Advancing clinical trial equity through integration of telehealth and decentralized treatment.

Innovative strategies to increase clinical trial accessibility and equity are needed. We conducted a retrospective review of a phase II investigator-initiated trial to determine whether the modification of clinical trial design to decentralize study treatment can improve trial accessibility among underrepresented groups. Sociodemographic characteristics, including area deprivation indices, as well as study site travel distance, time, and costs were compared between enrolled participants who received chemotherapy locally and participants who did not. Participants who received chemotherapy locally lived substantially farther from the study site (median = 95.90 vs 25.20 miles, P = .004), faced a greater time burden traveling to the study site (median = 115.00 vs 34.00 minutes, P = .002), and had higher travel-related costs for a single trip to the study site (median = $62.81 vs $16.51, P = .004). This study highlights opportunities for alleviating financial and time burdens associated with clinical trial participation, promoting equity in clinical research. Trial Registration: ClinicalTrials.gov identifier: NCT04380337.

Development, successes, and potential pitfalls of multidisciplinary chronic disease management clinics in a family health team: a qualitative study.

BACKGROUND: The creation of Family Health Teams in Ontario was intended to reconfigure primary care services to better meet the needs of an aging population, an increasing proportion of which is affected by frailty and multimorbidity. However, evaluations of family health teams have yielded mixed results. METHODS: We conducted interviews with 22 health professionals affiliated or working with a well-established family health team in Southwest Ontario to understand how it approached the development of interprofessional chronic disease management programs, including successes and areas for improvement. RESULTS: Qualitative analysis of the transcripts identified two primary themes: [1] Interprofessional team building and [2] Inadvertent creation of silos. Within the first theme, two subthemes were identified: (a) collegial learning and (b) informal and electronic communication. CONCLUSION: Emphasis on collegiality among professionals, rather than on more traditional hierarchical relationships and common workspaces, created opportunities for better informal communication and shared learning and hence better care for patients. However, formal communication and process structures are required to optimize the deployment, engagement, and professional development of clinical resources to better support chronic disease management and to avoid internal care fragmentation for more complex patients with clustered chronic conditions.

Mapping of Pelvic Ring Injuries From High-Energy Trauma Using Unfolded CT Image Technology.

OBJECTIVES: High-energy pelvic ring injuries are associated with significant morbidity and mortality, elevating the importance of injury pattern identification. The purpose of this study was to use a novel 3D computed tomography (CT) unfolding process to both evaluate high-energy pelvic ring injures and to produce injury frequency maps based on injury patterns. METHODS: Patients 18-65 years of age presenting to a level 1 trauma center with pelvic ring injuries between 2016 and 2020 were identified. Of the 482 patients reviewed, 355 were excluded primarily due to having a low energy mechanism, inadequate radiographs, or an isolated fracture. Unfolded pelvic CT images were created using syngo.via CT Bone Reading software. Pelvic ring injury frequency maps were created using the unfolded pelvic CT images and a previously described mapping technique. RESULTS: One hundred twenty-seven patients analyzed had a mean age of 32.7 years. The most common mechanisms of injury (MOI) were motor vehicle collision (30.7%) and fall from height (23.6%). The breakdown of pelvic ring injuries included LC1 = 44.1%, LC2 = 7.1%, LC3 = 14.2%, APC1 = 2.4%, APC2 = 15.0%, APC3 = 5.5%, and VS = 11.8%, with OTA/AO-61B = 74.0% and OTA/AO-61C = 26.0%. Pelvic ring mapping revealed that articular and bony injuries varied markedly between the different types of pelvic ring disruptions, both in type and location. CONCLUSIONS: Pelvic ring injury frequency maps created from unfolded CT images reflect consistent injury patterns providing distinctive information based on force vector mechanisms. Unfolded CT images allow for a novel way to visualize pelvic ring injuries which yield greater comprehension of failure patterns with implications for treatment.

Heliotropium procubens Mill: Taxonomic Significance and Characterization of Phenolic Compounds via UHPLC-HRMS- In Vitro Antioxidant and Enzyme Inhibitory Activities.

The aim of the present study was the phytochemical analysis of the aerial parts of Heliotropium procumbens Mill., a herb from Boraginaceae plant family not previously studied. The methanol (ME) and aqueous extracts (WE) of the aerial parts were assayed for their total phenolic and flavonoid content and antioxidant properties, using free radical scavenging (DPPH, ABTS), reducing power (FRAP, CUPRAC), phosphomolybdenum and metal chelating assays. The extracts displayed considerable free radical scavenging activity against DPPH and ABTS radicals, with potential values of 46.88 and 68.31 mg TE/g extract for ME, and 93.43 and 131.48 mg TE/g extract for WE, respectively. Key clinical enzymes involved in neurodegenerative diseases AChE and BChE, diabetes (α-amylase and α-glucosidase) and skin whitening (tyrosinase) were also assayed. The phytochemical profile of the studied species was determined through UHPLC-HRMS, whereby 26 secondary metabolites were identified, three of which (luteolin-7-glucoside, lithospermic and rosmarinic acids) were isolated and structurally determined by NMR spectral means. H. procubens was found to harbor bioactive metabolites and could, hence, serve as a source of biological activities which could be further explored and exploited for potential applications.

Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice.

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.

Hypericum Essential Oils-Composition and Bioactivities: An Update (2012-2022).

Hypericum genus, considered to comprise over 500 species that exhibit cosmopolitan distribution, has attracted human interest since ancient times. The present review aims to provide and summarize the recent literature (2012-2022) on the essential oils of the title genus. Research articles were collected from various scientific databases such as PubMed, ScienceDirect, Reaxys, and Google Scholar. Scientific reports related to the chemical composition, as well as the in vitro and in vivo pharmacological activities, are presented, also including a brief outlook of the potential relationship between traditional uses and Hypericum essential oils bioactivity.

Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin receptor (SSR) analogs is now an established systemic treatment for neuroendocrine tumors (NET). However, more short- and long-term data about renal and hepatotoxicity is needed. Here we present our experience in this clinical scenario. METHODS: Eighty-six patients with progressive SSR-expressing malignancies underwent PRRT with Lu-177 Dotatate and were followed up for up to 2 years. Laboratory tests were done 1 week before each cycle and every 2 months at follow-up. Hepatic and renal toxicity was determined based on NCI CTCAE V5.0. RESULTS: 55/86 (64%) patients completed all 4 cycles of PRRT; 18/86 (20.9%) are currently being treated; 13/86 (15.1%) had to discontinue PRRT: 4/13 (31%) due to hematologic toxicity, 9/13 (69%) due to non-PRRT-related comorbidities. Out of the patients who finished treatment, only transient grade 2 toxicities were observed during PRRT: hypoalbuminemia in 5.5% (3/55), and renal toxicity (serum creatinine and estimated glomerular filtration rate) in 1.8% (1/55). No grade 3 or 4 liver and renal toxicity occurred. Patients presenting with impaired liver or renal function prior to PRRT, either improved or had stable findings. No deterioration was observed. CONCLUSION: Peptide receptor radionuclide therapy does not have a negative impact on liver and renal function, even in patients with pre-existing impaired parameters. No grade 3 or 4 hepatic or renal toxicity was identified. Only transient grade 2 hypoalbuminemia in 5.5% and nephrotoxicity in 1.8% of patients were seen during PRRT.

Short cephalomedullary nail toggle: a closer examination.

OBJECTIVES: In patients with wide femoral canals, an undersized short nail may not provide adequate stability, leading to toggling of the nail around the distal interlocking screw and subsequent loss of reduction. The purpose of this study was to identify risk factors associated with nail toggle and to examine whether increased nail toggle is associated with increased varus collapse. DESIGN: Retrospective cohort study. SETTING: Level 1 and level 3 trauma center. PATIENTS/PARTICIPANTS: Seventy-one patients with intertrochanteric femur fractures treated with short cephalomedullary nails (CMN) from October 2013 to December 2017. INTERVENTION: Short CMN. MAIN OUTCOME MEASUREMENTS: Nail toggle and varus collapse were measured on intraoperative and final follow-up radiographs. Risk factors for nail toggle including demographics, fracture classification, quality of reduction, Dorr type, nail/canal diameter ratio, lag screw engaging the lateral cortex, and tip-apex distance (TAD) were recorded. RESULTS: On multivariate regression analysis, shorter TAD (P = .005) and smaller nail/canal ratio (P < .001) were associated with increased nail toggle. Seven patients (10%) sustained nail toggle >4 degrees. They had a smaller nail/canal ratio (0.54 vs 0.74, P < .001), more commonly Dorr C (57% vs 14%, P = .025), lower incidence of lag screw engaging the lateral cortex (29% vs 73%, P = .026), shorter TAD (13.4 mm vs 18.5 mm, P = .042), and greater varus collapse (6.2 degrees vs 1.3 degrees, P < .001) compared to patients with nail toggle < 4 degrees. CONCLUSIONS: Lower percentage nail fill of the canal and shorter TAD are risk factors for increased nail toggle in short CMNs. Increased nail toggle is associated with increased varus collapse.Level of evidence: Therapeutic Level III.

Circumferential Pelvic Antishock Sheeting.

Pelvic ring fractures range from low-energy falls in the elderly to high-energy mechanisms in young patients. These injuries can be a significant cause of morbidity and mortality and are frequently associated with additional injuries. Hemorrhage and resultant hemodynamic instability are often associated with high-energy injuries and require prompt management. Circumferential pelvic antishock sheeting is an effective and readily available tool for reducing pelvic volume at the accident scene or in the emergency department, while still allowing access to the abdomen and lower extremities for ongoing resuscitation. This article, and the associated instructional video, reviews the indications and proper technique for placing a pelvic sheet.

Acute myeloid leukaemia: recent data on prognostic gene mutations, in relation to stratified therapies for elderly patients.

TET2 protein is encoded by the gene TET2 which specifically catalyses the demethylation of 5-methylcytosine to cytosine. Mutations in TET2 have been identified in a number of haematological malignancies, including leukaemias and lymphomas. In acute myeloid leukaemia (AML), loss of TET2 function drives DNA methylation and gene silencing, contributing to disease pathogenesis and progression, making it an interesting target. Although such mutations are considered rare, there is an increasing body in the literature identifying them as unfavourable prognostic markers in AML. The hypomethylating agent nucleoside analogue 5-azacytidine is used in the treatment of AML and other haematological malignancies i.e. myelodysplastic syndrome (MDS). It functions by re-activating silenced genes is responsible for cytosine methylation, thereby driving differentiation and also promoting apoptosis of dysfunctional haematological cells. The present review article deals with the consequences of DNA methylation in relation to TET2 in AML, focusing on the potential prognostic effect of TET2 gene mutations, along with demethylating epigenetic strategies towards prediction of therapeutic response. The necessity for personalized therapeutic regimes, especially for older patients suffering from AML with mutated TET2 and/or other genetic alterations, along with its prognostication are also underlined.

Chemical constituents from Cordia alliodora and C. colloccoca (Boraginaceae) and their biological activities.

Two new natural products, 5-O-[ß-D-apiofuranosyl-(1→6)-ß-d-glucopyranosyl]-1-isoindolinone (1) as well as N-(2E)-3-[(2S,3R)-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]acryloylglycine (2), along with four known compounds (3-6), were isolated from the methanolic extract of Cordia alliodora root bark. Furthermore, the methanolic extract of Cordia colloccoca leaves, afforded the known flavonoids afzelin (7) and quercitrin (8). The isolated secondary metabolites were assayed for their antimicrobial activities against a panel of 6g positive and negative bacteria and three human pathogenic fungi. Moreover, their antiproliferative effect was also evaluated in vitro against the human non-small-cell bronchopulmonary carcinoma line NSCLC-N6, the epidermoid lung cancer cell line A549 as well as the normal human skin fibroblast cell line (AG01523).

Nutri-epigenetics and synthetic analogs in cancer chemoprevention.

Nutri-epigenetics has lately emerged as a new field in cancer epigenetic research. Cancer represents a multistage and heterogeneous disease that is driven by progressive genetic and epigenetic abnormalities. Epigenetic activity is influenced by several exogenous and endogenous factors including, nutrition, environment, disease, ethnicity, life style, medication, toxins, physical activity, age, gender and family genetics. Epigenetic therapy including mainly natural phenolics is a new area for drug development in cancer prevention. The current generation of epigenetic synthetic analogs are primarily target to inhibit the activity and expression of methyltransferases and histone deacetylases. Epigenetic mechanisms underlying nutrition seem very important tools nowadays in further understanding human health in general. New targeted natural and synthetic agents, along with the application of modern genomic methods, could substantially offer more specific armamentarium towards the prevention and therapy of cancer. The present short review demonstrates a selection of natural and recent synthetic chemopreventing compounds, in relation to their epigenetic mechanisms and current/future uses/limitations in therapeutics.

Management of complications of forearm fractures.

Forearm fractures may be complicated by the disruption of the distal radioulnar, proximal radioulnar, or radiocapitellar joints. The key principles in treating this unique subset of fractures include early recognition and management of the injury and restoration and maintenance of the anatomic alignment. This articles addresses radial diaphyseal fractures with distal radioulnar joint disruption, proximal ulnar fractures with radiocapitellar disruption, and disruption of the forearm longitudinal axis and how to properly recognize and manage these forearm fracture-dislocations.

Photocatalytic and photoelectrocatalytic degradation of the drug omeprazole on nanocrystalline titania films in alkaline media: Effect of applied electrical bias on degradation and transformation products.

Photocatalytic and photoelectrocatalytic degradation of the drug omeprazole has been studied in the presence of nanocrystalline titania films supported on glass slides or transparent FTO electrodes in alkaline environment. Its photocatalytic degradation rate was assessed by its UV absorbance and by HPLC, while its transformation products were analyzed by HR-LC-MS. Based on UV absorbance, omeprazole can be photocatalytically degraded at an average rate of 6.7×10(-4)min(-1) under low intensity UVA irradiation of 1.5mWcm(-2) in the presence of a nanoparticulate titania film. This corresponds to degradation of 1.4mg of omeprazole per gram of the photocatalyst per liter of solution per hour. The photodegradation rate can be accelerated in a photoelectrochemical cell by applying a forward bias. In this case, the maximum rate reached under the present conditions was 11.6×10(-4)min(-1) by applying a forward bias of +0.6V vs. Ag/AgCl. Four major transformation products were successfully identified and their profiles were followed by HR-LC-MS. The major degradation path includes the scission of the sulfoxide bridge into the corresponding pyridine and benzimidazole ring derivates and this is accompanied by the release of sulfate anions in the reaction mixture.

Photocatalytic and photoelectrocatalytic degradation of the antibacterial agent ciprofloxacin.

Photocatalytic and photoelectrocatalytic degradation of the antibacterial fluoroquinolone drug, ciprofloxacin, has been studied in the presence of nanocrystalline titania films supported on glass slides or transparent electrodes. The degradation has been examined either in pure water or in the presence of NaOH or NaCl. Titania films can photocatalytically or photoelectrocatalytically degrade ciprofloxacin. In the presence of NaOH, the degradation rate was lower than in pure water and this is explained by the fact that at high pH values attraction of ciprofloxacin to the titania surface is discouraged. In the presence of NaCl, the degradation rate was the highest, thanks to Cl-based radicals which can be photocatalytically created by interacting with photogenerated holes. Application of a forward (anodic) bias increased the photodegradation rate in the presence of both electrolytes while a reverse (cathodic) bias decreased the photodegradation rate. Electrocatalytic effects, i.e. degradation of ciprofloxacin in the dark or in the absence of a photocatalyst under an applied bias of up to ±1.0 V vs. Ag/AgCl, were not detected in the case of NaOH and were of limited importance in the case of NaCl.

Observational study on patient's satisfactions and quality of life (QoL) among cancer patients receiving treatment with palliative care intent in a tertiary hospital in Malaysia.

The main objective of palliative treatment for cancer patients has been to maintain, if not improve, the quality of life (QoL). There is a lack of local data on satisfaction and QoL among cancer patients receiving palliative treatment in Malaysia. This study covers patients with incurable, progressive cancer disease receiving palliative treatment in a teaching hospital in Kuala Lumpur, comparing the different components of QoL and correlations with patient satisfaction. A cross-sectional survey using Malay validated SF36 QoL and PSQ-18 (Short Form) tools was carried out between July 2012 -January 2013 with 120 cancer patients receiving palliative treatment, recruited into the study after informed consent using convenient sampling. Results showed that highest satisfaction were observed in Communication Aspect (50.6±9.07) and the least in General Satisfaction (26.4±5.90). The Mental Component Summary (44.9±6.84) scored higher when compared with the Physical Component Summary (42.2±7.91). In this study, we found that patient satisfaction was strongly associated with good quality of life among cancer patients from a general satisfaction aspect (r=0.232). A poor significant negative correlation was found in Physical Component (technical quality, r=-0.312). The Mental Component showed there was a poor negative correlation between time spent with doctor (r=-0.192) and accessibility, (r=-0.279). We found that feeling at peace and having a sense of meaning in life were more important to patients than being active or achieving good physical comfort. More studyis needed to investigate patients who score poorly on physical and mental component aspects to understand their needs in order to achieve better cancer care.

Antioxidant treatment strategies for hyperphenylalaninemia.

Hyperphenylalaninemia (HPA) leads to increased oxidative stress in patients with phenylketonuria (PKU) and in animal models of PKU. Early diagnosis and immediate adherence to a phenylalanine-restricted diet prevents HPA and, consequently, severe brain damage. However, treated adolescent and adult PKU patients have difficulties complying with the diet, leading to an oscillation of phenylalanine levels and associated oxidative stress. The brain is especially susceptible to reactive species, and oxidative stress might add to the impaired cognitive function found in these patients. The restricted PKU diet has a very limited nutrient content from natural foods and almost no animal protein, which reduces the intake of important compounds. These specific compounds can act as scavengers of reactive species and can be co-factors of antioxidant enzymes. Supplementation with nutrients, vitamins, and tetrahydropterin has given quite promising results in patients and animal models. Antioxidant supplementation has been studied in HPA, however there is no consensus about its always beneficial effects. In this way, regular exercise could be a beneficial addition on antioxidant status in PKU patients. A deeper understanding of PKU molecular biochemistry, and genetics, as well as the need for improved targeted treatment options, could lead to the development of new therapeutic strategies.