Withdrawal Symptoms Research Articles

Patterns of Use and Withdrawal Syndrome in Dual Cannabis and Tobacco Users (DuCATA_GAM-CAT): Protocol for a Mixed Methods Study

Background Approximately 1 in 6 cannabis users develop a cannabis use disorder (CUD) and the odds increase to 1 in 2 for daily users. Objective The Dual use of Cannabis and Tobacco Monitoreing through a Gamified Web app (DuCATA_GAM-CaT) project aims to identify cannabis-tobacco patterns of use and withdrawal symptoms among individuals with CUD who are attending substance abuse programs. Methods The project uses a mixed methods approach consisting of 3 studies. First, a participatory qualitative study involves focus groups comprising individuals with CUD, clinicians, project researchers, and an expert gamification company to co-design a gamified web app. Second, a longitudinal prospective study to follow up individuals over 6 weeks with CUD attending substance abuse programs . Participants report their cannabis-tobacco usage patterns, type and frequency of tobacco use, nicotine dependence, withdrawal symptoms, psychoemotional factors, and motivation to quit both substances. Predictive analysis techniques are used to analyze clinical, demographic, psychological, and environmental data to predict the probability of achieving abstinence. Third, homogeneous focus groups to explore participants’ experiences during their CUD treatment. Results By June 2024, the project had completed the first study, defining eligible cannabis user profiles, developed the initial web app prototype, and initiated recruitment across 10 centers, with 74 participants enrolled, aiming to reach 150 participants in total. Conclusions All participants are required to provide informed consent, and their information is kept confidential and anonymized following confidentiality rules. The research team is committed to disseminating the results obtained to professional and patient groups, as well as informing public health agents, to positively influence political and social decision makers and design programmers. Additionally, we aim to prioritize the publication of the results in high-impact journals specialized in drug abuse, public health, and health care services research. Trial Registration ClinicalTrials.gov NCT05512091; https://clinicaltrials.gov/study/NCT05512091 International Registered Report Identifier (IRRID) DERR1-10.2196/58335

Severe exacerbation of facial dermatitis with swelling following introduction of abrocitinib in a patient with atopic dermatitis

BackgroundAbrocitinib, an oral small-molecule Janus kinase 1 (JAK1) inhibitor, has been widely accepted for the treatment of moderate-to-severe atopic dermatitis (AD). Currently there is a paucity of data on the adverse events (AEs) after abrocitinib treatment, especially on rare events such as exacerbation of facial dermatitis, and their causal relationship and subsequent management remains poorly elucidated.Case presentationA 43-year-old female patient with moderate AD received dupilumab after failure of topical treatments. Facial dermatitis persisted and became refractory after dupilumab treatment, and the patient changed treatment to oral abrocitinib. Fifteen hours after the first dose of abrocitinib, she developed exacerbation of facial dermatitis with swelling. The patient was initially diagnosed as abrocitinib-induced hypersensitivity. However, a score of 3 of the Naranjo adverse drug reaction assessment indicates week correlation between abrocitinib therapy and exacerbation of facial dermatitis, and negative results from subsequent drug provocation test further suggests no causal relationship.ConclusionsThe present case report highlights the necessity of careful determination of abrocitinib-induced hypersensitivity, which should not be diagnosed simply based on the time sequence between drug exposure and symptom occurrence. In addition, caution should be exercised for drug withdrawal, especially when confirmative evidence is absent. Drug provocation test can be helpful and effective treatments could be continued unless severe AEs occur.

The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: A systematic review and meta-analysis.

The aim of this study was to investigate whether interventions to discontinue or down-titrate heart failure (HF) pharmacotherapy are feasible and associated with risks in older people. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to 8 March 2023. Randomized controlled trials (RCTs) and observational studies included people with HF, aged ≥50 years and who discontinued or down-titrated HF pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalization, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2< 70%). Sub-analysis by frailty status was conducted. Six RCTs (536 participants) and 27 observational studies (810 499 participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable chronic HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% more likely than continuation (risk ratio [RR] 1.76, 95% confidence interval [CI] 1.14-2.73), with no difference in mortality (RR 0.64, 95% CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95% CI 0.68-1.47). Participants were 25% more likely to re-initiate discontinued diuretics (RR 0.75, 95% CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalization compared to continuation. Worsening HF was the most common ADWE. One observational study measured frailty but did not report outcomes by frailty status. The appropriateness and associated risks of down-titrating or discontinuing HF pharmacotherapy in people aged ≥75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.

Correlates of fentanyl preference among people who use drugs in Rhode Island

BackgroundFentanyl is increasingly pervasive in the unregulated drug supply and is a driver of drug overdose deaths in the United States. The aims of this study were to characterize and identify correlates of fentanyl preference among people who use drugs (PWUD) in Rhode Island (RI).MethodsUsing bivariate analysis, we examined associations between fentanyl preference and sociodemographic and psychosocial characteristics at baseline among participants enrolled in the RI Prescription Drug and Illicit Drug Study from August 2020-February 2023. Fentanyl preference was operationalized based on responses to a five-point Likert scale: “I prefer using fentanyl or drugs that have fentanyl in them.” Participants who responded that they “strongly disagree,” “disagree,” or were “neutral” with respect to this statement were classified as not preferring fentanyl, whereas participants who responded that they “agree” or “strongly agree” were classified as preferring fentanyl.ResultsAmong 506 PWUD eligible for inclusion in this analysis, 15% expressed a preference for fentanyl or drugs containing fentanyl as their drug of choice. In bivariate analyses, preference for fentanyl was positively associated with younger age, white race, lifetime history of overdose, history of injection drug use, past month enrollment in a substance use treatment program, past month treatment with medications for opioid use disorder, and preferences for heroin and crystal methamphetamine (all p < 0.05). Descriptive data yielded further insight into reasons for fentanyl preference, the predominant having to do with perceived effects of the drug and desire to avoid withdrawal symptoms.ConclusionsOnly a relatively small subset of study participants preferred drugs containing fentanyl. Given the increased prevalence of fentanyl contamination across substances within the unregulated drug market, the result for PWUD is increasingly less agency with respect to choice of drug; for example, people may be forced to use fentanyl due to restricted supply and the need to mitigate withdrawal symptoms, or may be using fentanyl without intending to do so. Novel and more effective interventions for PWUD, including increased access to age-appropriate harm reduction programs such as fentanyl test strips and overdose prevention centers, are needed to mitigate fentanyl-related harms.

“Withdrawal Syndrome”: The Effects of Acts of Microaggression in the Classroom on Racialized Students

“Withdrawal Syndrome”: The Effects of Acts of Microaggression in the Classroom on Racialized Students

Similarities and differences in core symptoms of problematic smartphone use among Chinese students enrolled in grades 4 to 9: A large national cross-sectional study

Children and adolescents are highly susceptible to problematic smartphone usage. We employed network analysis to explore the similarities and differences in the core symptoms of problematic smartphone use across grades 4–9, using a large nationwide sample. This study included 8552 children and adolescents (Mage = 12.98, SD=1.51) who met the critical value for problematic smartphone use. The results showed that the core symptoms of problematic smartphone use exhibit both similarities and differences between grades 4 and 9. ’Withdrawal symptoms’ and ’preoccupation symptoms’ were the stable core symptoms of problematic smartphone use across grades 4 to 9, suggesting that problematic smartphone use begin to appear from earlier grades, such as grade 4. ’Feel impatient and fretful’, ’never give up’ and ’always thinking about’ were the core symptoms in grades 4 and 5. ’Longer than I had intended’ and ’hard to concentrate’ emerged as additional core symptoms in grade 6, with the intensity indicators peaking in grades 8 and 9, suggesting that the issue of problematic smartphone use among Chinese children and adolescents has become intensified and intricate. Symptoms of problematic smartphone use vary across grades and exhibit both continuity and stage specificity. Consequently, to address this issue, the formulation of intervention measures should comprehensively consider both the grade levels and symptoms.

Treatment of spondyloarthritis with disease-modifying anti-rheumatic drugs during pregnancy and breastfeeding: comparing the recommendations and guidelines of the principal societies of rheumatology.

This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

The effect of education provided with the escape room game on nursing students' learning of parenteral drug administration

AimThe present study was conducted to determine the effect of education provided to first-year nursing students with the escape room game on their learning of parenteral drug administration. BackgroundThe use of escape room games in education supports formal education in providing students with professional knowledge and skills. DesignA randomized controlled study design was used in this study. MethodThe current study was conducted with 72 first-year nursing students. Data were collected with the Descriptive Characteristics Questionnaire (DCQ), Parenteral Drug Administration Information Test (PDAIT), Parenteral Drug Administration Sub-Checklists (PDASC) and Game Evaluation Form (GEF) between May and June 2022. The initial knowledge and skills of all students participating in the study were measured after completing the parenteral drug administration theoretical course and laboratory skills course. Students were assigned to the intervention (n=36) and control (n=36) groups by the stratified block randomization method according to their initial knowledge and skill measurements. Unlike the control group, the intervention group played the escape room game once in groups of four. The control group was allowed to work freely in the laboratory during this period. The final knowledge and skills of the intervention and control groups were measured immediately after the intervention. Students' skills were measured with an objective structured clinical examination. ResultsIt was determined that the post-test knowledge level of the students in the intervention group and their post-test skill mean scores for drug withdrawal from an ampoule, subcutaneous injection administration, intradermal injection administration and intravenous push drug administration were higher than those of the students in the control group (p<0.05). Additionally, Intervention group students evaluated the escape room game positively. ConclusionThis study concluded that the escape room game supported formal education and could be used in teaching parenteral drug administration.

The Effect of a Caffeine and Nicotine Combination on Nicotine Withdrawal Syndrome in Mice

Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL/6J mice were subcutaneously injected four times a day with nicotine (2 mg/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg/kg or 0.1 mg/kg), or nicotine (0.1 mg/kg) and caffeine (20 mg/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation.

A protocol for enhancing the diagnostic accuracy and predictive validity of neonatal opioid withdrawal syndrome: The utility of non-invasive clinical markers.

Every 15 minutes in the US, an infant exposed to opioids is born. Approximately 50% of these newborns will develop Neonatal Opioid Withdrawal Syndrome (NOWS) within 5 days of birth. It is not known which infants will develop NOWS, therefore, the current hospital standard-of-care dictates a 96-hour observational hold. Understanding which infants will develop NOWS soon after birth could reduce hospital stays for infants who do not develop NOWS and decrease burdens on hospitals and clinicians. We propose noninvasive clinical indicators of NOWS, including newborn neurobehavior, autonomic biomarkers, prenatal substance exposures, and socioeconomic environments. The goals of this protocol are to use these indicators shortly after birth to differentiate newborns who will be diagnosed with NOWS from those who will have mild/no withdrawal, to determine if the indicators predict development at 6 and 18 months of age, and to increase NOWS diagnostic sensitivity for earlier, more accurate diagnoses.

What are the reasons for injected methadone use? A qualitative study of people who use drugs parenterally in Barcelona.

Oral methadone maintenance is a widely adopted and effective treatment for heroin and other opioid dependencies. However, injectable methadone usage may pose greater risks than heroin itself. Despite decades of oral methadone treatment in Spain, there is limited understanding of the motivations for parenteral consumption. This study aimed to examine the reasons for methadone injection, delineate its specific advantages and disadvantages compared with those of heroin use, and assess the benefits and drawbacks of supervised methadone injection within a harm reduction service from the perspective of people who inject drugs. A qualitative phenomenological study was conducted in 11 patients at a safe injection facility in Barcelona. Semistructured interviews revealed that the reasons for injecting methadone were its provision of a euphoric rush, the pleasurable sensation of needle insertion, and the avoidance of gastrointestinal discomfort associated with oral methadone use. The main attraction of methadone injection was its accessibility as a legal and fully state-funded treatment option in Spain, coupled with its effectiveness in relieving withdrawal symptoms. However, notable disadvantages included the risks inherent in injection. The benefits of supervised consumption rooms were its provision of immediate medical assistance in overdose situations, ease of access, and physical safety. Drawbacks included waiting times, limited opening hours, neighborhood stigmatization, and the distance people who inject methadone had to travel when obtaining methadone from the illicit market. Based on these findings, we make several recommendations aimed at reducing the harm associated with methadone injection and emphasize the need for comprehensive harm reduction strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Real-world analysis on the use of gamma-hydroxybutyric acid for alcohol withdrawal syndrome in hospitalized patients with diagnosis of cirrhosis.

The present real-world analysis aimed to evaluate and describe the use of gamma-hydroxybutyric acid (GHB) for alcohol withdrawal syndrome (AWS) in hospitalized patients with diagnosis of liver cirrhosis. An 11-year observational retrospective study on patients affected by liver cirrhosis and alcohol use disorder (AUD) was performed using data from the Medical Toxicology Unit of Careggi University Hospital in Florence (Italy). A multivariate logistic regression was performed to estimate the probability of having a CIWA-Ar Max 3-4 during hospitalization, an AWS length > 36h, a hospitalization > 9days, and the probability of developing drowsiness. A total of 166 AUD patients were included, of these 77 received GHB (70.13% within the first day of hospitalization) and 89 were treated without GHB. The majority were ≥ 40years of age (87.35%) and males (80.12%). GHB patients were more likely to have a CIWA-Ar Max 3-4 during hospitalization (OR 3.76 [CI 95% 1.02-13.85]), and a longer hospitalization (OR 3.08 [95% CI 1.23-7.71]). Early GHB administration decreased the probability of CIWA-Ar Max worsening (OR 0.06 [95% CI 0.01-0.49]). GHB dose ≥ 100mg/kg was not associated with the occurrence of drowsiness. Patients exposed to other sedative agents were more likely to experience drowsiness (OR 7.22 [95% CI 1.46-35.61]). The present real-world analysis underlines that GHB could be a valuable and safe option for the management of AWS in AUD patients affected by liver cirrhosis, also when administered early and even at higher than recommended dosages.

Anti-anxiety and anti-depressive effects of Thai Mucuna pruriens seed aqueous extract against ethanol withdrawal syndrome in mice

BackgroundThai Mucuna pruriens (T-MP) has been used as a traditional medicine for treating many neurological conditions due to its antioxidant and neurorestorative properties. Aim of the studyThis study was to explore the effects of T-MP seed extract on ethanol withdrawal syndrome (EWS) in mice. MethodsMice were administered either normal saline solution (NSS) or 2 g/kg of 20% ethanol intraperitoneally once daily for 10 days. Behavioral symptoms of EWS were evaluated at 12-, 24-, and 36-hours after the last dose of ethanol using the elevated plus maze (EPM), light-dark box (LDB), and tail suspension test (TST). After determining the best time interval to detect EWS, a new set of mice were induced to have EWS, at 23 h after the last ethanol dose, mice were treated with either NSS (PO), diazepam (4 mg/kg, IP), or T-MP seed extract (600 mg/kg, PO). Behavioral tests were conducted one hour after treatment. ResultsIn the ethanol withdrawal mice, anxiety- and depressive-like behavior representing EWS were seen in LDB, EPM and TST, especially at the 24-hour after the final ethanol dose. At 36-hour after the final ethanol dose, although the anxiety-like behavior could be seen in LDB and EPM, whereas no significant depressive-like in TST was observed. Treatment with DZP or T-MP could significantly reduce the anxiety- and depressive-like symptoms of EWS at 24-hour after last dose of ethanol. In addition, treatment with T-MP, but not DZP, significantly reduced the total immobility time when compared to the control ethanol withdrawal group. ConclusionAccording to this study, it was discovered that T-MP seed extract could potentially offer a beneficial effect in managing anxiety- and depression-like behaviors in EWS in mice.

Identification of gene co-expression modules from zebrafish brain data: Applications in psychiatry illustrated through alcohol-related traits

Cumulative evidence suggests that zebrafish is a useful model in psychiatric research. Weighted Gene Co-expression Network Analysis (WGCNA) enables the reduction of genome-wide expression data to modules of highly co-expressed genes, which are hypothesized to interact within molecular networks. In this study, we first applied WGCNA to zebrafish brain expression data across different experimental conditions. Then, we characterized the different co-expression modules by gene-set enrichment analysis and hub gene-phenotype association. Finally, we analyzed association of polygenic risk scores (PRSs) based on genes of some interesting co-expression modules with alcohol dependence in 524 patients and 729 controls from Galicia, using competitive tests. Our approach revealed 34 co-expression modules in the zebrafish brain, with some showing enrichment in human synaptic genes, brain tissues, or brain developmental stages. Moreover, certain co-expression modules were enriched in psychiatry-related GWAS and comprised hub genes associated with psychiatry-related traits in both human GWAS and zebrafish models. Expression patterns of some co-expression modules were associated with the tested experimental conditions, mainly with substance withdrawal and cold stress. Notably, a PRS based on genes from co-expression modules exclusively associated with substance withdrawal in zebrafish showed a stronger association with human alcohol dependence than PRSs based on randomly selected brain-expressed genes. In conclusion, our analysis led to the identification of co-expressed gene modules that may model human brain gene networks involved in psychiatry-related traits. Specifically, we detected a cluster of co-expressed genes whose expression was exclusively associated with substance withdrawal in zebrafish, which significantly contributed to alcohol dependence susceptibility in humans.

Food and Drug Administration (FDA) Approvals of Biological Drugs in 2023

An increase in total drug (small molecules and biologics) approvals by the Food and Drug Administration (FDA) was seen in 2023 compared with the previous year. Cancer remained the disease most targeted by monoclonal antibodies (mAbs), followed by autoimmune conditions. Our data reveal the prevalence of approvals for biologics even during years when the total number of authorizations was low, such as in 2022. Over half the drugs that received the green light in 2023 benefited from expedited programs, as the incidence of many diseases increased. In addition, over half of the biologics approved received Orphan Drug Designation from the FDA. This narrative review delves into details of the most significant approvals in 2023, including mAbs, enzymes, and proteins, explaining their mechanisms of action, differences from previous drugs, placebo, and standards of care, and outcomes in clinical trials. Given the varying number of drugs authorized annually by the U.S. health authority, this review also examines the limits of external influences over the FDA′s decisions and independence regarding drug approvals and withdrawals.

Distinct binding conformations of epinephrine with α- and β-adrenergic receptors.

Agonists targeting α2-adrenergic receptors (ARs) are used to treat diverse conditions, including hypertension, attention-deficit/hyperactivity disorder, pain, panic disorders, opioid and alcohol withdrawal symptoms, and cigarette cravings. These receptors transduce signals through heterotrimeric Gi proteins. Here, we elucidated cryo-EM structures that depict α2A-AR in complex with Gi proteins, along with the endogenous agonist epinephrine or the synthetic agonist dexmedetomidine. Molecular dynamics simulations and functional studies reinforce the results of the structural revelations. Our investigation revealed that epinephrine exhibits different conformations when engaging with α-ARs and β-ARs. Furthermore, α2A-AR and β1-AR (primarily coupled to Gs, with secondary associations to Gi) were compared and found to exhibit different interactions with Gi proteins. Notably, the stability of the epinephrine-α2A-AR-Gi complex is greater than that of the dexmedetomidine-α2A-AR-Gi complex. These findings substantiate and improve our knowledge on the intricate signaling mechanisms orchestrated by ARs and concurrently shed light on the regulation of α-ARs and β-ARs by epinephrine.

Distinct Trajectories of Prescription Opioid Exposure in Pregnancy and Risk of Adverse Birth Outcomes.

The aim of this study was to identify distinct trajectories of prescription opioid exposure in pregnancy-encompassing both medication for opioid use disorder (MOUD) and opioid analgesics-and explore their associations with birth outcomes. Trajectories were identified using latent class analysis among Wisconsin Medicaid-insured live births 2011-2019. Logistic regression estimated associations between these trajectories and neonatal opioid withdrawal syndrome (NOWS), small for gestational age, preterm birth, birth weight, and gestational age. Of 138,123 births, 27,293 (19.8%) had prenatal opioid exposure. Five trajectory classes were identified: (1) stable MOUD treatment (5.8%), (2) inconsistent MOUD treatment (3.9%), (3) chronic analgesic use (4.2%), (4) intermittent analgesic use (7.8%), and (5) low-level use of MOUD and analgesics (78.3%). NOWS incidence per 1000 infants was 667 for class 1 (adjusted odds ratio [aOR]: 21.74, 95% confidence interval [CI]: 17.89, 26.41), 570 for class 2 (aOR: 15.35, 95% CI: 12.49, 18.87), 235 for class 3 (aOR: 19.42, 95% CI: 15.93, 23.68), 67 for class 4 (aOR: 6.23, 95% CI: 4.99, 7.76), and 12 for class 5 (aOR: 1.73, 95% CI: 1.47, 2.02). Classes 1-4 had elevated risk of small for gestational age, preterm birth, lower birth weight, and shorter gestational age, with no significant differences among these classes. Among individuals with opioid use disorder, stable MOUD treatment was associated with higher birth weights and longer gestational ages compared to inconsistent treatment, despite higher odds of NOWS. Early initiation and consistent MOUD treatment may improve birth weight and gestational age. For pregnant individuals with opioid use disorder using chronic analgesics, transition to MOUD may promote birth outcomes.

Dosage Optimization: A Regulatory Perspective for Developing Oncology Drugs.

Optimized dosages provide a secure foundation for the development of well-tolerated and effective oncology drugs. Project Optimus, an initiative within the Oncology Center of Excellence, strives to reform the dosage optimization and dosage selection paradigm in oncology. This initiative stems from the availability of targeted drugs and from the demand for more tolerable dosages from patients, caregivers, and advocates. Reforming dosage optimization for oncology drugs requires a paradigm shift from the one employed for cytotoxic chemotherapy to one that understands and considers the unique attributes of targeted therapy, immunotherapy, and cellular therapy. Limited characterization of dosage during drug development may result in (1) patients not staying on a therapy long-term due to poor tolerability, (2) failure to establish positive benefit-risk in clinical trials for regulatory approval (3) withdrawal of drugs from the market (4) removal of indications of drugs from the market. Timely access to drugs is important for all patients with cancer, so it is vital to iteratively analyze all nonclinical and clinically relevant data at each stage of development and leverage quantitative approaches, innovative trial designs, and regulatory support to arrive at dosages with favorable benefit-risk. This review highlights the key challenges and opportunities to embracing this new paradigm and realizing the full potential of new oncology therapies.

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.

P105 RENAL DENERVATION WITH SPYRAL SIMPLICITY SYSTEM: A SINGLE CENTER EXPERIENCE IN COLOMBIA

Background and Objectives: Hypertension is the leading cause of death with 10,4 million deaths and 218 disability adjusted life years (DALYs) worldwide in 2017. Despite GDMT, about 10 to 20% of hypertensive subjects will be poorly controlled, meeting the definition for difficult to treat (DTTH) and refractory hypertension (RH). Renal denervation (RDN) with Spyral Simplicity SystemTM has become a promising nonpharmacological treatment for DTTH and RH, and it has shown to be an effective and safe procedure for RH patients in randomized clinical trials with up to 12 months follow-up. Methods: This is a single-center registry including 6 adults with DTTH and RH confirmed by ABPM and without secondary hypertension, underwent RDN in a tertiary hospital in Bucaramanga, Colombia. A 6-months follow-up was performed, recording clinical data (symptoms, NYHA functional class, number and type of antihypertensive medications, heart rate and ER visits) and paraclinical tests (ABPM, eGFR and echocardiogram). Results: Mean age was 73 ± 4,64 years-old with 50% females. Main comorbidities were dyslipidemia (100%), cardiovascular disease (100%), and type 2 diabetes (83,3%). Pre-procedural medication average was 5. All patients were in NYHA II, with preserved left ventricular EF and mild to moderate diastolic disfunction. At 6 months of follow-up, there was a mean reduction in systolic blood pressure (SBP) of 10 mmHg (145 to 135 mmHg) in ABPM and 26 mmHg (169 to 143 mmHg) in office. There were not significant changes between pre- and post-procedural mean HR (68 vs. 61 bpm), neither short- or long-term complications associated with the procedure. In average, one drug withdrawal was observed. All the subjects improved their NYHA functional class. There were no ER visits in the 6-month follow-up. Conclusions: RDN is effective and safe for patients with DTTH and RH, achieving significant reduction in ABPM and office SBP, reducing medication number, improving NYHA functional class and avoiding visits to ER in the mid-term follow-up.