Chronic Drug Use Research Articles

The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

Background.The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19–associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes.Methods.This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed.Results.Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA.Conclusions.This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Spontaneous Spleen Rupture Due to Infectious Mononucleosis

Spontaneous spleen rupture (SSR) is a fatal and rare pathology causing acute abdomen. SSR secondary to infectious mononucleosis (IM) is quite rare (0.06-0.5%), and it is the most common cause of IM associated death. A 43 years old male patient, who had no previous severe disease history, chronic drug use, or previous operation applied to our emergency outpatient clinic of general surgery. The patient had complaints of severe abdominal pain, nausea, vomiting, and diarrhea. In abdominal computerized tomography, diffuse free fluid with respectively increased in density (hemorrhage?) was observed. Emergency operation was decided, because patient developed acute peritonitis signs. During exploration in the operation, it was observed that spleen was ruptured at multiple sites, and bleeding was ongoing, and splenectomy was performed. Serology was consistent with the previous EBV infection. It was mentioned in the pathology report that there was no neoplastic infiltration, and infectious causes should be investigated. No problem has been encountered during approximately two years’ follow-up. SSR secondary to EMN is a rare, fatal, and very severe pathology. Diagnosis is delayed, or it is not even diagnosed because there is no trauma. Correct diagnosis on time, and decision of emergency surgical intervention can be life-saving.

Tuberculosis among People Living on the Street and Using Alcohol, Tobacco, and Illegal Drugs: Analysis of Territories in Extreme Vulnerability and Trends in Southern Brazil.

(1) Background: Tuberculosis presents an epidemiological trend toward inequality, especially among people in social exclusion and situations of vulnerability. This study aimed to analyze territories with a concentration of people diagnosed with tuberculosis in a street situation and who partake in chronic use of alcohol, tobacco, and illicit drugs. We also analyzed trends in this health condition in southern Brazil. (2) Methods: Ecological study, developed in the 399 municipalities of Paraná, southern Brazil, with all tuberculosis cases in the homeless population registered in the Information System of Notifiable Diseases between 2014 and 2018. For data analysis, we used descriptive statistics, the Prais–Winsten autoregression method for the time series, and the Getis-Ord Gi technique* for spatial analysis. (3) Results: in total, 560 cases were reported. We found a predominance of alcohol, smoking, and illicit drug users, with an increasing trend in the state and clusters of spatial risk in the East health macro-region. (4) Conclusions: We observed territories with critical levels of highly vulnerable people who use psychoactive substances and are in a street situation. The results highlight the importance of incorporating public policies of social protection for these individuals and resolutive health services that receive these cases and assist in eradicating TB.

Demographic features of patients followed up in COVID intensive care units during the pandemic period

Aim: Coronavirus disease is the third coronavirus infection defined in the world in the 21st century, after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).Material and Method: We planned to evaluate demographic characteristics retrospectively and present them to the literature with statistical data. The patients included in our study, positive PCR ( polymerase chain reaction) test, who is under treatment in the COVID-19 intensive care units of our hospital due to COVID-19 disease. Age, comorbid conditions, admission complaints, physical examination findings, acute phase reactants, tomography results, length of hospital stay, and treatments of these patients were scanned from the patient files.Results: Demographic characteristics were found to be similar to the literature, but there is not enough data in the literature about chronic drug use. Elderly age, cardiovascular diseases, and ıntensive care unit hospitalization were associated with mortality.Conclusion: The patient group who has a chronic disease and uses multiple drugs should be considered. We think that we contribute to the literature with this information in our study.

Associations of Prior Chronic Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Glucocorticoids With Cachexia Incidence and Survival.

BackgroundCachexia is an inflammatory and metabolic syndrome of unintentional weight loss through depletion of muscle and adipose tissue. There is limited knowledge of how chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids affect cachexia development. The purpose of this study was to investigate associations between prior long-term use of NSAIDs or glucocorticoids with cachexia incidence and post-diagnosis weight loss progression in a retrospective cancer patient cohort.MethodsOf 3,802 lung or gastrointestinal cancer patient records, 3,180 comprised our final cohort. Patient demographic information, tumor qualities, medication histories, and comorbidities were assessed. Cachexia was defined as having developed prior to oncologic treatment. Statistical evaluations included categorical, multivariate logistic regression, and log-rank survival analyses. Development of substantial post-diagnosis weight loss was calculated and interpreted for patients without cachexia at diagnosis.ResultsChronic prior use of any NSAID or glucocorticoid medication was associated with approximate absolute and relative reductions in cachexia incidence at diagnosis of 10 and 25 percent (P<0.0001). In multivariate analyses, NSAID medications demonstrated a 23 percent reduction in cachexia incidence likelihood (OR=0.770; 95% CI=0.594, 0.998; P=0.0481). Patients without cachexia at diagnosis were significantly more likely to develop substantial post-diagnosis weight loss from pre-diagnosis use groups of glucocorticoids (OR= 1.452; 95% CI=1.065, 1.979; P=0.0183) or NSAIDs (OR=1.411; 95% CI=1.082, 1.840; P=0.011).ConclusionsOur findings suggest a protective effect of prior anti-inflammatory medications, primarily NSAIDs, against manifestations of the cachexia phenotype at cancer diagnosis. These observations support further exploration of potential therapeutic benefits from anti-inflammatory medications early in cancer management.

Chaos Unleashed: The impact of recreational drugs and COVID on young adults

IntroductionThis case series reveals a number of young adults, whom after chronic use of recreational drugs, suffer the life-long consequence of severe chronic mental illness.Objectives• Review the illicit drugs that are commonly associated with psychotic symptoms. • Highlight exposures theorized to impact genetics associated with DSM 5 diseases. • Compare trends in illicit drug use during the worldwide COVID pandemic.MethodsA literature review is used to examine the impact of COVID pandemic on illicit drug use in metropolitan cities in European countries and compare the trends with what is seen by the consult liaison psychiatry service at a metropolitan community hospital in the USA.ResultsIn European Countries with data available, there were measurable differences in which illicit drugs were used most during the COVID 19 pandemic. In the US this data is not readily available at the time of submission for proper comparisson.ConclusionsAlthough definitive comparrison is pending, the results of extensive illicit drug use demostrate a high comorbidity with psychotic spectrum disorders in the DSM 5.DisclosureNo significant relationships.

0614 Polysomnographic Measures of Sleep Architectural Disruption and Incident Atrial Fibrillation and Stroke in a Large Clinical Cohort

Abstract Introduction Although epidemiologic studies have identified associations of architectural disruptions in sleep and atrial fibrillation (AF), inconsistencies in results limit understanding of longitudinal AF and stroke development in clinic-based cohorts. We hypothesize lower arousal index as a biomarker of prolonged respiratory events and objective measures of sleep disruption increase incident AF and stroke. Methods Cleveland Clinic patients (age&amp;gt;18) who underwent polysomnogram (PSG) or split studies 11/27/2004-12/30/2015 were examined. Arousal index, total sleep time (TST,hours), sleep efficiency (SE,%), and wake after sleep onset (WASO,hours) were assessed as predictors of incident AF. Cox proportional hazard models were fit with time from sleep study to AF diagnosis. Secondary analyses were conducted in the subset of patients with baseline AF, with time from sleep study to stroke. Covariates included age, sex, race, body mass index (BMI,kg/m2), cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia), heart failure, coronary artery disease, myocardial infarction, coronary artery bypass grafting, chronic obstructive pulmonary disease, tobacco use, and use of anti-arrhythmic drugs. Data were censored at date of last follow up or the 5-year mark. Results The sample comprised 43,634 patients: age 51.7±14.5, 51.9% male, 74.5% White, and 7.1%(n=3,090) with AF. Of those without baseline AF, 1,176(2.9%) developed 5-year incident AF. Incident AF increased by 9% (HR=1.09, 95%CI=1.04-1.13) for each hour of lost TST. For every 10 percentage point decreased SE, incident AF increased by 7% (HR=1.07, 95%CI=1.04-1.11). For every hour increased WASO, incident AF increased by 14% (HR=1.14, 95%CI=1.07-1.21). Arousal index conferred no statistically detectable change of incident AF. In secondary analyses, any association of arousal index and incident stroke was attenuated after accounting for confounding comorbidities (omnibus p=0.055). Conclusion Objective measures of disrupted sleep architecture predicted incident AF in this clinical cohort. However, arousal index was not associated with AF development, nor stroke development in secondary analyses. Further investigation is needed to elucidate the role of arousal in SDB, perhaps with hierarchal models to clarify the degree to which confounders attenuate or accentuate any relationship. Support (If Any) Cleveland Clinic Neurological Institute Center for Outcomes Research &amp; Education Pilot Grant

0745 Sleep-Related Hypoxemia Association with Incident Atrial Fibrillation in a Clinic-Based Cohort

Abstract Introduction Sleep disordered breathing (SDB) has been implicated in atrial fibrillation (AF) in population-based studies, however, its role remains unclear and inconsistent. We hypothesize greater risk of 5-year incident AF with SDB and sleep-related hypoxia in a clinic-based cohort. Methods Cleveland Clinic patients (age&amp;gt;18) who underwent polysomnogram (PSG) or split studies 11/27/2004-12/30/2015 with &amp;gt;3 hours diagnostic time were examined. Predictors include AHI, % sleep time oxygen saturation&amp;lt;90% (T90), and minimum and mean oxygen saturation(minSaO2 and meanSaO2, respectively). Cox proportional hazard models were fit with time from sleep study to AF diagnosis as the dependent variable. Covariates included age, sex, race, body mass index(BMI), cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia), heart failure, coronary artery disease, myocardial infarction, history of coronary artery bypass grafting, chronic obstructive pulmonary disease, tobacco use, and use of anti-arrhythmic drugs. Data were censored at date of last follow up or at 5-years. Results The sample was comprised of 43,634 patients: age 51.7±14.5, 51.9% male, 74.5% White, and 7.1%(n=3,090) with AF. Of those without AF, 1,176(2.9%) developed 5-year incident AF. For each 10% increase in T90, incident AF increased by 7% (HR=1.07, 95%CI=1.05-1.10). Compared to reference, patients with 25.01-50%, 50.01-75%, and 75.01-100% time T90 had 22% (HR=1.22, 95%CI=1.01-1.46), 49% (HR=1.49, 95%CI=1.20-1.85), and 65% (HR=1.65, 95%CI=1.26-2.15) higher incident AF, respectively. For every 10-unit increase in minSaO2 and meanSaO2, incident AF decreased by 11%(HR=0.89, 95%CI=0.83-0.95) and 23% (HR=0.77, 95%CI=0.68-0.86), respectively. AHI did not demonstrate a statistically significant relationship with incident AF at a significance level of 0.05. Conclusion Sleep-related hypoxemia, defined by cumulative burden below 90% SaO2, demonstrated an association with incident AF in this large clinic-based cohort, even considering confounding factors. On the other hand, SDB severity as defined by AHI did not demonstrate this relationship. These findings are consistent with experimental models that identify intermittent hypoxia and oxidative stress leading to alterations of the cardiac substrate, thus implicating sleep-related hypoxemic mechanisms as a salient driver in the evolution of atrial arrhythmogenesis. Support (If Any) Cleveland Clinic Neurological Institute Center for Outcomes Research &amp; Education Pilot Grant, Neuroscience Transformative Research Resource Development Award

Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19.

Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are among the most-frequently used medications. Although these medications have different mechanisms of action, they have similar indications and treatment duration has been positively correlated with cardiovascular risk although the degree of risk varies by medication. Our objective was to study treatment effects of chronic use of individual NSAID medications and acetaminophen on all-cause mortality among patients who tested positive for COVID-19 while accounting for adherence. We used the VA national datasets in this retrospective cohort study to differentiate between sporadic and chronic medication use: sporadic users filled an NSAID within the last year, but not recently or regularly. Using established and possible risk factors for severe COVID-19, we used propensity scores analysis to adjust for differences in baseline characteristics between treatment groups. Then, we used multivariate logistic regression incorporating inverse propensity score weighting to assess mortality. The cohort consisted of 28,856 patients. Chronic use of aspirin, ibuprofen, naproxen, meloxicam, celecoxib, diclofenac or acetaminophen was not associated with significant differences in mortality at 30 days (OR = 0.98, 95% CI: 0.95–1.00; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.97–1.01; and OR = 1.00, 95% CI: 0.99–1.02, respectively) nor at 60 days (OR = 0.97, 95% CI: 0.95–1.00; OR = 1.00, 95% CI: 0.99–1.01; OR = 0.99, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.97–1.00; OR = 0.99, 95% CI: 0.97–1.01; OR = 0.99, 95% CI: 0.97–1.01; and OR = 1.01, 95% CI: 0.99–1.02, respectively). Although the study design cannot determine causality, the study should assure patients as it finds no association between mortality and chronic use of these medications compared with sporadic NSAID use among those infected with COVID-19.

Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors.

Immune-related adverse events (irAEs) are a range of complications associated with the use of immune-checkpoint inhibitors (ICIs). Two major classes of ICIs widely used are Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed Cell death-1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors. High-grade irAEs are life-threatening and often cause a severe decline in performance status in such that patients do not qualify for any further anticancer treatments. It is difficult to generalize the evidence in the current literature on risk factors or biomarkers for the entire class of ICIs as the studies so far are either disease-specific (e.g., lung cancer or melanoma) or ICI agent-specific (e.g., pembrolizumab, ipilimumab) or irAE-specific (e.g., pneumonitis or gastritis). In this review, risk factors and biomarkers to consider before initiating or monitoring ICI are listed with a practical purpose in day-to-day practice. Risk factors are grouped into demographics and social history, medical history, and medication history, tumor-specific and agent-specific risk factors. A higher risk of irAE is associated with age <60 years, high body mass index, women on CTLA4 and men on PD-1/PD-L1 agents, and chronic smokers. Patients with significant kidney (Stage IV-V), cardiac (heart failure, coronary artery disease, myocardial infarction, hypertension), and lung (asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease) are at a higher risk of respective organ-specific irAEs. Pre-existing autoimmune disease and chronic use of certain drugs (proton pump inhibitors, diuretics, anti-inflammatory drugs) also increase the irAE-risk. Biomarkers are categorized into circulating blood counts, cytokines, autoantibodies, HLA genotypes, microRNA, gene expression profiling, and serum proteins. The blood counts and certain protein markers (albumin and thyroid-stimulating hormone) are readily accessible in current practice. High neutrophil-lymphocyte ratio, eosinophil/monocyte/lymphocyte counts; TSH and troponins at diagnosis and drop in the white count and lymphocyte count can predict irAE. Other biomarkers with limited evidence are cytokines, autoantibodies, HLA genotypes, microRNA, and gene expression profiling. With fast-expanding approvals for ICIs in various cancer types, knowledge on risk factors and biomarkers can help providers assess the irAE-risk of their patients. Prospective disease and agent-specific studies are needed to provide further insight on this essential aspect of ICI therapy.

Role of serology tests in COVID-19 non-hospitalized patients: A cross-sectional study.

IntroductionSevere acute respiratory syndrome coronavirus (SARS-CoV2) has imposed catastrophic impressions on the world. After all the focused researches conducted in the COVID-19 area, many features remain obscure. We have surveyed 1,363 outpatients with suspected COVID-19 in Tehran, Iran. The analysis emphasized on characteristics of patients with positive PCR or serology of SARS-CoV-2.MethodsThe nasopharyngeal swabs were tested for SARS-CoV2 PCR. Serum specimens were tested for SARS-CoV2 IgG and IgM. Clinical presentations of the patients, history of chronic diseases or drug use, contact with a possible COVID-19 patient and previous infection with SARS-COV2 were investigated.ResultsOf the total 1,363 investigated patients, 22% had positive SARS-CoV-2 PCRs, 82% had positive IgG, 38% had positive IgM, and 31% had both positive IgM and IgG values. Positive serologic tests were significantly associated with a positive PCR test obtained previously in the course of the current disease (P value<0.001).IgG and IgM antibody values were significantly associated with underlying disease, cough, fever, chills, fatigue, and myalgia (all P values <0.001). Dyspnea was significantly associated with IgG levels (P value = 0.01), yet it was not associated with IgM serology (P value = 0.2). Positive serology tests were not associated with symptoms of coryza.GI symptoms were not associated with positive IgG test (P value = 0.1), yet it did show an association with positive IgM test (P value = 0.02).Cough, fever, chills, myalgia fatigue, dyspnea, and GI symptoms were all significantly associated with positive PCR (all P values <0.001), and symptoms of coryza did not show a significant relationship (P value = 0.8).ConclusionAssessing antibody titers in outpatients is invaluable due to the epidemiological importance of investigations in mild or even asymptomatic cases. Since the number of such studies in non-hospitalized patients is not high, the current study can be used as a comparison model.

Altered neural processing of social reward in male heroin abstainers

Individuals who are addicted to drugs often face unfavourable social conditions and difficulty with social adaptation. Both may be closely related to impaired social cognitive ability. This study posits that social cognitive impairments likely arise from blunted social reward processing in drug users. This study aimed to explore the electrophysiological mechanism of social reward processing in people who abstain from using heroin (heroin abstainers). Twenty-eight male heroin abstainers and 27 matched controls completed the social incentive delay task. At the same time, their corresponding behaviour and electroencephalography data were recorded. The feedback-related negativity (FRN) elicited by positive outcomes was significantly more positive than that elicited by negative outcomes for the healthy controls. However, no significant difference in FRN was found between negative and positive outcomes among the heroin abstainers. There was no significant difference in P3 (a positive event-related potential component after FRN) elicited by negative and neutral outcomes in the heroin abstainers. Meanwhile, negative outcomes elicited greater P3 than neutral outcomes in the healthy controls. In addition, this study also found that withdrawal time was negatively correlated with the difference wave of FRN for the heroin abstainers. Heroin abstainers may be hyposensitive to the processing of social reward outcomes. In other words, they may have insufficient motivation to acquire social rewards. Abnormal social reward processing found in heroin abstainers can be improved with an increase in abstinence time. These results deepen our understanding of the social reward impairments associated with chronic drug use.

Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls

Chronic use of drugs may alter the brain’s reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the ‘CannTeen’ study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26–29 years) and adolescent (16–17 years) cannabis users (1–7 days/week cannabis use) and gender- and age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.

The effect of fetal hypoxia on myeloperoxidase levels in cord blood: a prospective study.

We aimed to compare myeloperoxidase (MPO) levels in cord blood samples of mothers with and without perinatal hypoxia, since fetal hypoxia results in decreased pH, base excess, and an increase in pCO<inf>2</inf> and lactate levels. We enrolled 42 pregnant women to this cross-sectional analytic study if they had met following criteria: uneventful gestational follow-ups, no known chronic or pregnancy-associated diseases, a BMI of <29.9, a singleton pregnancy, those with pregnancy over 34 weeks. The exclusion criteria for the study and control groups were as follows: presence of multiple pregnancies, fetal abnormality, any disease diagnosed before or during antenatal follow-up e.g., diabetes, hypertension, thyroid dysfunction, uncontrolled endocrine disease or abnormal kidney function, autoimmune disease, chronic inflammatory diseases, IUGR, preeclampsia), maternal age below 18 or above 35, intrauterine exitus, pregnancy with assisted reproductive technique, alcohol or smoking addiction, and any chronic drug use. The subjects were 1:1 randomized to either hypoxic newborns (N.=21) and those in the control group (N.=21) and their myeloperoxidase levels were measured from cord blood samples. Results were expressed as U/L. Patient data regarding age, gestation, parity, birth weight, birth length, APGAR scores, and neonatal complications were collected. All the women signed written informed consent forms and accepted verbal consent before being included in the study. The mean age of the study population was 26.9±5.3 years. The mean BMI was 28.3±3.5 kg/m2. For the hypoxic group, 21 newborns with cord blood below 7.25 were included in the study group. The bloods with pH above 7.25 formed the control group. Mean pH and five (5) minute APGAR scores were found to be significantly lower in the study group, while base excess (BE) was found to be significantly higher. In this study, we compared the MPO levels of hypoxic newborns and those in the control group, and we did not find a significant difference between the two groups (P=0.147). Pearson Correlation Analysis is at -0.566 with P value (0.008) showing significant negative correlation between MPO and pH in the study group. We found that MPO values are negatively correlated with cord blood pH among newborns diagnosed with fetal hypoxia.

Long-Term Follow-up of Over 600 Living Related Kidney Donors: Single-Center Experience.

Kidney transplant is the treatment of choice in patients with end-stage renal disease because it offers improved survival and better quality of life. Although most epidemiologic studies have suggested that living kidney donors have a minimal lifetime risk of developing end-stage renal disease, long-term complications and physiologic and psychologic sequelae resulting from donation remain unclear. Here, we examined the long-term results of living-related kidney donors who donated kidneys at the Başkent University Ankara Hospital over the past 25 years. We were able to examine 607 kidney transplant donors (mean age of 52.03 ± 11.54 years) who were seen at our center from 1986 to 2021 and who agreed to a general health evaluation. Collected data included donor age, sex, blood type, body mass index, duration after donation, blood pressure measurements, biochemical parameters, abdominal ultrasonograph for size, structure, and renal blood flow of the solitary kidney, comorbid conditions, chronic drug use, and surgical procedures after donation. Mean time after donation was 10.4 ± 3.2 years. Twenty-four donors (3.9%) were diagnosed with diabetes and 21 (3.4%) with thyroid disease, 64 (10.5%) developed hypertension, and 48 (8.8%) developed atherosclerotic cardiovascular disease. Obesity was found to be an increasing problem in our donor population, with 174 (28.6%) developing mild to moderate obesity (body mass index >25 kg/m2). Older age, obesity, smoking, and hyperlipidemia were found to be the major and independent risk factors of both hypertension and atherosclerotic cardiovascular disease in donors. None of our donors developed endstage renal disease. Obesity and hypertension were the most common comorbidities that developed in our kidney donor population. Our principle is to avoid unrelated and nondirected donors because of the possible long-term complications. Unrelated donors may be desperate if a family member needs donation in the future.

Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats.

Cocaine addiction is a complex pathology inducing long-term neuroplastic changes that, in turn, contribute to maladaptive behaviors. This behavioral dysregulation is associated with transcriptional reprogramming in brain reward circuitry, although the mechanisms underlying this modulation remain poorly understood. The endogenous cannabinoid system may play a role in this process in that cannabinoid mechanisms modulate drug reward and contribute to cocaine-induced neural adaptations. In this study, we investigated whether cocaine self-administration induces long-term adaptations, including transcriptional modifications and associated epigenetic processes. We first examined endocannabinoid gene expression in reward-related brain regions of the rat following self-administered (0.33mg/kg intravenous, FR1, 10days) cocaine injections. Interestingly, we found increased Cnr1 expression in several structures, including prefrontal cortex, nucleus accumbens, dorsal striatum, hippocampus, habenula, amygdala, lateral hypothalamus, ventral tegmental area, and rostromedial tegmental nucleus, with most pronounced effects in the hippocampus. Endocannabinoid levels, measured by mass spectrometry, were also altered in this structure. Chromatin immunoprecipitation followed by qPCR in the hippocampus revealed that two activating histone marks, H3K4Me3 and H3K27Ac, were enriched at specific endocannabinoid genes following cocaine intake. Targeting CB1 receptors using chromosome conformation capture, we highlighted spatial chromatin re-organization in the hippocampus, as well as in the nucleus accumbens, suggesting that destabilization of the chromatin may contribute to neuronal responses to cocaine. Overall, our results highlight a key role for the hippocampus in cocaine-induced plasticity and broaden the understanding of neuronal alterations associated with endocannabinoid signaling. The latter suggests that epigenetic modifications contribute to maladaptive behaviors associated with chronic drug use.

Vonoprazan in the management of gastric/peptic ulcers: a systematic review of safety data.

Although potassium-competitive acid blockers (P-CABs) prompted safety concerns when first developed, they ultimately proved to have a favourable safety profile. To assess the safety of vonoprazan in the management of gastroesophageal reflux disease (GERD), peptic ulcers, or gastroduodenal mucosal lesions induced by chronic use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs). From March to June 2021, a literature search was conducted using Medline via PubMed, Cochrane library, Lilacs, SciELO, and Centre for Reviews and Dissemination (CRD) electronic databases. After applying the eligibility criteria, 10 studies were included in this review. Of these 10 articles, vonoprazan was used as initial therapy in 6 and as maintenance therapy in 4. Adverse event rates were similar for vonoprazan and proton-pump inhibitors (PPIs). Our findings suggest that vonoprazan is a safe option for the management of erosive oesophagitis, gastric/peptic ulcers, or peptic ulcers induced by chronic use of aspirin or NSAIDs.

Chronic Antidepressant Use

Background: Chronic use of antidepressant drugs often results in drug-induced organ damage, which is mostly undetected and under-reported. The study aimed at evaluating the effect of selected antidepressants on organs and blood cell counts in adult albino rats. Materials and Methods: Adult rats were divided into four groups (n = 5): Group 1 (5 mL/kg of body weight/day normal saline), Group 2 (1 mg/kg of body weight/day risperidone), Group 3 (5 mg/kg of body weight/day fluoxetine), and Group 4 (15 mg/kg of body weight/day imipramine) for 14 days. The animals experienced different stressors during the treatment period to simulate physiological state of depression. On the 14th day, the animals were exposed to the forced swimming test 1 h after the respective treatments. On the 15th day, the animals were sacrificed under halothane anesthesia. Blood sample was collected. Liver and kidney were excised for histological examination. Results were analyzed using one-way analysis of variance. Results: Kidney histology was normal for all groups. Risperidone-exposed rats presented with hepatotoxicity with areas of zonal necrosis and partial central vein congestion. Neutrophil (%) was significantly reduced (P &lt; 0.01) in all treatment groups when compared with controls. White blood cell count was significantly increased (P &lt; 0.01) in the imipramine and risperidone treatment groups but significantly reduced (P &lt; 0.01) in the fluoxetine treatment group when compared with controls. Also, the platelet count was significantly increased (P &lt; 0.01) in the fluoxetine group but decreased in imipramine-and risperidone-treated groups. Conclusion: Chronic antidepressant use can cause changes in blood cell counts and drug-induced organ damage; hence, frequent organ function tests and blood count are required in patients undergoing chronic antidepressant therapy.

Mental capacity including testamentary capacity.

Mental capacity including testamentary capacity.

859. Suboptimal Uptake, Retention, and Adherence of Daily Oral PrEP Among People with OUD Receiving HCV Treatment

BackgroundDaily oral pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) effectively prevents HIV among people who use drugs (PWUD). Despite rising rates of HIV incidence and injection drug use, PrEP use remains low and limited research exists on PrEP adherence and retention in this population.MethodsBased in Washington, DC and Baltimore, the ANCHOR investigation evaluated a community-based model of care collocating hepatitis C (HCV) therapy, medication for opioid use disorder (OUD), and PrEP in people with chronic HCV, OUD, and drug use within 1 year. PrEP counseling was offered from HCV treatment Day 0 until Week 24 and subjects could start any time during this window. PrEP patients were followed for 48 weeks and assessed for adherence by self-report and dried blood spot analysis of TDF. ANCHOR PrEP study enrollment and participant retention along the PrEP continuum.Results198 participants enrolled in ANCHOR, of whom 185 (93%) were HIV-negative. 29 subjects (16% of HIV-negative group) initiated PrEP. 116 subjects (63%) met 2014 CDC criteria for PrEP initiation due to IDU (82, 44%), sex (9, 5%), or both (25, 14%). Those who initiated were more likely to meet both CDC sexual and IDU risk criteria than those who declined PrEP (P=0.006). Providers recommended PrEP to 94 subjects (51%), which was associated with uptake (P=0.02). While median treatment duration was 104 days (IQR 28, 276), only 8 subjects were retained through Week 48. The most common reason for discontinuation was side effects in 7 subjects or 24% of PrEP subgroup. Treatment interruptions occurred in one-third of the PrEP subgroup. Adherence of 4 to 7 pills per week was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. Demographic and epidemiological background of the ANCHOR study population. Total duration, in days, on PrEP in the ANCHOR study. Discontinued participants are grouped by reason for cessation of therapy.PrEP Adherence Adherence to PrEP by ANCHOR study timepoint, assessed via self-report (above) and dried bloodspot analysis of tenofovir level (below).ConclusionIn this cohort of people with OUD and HCV, 16% of subjects started PrEP. While clinical recommendation was associated with uptake, high rates of disruption and discontinuation, compounded by variable pill adherence, made daily oral TDF/FTC a suboptimal preventive strategy in this cohort. Emerging PrEP modalities like long-acting injectables have potential to address these barriers, but PWUD have been excluded from their research and development to date. Additional work to identify vulnerable individuals and to promote use, adherence, and retention will be critical in implementing PrEP more effectively in this key population.Disclosures Sarah Kattakuzhy, MD, Gilead Sciences (Scientific Research Study Investigator, Research Grant or Support) Elana S. Rosenthal, MD, Gilead Sciences (Research Grant or Support)Merck (Research Grant or Support)