Tenofovir Douche as HIV Preexposure Prophylaxis for Receptive Anal Intercourse: Safety, Acceptability, Pharmacokinetics, and Pharmacodynamics (DREAM 01).

BACKGROUND: Despite highly effective HIV preexposure prophylaxis (PrEP) options, no options provide on-demand, nonsystemic, behaviorally congruent PrEP that many desire. A tenofovir-medicated rectal douche before receptive anal intercourse may provide this option. METHODS: Three tenofovir rectal douches-220 mg iso-osmolar product A, 660 mg iso-osmolar product B, and 660 mg hypo-osmolar product C-were studied in 21 HIV-negative men who have sex with men. We sampled blood and colorectal tissue to assess safety, acceptability, pharmacokinetics, and pharmacodynamics. RESULTS: The douches had high acceptability without toxicity. Median plasma tenofovir peak concentrations for all products were several-fold below trough concentrations associated with oral tenofovir disoproxil fumarate (TDF). Median colon tissue mucosal mononuclear cell (MMC) tenofovir-diphosphate concentrations exceeded target concentrations from 1 hour through 3 to 7 days after dosing. For 6-7 days after a single product C dose, MMC tenofovir-diphosphate exceeded concentrations expected with steady-state oral TDF 300 mg on-demand 2-1-1 dosing. Compared to predrug baseline, HIV replication after ex vivo colon tissue HIV challenge demonstrated a concentration-response relationship with 1.9 log10 maximal effect. CONCLUSIONS: All 3 tenofovir douches achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effect exceeding oral TDF and with lower systemic tenofovir. Tenofovir douches may provide a single-dose, on-demand, behaviorally congruent PrEP option, and warrant continued development. Clinical Trials Registration . NCT02750540.

Clinical journey for patients with aortic regurgitation: A retrospective observational study from a multicenter database.

BACKGROUND: Data using real-world assessments of aortic regurgitation (AR) severity to identify rates of Heart Valve Team evaluation and aortic valve replacement (AVR), as well as mortality among untreated patients, are lacking. The present study assessed these trends in care and outcomes for real-world patients with documented AR. METHODS: Using a deidentified data set (January 2018-March 2023) representing 1,002,853 patients >18 years of age from 25 US institutions participating in the egnite Database (egnite, Inc.) with appropriate permissions, patients were classified by AR severity in echocardiographic reports. Rates of evaluation by the Heart Valve Team, AVR, and all-cause mortality without AVR were examined using Kaplan-Meier estimates and compared using the log-rank test. RESULTS: Within the data set, 845,113 patients had AR severity documented. For moderate-to-severe or severe AR, respectively, 2-year rates (95% confidence interval) of evaluation by the Heart Valve Team (43.5% [41.7%-45.3%] and 65.4% [63.3%-67.4%]) and AVR (19.4% [17.6%-21.1%] and 46.5% [44.2%-48.8%]) were low. Mortality at 2 years without AVR increased with greater AR severity, up to 20.7% for severe AR (p < 0.001). In exploratory analyses, 2-year mortality for untreated patients with left ventricular end-systolic dimension index > 25 mm/m2 was similar for moderate (34.3% [29.2%-39.1%]) and severe (37.2% [24.9%-47.5%]) AR. CONCLUSIONS: Moderate or greater AR is associated with poor clinical outcomes among untreated patients at 2 years. Rates of Heart Valve Team evaluation and AVR were low for those with moderate or greater AR, suggesting that earlier referral to the Heart Valve Team could be beneficial.

Pharmacokinetics of tenofovir alafenamide, emtricitabine, and dolutegravir in a patient on peritoneal dialysis.

INTRODUCTION: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited. METHODS: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose. RESULTS: Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR. CONCLUSIONS: In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.

Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study.

BACKGROUND AND AIMS: For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes. METHODS: The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year. RESULTS: Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure. CONCLUSIONS: In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

Applications, benefits and challenges of telehealth in India during COVID-19 pandemic and beyond: a systematic review.

BACKGROUND: India, the seventh-largest country in the world and the second-most populated faces enormous challenges when it comes to healthcare. The country's healthcare system was close to collapse due to the detrimental effects of the COVID-19 pandemic. Telehealth, which enables treating patients remotely, played a critical role during these challenging times. This systematic review investigates in detail the role of telehealth during COVID-19 and its application beyond the pandemic. METHODS: Database searches on PubMed, Scopus, Science Direct and Web of Science were carried out for studies published on telehealth, and articles were included if they focused on any audio or video telehealth consultation during the pandemic in India. Findings were synthesised into three main themes: applications, benefits and challenges of telehealth services. Methodological quality was assessed using JBI critical appraisal tools. RESULTS: The initial search on databases yielded 1143 articles. Of those, 19 met the eligibility criteria. Findings highlight the effective utilisation of telehealth across multiple medical specialities. Although insufficient technological infrastructure and other barriers due to the virtual consultation challenge the successful implementation of telehealth in India, it has the potential to bridge the rural-urban healthcare divide with cost-effective and easily accessible services. CONCLUSION: High patient/provider satisfaction underscores the need to integrate telehealth into routine healthcare practices in the country. However, the review urges the government and healthcare practitioners to address the telehealth challenges with prime importance to ensure quality healthcare throughout the nation even after the pandemic.

Ti3C2Tx-rGO-chitosan-based microcatheter sensor for real-time continuous monitoring of propofol: toward improved anesthetic management.

We are aiming to develop an electrochemical microcatheter sensor for the detection and real-time continuous monitoring of propofol (PPF), which is an anesthetic drug majorly used during medical treatment. This proposed microcatheter-based sensing strategy meets the challenge of real-time periodic and continuous monitoring of propofol by using d-Ti3C2Tx-rGO-chi-modified carbon paste microcatheter sensor transducer. The sensing methodology relies on voltammetry and chronoamperometry transduction methods. The reusable microcatheter sensor was fabricated by embedding the three electrodes into a few millimeters-wide Teflon tube. The nanocomposite was characterized using advanced analytical instruments such as XRD, FE-SEM, EDX, Raman spectroscopy, and XPS. Further, electrode interfacial properties were characterized with voltammetry and electrochemical impedance spectroscopy. The electroanalytical performance of the modified microcatheter sensor was tested for the detection of PPF in phosphate buffer by using chronoamperometry with a wide linear range of 5 to 110 µM (at an applied potential of 0.3 V vs. Ag/AgCl). The sensor's practical potency was confirmed in human serum with a dynamic linear range of 10 to 130 µM. The sensor exhibited a good limit of detection values in phosphate buffer (2 µM) and natural human plasma (4 µM). The new sensor displays different dimensions of information while displaying high sensitivity, selectivity, and long-term stability. The outstanding analytical performance of the developed sensor holds considerable promise for the continuous monitoring of propofol, its effective management, and optimization of the doses in the patient's body.

Population pharmacokinetics of tenofovir, emtricitabine and intracellular metabolites in transgender women.

AIMS: Transgender women (TGW) have been underrepresented in trials and use gender-affirming hormonal therapies (GAHT) that may alter renal function by significantly increasing creatinine clearance. Population pharmacokinetic (popPK) models and simulations would aid in understanding potential differences in emtricitabine/tenofovir disproxil fumarate (F/TDF) parent-metabolite concentrations in TGW on GAHT when compared to cisgender men (CGM) not exposed to GAHT. METHODS: Pharmacokinetic (PK) data from a Phase 1, open-label clinical trial with directly observed therapy of daily F/TDF consisting of 8 TGW and 8 CGM was utilized for model building. PopPK analysis was performed using nonlinear mixed effects modelling (NONMEM 7.5.0). Covariates of body weight, creatinine clearance, and gender were evaluated. Final models were subjected to Monte Carlo simulations to compare drug exposure following once daily and on-demand (IPERGAY 2 + 1 + 1) dosing of F/TDF. RESULTS: Tenofovir (TFV) and emtricitabine PK were best described by a 2-compartment model, first-order absorption/elimination with absorption lag time. Parent models were linked to their metabolites by first order formation and elimination. Creatinine clearance was a significant covariate influencing clearance in both models. Simulations demonstrated that at least 2, weekly 2 + 1 + 1 cycles of on-demand dosing in TGW on GAHT is necessary for TFV-diphosphate to reach similar exposure after the initial week of on-demand dosing in CGM not on GAHT. CONCLUSION: PopPK models of TFV, emtricitabine and intracellular metabolites in TGW were established. Dose simulations revealed that TGW should be treated for at least 2 weeks to have comparable exposures to CGM.

Clinical Profile and Treatment Outcomes of Patients With Acremonium Species Positive Keratitis Managed in a Tertiary Eye Care Center.

PURPOSE: To report the clinical profile and treatment outcomes of patients with culture-positive Acremonium keratitis. METHODS: This is a retrospective observational study. Medical records of all patients treated in a tertiary eye hospital for culture positive infective keratitis from March 2016 to February 2021 were screened, of which those positive for Acremonium species on fungal culture were reviewed. Demographic details, clinical presentation, clinical course, treatment given, total follow-up duration, time taken for ulcer to heal, scar size, and final visual acuity in the last follow-up were recorded. RESULTS: Fifty three cases of fungal keratitis caused by Acremonium species were identified, 22 females and 31 males, with average age of 46.39±18.64 years. The mean duration of symptoms being 54.47±50 days. Only five patients had a history of trauma with vegetative matter. Clinical presentation of patients showed a large number of variations, with 2 patients presenting as peripheral ulcerative keratitis and 1 with epithelial plaque. The mean visual acuity of patients at presentation was 2.43±0.46 logMAR units. Thirty-three of 53 patients presented with perforated corneal ulcer and underwent penetrating keratoplasty; 20 patients were medically managed on topical voriconazole 1%, natamycin 5%, and oral voriconazole. The mean duration of healing of epithelial defect was 95±60.62 days (range 60-165 days). CONCLUSION: Acremonium keratitis has a long and indolent course. A prolonged combination therapy of natamycin and voriconazole seems to be effective in the management. A delay in the diagnosis of Acremonium keratitis often leads to clinical worsening requiring keratoplasty.

Single-Atom Catalysts: A Sustainable Pathway for the Advanced Catalytic Applications.

A heterogeneous catalyst is a backbone of modern sustainable green industries; and understanding the relationship between its structure and properties is the key for its advancement. Recently, many upscaling synthesis strategies for the development of a variety of respectable control atomically precise heterogeneous catalysts are reported and explored for various important applications in catalysis for energy and environmental remediation. Precise atomic-scale control of catalysts has allowed to significantly increase activity, selectivity, and in some cases stability. This approach has proved to be relevant in various energy and environmental related technologies such as fuel cell, chemical reactors for organic synthesis, and environmental remediation. Therefore, this review aims to critically analyze the recent progress on single-atom catalysts (SACs) application in oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution reaction, and chemical and/or electrochemical organic transformations. Finally, opportunities that may open up in the future are summarized, along with suggesting new applications for possible exploitation of SACs.

Variation in the pharmacokinetics of glucosamine in healthy individuals.

OBJECTIVES: Clinical trial data for the efficacy of glucosamine in OA are conflicting. Reportedly, Rotta-manufactured glucosamine products are more likely to be effective, and a possible explanation is greater bioavailability than other brands. Specifically, the aim was to compare the steady-state pharmacokinetics of Rotta- and non-Rotta-manufactured glucosamine products in healthy volunteers and examine the interindividual variability. METHODS: In a crossover design, healthy adult participants ingested 1500 mg/day of a Rotta (DONA powder sachets; imported by Mylan Health, Carole Park, QLD, Australia) and a non-Rotta (glucosamine sulphate 1500 mg one-a-day tablet; Blackmores, Warriewood, NSW, Australia) glucosamine product/brand individually for 6 days. Blood samples were collected immediately before and for 12 h after the ingestion of the last dose of each brand and analysed to determine plasma levels of glucosamine. The pharmacokinetic parameters at steady state [including the minimum (Css min) and maximum (Css max) plasma concentration of glucosamine, time to reach Css max post-dosing (Tss max) and area under the plasma concentration vs time curve (AUCss 0-12)] for each brand were calculated and statistically compared. RESULTS: Fourteen participants [mean age 35.5 years (s.d. 8.8)] were recruited (64.2% males). No significant differences were observed in the pharmacokinetic parameters between the two brands. However, for both brands, the coefficient of variation for Css min, Tss max and AUCss 0-12 exceeded 20%, indicating considerable differences in the parameters between participants. No significant association of the pharmacokinetic parameters was observed with various dosing- and participant-related variables. CONCLUSION: Substantial interindividual differences in the absorption and elimination of glucosamine could be a cause of variable clinical outcomes in OA. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (http://www.ANZCTR.org.au/ACTRN12618000699268p.aspx), number ACTRN12618000699268p.

WSe2crystals on paper: flexible, large area and broadband photodetectors.

The paper-based photodetector has recently captivated a great deal of attention in various opto-electronics applications because of facile, cost effective and green synthesis. Two-dimensional transition metal dichalcogenides materials are promising for photodetection under the broad spectral range. In this work, we have fabricated paper-based device by rubbing the tungsten di-selenide (WSe2) crystals on paper substrate. Low-cost, facile and green synthesis technique was employed to make a high-performance paper-based WSe2photodetector. Paper-based photodetector was fabricated via non-toxic simply rubbing process of WSe2nanosheets on low-cost bio-degradable paper. The photodetector shows good responsivity of 72.5 µA W-1and detectivity at around 2.4 × 107Jones at very low bias (1.0 V) at wavelength of 780 nm, respectively. Due to good photo-absorption strength, photodetector exhibits excellent photo-response over wide wavelength range from visible to near infrared. This device also shows very good flexibility with a stable photo-response. This device shows a general and reliable study for the design of photodetectors that is eco-friendly and cost-effective. Overall studied results of the fabricated device indicate that they have the ability to be used in large-scale preparation of the device.

Comparative biological study between quinazolinyl-triazinyl semicarbazide and thiosemicarbazide hybrid derivatives.

Practical synthesis and biological activities of quinazolinyl-triazinyl semicarbazides (10a-j) and quinazolinyl-triazinyl thiosemicarbazides (11a-j) have been described. The novel semicarbazides and thiosemicarbazides were prepared by condensation of different nucleophiles like isocyanate and isothiocyanate by the displacement of chlorine atoms on the basis of functionality concept on varying conditions. The synthesized quinazolinyl-triazinyl semicarbazide and thiosemicarbazide derivatives were evaluated for their expected antimicrobial activity. All the final synthesized derivatives were characterized by their melting point, mass spectra, 1H NMR and 13C NMR as well as elemental microanalysis. The final analogues were then analyzed for their in vitro antimicrobial activity against bacteria (Gram positive and negative) and fungus using the agar streak dilution method as well as in vitro anti-HIV activity against two types of viral strains, viz. HIV type I (IIIB) and type II (ROD) by using MTT assay method. SAR and HOMO-LUMO studies were also carried out for proving the structural biological activity. Among them, compounds 10e, 10f, 11h and 11j gave best results as their energy gap is very low which makes their activity higher.

Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators.

Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.

Semi-automated vs. manual 3D reconstruction of central mesenteric vascular models: the surgeon's verdict.

BACKGROUND: 3D vascular anatomy roadmaps are currently being implemented for surgical planning and navigation. Quality of the reconstruction is critical. The aim of this article is to compare anatomical completeness of models produced by manual and semi-automatic segmentation. METHODS: CT-datasets from patients included in an ongoing trial, underwent 3D vascular reconstruction applying two different segmentation methods. This produced manually-segmented models (MSMs) and semi-automatically segmented models (SAMs) which underwent a paired comparison. Datasets were delivered for reconstruction in 4 batches of 6, of which only batch 4 contained patients with abnormal anatomy. Model completeness was assessed quantitatively using alignment and distance error indexes and qualitatively with systematic inspection. MSMs were the gold standard. Assessed vessels were those of interest to the surgeon performing D3-right colectomy. RESULTS: 24 CT-datasets (13 females, age 44-77) were used in a paired comparative analysis of 48 3D-models. Quantitatively, SAMs showed structural improvement from Batch 1 to 3. Batch 4, with abnormal vessels, showed the highest error-index values. Qualitatively, 91.7% of SAMs did not contain all mesenteric branches relevant to the surgeon. In SAMs, 1 (12.5%) right colic artery-RCA scored as a complete vessel. 3 (37.5%) RCAs scored as incomplete and 4 (50%) RCAs were absent. 6 (25%) of 24 middle colic arteries-MCA scored as complete vessels. 11 (45.8%) scored as incomplete while 7 (29.2%) MCAs were absent. 13 (54.2%) of 24 ileocolic arteries-ICA were complete vessels. 11 (45.8%) scored as incomplete. None (0%) were absent. Additionally, it was observed that 10 (41.7%) of SAMs contained all their jejunal arteries, when compared to MSMs. Calibers of "complete" vessels were significantly higher than in "missing" vessels (MCA p < 0.001, RCA p = 0.016, ICA p < 0.001, JAs p < 0.001). CONCLUSION: Despite acceptable results from quantitative analysis, qualitative comparison indicates that semi-automatically generated 3D-models of the central mesenteric vasculature could cause considerable confusion at surgery.

Use of mixed reality for improved spatial understanding of liver anatomy.

Introduction: In liver surgery, medical images from pre-operative computed tomography and magnetic resonance imaging are the basis for the decision-making process. These images are used in surgery planning and guidance, especially for parenchyma-sparing hepatectomies. Though medical images are commonly visualized in two dimensions (2D), surgeons need to mentally reconstruct this information in three dimensions (3D) for a spatial understanding of the anatomy. The aim of this work is to investigate whether the use of a 3D model visualized in mixed reality with Microsoft HoloLens increases the spatial understanding of the liver, compared to the conventional way of using 2D images.Material and methods: In this study, clinicians had to identify liver segments associated to lesions.Results: Twenty-eight clinicians with varying medical experience were recruited for the study. From a total of 150 lesions, 89 were correctly assigned without significant difference between the modalities. The median time for correct identification was 23.5 [4-138] s using the magnetic resonance imaging images and 6.00 [1-35] s using HoloLens (p < 0.001).Conclusions: The use of 3D liver models in mixed reality significantly decreases the time for tasks requiring a spatial understanding of the organ. This may significantly decrease operating time and improve use of resources.

Kinetic Driver of Antibacterial Drugs against Plasmodium falciparum and Implications for Clinical Dosing.

Antibacterial drugs are an important component of malaria therapy. We studied the interactions of clindamycin, tetracycline, chloramphenicol, and ciprofloxacin against Plasmodium falciparum under static and dynamic conditions. In microtiter plate assays (static conditions), and as expected, parasites displayed the delayed death response characteristic for apicoplast-targeting drugs. However, rescue by isopentenyl pyrophosphate was variable, ranging from 2,700-fold for clindamycin to just 1.7-fold for ciprofloxacin, suggesting that ciprofloxacin has targets other than the apicoplast. We also examined the pharmacokinetic-pharmacodynamic relationships of these antibacterials in an in vitro glass hollow-fiber system that exposes parasites to dynamically changing drug concentrations. The same total dose and area under the concentration-time curve (AUC) of the drug was deployed either as a single short-lived high peak (bolus) or as a constant low concentration (infusion). All four antibacterials were unambiguously time-driven against malaria parasites: infusions had twice the efficacy of bolus regimens, for the same AUC. The time-dependent efficacy of ciprofloxacin against malaria is in contrast to its concentration-driven action against bacteria. In silico simulations of clinical dosing regimens and resulting pharmacokinetics revealed that current regimens do not maximize time above the MICs of these drugs. Our findings suggest that simple and rational changes to dosing may improve the efficacy of antibacterials against falciparum malaria.

Fecal Coliform Bacterial Detection to Assess Enema Adherence in HIV Prevention Clinical Studies.

Evaluating the efficacy of any HIV prevention strategy is dependent on ensuring and objectively monitoring adherence to the intervention. Medicated rectal enemas are a potential method for providing topical, episodic HIV prophylaxis during receptive anal intercourse. Assessing adherence to recommended enema dosing regimens is essential in evaluating the utility of this strategy. We utilized fecal coliform bacteria on used enema tips as a marker for enema use. Enema tip coliforms were tested by repurposing a microtiter plate-based water quality test designed to detect fecal contamination of water. Coliform detection occurred with 100% sensitivity and specificity when tips were assayed on day of use. The assay performed well post-7 day sample storage at room temperature, yielding a sensitivity of 80% and specificity of 93%. All (n = 64) samples collected in a subset of the DREAM-01 rectal microbicide enema clinical trial tested positive, even when tips were evaluated > 7 days post-reported use. The coliform-based enema tip assay allows monitoring of adherence in interventions involving rectal enemas in a sensitive, specific and inexpensive manner. The test performs well in clinical trial settings.

Clinical Outcomes of Transcatheter Aortic Valve Implantation in Patients With Extremely Large Annulus and SAPIEN 3 Dimensions Based on Post-Procedural Computed Tomography.

BACKGROUND: Patients with severe aortic stenosis (AS) and an extra-large annulus (ELA) area (>683 mm2) can rarely be treated by transcatheter aortic valve replacement (TAVR) because of the size limitation of the transcatheter heart valves. This study aimed to evaluate the feasibility of TAVR using a 29-mm SAPIEN3 (S3) valve in patients with ELA and S3-dimensions by post-procedural computed tomography (post-CT). Methods and Results: We included 261 patients undergoing TAVR using a 29-mm S3: 30 patients with ELA and 231 with non-ELA were identified. S3-dimensions were evaluated at the S3 inflow and annulus level by post-CT in 129 patients. The ELA group had a greater aortic annulus area measured by pre-procedural CT (737.3±54.7 vs. 578.4±41.9 mm2, P<0.0001), higher balloon inflation volume (36 vs. 33 mL, P<0.0001), a larger S3 area at inflow by post-CT (729.6±42.2 vs. 682.2±35.0 mm2, P<0.001), and a correlation between the inflation volume and S3 area (r=0.71, P=0.0005). No differences were observed between groups in paravalvular aortic regurgitation (PAR) ≥mild (43.3% vs. 27.6%, P=0.09), PAR ≥moderate (3.3% vs. 1.3%, P=0.39) or 1-year mortality (10.0% vs. 9.1%, P=0.87). CONCLUSIONS: TAVR using a 29-mm S3 with extra inflation of the delivery balloon can be considered as a treatment option for patients with severe AS and ELA.

A novel screening method for potential naringinase-producing microorganisms.

Naringinase has high industrial importance, and the progress in naringinase research is still quite slow. The unavailability of an effective, simple screening method, which will be applicable to different microorganisms such as bacteria, fungi, and actinomycetes, is one of the main reasons for this gap. Therefore, a simple plate assay was developed for effective screening of microorganisms for naringinase by exposing to iodine vapors. This plate assay will fill the technological void for simple screening method and will lead to screen more potent industrially important naringinase-producing microorganisms.

Physicochemical stability of extemporaneously prepared clonidine solutions for use in neonatal abstinence syndrome.

WHAT IS KNOWN AND OBJECTIVE: Extemporaneously prepared clonidine admixture is increasingly used for the management of neonatal abstinence syndrome. However, its stability beyond 15 minutes at room temperature is currently unknown. Therefore, healthcare professionals must prepare clonidine admixtures multiple times a day while the treatment is indicated, resulting in subsequent limitations and problems. The aim of this study was to investigate the physicochemical stability of clonidine in commonly used pharmaceutical diluents at clinically relevant concentrations and temperatures. METHODS: Glass bottles (n = 18) and plastic syringes (n = 18) containing 0.5 and 5 µg/mL of clonidine in either 5% glucose, 10% glucose or 0.9% normal saline were prepared and stored at 4°C for 7 days and at 35°C for 24 hours, respectively. Aliquots were withdrawn at predefined time points and analysed for the concentration of clonidine, changes in pH and colour, and particle content. RESULTS AND DISCUSSION: No evidence of particle formation, or colour or pH change was observed throughout the study period. Clonidine retained more than 98% of its initial concentration when stored in the tested diluents at 4°C for 7 days and at 35°C for 24 hours. WHAT IS NEW AND CONCLUSION: Our findings will allow healthcare professionals to prepare weekly dose of clonidine in glass bottles for storage in a refrigerator. The daily required dose of clonidine can be drawn aseptically from the glass bottle each day and stored in a plastic syringe at room temperature. Clonidine present in a plastic syringe can be administered via the nasogastric route 4-6 times a day. This practice would not only save nursing time and avoid delays in the timely administration of clonidine, but also reduce the risk of potential medication errors as well as preparation-associated costs.