Optimal Prescription Research Articles

Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery

Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the drug and its bioavailability. The optimum formulation of 2 mg/mL BRT-ISG was obtained with 0.45% gellan gum as the gel matrix. In vitro release results showed that the water-soluble drug bromonidine tartrate in ocular in situ gels exhibited a high burst effect and fast release in solution. The results of dialysis membrane permeation showed that there was a significant difference between the commercially available and BRT-ISG groups after 45 min. The results of the pre-corneal retention study indicated that gellan gum can effectively prolong ocular surface retention. Preliminary stability results showed that it should be stored in a cool and dark place, and the formulation under long-term preservation can be basically stable. The pharmacokinetic study of the BRT-ISG in the anterior chamber of the rabbit eye was studied by microdialysis technique, and microdialysis samples were analyzed by LC-MS/MS. The pharmacokinetic study showed that the BRT-ISG reached Cmax (8.16 mg/L) at 93 min after administration, which was 2.7 times that of the BRT eye drops, and the AUC(0-t) (1397.08 mg·min/L) was 3.4 times that of the BRT eye drops. The optimal prescription can prolong the retention time of BRT in front of the cornea and significantly improve the bioavailability of BRT in the eye. Combined with the results of in vitro release, permeation and pre-corneal retention studies, the improvement of BRT-ISG bioavailability in rabbit eyes was found to be mainly due to the retention effect after the mixture of ISG and tears.

Optimization of Preparation Process and Pharmacokinetics of APAP Double-Release Pellet Capsules

In order to develop a kind of APAP double-release pellet capsules, which was prepared with the manual filling method, the immediate and sustained release pellets of a certain proportion were prepared by the fluidized bed coating and the extrusion spheroidization process, respectively. It was founded that both the prepared immediate-release pellets and sustained-release pellets had smooth and round surfaces. The particle size distribution ranged evenly from 16 to 35 mesh. Response surface plots showed that the optimal preparation prescription for immediate-release pellets were that ethanol concentration (X1) 70%, APAP 20%, MCC (X2) 40%, PVP K30 (X3) 20%, and sucrose pellet core 20%; and the optimal preparation prescription for sustained-release pellets were that HPMC concentration (X*3) 6.5%, APAP 30%, EC (X*1) 20%, MCC (X*2) 40%, PVP K30 4%, and lactose 6%. The results of pharmacokinetic analysis revealed that, after the APAP double-release pellet was orally administered, compared with that of conventional tablets, the plasma APAP levels in the blood circulation dramatically rose to significant peaks as a result of the quick and slow release of APAP from the capsules, which significantly prolonged the effective time of drugs in blood. Finally, immediate and sustained antipyretic-analgesic effects were obtained.

Biosynthesis and pharmacokinetics of Panax notoginseng enteric-coated soft capsules.

To investigate the biosynthesis and pharmacokinetic course of enteric-coated soft capsules of Panax notoginseng saponins (PNS) in a beagle dog model. To satisfy the enteric properties of soft capsules, the PNS enteric soft gelatin capsules were prepared by formaldehyde impregnation and orthogonal experimental design. The fluidity of gelatin and the disintegration time were selected as evaluation indexes; the soft gelatin capsule content was self-emulsifying, and the Km value and the optimal prescription were determined by making three-phase diagrams; in vivo pharmacokinetics studies were performed on six beagle dogs with 3 dogs in each group. Beagle dogs were divided into two groups randomly. One group was given PNS self-emulsifying enteric capsule and the other was given market conventional capsules. Plasma samples were collected at different times. After 1 week, the crossover experiment was carried out. The plasma concentration was detected by HPLC-MS (high performance liquid chromatography-mass spectrometry). Then the pharmacokinetic parameters were calculated by non-compartment model analysis. The range and variance analysis of the orthogonal test determined that the best prescription of total saponins of Panax notoginseng enteric soft capsule was:gelatin:glycerol:water =1:1:2, Soak the films in 1% formaldehyde for 1 hour. The contents of the soft capsule self-microemulsion are prescribed as: IPM (isopropyl myristate):Cremophor RH40:PEG400 (polyethylene glycol 400) =1:4.5:4.5 (with suitable PNS); the pharmacokinetic parameters of PNS self-emulsified enteric capsules and conventional capsules in the market are as follows: Rb1:Cmax is (18.05±0.26) and (15.50±0.51) ng/mL, Tmax is (2.00±0) and (3.00±0) h, AUC0→t is 98.49±1.16 and 34.46±2.02 (ng/mL)·h, relative bioavailability is 196.2%; Rg1: Cmax is 4.16±0.25 and 3.88±0.28 ng/mL, Tmax is 2.00±0 and 1.50±0 h, area under drug time curve (AUC)0→t is 11.80±2.93 and 10.45±2.29 (ng/mL)·h, relative bioavailability is 77.2%; R1:Cmax is 1.84±0.25 and 1.48±0.21 ng/mL, Tmax is 2.08±0.49 and 1.92±0.20 h, AUC0→t is 7.06±2.07 and 7.16±2.59 (ng/mL)·h, relative bioavailability is 117.7%. The experiment in vivo showed the higher relative bioavailability of PNS self-emulsifying enteric capsule compared with market conventional capsules. This will provide a potential application prospect for the clinical research and applications of PNS.

Relationship between Dialysate Bicarbonate Concentration and All-Cause Mortality in Hemodialysis Patients

Introduction: The optimal dialysate bicarbonate concentration (DBIC) for hemodialysis (HD) remains controversial. Herein, we analyzed the effect of dialysate bicarbonate levels on mortality in HD patients. Methods: Patients undergoing maintenance HD were recruited from the HD unit of the Daping Hospital. Patients were categorized into quartiles according to their DBIC level (quartile 1: <31.25 mmol/L, n = 77; quartile 2: 31.25–32.31 mmol/L, n = 76; quartile 3: 32.31–33.6 mmol/L; n = 81; quartile 4: ≥33.6 mmol/L, n = 79). Demographic and clinical data were collected. Survival curves were estimated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to estimate the association between DBIC and all-cause mortality. Results: We included 313 patients undergoing maintenance HD with a mean DBIC of 32.16 ± 1.59 mmol/L (range, 27.20–34.72 mmol/L). The patients in quartile 4 were more likely to have higher pre- and post-HD serum bicarbonate concentrations than those in other quartiles. The mortality rate was lowest in quartile 2 (10.53%). The survival time was significantly lower in the quartile 4 group than in the other quartiles (p = 0. 008, log-rank test). After full adjustment, the hazard ratio (per 3 mmol/L higher DBIC) for all-cause mortality was 4.29 (95% confidence interval, 2.11–8.47) in all patients, whereas no significant association was observed between DBIC and initial hospitalization. Conclusions: Our data indicate that DBIC is positively associated with all-cause mortality. A DBIC concentration of 31–32 mmol/L may benefit patient outcomes. This study provides an evidence-based medical basis for optimal dialysis prescription in the future.

Membrane-disruptive homo-polymethacrylate with both hydrophobicity and pH-sensitive protonation for selective cancer therapy.

The membrane-disruptive strategy, which involves host defense peptides and their mimetics, is a revolutionary cancer treatment based on broad-spectrum anticancer activities. However, clinical application is limited by low selectivity towards tumors. In this context, we have established a highly selective anticancer polymer, i.e. poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA), that can mediate the membrane-disruptive activity via a subtle pH change between physiological pH and tumor acidity for selective cancer treatment. Specifically, the resulting PEG-PAEMA can assemble into neutral nanoparticles and silence the membrane-disruptive activity at physiological pH and disassemble into cationic free-chains or smaller nanoparticles with potent membrane-disruptive activity after the protonation of the PAEMA block due to tumor acidity, resulting in high selectivity towards tumors. Dramatically, PEG-PAEMA exhibited a >200-fold amplification in hemolysis and <5% in IC50 against Hepa1-6, SKOV3 and CT-26 cells at pH 6.7 as compared to those at pH 7.4, thanks to the selective membrane-disruptive mechanism. Moreover, mid- and high-dose PEG-PAEMA demonstrated higher anticancer efficacy than an optimal clinical prescription (bevacizumab plus PD-1) and, significantly, had few side effects on major organs in the tumor-bearing mice model, agreeing with the highly selective membrane-disruptive activity in vivo. Collectively, this work showcases the latent anticancer pharmacological activity of the PAEMA block, and also brings new hope for selective cancer therapy.

A Novel Krill Herd Based Random Forest Algorithm for Monitoring Patient Health

Artificial Intelligence (AI) is finding increasing application in healthcare monitoring. Machine learning systems are utilized for monitoring patient health through the use of IoT sensor, which keep track of the physiological state by way of various health data. Thus, early detection of any disease or derangement can aid doctors in saving patients’ lives. However, there are some challenges associated with predicting health status using the common algorithms, such as time requirements, chances of errors, and improper classification. We propose an Artificial Krill Herd based on the Random Forest (AKHRF) technique for monitoring patients’ health and eliciting an optimal prescription based on their health status. To begin with, various patient datasets were collected and trained into the system using IoT sensors. As a result, the framework developed includes four processes: preprocessing, feature extraction, classification, and result visibility. Additionally, preprocessing removes errors, noise, and missing values from the dataset, whereas feature extraction extracts the relevant information. Then, in the classification layer, we updated the fitness function of the krill herd to classify the patient’s health status and also generate a prescription. We found that the results from the proposed framework are comparable to the results from other state-of-the-art techniques in terms of sensitivity, specificity, Area under the Curve (AUC), accuracy, precision, recall, and F-measure.

PS-C33-7: TRUE RESISTANT HYPERTENSION IN A TERTIARY HYPERTENSION CLINIC IN SAUDI ARABIA

Objective: Resistant hypertension(RH), defined as office blood pressure (BP) above goal despite the use of more than three anti-hypertensives (one ideally being a diuretic) or BP that requires more than four agents to achieve control, has received more attention with increased efforts to improve BP control rates and the emergence of device-based therapies. Based on this definition of RH, the prevalence rates vary around 15–30% worldwide. However, there is paucity of data on RH, particularly true RH in the Middle-East. The aim of this study was to explore the prevalence, clinical characteristics and choice of anti-hypertensives in a Saudi RH population. Design &amp; Methods: We analysed retrospectively clinic and ambulatory BP monitory (ABPM) data in Saudi patients between January 2016 to June 2018. Office HTN was defined as greater than 140 systolic or greater than 90 diastolic, mm Hg. HTN was confirmed using one of the following ABPM cut-offs; 24-hr greater than 130/80 or daytime greater than 135/85, mm Hg. Results were analysed using JMP version 13, p less than 0.05 considered significant. Results: The mean age of the population(n = 540) was 54 ± 15 years, 40% female. The overall prevalence of RH was 47% in our cohort, of which 35% was true RH. The patients with RH were older; 62 ± 13 vs. 50.5 ± 14 years with no significant gender difference. RH was associated with diabetes (OR = 6.2, CI%, 3–12); CAD(OR = 3.3, CI%, 2–5); history of coronary revascularization(CABG/PCI) (OR = 3, CI%, 2–5); CKD(OR = 5.7, CI%, 3–12) and heart failure(OR = 1.9, CI%, 1–3). The average number of anti-hypertensives was 4.2 ± 1 in RH compared with 1.1 ± 1 in control group. Only a third of the patients were prescribed spironolactone in the RH group with some 10% on an alpha blocker. Conclusions: To the best of our knowledge, this is the first study in the Middle-East to establish the prevalence of true RH using ABPM. With a high prevalence rate, our cohort of RH is complex with high number of co-morbidities, sub optimal prescription rates of spironolactone or alpha-blockers, representing a therapeutic challenge.

Thermolysis of petroleum oil and solubility of deposits

The article discusses the process of formation of deposits in the pipelines of the engine oil system and the factors affecting the conditions for their formation. The technological process of oxidation and the criteria for indicator parameters characterizing the thermolysis of used oil are shown. An extractive method is proposed that ensures the removal of deposits from the pipeline using special flushing process fluids based on regenerated petroleum oil. To search for cheap and efficient hydrocarbon raw materials, regenerated petroleum oils were chosen from among the renewable resources of oil refining. The proposed process fluid was prepared on the basis of low-viscosity spent and then purified petroleum oil. The viscosity of the petroleum oil was adjusted with the addition of petroleum kerosene or diesel. Diluted surfactant solutions were used as additives. and detergent additive (alkali metal salts). It was revealed that in the oil system of an automobile engine at high temperatures (200-350 0C) oil thermolysis occurs, and the resulting deposits contain asphaltenes, carbons and carboids. The efficiency of dissolution of deposits in the mixture under study at low temperatures and the concentration of surfactants were revealed. The dependence of the interfacial tension on the concentration of various surfactants is shown. The limiting amounts of the content of the constituent components are found and the ratio of oily extract, from deposits of oxidized oil, is selected. As a result of the tests, it was found that the washing liquid reduces the interfacial tension between the surface of the pipes and deposits and leads to an increase in the movement of the liquid. It has been established that the process of washing off deposits depends on the composition of the deposits, as well as on the composition of the oily extract. The optimal mode and prescription composition of the flushing liquid has been selected. The efficiency of washing off the studied liquid with other means is shown, while it should be noted that this liquid has a simple component composition and is much cheaper than other means.

Review of antibiotic prescriptions as part of antimicrobial stewardship programmes: results from a pilot implementation at two provincial-level hospitals in Viet Nam.

To investigate the feasibility of retrospective prescription-based review and to describe the antibiotic prescribing patterns to provide information for an antimicrobial stewardship programme in Viet Nam. This study was conducted in two provincial-level hospitals between February and April 2020. Reviews were done by a clinical team consisting of leaders/senior doctors of each ward to assess the optimal level (optimal/adequate/suboptimal/inadequate/not assessable) of antibiotic prescriptions. Mixed-effect logistic regression at prescription level was used to explore factors associated with optimal antibiotic use. The retrospective prescription-based review was accepted by study clinical wards with varied levels of participants. One hundred and eighty-three patients (326 prescriptions) in Hospital 1 and 200 patients (344 prescriptions) in Hospital 2 were included. One hundred and nineteen of the 326 (36.5%) antibiotic prescriptions in Hospital 1 and 51/344 (14.8%) antibiotic prescriptions in Hospital 2 were determined to be optimal by the review teams. The number of adequate antibiotic prescriptions were 179/326 (54.9%) and 178 (51.7%) in Hospital 1 and Hospital 2, respectively. The optimal level was lower for surgical prophylaxis antibiotics than for empirical therapy (OR = 0.06; 95% CI 0.01-0.45), higher in prescriptions in the ICU (OR = 12.00; 95% CI 3.52-40.92), higher in definitive antibiotic therapy (OR = 48.12; 95% CI 7.17-322.57) and higher in those with an indication recorded in medical records (OR = 3.46; 95% CI 1.13-10.62). This study provides evidence on the feasibility of retrospective prescription-based review, with adaption to the local situation. High and varying levels of optimal antibiotic prescriptions in clinical wards in hospitals were observed in Viet Nam.

Evaluating pediatric weight-based antibiotic dosing in a community pharmacy

BackgroundOwing to pharmacokinetic variations in pediatric patients, many antibiotics require weight-based dosing to ensure medication safety and antimicrobial stewardship. Despite the need for weight-based dosing, prescribers are not legally required to include the weight or diagnosis code on pediatric prescriptions that are necessary components to verify appropriateness. Clinical decision support system (CDSS) can help clinicians improve dosing appropriateness, but little is known about CDSS in a community pharmacy setting. To determine the impact of implementing CDSS in this setting, baseline information is necessary. ObjectivesThis study aimed to determine both the percentage of pediatric antibiotic prescriptions without optimal patient information required to evaluate weight-based dosing and the baseline percentage of prescriptions dosed outside of guideline recommendations. MethodsA retrospective chart review was conducted at a locally owned community pharmacy in rural Southeast Missouri. Prescriptions written for patients less than 18 years old for guideline recommended antibiotics used for acute otitis media or acute pharyngitis dispensed between October 1, 2020, and May 10, 2021, were included in the analysis. Prescriptions were considered optimal if they included both patient weight and diagnosis code. Optimal prescriptions were evaluated for adherence to guideline recommended dosing. The primary outcomes included percentage of prescriptions without patient weight, diagnosis code, or both and the percentage of optimal prescriptions prescribed outside of guideline recommended dosing for the specified condition. ResultsOf the 115 included prescriptions, 45 were missing a patient weight, diagnosis code, or both. Seventy prescriptions were considered optimal, and of those, 42 (60%) were prescribed outside of guideline recommended dosing. ConclusionPrescriptions were identified as missing important information at the time of dispensing. Of the optimal prescriptions, the majority were prescribed outside of current guideline recommended dosing, with subtherapeutic dosing being the most common.

Circulating Endothelial Progenitor and Mesenchymal Stromal Cells as Biomarkers for Monitoring Disease Status and Responses to Exercise.

Noncommunicable chronic diseases, such as obesity, cardiovascular disease (CVD), and type 2 diabetes (T2D), pose significant health challenges globally. Important advances have been made in the understanding of the pathophysiologal mechanisms and treatment of noncommunicable diseases in recent years. Lack of physical activity is a primary contributor to many noncommunicable diseases including metabolic syndrome, T2D, CVD, and obesity. Certain diabetes medications and non-pharmaceutical interventions, such as physical activity and exercise, are shown to be effective in decreasing the CVD risks associated with heart disease, stroke, obesity, prediabetes, and T2D. The ability to measure and analyze circulating adult stem cells (ASCs) has gained particular interest due to their potential to identify at-risk individuals and implications in various therapeutics. Therefore, the purpose of this narrative review is to (1) provide an overview of ASCs; specifically endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs), (2) describe the responses of these cells to acute and chronic exercise, and (3) highlight the potential effect of exercise on EPCs and MSCs in aging and disease. EPCs are circulating cells, abundantly available in peripheral blood, bone marrow, and umbilical cord, and are defined by cell surface markers such as CD34+. EPCs are expected to play an important role in angiogenesis and neovascularization and have been implicated in the treatment of CVD. MSCs are essential for maintaining tissue and organ homeostasis. MSCs are defined as multipotent heterogeneous cells that can proliferate in vitro as plastic-adherent cells, have fibroblast-like morphology, form colonies in vitro, and can differentiate into ostyeoblasts, adipocytes, chondroblasts, and myoblasts. In the presence of aging and disease, EPCs and MSCs decrease in quantity and functional capacity. Importantly, exercise facilitates EPC differentiation and production from bone marrow and also helps to promote migration and homing to the hypoxic and damaged tissue which in turn improve angiogenesis and vasculogenesis. Similarly, exercise stimulates increases in proliferation and migratory activity of MSCs. Despite the reported benefits of exercise on EPC and MSC number and function, little is known regarding the optimal exercise prescription for aging and clinical populations. Moreover, the interactions between medications and exercise on EPCs and MSCs is currently unclear. Use of ASCs as a biomarker have the potential to revolutionize the management of patients with a variety of metabolic and obesity related disorders and also pro-inflammatory diseases. Further investigation of clinical entities are urgently needed to understand the implications of interventions such as exercise, diet, and various medications on EPC and MSC quantity and function in aging and clinical populations.

Barriers to Delivery of Enteral Nutrition in Intensive Care Settings in Saudi Arabia: A Comparative Study of the Perceptions of Health Care Providers Working in Adult and Paediatric ICUs.

Achieving optimal nutrition prescription is challenging in critically ill patients. Many factors can hinder the adequate delivery of enteral nutrition (EN) in intensive care units (ICUs). In this study, we aim to describe EN barriers and compare the perceptions of health care practitioners working in adult and paediatric ICUs regarding these barriers. In this cross-sectional study, data were collected via online survey. All physicians, dietitians, and nurses working in adult or paediatric ICUs across Saudi Arabia were eligible to participate. The survey contained 24 potential EN barriers and participants were asked to rate their importance on a scale from 1 to 5. A total Likert rating score of the 24 items was later calculated. We recruited 244 health care providers working in adult and paediatric ICUs. The most important perceived barriers were "Delay in physician ordering EN initiation" (3.33 ±1.32), and 'Waiting for dietitians to assess patients' (3.22 ±1.20). There was a statistical difference between the responses of health care providers based on their work settings for the following items; "Nurses failing to progress feeds according to feeding protocol" (p=0.006) and 'Feeding being held too far prior procedures or operating-room visits' (p=0.021). Profession significantly influenced the total Likert rating score of the 24 items (r=-0.234, p=0.001). This study identified some barriers of EN delivery in ICUs and showed that participants' perceptions regarding these barriers were influenced by their roles. These findings shed light on the nutritional practices in Saudi hospitals and identify areas of improvement in EN practice and advancements in the field of critical care nutrition in the region.

Effects of structured exercise programmes on physiological and psychological outcomes in adults with inflammatory bowel disease (IBD): A systematic review and meta-analysis.

Exercise has been suggested to counteract specific complications of inflammatory bowel disease (IBD). However, its role as a therapeutic option remains poorly understood. Therefore, we conducted a systematic review and meta-analysis on the effects of exercise in IBD. Five databases (MEDLINE, Embase, CINAHL, CENTRAL and SPORTDiscus) and three registers (Clinicaltrials.gov, WHO ICTRP and ISRCTN) were searched from inception to September 2022, for studies assessing the effects of structured exercise of at least 4 weeks duration on physiological and/or psychological outcomes in adults with IBD. Two independent reviewers screened records, assessed risk of bias using the Cochrane Risk of Bias (RoB 2.0) and ROBINS-I tools, and evaluated the certainty of evidence using the GRADE method. Data were meta-analysed using a random-effects model. From 4,123 citations, 15 studies (9 RCTs) were included, comprising of 637 participants (36% male). Pooled evidence from six RCTs indicated that exercise improved disease activity (SMD = -0.44; 95% CI [-0.82 to -0.07]; p = 0.02), but not disease-specific quality of life (QOL) (IBDQ total score; MD = 3.52; -2.00 to 9.04; p = 0.21) when compared to controls. Although meta-analysis could not be performed for other outcomes, benefits were identified in fatigue, muscular function, body composition, cardiorespiratory fitness, bone mineral density and psychological well-being. Fourteen exercise-related non-serious adverse events occurred. The overall certainty of evidence was low for disease activity and very low for HRQOL as a result of downgrading for risk of bias and imprecision. Structured exercise programmes improve disease activity, but not disease-specific QOL. Defining an optimal exercise prescription and synthesis of evidence in other outcomes, was limited by insufficient well-designed studies to ascertain the true effect of exercise training. This warrants further large-scale randomised trials employing standard exercise prescription to verify this effect to enable the implementation into clinical practice. This systematic review was prospectively registered in an international database of systematic reviews in health-related research (CRD42017077992; https://www.crd.york.ac.uk/prospero/).

Treatment patterns, healthcare resource use, and costs associated with uncomplicated urinary tract infection among female patients in the United States.

We evaluated associations between antibiotic prescription and healthcare resource use and costs (Part A), and between antibiotic switching and healthcare resource use, costs, and uncomplicated urinary tract infection recurrence (Part B) in female patients with uncomplicated urinary tract infection in the United States. This retrospective cohort study of linked Optum and Premier Healthcare Database data included female patients ≥12 years old with an uncomplicated urinary tract infection diagnosis (index date), who were prescribed antibiotics during an outpatient/emergency department visit between January 1, 2013 and December 31, 2018. In Part A, patients were stratified by antibiotic prescription appropriateness: appropriate and optimal (compliant with Infectious Diseases Society of America 2011 guidelines for drug class/treatment duration) versus inappropriate/suboptimal (inappropriate drug class/treatment duration per Infectious Diseases Society of America 2011 guidelines, and/or treatment failure). In Part B, patients were stratified by treatment pattern (antibiotic switch vs no antibiotic switch). Healthcare resource use and costs during index episode (within 28 days of index date) and 12-month follow-up were compared. Of 5870 patients (mean age 44.5 years), 2762 (47.1%) had inappropriate/suboptimal prescriptions and 567 (9.7%) switched antibiotic. Inappropriate/suboptimal prescriptions were associated with higher healthcare resource use (mean number of ambulatory care and pharmacy claims [both p < 0.001]), and higher total mean cost (inpatient, outpatient/emergency department, ambulatory visits, and pharmacy costs) per patient ($2616) than appropriate and optimal prescriptions ($649; p < 0.001) (Part A). Antibiotic switching was associated with more pharmacy claims and higher total mean costs (p ≤ 0.01), and a higher incidence of recurrent uncomplicated urinary tract infection (18.9%) than no antibiotic switching (14.2%; p < 0.001) (Part B). Inappropriate/suboptimal prescriptions and antibiotic switching were associated with high costs, ambulatory care, and pharmacy claims, suggesting a need for improved uncomplicated urinary tract infection prescribing practices in the United States.

Pharmacogenetic effects of single nucleotide polymorphisms commonly associated with antiretroviral therapy metabolism

Introduction. Identification of pharmacogenetic effects on antiretroviral therapy (ART) has become an important milestone to reach in the advancement of personalised treatment for HIV-positive patients. The therapy schemes are accompanied by multiple side effects. Therapy effectiveness and adverse reactions can be dictated by individual genetic predisposition factors, which should be taken into account for an optimal prescription. Some genetic markers (HLA-B*57:01 and UGT1A1*28), were already proven to improve discontinuation rates, and efforts are allocated to expand the range of clinically-relevant genetic tests.Objective. In this review, an updated summary of genetic polymorphisms and their effects defining patients’ tolerability to ART is presented. The aim of this research is to assess single nucleotide polymorphisms (SNPs) present in the genes that encode proteins involved in ART metabolism and transport. This review will be used to develop a PCR-based testing methodology for the detection and confirmation of risk alleles in the Caucasian population.Materials and methods. Data from 46 original research papers and reviews was analysed. Allele frequencies of the most relevant polymorphisms were checked against the data for European population.Results. As an outcome of this review, a few most promising SNPs were selected for future research. Firstly, ABCC4 rs1751034 and rs3742106 and ABCC10 rs9349256 and rs2125739 were associated with an increased risk of renal impairment, higher plasma concentration, and toxicity when treated with tenofovir. Parallel analysis of ABCC4 and ABCC10 SNP effects on renal impairment together with CYP24A1 rs2248359 that was recently reported as a potential renal toxicity marker might be more informative. Secondly, CYP2B6 rs3745274 that was associated with an increased efavirenz plasma concentration, and increased risk of liver and CNS toxicity should be evaluated. SNPs in CYP2B6, CYP2A6 (rs28399433), and CYP3A4 (rs4646437) should be evaluated in parallel since possession of all three variants might put patients at a much higher risk.Conclusion. Identified alleles could become new markers used in drug prescription protocols if significant effect in Caucasian population will be found. The most relevant SNPs should be tested in in supporting future studies to evaluate the significance for patients with HIV in Russia.

Collapse Breakdown in Mid-Wavelength Infrared HgCdTe Avalanche Photodetector

HgCdTe avalanche photodetector is one of the most promising candidates in capturing ultra-weak signal or even single photon in mid-wavelength infrared. However, the limited breakdown voltage and the unresolved underlying physics still lay an inevitable obstacle to achieve high-performance photodetectors. Here, for the first time we propose a collapse breakdown mechanism to thoroughly demonstrate the physics that underpins the relatively low-voltage breakdown in traditional HgCdTe positive-intrinsic-negative structures both theoretically and experimentally. Temperature-change measurement of the homemade devices is conducted to reveal the competitive behavior in the breakdown phenomenon. Below 180 K, the collapse breakdown dominates the overall device breakdown; while above 180 K, the avalanche breakdown contributes the majority to the device breakdown. With optimized structure, we achieve photoelectric gain and dark current 1700 and 10-9 A @11.3V, respectively. Remarkably, a semi-empirical formula is derived to predict the optimal prescription of doping concentrations of different layers which are capable of realizing high gain and low dark current simultaneously. Reported results in literature are included to further confirm the flexibility and universality of the mechanism. This work represents a steady step forward to recognizing the breakdown mechanism and achieving high -performance avalanche single-photon photodetectors.

Identifying the Optimal Exercise Prescription for Patients with Coronary Artery Disease Undergoing Cardiac Rehabilitation: Protocol for a Systematic Review and Network Meta-Analysis of Randomized Control Trials.

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity. Exercise-based cardiac rehabilitation (EBCR) has been shown to improve clinical outcomes in these patients, and yet clinicians are often challenged to prescribe the most effective type of exercise training. Therefore, this systematic review and network meta-analysis (NMA) aims to formally quantify the optimal dose of exercise training interventions to improve exercise capacity and quality of life by undertaking direct and indirect pooled comparisons of randomized controlled trials. A detailed search will be conducted on PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), EMBASE and Web of Science. Two reviewers will screen the existing literature and assess the quality of the studies. Disagreements will be resolved through consensus. We anticipate that the analysis will include pairwise and Bayesian network meta-analyses. Most of the trials have studied the impact of exercise training comparing one or two modalities. As a result, little evidence exists to support which interventions will be most effective. The current NMA will address this gap in the literature and assist clinicians and cardiac rehabilitation specialists in making an informed decision. Results will be disseminated through peer-reviewed journals. Ethical approval is not applicable, as no research participants will be involved. PROSPERO Registration number: CRD42022262644.

Association between blood pressure and circadian timing of physical activity of Japanese workers.

High blood pressure (BP) is reported to be accounted for more than 10 million deaths, and the high prevalence of hypertension is a global issue. Exercise is known to reduce BP and the optimal exercise prescription has been discussed. Furthermore, since the circadian clock plays an important role in BP regulation and its related physiological functions, the time-of-day difference in the effect of exercise on BP is suggested. However, when people should regularly exercise for the prevention of hypertension remains unclear. In this cross-sectional research, we analyzed the association of habitual exercise and BP depending on their performed timing, time length, and frequency for three levels of intensity from an analysis of questionnaire answered by Japanese male workers (N = 2,343, mean age ± SE = 49.2 ± 0.2 years old, date: June 2021). From the subjects who responded, subjects with irregularly high or low BP, no regular physical activity or under the treatment of hypertension were excluded from the analysis. From the comparison of SBP and DBP between those who performed physical activity at each time period, vigorous or moderate physical activity in the evening (18:00–21:00) showed significantly lower average BP. On the other hand, those who walked in early morning (03:00–06:00) showed higher DBP. These time-specific differences were confirmed from multiple regression analysis, eliminating the confounding factors such as age and BMI. When participants were divided into groups according to their BP, compared to normal BP groups, higher BP groups exercised less in the evening. Our findings suggest that when to exercise is important, and that exercising in the evening (18:00–21:00) may be better to achieve the hypotensive effect of exercise.

Can exercise attenuate the negative effects of long COVID syndrome on brain health?

The impetus for many governments globally to treat the novel coronavirus (COVID-19) as an endemic warrant more research into the prevention, and management of long COVID syndrome (LCS). Whilst the data on LCS remains scarce, reports suggest a large proportion of recovered individuals will experience ongoing neuropsychological symptoms, even with mild disease severity. The pathophysiology underlying LCS is multifaceted. Evidence suggests that altered inflammatory, neurotrophic, and neurotransmitter pathways within the brain contribute to neuropsychological symptoms reported following COVID-19. Exercise or regular physical activity has long been shown to have positive effects on brain health and cognition through exerting positive effects on inflammatory markers, neurotransmitters, and neurotropic factors analogous to the neurophysiological pathways proposed to be disrupted by COVID-19 infection. Thus, exercise may serve as an important lifestyle behavior in the management of LCS. In this opinion article, we present the evidence to support the positive role of exercise in the management of cognitive symptom that manifest with LCS and discuss important considerations and interactions with cardiorespiratory and exercise tolerance complications that often present for individuals experiencing LCS. We highlight the need for more research and training of sports medicine practitioners and clinical exercise physiologists in the management of LCS with exercise and call for further research to understand the optimal dose-responses and exercise prescription guidelines for cognitive benefits and minimizing other complications.

Effects of Supervised Physical Exercise as Prehabilitation on Body Composition, Functional Capacity and Quality of Life in Bariatric Surgery Candidates: A Systematic Review and Meta-Analysis.

Background: Prehabilitation is a strategy used aiming to reduce the risk factors and complications of surgery procedures, but there is no consensus on the effectiveness of supervised physical exercise and its optimal prescription during this phase. Objectives: To determine the effects of exercise prehabilitation on body composition, functional capacity and quality of life in candidates for bariatric surgery. Search methods: A search was conducted in PubMed, Web of Science, SciELO, Scopus, MEDLINE and CINAHL. Selection criteria: Only randomized clinical trials that examined the effectiveness of supervised physical exercise were included. The main outcomes were body composition, functional capacity, quality of life and surgical outcomes. Data collection and analysis: Two researchers independently selected the literature, extracted the data and evaluated the risk of bias. A third researcher was consulted when a consensus was not reached. The risk of bias was assessed by the tool recommended by the Cochrane Collaboration, the quality of the evidence by GRADE, and to analyze the effects of prehabilitation on the primary objectives, RevMan software, version 5.3 was used. Main results: The search resulted in 4550 articles, of which 22 met the eligibility criteria, leaving 5 articles selected for this review. One article was assessed as a high bias risk and four as an uncertain risk, which included 139 candidates for bariatric surgery. Most of the studies evaluated the body composition, functional capacity and quality of life; none reported surgical outcomes. Conclusions: Supervised physical exercise has positive effects on the body composition, functional capacity and quality of life; there was no evidence for surgical outcomes, which opens up a field of study for future research of this population.