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Background: Since the 1970s, studies have examined potential risk factors associated with adverse drug reactions (ADRs) in a variety of settings. However, no pharmacoepidemiological study exists that incorporates clinical and laboratory parameters in a multiple regression model in order to consider predictors for ADRs.Objectives: To characterize risk factors associated with ADRs in patients admitted to university hospital departments of internal medicine.Design and Setting: Intensive pharmacovigilance was carried out in departments of internal medicine of two university hospitals. All admissions were followed prospectively for the occurrence of ADRs by members of a pharmacoepidemiological team consisting of physicians, pharmacologists and pharmacists. To identify patients at high risk for experiencing ADRs, patient histories and several clinical and laboratory data, determined at the time of admission, were taken into consideration. In addition to the drug prescribed, 40 parameters defined vital status at admission. These included temperature, heart rate, blood pressure (systolic-diastolic), body mass index, nicotine and alcohol use, and first laboratory test results after admission on nutrition status, inflammation, liver, kidney, pancreas or thyroid status, electrolytes, blood count and coagulation.Results: 907 patients were observed during the study period. The mean age of the study population was 60 +/- 16 years. The median number of different drugs administered per patient during hospitalization was 9.6 +/- 7.7. In 345 patients, 592 ADRs were evaluated: 33.4% possible, 61.5% probable and 4.7% highly probable. Two ADR-related deaths were observed during the study period. Analysing ADR predictors, 17 of 40 parameters reached significance in univariate analysis, but only five in a multivariate binary regression model: raised temperature (odds ratio [OR] 1.609; 95% CI 1.133, 2.285), low erythrocyte levels (OR 0.386; 95% CI 0.194, 0.768), low thrombocyte levels (OR 0.788, 95% CI 0.627, 0.989), high number of drugs (OR 1.117; 95% CI 1.076, 1.159) and female sex (OR 1.562; 95% CI 0.785, 2.013) were independent predictors for ADRs.Conclusion: For the patients investigated, of the large number of clinical data available only five independent factors predict ADR occurrence. Taking these results into account, physicians will be able to focus early on patients at risk for ADRs. To minimize ADR occurrence, ADR predictors should be integrated into the clinical pathway. [ABSTRACT FROM AUTHOR]

Objectives: Different approaches to partition the attributable risk into exposure-specific components are methodologically evaluated.Methods: Two methods of partitioning the attributable risk in a multifactorial situation have been suggested. One is based on a solution adopted from game theory, the Shapley value, whereas the other recently suggested approach uses a heuristically motivated proportional weighting scheme. These two concepts are reviewed and compared in a situation with three exposure factors. A hypothetical numerical example is discussed illustrating differences in the case of complex interaction structures.Results: The two methods are found to differ in two critical features that affect the outcome of partitioning: i) including or ignoring the full interaction structure between exposure factors involved in the partitioning, ii) using an equal or proportional weighting scheme for the marginal excess risks of the exposures. As a result, not only the individual partial attributable risks for the exposure factors may be quantitatively different between the methods, but also their ranking depends on the partitioning approach.Conclusions: The epidemiologic properties of the partitioning procedure based on the Shapley value are known and fit to the needs of epidemiologic applications. The alternative approach recently suggested can lead to considerably different results. As long as its epidemiologic properties are not fully understood, the traditional partitioning method should be given preference in practical applications. [ABSTRACT FROM AUTHOR]

The effect of ethanol on muscarine-stimulated release of [3H]NE was studied using the rat pheochromocytoma cell line, PC12. At concentrations of 25 mM and above, ethanol produced a dose dependent inhibition of muscarine-stimulated release of [3H]NE. The inhibition of musacrine-stimulated transmitter release occurred in the absence of any effect of ethanol on [3H]NE uptake, metabolism or on muscarinic binding to the cells. However, ethanol produced an inhibition of muscarine-stimulated elevation of intracellular free Ca2+ which corresponded with the inhibition of transmitter release. At concentrations greater than 100mM, ethanol produced both a stimulation of the release of [3H]NE as well as an increase in intracellular free Ca2+. The increase in basal transmitter release and itnracellular Ca2+ occurred independent of this inhibition by ethanol of muscarine-stimulated elevation of intracellular free Ca2+ or transmitter secretion. These results demonstrate the relationship of the effects of ethanol on cellular free Ca2+ and neurotransmitter release. [ABSTRACT FROM PUBLISHER]

Background and Objectives More knowledge about the reasons for non-return of blood donors (BD) would enable blood donation services (BDS) to improve the efficacy of recruitment and retention programmes. We interviewed returning (RBD) and non-returning apheresis BDs (NRBD) of our university hospital-based BDS. Materials and Methods A questionnaire was sent to 1218 individuals who passed the initial health check with no more than one subsequent blood donation. A similar questionnaire was answered by 235 randomly incoming RBDs. We asked for age, sex, profession, education level, motives to donate blood and, if applicable, reasons for non-return. These data were compared between NRBDs and RBDs and were analysed in relationship to the reasons for non-return. Results We received 267 answered questionnaires (21·9%). As 32 individuals indicated that they had been permanently deferred and 47 BDs had donated blood elsewhere, 188 NRBDs remained for further analysis. We found more women than men among NRBDs. Medical professions were less likely to return than students and trainees. Individuals motivated by personal experience, remuneration or a free health check were more likely to return than others. Whereas logistic reasons were of highest relevance for non-return in general, women indicated anxiety of blood donation as reason for non-return more often than men. Conclusion Reducing women's anxiety of blood donation, reminding medical professions more intensively on blood donation and appealing to personal experience or a free health check may be the most promising approaches to increase BDs’ return rates. [ABSTRACT FROM AUTHOR]

Inhibition of vascular endothelial growth factor (VEGF) by gene transfer techniques was effectively applied to control experimental tumor growth, whereas effects on systemic VEGF levels had not been investigated. Therefore, we evaluated the effect of VEGF inhibition by adenoviral-mediated gene delivery of a dominant-negative soluble fragment of FLK-1 (sFlk-1) on systemic VEGF levels, organ-specific VEGF-RNA expression and antitumor efficacy in a murine colorectal cancer (CRC) tumor model. Vector function of AdsFlk-1 was shown by Western blot analysis and transgene expression was documented over a time period of 42 days in the serum of treated mice. Although cell supernatant of CT26 cells contained considerable levels of VEGF, systemic VEGF levels in the serum of tumor-bearing mice remained unaffected. Interestingly, mice that were systemically treated with AdsFlk-1 showed a strong upraise of circulating VEGF, whereas VEGF remained at background levels in the control. Vascular endothelial growth factor was increased not only in tumor bearing but also in healthy, tumor-free mice. Vascular endothelial growth factor determination in liver tissue homogenates showed a 16.5-fold upraise in AdsFlk-1-treated animals as compared to the AdLacZ control. Consecutively, systemic small interfering RNA injection targeted against VEGF reverted elevated VEGF levels almost back to normal levels. In spite of elevated VEGF levels, AdsFlk-1 administration showed significant antitumor effects in a subcutaneous metastatic CRC tumor model. There was no significant correlation between antitumour treatment response and VEGF levels in this model. Collectively, we conclude that the systemic administration of AdsFlk-1 had significant inhibitory effects on metastatic CRC tumor growth in spite of elevated systemic VEGF levels and that VEGF serum concentrations did not correlate to tumor burden and antitumor treatment response in this model.Gene Therapy (2006) 13, 1198–1205. doi:10.1038/sj.gt.3302772; published online 13 April 2006 [ABSTRACT FROM AUTHOR]

Purpose: The region of growth (ROG) of geographic atrophy (GA) throughout the macular area has an impact on visual outcomes. Here, we developed multiple deep learning models to predict the 1-year ROG of GA lesions using fundus autofluorescence (FAF) images., Design: In this retrospective analysis, 3 types of models were developed using FAF images collected 6 months after baseline to predict the GA lesion area (segmented lesion mask) at 1.5 years, FAF images collected at baseline and 6 months to predict the GA lesion at 1.5 years, and FAF images collected 6 months after baseline to predict the GA lesion at 1 and 1.5 years. The 1-year ROG from the 6-month visit was derived by taking the difference between the GA lesion area (segmented lesion mask) at the 1.5-year and 6-month visits., Participants: Patients enrolled in the following lampalizumab clinical trials and prospective observational studies: NCT02247479, NCT02247531, NCT02479386, and NCT02399072., Methods: Datasets of study eyes from 597 patients were split into model training (310), validation (78), and test sets (209), stratified by baseline or initial lesion area, lesion growth rate, foveal involvement, and focality. Deep learning experiments were performed using the 2-dimensional U-Net; whole-lesion and multiclass models were developed., Main Outcome Measures: The performance of the models was evaluated by calculating the Dice score, coefficient of determination (R 2 ), and the squared Pearson correlation coefficient (r 2 ) between the true and derived GA lesion 1-year ROG., Results: The model using baseline and 6-month FAF images to predict GA lesion enlargement at 1.5 years had the best performance for the derived 1-year ROG. Mean Dice scores were 0.73, 0.68, and 0.70 in the training, validation, and test sets, respectively. The R 2 (0.77, 0.53, and 0.79) and r 2 (0.83, 0.61, and 0.79) showed similar trends across the 3 sets., Conclusions: These findings show the potential of using baseline and/or 6-month visit FAF images to predict 1-year GA ROG using a deep learning approach. This work could potentially help support decision-making in clinical trials and more informed treatment decisions in clinical practice., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Background: There is currently no practice-based, multicenter database of poisoned patients admitted to intensive care units (ICUs). The INTOXICATE study, endorsed by the ESICM and EAPCCT, aimed to determine the rate of eventful admissions among acutely intoxicated adult ICU patients., Methods: Ethical approval was obtained for this multicenter, prospective observational study, and data-sharing agreements were signed with each participating center. An electronic case report form was used to collect data on patient demographics, exposure, clinical characteristics, investigations, treatment, and in-hospital mortality data. The primary outcome, 'eventful admission', was a composite outcome defined as the rate of patients who received any of the following treatments in the first 24 h after the ICU admission: oxygen supplementation with a FiO2 > 40%, mechanical ventilation, vasopressors, renal replacement therapy (RRT), cardiopulmonary resuscitation, antidotes, active cooling, fluid resuscitation (> 1.5 L of intravenous fluid of any kind), sedation, or who died in the hospital., Results: Seventy-eight ICUs, mainly from Europe, but also from Australia and the Eastern Mediterranean, participated. A total of 2,273 patients were enrolled between November 2020 and June 2023. The median age of the patients was 41 years, 72% were exposed to intoxicating drugs. The observed rate of patients with an eventful ICU admission was 68% (n = 1546/2273 patients). The hospital mortality was 4.5% (n = 103/2273)., Conclusions: The vast majority of patients survive, and approximately one third of patients do not receive any ICU-specific interventions after admission in an intensive care unit for acute intoxication. High-quality detailed clinical data have been collected from a large cohort of acutely intoxicated ICU patients, providing information on the pattern of severe acute poisoning requiring intensive care admission and the outcomes of these patients., Trial Registration: OSF registration ID: osf.io/7e5uy., (© 2024. The Author(s).)

Purpose: To analyze whether sociodemographic characteristics influence the substance choice and preclinical and clinical course of suicidal poisoning., Methods: This was a retrospective single-center study in patients hospitalized due to suicidal poisoning and who received at least one psychiatric exploration during their inpatient stay. Patients' sociodemographic, anamnestic, preclinical, and clinical parameters were analyzed with respect to sex and age., Results: 1090 patients were included, 727 (67%) were females, median age was 39 years (min-max: 13-91) with 603 (55%) aged 18-44 years. 595 patients (54.8%) ingested a single substance for self-poisoning, 609 (59.5%) used their own long-term medication. Comparing to males, females preferred antidepressants (n = 223, 30.7%, vs n = 85, 23.4%; p = 0.013) and benzodiazepines (n = 202, 27.8%, vs n = 65, 17.9%; p < 0.001); males more often used cardiovascular drugs (n = 33, 9.1%, vs n = 34, 4.7%; p = 0.005) and carbon monoxide (n = 18, 5.0%, vs n = 2, 0.3%; p < 0.001). Use of Z-drugs (n = 1, 1.7%, to n = 37, 33.3%; p < 0.001) and benzodiazepines (n = 4, 6.9%, to n = 33, 29.7%; p = 0.003) increased with age (< 18 to > 64 years), while use of non-opioid analgesics (n = 23, 39.7%, to n = 20, 18.0%; p < 0.001) decreased. Average dose of substance in patients > 64 years was 12.9 ± 18.4 times higher than recommended maximum daily dose (compared to 8.7 ± 15.2 higher in those aged < 18 years; p < 0.001). Males more often required intensive care (n = 150, 41.3%, vs n = 205 females, 28.2%; p < 0.001)., Conclusion: These results underline the complexity of (para-)suicidal poisonings and identify potential measures for their prevention, such as restricting access and better oversight over the use of certain substances., (© 2024. The Author(s).)

Background: Toxicological analysis of patients with acute recreational drug poisoning can improve our understanding of substance use patterns, clinical symptoms, and improve treatment. Patient history alone may be incomplete or misleading. The objective was to assess the differences in patient history and analytical results, to describe the clinical characteristics, implications and hospital management, and to describe the drug use pattern over time., Methods: A retrospective study including all patients admitted to our toxicology unit with recreational drug toxicity and analytical testing from October 2014 to December 2022., Results: 872 patients were included. Patient history revealed a median of one ingested substance class: opiates/opioids, benzodiazepines/Z-drugs, and Pregabalin were predominant. Urine analysis revealed a median of three ingested substance classes ( p < 0.001). Benzodiazepines/Z-drugs, Pregabalin, and THC were severely underreported. Agitation and aggression, anxiety, hallucinations, and psychosis were frequent, associated with cocaine, cathinone/phenethylamine, and amphetamine/MDMA detection and required sedation. Coma was also frequent, associated with opiate/opioid, benzodiazepine/Z-drug, GBL/GHB, and Pregabalin detection and required intubation, and/or application of Naloxone and/or Flumazenil. Twelve patients arrived in cardiac arrest; all were positive for opiates/opioids. Four patients died: three with Benzodiazepines/Z-drugs, Pregabalin and opiates/opioids detected, one with cathinones/phenethylamines detected. While cathinones/phenethylamines and synthetic cannabinoid receptor agonists were mainly detected between 2014-2016, detection decreased significantly between 2017-2022 after NPS legislation passed. Pregabalin detection increased., Conclusions: Patient history is inaccurate, and patients frequently underreport ingested drugs. Opiates and opioids are still the main cause of morbidity and mortality. Pregabalin is increasingly abused. NPS legislation effectively decreased cathinone/phenethylamine and synthetic cannabinoid receptor agonist overdoses.