Determining Optimal Mean Arterial Blood Pressure Based on Cerebral Autoregulation in Children after Cardiac Surgery.

To evaluate the feasibility of continuous determination of the optimal mean arterial blood pressure (opt-MAP) according to cerebral autoregulation and to describe the opt-MAP, the autoregulation limits, and the time spent outside these limits in children within 48 h of cardiac surgery. Cerebral autoregulation was assessed using the correlation coefficient (COx) between cerebral oxygenation and MAP in children following cardiac surgery. Plots depicting the COx according to the MAP were used to determine the opt-MAP using weighted multiple time windows. For each patient, we estimated (1) the time spent with MAP outside the autoregulation limits and (2) the burden of deviation, defined as the area between the MAP curve and the autoregulation limits when the MAP was outside these limits. Fifty-one patients with a median age of 7.1 (IQR 0.7-52.0) months old were included. The opt-MAP was calculated for 94% (IQR 90-96) of the monitored time. The opt-MAP was significantly lower in neonates < 1 month old. The patients spent 24% (18-31) of the time outside of the autoregulation limits, with no significant differences between age groups. Continuous determination of the opt-MAP is feasible in children within the first 48 h following cardiac surgery.

Exploring physicians' prescribing behavior in patients with multiple sclerosis in Saudi Arabia: a sequential explanatory mixed-methods.

BACKGROUND: Multiple sclerosis (MS) is the most common disabling neurological disease in young adults worldwide with majority of patients manifest symptoms between 20 and 40 years of age. The aims of this study are to explore physicians' perspectives, views, and behaviors in diagnosing and treating patients with MS in Saudi Arabia and investigate the prescribing pattern of disease-modifying therapies (DMTs). METHODS: A sequential explanatory mixed-method approach was used to achieve the study objectives. The quantitative arm of the study consisted of patient data extracted from the Saudi MS registry from 2015 to 2018. The qualitative study consisted of in-depth semi-structured interviews with physicians using a validated interview topic guide comprising 28 open-ended questions. RESULTS: We extracted data of 2,507 patients from 20 different hospitals across Saudi Arabia. Patients' mean age was 34 ± 10 years; two-thirds (n = 1,668) were female. 92% (n = 2,292) had relapsing-remitting multiple sclerosis, and 5% (n = 126) had secondary-progressive multiple sclerosis. In general, patients with MS received at least one drug as the DMT or DMTs and corticosteroids for those with relapse. Qualitatively, nine physicians agreed to participate in the interviews. Of them, five (55%) were male and four were female from different regions. Thematic analysis yielded three main themes: practice, views, and challenges. CONCLUSIONS: The prevalence of MS in Saudi Arabia is raising but is still much lower than that reported in the Gulf region. A national MS guideline is needed to streamline diagnosis and treatment criteria, avoid any delay in treatment, and guide physicians who provide care for patients with MS.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Elevated Diaphragmatic Tonic Activity in PICU Patients: Age-Specific Definitions, Prevalence, and Associations.

OBJECTIVES: Tonic diaphragmatic activity (tonic Edi, i.e., sustained diaphragm activation throughout expiration) reflects diaphragmatic effort to defend end-expiratory lung volumes. Detection of such elevated tonic Edi may be useful in identifying patients who need increased positive end-expiratory pressure. We aimed to: 1) identify age-specific definitions for elevated tonic Edi in ventilated PICU patients and 2) describe the prevalence and factors associated with sustained episodes of high tonic Edi. DESIGN: Retrospective study using a high-resolution database. SETTING: Single-center tertiary PICU. PATIENTS: Four hundred thirty-one children admitted between 2015 and 2020 with continuous Edi monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We characterized our definition of tonic Edi using data from the recovery phase of respiratory illness (i.e., final 3 hr of Edi monitoring, excluding patients with significant persistent disease or with diaphragm pathology). High tonic Edi was defined as population data exceeding the 97.5th percentile, which for infants younger than 1 year was greater than 3.2 µV and for older children as greater than 1.9 µV. These thresholds were then used to identify patients with episodes of sustained elevated tonic Edi in the first 48 hours of ventilation (acute phase). Overall, 62 of 200 (31%) of intubated patients and 138 of 222 (62%) of patients on noninvasive ventilation (NIV) had at least one episode of high tonic Edi. These episodes were independently associated with the diagnosis of bronchiolitis (intubated patients: adjusted odds [aOR], 2.79 [95% CI, 1.12-7.11]); NIV patients: aOR, 2.71 [1.24-6.0]). There was also an association with tachypnea and, in NIV patients, more severe hypoxemia. CONCLUSIONS: Our proposed definition of elevated tonic Edi quantifies abnormal diaphragmatic activity during expiration. Such a definition may help clinicians to identify those patients using abnormal effort to defend end-expiratory lung volume. In our experience, high tonic Edi episodes are frequent, especially during NIV and in patients with bronchiolitis.

The association of center volume with transplant outcomes in selected high-risk groups in kidney transplantation.

BACKGROUND: In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined. METHODS: We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000-2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m2, receiving kidneys from donors with kidney donor profile index(KDPI) ≥ 85%, acute kidney injury(AKI), hepatitisC + . Average annual CV for the specific-high-risk KT categorized in tertiles. Death-Censored-Graft-Loss(DCGL) and death at 3 months, 1, 5, and 10 years were compared between CV tertiles using Cox-regression models. RESULTS: Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m2 had higher risk of DCGL in low CV(aHR = 1.11,95%CI = 1.03-1.19) at 10 years; recipients with age ≥ 70 years had higher risk of death in low CV(aHR = 1.07,95%CI = 1.01-14) at 10 years. There was no difference of DCGL or death in low CV for donors with KDPI ≥ 85%, hepatitisC + , or AKI. CONCLUSIONS: Recipients of high-risk KT with BMI ≥ 35 kg/m2 have higher risk of DCGL and recipients age ≥ 70 years have higher risk of death in low CV, compared to high CV. Future studies should identify care practices associated with CV that support optimal outcomes after KT.

In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic.

In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base-pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (α-amylase% inhibition), anti-Alzheimer's (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (α-amylase% inhibition), and anti-Alzheimer's (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study.

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds (2-8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

Pharmacy practice in hospital settings in GCC countries: Dispensing and administration.

Purpose: To outline dispensing and administration practices in hospital pharmacy across the Gulf Cooperation Councils (GCC) countries' hospitals. Paucity of data in appraising hospital pharmacy practice in GCC regions motivated us to conduct this study. Methods: A modified survey questionnaire was prepared from the American Society of Health-System Pharmacist (ASHP) survey questions. Three major domains of questions for general characteristics of the medication use process for dispensing and administration were identified. These were, (1) medication distribution system, and medication distribution technology, (2) technology used to compound sterile preparations, compounding I.V. medication and method of compounding nutrition support preparations, (3) medication administration practices, medication orders, medication administration records (MARs), and technician activities. A list of hospitals was obtained from the Ministry of Health of the targeted GCC countries. A secure invitation link containing a survey questionnaire was sent to the participants directly. Results: Sixty-four hospitals responded to this survey. The overall response rate was 52%. Most surveyed hospitals have centralized inpatient medications distribution system (75.0%). About 37.5% of hospitals used automated dispensing cabinets (ADCs) in their patient care areas. Compounding sterile preparations in the pharmacy, barcode verification technology, workflow management technology, and robotic technology were used by 17.2%, 15.6%, and 4.7% of hospitals, respectively. In using safety technology for medication administration, almost all hospitals have partially or completely implemented an electronic health record (EHR). About 40.6% of hospitals used electronic medication administration records (e-MARs), 20.3% used bar-code-assisted medication administration (BCMA), and 35.9% used smart infusion pumps. Conclusion: The results of this survey revealed an opportunity to improve the medication use management process on dispensing and administration practices in hospitals in GCC countries.

Cardiorespiratory alterations in a newborn ovine model of systemic viral inflammation.

BACKGROUND: Respiratory viruses can be responsible for severe apneas and bradycardias in newborn infants. The link between systemic inflammation with viral sepsis and cardiorespiratory alterations remains poorly understood. We aimed to characterize these alterations by setting up a full-term newborn lamb model of systemic inflammation using polyinosinic:polycytidylic acid (Poly I:C). METHODS: Two 6-h polysomnographic recordings were carried out in eight lambs on two consecutive days, first after an IV saline injection, then after an IV injection of 300 µg/kg Poly I:C. RESULTS: Poly I:C injection decreased locomotor activity and increased NREM sleep. It also led to a biphasic increase in rectal temperature and heart rate. The latter was associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Lastly, brainstem inflammation was found in the areas of the cardiorespiratory control centers 6 h after Poly I:C injection. CONCLUSIONS: The alterations in heart-rate variability induced by Poly I:C injection may be, at least partly, of central origin. Meanwhile, the absence of alterations in respiratory-rate variability is intriguing and noteworthy. Although further studies are obviously needed, this might be a way to differentiate bacterial from viral sepsis in the neonatal period. IMPACT: Provides unique observations on the cardiorespiratory consequences of injecting Poly I:C in a full-term newborn lamb to mimic a systemic inflammation secondary to a viral sepsis. Poly I:C injection led to a biphasic increase in rectal temperature and heart rate associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Brainstem inflammation was found in the areas of the cardiorespiratory control centers.

Rs10204525 Polymorphism of the Programmed Death (PD-1) Gene Is Associated with Increased Risk in a Saudi Arabian Population with Colorectal Cancer.

Checkpoint programmed death-1 (PD-1) has been identified as an immunosuppressive molecule implicated in the immune evasion of transformed cells. It is highly expressed in tumor cells in order to evade host immunosurveillance. In this study, we aimed to assess the association between single nucleotide polymorphisms (SNP) of PD-1 and the risk of colorectal cancer (CRC) in the Saudi population. For this case-control study, the TaqMan assay method was used for genotyping three SNPs in the PD-1 gene in 100 CRC patients and 100 healthy controls. Associations were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for multiple inheritance models (codominant, dominant, recessive, over-dominant, and log-additive). Moreover, PD-1 gene expression levels were evaluated using quantitative real-time PCR in colon cancer tissue and adjacent colon tissues. We found that the PD-1 rs10204525 A allele was associated with an increased risk of developing CRC (OR = 2.35; p = 0.00657). In addition, the PD-1 rs10204525 AA homozygote genotype was associated with a high risk of developing CRC in the codominant (OR = 21.65; p = 0.0014), recessive (OR = 10.97; p = 0.0015), and additive (OR = 1.98; p = 0.012) models. A weak protective effect was found for the rs2227981 GG genotype (OR = 2.52; p = 0.034), and no significant association was found between the rs2227982 and CRC. Haplotype analysis showed that the rs10204525, rs2227981, rs2227982 A-A-G haplotype was associated with a significantly increased risk of CRC (OR = 6.79; p =0.031).

Sage, Salvia officinalis L., Constituents, Hepatoprotective Activity, and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis.

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils' yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, ß-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs' essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema.

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

Phytochemical Analysis, Pharmacological and Safety Evaluations of Halophytic Plant, Salsola cyclophylla.

Salsola cyclophylla, an edible halophyte, is traditionally used for inflammation and pain. To confirm the claimed anti-inflammatory and analgesic properties, a detailed study on respective pharmacological actions was undertaken. The activities are contemplated to arise from its phytoconstituents. The LC-MS analysis of S. cyclophylla 95% aqueous-ethanolic extract revealed the presence of 52 compounds belonging to phenols, flavonoids, coumarins, and aliphatics class. A high concentration of Mn, Fe, and Zn was detected by atomic absorption spectroscopic analysis. The ethyl acetate extract showed the highest flavonoid contents (5.94 ± 0.04 mg/g, Quercetin Equivalents) and Fe2+-chelation (52%) potential with DPPH radicals-quenching IC50 at 1.35 ± 0.16 mg/mL, while the aqueous ethanolic extract exhibited maximum phenolics contents (136.08 ± 0.12 mg/g, gallic acid equivalents) with DPPH scavenging potential at IC50 0.615 ± 0.06 mg/mL. Aqueous ethanolic extract and standard quercetin DPPH radicals scavenging's were equal potent at 10 mg/mL concentrations. The aqueous ethanolic extract showed highest analgesic effect with pain reduction rates 89.86% (p = 0.03), 87.50% (p < 0.01), and 99.66% (p = 0.0004) after 60, 90, and 120 min, respectively. Additionally, aqueous ethanolic extract exhibited the highest anti-inflammation capacity at 41.07% (p < 0.0001), 34.51% (p < 0.0001), and 24.82% (p < 0.0001) after 2, 3, and 6 h of extract's administration, respectively. The phytochemical constituents, significant anti-oxidant potential, remarkable analgesic, and anti-inflammatory bioactivities of extracts supported the traditionally claimed anti-inflammatory and analgesic plant activities.

Value drivers for pharmaceutical products in health technology assessment (HTA) in Saudi Arabia: Results from a capacity Building, Multi-Stakeholder workshop.

OBJECTIVES: Capacity building exercises are important to increase understanding of healthcare processes by key stakeholders, and to facilitate open discussions to build consensus. This study explored the views of a multi-stakeholder group of local Saudi experts on possible value elements that could be important for health technology assessment (HTA) processes and methods regarding pharmaceutical products in Saudi Arabia ('value drivers'). METHODS: A diversified group of local experts were invited to a two-day capacity building workshop from 18 to 19 December 2019 in Riyadh, Saudi Arabia. Information regarding the participants' demographic and educational/professional background, along with their self-assessed knowledge and experience of HTAs and the concept of value in the pharmaceutical market was collected. For each of 22 value drivers identified during a targeted literature search, participants were asked either to 'opt out' of its consideration for future HTA assessments, or rate it from 1 to 10 (low-high) on feasibility and acceptability. RESULTS: Efficacy and safety were the highest rated value drivers for acceptability and feasibility. Explicit cost-effectiveness thresholds had the lowest ratings for acceptability and feasibility. Participants highlighted data availability and accuracy as a potential challenge to HTA implementation in Saudi Arabia. CONCLUSIONS: Participants valued a pharmaceutical product's efficacy and safety alongside the consideration of disease characteristics for HTA processes. Participants also valued a binding HTA recommendation and the use of local real-world evidence, where available, to support HTA submissions.

Pharmacy practice in hospital settings in GCC countries: Prescribing and transcribing.

PURPOSE: To outline hospital pharmacy practices across the Gulf Cooperation Councils (GCC) countries' hospitals. METHODS: A modified survey questionnaire was prepared from the original 2019 American Society of Health-System Pharmacist (ASHP) survey questions. Survey details were discussed with some pharmacy directors for clarity and relevance. A list of hospitals were obtained from the Ministry of Health of each of the targeted GCC countries. A secure invitation link containing a survey questionnaire was sent to the participants directly. RESULTS: Sixty four hospitals responded to this survey. The overall response rate was 52%. About 47% of the surveyed hospitals considered their drug formularies as closed, and strict. Additionally, only 44% of hospitals compare the effectiveness of products, when taking formulary decisions for drug inclusion. Forty-four percent of hospitals have computerized prescriber order entry (CPOE / EHR) system functionality for formulary system management. At about 39.1% hospitals, pharmacists have the responsibility for managing medication therapies, majority were engaged in providing anticoagulation therapies. About 61% of hospital pharmacies in GCC countries receive medication orders electronically, through CPOE/EHR. Majority (66%) of the hospitals in GCC countries have an active Antimicrobial Stewardship Program (ASP) while only 40% of pharmacists have a key role in providing clinical support. About 57.8% of hospital pharmacy directors reported that pharmacists do not provide ambulatory care clinical pharmacy services in their hospitals. CONCLUSION: In GCC countries' hospitals, there are major areas for improvement to patient care of which pharmacists are uniquely qualified as the medication experts to have the most meaningful outcomes in all of the domains of safe medication use, medication therapy management, antimicrobial stewardship program and participation in outpatient clinics.

Usability and safety of the new 5 French air-charged catheter for performing urodynamic studies on pediatric patients.

AIMS: To assess the performance and safety of the T-DOC® 5 French air-charged urodynamic catheters in pediatric patients and obtain feedback from providers related to usability performance. METHODS: Patients ages 12 years and younger undergoing urodynamics were prospectively recruited from two institutions. The T-DOC® 5 French air-charged catheters were used. Issues with catheter placement, adverse events (AEs), and pain scores were assessed. A follow-up telephone call was made to assess for post-urodynamic AEs. Providers completed a clinical user questionnaire. Likert scale was used (1 = most negative and 5 = most positive response) and reported in mean (range). RESULTS: A total of 28 patients completed the study. The mean age was 55 months (5-130) (10 females, 18 males). One problem was noted with the insertion of an abdominal catheter, secondary to stool impaction. Catheters stayed in place on all subjects, except for one related to patient hyperactivity. There were no AEs during the studies. In total four reported post-urodynamics AEs (one hematochezia, three dysuria). Among nine patients, pain level on the bladder and abdominal insertion was 3.6/10 (0-10) and 3.1/10 (0-10). Five providers completed the questionnaire. The overall ease of use was rated 4.3/5 (3-5). The ease of insertion was 4.1/5 (2-5) and set-up/clean-up time was 4.4/5 (3-5). Tracing stability, subtraction accuracy, and artifact sensitivity were all perceived favorably (respectively 4.8/5 [4-5], 4.6/5 [4-5], and 4.4/5 [4-5]). CONCLUSIONS: The T-DOC® 5 French air-charged catheter was considered safe and effective in pediatric patients. No AEs occurred during the studies. Providers, using the catheters, reported favorably on catheter usage.

Novel heterocyclic hybrids of pyrazole targeting dihydrofolate reductase: design, biological evaluation and in silico studies.

A novel series of pyrazole analogues including hydrazones, pyrazolo[4,3-c]-pyridazines, pyrazolo[3,4-e][1,2,4]triazine and pyrazolo[3,4-d][1,2,3]triazoles was designed, synthesised and screened for their in vitro antimicrobial and DHFR inhibition activity. Compounds bearing benzenesulphonamide moiety incorporated with 3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene) hydrazine 3a or 6-amino-7-cyano-3-methyl-5H-pyrazolo[4,3-c]pyridazine 6a revealed excellent and broad spectrum antimicrobial activity comparable to ciprofloxacin and amphotericin B as positive antibiotic and antifungal controls, respectively. Furthermore, these derivatives proved to be the most active DHFR inhibitors with IC50 values 0.11 ± 1.05 and 0.09 ± 0.91 µM, in comparison with methotrexate (IC50 = 0.14 ± 1.25 µM). The in silico studies were done to calculate the drug-likeness and toxicity risk parameters of the newly synthesised derivatives. Additionally, the high potency of the pyrazole derivatives bearing sulphonamide against DHFR was confirmed with molecular docking and might be used as an optimum lead for further modification.

Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity.

A new series of N'-(substituted phenyl)-2-(1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide derivatives (1 - 25) were prepared in good yields in an efficient manner. All the compounds were fully characterised by the elemental analysis and spectral data. Synthesised compounds were evaluated for antioxidant activity by DPPH method. Compounds 7 (R = 3-methoxyphenyl), 3 (R = 4-dimethylaminophenyl) and 23 (R = 2,4,5-trimethoxy phenyl) substitutions were found to be having highly potent antioxidant activity. Compound 3, with para dimethylaminophenyl substitution was found to be having highest antioxidant activity. It was further evaluated in vivo for various analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibitory activity in different animal models. Lead compound 3 was found to be significant anti-inflammatory and analgesic agent. It was also evaluated for ulcerogenic activity and demonstrated significant ulcerogenic reduction activity in ethanol and indomethacin model. The LD50 of compound 3 was found to be 131 mg/kg. The animals treated with compound 3 prior to cisplatin treatment resulted in a significant reduction in COX-2 protein expression when compared to cisplatin-treated group. Sulindac derivative with para dimethylaminophenyl substitution was found to be the most potent antioxidant, anti-inflammatory and analgesic agent as well as with significant gastric sparing activity as compared to standard drug sulindac. Compound 3 significantly downregulated liver tissue COX-2 gene expression.

Synthesis of Novel Sulfamethaoxazole 4-Thiazolidinone Hybrids and Their Biological Evaluation.

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (7a-l) by using a cyclocondensation reaction between 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide (4), aryl aldehyde (5a-l), and mercapto acetic acid (6) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against M. Bovis BCG and M. tuberculosis H37Ra (MTB) strains. The compounds 7d, 7g, 7i, 7k, and 7l revealed promising antimycobacterial activity against M. Bovis and MTB strains with IC90 values in the range of 0.058-0.22 and 0.43-5.31 µg/mL, respectively. The most active compounds were also evaluated for their cytotoxicity against MCF-7, HCT 116, and A549 cell lines and were found to be non-cytotoxic. Moreover, the synthesized compounds were also analyzed for ADME (absorption, distribution, metabolism, and excretion) properties and showed potential as good oral drug candidates.