Dosing Guidelines Research Articles

Cannabis-infused foods: Phytonutrients, health, and safe product innovations.

Cannabis-infused foods are currently on the rise in markets all around the world. Meanwhile, there are concerns over the health implications for consumers. Studies have explored the therapeutic potential and nutritional and economic benefits of cannabis usage. Yet, the phytonutrients, processing methods, and health implications of cannabis-infused foods have not been well explored. This review evaluates existing evidence on the nutritional, processing, safety, and phytonutrient composition of cannabis-infused food products and their medicinal and functional prospects. Cannabis seeds contain the highest amount of dietary nutrients, while flowers contain the highest amount of bioactive constituents. Oils, butter, seeds, flowers, and leaf extracts are the plant forms currently incorporated into food products such as beverages, baked products, cooking ingredients, functional foods, nutraceuticals, and nootropics. Cannabis-infused foods have been found to offer therapeutic benefits for pain management, brain function, gut health, and certain cancers. Findings also show significant constraints associated with cannabis-infused foods regarding dosage guidelines, limited research, efficacy, and long-term health effects on consumers. This is further worsened by the lack of policies that regulate the industry. To realize the full potential of cannabis use in the food and health industries and in research, regulatory guidelines are needed to control dosages and improve its efficient use in these industries. This will go a long way to ensure the safety of cannabis users and enhance responsible production, marketing, and distribution.

A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Replacement Dose for Overt Hypothyroidism Induced by Programmed Cell Death Protein 1 Antibodies May Be Higher than Recommended.

The present recommendations, consensus, or guidelines for the replacement dosage for hypothyroidism induced by programmed cell death protein 1 (PD-1) therapy are not uniform, and there are very few special clinical trials that have examined the replacement dosage for it. This article illustrates the clinical characteristics of hypothyroidism induced by PD-1 antibodies (Abs) and reports the recommended replacement dosage for hypothyroidism. Eighteen patients with overt primary hypothyroidism induced by PD-1 Abs (group 1) were selected from 655 patients with different tumor types. Retrospective analysis was performed on patients in group 1 and 18 patients with natural courses of overt primary hypothyroidism who were age- and sex-matched with the patients in group 1 (group 2). The replacement dosages required for the patients in the two groups were compared. Thyroid dysfunction occurred in group 1 after approximately 3.0 ± 1.4 cycles of PD-1 therapy (1-6 stages), with a median time of 61.5 days. The median time of onset of hypothyroidism among all patients was 87.5 days (30-240 days). Most of the patients with hypothyroidism were asymptomatic, and the onset of hypothyroidism was independent of age, sex, TPOAb, TgAb and TSH in group 1 (P>0.05). The average replacement dosage for patients in group 1 was 1.8 ± 0.6 μg/kg/d (0.6-3.2 μg/kg/d). Multiple linear regression analysis showed that sex, age, TPOAb, TgAb and TSH were not correlated with drug dosage. It seemed that the average maintenance dosage of levothyroxine might need to be 1.8 μg/kg/day for patients with overt hypothyroidism induced by PD-1 Abs.

Antimicrobial management in patients undergoing therapeutic plasma exchange: A Cross-Sectional Nationwide Survey.

There is little evidence of antimicrobial elimination via therapeutic plasma exchange (TPE) and no guidelines for antimicrobial optimal dosing in patients undergoing TPE. We aimed to assess current practices and knowledge regarding antimicrobial management during TPE. A structured online survey was conducted from May to November 2023, and physicians were invited to participate through national scientific platforms and professional societies. One hundred five participants completed the survey, of whom 61% were infectious disease physicians, with 68.6% having more than 10 years of experience. That the TPE procedure could significantly affect plasma concentrations of antimicrobial agents was reported by 74.3% of the respondents. Among the physicians, 42.9% suggest antimicrobial dose adjustment, and 38.1% recommend temporarily discontinuing antimicrobial drug administration during TPE. Therapeutic drug monitoring was recommended by 33.3% of the respondents for certain antimicrobials, mainly glycopeptides and aminoglycosides, in patients undergoing concurrent TPE. Furthermore, 59.3% of physicians sometimes consult with another healthcare professional for treatment management, most commonly a pharmacist or a clinical pharmacist and an infectious diseases specialist. The core questions regarding potential drug-, procedure-, and patient-related antimicrobial elimination factors via TPE were responded to accurately by less than half of the physicians. It was clear that they had a lack of clinical practices and knowledge regarding antimicrobial management during TPE. To ensure the therapeutic efficacy of antimicrobials and avoid treatment failure, physicians should improve their practice strategies and consider antimicrobial elimination factors with TPE in this data-poor setting.

Confirming the Suitability of a Gentamicin Dosing Strategy in Neonates Using the Population Pharmacokinetic Approach with Truncated Sampling Duration.

(1) Background: Gentamicin is known to be nephrotoxic and ototoxic. Although gentamicin dosage guidelines have been established for preterm and term neonates, reports do show attainment of recommended peak concentrations but toxic gentamicin concentrations are common in this age group. (2) Methods: This was a prospective, observational study conducted in Namibia with 52 neonates. A dose of 5 mg/kg gentamicin was administered over 3-5 s every 24 h in combination with benzylpenicillin 100,000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Two blood samples were collected from each participant using a truncated pharmacokinetic sampling schedule. (3) Results: The one-compartment linear pharmacokinetic model best described the data. Birthweight, postnatal age, and white blood cell count were predictive of clearance (CL), while birthweight was predictive of volume (V). For the typical neonate (median weight 1.57 kg, median postnatal age 4 days (0.011 years), median log-transformed WBC of 2.39), predicted CL and V were 0.069 L/h and 0.417 L, respectively-similar to literature values. Simulated gentamicin concentrations varied with respect to postnatal age and bodyweight. (4) Conclusions: A 5 mg/kg/24 h dosage regimen yielded simulated gentamicin concentrations with respect to age and birthweight similar to those previously reported in the literature to be safe and efficacious, confirming its appropriateness.

Blueberries in focus: Exploring the phytochemical potentials and therapeutic applications

Blueberries, which belong to the Vaccinium spp. Genus, have attracted considerable interest because of their abundant phytochemical composition and potential for medicinal uses. The present study examines the many phytochemicals found in blueberries, such as anthocyanins, flavonoids, phenolic acids, and stilbenes, as well as their biological activities contributing to the health benefits of blueberries. Anthocyanins, the primary pigments that give blueberries their unique color, are renowned for their powerful antioxidant capabilities. These substances counteract oxidative stress by neutralizing free radicals, decreasing the likelihood of developing chronic illnesses such as cardiovascular disease, cancer, and neurological disorders. Furthermore, the presence of flavonoids and phenolic acids in blueberries contributes to their ability to reduce inflammation, prevent cancer, and protect the brain, improving their potential for therapeutic use. This study delves into the bioavailability and metabolism of these phytochemicals, specifically examining the impact of factors like food composition, gut microorganisms, and individual metabolic variations on their effectiveness. Both clinical and preclinical studies provide strong evidence for the beneficial effects of blueberries on multiple health factors, such as enhanced cognitive function, lowered blood pressure, and improved insulin sensitivity. These findings suggest that blueberries may play a significant role in managing conditions like Alzheimer's disease, hypertension, and diabetes. Moreover, this study examines the synergistic impacts of blueberry phytochemicals, suggesting that the health advantages of blueberries arise not alone from individual substances but also from their collective interactions. Proposed future study areas include the advancement of functional foods and nutraceuticals derived from blueberries, as well as the need for standardized clinical studies to determine appropriate dose guidelines and ensure long-term safety. Overall, the significant variety of phytochemicals in blueberries and their potential for therapeutic use make them a promising functional food. Further research into these substances' mechanisms of action and therapeutic uses will clarify their function in enhancing human health and avoiding illness.

Antibiotics, Analgesic Sedatives, and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review.

Antibiotic, analgesic sedative, and antiseizure medications are among the most commonly used medications in preterm/sick neonates, who are at high risk of nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe and potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. The reported variability in the medications used in neonates indicates the lack of adequate neonatal studies regarding their effectiveness and safety. Important obstacles contributing to inadequate studies in preterm/sick infants include difficulties in obtaining parental consent, physicians' unwillingness to recruit preterm infants, the off-label use of many medications in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials (antifungals), analgesics (sedatives), and antiseizure medications in neonates, focusing on current evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage, and evidence-based guidelines for their optimal use in neonates. We also address the effects of early antibiotic use on the intestinal microbiome and its association with long-term immune-related diseases, obesity, and neurodevelopment (ND). Recommendations for empirical treatment and the emergence of pathogen resistance to antimicrobials and antifungals are also presented. Finally, future perspectives on the prevention, modification, or reversal of antibiotic resistance are discussed.

Exploring the Therapeutic Potential of High Dose Co-amoxiclav (1 gm) in Different Clinical Conditions: A Review.

Amoxicillin/clavulanate (co-amoxiclav) is a widely used antibiotic in community healthcare settings, combining amoxicillin and clavulanate potassium to combat β-lactamase-producing bacteria. Despite its extensive use, limited pharmacokinetic/pharmacodynamic data support current dosing guidelines. This review explores the significance of high-dose co-amoxiclav (875 mg/125 mg) in treating various infections amidst rising antibiotic resistance. A comprehensive narrative literature review was conducted using MEDLINE, PubMed, and Google Scholar, focusing on co-amoxiclav 875 mg/125 mg from 1992 to 2024. Keywords included "Co-amoxiclav 875mg/125mg," "amoxicillin 875mg," "Co-amoxiclav dosing," "pharmacology," "PK," and "safety." Studies on non-safety aspects, those on cost-effectiveness, non-English articles, and those without full-text access were excluded. Clinical efficacy studies demonstrate the effectiveness of co-amoxiclav (875 mg/125 mg) in treating conditions such as cutaneous actinomycosis, actinomycetoma, lower respiratory tract infections, acute bacterial maxillary sinusitis, and community-acquired pneumonia. Comparative studies reveal similar or superior efficacy of co-amoxiclav (875 mg/125 mg) compared to other dosing regimens and antibiotics such as clindamycin, cefaclor, cefuroxime, and ciprofloxacin. Safety and tolerability assessments indicate that co-amoxiclav is generally well-tolerated, with common mild-to-moderate gastrointestinal side effects. In summary, co-amoxiclav 1 gm remains a crucial antibiotic with optimized dosing regimens enhancing clinical outcomes while addressing resistance challenges.

Medical Cannabis Prescription Practices and Quality of Life in Thai Patients: A Nationwide Prospective Observational Cohort Study.

The legalization of cannabis in Thailand has renewed interest in its traditional medical use. This study aimed to explore the prescribing patterns of traditional practitioners and assess the impact of cannabis oil on patients' quality of life, with a specific focus on comparing outcomes between cancer and non-cancer patients. We conducted a prospective observational cohort study across 30 sites in 21 Thai provinces to analyze the use of "Ganja Oil," a cannabis extract in 10% coconut oil, prescribed for symptoms like pain, anorexia, and insomnia across a diverse patient group, including cancer and migraines. Quality of life was assessed using the Edmonton Symptom Assessment Scale (ESAS) and EQ-5D-5L at baseline, 1, 2, and 3 months. The study included a predefined subgroup analysis to compare the effects on cancer versus non-cancer patients. Data management was facilitated through Research Electronic Data Capture (REDCap), with statistical analysis performed using Stata/MP. Among 21,284 participants, the mean age was 54.10 ± 15.32 years, with 52.49% being male. The baseline EQ-5D-5L index was 0.85 ± 0.24. Significant differences in EQ-5D-5L indices were seen between cancer patients (0.79 ± 0.32) and non-cancer patients (0.85 ± 0.23; p < 0.001). ESAS scores also differed significantly between these groups for all symptoms, except anxiety. The most frequent prescription of Ganja Oil was oral administration at bedtime (88.26%), with the predominant dosage being three drops daily, approximately 0.204 mg of tetrahydrocannabinol in total. Posttreatment, significant improvements were noted: the EQ-5D-5L index increased by 0.11 points (95% CI: 0.11, 0.11; p < 0.001) overall, 0.13 points (95% CI: 0.12, 0.14; p < 0.001) for cancer patients, and 0.11 points (95% CI: 0.10, 0.11; p < 0.001) for non-cancer patients. ESAS pain scores improved by -2.66 points (95% CI: -2.71, -2.61; p < 0.001) overall, -2.01 points (95% CI: -2.16, -1.87; p < 0.001) for cancer patients, and -2.75 points (95% CI: -2.80, -2.70; p < 0.001) for non-cancer patients, with similar significant improvements in other symptoms. Our study indicates potential benefits of Ganja Oil for improving quality of life among Thai patients, as a complementary treatment. These findings must be viewed in light of the study's design limitations. Further controlled studies are essential to ascertain its efficacy and inform dosing guidelines.

Antimicrobial management of dental infections: Updated review.

Dental infections, which include anything from severe periodontal illnesses and abscess forms to routine tooth caries, are a major public health risk. This review article focuses on the pathophysiology and treatment of dental infections. A narrative review was conducted based on several published articles, relevant journals, and books in Google Scholar PubMed using the keywords dental caries, periodontal disease, gingivitis, and related diseases; we excluded duplicated information. Our review illustrated the types of dental infections and the proper antimicrobial drug that is suitable for this disease. Drawing from recent research findings and clinical evidence, we explore the spectrum of bacteria commonly associated with dental infections and their susceptibility profiles to various antibiotics. Emphasis is placed on understanding the mechanisms of antibiotic action and resistance in the context of dental pathogens, shedding light on optimal treatment regimens and potential challenges in clinical management. Additionally, we go over the clinical consequences of antibiotic therapy in dentistry, taking into account factors like patient selection, dose guidelines, and side effects. The management of dental infections through antimicrobial strategies has undergone significant advancements, as evidenced by this updated review. Besides the normal methods, emerging technologies such as 3D printing for drug delivery of antibiotics and disinfectants hold promise in enhancing treatment efficacy and patient outcomes. By leveraging the precision and customization afforded by 3D printing, dentistry can tailor antimicrobial interventions to individual patient needs, optimizing therapeutic outcomes while minimizing adverse effects.

Plasma and Tissue Amikacin Concentrations Following Regional Limb Perfusion of Chickens (Gallus gallus domesticus).

Intravenous regional limb perfusion (IVRLP) has been used in the treatment of pododermatitis and distal limb infections, which are significant causes of morbidity in avian species. This intravenous drug administration technique is designed to achieve high drug tissue concentrations while minimizing systemic toxic effects. Amikacin is commonly used for IVRLP in veterinary medicine, but dosing guidelines have not been established for its use in birds. The current study aimed to determine the tissue concentration of amikacin after a single IVRLP administration in healthy, euhydrated leghorn hen chickens (Gallus gallus domesticus). Chickens received a single IVRLP dose of 10 mg/kg amikacin and were euthanatized posttreatment at 1 hour (n = 6), 12 hours (n = 6), and 24 hours (n = 6) to assess tissue and synovial fluid concentrations of amikacin in the injected leg. Mean tissue concentrations were highest 1 hour post-IVRLP (synovial fluid = 153.0 µg/mL, metatarsal pad tissue = 26.05 µg/mL) before declining at the 12- and 24-hour time points. This indicates that administration of amikacin via IVRLP can reach minimum inhibitory concentrations of common bacterial isolates in tissues after a single treatment with 10 mg/kg amikacin. Regional limb perfusion every 24 hours is recommended, although the minimum days of treatment may be case dependent and vary based on response to therapy.

Implementing pharmacogenetic testing to optimize proton-pump inhibitors use among Indian population based on CPIC-CYP2C19-PPI dosing guidelines: The need of the hour.

Proton-pump inhibitors (PPIs) are widely prescribed to decrease stomach acid and treat various acid-related Gastrointestinal tract (GIT) diseases. However, genetic variations, particularly in the CYP2C19 gene, affect PPIs metabolism and efficacy. Variants in CYP2C19 can result in different rates of PPI metabolism, influencing their effectiveness. Personalized medicine strategies, such as genotyping for CYP2C19, have the potential to enhance the effectiveness of PPI therapy and patient safety. This review aims to describe the relevance of CYP2C19 genetic profiling in the indian population, including normal function (e.g. CYP2C19*1, *11, *13, *15, *18, *28, and 38), decreased function (e.g., CYP2C19*9, *10, *16, *19, *25, and 26), loss of function (e.g., CYP2C19*2, *3, *4, *5, *6, *7, *8, *22, *24, *35, *36, and *37), and increased function (e.g., CYP2C19*17) variants. This review also examines the clinical pharmacogenomics implementation consortium (CPIC)-CYP2C19-PPI guidelines to highlight the importance of pharmacogenomics (PGx)-informed personalized PPI therapy for gastroesophageal reflux disease and peptic ulcer disease treatment. On average, each person in India possesses eight pharmacogenetic (PGx) variants that can be clinically significant, underscoring the need for preemptive testing. Implementing CYP2C19 genetic testing in India requires expanding laboratory capacity, increasing accessibility in primary care, increasing public awareness, collaboration between pharmacovigilance and PGx programs, investing in advanced sequencing technologies, data management systems, and integration with electronic health records and clinical decision support systems. Addressing challenges such as genetic diversity, socioeconomic factors, health-care access issues, and shortage of trained professionals is essential for implementation. Due to the lack of definitive country-specific policies and PGx guidelines from Indian drug regulatory agencies, guidelines from international consortia such as the Clinical Pharmacogenetics Implementation Consortium and drug labeling offer crucial foundational evidence. This evidence can be used to enhance patient outcomes and ensure the safe and effective use of PPIs in India.

Impact of Chlorella vulgaris Intake Levels on Performance Parameters and Blood Health Markers in Broiler Chickens.

This systematic review examines the effects of cumulative Chlorella vulgaris intake levels on broiler chickens, focusing on growth performance and systemic health markers. The review establishes a clear relationship between cumulative C. vulgaris intake and significant outcomes in poultry nutrition and health through a detailed analysis of various studies. The correlation analysis revealed that cumulative C. vulgaris intake levels ranging from 0.8 to 718 g/bird influenced growth rates and feed efficiency, following sigmoid models. Specifically, intakes of approximately 20 g/bird maximized final body weight (R2 = 0.616, p < 0.001), cumulative body weight gain (R2 = 0.627, p < 0.001) and daily weight gain (R2 = 0.639, p < 0.001). The feed conversion ratio also improved with increasing C. vulgaris intakes up to this level, although this was non-significant (R2 = 0.289, p = 0.117). In addition, similar cumulative C. vulgaris intake levels impacted plasma health markers in broilers, leading to reductions in triacylglycerols and cholesterol and improvements in immunoglobulin levels. These findings underscore the importance of carefully calibrated C. vulgaris supplementation strategies to optimise poultry growth and health without adverse effects. Future research should focus on refining C. vulgaris dosing guidelines and further exploring its long-term effects and mechanisms of action to enhance poultry health and production sustainability.

Cancer therapy in patients with reduced kidney function.

Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.

THE ASSOCIATION BETWEEN CORTICOSTEROID DOSE AND PAIN REDUCTION FOLLOWING SACROILIAC JOINT INJECTIONS.

Sacroiliac joint (SIJ) mediated back pain has proven therapeutic benefit from fluoroscopically guided SIJ corticosteroid injections. We examined corticosteroid dose and pain relief following fluoroscopically guided SIJ injections to better understand their relationship. Retrospective observational cohort analysis of electronic health record data on 661 patients who received unilateral fluoroscopically guided SIJ intraarticular corticosteroid injection with 40 mg versus 80 mg of methylprednisolone from 2012 and 2019. Patients were injected by fellowship trained proceduralists after diagnosis by board certified physiatrists in an academic physiatry practice. Absolute change in pain scores (post-procedure and first follow up) was modeled using linear regression of methylprednisolone dosage (40 mg vs. 80 mg) controlling for age, sex, BMI, baseline pain scores, and follow-up time. Linear regression indicated that dosage of methylprednisolone, age and BMI were not statistically significantly associated with change in pain scores. Sex approached significance (p = 0.0501) indicating that females may have a lower degree of pain resolution than males. Practitioners should consider corticosteroid dose when performing these beneficial procedures. This could reduce cost and potential side effects associated with larger doses, while still providing therapeutic benefit. This pilot study can guide future research and dosing guidelines for fluoroscopic spine injections.

Drug disposition in cholestasis: An important concern.

Cholestasis, a chronic liver condition, disrupts bile acid homeostasis and complicates drug disposition, posing significant challenges in medicating cholestatic patients. Drug metabolism enzymes and transporters (DMETs) are pivotal in drug clearance. Research indicates that cholestasis leads to alterations in both hepatic and extrahepatic DMETs, with changes in expression and function documented in rodents and humans. This review synthesizes the modifications in key drug disposition components within cholestasis, focusing on cytochrome P450 (CYP450), drug transporters, and their substrates. Additionally, we briefly discuss certain drugs that have demonstrated efficacy in restoring DMET expression in cholestatic conditions. Ultimately, these insights necessitate a reevaluation of drug selection and dosing guidelines for patients with cholestasis.

Whole body physiology model to simulate respiratory depression of fentanyl and associated naloxone reversal

BackgroundOpioid use in the United States and abroad is an endemic part of society with yearly increases in overdose rates and deaths. In response, the use of the safe and effective reversal agent, naloxone, is being fielded and used by emergency medical technicians at a greater rate. There is evidence that repeated dosing of a naloxone nasal spray is becoming more common. Despite this we lack repeated dosing guidelines as a function of the amount of opiate the patient has taken.MethodsTo measure repeat dosing guidelines, we construct a whole-body model of the pharmacokinetics and dynamics of an opiate, fentanyl on respiratory depression. We then construct a model of nasal deposition and administration of naloxone to investigate repeat dosing requirements for large overdose scenarios. We run a single patient through multiple goal directed resuscitation protocols and measure total naloxone administered.ResultsHere we show that naloxone is highly effective at reversing the respiratory symptoms of the patient and recommend dosing requirements as a function of the fentanyl amount administered. We show that for increasing doses of fentanyl, naloxone requirements also increase. The rescue dose displays a nonlinear response to the initial opioid dose. This nonlinear response is largely logistic with three distinct phases: onset, rapid acceleration, and a plateau period for doses above 1.2 mg.ConclusionsThis paper investigates the total naloxone dose needed to properly reverse respiratory depression associated with fentanyl overdose. We show that the current guidelines for a rescue dose may be much lower than required.

An Overview on Pulmonary Insulin

Pulmonary insulin as an alternative to intravascular, intramuscular, and subcutaneous insulin administration, non-invasive insulin administration was created and implemented. It enters the lungs' alveoli through an as-yet-unidentified paracellular process, traverses the alveolar wall, and then circulates throughout the bloodstream. Inhaled insulin was divided into two categories based on its mechanism of action: 1. Rapid acting pulmonary insulin, which quickly disintegrates in the alveoli and circulates throughout the bloodstream as fine powder particles; and 2. slow acting pulmonary insulin. Recently, two technologies were developed: pulmosol powder technology, which employs a rapid drying procedure to make insulin particles of the right size and chemical stability, and AIR technology, which is a porous dry particle aerosol technology. Dry powders, liquid aerosols in cartridge-shaped inhalers, passive inhalers, Microprocessor-controlled inhalers, and liquid nebulizers were the various ways that inhaled insulin was delivered. Many studies have been conducted to examine various intrapulmonary delivery methods, and in January 2006, the US Food and Drug Administration authorized exubera, a dry powder passive inhaler, as the first pulmonary inhaled insulin. The pharmacokinetics of inhaled insulin, dosage guidelines, administration tools, benefits and drawbacks, and candidates for inhaled insulin administration are all discussed in this article.

Mapping the Pharmacogenetic Landscape in a Ugandan Population: Implications for Personalized Medicine in an Underrepresented Population.

Africans are extremely underrepresented in global genomic research. African populations face high burdens of communicable and non-communicable diseases and experience widespread polypharmacy. As population-specific genetic studies are crucial to understanding unique genetic profiles and optimizing treatments to reduce medication-related complications in this diverse population, the present study aims to characterize the pharmacogenomics profile of a rural Ugandan population. We analyzed low-pass whole genome sequencing data from 1998 Ugandans to investigate 18 clinically actionable pharmacogenes in this population. We utilized PyPGx to identify star alleles (haplotype patterns) and compared allele frequencies across populations using the Pharmacogenomics Knowledgebase PharmGKB. Clinical interpretations of the identified alleles were conducted following established dosing guidelines. Over 99% of participants displayed actionable phenotypes across the 18 pharmacogenes, averaging 3.5 actionable genotypes per individual. Several variant alleles known to affect drug metabolism (i.e., CYP3A5*1, CYP2B6*9, CYP3A5*6, CYP2D6*17, CYP2D6*29, and TMPT*3C)-which are generally more prevalent in African individuals-were notably enriched in the Ugandan cohort, beyond reported frequencies in other African peoples. More than half of the cohort exhibited a predicted impaired drug response associated with CFTR, IFNL3, CYP2B6, and CYP2C19, and approximately 31% predicted altered CYP2D6 metabolism. Potentially impaired CYP2C9, SLCO1B1, TPMT, and DPYD metabolic phenotypes were also enriched in Ugandans compared with other African populations. Ugandans exhibit distinct allele profiles that could impact drug efficacy and safety. Our findings have important implications for pharmacogenomics in Uganda, particularly with respect to the treatment of prevalent communicable and non-communicable diseases, and they emphasize the potential of pharmacogenomics-guided therapies to optimize healthcare outcomes and precision medicine in Uganda.

Effectiveness of Photobiomodulation in Reducing Pain and Disability in Patients With Knee Osteoarthritis: A Systematic Review With Meta-Analysis.

Photobiomodulation (PBM) is not implemented in routine clinical management for knee osteoarthritis. This study aims to systematically investigate the effects of PBM in patients with knee osteoarthritis, comparing with placebo to understand its true clinical effects. PubMed, EMBASE, Web of Science, and Cochrane databases were searched up to October 2023. Randomized placebo-controlled trials applying PBM versus placebo were included. Study characteristics, intervention parameters, and patient-reported and physical examination outcome measures were collected. The risk of bias was judged using the Cochrane risk-of-bias tool for randomized trials (version 2) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to interpret the certainty of results. Ten studies were included comprising 542 participants. All studies were judged with unclear to a high risk of bias. Meta-analysis for pain at rest (6 studies) showed that PBM significantly reduced pain at rest as compared to placebo (-0.7 [95% CI = -1.1 to -0.2]), moderate effect, very low certainty of evidence, whereas for the Timed "Up & Go" Test (three studies), no significant effect was detected. Statistically significantly within-group (PBM) mean improvement was detected for pain, Lequesne Index, and gait performance outcomes, but not always clinically relevant or significant when compared to placebo. PBM reduces pain intensity in patients with knee osteoarthritis and may improve disability. However, the very low certainty of evidence does not allow to recommend its isolated use but may be used to complement other widely recommended therapies. More rigorous clinical trials and the revision of the recommended dosage guidelines are warranted to increase the strength of evidence. The findings indicate that photobiomodulation can reduce pain and improve disability in patients with knee osteoarthritis. However, researchers should continue to investigate isolated photobiomodulation intervention versus placebo and extend the dosage guidelines to other types of light emitters.