Evaluation of Pharmacy Intern Interventions on Antimicrobial Use in University-Affiliated Hospitals: A Retrospective Analysis.

Background: Appropriate use of antimicrobials is essential to enhance therapeutic safety and efficacy. Clinical pharmacists play a crucial role in optimizing antimicrobial use; however, the contribution of pharmacy interns in antimicrobial use has not been studied. The objective of this study was to ascertain the quantity and nature of interventions related to antimicrobials documented by pharmacy interns, along with the rates at which physicians accepted these interventions. Methods: From August 2017 to March 2022, this study retrospectively evaluated antimicrobial-related interventions recorded by pharmacy interns during their rotations at King Khalid University. The categories of interventions included medication selection, addition of antimicrobials, dose or frequency adjustments, medication discontinuation, de-escalation, therapeutic drug monitoring, and others. Statistical analysis was conducted to identify patterns and correlations. Results: This study evaluated 1295 antimicrobial-related interventions, with high physician acceptance rates of 91.6% and 4.0% accepted with modifications. The most frequent interventions were dose/frequency adjustments (36.3%) and medication discontinuation (23%). Vancomycin, colistin, and meropenem were the most frequently intervened antimicrobials. Documented clinical outcomes included enhancing treatment efficacy (37.3%), reducing treatment toxicity (26.81%), and avoiding unnecessary antimicrobial exposure (21.8%). Significant correlations were observed between hospital units and intervention types, indicating unit-specific intervention patterns. Conclusions: Theses findings highlight the vital role of pharmacy interns in optimizing antimicrobial therapy. Future research should focus on evaluating the long-term clinical and economic benefits of their involvement.

Smart grading of diabetic retinopathy: an intelligent recommendation-based fine-tuned EfficientNetB0 framework.

Diabetic retinopathy is a condition that affects the retina and causes vision loss due to blood vessel destruction. The retina is the layer of the eye responsible for visual processing and nerve signaling. Diabetic retinopathy causes vision loss, floaters, and sometimes blindness; however, it often shows no warning signals in the early stages. Deep learning-based techniques have emerged as viable options for automated illness classification as large-scale medical imaging datasets have become more widely available. To adapt to medical image analysis tasks, transfer learning makes use of pre-trained models to extract high-level characteristics from natural images. In this research, an intelligent recommendation-based fine-tuned EfficientNetB0 model has been proposed for quick and precise assessment for the diagnosis of diabetic retinopathy from fundus images, which will help ophthalmologists in early diagnosis and detection. The proposed EfficientNetB0 model is compared with three transfer learning-based models, namely, ResNet152, VGG16, and DenseNet169. The experimental work is carried out using publicly available datasets from Kaggle consisting of 3,200 fundus images. Out of all the transfer learning models, the EfficientNetB0 model has outperformed with an accuracy of 0.91, followed by DenseNet169 with an accuracy of 0.90. In comparison to other approaches, the proposed intelligent recommendation-based fine-tuned EfficientNetB0 approach delivers state-of-the-art performance on the accuracy, recall, precision, and F1-score criteria. The system aims to assist ophthalmologists in early detection, potentially alleviating the burden on healthcare units.

Deep learning-based image annotation for leukocyte segmentation and classification of blood cell morphology.

The research focuses on the segmentation and classification of leukocytes, a crucial task in medical image analysis for diagnosing various diseases. The leukocyte dataset comprises four classes of images such as monocytes, lymphocytes, eosinophils, and neutrophils. Leukocyte segmentation is achieved through image processing techniques, including background subtraction, noise removal, and contouring. To get isolated leukocytes, background mask creation, Erythrocytes mask creation, and Leukocytes mask creation are performed on the blood cell images. Isolated leukocytes are then subjected to data augmentation including brightness and contrast adjustment, flipping, and random shearing, to improve the generalizability of the CNN model. A deep Convolutional Neural Network (CNN) model is employed on augmented dataset for effective feature extraction and classification. The deep CNN model consists of four convolutional blocks having eleven convolutional layers, eight batch normalization layers, eight Rectified Linear Unit (ReLU) layers, and four dropout layers to capture increasingly complex patterns. For this research, a publicly available dataset from Kaggle consisting of a total of 12,444 images of four types of leukocytes was used to conduct the experiments. Results showcase the robustness of the proposed framework, achieving impressive performance metrics with an accuracy of 97.98% and precision of 97.97%. These outcomes affirm the efficacy of the devised segmentation and classification approach in accurately identifying and categorizing leukocytes. The combination of advanced CNN architecture and meticulous pre-processing steps establishes a foundation for future developments in the field of medical image analysis.

Factors associated with applicant performance on the Saudi Pharmacist Licensure Examination (SPLE).

Background: Limited data are available on factors that are associated with passing rates for the Saudi Pharmacist Licensure Examination (SPLE). The aim of this study is to investigate student characteristics and academic performance characteristics that may predict their success on SPLE. Methods: This was a single-institution retrospective cohort study, which included pharmacy graduates from 2019 to 2021. Demographic, academic, and SPLE data were collected for each graduate. Binary logistic regression was used to explore the association between potential predictors and first-time SPLE pass status. A stepwise regression was then performed to develop multiple logistic models. Results: A total of 494 graduates were included in the study. Females, PharmD graduates, and on-time graduation had higher odds of passing SPLE (P = 0.0065, P = 0.0003, and P < 0.0001, respectively). For each 0.5 increase in GPA, the odds of passing SPLE increase by 3.5 times (OR 3.53; 95 % CI, 2.83-4.42; P < 0.0001). Of the tests taken prior to university admission, the overall high school score, general aptitude test (GAT) score, and qualifying score were significantly associated with higher SPLE first-time pass rates. When multiple logistic regression analysis was performed, GPA and GAT scores were the only significant predictors for higher SPLE first-time pass rates (P < 0.0001 and P = 0.0002, respectively). Conclusion: The current research has shown that there is an association between higher SPLE first-time pass rates and several factors, most importantly the GPA and GAT score. Further research is needed, as it has the potential to inform the decision when reviewing pharmacy admission criteria.

Short-Term and Long-Term Impact of COVID-19 on Quality of Life and Psychological Outcomes in Saudi Arabia: A Comparative Cross-Sectional Study.

Background: Prior research has revealed notable declines in health-related quality of life (HRQoL) and substantial psychological impacts among individuals infected with COVID-19. However, there is a noticeable gap in studies addressing the enduring long-term effects of COVID-19 on HRQoL and psychological well-being. Objective: The current study investigated and compared short and long-term effects of COVID-19 on HRQoL and psychological outcomes among the Saudi population. Methods: The Arabic version of the SF-36 questionnaire was used to assess HRQoL while Anxiety and depression were evaluated by the Hamilton Anxiety (HAM-A) and Depression Scales (HDRS). Participants (n=292) were categorized into three groups: the "never-been-infected" group (n=134), the "one-year infected group" (n=43), and the "more than one year infected" group (n=115). Descriptive statistics were presented using numerical values and frequencies. To compare the groups, a one-way analysis of variance (ANOVA) test was used. Results: Most SF-36 domains exhibited lower values while HAM-A and HDRS values were higher in individuals infected during last year compared to those who never infected. Social functioning subscale of the SF-36 showed a significant difference between the groups (F (2.289) = 6.094, p = 0.01) and the effect size was d = 0.95. Pairwise comparison showed a significant reduction in the social functioning component of SF-36 in "one-year group" compared to both groups "never-been-infected" group (mean difference -13.58 (4.40-22.76) p < 0.01) and "more than one year infected" group (mean difference -10.80 (1.44-20.16) p = 0.02). HAM-A and HDRS scores showed mild levels of anxiety (<17 score) and depression (8 to 16 score) in all groups. Conclusion: The influence of COVID-19 on psychological well-being and HRQoL is significant regardless of whether individuals infected with the virus. Overall, the consistent presence of mild anxiety and depression across all groups highlights the need for a holistic approach to mental health.

The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation.

BACKGROUND: Implementation of newer anti-tuberculosis (TB) drugs may prolong the QT interval, increasing the risk of arrythmias and sudden cardiac death. The potential for cardiac adverse events has prompted recommendations for frequent cardiac monitoring during treatment. However, unknowns remain, including the association between drug concentrations and QT interval. METHODS: An observational prospective cohort study design was used. Patients undergoing treatment for drug-resistant TB in Georgia were assessed. Serial blood samples were collected at 4-6 weeks for pharmacokinetics. Electrocardiograms were recommended to be performed monthly. A generalized estimating equation spline model was used to investigate (1) the effect difference between bedaquiline and delamanid, (2) the cumulative effect of number of anti-TB drugs, and (3) the relationship between serum drug concentrations on QTc interval. RESULTS: Among 94 patients receiving either bedaquiline (n = 64) or delamanid (n = 30)-based treatment, most were male (82%), and the mean age was 39 years. The mean maximum QTc increase during the first six months was 37.5 ms (IQR: 17.8-56.8). Bedaquiline- and delamanid-based regimens displayed similar increased mean QTc change from baseline during drug administration (P = 0.12). Increasing number of anti-TB drugs was associated with an increased QTc (P = 0.01), but participants trended back towards baseline after drug discontinuation (P = 0.25). A significant association between AUC, Cmin, Cmax, and increased QTc interval was found for bedaquiline (months 1-6) and levofloxacin (months 1-12). CONCLUSION: Bedaquiline- and delamanid-based regimens and increasing number of QT prolonging agents led to modest increases in the QTc interval with minimal clinical effect.

Self-reported depression and anxiety rates among females with cutaneous leishmaniasis in Hubuna, Saudi Arabia.

Background: Cutaneous leishmaniasis (CL) is a parasitic disease transmitted through the bite of infected sandflies, causing disfiguring skin lesions and a range of physical symptoms. However, the psychological impact of CL is often overlooked despite the significant burden it imposes on the affected individuals and communities. This is especially true in Saudi Arabia, where limited research exists on the psychological consequences of CL, particularly among females. This study aimed to address this knowledge gap by investigating the perceived psychological problems associated with CL among females living in the Hubuna area of Saudi Arabia. Methods: This cross-sectional study recruited 213 females with CL in the Hubuna area of Saudi Arabia using purposive sampling. Data was collected using a self-administered electronic questionnaire that included socio-demographic characteristics and measures of depression and anxiety using the BDI and GAD-7 tools. Descriptive analysis was used to determine the psychological impact of CL, including means and standard deviations for the BDI and GAD-7 scores, as well as frequencies and percentages for other variables of interest. Logistic regression was performed to identify independent predictors of anxiety and depression, including variables such as age, marital status, education, occupation, number and location of lesions. The significance level for all statistical tests was set at p < 0.05. The study was carried out between September and December of 2022. Results: The study found that the mean Beck Depression Inventory (BDI) and Generalized Anxiety Disorder-7 (GAD-7) scores among the participants were 8.67 ± 4.82 out of 63 and 8.20 ± 7.08 out of 21, respectively. Furthermore, the prevalence of depression and anxiety was 55.9% and 68.1%, respectively, indicating a significant psychological burden associated with CL in the study population. The results of the logistic regression analysis showed that anxiety and depression were significantly associated with age, marital status, number of lesions, and location of the lesions on the body, highlighting the importance of considering these factors when designing interventions aimed at improving the mental health of CL patients. Conclusions: In conclusion, this study highlights the significant psychological impact of CL among females in the Hubuna area of Saudi Arabia, calling for urgent action to address this neglected aspect of the disease. By integrating mental health considerations into CL prevention and management efforts, healthcare providers can improve the overall well-being of affected individuals and contribute to the broader goal of eliminating CL as a public health concern.

Individuals with knee osteoarthritis demonstrate increased passive stiffness of the hip flexor muscles.

BACKGROUND: People with knee osteoarthritis stand and walk with increased trunk flexion. This altered postural alignment increases hamstring activation, elevating mechanical knee loads during walking. Increased hip flexor stiffness may lead to increased trunk flexion. Therefore, this study compared hip flexor stiffness between healthy individuals and individuals with knee osteoarthritis. This study also sought to understand the biomechanical effect of a simple instruction to reduce trunk flexion by 5° during walking. METHODS: Twenty individuals with confirmed knee osteoarthritis and 20 healthy individuals participated. The Thomas test was used to quantity passive stiffness of the hip flexor muscles and three-dimensional motion analysis used to quantify trunk flexion during normal walking. Using a controlled biofeedback protocol, each participant was then instructed to decrease trunk flexion by 5°. RESULTS: Passive stiffness was greater in the group with knee osteoarthritis (effect size = 1.04). For both groups, there was relatively strong correlation between passive stiffness and trunk flexion in walking (r = 0.61-0.72). The instruction to decrease trunk flexion produced only small, non-significant, reductions in hamstring activation during early stance. CONCLUSIONS: This is the first study to demonstrate that individuals with knee osteoarthritis exhibit increased passive stiffness of the hip muscles. This increased stiffness appears to be linked to increased trunk flexion and may therefore underlie the increased hamstring activation which is associated with this disease. As simple postural instruction does not appear to reduce hamstring activity, interventions may be required which can improve postural alignment by reducing passive stiffness of the hip muscles.

A smart IoMT based architecture for E-healthcare patient monitoring system using artificial intelligence algorithms.

Generally, cloud computing is integrated with wireless sensor network to enable the monitoring systems and it improves the quality of service. The sensed patient data are monitored with biosensors without considering the patient datatype and this minimizes the work of hospitals and physicians. Wearable sensor devices and the Internet of Medical Things (IoMT) have changed the health service, resulting in faster monitoring, prediction, diagnosis, and treatment. Nevertheless, there have been difficulties that need to be resolved by the use of AI methods. The primary goal of this study is to introduce an AI-powered, IoMT telemedicine infrastructure for E-healthcare. In this paper, initially the data collection from the patient body is made using the sensed devices and the information are transmitted through the gateway/Wi-Fi and is stored in IoMT cloud repository. The stored information is then acquired, preprocessed to refine the collected data. The features from preprocessed data are extracted by means of high dimensional Linear Discriminant analysis (LDA) and the best optimal features are selected using reconfigured multi-objective cuckoo search algorithm (CSA). The prediction of abnormal/normal data is made by using Hybrid ResNet 18 and GoogleNet classifier (HRGC). The decision is then made whether to send alert to hospitals/healthcare personnel or not. If the expected results are satisfactory, the participant information is saved in the internet for later use. At last, the performance analysis is carried so as to validate the efficiency of proposed mechanism.

Comparison of Saudi Pharmacist Licensure Examination (SPLE) Pass Rates by Institution and Applicant Characteristics.

In 2019, the Saudi Pharmacist Licensure Examination (SPLE) was first administered to all pharmacy graduates and served as one of the prerequisites for obtaining a pharmacist license. The objective of this study was to evaluate whether institution and applicant characteristics are associated with first-time SPLE success. Passing status for 2284 SPLE first-time applicants was obtained from online public data for the years 2019 and 2020. The data included applicant sex, institution type (public vs. private), and college establishment year (2006 or earlier vs. after 2006). Overall, the SPLE first-time pass rate in 2020 was significantly higher than in 2019 (98.0 vs. 95.9%; p = 0.0062). Applicants from pharmacy colleges established in or before 2006 had a higher SPLE first-time pass rate, compared to those from pharmacy colleges established after 2006 (98.2 vs. 95.2%; p < 0.0001). The pass rate for male applicants was lower compared to female applicants (95.8 vs. 97.5%; p = 0.0221). The results of logistic regression showed that exam year (2020 vs. 2019), applicant sex (female vs. male), and pharmacy college establishment year (≤2006 vs. >2006) were statistically significant predictors. Further studies are needed in the upcoming years when more cumulative data are available.

Linezolid Exposure Is Associated with Cytopenias in Patients Treated for Multidrug-Resistant Tuberculosis.

Although linezolid is effective for multidrug-resistant TB (MDR-TB) tuberculosis treatment, it is associated with cytopenias after 4 weeks of administration. Data on toxicities with long-term use of linezolid and drug pharmacodynamics in MDR-TB treatment are limited, and concerns about toxicity present barriers to wider implementation. This was a secondary analysis of a prospective cohort study of patients treated for MDR-TB in the country of Georgia from 2015 to 2017. Intensive blood sampling 4 to 6 weeks after treatment initiation with linezolid 600 mg daily was performed for pharmacokinetic (PK) analysis, including linezolid trough concentration (Cmin) and area under the curve from 0 to 24 hours (AUC0-24). Linezolid exposure was defined using literature-reported thresholds. Cytopenias were defined using an NIH adverse event (AE) scale. Logistic regression was used to evaluate the relationship between linezolid exposure and cytopenias. Among 76 patients receiving linezolid in their baseline treatment regimen and who had PK data available, cytopenia AEs occurred in 30 (39.5%) for an incidence rate of 46 per 100 person-years. The median duration of linezolid therapy was 526 days. No patients required dose reduction or interruption due to cytopenias. Median linezolid Cmin was 0.235 mg/L (interquartile range [IQR], 0.069 to 0.529), and median AUC0-24 was 89.6 mg·h/L (IQR, 69.2 to 116.2). Cytopenias were associated with linezolid PK parameters (Cmin > 2 mg/L and AUC0-24 > 160 mg·h/L). Cytopenias occurred frequently with long-term use of linezolid 600 mg/day and were associated with PK parameters but did not result in the need for treatment interruption in the management of a cohort of patients with MDR-TB.

Increased trunk flexion may underlie elevated knee flexor activity in people with knee osteoarthritis.

BACKGROUND: Previous research has demonstrated elevated activation of the knee flexor muscles in people with knee osteoarthritis. People with this condition have also been observed to walk with increased trunk flexion; this may alter biomechanical loading patterns and change muscle activation profiles. Therefore, the aim of this study was to understand the biomechanical effect of increasing trunk flexion during walking. METHODS: Kinetic and EMG data were collected from a sample of 20 people with knee osteoarthritis and a sample of 20 healthy matched controls during normal walking. Using a biofeedback protocol, participants were subsequently instructed to walk with a 5° increase in trunk flexion. Sagittal moments, muscle activations and co-contractions were then compared across a window in early stance with a two-way ANOVA test. RESULTS: When trunk flexion was increased, there was a corresponding increase in activity of the medial and lateral hamstrings and gastrocnemius muscles as well as a rise in medial co-contraction. This effect was consistent across the two groups. The most pronounced effect was observed for semitendinosus, which showed a dramatic change in activation profile in the healthy group and a 127% increase in activation during early stance. CONCLUSIONS: This is the first study to demonstrate that increased trunk flexion in people with knee osteoarthritis may explain, to some degree, the elevated knee flexor activity and medial co-contraction which is associated with this disease. These findings motivate further work to understand the therapeutic potential of interventions designed to improve postural alignment.

Prevalence and Factors Associated with Musculoskeletal Disorders among Secondary Schoolteachers in Hail, Saudi Arabia: A Cross-Sectional Survey.

Musculoskeletal disorders (MSDs) are one of the most common occupational health hazards and serious health concerns among teachers. About 39% to 95% of teachers suffer from musculoskeletal pain that can lead to a decline in their performance, frequent sick leaves and early retirement, and can have a negative impact on their quality of life. The aim of this study was to investigate the prevalence of and risk factors for MSDs among secondary schoolteachers in Hail, Saudi Arabia. A cross-sectional study was conducted through an electronic survey. A self-reported and validated Arabic version of the Nordic Musculoskeletal Questionnaire (NMQ) was used. Participants were recruited randomly through a two-stage sampling technique. A total of 251 respondents (57.8% males and 42.2% females) returned the questionnaire. The overall prevalence of MSDs was 87.3%. Female teachers (95.3%) suffered more than their male counterparts (81.4%). The most common site was the lower back (62.55%), followed by the shoulders (53.39%) and knees (41.04%). Most of the participants (72.7%) reported MSDs in multiple sites. Binomial logistic regression predicted that smoking is a significant risk factor for lower back disorders (p < 0.05). A high prevalence of MSDs can be due to a substantial lack of awareness and practice of ergonomics, which warrant the development of preventive strategies and educational programs.

Is Hip Muscle Strength Associated with Dynamic Knee Valgus in a Healthy Adult Population? A Systematic Review.

This study aimed to systematically review research investigating the association between hip muscle strength and dynamic knee valgus (DKV). Four databases (MEDLINE, PubMed, CINAHL, and SPORTDiscus) were searched for journal articles published from inception to October 2020. Seven studies investigating the association between hip muscle strength and DKV using a two-dimensional motion analysis system in healthy adults were included. The relationship between hip abductor muscle strength and DKV was negatively correlated in two studies, positively correlated in two studies, and not correlated in three studies. The DKV was associated with reduced hip extensor muscle strength in two studies and reduced hip external rotator muscle strength in two studies, while no correlation was found in three and five studies for each muscle group, respectively. The relationship between hip muscle strength, including abductors, extensors, and external rotators and DKV is conflicting. Considering the current literature limitations and variable methodological approaches used among studies, the clinical relevance of such findings should be interpreted cautiously. Therefore, future studies are recommended to measure the eccentric strength of hip muscles, resembling muscular movement during landing. Furthermore, high-demand and sufficiently challenging functional tasks revealing lower limb kinematic differences, such as cutting and jumping tasks, are recommended for measuring the DKV.

Trend of recognizing depression symptoms and antidepressants use in newly diagnosed Parkinson's disease: Population-based study.

OBJECTIVES: Although depression symptoms are common among patients with Parkinson's disease (PD), the medical literature still reports underrecognition of depression in patients with PD. Our main objective is to examine the trend of depression recognition during the first year of PD diagnosis using large population data. METHODS: We conducted a population-based study of residents in Wales, using the Secure Anonymized Information Linkage (SAIL) Databank. We included newly diagnosed patients with PD aged 40 years or older with a first PD diagnosis between 2000 and 2015. Depression and antidepressants related data were extracted from SAIL. A series of multilevel logistic regressions were run to determine the factors affecting depression recognition. The results were presented using odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: The study included 6596 patients with PD. About 38% of patients had a recorded code of antidepressants, depression diagnosis, or both within the first year of PD diagnosis. There was a significant association of depression diagnosis, antidepressant use, or both with the year of PD diagnosis (OR 0.972, 95% CI 0.962-0.983). We also found that patients who used monoamine oxidase inhibitors (MAO-B inhibitors) were associated with a lower depression diagnosis, use antidepressants, or both, compared to those who did not use MAO-B inhibitors (OR 0.769, 95% CI 0.627-0.943). CONCLUSION: There is a slight decrease in depression recognition in PD patients between 2000 and 2015, which could be due to an increase in depression recognition during the prodromal phase of PD.

Pharmacogenetic predictors of nevirapine pharmacokinetics in Ghanaian children living with HIV with or without TB coinfection.

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of human immunodeficiency virus (HIV) infection in children younger than 3 years old. Identifying genetic predictors of NVP pharmacokinetics (PK) in young children is important because inter-individual variability in NVP concentrations contributes to variable treatment response and the information may be used to individualize dosing decisions. We examined the relationship between genetic variations in relevant drug disposition genes and NVP PK parameters in Ghanaian children living with HIV eligible to initiate NVP-based antiretroviral therapy. Participants received NVP plus zidovudine and lamivudine or abacavir and lamivudine twice daily, and those with tuberculosis (TB) coinfection received concurrent anti-TB therapy with NVP. Pharmacokinetic sampling was performed after at least 4 weeks of antiretroviral therapy. Nevirapine minimum concentration (Cmin), area under the concentration-time curve from time 0 to 12 h (AUC0-12h), and apparent clearance (CL/F) were calculated using non-compartmental analysis using Phoenix v8.0 software. Genotyping for CYP2B6, CYP2A6, CYP3A5, ABCB1, NR1I2, and NR1I3 single nucleotide polymorphism (SNPs) was performed by TaqMan® allelic discrimination method. The median (range) NVP dose received was 10 (7-14) mg/kg. Of the 53 participants, the median (range) Cmin was 3.3 (0.0-14.0) mg/L and AUC0-12h was 56.0 (16.7-202.6) mg.hr/L. Using step-wise regression, CYP2B6 rs3745274 and NR1I2 rs6785049 SNPs were independent as well as joint predictors of NVP AUC0-12h, Cmin, and CL/F. We concluded that genotyping for CYP2B6 rs3745274, and the NR1I2 rs6785049 G > A SNP (which encodes the transcriptional factor, pregnane X receptor), could improve prediction of NVP PK for individualized therapy.

The effect of increasing trunk flexion during normal walking.

BACKGROUND: The head, arms and trunk segment constitute a large proportion of the body's mass. Therefore, small alterations in trunk inclination may affect lower limb joint moments and muscle activation patterns. Although previous research has investigated the effect of changing frontal plane inclination of the trunk, it is not clear how increasing trunk flexion will impact on the activation of the lower limb muscles. RESEARCH QUESTION: What is the effect of independently manipulating trunk flexion angle on lower limb kinematics, moments and muscle function? METHODS: Gait analysis was carried out on 20 healthy people under four trunk flexion conditions: normal walking (NW), NW-5°, NW+5° and NW+10°. For the latter three conditions, a biofeedback approach was used to tightly control trunk flexion angle. A linear mixed model was used to investigate the effect of changing trunk flexion on joint angles, moments, and knee muscle activation. RESULTS: There were clear increases in hip and ankle moments as trunk flexion was increased, but no change in knee moments. The results also showed a linear increase in knee flexor muscle activity and a corresponding increase in co-contraction as trunk flexion increased. Interestingly, there was a dramatic change in the profile of hamstring activity. In the medial hamstrings, this change led to a 100% increase in activation during early stance as flexion was increased by 5° from NW. SIGNIFICANCE: This is the first study to demonstrate a strong dependence of knee flexor muscle activity on trunk flexion. This is important as people with knee osteoarthritis have been observed to walk with elevated muscle activation and this has been linked to increased joint loads. It is possible that these altered muscle patterns may result from increased trunk flexion during walking.

Pharmacokinetics of bedaquiline, delamanid and clofazimine in patients with multidrug-resistant tuberculosis.

BACKGROUND: Pharmacokinetic data are needed for newly implemented anti-tuberculosis drugs to help optimize their use. OBJECTIVES: To help fill existing knowledge gaps, we evaluated the pharmacokinetic parameters of novel and repurposed anti-tuberculosis drugs among patients with drug-resistant pulmonary tuberculosis. METHODS: A prospective cohort study among patients ≥16 years with confirmed pulmonary drug-resistant TB was conducted in Tbilisi, Georgia. Patients receiving bedaquiline, delamanid and/or clofazimine were included. Blood samples were collected 4-6 weeks after drug initiation, and serum concentrations were measured using validated liquid chromatography tandem mass spectrometry assays. A non-compartmental analysis was performed, and the association of exposure parameters with covariates was explored. RESULTS: Among 99 patients, the average age and weight were 40 years and 65 kg, respectively. The median Cmin was 0.68 mg/L for bedaquiline, 0.17 mg/L for delamanid, and 0.52 mg/L for clofazimine. The median AUC0-24 was 30.6 mg·h/L for bedaquiline, 16.1 mg·h/L for clofazimine, and the AUC0-12 was 2.9 mg·h/L for delamanid. Among the significant covariates associated with drug exposure parameters were weight and sex for bedaquiline, alcohol use for delamanid, and weight for clofazimine. CONCLUSIONS: We found a strong association of weight with bedaquiline and clofazimine exposure parameters, suggesting the need for weight-based dosing for those agents.

Clinical pharmacology applications in clinical drug development and clinical care: A focus on Saudi Arabia.

Drug development, from preclinical to clinical studies, is a lengthy and complex process. There is an increased interest in the Kingdom of Saudi Arabia (KSA) to promote innovation, research and local content including clinical trials (Phase I-IV). Currently, there are over 650 registered clinical trials in Saudi Arabia, and this number is expected to increase. An important part of drug development and clinical trials is to assure the safe and effective use of drugs. Clinical pharmacology plays a vital role in informed decision making during the drug development stage as it focuses on the effects of drugs in humans. Disciplines such as pharmacokinetics, pharmacodynamics and pharmacogenomics are components of clinical pharmacology. It is a growing discipline with a range of applications in all phases of drug development, including selecting optimal doses for Phase I, II and III studies, evaluating bioequivalence and biosimilar studies and designing clinical studies. Incorporating clinical pharmacology in research as well as in the requirements of regulatory agencies will improve the drug development process and accelerate the pipeline. Clinical pharmacology is also applied in direct patient care with the goal of personalizing treatment. Tools such as therapeutic drug monitoring, pharmacogenomics and model informed precision dosing are used to optimize dosing for patients at an individual level. In KSA, the science of clinical pharmacology is underutilized and we believe it is important to raise awareness and educate the scientific community and healthcare professionals in terms of its applications and potential. In this review paper, we provide an overview on the use and applications of clinical pharmacology in both drug development and clinical care.