Concomitant Prescription Research Articles

Association of Benzodiazepine Prescription With Short-Term Prognosis in Elderly Patients Attended in Emergency Department: Results From the EDEN PROJECT.

Benzodiazepine prescription is a growing phenomenon among the elderly population. However, information related to the frequency of these drugs among the elderly population attending in emergency departments (ED) and its impact over prognosis is scarce. The aim of this study is to assess the prevalence of benzodiazepine prescription and to analyze its association with short-term prognosis in elderly patients attended in ED. A retrospective analysis of the EDEN (Emergency Department Elderly in Need) cohort was conducted. This registry included all elderly patients attending in 52 Spanish EDs for any condition, between April 1st and 7th in 2019. Socio-demographic data, comorbidities, and medication were recorded by consulting the patient's electronic health records. The assessed outcomes consisted on new ED visit, hospitalization, and mortality at 30 days after the first ED visit, associated with the use of benzodiazepines at baseline in comparison with no prescription of benzodiazepines. Crude and adjusted logistic regression analyses including patient's comorbidities were performed. Two sensitivity analyses were performed considering concomitant prescription of other central nervous system depressants as well as direct discharge from the ED. 25 557 patients were evaluated (mean age 78 [IQR: 71-84]). 7865 (30.8%) patients were taken benzodiazepines at admission. After adjustment for comorbidities and other central nervous system drugs, benzodiazepine prescription was associated with ED revisit [OR: 1.10 (95%CI: 1.03-1.18)]. Similar results were found in the sensitivity analysis, eliminating patients with central nervous depressors [OR: 1.11 (1.03-1.25)] and patients discharged to home [OR: 1.13 (1.04-1.23)]. No association was found between the use of these drugs and new hospitalizations [OR: 0.90 (0.77-1.05)] or mortality 30 days after discharge [OR: 1.01 (0.88-1.18)]. The results held for all three outcomes in the sensitivity analyses. The use of benzodiazepines is a frequent phenomenon among the elderly population attended in the ED, being associated with an increased risk of new visits to the emergency room, but not with an increased risk of 30-day hospitalization or mortality.

Analysis of methotrexate use practice in patients with rheumatoid arthritis and psoriatic arthritis

Background. Pharmacoepidemiological studies play a key role in optimizing pharmacotherapy for various diseases. In particular, significant progress in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) necessitates a detailed analysis of the consumption of disease-modifying antirheumatic drugs. The modern therapeutic concept for these conditions focuses on achieving and maintaining long-term remission, which positions methotrexate (MTX) as a first-line agent, characterized by high effectiveness, safety and advantageous pharmacoeconomic profiles.Objective: to investigate the characteristics of MTX use in real clinical practice among patients with RA and PsA during outpatient medical care.Material and methods. The study comprised two parts: a retrospective cross-sectional analysis of MTX consumption dynamics in 2018, 2020, and 2023 via ATC/DDD (Anatomical Therapeutic Chemical classification, ATC; defined daily dose, DDD) methodology, and a longitudinal non-interventional pharmacoepidemiological study conducted in 2023 using the medical information system “BARS. Healthcare”.Results. The ATC/DDD analysis demonstrated a significant increase in MTX consumption among patients with RA and PsA: from 302,428.6 to 319,114.3 DDDs per 1,000 patients per year for RA, and from 28,157.1 to 310,771.6 DDDs per 1,000 patients per year for PsA in 2018 and 2023, respectively. The most frequently prescribed dose of MT was 15 mg/week. The primary therapeutic combination for 55.8% of patients was “MT + nonsteroidal anti-inflammatory drugs”, with 32.7% of patients also receiving glucocorticoids (GCs) as part of this combination. The study identified a high frequency of prescriptions for proton pump inhibitors, GCs, and cholecalciferol, highlighting the activity of diseases under consideration, potential complications, and the necessity for the prevention of clinically significant drug interactions.Conclusions. The conducted study confirmed that MTX remains the main drug for the treatment of RA and PsA. The ATC/DDD analysis demonstrated a significant increase in MTX consumption in recent years, correlating with its therapeutic effectiveness and accessibility. The high frequency of concomitant prescriptions underscores the complexity of treating RA and PsA and the need for an interdisciplinary approach to ensure safety and efficacy of the therapy.

Impact of concomitant prescriptions and lifestyle factors on the initial course of newly diagnosed inflammatory bowel disease

Introduction: There is a close relationship between the relapse of inflammatory bowel disease (IBD) and lifestyle factors, including concomitant medications such as non-steroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, smoking status, and alcohol consumption. However, solid evidence is limited regarding the risk factors at diagnosis and initial disease course. This study aimed to explore the impact of concomitant prescriptions and lifestyle factors in patients with newly diagnosed IBD using a large-scale real-world database. Methods: This is a retrospective inception cohort study using the insurance claims database. Newly diagnosed patients with UC and CD were enrolled between January 2005 and May 2020. Concomitant prescriptions and lifestyle factors were assessed for new biologics use, surgery, and hospitalization during the first year. Results: In total, 6,743 patients with UC and 1,000 patients with CD were enrolled. Proton pump inhibitors, antithrombotics, antibiotics, and NSAIDs were identified as associated factors for both biologics use and hospitalization in UC patients (all p<0.01), and antithrombotics were identified as associated factors for both biologics use and hospitalization in CD patients (all p<0.01) in multivariable analyses. Interestingly, smoking was protective against hospitalization in UC patients (p<0.01), but not in CD patients (p=0.997), analyzed by univariate analysis. Alcohol consumption was protective against hospitalization outcomes in UC patients (p=0.02) but not in CD patients (p=0.27), analyzed by univariate analysis. Conclusion: Immediate attention should be paid to concomitant medications at diagnosis, because they may have impact on the initial course of IBD.

CML-628 Impact on Healthcare Resource Utilization and Cost of Care of Concomitant Prescribing of Acid-Reducing Agents With Tyrosine Kinase Inhibitors: A US Payer Perspective

CML-628 Impact on Healthcare Resource Utilization and Cost of Care of Concomitant Prescribing of Acid-Reducing Agents With Tyrosine Kinase Inhibitors: A US Payer Perspective

Evaluation of prescribing patterns of switching to and add-on lemborexant in patients treated with hypnotic medication: a nationwide claims database study in Japan

ABSTRACT Background When considering changing hypnotic pharmacotherapy, lemborexant has attracted attention as a candidate due to its effectiveness and safety profile. However, few studies have investigated switching patterns in clinical practice. Research design and methods We conducted a retrospective cohort study using a nationwide claims database. Patients prescribed a single hypnotic who either subsequently switched to (switching cohort) or were additionally prescribed (add-on cohort) lemborexant between July 2020 and December 2021 were identified. Proportion of successful switching was defined as remaining on lemborexant alone or without any hypnotic at 6 months after lemborexant initiation. Results The success proportion was 70.1% in the switching cohort (n = 4,861) and 38.6% in the add-on cohort (n = 9,423). In the add-on cohort, the success proportion was lower in patients with a hypnotic history of ≥180 days (31.4%) and in patients whose prescribed hypnotic was a benzodiazepine or non-benzodiazepine (31.5% and 37.6%, respectively). Conclusion The proportion of successful switching was higher in patients who switched to lemborexant than in those who added lemborexant as a concomitant treatment. The lower success proportion in the add-on cohort might be related to clinically more severe insomnia, and/or a concomitant prescription of benzodiazepine or non-benzodiazepine, from which discontinuation may be challenging.

Treatment of bipolar depression: clinical practice vs. adherence to guidelines-data from a Bavarian drug surveillance project.

Pharmacotherapy of bipolar depression (BPD) is confronted with major clinical challenges, like limited evidence-based treatment options, regular cases of treatment resistance, and risk of treatment-emergent affective switches. Medical guidelines can support practitioners to make decisions based on current scientific evidence. The objective of this study is to evaluate to what extent recommendations of the 2019 German S3 guidelines "Diagnosis and Treatment of Bipolar Disorders" are reflected in clinical practice in inpatient treatment. We conducted a descriptive analysis of prescription numbers in 2,627 patients with BPD in a naturalistic inpatient setting analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014-2022. Of the patients, 38% were not administered any drug explicitly recommended for treatment of BPD, that is, quetiapine, lamotrigine, carbamazepine, or olanzapine. Only 6% of the patients received monotherapy with one of those drugs. Of the patients, 34% were administered ≥4 psychotropic drugs simultaneously. Patients received 912 different therapy regimens of mono or combination therapy with mood stabilizers (MS), atypical antipsychotics (AAP), and antidepressants. Of the patients, 72% received an antidepressant and 6% without concomitant prescription of an AAP or MS. Prescription rates of venlafaxine (21% to 14%) and tricyclic antidepressants (9% to 6%) decreased significantly from the first (2014-2016) to the last (2020-2022) observed time period. Of the patients, 60% received an MS. Prescription rate of valproate (22% to 14%) decreased significantly, while lithium prescription increased significantly (29% to 35%). Of the patients, 71% were administered an AAP. Quetiapine was the most prescribed drug overall (43%). Only two patients were administered a combination of olanzapine and fluoxetine. Our results demonstrate a substantial gap between guideline recommendations and current clinical practice. The remarkable heterogeneity in treatment regimens, with no discernible dominant treatment approach, is in part a reflection of the complexity of bipolar disorder but also substantiates the need of comprehensive recommendations regarding combination therapies. Increase in lithium prescription is an encouraging development due to its unique efficacy in maintenance treatment. To improve the quality of clinical practice guideline implementation, more randomized controlled trials shouldbeconducted in the future to prospectively investigate different implementation strategies.

Salt substitute recommendations for heart failure patients may influence guideline-directed medical therapies titration.

Reducing sodium intake is necessary for patients with chronic heart failure (CHF). Salt substitutes (saltSubs) have become increasingly popular as recommendations by healthcare professionals (HCPs) as well as options for patients and their caregivers. However, their consumption is generally potassium based and remains poorly evaluated in CHF management. Their impact on guideline-directed medical therapies (GDMTs) also remains unknown. The primary objective of this study was to provide a description and estimate of HCP recommendations and reported use of saltSubs in France. Secondary objectives were to identify if there was an association between these recommendations by HCPs and the use of GDMTs. A nationwide, questionnaire-based, cross-sectional, epidemiological study was conducted from September 2020 to July 2021. Data collection included baseline characteristics, the use and recommendations of saltSubs, and the use of GDMTs, which included (i) angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNis), (ii) mineralocorticoid receptor antagonists (MRAs), and/or (iii) beta-blockers (BBs). In total, 13% of HCPs advised saltSubs and 17% of patients and 22% of caregivers reported their consumption. CHF patients advised to take saltSubs did not differ in terms of left ventricular ejection fraction (EF) <40%, ischaemic origin, and New York Heart Association III-IV class, but were more recently hospitalized for acute HF (P=0.004). HCPs who recommended saltSubs to patients were more likely to advise an anti-diabetic diet (P<0.001), cholesterol-lowering diet (P<0.001), and exercise (P=0.018). In the overall population, ACEi/ARB/ARNi use was less frequent in case of saltSub recommendations (74% vs. 82%, P=0.012). The concomitant prescription of none, one, two, or three GDMTs was less favourable in case of saltSub recommendations (P=0.046). There was no significant difference for the presence of MRA (56% vs. 58%) and/or BB (78% vs. 82%). The under-prescription of ACEi/ARB/ARNi was found when patients had EF<40% (P=0.029) and/or EF≥40% (P=0.043). In the subgroup with left ventricular EF≥40%, we found a higher thiazide use (P=0.014) and a less frequent use of low EF GDMTs (P=0.044) in case of being recommended saltSubs. Beyond the well-established risk for hyperkalaemia, our preliminary results suggest a potentially negative impact of saltSubs on GDMT use, especially for ACEis/ARBs/ARNis in CHF management. saltSub recommendations and their availability from open sale outlets should be considered to avoid possible misuse or deference from GDMTs in the future. Informed advice to consumers should also be considered from HCPs or pharmacists.

Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

Prevalence and characteristics of patients prescribed opioids and central nervous system depression agents on discharge to hospice care.

Hospice patients with end-stage liver disease (ESLD) have an increased risk of adverse drug events due to physiological changes and changes in pharmacokinetic and pharmacodynamic properties of medications; however, the use of opioid and central nervous system (CNS) depressant prescribing among patients with ESLD is prevalent. This study quantified the frequency and distribution of opioid and concomitant respiratory and CNS depressant prescribing among hospice patients with ESLD compared to other common hospice diagnoses of cancer, chronic obstructive pulmonary disorder (COPD), heart failure, and end-stage renal disease. This was a cross-sectional study of adult (age 18 years or older) decedents of a large hospice chain. Patients included had a primary diagnosis of liver, cancer, cardiovascular, or respiratory disease. Among 119,424 hospice decedents, mean age of 77.9 years (standard deviation =13.5 years), 54.6% were female, and 58.9% were of a non-Hispanic white race. There was a similar frequency of prescribing a "scheduled" and "as needed [pro re nata (PRN)]" opioid or benzodiazepine in patients with ESLD compared to other common hospice diagnoses. In addition, there was a high prevalence of concurrent opioid and benzodiazepine prescriptions among patients with ESLD compared to cardiovascular and respiratory disease at admission (65.4% vs. 63.9% and 64.9%). Opioid requirements, oral morphine equivalent (OME) median [interquartile range (IQR)] at discharge were similar between cancer, liver, and respiratory disease, 120 OME [60-300], 120 OME [50-240], and 120 OME [50-240], respectively. We observed a high frequency of opioid and CNS depressant prescribing in a hospice patient population with ESLD which was similar to other common admitting hospice diagnoses.

Opioid Prescribing for Noncancer Patients—Issues of Drug Therapy Safety: Results from a German Study Based on Routine Data

Opioids are highly effective drugs but need close monitoring to avoid harm to patients. The aim of this study was to analyze how guideline recommendations are met for (i) the avoidance of the concomitant use of anxiolytics, hypnotics, or sedatives; (ii) the prescribing of laxatives in long-term opioid treatment; (iii) the co-prescribing of drugs to control the emetic effect of opioids; (iv) pretreatment with non-opioids; and (v) screening for depression when initiating opioids. The results are based on a routine data analysis of a large German health insurance fund. Different study populations of noncancer patients (18+ years old) treated with opioids were analyzed: 10.4% of the opioid recipients in 2021 received at least one concomitant prescription with anxiolytics, hypnotics, or sedatives; 69.3% of those with long-term opioid treatment received at least one laxative prescription. Of those with first-time opioid prescriptions, 4.8% received an antiemetic drug; 47.3% of those with a newly initiated opioid therapy received a non-opioid prescription within three months before the start of the opioid therapy; and 22.0% of patients with incident opioid prescription had at least one documentation of a depression diagnosis within three months of the first prescription. There is an urgent need to improve opioid prescribing to avoid risky combinations and adverse effects.

Evaluation of Gabapentin and Pregabalin Use in Hospitalized Patients With Decreased Kidney Function.

Background: Gabapentin and pregabalin are well-tolerated medications primarily cleared by the kidney. Patients receiving higher gabapentinoid doses with decreased kidney function may be at an increased risk of adverse effects (AEs), but limited evidence exists evaluating gabapentinoid dosing and AEs in this population. Objective: To determine whether patients with decreased creatinine clearance (CrCl) experienced increased frequency of AEs related to gabapentinoid dose at hospital admission. Methods: Single-center retrospective cohort study in adults with a gabapentinoid prescription and serum creatinine measurement documented on hospital admission. The primary outcome was the appropriateness of gabapentinoid prescription based on CrCl (stratified by CrCl ≥60 mL/min, <60 mL/min, 15-29 mL/min, and <15 mL/min) at admission. Secondary outcomes included the incidence of AEs related to gabapentinoids and concomitant opioid and psychiatric prescriptions. Results: A total of 286 patients were included in this study (gabapentin n = 234, pregabalin n = 52). Patients with a CrCl <60 mL/min and doses above the manufacturer's recommendation were prescribed gabapentin (34%) and pregabalin (22.7%). For patients with a CrCl of 15 to 29 mL/min and <15 mL/min groups, inappropriately high doses were prescribed for gabapentin (48.8%) and pregabalin (45%). A significant increase in recorded falls (P = 0.029) was identified in patients with a CrCl <60 mL/min. Concomitant opioid and psychiatric medications contributed to a higher prevalence of AEs regardless of CrCl. Conclusions: Patients with a CrCl <60 mL/min were frequently prescribed inappropriately high doses of gabapentinoids. The relationship between gabapentinoid dosing, kidney function, and the incidence of gabapentinoid-related AEs at hospital admission requires larger, multicentre studies.

Efficacy and safety aspects of renal denervation in treatment of arterial hypertension: a systematic review and meta-analysis

Abstract Introduction Current guidelines for the management of arterial hypertension 2018 of European Society for Cardiology (ESC) do not recommend use of renal denervation (RDN) (as device-based therapy) for treatment of hypertension except as part of clinical studies. However, in the meantime several randomized sham-controlled clinical trials were designed using second generation radiofrequency (RF) (SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED), ultrasound (RADIANCE-HTN SOLO, RADIANCE-HTN TRIO) or alcohol-mediated renal denervation (TARGET BP-OFF) devices. We aimed to perform a comprehensive meta-analysis from all published and unpublished randomized, sham-controlled clinical trials which explored the effects of renal denervation on blood pressure across different devices. Methods We searched MEDLINE and Embase via OVID@ for eligible trials. Of note, we also included unpublished data from the SPYRAL-ON Extension and TARGET BP OFF trials. Pooling the data from all studies, we explored the efficacy (ambulatory and office systolic and diastolic BP) and safety (all cause death, vascular complication, renal artery stenosis &amp;gt;70%, hypertensive crisis) of RDN. Results Analysis included 9 eligible trials (i.e. SYMPLICITY HTN-3, ReSET, SPYRAL HTN OFF MED, Desch et al., RADIANCE-HTN SOLO, RADIANCE-HTN TRIO, RADIANCE, TARGET BP OFF, SPYRAL HTN ON MED extension) comprising 2,091 patients (Table 1). RDN reduced ambulatory systolic (-3.10 mmHg, 95% CI -4.22, -1.97, p&amp;lt;0.00001) and office systolic (-5.15 mmHg, 95% CI -6.65, -3.66, p&amp;lt;0.00001) BP and ambulatory diastolic (-1.58 mmHg, 95% CI -2.54, -0.63, p=0.001) and office diastolic (-2.74 mmHg, 95% CI -3.65, -1.83, p&amp;lt;0.00001) BP compared with sham groups. There was no difference concerning ambulatory SBP reduction between trials with ON medication design (-2.94 mmHg, p&amp;lt;0.0001) and those with OFF medication design (-3.37 mmHg, p&amp;lt;0.0001) (p for interaction 0.69). Similarly, office SBP reduction was comparable between trials with (-4.38 mmHg, p&amp;lt;0.0001) and without concomitant antihypertensive drugs prescription (-6.27 mmHg, p&amp;lt;0.00001) (p for interaction 0.22). The rate of vascular complications (OR 1.21, 95% CI 0.28, 5.25, p=0.80), renal artery stenosis (OR 1.50, 95% CI 0.06, 36.97, p=0.80), hypertensive crisis (OR 1.39, 95% CI 0.50, 3.92, p=0.53) and all cause death (OR 0.52, 95% CI 0.10, 2.83, p=0.45) was not different between treatment and sham groups. Conclusions RDN is associated with clinically significant reductions in ambulatory and office SBP as compared with sham in the presence and absence of antihypertensive medication. The procedure use was not associated with an excess in safety events compared with sham group.

Impact of proton pump inhibitor on quality of anticoagulant control and outcomes in atrial fibrillation patients treated with an oral anticoagulant in the COOL-AF registry

Abstract Introduction Proton pump inhibitor (PPI) is commonly prescribed in patients treated with antithrombotic therapy, assuming it will reduce bleeding risk irrespective of the risk of bleeding. Although PPI may reduce the risk of gastrointestinal bleeding in those treated with an oral anticoagulant, PPI may increase INR by accelerating warfarin absorption, thereby increasing the risk of bleeding. We aimed to assess the impact of PPI use on outcomes and quality of anticoagulant control in AF patients treated with OAC. Methods The COOL-AF registry was a nationwide prospective observational study enrolling AF patients from 27 hospitals in Thailand between 2014 and 2017. The registry aimed to evaluate antithrombotic patterns, quality of OAC control, and clinical outcomes. Clinical information of patients was collected every six months and until three years. Patients treated with oral anticoagulants (either warfarin or non-vitamin K antagonist OAC (NOAC)) were included in the present analysis. Patients receiving any PPI type and dosage at the registry entry were counted as PPI users. Poor anticoagulant control was defined as time to therapeutic range (TTR) less than 65%. The association between PPI use and outcomes, including GI bleeding, overall bleeding, all-cause mortality, and ischemic stroke or systemic embolization, were assessed in the Cox model adjusted for age, prior GI bleeding, chronic alcohol use, chronic kidney disease, liver disease, smoking, and baseline anemia. Subgroup analyses were performed in patients at high bleeding risk (HAS-BLED score ≥ 3), and in patients concomitantly treated with antiplatelet. Results Of 3,402 patients in the registry, 2568 (75.5%) were treated with OAC at baseline. The prevalence of females was 43.4%, with a mean age of 68.4 years. The majority of patients (91.1%) received warfarin. The incidence of major bleeding was 2.11 (1.79–2.48) per 100 person-years. PPI was used at baseline in 707 patients (20.8%). Compared with their counterpart, PPI was more frequently used in high-bleeding risk patients (27.3% vs. 18.1%, p &amp;lt; 0.001) and in those with concomitant antiplatelet therapy (37.5% vs. 17.1%, p &amp;lt; 0.001). The mean TTR was similar between PPI and non-PPI users (52.5% vs. 53.8%, p 0.37). PPI use was not associated with poor anticoagulant control (adjusted OR 1.12, 95% 0.89-1.40). The risk of GI bleeding in PPI users was similar to non-user (adjusted HR 1.01, 95%CI 0.59-1.75). The risk of all-cause mortality, ischemic stroke or systemic embolization, and overall bleeding was not different between PPI and non-PPI users. There was no significant interaction between PPI use and bleeding risk or concomitant antiplatelet therapy on adverse outcomes. Conclusion PPI use has no impact on major outcomes, including bleeding in AF patients treated with OAC. The practice of concomitant prescribing of PPI in patients treated with OAC is needed to be re-examined, given the potentially high impact of health care costs.PPI use and outcomes

New Persistent Opioid Use After Childbirth.

To examine factors associated with new persistent opioid use after childbirth. We conducted a population-based cohort study of individuals who initiated opioid therapy within 7 days of discharge from hospital after delivery between September 1, 2013, and September 30, 2021. The primary outcome was new persistent opioid use , which was defined as one or more prescriptions for an opioid within 90 days of the first postpartum prescription and one or more subsequent opioid prescriptions in the 91-365 days afterward. We used multivariable logistic regression to assess patient-, pregnancy-, and prescription-related factors associated with new persistent opioid use after delivery. We identified 118,694 unique deliveries after which opioids were initiated, including 99,399 cesarean (83.7%) and 19,295 vaginal (16.3%) deliveries. Among mothers who initiated an opioid after delivery, 1,282 (10.8/1,000 deliveries) met our definition of new persistent opioid use in the subsequent year. Rates of new persistent opioid use were appreciably higher after vaginal (16.0/1,000) compared with cesarean (9.8/1,000) deliveries. Each additional 30 morphine milligram equivalents in the initial opioid prescription was associated with an increased risk of new persistent use after cesarean (adjusted odds ratio [aOR] 1.06, 95% CI 1.04-1.08) and vaginal (aOR 1.05, 95% CI 1.02-1.08) delivery. A concomitant benzodiazepine prescription after cesarean delivery was associated with a markedly increased risk of persistent opioid use (aOR 2.69, 95% CI 1.60-4.52). Among people who filled an opioid prescription after delivery, about 1% displayed evidence of persistent opioid use in the subsequent year. Initial prescriptions for large quantities of opioids and a concurrent benzodiazepine prescription may be important modifiable risk factors to prevent new persistent opioid use after delivery.

Real-world practice of estrogen and progestogen prescriptions in menopausal women in Japan: A descriptive study using a Japanese claims database.

This study aimed to investigate the real-world clinical practice of estrogen and progestogen prescriptions for menopausal women. Using a health care database in Japan, we conducted a cross-sectional study on estrogen prescriptions and detailed analyses of newly initiated estrogens and concomitant prescriptions of progestogens. Data between January 2005 and December 2021 were analyzed. In 2021, the proportion of women aged 45-49 years receiving estrogens was 25.8 [95% confidence interval (CI): 25.3, 26.3] per 1000 women, while it was 6.4 [95% CI: 6.0, 6.7] for those aged ≥60 years. The prescription of estrogens gradually increased in women aged 50-59 years after 2009. In women without a history of hysterectomy, transdermal estradiol was the primary form of estrogens prescribed for ≥180 days, in women aged <60 years. The proportion of transdermal estradiol gradually increased each year, whereas that of oral-conjugated equine estrogens decreased. Among progestogen, the proportions of dydrogesterone and transdermal norethisterone acetate increased over time, while that of medroxyprogesterone acetate decreased. Approximately 30% of women prescribed estrogens for ≥180 days did not initiate progestogen concurrently. In women undergoing hysterectomy, progestogen was not initiated in >90% of cases, and transdermal estradiol was prescribed in approximately 80% of cases in 2021. This study reviewed the prescription of estrogens in menopausal women in Japan. A considerable number of women with a uterus are receiving estrogen therapy rather than estrogen-progestogen therapy (EPT), despite the guidelines recommending the use of EPT in these 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.

Outpatient opioid prescribing by Alzheimer’s diagnosis among older adults with pain in United States

ObjectiveTo examine opioid prescribing practices for pain in older adults with and without Alzheimer’s Disease and Related Dementias (ADRD).MethodsThis cross-sectional study used National Ambulatory Medical Care Survey data (2014–2016, and 2018). Adults aged ≥ 50 years with pain were analyzed. Prescribing of opioid and concomitant sedative prescriptions (including benzodiazepines, Z-drugs, and barbiturates) were identified by the Multum lexicon code. Multivariable logistic regression evaluated the risk of opioid prescribing or co-prescribing of opioid and sedative associated with ADRD in older adults with pain.ResultsThere were 13,299 office visits in older adults with pain, representing 451.75 million visits. Opioid prescribing occurred in 27.19%; 30% involved co-prescribing of opioids and sedatives. ADRD was not associated with opioid prescribing or co-prescribing of opioid and sedative therapy.ConclusionsOpioid and sedatives are commonly prescribed in older adults with pain. Longitudinal studies need to understand the etiology and chronicity of opioid use in older patients, specifically with ADRD.

Trends in the Use of Gabapentinoids and Opioids in the Postoperative Period Among Older Adults

In response to the opioid epidemic, recommendations from some pain societies have encouraged surgeons to embrace multimodal pain regimens with the intent of reducing opioid use in the postoperative period, including by prescribing gabapentinoids. To describe trends in postoperative prescribing of both gabapentinoids and opioids after a variety of surgical procedures by examining nationally representative Medicare data and further understand variation by procedure. This serial cross-sectional study of gabapentinoid prescribing from January 1, 2013, through December 31, 2018, used a 20% US Medicare sample. Gabapentinoid-naive patients 66 years or older undergoing 1 of 14 common noncataract surgical procedures performed in older adults were included. Data were analyzed from April 2022 to April 2023. One of 14 common surgical procedures in older adults. Rate of postoperative prescribing of gabapentinoids and opioids, defined as a prescription filled between 7 days before the procedure and 7 days after discharge from surgery. Additionally, concomitant prescribing of gabapentinoids and opioids in the postoperative period was assessed. The total study cohort included 494 922 patients with a mean (SD) age of 73.7 (5.9) years, 53.9% of whom were women and 86.0% of whom were White. A total of 18 095 patients (3.7%) received a new gabapentinoid prescription in the postoperative period. Of those receiving a new gabapentinoid prescription, 10 956 (60.5%) were women and 15 529 (85.8%) were White. After adjusting for age, sex, race and ethnicity, and procedure type in each year, the rate of new postoperative gabapentinoid prescribing increased from 2.3% (95% CI, 2.2%-2.4%) in 2014 to 5.2% (95% CI, 5.0%-5.4%) in 2018 (P < .001). While there was variation between procedure types, almost all procedures saw an increase in both gabapentinoid and opioid prescribing. In this same period, opioid prescribing increased from 56% (95% CI, 55%-56%) to 59% (95% CI, 58%-60%) (P < .001). Concomitant prescribing also increased from 1.6% (95% CI, 1.5%-1.7%) in 2014 to 4.1% (95% CI, 4.0%-4.3%) in 2018 (P < .001). The findings of this cross-sectional study of Medicare beneficiaries suggest that new postoperative gabapentinoid prescribing increased without a subsequent downward trend in the proportion of patients receiving postoperative opioids and a near tripling of concurrent prescribing. Closer attention needs to be paid to postoperative prescribing for older adults, especially when using multiple types of medications, which can have adverse drug events.

Prescription drug dependence with and without concurrent illicit drug use: a multicenter cross-sectional survey among an addiction treatment seeking population.

Dependence on prescription drugs and illicit drugs imposes a global health and social burden. Despite accumulating evidence of prescription drugs and illicit drugs dependence, none of the systematized studies has explored the magnitude of this problem in Pakistan. The aim is to investigate the extent and associated factors of prescription drug dependence (PDD), as opposed to concomitant prescription drug dependence and illicit drug use (PIDU), within a sample of individuals seeking addiction treatment. The cross sectional study was conducted on the sample recruited from three drug treatment centers in Pakistan. Face-to-face interviews were conducted with participants who met ICD-10 criteria for prescription drug dependence. Several aspects like substance use histories, negative health outcomes, patient attitude, pharmacy and physician practices also collected to predict the determinants of (PDD). Binomial logistic regression models examined the factors associated with PDD and PIDU. Of the 537 treatment seeking individuals interviewed at baseline, close to one third (178, 33.3%) met criteria for dependence on prescription drugs. The majority of the participants were male (93.3%), average age of 31 years, having urban residence (67.4%). Among participants who met criteria for dependence on prescription drugs (71.9%), reported benzodiazepines as the most frequently used drug, followed by narcotic analgesics (56.8%), cannabis/marijuana (45.5%), and heroin (41.5%). The patients reported alprazolam, buprenorphine, nalbuphine, and pentazocin use as alternatives to illicit drugs. PDD was significantly negatively associated with injectable route (OR = 0.281, 95% CI, 0.079-0.993) and psychotic symptoms (OR = 0.315, 95% CI, 0.100, 0.986). This implies that PDD is less likely to be associated with an injectable route and psychotic symptoms in contrast to PIDU. Pain, depression and sleep disorder were primary reasons for PDD. PDD was associated with the attitude that prescription drugs are safer than illicit drugs (OR = 4.057, 95%CI, 1.254-13.122) and PDD was associated with being on professional terms (i.e., having an established relationship) with pharmaceutical drugs retailers for acquisition of prescription drugs. The study found benzodiazepine and opioid dependence in sub sample of addiction treatment seekers. The results have implications for drug policy and intervention strategies for preventing and treating drug use disorders.

Medical cannabinoids for painful symptoms in patients with severe dementia: a randomized, double-blind cross-over placebo-controlled trial protocol.

In an observational study in Geneva (Switzerland), we found that administering a standardized THC/CBD oil was feasible, safe, and beneficial in an elderly polymedicated population with severe dementia, behavioral troubles, and pain. Those findings need to be confirmed in a randomized clinical trial. The MedCanDem trial is a randomized, double-blind cross-over placebo-controlled trial to study the efficacy of cannabinoids in improving painful symptoms during severe dementia disorders in patients living in long-term care facilities in Geneva. This manuscript describes the MedCanDem trial protocol. Participants will be patients suffering from severe dementia associated with pain and behavioral troubles and living in long-term care facilities. We selected five facilities specialized in caring for severely demented patients in Geneva (Switzerland). A total of 24 subjects will be randomized 1:1 to the sequence study intervention/placebo or the sequence placebo/study intervention. Patients will receive study intervention treatment or placebo for eight weeks, and then after a one-week wash-out, treatments will be inversed for another eight weeks. The intervention will be a standardized THC/CBD 1:2 oil extract, and the placebo will be a hemp seed oil. The primary outcome is the reduction from the baseline of the Cohen-Mansfield score; secondary outcomes include the reduction in the Doloplus scale, the reduction of rigidity, the monitoring of concomitant drugs prescription and de-prescription, the safety assessment, and a pharmacokinetic evaluation. The primary and secondary outcomes will be assessed at the baseline, after 28 days, and at the end of both study periods. In addition, safety laboratory analysis, pharmacokinetic evaluation, and therapeutic drug monitoring for the cannabinoids will be evaluated through a blood sample analysis conducted at the beginning and the end of both study periods. This study will allow us to confirm the clinical results observed during the observational study. It represents one of the few studies aiming to prove natural medical cannabis efficacy in a population of non-communicating patients with severe dementia, experimenting with behavioral troubles, pain, and rigidity. The trial has Swissethics authorization (BASEC 2022-00999), and it is registered on clinicaltrials.gov (NCT05432206) and the SNCTP (000005168).