The clinical and financial impact of remote clinical oncology pharmacist engagement in community-based practices within The US Oncology Network.

INTRODUCTION: The integration of clinical oncology pharmacists into multidisciplinary healthcare teams is not well-described in the community practice setting. This study aims to analyze the clinical and financial impact of a remote-based clinical oncology pharmacist in four community oncology practices within The US Oncology Network. METHODS: Oncology-trained clinical pharmacists electronically reviewed chemotherapy orders for clinical optimization and financial stewardship within four community oncology practices. Each pharmacist was appointed at 0.5 full-time equivalents per practice. Financial, clinical, and workload metrics were tracked to monitor the impact of pharmacist engagement. RESULTS: Over 12 months, 5716 order reviews were completed with an intervention rate of 57%. The most common interventions identified by the pharmacists were interventions with clinical impact on the patient (36%), followed by dose rounding (35%) and therapeutic interchange (30%). Overall, interventions improved the cumulative practice margins by $1,455,033 and reduced total medication costs by $5,962,551. The average program return on investment was 415% (range 100-915%). CONCLUSION: Community oncology practices seek to provide high-value care in a lean, resource-constrained model. An oncology clinical pharmacist is a cost-effective and clinically invaluable care team member in community oncology practice. Pharmacists in this setting identified opportunities to improve medication safety and regimen optimization and demonstrated a significant tremendous financial impact on small-scale budgets in community oncology.

Systolic anterior motion of the anterior mitral valve leaflet begins in subclinical hypertrophic cardiomyopathy.

AIMS: Anterior mitral valve leaflet (AMVL) elongation is detectable in overt and subclinical hypertrophic cardiomyopathy (HCM). We sought to investigate the dynamic motion of the aorto-mitral apparatus to understand the behaviour of the AMVL and the mechanisms of left ventricular outflow tract obstruction (LVOTO) predisposition in HCM. METHODS AND RESULTS: Cardiovascular magnetic resonance imaging using a 1.5 Tesla scanner was performed on 36 HCM sarcomere gene mutation carriers without left ventricular hypertrophy (G+LVH-), 31 HCM patients with preserved ejection fraction carrying a pathogenic sarcomere gene mutation (G+LVH+), and 53 age-, sex-, and body surface area-matched healthy volunteers. Dynamic excursion of the aorto-mitral apparatus was assessed semi-automatically on breath-held three-chamber cine steady-state free precession images. Four pre-defined regions of interest (ROIs) were tracked: ROIPMVL: hinge point of the posterior mitral valve leaflet; ROITRIG: intertrigonal mitral annulus; ROIAMVL: AMVL tip; and ROIAAO: anterior aortic annulus. Compared with controls, normalized two-dimensional displacement-vs.-time plots in G+LVH- revealed subtle but significant systolic anterior motion (SAM) of the AMVL (P < 0.0001) and reduced longitudinal excursion of ROIAAO (P = 0.014) and ROIPMVL (P = 0.048). In overt and subclinical HCM, excursion of the ROITRIG/AMVL/PMVL was positively associated with the burden of left ventricular fibrosis (P < 0.028). As expected, SAM was observed in G+LVH+ together with reduced longitudinal excursion of ROITRIG (P = 0.049) and ROIAAO (P = 0.008). CONCLUSION: Dyskinesia of the aorto-mitral apparatus, including SAM of the elongated AMVL, is detectable in subclinical HCM before the development of LVH or left atrial enlargement. These data have the potential to improve our understanding of early phenotype development and LVOTO predisposition in HCM.

Diagnostic performance of S100B as a rule-out test for intracranial pathology in head-injured patients presenting to the emergency department who meet NICE Head Injury Guideline criteria for CT-head scan.

BACKGROUND: Traumatic brain injury is a common ED presentation. CT-head utilisation is escalating, exacerbating resource pressure in the ED. The biomarker S100B could assist clinicians with CT-head decisions by excluding intracranial pathology. Diagnostic performance of S100B was assessed in patients meeting National Institute of Health and Clinical Excellence Head Injury Guideline (NICE HIG) criteria for CT-head within 6 and 24 hours of injury. METHODS: This multicentre prospective observational study included adult patients presenting to the ED with head injuries between May 2020 and June 2021. Informed consent was obtained from patients meeting NICE HIG CT-head criteria. A venous blood sample was collected and serum was tested for S100B using a Cobas Elecsys-S100 module; >0.1 µg/mL was the threshold used to indicate a positive test. Intracranial pathology reported on CT-head scan by the duty radiologist was used as the reference standard to review diagnostic performance. RESULTS: This study included 265 patients of whom 35 (13.2%) had positive CT-head findings. Within 6 hours of injury, sensitivity of S100B was 93.8% (95% CI 69.8% to 99.8%) and specificity was 30.8% (22.6% to 40.0%). Negative predictive value (NPV) was 97.3% (95% CI 84.2% to 99.6%) and area under the curve (AUC) was 0.73 (95% CI 0.61 to 0.85; p=0.003). Within 24 hours of injury, sensitivity was 82.9% (95% CI 66.4% to 93.44%) and specificity was 43.0% (95% CI 36.6% to 49.7%). NPV was 94.29% (95% CI 88.7% to 97.2%) and AUC was 0.65 (95% CI 0.56 to 0.74; p=0.046). Theoretically, use of S100B as a rule-out test would have reduced CT-head scans by 27.1% (95% CI 18.9% to 36.8%) within 6 hours and 37.4% (95% CI 32.0% to 47.2%) within 24 hours. The risk of missing a significant injury with this approach would have been 0.75% (95% CI 0.0% to 2.2%) within 6 hours and 2.3% (95% CI 0.5% to 4.1%) within 24 hours. CONCLUSION: Within 6 hours of injury, S100B performed well as a diagnostic test to exclude significant intracranial pathology in low-risk patients presenting with head injury. In theory, if used in addition to NICE HIGs, CT-head rates could reduce by one-quarter with a potential miss rate of <1%.

Efficacy of supplemental MCT oil on seizure reduction of adult drug-resistant epilepsy - a single-center open-label pilot study.

OBJECTIVE: We set out to determine whether adding medium chain triglyceride (MCT) oil as a dietary supplement to standard diet in adult subjects with intractable epilepsy in a U.S. neurology clinical practice was associated with a reduction in number of seizures. We secondarily aimed to determine whether subjects experienced any side effects and whether there was a presence of urinary ketones while using MCT oil as a dietary supplement. METHODS: Adult patients with intractable epilepsy were recruited at standard of care clinical visits with their epileptologist. Once enrolled, subjects were instructed to supplement their diet with MCT oil as tolerated twice daily for three months (including a 1-2 week titration period, followed by a 1-2 week tapering off window) while keeping a seizure diary to record total number of seizures, presence of urinary ketones, and any side effects. RESULTS: Our data although limited by small sample size, shows that there is an estimated 42% reduction (p < 0.0001) in the rate of seizures. The MCT oil supplementation was well tolerated by most subjects except for minor GI side effects like nausea and loose stools. Most subjects developed ketones in their urine at some point during the trial. CONCLUSIONS: MCT oil supplementation reduced seizure frequency in study participants. The reported side effects included mild nausea, stomachache, loose stools. A placebo-controlled study will be more informative.

Reliability of ultrasound ovarian-adnexal reporting and data system amongst less experienced readers before and after training.

BACKGROUND: The 2018 ovarian-adnexal reporting and data system (O-RADS) guidelines are aimed at providing a system for consistent reports and risk stratification for ovarian lesions found on ultrasound. It provides key characteristics and findings for lesions, a lexicon of descriptors to communicate findings, and risk characterization and associated follow-up recommendation guidelines. However, the O-RADS guidelines have not been validated in North American institutions or amongst less experienced readers. AIM: To evaluate the diagnostic accuracy and inter-reader reliability of ultrasound O-RADS risk stratification amongst less experienced readers in a North American institution with and without pre-test training. METHODS: A single-center retrospective study was performed using 100 ovarian/adnexal lesions of varying O-RADS scores. Of these cases, 50 were allotted to a training cohort and 50 to a testing cohort via a non-randomized group selection process in order to approximately equal distribution of O-RADS categories both within and between groups. Reference standard O-RADS scores were established through consensus of three fellowship-trained body imaging radiologists. Three PGY-4 residents were independently evaluated for diagnostic accuracy and inter-reader reliability with and without pre-test O-RADS training. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), and area under the curve (AUC) were used to measure accuracy. Fleiss kappa and weighted quadratic (pairwise) kappa values were used to measure inter-reader reliability. Statistical significance was P < 0.05. RESULTS: Mean patient age was 40 ± 16 years with lesions ranging from 1.2 to 22.5 cm. Readers demonstrated excellent specificities (85%-100% pre-training and 91%-100% post-training) and NPVs (89%-100% pre-training and 91-100% post-training) across the O-RADS categories. Sensitivities were variable (55%-100% pre-training and 64%-100% post-training) with malignant O-RADS 4 and 5 Lesions pre-training and post-training AUC values of 0.87-0.95 and 0.94-098, respectively (P < 0.001). Nineteen of 22 (86%) misclassified cases in pre-training were related to mischaracterization of dermoid features or wall/septation morphology. Fifteen of 17 (88%) of post-training misclassified cases were related to one of these two errors. Fleiss kappa inter-reader reliability was 'good' and pairwise inter-reader reliability was 'very good' with pre-training and post-training assessment (k = 0.76 and 0.77; and k = 0.77-0.87 and 0.85-0.89, respectively). CONCLUSION: Less experienced readers in North America achieved excellent specificities and AUC values with very good pairwise inter-reader reliability. They may be subject to misclassification of potentially malignant lesions, and specific training around dermoid features and smooth vs irregular inner wall/septation morphology may improve sensitivity.

Universal posttransplant cyclophosphamide after allogeneic transplant, a retrospective single institution study.

BACKGROUND: The excellent results of posttransplant cyclophosphamide in decreasing graft-versus-host disease (GVHD) after haploidentical (HI) allogeneic transplant have challenged current donor selection algorithms. PATIENTS AND METHODS: We compared outcomes after matched sibling (MSD) versus alternative donor transplant using identical graft-versus-host disease (GVHD) prophylaxis including posttransplant cyclophosphamide (PTCy. Endpoints included engraftment, time outside of the hospital in the first 100 days after transplant, overall survival (OS), non-relapse mortality (NRM) and percentage of patients disease-free and off immunosuppression (DFOI) at one year and at the last follow-up. RESULTS: There were significant differences at baseline between matched donor versus HI donor transplants with higher disease-risk index (DRI), more female-to-male donor recipient pairs and a higher percentage of Black patients in the HI group. Engraftment and time out of the hospital favored MSD and matched unrelated donor transplants. Multivariate analysis showed that high DRI and Black race were associated with decreased survival and Black race was associated with a higher NRM. CONCLUSIONS: With the use of PTCy, our results support current donor selection algorithms. The finding of decreased survival and increased NRM in Black patients requires confirmation in a larger number of patients as well as the development of mitigation strategies.

Neuronal Glial Crosstalk: Specific and Shared Mechanisms in Alzheimer's Disease.

The human brain maintains billions of neurons functional across the lifespan of the individual. The glial, supportive cells of the brain are indispensable to neuron elasticity. They undergo various states (active, reactive, macrophage, primed, resting) and carefully impose either quick repair or the cleaning of injured neurons to avoid damage extension. Identifying the failure of these interactions involving the relation of the input of glial cells to the inception and/or progression of chronic neurodegenerative diseases (ND) is crucial in identifying therapeutic options, given the well-built neuro-immune module of these diseases. In the present review, we scrutinize different interactions and important factors including direct cell-cell contact, intervention by the CD200 system, various receptors present on their surfaces, CXC3RI and TREM2, and chemokines and cytokines with special reference to Alzheimer's disease (AD). The present review of the available literature will elucidate the contribution of microglia and astrocytes to the pathophysiology of AD, thus evidencing glial cells as obligatory transducers of pathology and superlative targets for interference.

Predatory Journals- The Power of the Predator Versus the Integrity of the Honest.

Over the last few decades, the authenticity and confidence of scientific work from around the world has been systematically corrupted by predatory journals and their affiliated publication houses. These journals predominantly prey on both aspiring and established academics and researchers from around the world, but primarily on individuals from developing countries, by aggressively soliciting manuscripts for a nominal publication fee without providing a robust editorial service or peer review system and ultimately promising fast track publication in a few days to weeks. Such journals may also diminish the opportunity for authors in developing countries from getting their original work published in legitimate journals. A majority of the work published in these pseudo journals aside from being incorrect and mundane, provide no advancement to science. But more importantly, the negative impact of these journals can have direct implications on patient health care and research.

Erratum: Chest radiographs of cardiac devices (Part 1): Cardiovascular implantable electronic devices, cardiac valve prostheses and Amplatzer occluder devices.

[This corrects the article DOI: 10.4102/sajr.v23i1.1730.].

Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".

The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.

Design and In-silico study of bioimaging fluorescence Graphene quantum dot-Bovine serum albumin complex synthesized by diimide-activated amidation.

Graphene quantum dot possesses advantageous characteristics like tunable fluorescence, nanometer size, low cytotoxicity, high biocompatibility enabling them as an ideal material for fluorescence bio-imaging. It exhibits a unique characteristic of DNA cleavage activity enhancer, gene/drug carrier, and anticancer targeting applications. In this article, we discussed the preparation of graphene quantum dot through the bottom-up method. Carbodiimide-activated amidation reactions were used for the functionalization of graphene quantum dot with Bovine Serum Albumin. Fluorescence spectroscopy data showed that the graphene quantum dot has size-dependent fluorescence emission. TEM and AFM studies showed that the size of graphene quantum dot was around 20 nm with narrow size distribution. Carbodiimide-activated amidation conjugation was successful in binding the protein onto graphene quantum dot and these conjugates were characterized by DLS, FTIR, fluorescence spectroscopy, and agarose gel electrophoresis. We also studied the structural-based in-silico molecular dynamic simulation by AutoDock, PyRx, and Discovery Studio Visualizer. Based on the virtual screening analysis and higher negative energy incorporation, it is observed that graphene quantum dot conjugated with bovine serum albumin quickly and formed is highly stable complex, which makes them a potential candidate for future applications in the field of bio-imaging, bio-sensing, gene/drug delivery, and tumor theragnostic.

Development of Mucoadhesive Buccal Film for Rizatriptan: In Vitro and In Vivo Evaluation.

The reduced therapeutic efficacy of rizatriptan in migraine treatment is primarily due to low oral bioavailability and extensive first pass metabolism. The purpose of this investigation was to optimize the thin mucoadhesive buccal film of rizatriptan and assess the practicability of its development as a potential substitute for conventional migraine treatment. Buccal films (FR1-FR10) were fabricated by a conventional solvent casting method utilizing a combination of polymers (Proloc, hydroxypropyl methylcellulose and Eudragit RS 100). Drug-loaded buccal films (F1-F4) were examined for mechanical, mucoadhesive, swelling and release characteristics. In vivo pharmacokinetics parameters of selected buccal film (F1) in rabbits were compared to oral administration. Films F1-F4 displayed optimal physicomechanical properties including mucoadhesive strength, which can prolong the buccal residence time. A biphasic, complete and higher drug release was seen in films F1 and F4, which followed Weibull model kinetics. The optimized film, F1, exhibited significantly higher (p < 0.005) rizatriptan buccal flux (71.94 ± 8.26 µg/cm2/h) with a short lag time. Film features suggested the drug particles were in an amorphous form, compatible with the polymers used and had an appropriate surface morphology suitable for buccal application. Pharmacokinetic data indicated a significantly higher rizatriptan plasma level (p < 0.005) and Cmax (p < 0.0001) upon buccal film application as compared to oral solution. The observed AUC0-12h (994.86 ± 95.79 ng.h/mL) in buccal treatment was two-fold higher (p < 0.0001) than the control, and the relative bioavailability judged was 245%. This investigation demonstrates the prospective of buccal films as a viable and alternative approach for effective rizatriptan delivery.

Diagnostic accuracy and inter-observer reliability of the O-RADS scoring system among staff radiologists in a North American academic clinical setting.

PURPOSE: The objective of this study is to evaluate the diagnostic accuracy, interobserver variability, and common lexicon pitfalls of the ACR O-RADS scoring system among staff radiologists without prior experience to O-RADS. MATERIALS AND METHODS: After independent review of the ACR O-RADS publications and 30 training cases, three fellowship-trained, board-certified staff radiologists scored 50 pelvic ultrasound exams using the O-RADS system. The diagnostic accuracy and area under receiver operating characteristic were analyzed for each reader. Overall agreement and pair-wise agreement between readers were also analyzed. RESULTS: Excellent specificities (92 to 100%), NPVs (92 to 100%), and variable sensitivities (72 to 100%), PPVs (66 to 100%) were observed. Considering O-RADS 4 and O-RADS 5 as predictors of malignancy, individual reader AUC values range from 0.94 to 0.98 (p < 0.001). Overall inter-reader agreement for all 3 readers was "very good," k = 0.82 (0.73 to 0.90, 95% CI, p < 0.001). Pair-wise agreement between readers were also "very good," k = 0.86-0.92. 14 out of 150 lesions were misclassified, with the most common error being down-scoring of a solid lesion with irregular outer contours. CONCLUSION: Even without specific training, experienced ultrasound readers can achieve excellent diagnostic performance and high inter-reader reliability with self-directed review of guidelines and cases. The study highlights the effectiveness of ACR O-RADS as a stratification tool for radiologists and supports its continued use in practice.

Maximal Wall Thickness Measurement in Hypertrophic Cardiomyopathy: Biomarker Variability and its Impact on Clinical Care.

OBJECTIVES: The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD). METHODS: A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death. RESULTS: MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk). CONCLUSIONS: Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.

The current and future aspects of glioblastoma: Immunotherapy a new hope?

Glioblastoma (GBM) is the most perilous and highly malignant in all the types of brain tumor. Regardless of the treatment, the diagnosis of the patients in GBM is very poor. The average survival rate is only 21 months after multimodal combinational therapies, which include chemotherapy, radiation, and surgery. Due to the intrusive and infiltrative nature of GBM, it requires elective therapy for specific targeting of tumor cells. Tumor vaccine in a form of immunotherapy has potential to address this need. Nanomedicine-based immunotherapies have clutch the trigger of systemic and specific immune response against tumor cells, which might be the approach to eliminating the unrelieved cancer. In this mechanism, combination of immunomodulators with specific target and appropriate strategic vaccines can stifle tumor anti-immune defense system and/or increase the capabilities of the body to move up immunity against the tumor. Here, we explore the different types of immunotherapies and vaccines for brain tumor treatment and their clinical trials, which bring the feasibility of the future of personalized vaccine of nanomedicine-based immunotherapies for the brain tumor. We believe that immunotherapy could result in a significantly more stable reaction in GBM patients.

Clinical presentation, diagnosis and management of aerodigestive tract foreign bodies in the adult population: Part 1.

In the adult population, foreign bodies may be accidentally or intentionally ingested or even inserted into a body cavity. The majority of accidentally ingested foreign bodies pass through the alimentary tract without any complications and rarely require intervention. Accidentally ingested foreign bodies are usually fish bones, bones of other animals, and dentures. Oesophageal food impaction is the commonest cause of oesophageal foreign bodies in the Western hemisphere. Intentionally ingested foreign bodies may be organic or inorganic, and often require intervention; these patients have either underlying psychological or mental disease or are involved in illegal activities such as body packing, which involves trafficking narcotics. Imaging plays a crucial role in not only identifying the type, number and location of the foreign body but also in excluding any complications. In this comprehensive pictorial review, we provide an overview of the spectrum of foreign bodies ingested in adults, emphasising the role of various imaging modalities, their limitations and common foreign body mimickers on imaging.

Clinical presentation, diagnosis and management of aerodigestive tract foreign bodies in the paediatric population: Part 2.

Children, especially toddlers, because of their behaviour, physiology and anatomical characteristics such as oral exploration of their surroundings, have a tendency to place objects in their mouth. Therefore, ingestion or aspiration of foreign bodies (FBs) in children is a potentially life-threatening and common problem seen across the world. In this second part of our pictorial review on ingested and aspirated FBs, we focus on the paediatric population, reviewing the current literature and examining the epidemiology, clinical presentation, anatomic considerations, appropriate imaging modalities, key imaging characteristics associated with clinically relevant FBs in the emergency department (ED) and current management protocols.

Enhanced Solubility and Bioavailability of Dolutegravir by Solid Dispersion Method: In Vitro and In Vivo Evaluation-a Potential Approach for HIV Therapy.

Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased Cmax (14.56 µg/mL) when compared to the physical mixture (4.12 µg/mL) and pure drug (3.45 µg/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99±10.07 µg/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45±6.58 µg/h/mL) and pure drug (49.27±6.16 µg/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.

Alcohol and acute traumatic brain injury in the emergency department.

OBJECTIVE: There is limited research from Australasian EDs describing the demographic make-up, injury severity and impact of alcohol in patients requiring computed tomography (CT) for suspected traumatic brain injury (TBI). The present study aims to review the frequency and presenting patterns of patients who consume alcohol prior to presenting with suspected TBI. METHODS: Retrospective observational study of patients referred for head CT to exclude TBI from a major referral centre and regional ED in New Zealand, between 1 September 2018 and 31 August 2019. Comparison groups were defined as 'alcohol involved' or 'no alcohol involved'. RESULTS: 97/425 (22.8% [95% CI 18.3-27.4]) of included TBI presentations involved alcohol. 73/97 (75.3% [95% CI 58.6-93.5]) were male and 41/97 (42.3% [95% CI 29.3-55.2]) were aged 18-30 years. The alcohol group were more likely to report assault as the injury mechanism (19.6% [95% CI 10.8-28.4] vs 5.2% [95% CI 2.7-7.7], P < 0.05) and have Glasgow Coma Scale scores reflecting more moderate (13.5% [95% CI 5.9-21.1] vs 3.5% [95% CI 1.5-5.6]) and severe (5.6% [95% CI 0.7-10.5] vs 3.2% [95% CI 1.2-5.2] TBI. Presentation times post-injury were delayed compared to the no alcohol group (3.4 h [interquartile range 1.9-14.8] vs 2.8 h [interquartile range 1.8-6.6], P < 0.05). CONCLUSION: One quarter of patients with suspected TBI had consumed alcohol prior to their injury. Predominantly, those affected were young males who reported higher rates of assault; however, alcohol use was recorded in all age groups and sex. Alcohol-affected patients presented later, potentially delaying time to diagnosis. The present study supports the call for public health interventions that aim to reduce alcohol misuse.

Nanotherapeutics in Neuropathologies: Obstacles, Challenges and Recent Advancements in CNS Targeted Drug Delivery Systems.

Neurology and associated nanotherapeutics are a complex field in terms of therapeutics and neurological disorder complexity. The brain is an intricate appendage and requires more precise embattled treatment for the particular diseases and hence it is a broad scale for developing more targeted drug deliveries. The brain is one of the most inaccessible tissues of the body due to the existence of the blood-brain barrier (BBB), thus delivery of drugs inside the brain is a striking dare and it is also tricky to treat central nervous system (CNS) complications pharmacologically. The therapeutic aspiration is to accomplish the lowest drug meditation in the brain tissues so as to gain favoured therapeutic results. To devastate this obstacle, nanotechnology is engaged in the field of targeted brain drug delivery and neuropathology targeting. These carriers hold myriad abilities as they may augment the drug delivery into the brain by shielding them from degradation and prolonging their transmission in the blood, as well as promoting their transport through the BBB. Nanopharmaceuticals are quickly sprouting as a new avenue that is engaged with the drug-loaded nanocarriers to demonstrate unique physicochemical properties and tiny size range for penetrating the central nervous system. The enchantment behind their therapeutic achievement is the condensed drug dose and inferior toxicity, whereby restricting the therapeutic compound to the specific site. Therefore, in this article, we have tried to recapitulate the advances of the novel scopes for the brain targeted drug delivery for complex neurological disorders.