Concomitant Drug Use Research Articles

Analysis of Risk Factors for Developing Tuberculosis in Patients Who Received Prophylactic Latent Tuberculosis Infection Treatment with Experience of Biologic Medications.

Biologic medications have dramatically improved the treatment outcomes of immunological inflammatory diseases, but their immunosuppressive effects put patients at risk for tuberculosis (TB). We investigated the risk factors for developing TB in patients treated for latent tuberculosis infection (LTBI) who also had experience of using biologic medications. At Keio University Hospital, we retrospectively investigated patients treated with anti-mycobacterial drugs before or concurrently with biologic medications from January 2012 to August 2020. Patients in the 'follow-on cases group' who had a positive TB screening test after initiating biologic medications and subsequently started LTBI treatment were excluded. We researched and compared the patient characteristics for TB and non-TB patient groups. Of the 146 eligible patients, 5 (3.4%) developed TB. The incidence rate was 600/100000 person-years. There were no significant differences between TB and non-TB patient groups in the history of TB, interferon-gamma release assay (IGRA), duration of biologic medication therapy, LTBI treatment periods, concomitant use of calcineurin inhibitors or anti-rheumatic drugs. The percentage of patients who received prednisolone at a dose of ≥15 mg for more than 1 month was higher in those who developed TB than in those who did not (40.0 vs. 7.1%, p = 0.054); however, this difference was not statistically significant. Regular monitoring of TB is necessary for long-term concomitant use of high prednisolone doses during and after the administration of biologic medications.

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy.

Perampanel is a promising option for the treatment of pediatric epilepsy, but its plasma concentration varies among patients. This retrospective study aimed to investigate the initial target attainment of perampanel plasma concentration in pediatric patients with epilepsy in China. Inpatients admitted from January 2020 to December 2021 in a tertiary hospital were retrospectively included according to pre-set criteria. Demographic characteristics of patients and dosing strategies and therapeutic drug monitoring results were collected. A total of 137 pediatric patients (84 females and 53 males, aged from 0.6 to 16.4years) were include for analysis. The perampanel concentrations varied greatly from 60 to 1,560mg/L among patients, but 89.8% had suitable perampanel concentrations (100-1,000ng/mL). The concomitant use of enzyme-inductive antiepileptic drugs (AEDs) was the only identified risk factor associated with target nonattainment (OR = 5.92, 95% confidence interval 1.68-20.9). Initial perampanel target attainment in pediatric patients is satisfactory. Routine therapeutic drug monitoring to achieved the suggested concentration range for these patients may be unnecessary, except for those receiving combined enzyme inductive AEDs.

Venous thromboembolism in users of hormonal contraception and non-steroidal anti-inflammatory drugs: a nationwide cohort study

Abstract Objective To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism. Design: Nationwide cohort study. Setting: Denmark through national registries. Participants: All 15-49-year-old women living in Denmark between the years 1996-2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment. Main outcome measure: A first-time discharge diagnosis of lower-limb deep venous thrombosis or pulmonary embolism. Results Among 2.0 million women followed for 21.0 million person-years, 8710 venous thromboembolic events occurred. Compared to non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 8.1 (95% confidence interval (CI) 6.9 to 9.6) in women not using hormonal contraception, 12.1 (10.6 to 13.9) in women using high-risk hormonal contraception, 8.7 (6.5 to 11.6) in users of medium-risk hormonal contraception, and 5.1 (2.9 to 9.1) with low/no-risk hormonal contraception. Compared to non-use of NSAIDs, the number of extra venous thromboembolic events per 100,000 one-week NSAID treatments was 4 in women not using hormonal contraception, 18 in women using high-risk hormonal contraception, 9 in users of medium-risk hormonal contraception, and 2 in women using low/no-risk hormonal contraception. Conclusions NSAID use was positively associated with the development of venous thromboembolism. The association was stronger in women concomitantly using high-risk hormonal contraceptives and weaker in women using low/no-risk hormonal contraception. Women requiring both hormonal contraception and regular use of NSAIDs should be advised accordingly.

Efficacy, retention rate and safety of adalimumab treatment in patients with non-infectious uveitis and scleritis: a real-world, retrospective, single-centre study.

To evaluate the outcomes of adalimumab (ADA) treatment of patients with non-infectious uveitis and scleritis, focusing on efficacy, retention rate, and safety. This retrospective, clinical cohort study included 62 patients (104 eyes) with active ocular inflammation treated with ADA. Primary outcomes were efficacy and cumulative drug retention rate (DRR) of ADA. The secondary outcomes included changes in ocular inflammatory parameters, changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT), corticosteroid-sparing effect, impact of concomitant use of disease-modifying antirheumatic drug (DMARD) and ADA as first or ≥2nd biotherapy line on DRR, and adverse events. Forty-five patients (72.6%) achieved inactive disease at the end of follow-up. DRR at 6, 12, 24, and 48 months was 96.8%, 89.2%, 63.1%, and 63.1%, respectively. Of the 18 patients whose bi-weekly ADA treatment was escalated to weekly ADA due to primary or secondary inefficacy, 10 patients had inactive disease finally. BCVA improved (p < 0.001) and CMT decreased (p < 0.001) significantly at 6, 12, and 24 months after ADA therapy compared to baseline. Percentage of patients treated with ≥10 mg/day corticosteroid (61.3% vs. 6.4%) and DMARDs combined with ADA (46.8% vs. 37.1%) were lower at 6 months than at baseline. Concomitant DMARDs (p = 0.579) and use of ADA as first or ≥2nd biotherapy line (p = 0.527) had no significant effect on DRR. Most common adverse event was tuberculosis-related infections. ADA seems to be effective and safe with good DRR to control ocular inflammation. Escalation to weekly ADA treatment may be an effective option in patients with primary or secondary inefficacy.

The role of oestrogen therapy in reducing risk of Alzheimer's disease: systematic review.

Studies have shown a relationship between oestrogen and Alzheimer's disease. However, there is neither clear nor strong evidence on the use of oestrogen-only therapy in reducing the risk of Alzheimer's disease. To assess the effects of oestrogen-only therapy on reducing the risk of Alzheimer's disease. Inclusion criteria was determined with the PICO framework. Outcome was cognitive function measured by neuropsychological tests and strict protocols. Exclusion criteria included non-Alzheimer's dementia, progesterone-only therapy and pre-menopausal women. Searches were conducted in nine electronic healthcare databases, last searched in July 2022. Quality assessments conducted on randomised controlled trials (RCTs) were performed with the GRADE assessment, and cohort studies and case-control studies were assessed with the Newcastle-Ottawa Scale. Extracted data were used to analyse participants, interventions and outcomes. Twenty-four studies satisfied the search criteria (four RCTs, nine cohort studies, 11 case-control studies). Fifteen studies showed positive associations for oestrogen-only therapy reducing the risk of Alzheimer's disease, and the remaining nine found no evidence of association. Fifteen studies showed that oestrogen-only therapy effectively reduced the risk of Alzheimer's disease, whereas nine showed no correlation. Studies also investigated oestrogen-related variables such as length of oestrogen exposure, being an apolipoprotein E ε4 carrier and concomitant use of non-steroidal anti-inflammatory drugs, and their role in neuroprotection. This review was limited by the limited ranges of duration of oestrogen treatment and type of oestrogen-only therapy used. In conclusion, oestrogen-only therapy has potential for use in preventing Alzheimer's disease, although current evidence is inconclusive and requires further study.

Antiplatelet drugs may increase the risk for checkpoint inhibitor-related pneumonitis in advanced cancer patients

Immune checkpoint inhibitors (ICIs) are indicated for various cancers and are the mainstay of cancer immunotherapy. They are often associated with ICI-related pneumonitis (CIP), however, hindering a favorable clinical course. Recently, non-oncology concomitant drugs have been reported to affect the efficacy and toxicity of ICIs; however, the association between these drugs and the risk for CIP is uncertain. The aim of this study was to assess the impact of baseline concomitant drugs on CIP incidence in ICI-treated advanced cancer patients. This was a single-center retrospective study that included a cohort of 511 patients with advanced cancer (melanoma and non-small-cell lung, head and neck, genitourinary, and other types of cancer) treated with ICIs. Univariable analysis was conducted to identify baseline co-medications associated with CIP incidence. A propensity score matching analysis was used to adjust for potential CIP risk factors, and multivariable analysis was carried out to assess the impact of the identified co-medications on CIP risk. Forty-seven (9.2%) patients developed CIP. In these patients, the organizing pneumonia pattern was the dominant radiological phenotype, and 42.6% had grade ≥3 CIP, including one patient with grade 5. Of the investigated baseline co-medications, the proportion of antiplatelet drugs (n= 50, 9.8%) was higher in patients with CIP (23.4% versus 8.4%). After propensity score matching, the CIP incidence was higher in patients with baseline antiplatelet drugs (22% versus 6%). Finally, baseline antiplatelet drug use was demonstrated to increase the risk for CIP incidence regardless of cancer type (hazard ratio, 3.46; 95% confidence interval 1.21-9.86). An association between concomitant antiplatelet drug use at baseline and an increased risk for CIP was seen in our database. This implies the importance of assessing concomitant medications for CIP risk management.

Exploring signals of myopathy associated with statin and contraindicated comedications in the realworld.

Using statins in combination with other drugs was reported to increase the risk of myopathy. However, there was a sparse number of studies on the incidence of adverse events (AEs) associated with the concomitant use of statin and contraindicated drugs in the real world. This study aimed to identify the risk of concomitant use of statins with contraindicated drugs by exploring signals related to statin-drug interactions. We performed a disproportionality analysis for drugs and AEs by applying the case/non-case study using the KIDS-KAERS database (KIDS-KD), 2016-2020. A case was defined as an individual case safety reports (ICSRs) including "rhabdomyolysis/myopathy." A non-case was defined as an ICSR, including all other AEs. We applied Ω shrinkage measure model, chi-square statics model, additive model, multiplicative model, and combination risk ratio model to detect signals of myopathy due to statin with concomitant drugs including antiviral agents, immunosuppressants, and antifungals. Among 1 011 234 ICSRs, 2708 were cases, with 861 cases of statin monotherapy and 1248 of concomitant uses of statin. The adjusted reporting odds ratios were 3.27 (95% confidence interval [CI]: 3.11-3.43), 8.70 (95% CI: 8.04-9.40), and 1.83 (95% CI: 1.73-1.94), respectively. Several combinations of signals were detected through an additive model or multiplicative model. Signals of an increased risk of myopathy associated with the use of statins with concomitant drugs, including contraindicated drugs, were confirmed in a real-world setting.

A Survey of the Status of Methadone Switching in Japan Using a Hospital-Based Administrative Claims Database.

Methadone is generally used for the management of cancer pain in patients who cannot obtain adequate analgesia from other strong opioids; however, it has a complicated and inconsistent conversion ratio from pre-switching opioid dosage to methadone. This issue may be pronounced in Japan because only oral tablets are commercially available. We aimed to elucidate the status of methadone switching in Japan, focusing on its dosage. Using a Japanese hospital-based administrative claims database, we included patients who switched to methadone between April 2008 and January 2021. The proportion of methadone switching completion that required more than the defined conversion ratio in the Japanese package insert (called "high-dose methadone switching") was evaluated as a primary endpoint. Other endpoints included "the duration from initiation to completion of methadone switching" and "factors affecting high-dose methadone switching by using multivariate logistic regression analysis". Of 1585 patients who received methadone, 370 were enrolled. Among those, 130 (35.1%) received high-dose methadone switching. The median duration of methadone switching completion (12 days) was longer in the high-dose methadone switching group than in other patients. Four variables were identified as factors affecting high-dose methadone switching. Younger age and outpatient status increased the risk of requiring high-dose methadone switching, whereas the concomitant use of nonsteroidal anti-inflammatory drugs and fentanyl as a pre-switching opioid decreased the risk. In conclusion, more than 30% of the patients underwent high-dose methadone switching and required long completion periods, suggesting that methadone switching remains challenging in Japan.

PB0021 Clinical Outcomes of Direct Oral Anticoagulants in Patients with Concomitant Use of Antiepileptic Drugs in the Real-World Registry MACACOD

PB0021 Clinical Outcomes of Direct Oral Anticoagulants in Patients with Concomitant Use of Antiepileptic Drugs in the Real-World Registry MACACOD

Clinical Review of Risk of Nephrotoxicity with Acyclovir Use for Treatment of Herpes Simplex Virus Infections in Neonates and Children.

This study aims to clarify the risk of nephrotoxicity with intravenous use of acyclovir (ACV) for the treatment of neonates (ages <3 months) and children (ages ≥3 months to <12 years) with herpes simplex virus (HSV) infections and to identify gaps in knowledge that could be further investigated. Multiple databases were searched to identify studies on risk of nephrotoxicity with ACV use for treatment of invasive HSV infections, defined as any neonatal infection or HSV encephalitis (HSE) in children. There were 5 and 14 studies that evaluated the risk of ACV-associated nephrotoxicity in neonates and children, respectively. The US Food and Drug Administration (FDA) delayed the approval of high (HD; 60 mg/kg/day) ACV in neonates secondary to risk of toxicity. Based on our review, the risk of ACV-associated nephrotoxicity was lower in the neonatal compared with the pediatric population. Acyclovir dose >1500 mg/m2, older age, and concomitant use of nephrotoxic drugs were identified as variables that increased the risk of ACV nephrotoxicity in children. Although the FDA has approved the use of HD ACV for the treatment of HSE in children, the American Academy of Pediatrics recommends a lower dose to minimize the risk of toxicity. The efficacy and safety of high vs lower doses of ACV for the management of HSE in children has yet to be evaluated. The risk of ACV-associated nephrotoxicity was lower among neonates compared with older children. Future studies are needed to identify the optimal dosage that minimizes toxicities and maximizes the efficacy of ACV in children with HSE.

Alternative beliefs in psychedelic drug users

Previous research has suggested that classical psychedelics can foster significant and enduring changes in personality traits and subjective wellbeing. Despite the lack of evidence for adverse effects on mental health stemming from psychedelic use, concerns persist regarding the capacity of these substances to modulate information processing and attitudes towards factual data. The aim of the present study was to investigate the propensity for accepting alternative facts and the general treatment of knowledge within a sample of 392 participants, 233 of whom reported at least a single incidence of psychedelic use in their lifetime. To do this, we leveraged step-wise methods of linear modelling investigating effects of demographics, psychiatric conditions and concomitant drug use. Our findings revealed a moderate positive association between psychedelic use and beliefs in alternative facts, as well as the specific belief that facts are politically influenced. However, no links were found for favouring intuition over evidence when confirming facts. Among other investigated drugs, only alcohol was negatively associated with beliefs in alternative facts. Taken together, our results support the link between psychedelic use and non-conformist thinking styles, which can be attributed to the psychological effects of the drugs themselves, but may also mirror a common trait related to unconventional beliefs and illicit substance use.

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs.

Aim: We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in a retrospective chart review. Methodology: A total of 1,816 reports of adverse events were evaluated. Cases were included in the analysis if the pharmacoepidemiological analysis showed the presence of a high probability of a causal relationship between an adaptogen and antidepressant interaction and the occurrence of adverse events. The following data were extracted from the reports: age, sex, antidepressant, plant products containing adaptogens, other concomitant medications, and clinical consequences of the interactions and their possible mechanisms. Results: Adaptogens were involved in 9% of adverse events associated with the concomitant use of antidepressants and other preparations. We identified 30 reports in which side effects presented a causal relationship with the use of antidepressants and adaptogens. Here, we present the list of adaptogens with the corresponding antidepressants and the side effects caused by their interactions: Withania somnifera: reboxetine (testicle pain and ejaculatory dysfunctions), sertraline (severe diarrhea), escitalopram (myalgia, epigastric pain, nausea, vomiting, restless legs syndrome, and severe cough), and paroxetine (generalized myalgia, ophthalmalgia, and ocular hypertension); Eleutherococcus senticosus: duloxetine (upper gastrointestinal bleeding), paroxetine (epistaxis), sertraline (vaginal hemorrhage), and agomelatine (irritability, agitation, headache, and dizziness); Schisandra chinensis: bupropion (arthralgia and thrombocytopenia), amitriptyline (delirium), and fluoxetine (dysuria); Tribulus terrestris: citalopram (generalized pruritus), escitalopram (galactorrhea), and trazodone (psoriasis relapse); Coptis chinensis: mianserin (arrhythmias), mirtazapine (edema of lower limbs and myalgia), and fluoxetine (gynecomastia); Cimicifuga racemosa: mianserin (restless legs syndrome), paroxetine (gynecomastia and mastalgia), and venlafaxine (hyponatremia); Bacopa monnieri: agomelatine (back pain and hyperhidrosis) and moclobemide (myocardial infarction); Gynostemma pentaphyllum: duloxetine (back pain); Cordyceps sinensis: sertraline (upper gastrointestinal bleeding); Lepidium meyenii: mianserin (restless legs syndrome); and Scutellaria baicalensis: bupropion (seizures). Conclusion: Clinicians should monitor the adverse events associated with the concomitant use of adaptogens and antidepressant drugs in patients with mental disorders. Aggregation of side effects and pharmacokinetic interactions (inhibition of CYP and p-glycoprotein) between those medicines may result in clinically significant adverse events.

Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study

ObjectiveTo study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism.DesignNationwide cohort study.SettingDenmark through national registries.ParticipantsAll 15-49 year old women...

Prescription high-risk polysubstance use among opioid maintenance treatment patients.

Among individuals receiving buprenorphine or methadone as opioid maintenance treatment (OMT), concomitant use of other central nervous system depressants, including prescription drugs, can increase risk of overdose. We aimed to 1) determine the prevalence of use of high-risk prescription drugs (opioid analgesics, benzodiazepines, benzodiazepine-related drugs, and gabapentinoids) among OMT patients, 2) calculate its associations with different mental health and pain-related diagnoses, and 3) compare prevalence of concomitant use with the general population. A national sample comprising all individuals filling at least one prescription of OMT drugs in Norway in 2019 was formed. Healthcare registry data were linked to investigate high-risk prescription drug use and different diagnoses. We calculated one-year prevalence of use, amount dispensed in defined daily doses (DDDs), and the number of prescribers for the different high-risk prescription drugs. Logistic regression was used to determine associations (adjusted odds ratios; aOR, 95% confidence intervals (CIs)) between diagnoses and use. Prevalence of use was calculated both in the OMT patient sample and the general population. Among the OMT patient sample (n=7,299), 47.6% (n=3,476) filled prescriptions for benzodiazepines. For each high-risk prescription drug group, there was a median of 1-2 prescribers. Musculoskeletal diagnoses were the strongest factor for concomitant high-risk prescription drug use for both males (aOR 3.23, CI: 2.72-3.85) and females (aOR 3.07, CI: 2.42- 3.90). The 1-year prevalence of benzodiazepine use was 11.4 times higher for males and 7.1 times higher for females in OMT than the general population. The amount in DDDs was higher for every drug for OMT patients than the general population, particularly for benzodiazepines. OMT patients frequently filled prescriptions for high-risk drugs, and in higher dosages than the general population. However, we found little evidence of 'doctor shopping.' Given that these prescription drugs carry overdose risk, particularly when combined with OMT drugs, our findings emphasize the continued need for education and caution to both prescribers and patients on their concomitant use with OMT.

Characteristics of polypharmacy in nonagenarians and centenarians

Introduction: Nonagenarians and centenarians are often affected by multiple morbidities that require the concomitant use of several drugs. Polypharmacy is defined as the consumption of five or more drugs and poses a cautionary challenge in healthcare. It is important to ensure the correct and safe use of medications. Objectives: To study the sociodemographic and clinical characteristics of polypharmacy in nonagenarians and centenarians. Methods: The location of the descriptive, cross-sectional, retrospective study was in the capital of the southern region of Brazil. A total of 243 nonagenarians and centenarians were evaluated between June 2016 to November 2016. Results: A total of 1450 medications were identified, corresponding to 5.9 ±2.87 medications perparticipant. Among the participants, 163 (67%) were considered as polypharmacy. The frequency of polypharmacy was higher than most reports in the literature, related to poor vision (74.18%, p=0.025), a history of cardiovascular diseases (78.00%, p&lt;0.001), gastric diseases (77.33%, p=0.023), anxiety (80.00%, p=0.041), respiratory diseases (83.33%, p=0.014), arthrosis (76.53, p=0.010), thyroid disease (82.00%, p=0.012), symptoms of xerostomia (75.65%, p=0.008), dyspnea (78.85%, p=0.042), wheezing (81.10%, p=0.049), and fear of falling (72.90%, p=0.049). Conclusion: We concluded that polypharmacy is a prevalent phenomenon among nonagenarians andcentenarians; importance of sociodemographic and clinical characteristics must be taken into consideration when providing primary healthcare to this population.

Artificial Neural Network Analysis of Determinants of Tacrolimus Pharmacokinetics in Liver Transplant Recipients.

The efficacy and toxicity of tacrolimus are closely related to its trough blood concentrations. Identifying the influencing factors of pharmacokinetics of tacrolimus in the early postoperative period is conducive to the optimization of the individualized tacrolimus administration protocol and to help liver transplant (LT) recipients achieve the target blood concentrations. This study aimed to develop an artificial neural network (ANN) for predicting the blood concentration of tacrolimus soon after liver transplantation and for identifying determinants of the concentration based on Shapley additive explanation (SHAP). In this retrospective study, we enrolled 31 recipients who were first treated with liver transplantation from the Department of Liver Transplantation and Hepatic Surgery, the First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) from November 2020 to May 2021. The basic information, biochemical indexes, use of concomitant drugs, and genetic factors of organ donors and recipients were used for the ANN model inputs, and the output was the steady-state trough concentration (C0) of tacrolimus after oral administration in LT recipients. The ANN model was established to predict C0 of tacrolimus, SHAP was applied to the trained model, and the SHAP value of each input was calculated to analyze quantitatively the influencing factors for the output C0. A back-propagation ANN model with 3 hidden layers was established using deep learning. The mean prediction error was 0.27 ± 0.75 ng/mL; mean absolute error, 0.60 ± 0.52 ng/mL; correlation coefficient between predicted and actual C0 values, 0.9677; and absolute prediction error of all blood concentrations obtained by the ANN model, ≤3.0 ng/mL. The results indicated that the following factors had the most significant effect on C0: age, daily drug dose, genotype at CYP3A5 polymorphism rs776746 in both recipient and donor, and concomitant use of caspofungin. The predicted C0 value of tacrolimus in LT recipients increased in a dose-dependent manner when the daily dose exceeded 3 mg, whereas it decreased with age when LT recipients were older than 48 years. The predicted C0 was higher when recipients and donors had the genotype CYP3A5*3*3 than when they had the genotype CYP3A5*1. The predicted C0 value also increased with the use of caspofungin or Wuzhi capsule. The established ANN model can be used to predict the C0 value of tacrolimus in LT recipients with high accuracy and good predictive ability, serving as a reference for personalized treatment in the early stage after liver transplantation.

Selective serotonin reuptake inhibitors related bleeding risk: case report and review of literature

Gastrointestinal bleedings are relevant side effects in patients during anticoagulant therapy for atrial fibrillation. Direct oral anticoagulants (DOACs) are less correlated with major bleeding events than vitamin K antagonists (VKAs), but concerns are present about the relative risk of gastrointestinal bleeding. Here we report the case of a patient with atrial fibrillation and dementia on DOAC treatment who developed a SSRI-associated thrombocytopenia with subsequent life-threatening bleeding. Physicians should be aware of the possible correlation between SSRI-induced thrombocytopenia and concomitant use of anticoagulant and/or antiplatelet drugs, thus preventing life-threatening bleedings.

Concomitant Drug Use among Opioid-Dependent Patients with and without Attention Deficit Hyperactivity Disorder: Does Methylphenidate Merit a Trial?

Introduction: Concomitant drug use is common among opioid-dependent patients in maintenance therapy. Attention deficit hyperactivity disorder (ADHD), a common comorbidity among opioid users, is associated with a higher risk of concomitant drug use. Earlier studies showed that methylphenidate (MPH) can reduce cocaine consumption among patients with ADHD. The use of MPH as an agonist-replacement or maintenance therapy in cocaine-dependent patients without ADHD is also common in Switzerland, despite a lack of supporting evidence. The aim of this study was to assess concomitant cocaine, amphetamine, MDMA, MPH, and heroin use among patients in opioid maintenance therapy either with or without comorbid ADHD. We expected stimulant consumption to be higher in patients with cocaine dependence and comorbid ADHD and that use of MPH would not lead to a reduction in cocaine consumption in patients without ADHD. We therefore evaluated correlations between use of MPH and cocaine consumption and between MPH consumption and cocaine craving within the two groups. Methods: This cross-sectional study included 94 opioid-dependent patients in maintenance therapy in an outpatient department of the Psychiatric Hospital of Zurich. The patients were divided into two groups based on comorbid ADHD; a group with ADHD (N = 27) and a group without ADHD (N = 67). Drug use was assessed using 3-month hair analysis. Results: We did not find significant differences in the number of patients using cocaine, amphetamine, MDMA, or heroin between groups with or without ADHD. With respect to cocaine use, 85.2 percent of patients in the ADHD group and 73.1 percent in the non-ADHD group were users. The non-ADHD group showed a significant positive correlation between the concentration of MPH and cocaine in hair samples (p < 0.05), and a positive correlation between cocaine craving and the concentration of MPH in hair samples (p = 0.065). These two trends were not evident in the ADHD group. Conclusion: Among patients without ADHD, use of MPH correlates with higher cocaine consumption and craving. Conversely, no significant correlation was found between MPH and cocaine use in patients with ADHD. Our study adds to the evidence that MPH confers negative effects in cocaine users without ADHD and should thus have no place in the treatment of these patients.

Safety and effectiveness of ambrisentan in real clinical practice in pulmonary arterial hypertension: Results from the Korean post-marketing surveillance.

This regulatory post-marketing surveillance (PMS) was organized to identify the safety and effectiveness of ambrisentan in the Korean population. This was an open-label, multi-center PMS conducted from 31 institutions in Korea for 6 years from August 2015 to 2021, to evaluate the use of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). Inclusion criteria are Korean subjects with the World Health Organization functional classification (WHO Fc) II or III PAH who are new users or repeated users with ambrisentan (Volibris®) Tablet 5 or 10 mg per day (age >18 years old). A total of 293 cases were analyzed. The overall incidence of adverse events (AE) was 52.22% and adverse drug reactions (ADR) was 10.92%. Severe AEs occurred in 20.82% of patients. However, only 2 subjects (0.68%) reported serious ADR. The difference in AE incidence was statistically significant for concomitant medications other than PAH medications in the safety analysis and the new users (p = 0.0041 and p = 0.0299, respectively) and elderly population in the repeated users (p = 0.0319). Among the long-term 223 subjects, the WHO Fc II and III were 41.26% and 58.74% before ambrisentan, and changed after treatment to 3.09%, 66.05%, and 30.86% for Fc I/II/III, respectively. 217 of 249 subjects (87.15%) considered their symptoms to have 'improved' after the last administration. In real-world practice, ambrisentan demonstrated tolerable safety and favorable effectiveness in PAH patients in Korea. Age and concomitant drug use can affect the occurrence of AE.

Effectiveness of long term therapy of inhaled Steroids in Childhood Asthma: A Systemic Review

Asthma exacerbations are a common and important cause of attendance at emergency departments and subsequent hospital admissions. This systemic review aimed to evaluate the effectiveness of long term therapy of inhaled steroids in childhood asthma. A search of PubMed (Medline) from January 1996 through February 2021 by using the keywords inhaled steroids in childhood asthma, identified potential studies. All randomized controlled trials and clinical trials of prophylactic inhaled steroid therapy for childhood asthma that included data on clinical outcomes (symptoms improvement and concomitant drug use) or laboratory outcomes (peak expiratory flow rate PEFR and (or) forced expiratory volume in first second FEV1) were included. Studies of children (?18?years old) with mild-to-moderate chronic or persistent asthma will be included.Results: In total, 15 of 116 studies met the inclusion criteria. Inhaled corticosteroids (ICS)versus placebo(3studies): ICS show good control on bronchial asthma by ratio(66.7%) and there was no improvement by placebo.ICS versus Mast cell stabilizer (DSCG, cromolyn sodium or nedocromil)(6 studies): by ICS there was better control of asthma, lower of airway hyperresponsivness, decrease risk for hospitalization in comparing to mast cell stabilizers by ratio of (66.7%).ICS versus LTRA (Montelukast)(3 studies) : by ICS better control of symptoms, modified exacerbation risk, improvement of pulmonary function in comparing to LTRA by ratio of (66.7%).ICS versus OCS (2 studies):more rapid clinical improvement results by OCS (50%), more improvement in the inflammatory markers by ICS(50%), reduction in rescue medication in both groups(100%).ICS alone (3 studies): good control of asthma including exercise asthma(66.7%).This Research concluded that the prophylactic inhaled steroids are more effective compared to placebo, mast cell stabilizer drugs and leukotriene receptor antagonist. ICS improving both clinical and laboratory outcomes in childhood asthma.&#x0D;