Patient Dose Research Articles

Evaluation of radiation dose and cancer risk for paediatric digital radiography in a Moroccan hospital

Pediatric radiography is the first line of most diagnostic examinations and an effective tool that provides important information about the patient's health status.This study aims to investigate the Entrance Surface Dose (ESD) and organ doses for pediatric patients undergoing imaging procedures of the abdomen, chest, pelvis, and nasopharynx using Optically Stimulated Luminescence Dosimeters OSLDs and an anthropomorphic phantom.An ATOM pediatric 5-year-old phantom was imaged using a Digital Radiography (DR) based on similar conditions of routine radiography (exposure parameters kVp, mAs, SID: Source Image receptor Distance). The OSLDs were inserted at the appropriate sites to measure localized doses in the sensitive organs.The results showed that the entrance surface doses for the pediatric patients were 0.17 ± 0.03 mGy, 0.10 ± 0.00 mGy, 0.46 ± 0.00 mGy, and 0.42 ± 0.02 mGy, respectively, for the abdomen (AP), chest (AP), pelvis (AP), and nasopharynx (LAT). The range of organ doses were 0.05-0.45 mGy, 0.01-0.44 mGy, 0.13-1.05 mGy, and 0.084 -0.99 mGy for the abdomen, chest, pelvis, and nasopharynx examination, respectively. Effective doses (ED) were 0.088 ± 0.021 mSv, 0.011 ±0.004 mSv, 0.058 ±0.007 mSv, and 0.044 ±0.024 mSv for the abdomen, chest, pelvis, and nasopharynx examination, respectively.The likelihood of cancer, as determined by the ICRP health risk model with a rate of 500 cases per 10,000 person-Sv (5% per sievert), estimated that a 0.015 case of health risk (0.3 person-Sv × 5% per sievert) may in the future be attributable to four X-ray pediatric procedures conducted in 2022.The ESD, ED, and organ dose values are deemed acceptable compared to those reported in the literature. Although the risk of incidence and mortality from cancer during life is minimal, it should not be ignored.

CT surveillance for type 1 autoimmune pancreatitis: cumulative radiation dose and diagnostic performance for disease relapse.

Long-term follow-up is essential for type 1 autoimmune pancreatitis (AIP) patients due to high relapse rates. The cumulative radiation dose from repeated CT scans during follow-up should not be ignored. We aim to investigate the cumulative radiation dose in AIP patients undergoing CT surveillance and the diagnostic performance of CT in detecting disease relapse. The diagnostic performance of MRI from a secondary cohort during the same period was also investigated. This retrospective single-institutional study included 247 type 1 AIP patients with one or more follow-up CT scans, and 120 patients with MR follow-ups. Four metrics were utilized to report the radiation dose, including the volume computed tomography dose index, the dose length product, size-specific dose estimate and effective dose. The diagnostic performance for AIP relapse was assessed, taking the final clinical diagnosis in retrospect as the reference standard. With a median 2.3-year follow-up period, AIP patients followed up with CT exhibited a median cumulative radiation dose of 37.5 mSv. 11.3% of patients have accumulated doses exceeding 100 mSv. For the 169 patients followed over a year, 30.8% sustained an average annual radiation dose surpassing 20 mSv. The sensitivity/specificity/accuracy of CT for detecting abdominal organ relapse was 64.1%/99.6%/97.0%. For AIP patients followed up with MRI, the sensitivity for detecting disease relapse was 90.5%. Considering the accumulation of radiation dose in AIP patients and the insufficient sensitivity in detecting disease relapse with CT, safer and more sensitive imaging follow-up strategies should be explored. Question CT, as the primary imaging modality for autoimmune pancreatitis (AIP) follow-up, raises concerns regarding radiation exposure and lacks reported diagnostic performance in detecting AIP relapse. Findings CT in AIP follow-up causes significant cumulative radiation exposure and exhibits insufficient sensitivity in relapse detection. Clinical relevance Type 1 AIP necessitates long-term imaging follow-up, yet current guidelines lack consensus regarding the prioritization of CT or MRI for such follow-up. CT is widely used but has radiation concerns and limited sensitivity, calling for safer, efficient strategies.

Comparison of long term efficacy and cost-effectiveness of omalizumab in 150 mg and 300 mg doses in patients with chronic spontaneous urticaria

BackgroundChronic spontaneous urticaria (CSU) is a clinical condition that affects patients quality of life. Omalizumab is preferred in antihistamines resistant CSU cases. Urticaria activity score-7 (UAS-7) is a scale that shows the severity of the disease. ObjectivesThe authors aimed to compare the long-term (60 months) efficacy and side effects of 150 mg and 300 mg doses of omalizumab in patients with CSU. Methods108 patients followed up at the clinic with the diagnosis of CSU were included. Omalizumab was started in patients who were resistant to conventional CSU treatment. Two groups were formed to receive 150 mg and 300 mg doses of omalizumab. Urticaria activity score (UAS-7), antihistamine usage, time to achieve disease-free stage, relapse after treatment, and side effects of omalizumab treatment were compared in the two groups. ResultsThere were no statistically significant differences between the groups regarding basal characteristics and laboratory findings. Average follow-up time was sixty months. UAS-7 scores were similar in the follow-up. There were no adverse events in both groups. Study limitationsRetroactive design and single-center nature to reach a more significant number of patients. Lack of patients receiving the lowest dose 75 mg and the highest dose 600 mg of omalizumab. Absence of total body mass indexes of all patients. Besides, the use of distinct drugs may contribute to non confident results and is another limitation of this study. ConclusionSince there is no significant difference between 150–300 mg omalizumab doses regarding long-term treatment efficacy and side effects in CSU patients, starting treatment with a 150 mg dose may be suitable. In patients who do not respond to 150 mg, the omalizumab dose can be increased to 300 mg. It will prevent unpredictable dose and time-dependent complications and will be a cost-effective approach even in strong economies.

Longer duration of high-dose corticosteroids provides benefit for hospitalized COVID-19 patients with high oxygen requirement

The optimal corticosteroids dose in patients with coronavirus disease 2019 (COVID-19) requiring high oxygen remains unknown. In this retrospective study of patients with COVID-19 requiring high oxygen and receiving corticosteroids, the efficacy, safety, and duration of high-dose treatment were evaluated. The primary outcome was all-cause mortality during follow-up. Safety outcomes included infection, gastrointestinal bleeding, and venous thromboembolic events. 210 patients were included, with 126 in Group A (corticosteroids at a equivalent dose <1 mg/kg/d prednisone), 44 in Group B (corticosteroids at a equivalent dose ≥1 mg/kg/d prednisone for ≤5 days), and 40 in Group C (corticosteroids at a equivalent dose ≥1 mg/kg/d prednisone for >5 days). The all-cause mortality risk was lower in Group C but higher in Group B than in Group A. Safety outcomes did not differ significantly, except for Group C, which had the highest venous thromboembolism rate. Our results suggest that high-dose corticosteroids for a longer course decrease mortality with comparable safety outcome.

Bioactive Compounds Aimed at the AMPK Pathway: A Window into their Therapeutic Potential

Abstract: Current investigations have proposed that focusing on malignancy cell metabolism is an elective restorative methodology in cancer treatment. AMPK is the significant energy sensor regulating ordinary as well as malignancy cell metabolism. Drugs as AMPK activators can quell malignancy cell development through the various signalling cascade. AMPK enactment in light of natural AMPK activators, for example, BME, ICT, Thymoquinone, has been displayed to constrict mTOR, approving that BME can restrain cell development in ovarian malignant growth cells utilizing suppressing mTOR-mediated protein translation process. Nutraceuticals as well as traditional medicines operate as natural AMPK activators that regulate AMPK movement through a mechanism that is independent of AMP. These naturally occuring AMPK activators might straightforwardly actuate AMPK through single or more than one mechanism in AMPK initiation. Exploring the synergistic effects of compounds with existing cancer treatments could open new avenues for combinatorial therapy, potentially enhancing efficacy and reducing side effects. Moreover, understanding the precise molecular pathways through which these natural AMPK activators exert their effects will be crucial in designing targeted therapies that maximize their therapeutic potential. The integration of these nutraceuticals into standard cancer treatment protocols requires rigorous clinical trials to establish their safety, optimal dosing, and long-term benefits in cancer patients. With further investigation, the possibility of using natural AMPK activators in addition to traditional medicines could transform cancer treatment by providing more patient-friendly and comprehensive options.

Quality assurance of internal mammary node irradiation in the DBCG IMN2 study

Purpose/objectiveThe Danish Breast Cancer Group (DBCG) IMN2 study investigated the gain from internal mammary node irradiation (IMNI) in node-positive breast cancer (BC) patients. IMNI was indicated in right-sided patients, but not in left-sided. Target volume delineations were based on bony landmarks in contrast to the contemporary vessel-based ESTRO consensus guideline. Our objective was to compare IMNI doses in right-sided versus left-sided patients. Material/methodsTreatment plans and delineated structures including CTVn_IMN (IMN_old) from 2008 to 14 were collected from the DBCG RT Nation study. During the study period, IMN_old was only delineated in right-sided patients. Right and left-sided CTVn_IMN structures were auto-segmented following the ESTRO guidelines (IMN_ESTRO). Due to cranial discordance between IMN_old and IMN_ESTRO, the IMN_ESTRO models were separated into IMN_ESTRO_cranial and IMN_ESTRO_intercostal space(IC)1-3, IC1-4, and IC4_only. ResultsTreatment plans for 2,837 patients were available (62.5 % of patients in the IMN2 study). In right-sided patients, the median IMN_old dose coverage (92.4 %) was higher than IMN_ESTRO (71.7 %), p < 0.001. Dose coverage in IMN_ESTRO_IC1-3 was comparable to IMN_old. Comparing IMN_ESTRO_IC1-3 in all patients by laterality, the median CTVn_V90% was 94.6 % (IQR 64.8–100.0) in right-sided patients and 20.4 % (IQR 0.9–55.8) in left-sided patients, p < 0.001. For right-sided patients, CTV_V90% was 82.3 % in IMN_ESTRO_IC4_only.Median mean heart doses were lower in right-sided patients (1.2 Gy) than in left-sided (2.3 Gy), p < 0.001. Median mean lung doses were higher in right-sided patients (16.0 Gy) than in left-sided (12.7 Gy), p < 0.001. ConclusionFor IMN_ESTRO_IC1-3, we found a significantly higher IMN dose coverage in right-sided than in left-sided patients supporting treatment according to study guidelines.

Evaluation of radiation dose to Korean population by general radiography

General radiography has the highest usage among diagnostic radiology in Korea, resulting in high radiation dose by general radiography. For the medical radiation safety of patients, it is necessary to evaluate Korean population dose by general radiography. In this study, collective dose and per capita effective dose from general radiography in the Korean population were calculated. To this end, the raw data on the usage of general radiography in Korea as of 2017 was analyzed. Moreover, information on radiation dose from domestic general radiography was collected and PCXMC was used to evaluate the effective dose for patients during general radiography. As of 2017, the usage rate for lower extremity and chest examinations was high, accounting for more than 20 % of the total general radiography examinations. The effective dose depending on the examination type was the highest for whole-spine AP (1.06 mSv), followed by whole-spine LAT (0.61 mSv), and lumbar spine AP (0.51 mSv). As a result of evaluating Korean population dose by general radiography, the collective dose was 22,066 man∙Sv and the per capita effective dose was 0.43 mSv. The evaluation results of the Korea population dose obtained from this study can contribute to patient dose management in general radiography.

A Delphi consensus project to capture experts' opinion on hyperkalaemia management across the cardiorenal spectrum.

The main purpose of this project was to capture experts' opinion on hyperkalaemia management and form best practice recommendations for cardiorenal patients in Greece. A steering committee of nephrologists and cardiologists developed 37 statements. An online questionnaire completed by 32 experts in cardiorenal management in Greece. Median score used to determine the level of agreement and disagreement index (DI) used to determine the level of consensus for each statement. Statements divided in four sectors: hyperkalaemia risk management, preventative measures, treatment and collaboration between specialties. The rate of the first round of the consensus was 94.6%. Median score was >7 for 36 of 37 statements and DI≤1 for 35 of 37. Among other statements, consensus reached for recognizing levels K+>5.0mEq/L as associated with elevated mortality risk; retaining renin-angiotensin-aldosterone system inhibitors (RAASi) on maximum recommended dose for cardiorenal patients; and using novel K+ binders to help enabling guideline-recommended doses of RAASi therapy. Cardiologists compared to nephrologists showed higher reluctance to discontinue down-titrate RAASi and MRA in patients with K+ levels above 5mEq/L. Additionally, 88.9% of nephrologists and 71.4% of cardiologists agreed that cross-specialty alignment on a serum K+ concentration level (K>5.5mEq/L) is needed to initiate hyperkalaemia treatment. Both cardiologists and nephrologists showed disagreement with the statement on keeping titration in cardiorenal patients with K+>5.5mEq/L or preserving fruit and vegetable consumption when moderate or severe hyperkalaemia exhibits. This Delphi project pointed out nephrologists' and cardiologists' agreement on hyperkalaemia management in cardiorenal patients; thus, it can help a cross-specialty optimal management of cardiorenal patients, with hyperkalaemia not being an obstacle for disease-optimizing therapy. Novel potassium binding agents can enable guideline-recommended doses of potassium-sparing medication.

Can the Charlson comorbidity index help to guide DOAC dosing in patients with atrial fibrillation and improve the efficacy and safety of treatment? A subanalysis of the MAS study

BackgroundFrailty influences the effectiveness and safety of anticoagulant therapy in patients with atrial fibrillation (AF). The age-weighted Charlson comorbidity index may offer a valuable tool to assess the risk of adverse events in AF patients treated with direct oral anticoagulants (DOACs). This sub-analysis of MAS trial data aimed to assess whether using the Charlson index, instead of the standard criteria, would have led to different dosing and improved adverse event occurrence during treatment. MethodsThe MAS study looked for a relationship between DOAC levels assessed at baseline and adverse events during follow-up. The study is described in detail elsewhere. ResultsAmong the 1,657 patients studied, 832 (50.2 %) had a relatively low Charlson index (up to 6, general median class), of whom 132 (15.9 %) were treated with reduced doses. Conversely, among the 825 patients with a high Charlson index (≥7), 257 (31.1 %) received standard doses. A weak but statistically significant positive correlation (r = 0.1413, p < 0.0001 by ANOVA) was observed between increasing Charlson classes and DOAC levels standardized to allow comparability among drug results. However, no significant differences were found in the incidence or number of adverse events during follow-up, or in other parameters, between patients with low and high Charlson's scores. ConclusionsUtilizing the Charlson index would have led to notable differences in DOAC dosing compared to standard criteria. However, we found no evidence that its use would have improved the prediction of adverse events in AF patients enrolled in the MAS study.

Evidence-Informed Provision of Doxycycline Post-Exposure Prophylaxis for Prevention of Bacterial Sexually Transmitted Infections.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces the risk of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. In the United States, doxy-PEP is in an early stage of integration into clinical practice, and national guidelines for its use were recently released. The goal of this manuscript is to provide practical guidance for clinicians who are considering or currently prescribing doxy-PEP. We address five clinical questions using post hoc analyses of data from the DoxyPEP randomized controlled trial and discuss the potential implications and limitations of each question with the goal of informing clinical practice and implementation of doxy-PEP programs. The questions address patient eligibility criteria for doxy-PEP, the expected benefit and associated doxy-PEP doses for the average patient, the initial number of doses prescribed, and laboratory monitoring of persons taking doxy-PEP.

Cardioprotective effects of novel antioxidants post-myocardial infarction: An integrative review of preclinical and clinical data

Myocardial infarction (MI), is still a major public health problem, and oxidative stress contributes to the degree of myocardial damage after MI. Oxygen-derived free radicals (ODFR) worsen myocardial injury and result in chronic heart failure in many patients. These harms have led to interest in antioxidant treatment to reduce these adverse effects; new antioxidants with the potential for cardioprotection are the subject of significant interest. This review summarizes basic and clinical research comparing the effectiveness of newly synthesized antioxidants in attenuating oxidative stress and enhancing recovery after myocardial infarction. The review synthesizes evidence of a reduction in infarct size, enhancement of cardiac function, and repression of apoptosis in myocardial cells by the use of antioxidants from animal models. Melatonin, N-acetylcysteine, edaravone, and coenzyme Q10 demonstrated a wide range of preclinical positive effects by acting as ROS free radicals scavengers, modulating mitochondria dysfunction, and reducing inflammation. These findings are extrapolated from humans, although advances in antioxidant therapy are beginning to be viewed in initial clinical trials. From human data, although clinical trials are scarce, the evidence of new antioxidants can improve point and long-term outcomes in patients undergoing MI, help to increase the contractility of the injured myocardium, and decrease the mortality level. However, some issues are still there, such as high inter- and intra-individual variability in patient response and dosing schedule, as well as adverse effects such as pro-oxidant activity at high Oral administered doses of melatonin. The limitations of the current research discussed in this review include the general lack of large-scale, well-controlled clinical trials and the need for long-term follow-up studies. This review also proposed future research directions for improving antioxidant applications in post-MI management.

Relationship between Vitamin D and Insomnia in Older Adults

Vitamin D is one of the common fat-soluble vitamins, which can be obtained from ultraviolet exposure and intake from particular food or supplementation. Insomnia caused by many reasons like diseases or health status, would also increase possibilities of suffering from other diseases, and has a prevalence to be common among all sorts of people, especially in older adults. Researchers found vitamin D associated with neurotransmitters, oxidative stress and inflammation. Many research also suggest vitamin D are relevant to insomnia, people with low serum vitamin D concentration have a higher possibility to suffer from insomnia, after a period time of supplementation of vitamin D insomnia patients, many of them get improved, but there are no significant difference on some on them either. The mechanism about vitamin D improving insomnia symptoms is not clear, there is no determine recommended dose and duration for patient, and also not enough clinical trials for further exploration. As an auxiliary means of insomnia treatment, vitamin D may have a good performance combined with other therapies. The current review summarizes some mechanism of vitamin D, both positive and negative evidence associated with vitamin D improves insomnia symptom, and have an outlook for the future study on insomnia between vitamin D.

Effect of sodium-glucose cotransporter-2 inhibitor (SGLT2-i) in patients with LVAD: a systematic review and meta-analysis

Abstract Introduction Sodium-glucose cotransporter-2 inhibitor (SGLT2-i) have been shown to reduce risks of clinical events in patients with heart failure (HF). However, data on the use of SGLT2-i in patients with left ventricular assist devices (LVAD) are scarce. We thought to assess the efficacy and safety of SGLT2-i in patients with LVAD Methods A systematic search was done in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to December 2023. We used all relevant words for "SGLT2-i" and "LVAD" to search in databases and we included studies and published abstracts in peer-reviewed journals of studies assessed SGLT2-i in patients with LVAD. The efficacy and safety data were extracted across the studies. RevMan 5.4.1 was used for meta-analysis. Results Three studies and eight abstracts totaling 209 patients using SGLT2-i were included. Empagliflozin, Dapagliflozin, and Canagliflozin were the used SGLT2-i across the included studies. SGLT2-i effectively decreased hemoglobin A1c (HbA1c) (Mean = -0.44, 95% CI [-0.79, -0.09], p = 0.01) and diuretic dose (Mean=-2.54, 95% CI [-3.56, 1.51], p&amp;lt; 0.00001) from baseline. No significant improvement was found for glomerular filtration rate (GFR), B-type natriuretic peptide (BNP), or mean pulmonary artery pressure (MPAP). Regarding safety, the pooled percentage of people with driveline infection was 9.33%, 95% CI [2.05, 16.60], p=0.01. Conclusion SGLT2-i effectively improves HbA1c and diuretic dose in patients using LVAD. Further randomized studies with a large number of participants may be warranted.

Edoxaban dose, frailty, and outcomes in patients with atrial fibrillation: the ETNA-AF-Europe 4-year follow-up

Abstract Background Frailty is a common reason to choose non-recommended (non-rec) doses of non-vitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation (AF); however, it is not known how this practice affects stroke and bleeding outcomes. Purpose To assess clinical outcomes in frail patients with AF receiving non-rec vs recommended (rec) doses of edoxaban using 4-yr follow-up data from ETNA-AF-Europe. Methods The prospective, observational ETNA-AF-Europe study followed patients with AF receiving edoxaban for up to 4 yrs. In ETNA-AF-Europe, perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a simplified adaptation of the Rockwood’s Frailty Index. For objective frailty, patients with missing index were categorised as non-frail. Patients with perceived or objective frailty were combined for this analysis. Baseline characteristics and hazard ratios (HRs) with 95% confidence intervals (CIs) assessing risk of outcomes in frail patients prescribed non-rec vs rec edoxaban doses (i.e., non-rec 60mg vs rec 30mg and non-rec 30mg vs rec 60mg) are presented. Data were adjusted for age, sex, and derived versions of the CHA2DS2-VASc and HAS-BLED scores. Net clinical benefit was defined as any stroke/systemic embolic event (SEE), transient ischaemic attack, venous thromboembolic event, major bleeding, or cardiovascular death, whichever came first. Results Of 13164 patients, 1786 were frail (13.6%; perceived frailty [n=1410], age [IQR]: 82.0 [78.0-86.0] yrs, women: 57.9%; objective frailty [n=540], age [IQR]: 77.0 [71.0-82.0] yrs, women: 31.9%; both, n=164). Baseline characteristics are reported in Table 1. Risk of all-cause death was higher in frail patients treated with non-rec 30mg vs rec 60mg (HR [95% CI]: 1.44 [1.06,1.96]). The annualised rate [CI] of any stroke/SEE was non-significantly higher (HR [95% CI]:1.60 [0.80,3.20]) with non-rec 30mg (n=169; 2.25 [1.25,4.06]) vs rec 60mg (n=622; 1.54 [1.08,2.20]). There was, however, no association between treatment received and risk (HR [95% CI]) of major bleeding (1.19 [0.58,2.43]) or net clinical benefit (1.26 [0.84,1.87]) (Figure 1). In frail patients who received non-rec 60mg (n=183) vs rec 30mg (n=695), risk of any stroke/SEE (HR [95% CI]) was higher (2.15 [1.03,4.49]), but there were no significant differences in the risk (HR [95% CI]) of major bleeding (1.03 [0.52,2.01]), net clinical benefit (1.15 [0.78,1.71]), or all-cause death (0.79 [0.59,1.05]) (Figure 1). Conclusions In this large European AF registry, the presence of frailty should not drive dosing recommendations for edoxaban. In particular, when compared with the rec 60mg dose, the non-rec 30mg (reduced) dose, was associated with more all-cause death and no benefits on major bleeding.Baseline Characteristics

Twelve-month outcome of robotic assisted PCI

Abstract Background Robotics in interventional cardiology (R-PCI) is a technique with high potential for optimising the outcome of patients with coronary heart disease. In order to compare R-PCI with conventional, manual PCI (M-PCI), it is necessary to analyse both the index procedure during the initial hospital stay and, in particular, the long-term outcome. Methods We report twelve-month follow up data of our prospective FRiK registry, started in mid 2021. This registry focuses on success rates and safety, radiation dose of patients and personnel as well as long-term outcome (after 6 and 12 months). Moreover, R-PCI is compared with M-PCI in these categories. Results 73 patients received R-PCI. PCI success rate was 100%, with 17.8% requiring manual assistance. Rate of complications (MACE - major adverse cardiovascular events) was 0%. Compared with 152 M-PCI patients, treated by the same interventionalists, there was a higher median procedural time (diagnostic and intervention) 102.5 (82.8-123.5) min vs. 73 (51-101.5) (p&amp;lt;0.001) and fluoroscopy time 18.3 (14.4-26.6) min vs. 16.2 (9.8-23.4) min (p=0.037) in R-PCI patients. However, there was no significant difference between the dose-area product 4062 (2337-5990) cGycm² vs. 3747 (2238-5904) cGycm² (p=0.878) and contrast volume use 180 (140-250) ml vs. 180 (135-235) ml (p=0.370, figure 1). Twelve months after the intervention, all patients in both groups were alive. R-PCI and M-PCI had comparable rates of rehospitalisation (11.4% vs. 8.1%, p=0.903) and unscheduled PCI (4.3% vs. 2.7%, p=0.932, figure 2). Target vessel failure occurred in one vs. two patients in the R-PCI and M-PCI group, respectively (1.4% vs. 1.3%, p=0.932). Conclusion R-PCI showed a high success rate, low rates for need of manual assistance, and a very high safety profile without any complications. Also at 12-month follow-up, R-PCI was comparable to the M-PCI in all categories.Comparison of procedural characteristicsComparison of twelve-month outcome

Comparison of 600 mg VS 300 mg clopidogrel loading dose for patients with ischemic heart disease: a meta-analysis of randomized controlled trials

Abstract Background While a 600-mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300-mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether a higher clopidogrel LD regimen in primary percutaneous coronary intervention outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease. Purpose The objective of this meta-analysis is to validate current randomized trials that investigate the efficacy and safety of two clopidogrel loading regimens (600 mg vs 300 mg) in patients with ischemic heart disease treated with primary percutaneous coronary intervention. Method A systematic literature search for randomized controlled trials was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects. Result Nine randomized control studies involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only 8 studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced incidence of overall MACE (OR:0.82, 95% CI:0.74-0.91, p=0.0002), nonfatal myocardial infarction (OR:0.56; 95% CI:0.32-0.99, p = 0.15) and target vessel revascularization (OR 0.63; 95% CI 0.41 to 0.95, p = 0.03 ), without significant difference in terms of cardiac death (OR:0.89; 95% CI:0.76-1.04, p=0.15) and stroke (OR 0.92; 95% CI 0.67 to 1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR:1.27; 95% CI:1.08-1.49, p=0.005] without significant difference in minor bleeding (OR:1.05; 95% CI:0.94-1.17, p=0.35). Conclusion The administration of 600 mg of clopidogrel LD reduces the overall risk of MACE with an associated increased risk of major bleeding in patients with ischemic heart disease undergoing primary percutaneous coronary intervention.MACE OUTCOMES

Assessment of enoxaparin‐related knowledge, administration technique, and self‐reported adherence among women after caesarean section delivery

AbstractBackgroundVenous thromboembolism is among the main causes of maternal morbidity and mortality, with caesarean section (CS) delivery carrying greater risk. Outpatient thromboprophylaxis, such as enoxaparin, is administered subcutaneously and prescribed as an outpatient; raising the issue of medication adherence.AimThis study aimed to evaluate women's adherence to enoxaparin administration after CS delivery, explore the reasons for non‐adherence, and assess the factors associated with patients' adherence to enoxaparin.MethodWomen after CS delivery, who had been given enoxaparin at discharge were included in the study. Eligible patients were contacted via telephone at the middle and the end of the enoxaparin treatment. Syringe count determined the main outcome of adherence during direct telephone interviews with the patient. Optimal adherence was defined as all the doses of enoxaparin being administered and suboptimal adherence was at least one dose not administered. Ethical approval was granted by the Malaysian Registry Ethics Committee belonging to National Medical Research Registry (Reference no: NMRR ID‐22‐02859‐P41) and the study conforms with the Declaration of Helsinki. Informed consent was obtained from all participants through completion of written consent forms, after an explanation of the study was provided by investigators.ResultsOut of 201 women included, the majority (91.5%) were fully adherent to enoxaparin, while 8.5% missed at least one dose. Most patients administering at home missed the dose due to reporting they were unwell (n = 6), busy (n = 4), or forgot to administer (n = 2). Among missed doses in patients administered in a healthcare setting, all participants (n = 5) forgot to bring their medication to the appointment. Only medication knowledge had a significant association with adherence to enoxaparin administration (p = 0.008).ConclusionThe study raised concern about the substantial percentage of patients missing at least one dose of enoxaparin, particularly among patients injecting at home. Initiatives should focus on customised enoxaparin administration counselling and providing educational materials.

Traumatic Optic Neuropathy Treatment Trial 2 (TONTT-2): evaluating the efficacy of different doses of erythropoietin – a multicentre, randomised, double-blind clinical trial

AimThe aim is to compare the efficacy and safety of three different weight-adjusted intravenous erythropoietin (EPO) doses in patients with indirect traumatic optic neuropathy (TON).MethodsThis study is a multicentre, randomised,...

Genetic profiling of NUDT15 in the Slovenian population.

Determining variant TPMT alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the TPMT-adjusted thiopurine dosing, some TPMT wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene NUDT15 has emerged as a significant co-modulator of thiopurine therapy. Initially, NUDT15 was considered important predominantly in Asian populations, but recent studies have highlighted its relevance in European populations as well.To evaluate the pharmacogenetic significance of NUDT15 in the Slovenian population, we sequenced extended regions of exon 1 and exon 3 in 109 healthy individuals and 37 patients with acute lymphoblastic leukemia.We identified eight variants, including one with established clinical significance (allele *3) and one extremely rare variant (Chr13 at 48045861; GRCh38, NC_000013.11). The frequencies of most previously described variants in both the general population and in the ALL cohort were consistent with those reported in other European populations, except for rs45465203, which was less frequent in the Slovenian population. None of the variants, except for NUDT15*3, were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.

Lipschütz ulcer following first dose of COVID-19 tozinameran vaccine: Report of a case and review of a World Health Organization pharmacovigilance database.

Lipschütz ulcer (LU) is a condition known for painful vulvar ulcers, typically affecting young women and often linked to infectious agents. Recent reports have indicated a potential connection between LU and COVID-19 vaccination, particularly after the second or booster doses. This study presents a case of LU following the first dose of tozinameran in a young woman who had a previous SARS-CoV-2 infection and investigates similar cases globally. An 18-year-old woman experienced vulvar pain and ulcers 2-days after her initial COVID-19 vaccine dose. After ruling out infections through serological tests, a diagnosis of LU was made, and her symptoms resolved after 10 days. A literature search and VigiBase® analysis revealed 11 cases of LU following COVID-19 vaccination, and 519 vulvovaginal ulcer cases associated with these vaccines were identified in Vigibase®, with a median onset of 2 days. Most LU cases occurred after the second dose or booster shots. The primary hypothesis for this association is a type 3 hypersensitivity reaction mediated by immune complexes, possibly triggered by prior exposure, as many cases occurred after the second dose. Interestingly, the presented case suggests that prior COVID-19 infection could serve as sensitization. In conclusion, this study highlights the potential occurrence of LU after the initial COVID-19 vaccine dose in young patients with prior COVID-19 infection. While the risk of recurrence after subsequent vaccinations or infections remains uncertain, the benefits of vaccination outweigh the risks. Clinicians and patients should be aware of this potential issue to make informed decisions regarding vaccination.