19/mo, 95% CI 13.5-26.1), meeting the stop-go criterion of 18 participants per month to proceed with the RCT. All parents were satisfied or very satisfied with the study procedures. Parents (n=12) recruited to assess STEPS’ usability described it as easy to navigate and use and as having an attractive combination of colors and visual design. They described the content as useful, pitched at the right level, and sensitively presented. Suggested improvements included adding captions to videos or making the recorded reflections editable.

CONCLUSIONS: Remote recruitment and study procedures for testing a parenting intervention app are feasible and acceptable for parents. The parents felt that STEPS was a useful and easy-to-use digital parenting support tool.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s40814-021-00959-0.

PMID:37695667 | DOI:10.2196/47035

J Biomol Struct Dyn. 2023 Sep 11:1-19. doi: 10.1080/07391102.2023.2256876. Online ahead of print.

ABSTRACT

Cancer is one of the most prominent causes of death worldwide and tubulin is a crucial protein of cytoskeleton that maintains essential cellular functions including cell division as well as cell signalling, that makes an attractive drug target for cancer drug development. 1,3,4-oxadiazoles disrupt microtubule causing G2-M phase cell cycle arrest and provide anti-proliferative effect. In this study, field-based 3D-QSAR models were developed using 62 bioactive anti-tubulin 1,3,4-oxadiazoles. The best model characterized by PLS factor 7 was rigorously validated using various statistical parameters. Generated 3D-QSAR model having high degree of confidence showed favourable and unfavourable contours around 1,3,4-oxadiazole core that assisted in defining proper spatial positioning of desired functional groups for better bioactivity. A five featured pharmacophore model (AAHHR_1) was developed using same ligand library and validated through enrichment analysis (BEDROC160.9 value = 0.59, Average EF 1% = 27.05, and AUC = 0.74). Total 30,212 derivatives of 1,3,4-oxadiazole obtained from PubChem database was prefiltered through validated pharmacophore model and docked in XP mode on binding cavity of tubulin protein (PDB code: 1SA0) which led into the identification of 11 HITs having docking scores between -7.530 and -9.719 kcal/mol while the reference compound Colchicine exerted docking score of -7.046 kcal/mol. Following the analysis of MM-GBSA and ADME studies, HIT1 and HIT4 emerged as the two promising hits. To verify their thermodynamic stability at the target site, molecular dynamic simulations were carried out. Both HITs were further subjected to DFT analysis to determine their HOMO-LUMO energy gap for ensuring their biological feasibility. Finally, molecular docking based structural exploration for 1,3,4-oxadiazoles to set up a lead of Formula I for further advancements of tubulin polymerization inhibitors as anti-cancer agents.Communicated by Ramaswamy H. Sarma.

PMID:37695635 | DOI:10.1080/07391102.2023.2256876

J Cardiovasc Med (Hagerstown). 2023 Sep 6. doi: 10.2459/JCM.0000000000001536. Online ahead of print.

ABSTRACT

AIMS: Data regarding the risk of incident pericarditis in coronavirus disease 2019 (COVID-19) recovered patients are lacking. We determined the risk of incident pericarditis after COVID-19 infection by performing a systematic review and meta-analysis of available data.

METHODS: Following the PRISMA guidelines, we searched MEDLINE and Scopus to locate all articles published up to 11 February 2023 reporting the risk of incident pericarditis in patients who had recovered from COVID-19 infection compared to noninfected patients (controls) defined as those who did not experience the disease over the same follow-up period. Pericarditis risk was evaluated using the Mantel-Haenszel random effects models with hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I2 statistic.

RESULTS: Overall, 16 412 495 patients (mean age 55.1 years, 76.8% males), of whom 1 225 715 had COVID-19 infection, were included. Over a mean follow-up of 9.6 months, pericarditis occurred in 3.40 (95% CI: 3.39-3.41) out of 1000 patients who survived COVID-19 infection compared with 0.82 (95% CI: 0.80-0.83) out of 1000 control patients. Recovered COVID-19 patients presented a higher risk of incident pericarditis (HR: 1.95, 95% CI: 1.56-2.43, I2: 71.1%) compared with controls. Meta-regression analysis showed a significant direct relationship for the risk of incident pericarditis using HT (P = 0.02) and male sex (P = 0.02) as moderators, while an indirect association was observed when age (P = 0.01) and the follow-up length (P = 0.02) were adopted as moderating variables.

CONCLUSIONS: Recovered COVID-19 patients have a higher risk of pericarditis compared with patients from the general population.

PMID:37695617 | DOI:10.2459/JCM.0000000000001536

Eur J Gastroenterol Hepatol. 2023 Sep 11. doi: 10.1097/MEG.0000000000002638. Online ahead of print.

ABSTRACT

Restorative proctocolectomy (RPC) is the most common surgical procedure to restore gastrointestinal continuity after surgical resection of the colon and rectum. Pouchitis is a common complication with several different modalities that can be used to aid diagnosis. This systematic review and meta-analysis aimed at exploring the sensitivity and specificity these diagnostic modalities. The medical literature was searched using MEDLINE, EMBASE and EMBASE classic and PubMed from 1978 to June 2022. We calculated descriptive statistics using sensitivity, specificity, and false-positive rate of the primary studies and also their positive and negative likelihood ratios, and their diagnostic odds ratios. The screen found 5477 records with 13 studies being included. Faecal lactoferrin was found to have the highest pooled sensitivity and specificity of 98% and 88% respectively with imaging modalities coming in second and faecal calprotectin third with pooled sensitivities and specificities of 87% and 79% and 74% and 81% respectively. Faecal biomarkers particularly lactoferrin and imaging modalities may have an important role to play in diagnosing pouchitis. Importantly due to delays in availability of pouchoscopy, our data supports early ordering of these tests to help delineate from other causes. Further studies are required with larger cohort sizes to further validate these tests.

PMID:37695613 | DOI:10.1097/MEG.0000000000002638

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