Concomitant Drug Use Research Articles

Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis

BackgroundThe role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis. MethodsWe searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models. ResultsSix observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I2 = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02). ConclusionsEvidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.

Determinants and Clinical Significance of Musculoskeletal Symptoms in Patients With Chronic Graft-Versus-Host Disease.

Musculoskeletal symptoms in chronic graft-versus-host disease (cGVHD) are rare manifestations contributing to disease burden. This study assesses the frequency of muscle cramps, joint and muscle aches, and muscle weakness in a cohort of patients severely affected by cGVHD. Three hundred thirty-four patients participated in the NCI natural history study of cGVHD (NCT00092235) from October 2004 to March 2017. Five-point Lee cGVHD Symptom Scale was dichotomized (less symptom bother—0, 1, 2; severe symptom bother—3, 4) and tested for associations with: Short Form 36 (SF36), 2-minute walk test, grip strength, joint range of motion, and human activity profile, clinical and laboratory data. Seventy-five point four percent of patients reported joint and muscle aches (36.8% severe, Lee Symptom Scale score 3–4), 74.3% muscle cramps (33.5% severe), and 82.34% muscle weakness (45.51% severe), which were associated with reduced functional capacity (SF36 Physical Component Scale, P < 0.0001). Muscle cramps were associated with limited joint movement (P < 0.0001) and skin manifestations (skin thickening, P = 0.0008; itchy skin, P = 0.0003). Muscle cramps did not show association with potential causative agents, such as concomitant calcineurin inhibitors therapy, statins, or use of antidiabetic drugs. Joint and muscle aches showed associations with multiple variables (including strong associations with mood symptoms and fatigue, P < 0.0001). Muscle weakness was not associated with steroid dose, but was significantly associated with depression (P < 0.0001) and anxiety (P = 0.0009). This study documents a high frequency of musculoskeletal symptoms in a cohort of adult patients with cGVHD. The multivariable logistic regression models showed that a joint set of factors were moderately well associated with musculoskeletal symptoms in this study.

Association study identifies genetic determinants and non-genetic factors on steady-state plasma and therapeutic outcome of galantamine in mixed dementia.

This study aimed to evaluate the influence of genetic polymorphisms of drug-metabolizing enzyme genes, transporter gene, pathological gene (APOE), and non-genetic factors on therapeutic outcomes as well as steady-state plasma concentrations (Cpss) of galantamine in Thai patients with mixed dementia. Fifty-one Thai patients with mixed dementia who received galantamine for at least 6months were recruited. CYP2D6, CYP3A5, and ABCB1 polymorphisms were detected by TaqMan® Genotyping Assay. UGT1A1 and APOE polymorphism was detected by direct Sanger sequencing technique and restriction fragment length polymorphism technique. Cpss of galantamine was measured by ultra-performance liquid chromatography. Associations of genetic and non-genetic factors with Cpss and clinical outcomes (change in cognitive function as measured by the Thai Mental State Examination (ΔTMSE) scores) were determined by using univariate and multivariate analysis. The multivariate regression model revealed that patients who carried one or more detrimental allelic variant (CYP2D6, CYP3A5, and UGT1A1) showed a tendency toward a higher galantamine adjusted Cpss (B = 34.559, 95% CI = 0.741-68.377, p value = 0.045). Logistic regression analysis also revealed CYP2D6*10 carriers were significantly associated with higher ΔTMSE (B = 5.227, 95% CI = 2.395-8.060, p value = 0.001). UGT1A1 mutant alleles and non-genetic factors including concomitant use of statin drugs and higher education level can attenuate therapeutic outcomes of galantamine. Pharmacokinetic-related genes including CYP2D6*10 and UGT1A1 mutant alleles were significantly associated with galantamine adjusted Cpss and cognitive function. Determination of Cpss and genotype could be an adjunct examination to provide further explanation in interindividual variability of galantamine therapeutic outcome.

Prevalence of Housing Insecurity in Survivors of Traumatic Injury.

Almost 20% of the US population are housing insecure (HI) due to inadequate living conditions, imbalanced costs to income, nonsustainable shelter, or overcrowding. Housing insecure and physical trauma share similar risk factors, but their direct association is not well elucidated. The objective of our study was to determine the prevalence of HI in survivors of traumatic injury. We conducted a prospective cohort study at an urban, level 1 trauma center. A survey on social determinants of health was administered to adult patients, and demographic, injury specifics, and clinical outcomes data were collected. HI was defined by affirmative answers to questions related to history of homelessness or concern about sustainable shelter. The cohort was stratified by HI; groups were compared using the Mann-Whitney U and Fisher exact tests, as appropriate. Of 116 study participants, four were excluded due to missing data. Of the 112, 42 (37.8%) reported HI and most were black (69%) males (73.8%). There were no demographic differences between groups. Conversely, HI patients had a higher rate of penetrating traumatic injury (34.1% vs 14.5%, P-value = .03) and were significantly less educated compared to secure participants (P-value = .03) [no degree (26.2% vs 10.3%), high school degrees (21.4% vs 41.2%)] with concomitant illicit drug use (63.4% vs 27.9%, P < .001), and history of addiction (52.4% vs 7.2%, P < .001). HI far exceeds national averages in our cohort. Although difficult to ascertain a cause-effect relationship, HI may be a modifiable risk factor for trauma that negatively influences outcomes.

Important Risk Factors in Patients with Nonvalvular Atrial Fibrillation Taking Dabigatran Using Integrated Machine Learning Scheme-A Post Hoc Analysis.

Our study aims to develop an effective integrated machine learning (ML) scheme to predict vascular events and bleeding in patients with nonvalvular atrial fibrillation taking dabigatran and identify important risk factors. This study is a post-hoc analysis from the Randomized Evaluation of Long-Term Anticoagulant Therapy trial database. One traditional prediction method, logistic regression (LGR), and four ML techniques—naive Bayes, random forest (RF), classification and regression tree, and extreme gradient boosting (XGBoost)—were combined to construct our scheme. Area under the receiver operating characteristic curve (AUC) of RF (0.780) and XGBoost (0.717) was higher than that of LGR (0.674) in predicting vascular events. In predicting bleeding, AUC of RF (0.684) and XGBoost (0.618) showed higher values than those generated by LGR (0.605). Our integrated ML feature selection scheme based on the two convincing prediction techniques identified age, history of congestive heart failure and myocardial infarction, smoking, kidney function, and body mass index as major variables of vascular events; age, kidney function, smoking, bleeding history, concomitant use of specific drugs, and dabigatran dosage as major variables of bleeding. ML is an effective data analysis algorithm for solving complex medical data. Our results may provide preliminary direction for precision medicine.

Effect of Concomitant Use of Analgesics on Prognosis in Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BackgroundDrug–drug interactions (DDIs) pose new challenges beyond traditional pharmacodynamics in the context of optimizing the treatment options with immune checkpoint inhibitors (ICIs). To alleviate cancer-related pain, analgesics are of absolute vital importance as chronic medications used by cancer patients. However, the possible outcome of ICI treatment concomitant with analgesics remains unclear.MethodsOriginal articles describing the possible influence of analgesics use on ICI treatment published before December 1, 2021 were retrieved from PubMed, Embase, and the Cochrane Library. Odds ratio (OR) with 95% confidence interval (CI) for objective response rate (ORR), hazard ratio (HR) with 95% CI for progression-free survival (PFS), and overall survival (OS) were calculated using the random-effects or fixed-effects model, and heterogeneity was assessed using the χ 2-based Q-test. Publication bias was examined by funnel plot analysis.ResultsA total of 11 studies involving 4,404 patients were included. The pooled OR showed that opioid use decreased the response of opioid users to ICIs compared to non-opioid users (OR = 0.49, 95% CI = 0.37–0.65, p < 0.001). Compared to patients who did not receive opioids, opioid users had an increased risk of progression and mortality (HR = 1.61, 95% CI = 1.37–1.89, p < 0.001; HR = 1.67, 95% CI =1.30–2.14, p < 0.001, respectively). Furthermore, the concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) was not significantly associated with differences in ORR, PFS, and OS in patients treated with ICIs (OR = 1.40, 95% CI = 0.84–2.32, p = 0.190; HR = 0.90, 95% CI = 0.77–1.06, p = 0.186; HR = 0.90, 95% CI = 0.71–1.14, p = 0.384, respectively).ConclusionThe concomitant use of opioids during ICI treatment has an adverse effect on patient prognosis, while the use of NSAIDs is not significantly associated with the prognosis in patients treated with ICIs.

Trends in glycemic control in patients with insulin therapy compared with non-insulin or no drugs in type 2 diabetes in Japan: a long-term view of real-world treatment between 2002 and 2018 (JDDM 66)

IntroductionWe investigated trends in the proportion of diabetes treatment and glycemic control, which may be altered by recent advances in insulin and non-insulin drugs, in Japanese patients with type 2...

Statin discontinuation in persons with and without Alzheimer’s disease

BackgroundAlthough statin use is reported to decrease after dementia diagnosis, time to statin discontinuation and factors associated with discontinuation have not been studied in persons with Alzheimer’s disease (AD). We compared the risk of discontinuation and factors associated with discontinuation, including secondary and primary prevention indication, in statin users with and without AD.MethodsThe register-based Medication Use and Alzheimer’s Disease (MEDALZ) cohort includes community dwellers with a clinically verified AD diagnosed during 2005–2011 in Finland. On the AD diagnosis date (index date), each person with AD was matched with a comparison person without AD. We included 25,137 people with AD and 22,692 without AD who used statin on the index date or initiated within 90 days after. Cox regression models restricted to 4-year follow-up were conducted.ResultThe median time to statin discontinuation was 1.46 years in people with AD and 1.36 years in people without AD. People with AD were more likely to discontinue than people without AD (adjusted HR (aHR) 1.20 (95% CI 1.18–1.24)). This was observed for both primary (aHR 1.11 (1.06–1.16)) and secondary prevention (aHR 1.30 (1.25–1.35)) purpose. Factors associated with discontinuation included higher age and female gender, whereas concomitant cardiovascular drug use and previous statin use were associated with decreased risk.ConclusionThe absolute difference in discontinuation rates was small, and the same factors were associated with statin discontinuation in people with and without AD. The findings suggest that cognitive decline plays a minor role on statin discontinuation.

COVID-19 and Cardiac Arrhythmias: a Contemporary Review.

Purpose of ReviewA significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions.Recent FindingsArrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death.SummaryArrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.

Characteristics of patients with lung cancer in clinical practice and their potential eligibility for clinical trials evaluating tyrosine kinase inhibitors or immune checkpoint inhibitors

IntroductionIn- and exclusion criteria of randomized clinical trials (RCTs) aim to include a homogeneous study-population. This study compared characteristics of lung cancer patients from phase III RCTs evaluating tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) with characteristics of lung cancer patients in a real world setting in the United Kingdom. MethodsA retrospective study was conducted using the Clinical Practice Research Datalink GOLD. Patients (N = 9239) with a first ever lung cancer registration between 2014 and 2018 were identified. Eligibility for inclusion was assessed for twelve RCTs (evaluating TKIs or ICIs). Reasons for potential exclusion and the number of unmet criteria were assessed for each RCT independently. OS was assessed using Kaplan-Meier and Cox proportional hazards analyses. ResultsThe proportion of potentially eligible patients was 74.3% and 51.9% for TKI and ICI RCTs, respectively. History of another malignancy, renal insufficiency or concomitant drug-use were main reasons for exclusion. OS was considerably longer for potentially eligible patients. Hazards ratios varied from 1.17 (95% confidence interval, 1.11–1.24) to 1.35 (1.20–1.42) across the RCTs. ConclusionThis study showed that a considerable proportion of lung cancer patients in a real-world setting would have been ineligible for participation in phase III RCTs and that potentially ineligible patients experienced a shorter OS.

Effect of 15-mg Edoxaban on Clinical Outcomes in 3 Age Strata in Older Patients With Atrial Fibrillation

Long-term use of oral anticoagulants (OACs) is necessary for stroke prevention in patients with atrial fibrillation (AF). The effectiveness and safety of OACs in extremely older patients (ie, aged 80 years or older) with AF and at high risk of bleeding needs to be elucidated. To examine the effects of very low-dose edoxaban (15 mg) vs placebo across 3 age strata (80-84 years, 85-89 years, and ≥90 years) among patients with AF who were a part of the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial. This prespecified subanalysis of a phase 3, randomized, double-blind, placebo-controlled trial was conducted from August 5, 2016, to December 27, 2019. Patients with AF aged 80 years or older who were not considered candidates for standard-dose OACs were included in the study; reasons these patients could not take standard-dose OACs included low creatinine clearance (<30 mL per minute), low body weight (≤45 kg), history of bleeding from critical organs, continuous use of nonsteroidal anti-inflammatory drugs, or concomitant use of antiplatelet drugs. Eligible patients were recruited randomly from 164 hospitals in Japan and were randomly assigned 1:1 to edoxaban or placebo. Edoxaban (15 mg once daily) or placebo. The primary efficacy end point was the composite of stroke or systemic embolism. The primary safety end point was International Society on Thrombosis and Hemostasis-defined major bleeding. A total of 984 patients (mean [SD] age: age group 80-84 years, 82.2 [1.4] years; age group 85-89 years, 86.8 [1.4] years; age group ≥90 years, 92.3 [2.1] years; 565 women [57.4%]) were included in this study. In the placebo group, estimated (SE) event rates for stroke or systemic embolism increased with age and were 3.9% (1.2%) per patient-year in the group aged 80 to 84 years (n = 181), 7.3% (1.7%) per patient-year in the group aged 85 to 89 years (n = 184), and 10.1% (2.5%) per patient-year in the group aged 90 years or older (n = 127). A 15-mg dose of edoxaban consistently decreased the event rates for stroke or systemic embolism with no interaction with age (80-84 years, hazard ratio [HR], 0.41; 95% CI, 0.13-1.31; P = .13; 85-89 years, HR, 0.42; 95% CI, 0.17-0.99; P = .05; ≥90 years, HR, 0.23; 95% CI, 0.08-0.68; P = .008; interaction P = .65). Major bleeding and major or clinically relevant nonmajor bleeding events were numerically higher with edoxaban, but the differences did not reach statistical significance, and there was no interaction with age. There was no difference in the event rate for all-cause death between the edoxaban and placebo groups in all age strata. Results of this subanalysis of the ELDERCARE-AF randomized clinical trial revealed that among Japanese patients aged 80 years or older with AF who were not considered candidates for standard OACs, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism consistently across all 3 age strata, including those aged 90 years or older, albeit with a higher but nonstatistically significant incidence of bleeding. ClinicalTrials.gov Identifier: NCT02801669.

Risk of New-Onset Diabetes Mellitus Associated with Antirheumatic Drugs in Patients with Rheumatoid Arthritis: A Nationwide Population Study.

Background: This study aimed to investigate the effect of disease-modifying antirheumatic drugs (DMARDs) on diabetes mellitus (DM) development in rheumatoid arthritis (RA). Methods: This nested case–control study with a cohort of 69,779 DM-naïve adult patients with RA was conducted from 2011 to 2019 in South Korea. Cases with incident DM were identified and individually matched to randomly selected controls (1:4). DMARDs use was measured for 1 year before the index date and stratified by exposure duration. The association of each DMARD use with DM risk was estimated using conditional logistic regression adjusted for comorbidities and concomitant drug use. Results: Of the patients, 5.4% were newly diagnosed with DM. The use of statins and a higher cumulative dose of corticosteroids were associated with an increased DM risk. In a multivariable-adjusted analysis, cumulative duration of exposure (CDE) >270 days/year, hydroxychloroquine (HCQ; adjusted odds ratio [aOR], 0.76) and methotrexate (MTX; aOR, 0.81) were associated with a significant decrease in DM risk, and tacrolimus (TAC; aOR, 1.27) was associated with an increased risk. Conclusions: Long-term use of HCQ and MTX (>270 days/year) was associated with a reduction in DM incidence as opposed to TAC.

Single Acute Mechanical Circulatory Support Device Use is Associated with Reduced Mortality Compared to Multi-Agent Drug Therapy Alone for Cardiogenic Shock: An Analysis of the Cardiogenic Shock Working Group Registry

<h3>Purpose</h3> Real world evidence evaluating outcomes in cardiogenic shock complicating heart failure or ST-segment elevation myocardial infarction (HF-CS and STEMI-CS) in the contemporary era of acute mechanical circulatory support (AMCS) remains a major unmet need. We studied the utility of the recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) stages in HF- and STEMI-CS. <h3>Methods</h3> The Cardiogenic Shock Working Group registry includes CS patients from 15 US hospitals enrolled between 2016-2021. Patients were classified by the maximum SCAI stage (B-E) reached during hospitalization based on drug (vasopressors or inotropes) and device use. In-hospital mortality was evaluated for association with SCAI stages. <h3>Results</h3> Of the 3171 patients with CS, 1680 (53%) and 739 (23%) were due to HF or STEMI. In-hospital mortality was 24% vs 42% (p<0.01) for HF or STEMI CS respectively. In-hospital mortality was associated with increasing SCAI stage among patients with HF-CS (Odds Ratio [95% CI], 3.129 [2.59-3.78], p<0.001) or STEMI-CS (Odds Ratio [95% CI], 2.158 [1.78-2.62], p<0.001; Fig A-D). Compared to patients receiving ≥3 drugs and no AMCS device, in-hospital mortality was lower among HF-CS patients receiving 1 AMCS device with ≤2 drugs (Fig E) and lower among STEMI-CS patients receiving 1 AMCS device irrespective of concomitant drug use (Fig F). <h3>Conclusion</h3> Using one of the largest, contemporary, multi-center, real-world practice registries of CS, our findings support a direct association between SCAI stages and in-hospital mortality in HF-CS and STEMI-CS and further identify that compared to multi-agent drug therapy alone, single AMCS device use may be associated with lower mortality. These findings support the need for randomized clinical trials in HF- and STEMI-CS.

Combined Use of Calcium-channel Blockers With Ombitasvir/Paritaprevir/Ritonavir Exacerbates Peripheral Edema in Elderly Japanese Patients

The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potential adverse drug reaction possibly caused by the anti-hepatitis C virus (HCV) regimen of ombitasvir/paritaprevir/ritonavir (OPR) and CCBs. We enrolled Japanese patients prescribed OPR for HCV infection. Peripheral edema was graded according to the Common Terminology Criteria for Adverse Events ver. 4. Plasma samples were collected on days 0, 7, 14, 28, and 42 after antiviral treatment, at the trough level. Out of 52 patients, 64% experienced grade 1 or grade 2 peripheral edema, but not grade 3. Concomitant use of CCBs significantly increased the emergence of grade 2 edema (62%), compared with patients treated solely with OPR (48%). The use of OPR significantly increased the plasma concentration of amlodipine. Peripheral edema in patients treated with OPR and CCBs, although tolerable, should be closely monitored.

Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review.

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is the leading cause of death worldwide, and antipsychotic medications are associated with numerous cardiac side effects. A possible link exists between antipsychotic medications and sudden cardiac death. Common prescribing patterns that may influence cardiovascular events include the use of multiple antipsychotics and/or additional drugs commonly prescribed to patients on antipsychotics. The results of this review reflect an association between antipsychotic drugs and increased risk of ventricular arrhythmias and sudden cardiac death by iatrogenic prolongation of the QTc interval. QTc prolongation and sudden cardiac death exist in patients taking antipsychotic monotherapy. The risk increases for the concomitant use of specific drugs that prolong the QTc interval, such as opioids, antibiotics, and illicit drugs. However, evidence suggests that QTc intervals may not adequately predict sudden cardiac death. In considering the findings of this narrative review, we conclude that it is unclear whether there is a precise association between antipsychotic polypharmacy and sudden cardiac death with QTc interval changes. The present narrative review warrants further research on this important potential association.

Exploring the self-reported motivations of kratom (Mitragyna speciosa Korth.) use: a cross-sectional investigation

ABSTRACT Background Kratom (Mitragyna speciosa Korth.) use outside of Southeast Asia has increased over the past decade. Objectives This investigation clarifies kratom’s role in perceived well-being, overall health, and temporal correlation with drug use to understand kratom’s role in the self-treatment of substance use disorders (SUDs). Methods Between July 2019 and July 2020 an anonymous, cross-sectional, online survey was taken by 7,381 people who use kratom (PWUK) recruited through social media and other online resources. This included an assessment of (a) the relationship between self-reported overall health, concomitant use of drugs of misuse, and demographics; (b) the perceived effectiveness of kratom in self-treating diagnosed health conditions or symptoms; (c) the profile of PWUK primarily for drug dependence, pain, and mood or mental health conditions based on demographics. Results A total of 5,152 valid responses (45.9% females/53.7% males) were collected. Kratom was primarily used for self-treating pain (73.0%) and improving emotional or mental health conditions (42.2%) without clinical supervision. Those with a SUD (synthetic opioids, methadone, benzodiazepines, or heroin) used kratom after discontinuing illicit or other drugs (94.8%). The primary substances taken before or concomitantly with kratom were cannabis, cannabidiol, benzodiazepines, or kava. PWUKs report a dose-dependent benefit for alleviating pain and relieving negative moods. Adverse effects were primarily gastrointestinal, typically at high (>5 g/dose) and frequent (>22 doses/week) dosing. Conclusions Kratom was primarily used as a harm-reduction agent for SUDs and self-treatment of chronic conditions. Healthcare professionals need better information about kratom, its potential adverse effects, and clinically significant drug interactions.

Prevalence and management of drug interactions between nonsteroidal anti-inflammatory drugs and antithrombotics in ambulatory care.

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents is associated with increased risks of both bleeding and thromboembolism. In this prospective intervention study, community pharmacists screened for NSAID-antithrombotic interactions and contacted the prescribing physician to discuss interaction management. We included 782 interactions; these were found in an older, polymedicated patient population (mean age: 68 y, median of 5 other drugs). Ibuprofen (in 43.0% of cases) and low-dose aspirin (78.8%) were the most frequently involved NSAID and antithrombotic, respectively. Anticoagulants were involved in 16.1% of interaction cases. For 61% of cases, the interacting drugs were prescribed by the same physician. The pharmacist-physician discussion about how to manage the interaction mostly resulted in no change of pharmacotherapy (60.7%); the most frequent reason given by physicians was that the NSAID was for short-term use only. In 39.3% of cases the discussion resulted in a pharmacotherapy change; replacing the NSAID by paracetamol was the most common change.

Relationship of concomitant anti-diabetic drug administration with sodium-glucose co-transporter 2 inhibitor-related ketosis.

ObjectiveThe use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) may be associated with ketoacidosis. Therefore, the associated risk factors should be identified. In particular, information regarding the effects of the co-administration of anti-diabetic drugs is lacking.MethodsWe performed a retrospective study of 68 consecutive patients with diabetes who were taking an SGLT2i and attending a single medical center. After a period of treatment (median 78 days), their circulating ketone concentrations were measured. The concomitant use of other anti-diabetic drugs was analyzed to identify independent risk factors associated with ketosis.ResultsTwenty-five participants were taking empagliflozin, 23 were taking dapagliflozin, and 20 were taking canagliflozin. During the treatment period, no ketoacidotic events were recorded and their mean circulating ketone concentrations at the end of the study period were similar (0.3 mmol/L in the empagliflozin group, 0.26 mmol/L in the dapagliflozin group, and 0.25 mmol/L in the canagliflozin group). After adjustment for the use of anti-diabetic drugs, pioglitazone was found to be independently associated with a risk of high circulating ketone concentration (B value: 0.361, 95% confidence interval: 0.181–0.541).ConclusionSGLT2i-associated ketoacidosis was found to be infrequent, but the concomitant use of pioglitazone was associated with a higher risk of ketosis.

Use of Drugs With Risk of Heart Rate-Related Problems is Common in Norwegian Dementia Patients Treated With Acetylcholinesterase Inhibitors: A Prevalence Study Based on the Norwegian Prescription Database

Background: Drugs commonly prescribed for heart rate control may induce adverse drug reactions in Alzheimer patients treated with acetylcholinesterase inhibitors (AChEIs). We have studied use of drugs with a known risk of Torsades de pointes (TdP) and drugs used to treat behavioral and psychological symptoms of dementia, as well as a combination of drugs with a known risk of TdP and drugs with a known heart rate-lowering effect, before and after initiating treatment with AChEIs. Methods: The study applied data from the Norwegian Prescription Database for the period 2004–2016. Prescriptions of concomitant use of drugs in persistent users of AChEIs was studied in a follow-up period from 4 years before to 2 years after AChEI initiation in men and women of two age groups: 37–80 and 81–88 years. Results: A small number of patients were prescribed haloperidol (∼1.5% The second year after AChEI initiation), digoxin/digitoxin (∼3%), and verapamil (∼1.3%), while a substantial proportion of the patients were prescribed betablockers (∼28%) and citalopram/escitalopram (∼17%). During follow-up, up to 6% of the study population were prescribed both betablockers and citalopram/citalopram in addition to AChEIs, a combination that increased over the follow-up period and was observed most frequently in women in the oldest age group. Conclusions: A large proportion (∼44%) of patients treated with AChEIs were prescribed drugs that could cause bradycardic and prolonged time from the start of the Q wave to the end of the T wave (QT interval). Thus, action should be taken to reduce the combination of drugs with risk of bradycardia and prolonged QT interval. Medication review on a regular basis could be an option as an important risk-reducing intervention.

Post Hoc Analysis of Predictors of Clinical Response to Repository Corticotropin Injection in Persistently Active Rheumatoid Arthritis.

IntroductionA phase IV clinical trial confirmed the safety and efficacy of repository corticotropin injection (RCI, Acthar® Gel) in patients with refractory rheumatoid arthritis (RA) that was nonresponsive to standard-of-care therapies. The objective of this post hoc analysis was to identify baseline demographics and clinical characteristics that may be predictors of response to RCI.MethodsThe phase IV trial was a two-part, randomized, placebo-controlled withdrawal study. Post hoc analysis was conducted with the open-label portion of the trial data, in which all 258 subjects received RCI (80 U) twice weekly for 12 weeks. Responders were subjects who achieved low disease activity (LDA) by a Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) of < 3.2 at week 12. Responders were compared with nonresponders by assessing the proportion of subjects in each group for demographics and clinical characteristics, including weight, disease duration, medical history including osteoarthritis and unrelated joint conditions, hemoglobin A1c, C-reactive protein, ESR, DAS28-ESR, Clinical Disease Activity Index (CDAI), depression, anxiety, tender joint count (TJC), and swollen joint count (SJC). Bivariate analysis followed by multiple logistic regression analysis were conducted to identify significant baseline predictors for the outcome of achieving LDA by week 12.ResultsBivariate analysis showed that RCI responders had significantly lower baseline TJC (p = 0.0310), SJC (p = 0.0018), ESR (p = 0.0487), and CDAI (p = 0.0112) and shorter RA disease duration (p = 0.0446). Subjects were less likely to achieve LDA if they had osteoarthritis (p < 0.0001), other joint-related conditions unrelated to RA (p < 0.0001), anemia (p = 0.0132), depression (p = 0.0006), or prior or concomitant use of targeted-synthetic or biologic disease-modifying antirheumatic drugs (p < 0.0001). Multiple logistic regression analysis revealed that, of the above, only ongoing osteoarthritis (p = 0.0272) or other joint-related conditions (p = 0.0193) were significant negative predictors of RCI response.ConclusionsThese results identify specific patient characteristics that may be considered predictors of positive or negative clinical response to RCI.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00429-w.