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1.
Chronic kidney disease-associated pruritus: what is known and its application in children.
Shah, S, Onugha, E, Swartz, SJ
Pediatric nephrology (Berlin, Germany). 2024;(1):25-35
Abstract
Chronic kidney disease-associated pruritus (CKD-aP) or uremic pruritus (UP) is a frequent symptom in patients with kidney failure receiving kidney replacement therapy. Severe chronic kidney disease-associated pruritus correlates with poor outcome in patients on dialysis. It is multifactorial in etiology and has a significant impact on quality of life. There is, however, limited data for children. This review summarizes current epidemiology, clinical characteristics, pruritus scoring systems, and available therapeutic options for pruritus in patients with chronic kidney disease and those receiving dialysis. Optimal care requires proper awareness of the severity of symptoms, the impact on quality of life, and the possible long-term outcomes. Optimizing dialysis prescription and correcting electrolyte abnormalities are important treatment targets. A wide range of therapeutic options is also available although none are well-studied in children. An earlier recognition of this debilitating symptom in children and treatment is imperative. A higher resolution version of the Graphical abstract is available as Supplementary information.
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2.
Tolvaptan and urea in paediatric hyponatraemia.
Veligratli, F, Alexandrou, D, Shah, S, Amin, R, Dattani, M, Gan, HW, Famuboni, A, Lopez-Garcia, C, Trompeter, R, Bockenhauer, D
Pediatric nephrology (Berlin, Germany). 2024;(1):177-183
Abstract
BACKGROUND The syndrome of inappropriate antidiuretic hormone (SIADH) is usually treated with fluid restriction. This can be challenging in patients with obligate fluid intake for nutrition or medication. Pharmaceutical treatment with tolvaptan and urea is available but minimal paediatric data are available. We review the efficacy and safety of tolvaptan and urea in paediatric patients with SIADH. METHODS Retrospective review of paediatric inpatients with clinical diagnosis of SIADH. Patients were identified from pharmacy records based on tolvaptan and urea prescriptions. Relevant information was extracted from patient electronic records. The main outcome measures included the number of days to sodium normalisation, the daily change in plasma sodium concentration, and the maximum increase of plasma sodium concentration in 24 h. Reported side effects were captured. RESULTS Thirteen patients received tolvaptan and six urea. Five patients had both agents (tolvaptan converted to urea). Tolvaptan led to plasma sodium normalisation in 10/13 (77%) within 6 days (median 2.5 days, range [1, 6]), with a median change of sodium concentration of 7 mmol/L (- 1, 14) within the first 24 h of treatment. Three patients experienced a change in plasma sodium > 10 mmol/l/day but had no apparent side effects. Urea led to sodium normalisation in 5/6 (83%) patients. The median number of days to normalisation with urea was 2 (1, 10) with a median change of plasma sodium concentration of 2 mmol/L (- 1, 6) within the first 24 h. All patients tolerated tolvaptan and/or urea without unexpected side effects. CONCLUSIONS Tolvaptan and urea appear to be safe and effective when fluid restriction is challenging in paediatric SIADH. A higher resolution version of the Graphical abstract is available as Supplementary information.
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3.
Impact and process evaluation of a primary-school Food Education and Sustainability Training (FEAST) program in 10-12-year-old children in Australia: pragmatic cluster non-randomized controlled trial.
Karpouzis, F, Lindberg, R, Walsh, A, Shah, S, Abbott, G, Ball, K
BMC public health. 2024;(1):657
Abstract
BACKGROUND Environmentally sustainable food initiatives accompanying nutrition education, such as the Food Education and Sustainability Training (FEAST) program, have gained traction in school settings. The aim of this trial was to conduct an impact and process evaluation of FEAST, to evaluate its effect on children's fruit and vegetable (F&V) intakes, and secondary outcomes: F&V variety consumed, nutrition knowledge, food preparation/cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours, and food production knowledge. METHODS FEAST was a 10-week curriculum-aligned program, designed to educate children about healthy eating, food waste, and sustainability, while teaching cooking skills. It was implemented by classroom teachers, face-to-face and online, during COVID-19 school closures, in Australia in 2021. A custom designed survey was used to collect baseline and post-intervention data from students. Generalised linear mixed models (GLMM) estimated group differences in pre-post changes for primary and secondary outcomes. Surveys were also administered to students and teachers to evaluate intervention implementation. RESULTS Twenty schools participated and self-selected to be either intervention schools (n = 10) or wait-list control (WLC) schools (n = 10). A total of 977, 5th and 6th grade children participated in the trial with a mean age of 11.1 years (SD ± 0.7). The FEAST intervention, compared to WLC, did not result in significant increases in primary outcomes nor secondary outcomes. The process evaluation revealed FEAST was well-received by students and teachers, but COVID-19 school closures hindered implementation fidelity with a less intense program delivered under the constraints of pandemic lockdowns. CONCLUSIONS This is the first cluster non-randomized controlled trial designed to independently evaluate FEAST in the primary-school setting. No evidence was found for improved F&V intakes in children, nor secondary outcomes. However, the positive process evaluation results suggest that further trials of the program are warranted. If implemented as originally designed (pre-pandemic), with increased duration and complemented by supporting school policies, such programs have the potential to improve children's daily F&V intakes, cooking skills and food waste behaviours. This would support the Australian curriculum and contribute to: health promotion within schools and sustainable schools initiatives, the national agenda to reduce food waste and sustainable development goals. AUSTRALIAN AND NEW ZEALAND CLINICAL TRIALS REGISTRY [ACTRN12620001347954]- Registered prospectively on 14/12/2020.
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4.
Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention.
Huang, Y, Liu, Y, Pandey, NK, Shah, S, Simon-Soro, A, Hsu, JC, Ren, Z, Xiang, Z, Kim, D, Ito, T, et al
Nature communications. 2023;(1):6087
Abstract
Dental caries is the most common human disease caused by oral biofilms despite the widespread use of fluoride as the primary anticaries agent. Recently, an FDA-approved iron oxide nanoparticle (ferumoxytol, Fer) has shown to kill and degrade caries-causing biofilms through catalytic activation of hydrogen peroxide. However, Fer cannot interfere with enamel acid demineralization. Here, we show notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, we discover that the stability of SnF2 is enhanced when mixed with Fer in aqueous solutions while increasing catalytic activity of Fer without any additives. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, even at four times lower concentrations, without adverse effects on host tissues or oral microbiome. Our results reveal a potent therapeutic synergism using approved agents while providing facile SnF2 stabilization, to prevent a widespread oral disease with reduced fluoride exposure.
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5.
Monkeypox: Treatment, Vaccination, and Prevention.
Shah, S, Fulmali, D
Cureus. 2023;(1):e33434
Abstract
In regions where the disease is endemic, Monkeypox (MPV) transmission related to healthcare has been seen on numerous occasions. This disease has episodes of occurrence in certain regions around the globe, such as in the Democratic Republic of Congo's (DRC) Tshuapa region. Here, the disease was found with a prevalence of 0.35 per 1000, as per data collected by the Centers for Disease Control and Prevention (CDC) of the United States (US). Data also shows approximately 100 confirmed cases of MPV for every infection among Healthcare Workers (HCWs). These findings and scientific research on burns, superficial wounds, herpes, eczema vaccine, and other conditions indicate that MPV sufferers might get an advantage from medical care to lessen the effects of weakened skin and mucosa. This should involve guarding delicate anatomical areas like the eyes and genitalia, maintaining enough hydration and nourishment, and preventing and treating consequences like secondary bacterial diseases. In the DRC, this disease was first recognized in 1970. Since then, it has spread to numerous nations around the globe and gained substantial epidemiological significance. The most recent epidemic has taken place in 2022 worldwide. The viruses that cause MPV and cowpox are currently regarded as emerging. Because of the rise in international travel, the popularity of exotic pets, and the decline in smallpox vaccination rates, they pose a significant danger of spreading. Although it is believed that this viral illness will eventually go away on its own, the possibility of the pandemic raises several serious problems for the general public's health. In addition to providing a broad overview of the Monkeypox Virus (MPXV), this study will detail the epidemiology, clinical hallmarks, assessment, and treatment of MPV sufferers.
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6.
Investigating the potential anti-depressive mechanisms of statins: a transcriptomic and Mendelian randomization analysis.
Jiang, JC, Hu, C, McIntosh, AM, Shah, S
Translational psychiatry. 2023;(1):110
Abstract
Observational studies and randomized controlled trials presented inconsistent findings on the effects of cholesterol-lowering statins on depression. It therefore remains unclear whether statins have any beneficial effects on depression, and if so, what the underlying molecular mechanisms are. Here, we aimed to use genomic approaches to investigate this further. Using Connectivity Map (CMap), we first investigated whether statins and antidepressants shared pharmacological effects by interrogating gene expression responses to drug exposure in human cell lines. Second, using Mendelian randomization analysis, we investigated both on-target (through HMGCR inhibition) and potential off-target (through ITGAL and HDAC2 inhibition) causal effects of statins on depression risk and depressive symptoms, and traits related to the shared biological pathways identified from CMap analysis. Compounds inducing highly similar gene expression responses to statins in HA1E cells (indicated by an average connectivity score with statins > 90) were found to be enriched for antidepressants (12 out of 38 antidepressants; p = 9E-08). Genes perturbed in the same direction by both statins and antidepressants were significantly enriched for diverse cellular and metabolic pathways, and various immune activation, development and response processes. MR analysis did not identify any significant associations between statin exposure and depression risk or symptoms after multiple testing correction. However, genetically proxied HMGCR inhibition was strongly associated with alterations in platelets (a prominent serotonin reservoir) and monocyte percentage, which have previously been implicated in depression. Genetically proxied ITGAL inhibition was strongly associated with basophil, monocyte and neutrophil counts. We identified biological pathways that are commonly perturbed by both statins and antidepressants, and haematological biomarkers genetically associated with statin targets. Our findings warrant pre-clinical investigation of the causal role of these shared pathways in depression and potential as therapeutic targets, and investigation of whether blood biomarkers may be important considerations in clinical trials investigating effects of statins on depression.
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7.
Multifaceted roles of pollen in the management of cancer.
Kolipaka, T, Khairnar, P, Phatale, V, Pandey, G, Famta, P, Shah, S, Asthana, A, Nanduri, S, Raghuvanshi, RS, Srivastava, S
International journal of pharmaceutics. 2023;:123278
Abstract
Oral drug delivery of microparticles demonstrates shortcomings like aggregation, decreased loading capacity and batch-to-batch variation, which limits its scale-up. Later, porous structures gained attention because of their large surface-to-volume ratio, high loading capacity and ability to carry biomacromolecules, which undergo degradation in GIT. But there are pitfalls like non-uniform particle size distribution, the impact of porogen properties, and harsh chemicals. To circumvent these drawbacks, natural carriers like pollen are explored in drug delivery, which withstands harsh environments. This property helps to subdue the acid-sensitive drug in GIT. It shows uniform particle size distribution within the species. On the other side, they contain phytoconstituents like flavonoids and polysaccharides, which possess various pharmacological applications. Therefore, pollen has the capability as a carrier system and therapeutic agent. This review focuses on pollen's microstructure, composition and utility in cancer management. The extraction strategies, characterisation techniques and chemical structure of sporopollenin exine capsule, its use in the oral delivery of antineoplastic drugs, and emerging cancer treatments like photothermal therapy, immunotherapy and microrobots have been highlighted. We have mentioned a note on the anticancer activity of pollen extract. Further, we have summarised the regulatory perspective, bottlenecks and way forward associated with pollen.
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8.
Fill levels, cost comparisons, and expulsion force requirements of commonly used topical ophthalmic nonsteroidal anti-inflammatory drugs.
Heath, M, McDonald, MC, Murphy, DA, Shah, SV, Shah, S, Ding, K, Riaz, KM
Journal of cataract and refractive surgery. 2023;(7):747-753
Abstract
PURPOSE To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) commonly perioperatively in the United States. SETTING Tertiary care academic medical center. DESIGN Prospective laboratory investigation. METHODS 8 commercially available NSAIDs (3 branded, 5 generic) were tested: branded bromfenac 0.07%, generic bromfenac 0.09%, diclofenac 0.1%, flurbiprofen 0.03%, generic ketorolac 0.5%, branded ketorolac 0.5%, ketorolac 0.47%, and branded nepafenac 0.3%. 10 bottles of each medication were tested, with an additional bottle tested for expulsion force requirements. A double-blinded method was used to measure the actual bottle fill volume and number of drops per bottle. The total cost per drop was calculated using published cash prices. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Dwass, Steel, Critchlow-Fligner Method. RESULTS 2 branded NSAIDs (bromfenac and nepafenac) had slightly lower-than-sticker volumes while generics other than ketorolac had higher-than-sticker volumes. Diclofenac and branded bromfenac had the highest and lowest adjusted number of drops respectively. Generic bromfenac and generic ketorolac had the highest and lowest adjusted volume compared with sticker volume respectively. Branded bromfenac was the most expensive medication, while generic diclofenac was the least expensive. Force expulsion requirements varied significantly among generic and branded NSAIDs. CONCLUSIONS Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical NSAID medications vary significantly. Surgeons may wish to consider these factors when deciding how best to use these medications perioperatively.
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9.
Efficacy and Safety of Vedolizumab and Tumor Necrosis Factor Inhibitors in the Treatment of Steroid-refractory Microscopic Colitis: A Systematic Review and Meta-analysis.
El Hage Chehade, N, Ghoneim, S, Shah, S, Pardi, DS, Farraye, FA, Francis, FF, Hashash, JG
Journal of clinical gastroenterology. 2023
Abstract
BACKGROUND Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab, have been investigated as treatment options for patients with steroid-refractory microscopic colitis. AIMS To evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory microscopic colitis. METHODS Retrospective studies and case series involving patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Pooled proportional meta-analyses were used to calculate the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Statistical analysis was performed in R using the metafor and meta packages. RESULTS A total of 14 studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% [95% CI (0.483; 0.776), I2=43% P=0.08], 57.8% [95% CI (0.3895; 0.7571), I2=0%, P=0.7541], and 39.3% [95% CI (0.0814; 0.7492), I2=66%, P=0.02] for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rates were 65.9% [95% CI (0.389; 0.889), I2=67%, P=0.02], 45.3% [95% CI (0.1479; 0.7747), I2=0%, P=0.36] and 32.5% [95% CI (0.000; 0.8508), I2=53%, P=0.14] in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biological-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively. CONCLUSION Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory microscopic colitis and with a tolerable safety profile. Future randomized controlled trials are needed to compare vedolizumab with TNF-α inhibitors and examine treatment effect on patients' quality of life.
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10.
Intraoperative Fluorophores: An Update on 5-Aminolevulinic Acid and Sodium Fluorescein in Resection of Tumors of the Central Nervous System and Metastatic Lesions-A Systematic Review and Meta-Analysis.
Shah, S, Ivey, N, Matur, A, Andaluz, N
Tomography (Ann Arbor, Mich.). 2023;(5):1551-1567
Abstract
INTRODUCTION Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the morbidity and mortality of the surgery. One area of recent interest has been the use of intraoperative fluorophores for tumor visualization such as 5-aminolevulinic acid (5-ala) and sodium fluorescein. We performed a systematic review and meta-analysis on the utility of fluorophore administration and EOR with each fluorophore to update the current literature. METHODS We conducted a systematic review and meta-analysis on the use of intraoperative 5-ala or fluorescein between 2021 and 2023 using the PubMed, SCOPUS, and WOS databases. The initial search yielded 8688 results. After inclusion and exclusion criteria were met, 44 studies remained for review. A meta-analysis was performed to compare the EOR between studies for each fluorophore and to compare the presence of intraoperative fluorescence by tumor type. Odds ratios (OR) were calculated for gross total resection (GTR), and two-way ANOVA tests were performed to compare rates of intraoperative fluorescence by fluorophore and tumor type. RESULTS In all groups except low-grade glioma, fluorescence was present after 5-ala administration; fluorescence was present for all groups after fluorescein administration. Two-way ANOVA analysis for both fluorophores demonstrated no statistically significant difference in presence of fluorescence between type of tumor resected. Meta-analysis of EOR did show a higher, but not significant, rate of GTR in the 5-ala group compared to controls (OR = 1.29, 95% CI = 0.49; 3.37). In the fluorescein group, there were statistically significant higher odds of GTR compared to the control group (OR = 2.10, 95% CI = 1.43; 3.10, I2 = 0%). CONCLUSIONS Both 5-ala and sodium fluorescein demonstrated intraoperative fluorescence among various tumor types in both cranial and spinal tumors, as well as efficacy in improving EOR. Both fluorophores merit further investigation for use in surgery of CNS tumors.