Parenteral Drugs Research Articles

Utilization Trend of Parenteral Antidiabetic Drugs in Type 2 Diabetic Patients Covered by Iran Health Insurance Organization from 2011 to 2030.

Exploring and analyzing the cost of medicines is an important tool for their management and planning. This study aims to analyze the utilization and costs of parenteral anti-diabetic medications during the past decade and predict the future trend of these medications from 2021 to 2031 in people that are covered by Iran Health Insurance Organization (IHIO). This study was based on secondary analysis of data routinely reported to IHIO from 2011 to 2019. For each drug, the Defined Daily Dose (DDDs) and DDDs per 1000 inhabitants per day were calculated for the last 9 years according to the WHO protocol. Then a regression analysis was used to predict the utilization trend of each drug for the following 10 years. The overall utilization of injectable antidiabetic drugs has constantly increased during the last nine years. This increasing trend is estimated to continue during the next decade. In Iran, the increase in the diabetic population and better access in the future will be the main reasons for the increase in the utilization of various insulins. The increasing trend of utilizing injectable anti-diabetic drugs in Iran might be partly due to new patients and partly because of improvement in patient access to new treatments. This also suggests that, compared to the average in the commonwealth countries, Iranian diabetic patients has faced lack of drug utilization in the past decade that is gradually reducing.

An Aza-michael Addition Product Causes Incompatibility Between Etacrynic Acid and Theophylline in a Paediatric Cardiological ICU.

In a compatibility study of parenteral drugs commonly used in paediatric cardiological intensive care units, an unknown reaction product was found in a mixture of etacrynic acid and theophylline. The conditions in terms of the concentration of etacrynic acid and theophylline as well as the materials used corresponded to the conditions in the intensive care unit. Initially, the reaction product appeared as a significant and increasing peak in the chromatograms when determining the content of etacrynic acid and theophylline via HPLC. At the same time, the concentrations of both drugs decreased. A literature search in the chemical databases Reaxys® and Scifinder ® revealed a patent from 1967 describing an aza-Michael addition between etacrynic acid and theophylline to either N-7 or N-9. Using LC-MS/MS experiments, we were able to confirm that Michael-like reaction between etacrynic acid and theophylline occurs. To elucidate the exact structure of the reaction product we performed NMR experiments (COSY, HSQC and HMBC). With the acquired data we were finally able to identify the unknown compound as the N-7 substituted adduct [2-(2,3-dichloro-4-{2-[(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl]butanoyl}phenoxy)acetic acid]. Our findings show that etacrynic acid and theophylline should not be mixed and should be administered through separate venous lines when infused.

Pharmacology and Clinical Development of Factor XI Inhibitors

Therapeutic anticoagulation is indicated for a variety of circumstances and conditions in several fields of medicine to prevent or treat venous and arterial thromboembolism. According to the different mechanisms of action, the available parenteral and oral anticoagulant drugs share the common principle of hampering or blocking key steps of the coagulation cascade, which unavoidably comes at the price of an increased propensity to bleed. Hemorrhagic complications affect patient prognosis both directly and indirectly (ie, by preventing the adoption of an effective antithrombotic strategy). Inhibition of factor XI (FXI) has emerged as a strategy with the potential to uncouple the pharmacological effect and the adverse events of anticoagulant therapy. This observation is based on the differential contribution of FXI to thrombus amplification, in which it plays a major role, and hemostasis, in which it plays an ancillary role in final clot consolidation. Several agents were developed to inhibit FXI at different stages (ie, suppressing biosynthesis, preventing zymogen activation, or impeding the biological action of the active form), including antisense oligonucleotides, monoclonal antibodies, small synthetic molecules, natural peptides, and aptamers. Phase 2 studies of different classes of FXI inhibitors in orthopedic surgery suggested that dose-dependent reductions in thrombotic complications are not paralleled by dose-dependent increases in bleeding compared with low-molecular-weight heparin. Likewise, the FXI inhibitor asundexian was associated with lower rates of bleeding compared with the activated factor X inhibitor apixaban in patients with atrial fibrillation, although no evidence of a therapeutic effect on stroke prevention is available so far. FXI inhibition could also be appealing for patients with other conditions, including end-stage renal disease, noncardioembolic stroke, or acute myocardial infarction, for which other phase 2 studies have been conducted. The balance between thromboprophylaxis and bleeding achieved by FXI inhibitors needs confirmation in large-scale phase 3 clinical trials powered for clinical end points. Several of such trials are ongoing or planned to define the role of FXI inhibitors in clinical practice and to clarify which FXI inhibitor may be most suited for each clinical indication. This article reviews the rationale, pharmacology, results of medium or small phase 2 studies, and future perspectives of drugs inhibiting FXI.

A Nontrivial Analysis of Patient Safety Risk from Parenteral Drug- and Medical Device-Borne Endotoxin.

A thorough and systematic analysis of potential endotoxin-related safety issues from parenteral drugs and devices is important to ensure appropriate current Good Manufacturing Practices, compendial requirements, standards and regulatory guidance. Lately, the US Food and Drug Administration has been expecting pharmaceutical firms to apply an arbitrary safety factor to compendial compliant drug specifications for endotoxin, potentially causing manufacturing challenges, supply issues and additional unwarranted costs. The aim of this study was to evaluate data from three disparate sources over an extended period of time, from 2008 to 2021, to determine if there exists an industry-wide risk to patients from parenteral drugs and devices, thereby evaluating if changes to current Good Manufacturing Practices or compendial requirements are indeed warranted. Food and Drug Administration data from current Good Manufacturing Practices non-compliance observations, product recalls and the FDA Adverse Event Reporting System were used as the three sources of data. Parenteral products were separated into drugs and devices, potential endotoxin-related patient safety issues were characterised in terms of the available non-compliance information, the type and number of product recalls, and the type and number of potential adverse events. Descriptive statistics in Microsoft Excel 2019 and Pivot tables were used for the analysis and presentation of the data. From 2011 to 2021, a total of 188 endotoxin-related current Good Manufacturing Practices compliance observations were recorded, 70% and 30% were associated with laboratory and manufacturing origins, respectively. Finished drug product testing accounted for 56% of these. In contrast, 95% of all endotoxin-related product recalls were associated solely with medical devices. Over the years 2008-2021, approximately 1.4% of all adverse events (23,663,780) were recorded with some reference to pyrexia (fever); however, there are sparse data categorically attributing this to the administration of parenteral drugs or devices or combinations of these possessing high levels of endotoxin. Analysis of data concerning drug- and device-borne endotoxin obtained from FDA data from current Good Manufacturing Practices non-compliance observations, product recalls and the FDA Adverse Event Reporting System demonstrated the absence of industry-wide issues with endotoxin contamination. Based upon these data, changes to current Good Manufacturing Practices and the compendial methodology of setting endotoxin specifications (and hence the compendial methodology of testing for endotoxins) are unwarranted.

Stability and Activity of Interferon Beta to Treat Idiopathic Pulmonary Fibrosis with Different Nebulizer Technologies.

Background: Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by lung scarring, which results in breathing difficulty. Currently, patients with IPF exhibit a poor survival rate and have access to very limited therapeutic options. Interferon beta (IFN-β) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis, and it has also been shown to exhibit therapeutic potential in IPF. However, clinical use of IFN-β did not lead to improved overall survival in IPF patients in existing studies. One possibility is the limited efficiency of IFN-β delivery through intravenous or subcutaneous injection. Materials and Methods: The aerosol particle size distribution was determined with a laser diffraction particle size analyzer to characterize the droplet size and fine particle fraction generated by three types of nebulizers: jet, ultrasonic, and mesh. A breathing simulator was used to assess the delivery efficiency of IFN-β, and the temperature in the medication reservoirs was monitored with a thermocouple during nebulization. To further evaluate the antifibrotic activity of IFN-β pre- and postnebulization, bleomycin (BLM)- or transforming growth factor-beta (TGF-β)-treated human lung fibroblast (HLF) cells were used. Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Transwell migration assay and Q-PCR analysis were used to evaluate cell migration and the myofibroblast differentiation ability, respectively. IFN-β protein samples were prepared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) sample loading buffer, and the expression of IFN-β was assessed by western blotting. Results: Among the current drug delivery systems, aerosolized medication has shown increased efficacy of drug delivery for treating respiratory diseases when compared with parenteral drugs. It was found that neither the structural integrity nor the biological function of nebulized IFN-β was compromised by the nebulization process of the mesh nebulizer. In addition, in BLM dose-response or TGF-β-induced lung fibroblast proliferation assays, these effects could be reversed by both parenteral and inhaled IFN-β nebulized with the mesh nebulizer. Nebulized IFN-β with the mesh nebulizer also significantly inhibited the migration and myofibroblast differentiation ability of TGF-β-treated HLF cells. Conclusions: The investigations revealed the potential efficacy of IFN-β in the treatment of IPF with the mesh nebulizer, demonstrating the higher efficiency of IFN-β delivered through the mesh nebulizer.

Analysis of production time and capacity for manual and robotic compounding scenarios for parenteral hazardous drugs

BackgroundThe increasing amount of hazardous preparations in combination with shortages leads to a call for more efficient compounding methods. This research aims to evaluate the required amount of time, production...

US-guided central venous catheter placement in the neonatal intensive care unit: Brachiocephalic vein or internal jugular vein?

Centrally inserted central catheters (CICCs) are commonly used to monitor venous pressure and administer parenteral nutrition and drugs in newborns. In the present study, we evaluated cannulation success rates, cannulation time, and frequency of complications in catheterization of the internal jugular vein (IJV) and brachiocephalic vein (BCV). The present study included patients who underwent IJV and BCV catheterization under ultrasound (US) guidance. The patients were divided into two groups, IJV and BCV, depending on the vein in which the CICC was utilized. We documented the diameters of the IJVs and BCVs, first attempt and overall success rates, mean cannulation time, and complication rates. A total of 79 patients were evaluated, 37 in the BCV group and 42 in the IJV group. No significant differences were observed between the two groups in terms of sex, mean age, or weight range (p > 0.05).The mean vein diameter was significantly larger in the BCV group than in the IJV group (p < 0.001); the mean number of attempts was significantly higher in the IJV group than in the BCV group (p < 0.001); the mean cannulation time was significantly longer in the IJV group than in the BCV group (p < 0.001); and the first attempt success rate was 50% in the IJV group, versus 94.6% in the BCV group. The overall success rate was 100% in both groups. The rate of complications was 8.6% in the IJV group, while no complications developed in the BCV group. Given the larger diameter of the vessel, BCV catheterization was found to result in quicker cannulation and lower complication rates. The results of the present study suggest that BCV catheterization should be the first choice for neonatal intensive care unit (NICU) patients who require parenteral support or close venous pressure monitoring.

Reporting of Adverse Drug Reactions with Parenteral Drugs for the On-Demand Treatment of Hereditary Angioedema Attacks – Analysis of the FAERS Database 2009 to 2022

Analysis assessed the post-marketing reporting rates for adverse drug reactions (ADRs) in patients treated with parenteral on-demand hereditary angioedema (HAE) drugs utilizing the FDA’s Adverse Event Reporting System (FAERS).

Process Evaluation of Facility Delivery Services in Northwest Ethiopia: In the Case of Public Health Centers.

Even if giving birth at health facility is vital for both the mothers and their newborns, the coverage of institutional delivery in Ethiopia is very low (50%). In that regard, several studies have shown the possible factors of low delivery service uptake from the patients' side, but evidences on delivery services at the health centers are meagre. This study aimed to evaluate the process of delivery services in public health centers of northwest Ethiopia. A case study evaluation design with an embedded mixed-method was used to evaluate institutional delivery in public health centers of Gondar city. Dimensions from the access (availability, accommodation, and acceptability) and implementation fidelity (compliance) frameworks were used. A total of 363 mothers, 32 document reviews, 32 direct observations, and 17 key informants were included. The qualitative data were transcribed, translated, coded, and analysed using a thematic analysis approach. The overall process of institutional delivery services was measured based on pre-determined judgmental criteria. The overall facility delivery process was 75.1%, judged by availability (78.5%), compliance (70.6%), accommodation (68.8%), and acceptability (80.2%) of services. Essential medicines in some of the health centers were stockout, insufficient delivery rooms and inadequate training of health workers on obstetric and newborn care were observed. Using partograph and examining vulval-perineal region for possible laceration during intrapartum period were less practiced. Residence (AOR: 0.13, 95% CI: 0.06-0.30), ANC 1 to 3 visits (AOR: 2.65, 95% CI: 1.05-6.74) and ANC4+ (AOR: 5.57, 95% CI: 2.09, 14.84) were factors affected acceptability of delivery services. Major constraints were in the accommodation of delivery services which needs a holistic effort from all stakeholders. Therefore, implementors with other stakeholders shall improve delivery rooms, facilitate training, and provide parenteral drugs as part of the obstetric and newborn care to improve the facility delivery services in Ethiopia.

Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where Do Equine Medications Stand?

While the global market for veterinary products has been expanding rapidly, there is still a lack of specialist knowledge of equine pharmaceutics. In many cases, the basic structure of the gastrointestinal tract (GIT) and integumentary system of the horse shares similarities with those of humans. Generally, the dosage form developed for humans can be repurposed to deliver equine medications; however, due to physiological variation, the therapeutic outcomes can be unpredictable. This is an area that requires more research, as there is a clear deficiency in literature precedence on drug delivery specifically for horses. Through a careful evaluation of equine anatomy and physiology, novel drug delivery systems (NDDSs) can be developed to adequately address many of the medical ailments of the horse. In addition to this, there are key considerations when delivering oral, topical, and parenteral drugs to horses, deriving from age and species variation. More importantly, NDDSs can enhance the duration of action of active drugs in animals, significantly improving owner compliance; and ultimately, enhancing the convenience of product administration. To address the knowledge gap in equine pharmaceutical formulations, this paper begins with a summary of the anatomy and physiology of the equine gastrointestinal, integumentary, and circulatory systems. A detailed discussion of potential dosage-form related issues affecting horses, and how they can be overcome by employing NDDSs is presented.

Transdermal opioids for acute postoperative pain: A road less travelled!

Dear Editor, Transdermal delivery system (TDS) is a simple, reliable, noninvasive analgesic delivery method that has been used extensively for chronic pain management. After application, drug in TDS forms a depot in the upper layers of skin that slowly increases serum concentration.[4] Both fentanyl and buprenorphine have high lipid solubility and low molecular weight which makes them ideal candidates for a TDS. The perceived advantages of TDS for acute postoperative pain include sustained blood level of the drug and reduced side effects. Transdermal buprenorphine (TDB) provides convenient once-weekly dosing, has ceiling effect for respiratory, lower abuse potential, and does not require dose alterations patients with renal dysfunction, unlike fentanyl (full μ-opioid receptor agonist).[1] Khandelwal et al. compared two doses of buprenorphine (10 μgh-1 and 20 μgh-1) with fentanyl (25 μgh-1) in adult patients undergoing lower limb arthroscopic surgery.[2] They found TDB patch (20 μgh-1) to be an effective postoperative analgesic without any significant undesirable effects. The concentration of TDS drugs tends to be higher in the first 24 h and several factors like variability in body temperature, factors that increase cutaneous blood flow (warming blanket, sepsis or regional anesthesia), previous opioid use, hemodynamics, and patient’s general condition may make TDS opioid absorption unpredictable.[3] There have been reports of serious, life-threatening respiratory depression and death following transdermal fentanyl.[4] Buprenorphine is 60 times while fentanyl is 100 times as potent as morphine and the duration of action for fentanyl (3d) and TBD (7d) is different. So, equianalgesic doses of both[ratio 3:5]should be compared but the authors in the study have used a non-equianalgesic dosage (10:25 and 20:25). The peak effect comes in 12 h (fentanyl) to 24 h (buprenorphine). So, the patches are generally applied a day before surgery, but this may not be the ideal scenario in daycare settings. Alternative analgesics should be started till the effect of TDS drugs comes in 12–24 h, whereas in the index study, the usual analgesics were withheld the day before surgery when the patches were applied.[2] Many dose formulations are available and according to recommendations from the manufacturer, opioid-naive patients should initially receive the lowest strength patch.[5] Authors of present study evaluating the use of TDS in postoperative pain management concluded that further prospective randomized studies are required to conclusively find the optimum dose.[2] TDS are amenable to abuse, serious side effects like respiratory depression, and cognitive dysfunction, may increase duration of hospital stay and overall cost of daycare procedures. Despite their success for chronic pain management, TDS opioids for acute postoperative pain is a new and off-label use and should be undertaken if the benefits outweigh the risks involved. The main rebuke for TDS is its lack of titrability, long latency for onset, and slow offset making it an inferior alternative compared to other commonly used modes of analgesic delivery such as patient-controlled analgesia. Moreover, they are an expensive alternative to parenteral and oral drugs and may not be ideal in our setting. Hence, we would urge caution in the indiscriminate usage of TDS as a sole modality of postoperative analgesia until further robust evidence proves the contrary. Whenever chosen, they should be used in monitored settings for opioid naïve patients. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Methodological approach to the pharmaceutical development of solutions for injection in polymer packaging

Medicines in the form of solutions for injections are the most effective in terms of dosage accuracy and speed of pharmacological action. Pharmaceutical development of drugs is one of the key stages of their life cycle, which main task is to create a high-quality medicine during the production process.&#x0D; The aim of the work is to develop a methodological approach to the pharmaceutical development of parenteral drugs, namely solutions for injections in polymer packaging.&#x0D; The objects of the study were sources of scientific literature, regulatory documents, manuals, textbooks and reports of the pharmaceutical development of medicinal products, documents of the registration dossier, reports of regulatory authorities on the examination of medicinal products. Informational and empirical research methods are used in the work by studying, summarizing and comparing documentary data.&#x0D; Compositions and technologies for the production of solutions for injections of domestic manufacturing based on medicinal substances of different chemical nature and their concentrations have been developed, taking into account data from scientific sources regarding their stability in aqueous solutions and the results of research into the chemical and technological properties of substances. The popular opinion about the inertness of auxiliary substances in the composition of the dosage form has been shown is not entirely reliable; since their appropriate and rational choice has a significant impact to the quality of the final product in the manufacture of solutions for injection. Therefore, in order to ensure the stability and safety of active pharmaceutical ingredients, as well as to improve the physicochemical parameters during the production of solutions for injections, it was necessary to introduce auxiliary substances into their composition. The methodological role of the stage of choosing the primary packaging with a comprehensive research of its properties in the production of specific solutions for injections was outlined.&#x0D; A methodological approach to the pharmaceutical development of solutions for injections in polymer packaging has been developed. As a result of the analysis of literary sources devoted to the theory and practice of creating medicinal forms and based on general methodological approaches to the development of medicinal products, as well as on the basis of practical work experience; an improved methodological approach to the creation of high-quality, effective and safe solutions for injections has been proposed.

Alternative Excipients for Protein Stabilization in Protein Therapeutics: Overcoming the Limitations of Polysorbates.

Given their safety and efficiency in protecting protein integrity, polysorbates (PSs) have been the most widely used excipients for the stabilization of protein therapeutics for years. In recent decades, however, there have been numerous reports about visible or sub-visible particles in PS-containing biotherapeutic products, which is a major quality concern for parenteral drugs. Alternative excipients that are safe for parenteral administration, efficient in protecting different protein drugs against various stress conditions, effective in protein stabilization in high-concentrated liquid formulations, stable under the storage conditions for the duration of the product's shelf-life, and compatible with other formulation components and the primary packaging are highly sought after. The aim of this paper is to review potential alternative excipients from different families, including surfactants, carbohydrate- and amino acid-based excipients, synthetic amphiphilic polymers, and ionic liquids that enable protein stabilization. For each category, important characteristics such as the ability to stabilize proteins against thermal and mechanical stresses, current knowledge related to the safety profile for parenteral administration, potential interactions with other formulation components, and primary packaging are debated. Based on the provided information and the detailed discussion thereof, this paper may pave the way for the identification or development of efficient excipients for biotherapeutic protein stabilization.

Pathogenesis and management of multiple sclerosis revisited

BackgroundMultiple sclerosis is an autoimmune chronic inflammatory disease characterized by selective destruction of myelin in the CNS neurons (including optic nerve). It was first described in the 19th century and remained elusive owing to the disease's unique relapsing and remitting course. The widespread and debilitating prevalence of multiple sclerosis (MS) has prompted the development of various treatment modalities for its effective management. Methods and objectivesA literature review was conducted using the electronic databases PubMed and Google Scholar. The main objective of the review was to compile the advances in pathogenesis, classifications, and evolving treatment modalities for MS. ResultsThe understanding of the pathogenesis of MS and the potential drug targets for its precise treatment has evolved significantly over the past decade. The experimental developments are also motivating and present a big change coming up in the next 5 years. Numerous disease-modifying therapies (DMTs) have revolutionized the management of MS: interferon (IFN) preparations, monoclonal antibodies—natalizumab and ocrelizumab, immunomodulatory agents—glatiramer acetate, sphingosine 1-phosphate receptor 1 (S1PR1) modulators (Siponimod) and teriflunomide. The traditional parenteral drugs are now available as oral formulations improving patient acceptability. Repurposing various agents used for related diseases may reinforce the drug reserve to manage MS and are under trials. Although at a nascent phase, strategies to enhance re-myelination by stimulating oligodendrocytes are fascinating and hold promise for better outcomes in patients with MS. ConclusionsThe recent past has seen staggering inclusions to the management of multiple sclerosis catalyzing a significant turnabout in our approach to diagnosis, treatment, and prognosis. Since the advent of DMTs various other oral and injectable agents have been approved. The advances in MS therapeutics and diagnostics have laid the ground for further research and development to enhance the quality of life of afflicted patients.

Development of fiber optic in vitro release testing method for dexamethasone release from the oil solutions.

For many parenteral drugs, there is still no standardized method for in vitro release (IVR) testing available. This article presents the development of a new IVR method for oil solutions using a dialysis membrane and USP II apparatus coupled to a fiber optic UV-Vis spectrometer. Experiments were performed using dexamethasone formulations containing castor oil as a solvent with the addition of cosolvents, 20 % (v/v) of isopropanol or Capryol® 90. Based on solubility testing results, castor oil was chosen as the best solvent amongst other vegetable oils, while a significant increase in solubility was obtained by adding either of the two cosolvents. Partitioning experiments were performed to ensure these formulations could achieve prolonged drug release. IVR testing was performed with model formulations and critical test parameters were varied in order to examine the method's sensitivity. The developed method was sensitive to temperature and stirring rate, while coupling the USP II apparatus with a fiber optic UV-Vis spectrometer enabled complete automation. Moreover, due to the interference of excipients on fiber optic detection of dexamethasone during the release testing, derivative spectroscopy was successfully introduced for the elimination of the interference. The developed IVR method described herein could be useful in preformulation investigations and the early development of novel formulations.

Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions.

Oral inhibitors of the platelet P2Y12 receptor are indispensable in the treatment of ST-elevation myocardial infarction (STEMI), improving outcomes and even reducing mortality in some studies. However, these drugs are limited by delayed absorption and suboptimal platelet inhibition at the time of primary percutaneous coronary intervention. Despite efforts to achieve faster and more sustained platelet inhibition, strategies such as prehospital administration, higher loading doses, and crushed formulations have not led to improved coronary reperfusion. Parenteral glycoprotein IIb/IIIa inhibitors act sooner and are more potent than oral P2Y12 inhibitors, but their use has been limited by the increased risk of major bleeding and thrombocytopenia. Hence, there is a clinical need to refine drugs that deliver rapid, effective, yet safe platelet inhibition in the setting of STEMI. Novel parenteral antiplatelet drugs, such as cangrelor, selatogrel, and zalunfiban, have been recently developed to achieve rapid, potent antiplatelet effects while preserving hemostasis. We provide a description of currently available parenteral antiplatelet agents and of those in clinical development for prehospital administration in STEMI patients.

Anti-osteoporotic treatment and COVID-19 risk: is there an association?

Introduction. Despite the recent ASBMR, AACE, Endocrine Society, ECTS&amp;NOF guidelines for osteoporosis management in the era of COVID-19 the impact of antiosteoporotic drugs on disease risk and severity is insufficiently studied. The purpose of this study was to assess the COVID-19 risk for the patients receiving the parenteral bisphosphonate or Denosumab treatment, and the severity of its course in patients with systemic osteoporosis. Materials and methods. We performed the phone survey and studied the results of 195 patients (92 % women; mean age – 62.7±10.8 years) with systemic osteoporosis depending on the current use of parenteral antiresorptive drugs (Zoledronic, Ibandronic acids, or Denosumab, n = 125) and compared the results with data of the patients with osteoporosis who did not use any anti-osteoporotic drugs previously (n = 70). Results. The group of patients with COVID-19 included 32.9 % of patients who did not receive previously any anti-osteoporotic treatment and 33.3 % of osteoporotic patients treated with parenteral antiresorptive drugs. The share of the patients taking the Zoledronic acid who fell ill with COVID-19 was 29.2 %, the share of those taking the Ibandronic acid was 34.4%, and the share of those taking Denosumab was 42.9 %. We did not reveal any significant differences in the COVID-19 frequency and severity depending on the presence and type of parenteral anti-osteoporotic therapy. Additionally, there were no differences depending on the patients' age, gender, obesity, and other osteoporosis risk factors. The risk of COVID-19 in the patients with systemic osteoporosis did not differ depending on antiresorptive drug use, amounting (odds ratio (OR) 95 % CI) 1.1 (0.6-2.0), or on the use of the definite anti-osteoporotic drug (for the Zoledronic acid – 0.9 (0.4-2.0), the Ibandronic acid – 1.1 (0.5-2.3), and for the Denosumab – 1.6 (0.5-5.2). Conclusions. Parenteral anti-osteoporotic drugs (Zoledronic acid, Ibandronic acid, or Denosumab) do not have any influence on COVID-19 frequency and severity and can be recommended for the continuation of the treatment of patients with osteoporosis.

Antibiotic prescription pattern of cardiovascular thoracic surgery department in a tertiary care hospital of North Mumbai- A retrospective study

Cardiovascular diseases are the most common cause of morbidity and mortality. Prevention of surgical site infection is the major concern in cardiac surgery because deep sternal infection leads to prolonged hospital stay, increased cost of treatment and even death. The cardiac surgeons have used many different therapeutic protocols for antimicrobial prophylaxis. The aim of this study is to evaluate the prescribing pattern of antibiotics in patients undergoing cardiovascular thoracic surgery (CVTS). A single centre retrospective study was conducted in the CVTS department from January 2017 to October 2018. The hospital has centralised electronic medical and laboratory record database that uses unique identification numbers. The data was obtained from medical record department of the hospital. All records including patient’s age, gender, admission period, investigations performed, antibiotics advised during indoor stay and at discharge along with their administration routes, dosages and duration were noted. The pre-existing comorbidities and surgical intervention were also recorded. Among the total 86 patients reviewed, 88.84% were males with the mean age of 58.7 years. 87.21% of the patients received parenteral antibiotics, 98.83% received more than one antibiotic, either in oral or parenteral formulations. The most commonly used generic antibiotics were cefoperazone – sulbactam (69.77%), levofloxacin (59.30%), cefuroxime (25.58%), cefoperazone (11.63%) and amoxicillin – clavulanic acid (43.02%). While in admitted patients, beta lactam / beta lactamase inhibitors combination (98.83%), fluoroquinolones (69.77%), cephalosporins (34.88%), glycopeptides (3.49%) and carbapenem (2.33%) were used and on the other hand at the time of discharge, fluoroquinolones (43.02%), cephalosporins (32.56%) and beta lactam / beta lactamase inhibitors combination (39.53%) were prescribed. The indications for admission were Coronary artery bypass grafting (90.7%), Aortic valve replacement (5.81%), Mitral valve replacement (2.33%) and Dual valve replacement (1.16%). The most common associated comorbidities were ischemic heart disease (73.26%), diabetes mellitus (47.67%), hypertension (56.98), chronic kidney disease (5.81%) and chronic obstructive pulmonary disease (3.49%). The mean duration of usage of parenteral drugs was 5.20 days whereas it was 5.14 days for the oral drugs. There was an irrational usage of antibiotics in patients undergoing surgery in the CVTS department. The prescription pattern varied according to the surgeon’s preference or experience. This study strongly recommends the implementation of antimicrobial stewardship programme and written protocol driven antibiotics prescription.

Drug development challenges in nontuberculous mycobacterial lung disease: TB to the rescue.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is treated with multiple repurposed drugs. Chemotherapy is long and often toxic, includes parenteral drugs, and suffers from poor cure rates. There is an urgent need for more efficacious, tolerated, and oral antibiotics optimized towards the treatment of NTM-PD, adapted to the spectrum of disease. In contrast to the empty NTM pipeline, drug development for the related tuberculosis lung disease has experienced a renaissance. Here, we argue that applying lessons learned from tuberculosis will facilitate the discovery of curative oral regimens for NTM-PD.

Monomeric lipopolysaccharide (LPS) activity affected by dimerization of receptors is the key for the similarity between the Limulus amebocyte lysate (LAL) test and the rabbit pyrogen test

Endotoxin or lipopolysaccharide (LPS) triggers inflammatory cytokine production of mammal cells through Toll-like receptor 4 (TLR4) activation. This reaction causes pyrogenicity in rabbits. The rabbit pyrogen test has been used for the pyrogen detection in parenteral drugs and medical devices. Limulus amebocyte lysate (LAL) test, adopted as an alternative test for the rabbit pyrogen test in pharmacopoeias, has been safely used for more than 40 years. Even though the mechanisms of these biological assays are different, there should be similarity between the LAL test and the rabbit pyrogen test. Biological activity relates to the aggregation states of LPS, and there is still controversy whether the biologically active form of LPS is monomers or aggregates. Previous studies showed inconsistent results in biological activities of monomeric LPS. This suggests the difficulty to prepare monomeric LPS. Therefore, a simulation can be helpful to understand the activity of different status of LPS. In this study, the TLR4 activation was simulated by using simplified models, and compared the activity of LPS in different forms. The activation of TLR4 and the LAL activation require dimerization of receptors, which reduces the activity of monomeric LPS. The inert monomeric LPS caused by the dimerization of the receptors is the key to the similarity between the LAL test and the rabbit pyrogen test.