Dose Of Medication Research Articles

Personalized dosimetry assessment of [177Lu]Lu-PSMA-617 radioligand therapy in the management of metastatic castration-resistant prostate cancer

Introduction Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is revolutionizing the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) patients. This study aimed to establish patient-specific radiation dosimetry for [177Lu]Lu-PSMA-617 RLT in Iranian patients with mCRPC. Method Twelve biopsy-proven prostate cancer patients (aged 68.73 ± 5.26 yr) underwent 6.62 ± 0.36 GBq [177Lu]Lu-PSMA-617 RLT. Post-therapy whole-body planar scans were acquired approximately at 4, 48, and 72 h post-administration, alongside a single SPECT/CT around 48 h using Siemens Symbia T2 to obtain cumulated activity. An imaging protocol and dosimetry approach were designed to balance between time efficacy and accuracy in post-therapeutic dosimetry. Using accurate activity calibration, S-values were calculated by importing SPECT/CT images as the source/geometry into the Geant4 application for the tomographic emission (GATE) Monte Carlo (MC) toolkit. The Medical Internal Radiation Dose (MIRD) scheme was followed for subsequent absorbed dose (AD) calculations in organs at risk (OAR) and tumoral lesions using the dose actor and accumulated activities for precise dose estimations. Results Using the MC approach, the mean ADs to the liver, spleen, right and left kidneys, and tumor lesions were 0.11 ± 0.04 Gy/GBq, 0.08 ± 0.03 Gy/GBq, 0.34 ± 0.09 Gy/GBq, 0.34 ± 0.10 Gy/GBq, and 0.83 ± 0.54 Gy/GBq, respectively. Notably, tumoral lesions demonstrated significantly higher ADs, indicating enhanced uptake of radiopharmaceuticals by malignant cells. Conclusions This study indicates that the ADs of OARs and tumoral lesions from [177Lu]Lu-PSMA-617 RLT in patients with mCRPC are consistent with existing literature. The dosimetry findings suggest that increasing the administered activity of [177Lu]Lu-PSMA-617 RLT is feasible and does not pose a significant risk of adverse effects on OARs, as supported by our data. However, to validate the safety and efficacy of higher doses, further clinical follow-up studies are recommended.

Efficacy and safety of SKCPT in patients with knee osteoarthritis: A multicenter, randomized, double-blinded, active-controlled phase III clinical trial

Ethnopharmacological relevanceOsteoarthritis (OA) is the most prevalent type of arthritis worldwide and a leading cause of years lost to pain and disability. Among the current pharmacological treatments for OA, symptomatic slow-acting drugs for OA (SYSADOA) induce pain relief and aim to improve joint function by relieving inflammation while causing fewer gastrointestinal and cardiovascular adverse events than non-steroidal anti-inflammatory drugs (NSAIDs). SKCPT is a herbal SYSADOA formulated from Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris powdered extracts. This preparation has been shown to induce cartilage protection and anti-inflammatory effects in preclinical studies and inhibit glycosaminoglycan degradation and catabolic gene expression in human OA chondrocytes and cartilage. Aim of the studyWe aimed to evaluate the non-inferiority of SKCPT to celecoxib and safety for treating knee OA. Materials and methodsThis multicenter, randomized, double-blind, phase III clinical trial enrolled adults with primary knee OA who were randomized (1:1) to SKCPT 300 mg twice daily or celecoxib 200 mg once daily for 12 weeks. ResultsIn total, 278 patients were assigned to treatment (SKCPT, 136; celecoxib, 142) for approximately 12 weeks. The primary endpoint was the mean change of Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) pain subscale scores from baseline to Day 84. The mean change (least squares [LS] mean ± standard error) from baseline to Day 84 was −23.74 ± 1.48 for SKCPT and −25.88 ± 1.44 for celecoxib. The two-sided 95% confidence interval of the difference (LS mean) between groups was [−1.94, 6.20], confirming that the upper limit was less than the non-inferiority margin of 10. Additionally, there were no significant differences in the secondary endpoints (mean changes of K-WOMAC pain, physical, stiffness subscale, and total score, and the frequency and number of doses of rescue medications) between groups at all time points. Differences between groups in adverse events and adverse drug reactions were not significant, and no serious adverse events occurred. ConclusionsSKCPT efficacy was non-inferior, and its safety profile was similar, to celecoxib. Building on previous results showing that SYSADOA reduce NSAID intake, the present results suggest that the SYSADOA SKCPT could effectively replace NSAIDs in knee OA treatment while avoiding long-term side effects.

Ethambutol induced optic neuropathy: A remerging ocular emergency needing strict vigilance and screening

: To investigate the clinical manifestations and incidence of ethambutol induced optic neuropathy (EON) and identify its risk factors.: A cross sectional, hospital based observational study was conducted in 100 patients, who were on anti-tubercular drugs (ATT) and complained of diminution of vision. The following data was collected in every patient regarding age, gender, co-morbid conditions, clinical manifestation of (tuberculosis)TB, duration and dose of ethambutol. Complete ophthalmic examination was conducted in every patient including best corrected visual acuity (BCVA), color vision, relative afferent pupillary defect (RAPD), fundus examination, visual field analysis and OCT RNFL & GCL. Statistical analysis of the data was done and represented suitably using appropriate statistical tests that included Chi Square test for checking associations and T test for comparing quantitative data with the help of SPSS ver. 26.0 software. All p-values reported were two sided and a value less than 0.05 was considered significant. :Out of 100 patients, only 18 patients were diagnosed with EON and calculated incidence was 1.8%. The most common presenting feature of EON was bilateral diminution of vision (89%) followed by abnormal color vision (11%). On examination, RAPD was seen in 40% cases because of asymmetrical optic nerve involvement and disc abnormality was present in 66% cases. The duration and dose of ethambutol medication, advanced age (>65 years), hypertension, chronic smoking and presence of renal dysfunction were shown to be positively correlated with EON development.:At present, there is no effective treatment for EON except supplementation of zinc, copper, methylcobalamine and pyridoxine. Therefore, early detection and discontinuation of ethambutol is only way to prevent permanent loss of vision, as in early stage it is reversible.

Guiding Diffusion of Magnetic Nanoparticles from Nose to the Brain Using Permanent Magnet is Theoretically Feasible but Practically Challenging

The blood-brain barrier (BBB) presents a significant challenge in delivering medications to the brain, impeding direct targeting of specific brain regions in humans. Currently, effective methods for overcoming this protective barrier are limited. Targeted drug delivery to the brain from the nose has been utilized successfully, albeit the delivered dose of medication directly to the brain predominantly depends on circulation. One promising strategy involves guiding magnetic nanoparticles through the cribriform plate from the nose to the brain. Unlike other areas, the nose and circumventricular organs provide a less restrictive pathway where the BBB is permeable. The concept of guiding the diffusion of magnetic nanoparticles through the cribriform plate appears feasible in theory. However, the complexity of such a delivery system necessitates a heuristic approach for practical implementation. In our recent study, we attempted to guide the diffusion of fluorescent magnetic nanoparticles using neodymium magnets in different media and animal brain tissues. Although, we did not successfully demonstrate this method of delivery with simplistic approach, we argue that an interprofessional effort is essential to tackle this mode of drug delivery by passing the challenges posed by the BBB and to innovate targeted drug delivery solutions for the brain. By leveraging diverse perspectives and specialized knowledge, we can advance towards more effective therapies that harness the potential of magnetic nanoparticle technology for neurological treatments. Keywords: magnetic nanoparticles, targeted drug delivery, nasal drug delivery, bypass blood brain barrier, olfactory epithelium

Factors Contributing to Lack of Adherence to Antihypertensive Medications Among Patients at Nishtar Hospital in Multan, Pakistan.

Hypertension affects 26.7% of Pakistan's population, with only 6% achieving control. This study investigates antihypertensive medication adherence in Multan, focusing on socioeconomic and patient-related factors influencing non-adherence to study the lack of adherence to antihypertensive medications in hypertensive patients and its associated factors at Nishtar Hospital in Multan, Pakistan. This cross-sectional study was conducted among hypertensive patients admitted at Nishtar Hospital Multan, Pakistan. Patients under the age of 20 years were excluded from the study. A self-developed questionnaire was used to gather the demographic details of patients. The Hill-Bone Medication Adherence Scale was used via a non-probability convenience sampling technique to deduce the adherence level in patients. Data analysis was done using SPSS (Statistical Package for the Social Sciences) v23 (IBM Corp., Armonk, NY). p-value < 0.05 was considered significant. Out of 217 respondents, most were female, married, unemployed, and residing in urban areas. Most of them had a higher level of education and a monthly income averaging below 30,000 PKR (Pakistani Rupee). The insight into the hypertensive history showed that most of them had a positive family historyand comorbid conditions, and were hypertensive for more than five years. The majority of the patients had a complex regimen prescribed to them with multiple doses throughout the day. The minority were smokers and had medications provided to them for free, through public or government-funded institutions. More importantly, adherence to the antihypertensive therapy was negatively correlated with the age of the patients (p = 0.004, r = -0.195), complexity of regimen (p = 0.041), multiple dosing (p = 0.039), and cost of medication (p = 0.043). All of these relations were statistically significant. Lack of adherence to antihypertensive medications in hypertensive patients is more common inpopulations belonging to older age groups, complex regimens, multiple doses, and higher medicine fees.

Evaluation of a novel pediatric asthma inhalation drug delivery device: a focus on patient accessibility, ease of use, dosage feedback, and future directions

Objective Pediatric asthma management faces challenges in medication delivery through oral inhalation devices. While dry powder inhalers (DPIs) are increasingly prescribed to children, many do not receive their prescribed dosage due to insufficient inspiratory flow. This study investigates the utilization of metered-dose inhalers (MDIs) and DPIs among pediatric patients with asthma, focusing on medication delivery challenges. Methods Two survey cohorts comprising a total of 42 caregivers of patients with asthma were conducted. Modifications in the second cohort addressed neutral Likert scale responses to obtain more nuanced feedback. Results Caregivers expressed concerns about uncertainties in their child’s ability to use both MDIs and DPIs and challenges in ensuring proper dosage. Notably, 42% of caregivers in the second cohort rated their child’s inhaler usage as unable, indicating a significant worry about the efficacy of current delivery methods. Additionally, 50% of caregivers across both cohorts expressed uncertainties about their child receiving the full medication dosage. In response to identified challenges with DPIs, an adaptor device emerged as a potential solution, with caregivers exhibiting positive perceptions post-exposure. Features prioritized for the device include ease of use and assurance of dose delivery. Conclusions The study highlights caregiver preferences and the need for innovations to ensure effective medication delivery for pediatric asthma patients. A DPI adaptor device shows promise in addressing technical issues and alleviating caregiver concerns, ultimately contributing to more effective asthma management. Future research should refine these devices based on caregiver feedback to meet the evolving needs of the pediatric asthma population.

Bilateral superselective adrenal artery embolization for bilateral primary aldosteronism: a novel approach in an efficacy and safety proof-of-principle trial.

Superselective adrenal artery embolization (SAAE) offers a novel approach for treating primary aldosteronism (PA). In this study, we aimed to assess the efficacy and safety of SAAE for the treatment of PA based on the lateralization results obtained from adrenal vein sampling (AVS).In this prospective study, we enrolled 40 patients with PA who underwent SAAE. The patients were categorized into two groups, unilateral PA and bilateral PA, based on AVS results. Clinical parameters and biochemical markers were assessed at 3 and 12 months postoperatively. The primary outcomes were changes in blood pressure and defined daily dose (DDD) of antihypertensive medications compared to baseline. Thirty-eight patients achieved technical success, with favorable clinical and biochemical efficacy rates. At three months postoperatively, the clinical efficacy rates were 79.2% and 78.6% for the UPA and BPA groups, respectively. At 12 months, the rates were 83.3% and 71.4%, respectively. Both groups exhibited a significant decrease in average blood pressure at 3 and 12 months compared with baseline (P < 0.001), and there was also a notable reduction in DDD (P < 0.05). At three months, the biochemical efficacy rates were 61.9% and 58.3% in the UPA and BPA groups, respectively. Due to loss to follow-up, biochemical indicators were not assessed at 12 months postoperatively. No severe adverse reactions occurred during or after SAAE. Patients with both UPA and BPA can benefit from SAAE. The superiority of bilateral adrenal artery embolization in the treatment of BPA over unilateral adrenal artery embolization requires further investigation.

Factors Associated With Pain Perception and Management Among Paediatric Nurses and Nursing Students Using Virtual Children: A Comparative Study.

To identify and compare factors associated with pain perception and management among paediatric nurses and nursing students using virtual human technology. This study employed a comparative, cross-sectional design. Fifty-one paediatric nurses from a tertiary hospital and 50 senior nursing students from a nursing college, both located in South Korea, participated in the study. Virtual vignettes, including scenarios with virtual children and their clinical information, were used to assess participants' pain perception and management. The virtual children, created from real face photos, varied in age (young/old), sex (boy/girl) and facial expressions (smile/grimace). Participants rated perceived pain scores and selected management choices for eight virtual vignettes, which were randomly presented. The Korean version of the Paediatric Nurses' Knowledge and Attitude Survey was completed along with demographic information. Both paediatric nurses and nursing students rated pain scores lower than the actual pain scores reported by virtual children. Nurses rated higher pain scores and accordingly selected more medication doses compared to students. Beyond pain-related knowledge, the facial expression of the virtual child influenced pain rating and medication choices, while age and sex had no effect. Nursing students were more sensitive to the facial expressions of virtual children when rating their pain compared to nurses. Future studies should explore how paediatric nurses' clinical experiences impact their assessment and management of child patient pain. Paediatric nurses' knowledge of pain is inadequate, necessitating ongoing education in pain management. Both nurses and nursing students should self-reflect on their pain assessment practices to ensure unbiased care regardless of child patients' characteristics. Virtual human technology can be utilised to train nurses and students to identify and address any biases in their assessment of patients' pain perception. STROBE checklist, cross-sectional. Digital face photos of four healthy children were used as the fundamental material for creating virtual children, with their parents' consent.

Vacuum-filtration fabrication of copper-based halide scintillation screen for high-resolution X-ray imaging

Zero-dimensional (0D) organic-inorganic Cu(I)-based halides have garnered significant attention due to their low toxicity, efficient emission, and moderate fabrication conditions. However, the challenge remains in developing stable and efficient 0D hybrid Cu(I)-based halides for effective X-ray imaging. In this study, a yellow-emitting 0D hybrid copper halide, (ETPP)2Cu2I4 (Ethyl triphenylphosphonium, ETPP), was successfully synthesized via a slow evaporation method. This compound demonstrated an impressive steady-state light yield of 23,200 photons/MeV under X-ray radiation and an ultralow detection limit of 150.9 nGyair s−1, approximately 35 times lower than the standard medical examination dosage. Utilizing a vacuum-filtration method, we fabricated a flexible film that outperforms traditional methods and achieved an exceptional X-ray imaging resolution of 16.0 lp/mm. This study introduces a novel approach to fabricating high-performance X-ray imaging scintillators based on 0D Cu-based halides, showcasing excellent scintillation performance and stability for non-destructive testing.

Pharmacists Impact on Promoting the Public Health

Because they can guarantee that patients receive safe and effective medications, pharmacists are essential members of the healthcare team. In an effort to maximize patient results, they work in tandem with other medical specialists to evaluate pharmacological therapy, dispense medication, counsel patients on drug interactions and side effects, and monitor medication schedules. Pharmacists also give patients advice on managing illnesses, changing lifestyles, and adhering to medication regimens. The range of work that pharmacists do has expanded with the emergence of numerous global health issues. Safe and efficient drug usage by community and clinical pharmacists is necessary to provide the best possible patient outcomes. The public is still ignorant about the pharmacist's contribution to national and international health, nevertheless. They also perform drug use assessments, act as drug information specialists, and offer advice on the proper choice and dosage of medications. Pharmacists play a critical role in healthcare organizations as they strive to reduce prescription errors, enhance patient safety, and manage costs. The pharmacist can improve public health in a beneficial way. Thus far, the rise in the importance of pharmacists has been more influenced by the expansion of patient services than by a population-based approach to health. Pharmacists may find that integrating the five public health core competencies—social and behavioral science, health policy and administration, epidemiology, biostatistics, and environmental health sciences—into their pharmacy practice increases their efficacy and influence.

Combination certainty factor method and fuzzy expert system module to determine the dose of leukemia drugs

Leukemia is a type of blood cancer. Treatment for leukemia patients can last for years because the dose of medication given is adjusted to the patient's immune system. The aim of this research is the use of information technology through a combination of certainty factors and the development of a fuzzy expert system (FES) module to determine the therapeutic schedule for administering leukemia drugs. The urgency of this research is to help medical personnel in measuring the dose of leukemia medication to be given to patients so as to increase the cure rate for leukemia patients. The method used is certainty factor and fuzzy logic. The combination of the certainty factor method and the FES module which is carried out using input variables in the form of the severity of the leukemia suffered by the patient is to produce an appropriate therapeutic schedule for administering leukemia drugs. The result of this research is a combination of the factor certainty method and the FES module which has been tested and the accuracy level is 95.17%, the same as recommendations from experts.

A Phenomenological Study To Assess The Lived Experience Of Health Related Quality Of Life Of Diabetic Patient In Selected Hospitals Of Pune City

Diabetes is the top health emergencies from the 21st century. Every year more people live with diabetes that could be a result of sedentary life and health related complication. First world health organization’s global report in (2016) about diabetes shows that the numbers of peoples with diabetes, almost from the year 1980 to 2014, has quadrupled. The number of peoples with diabetes has been increased from 108 million in 1980 to 422 million in 2014.The study aims to assess the Health related quality of life of diabetic patients. Phenomenological research designwas used with Purposive sampling technique to select the participants. Sample size was 10 as determined by data saturation technique using a semi-structured questionnaire technique was adapted to collected data using colaizzi approach. The study finding revealed that in Baseline data 30% of the diabetic patients had age 25-35 years and 70% of them had age 35-45 years.50% of them were females and 50% of them were male.50% of them had higher secondary, 40% of them were illiterate and 10% of them had secondary education.90% of them were married and 10% of them were unmarried and 30% of them had 5-10 years of working experience.10% of them were non-vegetarians and 90% of them were vegetarians.All of them had family history of diabetes.40% of their fathers having diabetes and 60 of their mothers had diabetes mellitus. And common themes were found like confusion, giddiness, restlessness and uncomfortable, effect of the medications as Anger, Anxiety, Frustration, Headache, Irritation, Nausea, Stress and Vomiting, 'Confusion about the dose', 'Difficult to manage', 'Difficult to remember dose', 'Easy to manage' and 'Forget amount and dose of medication'.Joint pain, Tenderness, Tiredness Uncomfortable and Weakness

Management of intensive care unit withdrawal syndrome

Intensive care unit (ICU) patients frequently develop physical and psychological dependence on analgesic and sedative medications, which can lead to Iatrogenic withdrawal syndrome (IWS) upon discontinuation or tapering. The incidence of IWS in adult ICU patients varies significantly, with reported rates ranging from 12% to 100%. Identified risk factors for IWS include advanced age, obesity, medication dosage, and duration of exposure. The clinical manifestations of IWS are varied and include increased excitability of the central nervous system, gastrointestinal disturbances, and sympathetic nervous system hyperactivity. Preventive and therapeutic strategies for IWS encompass individualized medication regimens, structured withdrawal protocols, and a combination of pharmacological and non-pharmacological interventions. This review emphasizes the critical need for heightened awareness and improved management strategies to mitigate the incidence of IWS in ICU patients.

Abstract P117: Provider Concordance to the Current 2017 High Blood Pressure (BP) Clinical Practice Guidelines and Patient Blood Pressure Control

Introduction: The AHA/ACC 2017 High BP guidelines introduced key changes, compared to previous guidelines, including a new hypertension definition (≥130/80 mm Hg) and lower medication thresholds for patients at cardiovascular risk. The impact of provider adherence to these guidelines on patient BP control has not been fully explored. Methods: We identified 3,749 new stage 1 hypertension patients (7,214 visits) and 11,013 new stage 2 hypertension patients (33,321 visits), aged ≥18, from the Vanderbilt University Medical Center database. We scrutinized outpatient BP levels, prescribed medications, follow-up visits, lab results, demographics, comorbid conditions, and physician notes from January 2018 to December 2022. This data was compared to hypertension treatment criteria developed from the 2017 guidelines that was validated by six hypertension experts. Active primary care patients (with 1 visit per year) were included. Mixed-effects Poisson regression and mixed-effects linear regression examined the relationship between guideline adherence and controlled BP (&lt;130/80 mm Hg) and continuous BP, respectively. Results: Among stage 1 hypertension visits, 12.2% were treated with at least one antihypertensive drug according to guidelines, resulting in a 13% increase in BP control and a reduction in systolic BP by 2.02 mm Hg. For stage 2 hypertension visits, 26% received treatment with at least two first-line antihypertensive drug classes, leading to a 45% increase in BP control and reductions in systolic and diastolic BP by 3.79 mm Hg and 1.93 mm Hg, respectively. No significant difference in BP control was observed among stage 2 patients treated with two versus one first-line drug. Adherence to follow-up guidelines resulted in a 24% improvement in BP control for stage 1 patients and stage 2 patients when their follow-up visit occurred within 1 month. Subsequent follow-up visits within 1-month improved BP control by 34% if BP was not controlled previously. Additionally, 42.4% of patients with uncontrolled BP for 1 month received an increase in medication dose or a change/addition of medication class and showed a 7% increase in BP control within next month. Conclusion: Provider adherence to recommended antihypertensive drug treatment guidelines (12%-26%), follow-up assessments guidelines (29%-37%), and treatment intensification (42.4%) were poor. However, patients treated according to the guidelines showed significant improved BP control.

Sequential and parallel testing for microbiological confirmation of tuberculosis disease in children in five low-income and middle-income countries: a secondary analysis of the RaPaed-TB study

Despite causing high mortality worldwide, paediatric tuberculosis is often undiagnosed. We aimed to investigate optimal testing strategies for microbiological confirmation of tuberculosis in children younger than 15 years, including the yield in high-risk subgroups (eg, children younger than 5 years, with HIV, or with severe acute malnutrition [SAM]). For this secondary analysis, we used data from RaPaed-TB, a multicentre diagnostic accuracy study evaluating novel diagnostic assays and testing approaches for tuberculosis in children recruited from five health-care centres in Malawi, Mozambique, South Africa, Tanzania, and India conducted between Jan 21, 2019, and June 30, 2021. Children were included if they were younger than 15 years and had signs or symptoms of pulmonary or extrapulmonary tuberculosis; they were excluded if they weighed less than 2 kg, had received three or more doses of anti-tuberculosis medication at time of enrolment, were in a condition deemed critical by the local investigator, or if they did not have at least one valid microbiological result. We collected tuberculosis-reference specimens via spontaneous sputum, induced sputum, gastric aspirate, and nasopharyngeal aspirates. Microbiological tests were Xpert MTB/RIF Ultra (hereafter referred to as Ultra), liquid culture, and Löwenstein-Jensen solid culture, which were followed by confirmatory testing for positive cultures. The main outcome of this secondary analysis was categorising children as having confirmed tuberculosis if culture or Ultra positive on any sample, unconfirmed tuberculosis if clinically diagnosed, and unlikely tuberculosis if neither of these applied. Of 5313 children screened, 975 were enrolled, of whom 965 (99%) had at least one valid microbiological result. 444 (46%) of 965 had unlikely tuberculosis, 282 (29%) had unconfirmed tuberculosis, and 239 (25%) had confirmed tuberculosis. Median age was 5·0 years (IQR 1·8-9·0); 467 (48%) of 965 children were female and 498 (52%) were male. 155 (16%) of 965 children had HIV and 110 (11%) children had SAM. 196 (82%) of 239 children with microbiological detection tested positive on Ultra. 110 (46%) of 239 were confirmed by both Ultra and culture, 86 (36%) by Ultra alone, and 43 (18%) by culture alone. 'Trace' was the most common semiquantitative result (93 [40%] of 234). 481 (50%) of 965 children had only one specimen type collected, 99 (21%) of whom had M tuberculosis detected. 484 (50%) of 965 children had multiple specimens collected, 141 (29%) of whom were positive on at least one specimen type. Of the 102 children younger than 5 years with M tuberculosis detected, 80 (78%) tested positive on sputum. 64 (80%) of 80 children who tested positive on sputum were positive on sputum alone; 61 (95%) of 64 were positive on induced sputum, two (3%) of 64 were positive on spontaneous sputum, and one (2%) was positive on both. High rates of microbiological confirmation of tuberculosis in children can be achieved via parallel sampling and concurrent testing procedures. Sample types and choice of test to be used sequentially should be considered when applying to groups such as children younger than 5 years, living with HIV, or with SAM. European and Developing Countries Clinical Trials Partnership programme, supported by the EU, the UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung, the German Center for Infection Research, and Beckman Coulter.

Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study.

Savolitinib has been approved in China for advanced or metastatic non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations in previously treated patients and those unable to receive platinum-based chemotherapy. We report results from a treatment-naive cohort of a phase 3b study that was designed to evaluate the efficacy and safety of savolitinib in locally advanced or metastatic METex14-mutated NSCLC. This single-arm, multicohort, multicentre, open-label, phase 3b study was done at 48 hospitals in China in adult (≥18 years) patients with locally advanced or metastatic METex14-mutated NSCLC who had not received previous systemic antitumour therapy. Patients with a bodyweight of 50 kg or more and those with a bodyweight of less than 50 kg received savolitinib once daily at 600 mg or 400 mg, respectively, in 21-day cycles. The primary endpoint was objective response rate assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours, version 1.1. The full analysis set comprised all patients who received at least one dose of study medication, which was used to assess the efficacy endpoints and baseline and safety data. This study is registered with ClinicalTrials.gov (NCT04923945) and is closed to accrual. Between Aug 31, 2021, and Oct 20, 2023, 125 treatment-naive patients were assessed for eligibility, of whom 87 were enrolled and received savolitinib. The median age of patients was 70·0 years (IQR 65·2-75·8) and 51 (59%) of 87 patients were male and 36 (41%) were female. In the full analysis set, the IRC-assessed objective response rate was 62% (95% CI 51-72) and the investigator-assessed objective response rate was 60% (49-70), showing a high concordance rate (84%). Treatment-related adverse events were reported in 85 (98%) of 87 patients, with peripheral oedema (54 [62%]) being the most common. Two of these treatment-related adverse events led to death (cardiac failure n=1, unknown reasons n=1). Savolitinib showed manageable toxicity and promising efficacy in treatment-naive patients with advanced or metastatic METex14-mutated NSCLC. HUTCHMED and AstraZeneca.

Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial

Access to allogeneic haematopoietic stem-cell transplantation (HSCT) remains challenging for older patients (aged >60 years) with acute myeloid leukaemia. We aimed to evaluate the efficacy of venetoclax plus decitabine as first-line therapy and bridge to transplantation in this patient population. This multicentre, single-arm, phase 2 trial was conducted in 20 Gruppo Italiano Trapianto Midollo Osseo (GITMO) centres in Italy. Patients aged ≥60 and <75 years, with newly diagnosed acute myeloid leukaemia categorised as intermediate or high risk according to 2016 WHO and 2017 European LeukemiaNet, an ECOG performance status of less than 2, and considered fit for allogeneic HSCT were included. Patients received oral venetoclax with a 3-day ramp-up: 100 mg on day 1, 200 mg on day 2, and 400 mg once per day from day 3 of cycle one, and then every 28 days of each cycle (two to four in total). Decitabine was administered intravenously at a dose of 20 mg/m2 from days 1 to 5 every 28 days. At cycle one, patients were admitted to hospital for a minimum of 24 h, whereas subsequent cycles could be administered on an outpatient basis. Two additional cycles were allowed while waiting for allogeneic HSCT or for those with no response or partial response after cycle two. The primary endpoint was the proportion of patients who had allogeneic HSCT performed during first complete remission, assessed in all patients who received at least one dose of the study medication. This study was registered with ClinicalTrials.gov (NCT04476199, ongoing) and EudraCT (2020-002297-26). Between June 1, 2021, and Dec 30, 2022, 93 patients were enrolled and started venetoclax plus decitabine induction (44 [47%] at intermediate risk and 49 [53%] at high risk). The median age was 68·5 (IQR 60·3-74·7). All 93 participants were White, of whom 43 (46%) were female and 50 (54%) were male. The median follow-up was 236 days (IQR 121-506). 64 (69%) of 93 patients reached complete remission and 53 (57%) underwent allogeneic HSCT in complete remission. 53 (83%) of 64 with a complete remission underwent allogeneic HSCT. Five (8%) of 64 patients in complete remission relapsed before transplantation and four died as a consequence. Adverse events (grade ≥3) occurred in 49 (53%) of 93 patients. The most common adverse events were infections (including pneumonia, bacterial sepsis, and SARS-CoV-2 causing seven deaths among 28 [57%] of 49 patients), neutropenia (17 [35%]), thrombocytopenia (two [4%], including one fatal CNS bleeding), and cardiac events (four [8%], including one fatal heart failure). No treatment-related deaths were observed. Venetoclax plus decitabine induction can significantly enhance the feasibility of allogeneic HSCT in older patients with acute myeloid leukaemia who are deemed fit for transplantation. AbbVie and Johnson & Johnson.

A Comprehensive Review on Understanding Magnesium Disorders: Pathophysiology, Clinical Manifestations, and Management Strategies.

Magnesium is vital in a broad spectrum of physiological processes, including enzyme activity, energy production, and neuromuscular function. Despite its crucial role, magnesium disorders - comprising both deficiency (hypomagnesemia) and excess (hypermagnesemia) - are frequently underrecognized and inadequately managed in clinical practice. Magnesium deficiency is widespread, particularly among populations with chronic illnesses, the elderly, and those experiencing malnutrition, often leading to significant neuromuscular, cardiovascular, and metabolic complications. Conversely, hypermagnesemia, though less common, poses serious risks, especially in individuals with impaired renal function or those receiving high doses of magnesium supplements or medications. This review comprehensively examines magnesium disorders, detailing their pathophysiology, clinical manifestations, and management strategies. It highlights the essential functions of magnesium in maintaining cellular integrity, cardiovascular health, and bone structure and discusses the global prevalence and risk factors associated with magnesium imbalances. By offering insights into the current understanding of magnesium homeostasis and its disruptions, this review aims to enhance the awareness and treatment of magnesium-related conditions, ultimately improving patient outcomes across diverse clinical settings.

Abstract P327: Comparing the Blood Pressure Response to Antihypertensive Treatment Intensification and Dose Increase to No Action for Uncontrolled Hypertension

Background: The addition of a new antihypertension medication class (CA) or dose increase (DI) in patients with hypertension (HTN) is relatively infrequent when HTN is uncontrolled (blood pressure [BP, mmHg] ≥ 140/90) during outpatient visits. We compared systolic (S)BP changes following CA, DI, or no medication changes for uncontrolled BP. Methods: A patient cohort from 6 diverse healthcare organizations, engaged in a quality improvement program, was identified with previously diagnosed HTN. Uncontrolled outpatient SBP measurements observed at participating program sites were compared to follow-up measurements within 7 to 120 days for evaluating SBP change. ANCOVA and linear regression analyses were used to control clinical and demographic covariates and assess differences in SBP change following treatment decision. Results: A prospective cohort of 124,068 patients with HTN spanning 280,937 events was identified, mean age 63.3 ± 13.9. Class addition reduced SBP 2.0 mmHg (95% CI, 1.81 – 2.24), whereas dose increase did not lower SBP [-0.07 (95% CI, -0.31, 0.16)]. Conclusion: In this study, CA lowered BP modestly, whereas DI appeared ineffective. Since patients were not randomized, our results may under-estimate the effects of CA and DI on BP, i.e., clinicians may have expected a greater decline of SBP than simply regression to the mean for patients with uncontrolled hypertension in the absence of DI or TI. Our data are consistent with reports that CA has a greater effect to lower BP than DI. Our findings also highlight some challenges of interpreting real world data compared to randomized clinical trials.

Effects of in utero exposure to Δ-9-tetrahydrocannabinol on cardiac extracellular matrix expression and vascular transcriptome in rhesus macaques.

Delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, remains a schedule I substance, thus safety data regarding the effects on the cardiovascular and prenatal health are limited. Importantly, there is evidence showing prenatal cannabis exposure can negatively impact fetal organ development, including the cardiovascular system. THC can cross the placenta and bind to cannabinoid receptors expressed in the developing fetus, including on endothelial cells. To understand the impact of prenatal THC exposure on the fetal cardiovascular system, we used our rhesus macaque model of prenatal daily edible THC consumption. Before conception, animals were acclimated to THC (2.5 mg/7 kg/day, equivalent to a heavy medical cannabis dose) and maintained on this dose daily throughout pregnancy. Fetal tissue samples were collected at gestational day 155 (full term is 168 days). Our model showed that in utero THC exposure was associated with a decreased heart weight-to-body weight ratio in offspring, warranting further mechanistic investigation. Histological examination of the fetal cardiac and vascular tissues did not reveal any significant effect of THC exposure on the maturity of collagen within the fetal heart or the aorta. Total collagen III expression and elastin production and organization were unchanged. However, bulk RNA-sequencing of vascular cells in the umbilical vein, umbilical artery, and fetal aorta demonstrated that THC alters the fetal vascular transcriptome and is associated with upregulated expression of genes involved in carbohydrate metabolism and inflammation. The long-term consequences of these findings are unknown but suggest that prenatal THC exposure may affect cardiovascular development in offspring.NEW & NOTEWORTHY Prenatal cannabis use is increasing and despite the public health relevance, there is limited safety data regarding its impact on offspring cardiovascular health outcomes. We used a translational, nonhuman primate model of daily edible Δ-9-tetrahydrocannabinol (THC) consumption during pregnancy to assess its effects on the fetal cardiovascular system. THC-exposed fetal vascular tissues displayed upregulation of genes involved in cellular metabolism and inflammation, suggesting that prenatal THC exposure may impact fetal vascular tissues.