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Naunyn-Schmiedeberg's Archives of... Jun 2024Little is known about how pharmacological and toxicological knowledge evolves. The aim of this study was to investigate the changes in the presentation of the poison...
Little is known about how pharmacological and toxicological knowledge evolves. The aim of this study was to investigate the changes in the presentation of the poison hydrogen cyanide in sixteen German-language pharmacology and toxicology textbooks from 1878 to 2020. The categories of structure, molecular mechanism of action, occurrence, effects, resorption, areas of application, lethal dose, acute symptoms of intoxication, treatment of hydrogen cyanide poisoning, and recommended therapeutic preparations were evaluated. The knowledge on the structure, lethal dosage, and occurrence of hydrogen cyanide has remained constant. In contrast, knowledge on molecular mechanism of action and recommended preparations of the poison has changed dramatically. Until 1944, the binding of hydrogen cyanide to hemoglobin was considered the mechanism of action, whereas from 1951 onwards, the interaction of hydrogen cyanide with the Fe of cytochrome oxidase was described. The number of preparations containing hydrogen cyanide decreased into obsolescence until 1951. The areas of application of hydrogen cyanide also show a change, as from 1919 onwards, mainly industrial areas of application of the poison are described instead of medical ones, and from 1951 onwards, criminalistic areas of application are also mentioned. Thus, pharmacological and toxicological knowledge develops non-linearly, molecular mechanism and uses being the most dynamic areas, whereas the knowledge about hydrogen cyanide's chemical structure, lethal dose, and occurrence remained constant. Older pharmacology and toxicology textbooks were better than newer ones at discussing changes in scientific concepts. Pharmacology and toxicology textbooks also mostly failed to discuss the misuse of hydrogen cyanide (Zyklon B) during the Nazi regime, missing an important opportunity to showcase the ethical responsibility of pharmacology and toxicology. Thus, future pharmacology and toxicology textbooks should improve on discussing the development of pharmacological and toxicological concepts and the ethical responsibility of the discipline.
PubMed: 38900251
DOI: 10.1007/s00210-024-03227-z -
Indian Journal of Dermatology,... Jun 2024Background Several studies have reported that psoriasis has a positive correlation with type 2 diabetes mellitus (DM). Understanding the risk of psoriasis in diabetic...
Background Several studies have reported that psoriasis has a positive correlation with type 2 diabetes mellitus (DM). Understanding the risk of psoriasis in diabetic patients is significant because it allows for early intervention and potential insights into the common pathways between the two conditions. Objectives We analysed the risk of psoriasis according to the estimated glomerular filtration rate (eGFR) and proteinuria level in DM patients using Korean population-based data. Methods This study was a retrospective cohort study using data collected from the country in the form of exploratory data analysis. A total of 927,234 participants diagnosed with DM were enrolled. Patients under the age of 20 with existing psoriasis or psoriasis developed within 1 year and missing data were excluded. The development of psoriasis was the primary outcome within a follow-up period of 7.83 ± 1.68 years. Results Of the 840,395 final participants, 28,010 (3.33%) patients developed psoriasis. In multivariate-adjusted Cox proportional hazards regression models, the DM patients with eGFR < 30 had a higher risk of psoriasis after adjustment (eGFR 60-90, hazard ratio [HR] 1 (Ref.); eGFR < 30, HR 1.173, 95% CI 1.089-1.264). In addition, there was an increased psoriatic risk of patients with DM and proteinuria after adjustment (negative, HR 1 (Ref.); 2+, HR 1.164, 95% CI 1.080-1.254; 3+, HR 1.433, 95% CI 1.273-1.613; 4+, HR 1.508, 95% CI 1.177-1.931). Limitations The severity of psoriasis was not measured since the occurrence of psoriasis was the outcome. Details of oral hypoglycaemic agents such as type and dose were not investigated. Conclusion This study showed that a decrease in eGFR and aggravation of proteinuria increase the risk of psoriasis in diabetic patients. Therefore, by using eGFR and proteinuria as predictive risk factors of psoriasis in DM patients, early and proactive treatment may play a vital role in managing diabetic patients.
PubMed: 38899413
DOI: 10.25259/IJDVL_669_2023 -
Journal of Clinical Medicine May 2024A complete medication plan (MPlan) increases medication safety and adherence and is crucial in care transitions. Countries that implemented a standardized MPlan reported...
A complete medication plan (MPlan) increases medication safety and adherence and is crucial in care transitions. Countries that implemented a standardized MPlan reported benefits on patients' understanding and handling of their medication. Austria lacks such a standardization, with no available data on the issue. This study aimed to investigate the current state of all medication documentations (MDocs) at hospital admission in a population at high risk for polypharmacy in Austria. We enrolled 512 consecutive patients undergoing elective coronary angiography. Their MDocs and medications were recorded at admission. MDocs were categorized, whereby a MPlan was defined as a tabular list including medication name, dose, route, frequency and patient name. Out of 485 patients, 55.1% had an MDoc (median number of drugs: 6, range 2-17), of whom 24.7% had unstructured documentation, 18.0% physicians' letters and 54.3% MPlans. Polypharmacy patients did not have a MDoc in 31.3%. Crucial information as the patients's name or the originator of the MDoc was missing in 31.1% and 20.4%, respectively. Patients with MDoc provided more comprehensive medication information ( = 0.019), although over-the-counter-medication was missing in 94.5% of MDocs. A discrepancy between the MPlan and current medication at admission existed in 64.4%. In total, only 10.7% of our patient cohort presented an MPlan that was in accordance with their current medication. The situation in Austria is far from a standardized MPlan generated in daily routine. Numerous MPlans do not represent the current medication and could pose a potential risk for the effectiveness and safety of pharmacotherapy.
PubMed: 38892897
DOI: 10.3390/jcm13113187 -
Healthcare (Basel, Switzerland) May 2024Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are...
BACKGROUND
Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are limited. This study aimed to investigate the in-depth experiences and impacts of IMD on AYAs.
METHODS
Participants were recruited from two Australian states, Victoria and South Australia. We conducted qualitative, semi-structured interviews with 30 patients diagnosed with IMD between 2016 and 2021. The interview transcripts were analyzed thematically.
RESULTS
Of the participants, 53% were aged 15-19 years old, and 47% were aged 20-24. The majority (70%) were female. Seven themes relating to the participants' experience of IMD were identified: (1) underestimation of the initial symptoms and then rapid escalation of symptoms; (2) reliance on social support for emergency care access; (3) the symptoms prompting seeking medical care varied, with some key symptoms missed; (4) challenges in early medical diagnosis; (5) traumatic and life-changing experience; (6) a lingering impact on HRQoL; and (7) gaps in the continuity of care post-discharge.
CONCLUSION
The themes raised by AYA IMD survivors identify multiple areas that can be addressed during their acute illness and recovery. Increasing awareness of meningococcal symptoms for AYAs may help reduce the time between the first symptoms and the first antibiotic dose, although this remains a challenging area for improvement. After the acute illness, conducting HRQoL assessments and providing multidisciplinary support will assist those who require more intensive and ongoing assistance during their recovery.
PubMed: 38891151
DOI: 10.3390/healthcare12111075 -
BMC Medicine Jun 2024Most women use medication during pregnancy. Pregnancy-induced changes in physiology may require antenatal dose alterations. Yet, evidence-based doses in pregnancy are...
BACKGROUND
Most women use medication during pregnancy. Pregnancy-induced changes in physiology may require antenatal dose alterations. Yet, evidence-based doses in pregnancy are missing. Given historically limited data, pharmacokinetic models may inform pregnancy-adjusted doses. However, implementing model-informed doses in clinical practice requires support from relevant stakeholders.
PURPOSE
To explore the perceived barriers and facilitators for model-informed antenatal doses among healthcare practitioners (HCPs) and pregnant women.
METHODS
Online focus groups and interviews were held among healthcare practitioners (HCPs) and pregnant women from eight countries across Europe, Africa and Asia. Purposive sampling was used to identify pregnant women plus HCPs across various specialties prescribing or providing advice on medication to pregnant women. Perceived barriers and facilitators for implementing model-informed doses in pregnancy were identified and categorised using a hybrid thematic analysis.
RESULTS
Fifty HCPs and 11 pregnant women participated in 12 focus groups and 16 interviews between January 2022 and March 2023. HCPs worked in the Netherlands (n = 32), the UK (n = 7), South Africa (n = 5), Uganda (n = 4), Kenya, Cameroon, India and Vietnam (n = 1 each). All pregnant women resided in the Netherlands. Barriers and facilitators identified by HCPs spanned 14 categories across four domains whereas pregnant women described barriers and facilitators spanning nine categories within the same domains. Most participants found current antenatal dosing information inadequate and regarded model-informed doses in pregnancy as a valuable and for some, much-needed addition to antenatal care. Although willingness-to-follow model-informed antenatal doses was high across both groups, several barriers for implementation were identified. HCPs underlined the need for transparent model validation and endorsement of the methodology by recognised institutions. Foetal safety was deemed a critical knowledge gap by both groups. HCPs' information needs and preferred features for model-informed doses in pregnancy varied. Several pregnant women expressed a desire to access information and partake in decisions on antenatal dosing.
CONCLUSIONS
Given the perceived limitations of current pharmacotherapy for pregnant women and foetuses, model-informed dosing in pregnancy was seen as a promising means to enhance antenatal care by pregnant women and healthcare practitioners.
Topics: Humans; Female; Pregnancy; Qualitative Research; Focus Groups; Health Personnel; Pregnant Women; Adult; Prenatal Care; Africa; Asia; Europe; Uganda
PubMed: 38886762
DOI: 10.1186/s12916-024-03450-8 -
The International Journal of Risk &... Jun 2024The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the...
BACKGROUND
The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the baseline rate varies with age. Time-varying baseline risk adjustments with data from unexposed cohorts are utilised. Self-controlled risk interval (SCRI), with a shorter observation period, can also mitigate the problem by studying a control period close to the risk period.
OBJECTIVE
An Indian rotavirus vaccine has previously been studied using SCCS. The risk of intussusception in the high-risk windows (21 days after vaccination) was comparable to the background risk. The aim was to re-analyse data of an existing SCCS study using alternate statistical methods to examine vaccine safety.
METHODS
We examined the mean age of intussusception in the vaccinated and the unvaccinated. We performed an SCRI analysis of the surveillance data from the SCCS study, limiting the observation period to 180 days. We analysed the time-to-intussusception from the last vaccination. Finally, we performed an SCCS analysis, excluding unvaccinated cases from the analysis.
RESULTS
We found that the mean age of intussusception was significantly lower in the vaccinated (205 days) compared to the unvaccinated (223 days) (p-value 0.0026). The Incident Risk Ratio (IRR) on SCRI analysis was 1.62 (95% CI 1.07-2.44). There were significantly more intussusceptions in the first 30 days after vaccination compared to the next 30-day window. (92 vs 63 p-value = 0.009). We found that excluding unvaccinated infants from the SCCS analysis demonstrated significantly increased risk for the risk period 1-21 days after the 3rd dose (IRR 2.47, 95% CI 1.70-3.59). The risks of intussusception were missed in traditional SCCS analysis using unvaccinated infants as controls.
CONCLUSION
Traditional risk adjustments using data from unexposed cohorts in SCCS may not be appropriate for investigating the risk of intussusception where vaccination lowers the mean age of intussusception.
PubMed: 38875047
DOI: 10.3233/JRS-230049 -
Acta Neurochirurgica Jun 2024The management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main...
BACKGROUND
The management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main issue in debate are the dose and initiation time of pharmacologic VTE prevention to balance the risk of VTE-based morbidity and potentially life-threatening bleeding. Mechanical VTE prophylaxis with intermittend pneumatic compression (IPC), however, is established in only a few neurosurgical hospitals, and its efficacy has not yet been demonstrated. The objective of the present study was to analyze the risk of VTE before and after the implementation of IPC devices during elective neurosurgical procedures.
METHODS
All elective surgeries performed at our neurosurgical department between 01/2018-08/2022 were investigated regarding the occurrence of VTE. The VTE risk and associated mortality were compared between groups: (1) only chemoprophylaxis (CHEMO; surgeries 01/2018-04/2020) and (2) IPC and chemoprophylaxis (IPC; surgeries 04/2020-08/2022). Furthermore, general patient and disease characteristics as well as duration of hospitalization were evaluated and compared to the VTE risk.
RESULTS
VTE occurred after 38 elective procedures among > 12.000 surgeries. The number of VTEs significantly differed between groups with an incidence of 31/6663 (0.47%) in the CHEMO group and 7/6688 (0.1%) events in the IPC group. In both groups, patients with malignant brain tumors represented the largest proportion of patients, while VTEs in benign tumors occurred only in the CHEMO group.
CONCLUSION
The use of combined mechanical and pharmacologic VTE prophylaxis can significantly reduce the risk of postoperative thromboembolism after neurosurgical procedures and, therefore, reduce mortality and morbidity.
Topics: Humans; Neurosurgical Procedures; Venous Thromboembolism; Female; Male; Middle Aged; Intermittent Pneumatic Compression Devices; Aged; Adult; Postoperative Complications; Retrospective Studies; Elective Surgical Procedures; Anticoagulants; Risk Factors
PubMed: 38874608
DOI: 10.1007/s00701-024-06129-4 -
Genome Medicine Jun 2024Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk...
BACKGROUND
Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population.
METHODS
To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRS). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants.
RESULTS
Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose-response effect of PRS on incident colorectal neoplasms. Incorporating PRS with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32).
CONCLUSIONS
Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity.
Topics: Humans; Colorectal Neoplasms; Female; Early Detection of Cancer; Male; Middle Aged; Aged; Risk Assessment; Polymorphism, Single Nucleotide; Bayes Theorem; Risk Factors
PubMed: 38872215
DOI: 10.1186/s13073-024-01355-y -
Expert Review of Neurotherapeutics Jun 2024To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most...
BACKGROUND
To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important.
DESIGN AND METHODS
The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used.
RESULTS
Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.
PubMed: 38870024
DOI: 10.1080/14737175.2024.2365312 -
The International Journal of Pharmacy... Jun 2024Medication recycling within hospitals has proven financial and possible environmental benefits according to local evaluations done in British Columbia. Despite this, the...
BACKGROUND
Medication recycling within hospitals has proven financial and possible environmental benefits according to local evaluations done in British Columbia. Despite this, the extent of medication recycling in Canadian hospitals remains unclear in the literature.
OBJECTIVE(S)
To determine if Canadian hospitals recycle medications, provide an estimate of how much medication is recycled by dosage form, and identify medication recycling barriers through the distribution of a cross-sectional survey.
METHODS
A nine-question survey was distributed to 171 hospital pharmacy departments across Canada that consented to complete the survey. The survey identified whether sites recycled unused medications, an estimate of how much is recycled based on dosage form, and barriers to recycling.
KEY FINDINGS
Of 62 respondents, the majority indicated they do have medication recycling procedures; however, the frequency of recycling is suboptimal (30-50% of medications are not recycled), and not all medication types are always recycled. Individually packaged oral tablets were most often recycled, and oral liquid medications were least often recycled. Many multi-dose medications were not tamper-proofed. Most respondents selected "sanitization/infection control" and "resource constraint" as reasons for not recycling all medications.
CONCLUSIONS
Among respondents, the proportion and type of unused medicines that are recycled varied. For sites that did not respond, this might suggest that medication recycling is not a priority. This could represent a missed opportunity to standardize practices and increase medication recycling in hospitals, both of which could represent a meaningful step towards responsible use of medications and reduction of negative impacts on human health and the environment.
PubMed: 38865359
DOI: 10.1093/ijpp/riae026