Comorbid Drug Research Articles

Profile of Substance Misuse among Adolescent and Young Adult Gabapentinoid Users: A Register-Based Follow-up Study of Former Adolescent Psychiatric Inpatients

Aims: Our study examined characteristics of adolescent and young adult study participants using gabapentinoids (gabapentin, pregabalin), with previous history of adolescent psychiatric inpatient hospitalization. Particular focus was on temporal association of age, at first prescription for gabapentinoids, to age at tobacco smoking initiation, regular alcohol use, diagnosis of substance dependence and prescriptions for benzodiazepines and opioids. Methods: The initial study population contained 508 adolescents (300 females, 208 males) admitted to psychiatric inpatient care in Oulu University hospital between the ages 13–17 years. Register-based follow-up information on prescriptions for gabapentinoids, benzodiazepines and opioids, as well as ICD-10 diagnosis for hospital-treated substance dependence, was obtained from the Finnish national health care registers. Results: The users of gabapentinoids accounted for 9.1% of the initial study population. Of adolescence-related characteristics, suicidal ideation, suicide attempts and non-suicidal self-injury was emphasized in females using gabapentinoids. The majority of participants using gabapentinoids had benzodiazepines (80.4%) and opioids (71.7%) as comorbid drugs. Initiation of tobacco smoking and alcohol use and first prescriptions for of benzodiazepines and opioids, and a diagnosis of substance dependence commonly predated first prescriptions for gabapentinoids. Conclusions: In clinical practice, the decision to prescribe gabapentinoids to adolescents or young adults must be made with caution, particularly for those with substance use problems and/or without a clinically approved indication.

Economic evaluations of chronic obstructive pulmonary disease pharmacotherapy: how well are the real-world issues of medication adherence, comorbidities and adverse drug-reactions addressed?

ABSTRACT Introduction When estimating the cost-effectiveness or budget impact of chronic obstructive pulmonary disease (COPD) medication, it is common practice to use trial data for clinical inputs. However, such inputs do not always reflect the real-world situation. Previous reviews recognized the need for taking real-world data (medication adherence, comorbidity and adverse drug reactions [ADRs]) into account. Whether recent cost-effectiveness analyses of COPD medication implemented those recommendations is unknown. Areas covered The authors reviewed recent economic evaluations of COPD-maintenance treatments focusing on medication adherence, comorbidity and ADRs. Expert opinion In most registration trials of COPD treatment, strict inclusion and exclusion criteria are applied. During trials, patient monitoring is well controlled. As such, medication adherence is often higher than seen in less controlled, real-world environments with more heterogeneous characteristics. Additionally, safety data collected in trials may not be widely generalizable due to more comorbidity and polypharmacy in the real-world. Consequently, when merely relying on trial data, the impact of adherence, comorbidity and ADRs on the cost-effectiveness can be underestimated. To overcome these real-world data gaps, use of pragmatic trials and observational studies in addition to strictly controlled trial data is recommended. To catalyze implementation of these real-world issues, reporting checklists should be updated.

Adherence to Lipid-Lowering Medication in People Living with HIV: An Outpatient Clinic Drug Direct Distribution Experience.

Objective:Adherence to lipid-lowering drugs could be challenging in our patients as it is in the general population, which is described as low as 25%. Our aim was to evaluate adherence to statins and to investigate clinical event impact on it.Methods:This retrospective study on HIV+ patients attending to Clinic of Modena (Italy) was conducted in order to evaluate characteristics, clinical events, and adherence on lipid-lowering drugs. All drugs for comorbidities are distributed by the hospital pharmacy and recorded in an electronical database. Adherence was also evaluated in patients who were supplied with antilipemics in external pharmacies through phone calls. Patients were considered adherent if the percentage of correct time of drug refill was >80%.Findings:Totally 1123 patients were evaluated. Lipid-lowering drugs (statins, fenofibrate, and omega-3 oil) were prescribed in 242 patients (21.5%). Prescription occurred mainly in those who were older, males, and Italians. Two hundred of them (82.6%) used statins alone, 23 (9.5%) only fenofibrate or omega-3 oil, and 19 (7.8%) a combination of both drugs. The median adherence was 90% while patients with adherence >80% resulted 153 (63.2%). Forty-six (19%) had a clinical history of cardiovascular events; 59% of them, placed in secondary prophylaxis, and 76%, already in treatment, continued to adhere. No differences in terms of adherence according to the type of drug distribution (hospital pharmacy or outside pharmacies) were found.Conclusion:Linking the supply of these drugs to that of antiretrovirals led to a good level of adherence higher than that described in the general population. The majority of the patients who experienced a cardiovascular event remain adherent to the prescribed therapy.

Psychiatric Medication Changes Associated With Increased Rate of Medical Readmissions in Patients With Serious Mental Illness.

To identify the impact of postdischarge psychiatric medication changes on general medical readmissions among patients with serious mental illness (SMI; bipolar disorder, major depressive disorder, and schizophrenia), claims from a 5% national sample of Medicare fee-for-service (FFS) beneficiaries hospitalized between 2013 and 2016 were studied. A total of 165,490 Medicare FFS beneficiaries with SMI 18 years or older with at least 1 year of continuous Medicare enrollment were identified. Within 30 days of discharge from index admission, 47.4% experienced a psychiatric medication change-including 75,892 beneficiaries experiencing a deletion and 55,713 experiencing an addition. After adjusting for potential confounders, those with a medication change experienced an 10% increase in the odds of 30-day readmission (odds ratio, 1.10; SE, 0.019; p < 0.001). Comorbid drug use disorder was also associated with an increased odds of readmission after controlling for other covariates. These findings suggest important factors that clinicians should be aware of when discharging patients with SMI.

Adrenalectomy in Japanese patients with subclinical Cushing syndrome: 1-mg dexamethasone suppression test to predict the surgical benefit.

To investigate whether the result of the 1-mg dexamethasone suppression test can predict the improvement of comorbidities after adrenalectomy in patients with subclinical Cushing syndrome. This retrospective study included 117 subclinical Cushing syndrome patients who underwent adrenalectomy. The numbers of prescribed drugs for metabolic comorbidities and the clinical variables at diagnosis were compared with those at the follow up. Patients were classified into subgroups according to the result of the 1-mg dexamethasone suppression test. Significant improvements in blood pressure, serum cholesterol and body mass index were observed. Furthermore, a significant improvement in glycated hemoglobin was observed in patients with diabetes mellitus. These improvements led to a discontinuation or reduction of prescribed drugs after surgery. In addition, the greatest reduction of prescribed drugs was observed in patients whose serum cortisol levels were between 1.8 and 3.0µg/dL after the 1-mg dexamethasone suppression test. The result of the 1-mg dexamethasone suppression test can be a useful factor predicting the improvement of comorbidities after adrenalectomy. Current data might give us a new insight into the decision-making for the treatment of subclinical Cushing syndrome.

Opioid prescribing and risk of drug-opioid interactions in older discharged patients with polypharmacy in Australia.

Background Opioids are commonly prescribed to managing chronic pain in older persons. However, these patients are often at risk of drug-opioid interactions due to polypharmacy. Objectives To identify the prevalence of opioid prescribing and drug-opioid interactions in poly-medicated older patients and factors associated with opioid prescribing. Setting Patients were included if they were admitted to the Royal Adelaide Hospital between September 2015 and August 2016, aged ≥ 75years and took ≥ 5 medications at discharge. Methods After ethics approval, data of were retrospectively collected from case notes. The Charlson Comorbidity Index and Drug Burden Index were determined and opioids were classified as strong or weak. The association between opioid use and concurrent medications was computed using logistic regression and the results presented as odds ratios (OR) and 95% confidence intervals (95% CI), adjusted for age, sex, Charlson Comorbidity Index, number of prescribed medications and modified-Drug Burden Index. Main outcome measure Association between concurrent medications and opioid prescribing. Results 15,000 geriatric admissions were identified, of which 1192 were included. A total of 283 (23.7%) patients were prescribed opioids, with oxycodone accounting for 56% of these prescriptions. Opioid users were prescribed more medications (11.2 vs. 9.0, P < 0.001) and had higher Drug Burden Index (1.2 vs. 0.14, P < 0.001) compared to non-users. Opioid use was associated with concurrent prescription of antiepileptics (OR = 1.7, 95%CI 1.1-2.6), and negatively associated with Charlson Comorbidity Index (OR = 0.9, 95%CI 0.8-0.98) and concurrent use of antipsychotics (OR = 0.5, 95%CI 0.3-0.9) and beta blocking agents (OR = 0.4, 95%CI 0.3-0.6). Conclusions Strong opioids were prescribed more often than weak opioids and opioid users presented with characteristics and concurrent medications which increased the risk of opioid related adverse drug effects.

Relationship between Comorbid Drug Use Disorders, Affective Disorders, and Current Smoking

Objective: This study aimed to identify subgroups of adults based on comorbid psychiatric disorders and to examine the relationship with current smoking. Method: The National Epidemiologic Survey on Alcohol and Related Conditions-III, 2012–2013, sampled, recruited, and assessed 36,309 adults, with interviews on drug use and other characteristics. The Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-5 Version (AUDADIS-5) was used to identify psychiatric conditions. Latent class models were developed based on various psychiatric diagnoses. Multinomial logistic regression estimated the significance of covariates in predicting class membership. Results: Four latent classes optimally distinguished the population: no comorbid conditions (63%), comorbid affective disorders (16%), those with alcohol use disorder (AUD; 17%), and a highly comorbid subgroup (i.e., co-occurring affective and drug use disorders; 4%). Current smoking was about twice as prevalent in the classes defined by psychiatric conditions compared to the group with no comorbid conditions. The highly comorbid class was more likely to be current smokers than the comorbid affective disorders class and the AUD class. Furthermore, the highly comorbid class was younger and had lower income, and the AUD class had a higher proportion of males than the other classes. Conclusions: Cigarette smoking was higher in the nearly 40% of respondents characterized by psychiatric disorders, particularly those with drug use disorders. Correlates of membership in these classes were consistent with known vulnerabilities for smoking, highlighting the need for mental health interventions and future research to explicitly address tobacco cessation in clinical settings based on psychiatric diagnoses.

Homicide by men diagnosed with schizophrenia: national case-control study.

Some people diagnosed with schizophrenia are more prone to committing acts of serious violence, especially in the presence of drug or alcohol misuse. The rarity of homicide has meant that no large controlled study has previously examined clinical risk factors. To determine the risk factors for homicide by males diagnosed with schizophrenia. A national nested case-control study of all previously admitted males diagnosed with schizophrenia, convicted of homicide between 1 January 1997 and 31 December 2012. Univariate and multivariable conditional logistic regression models were fitted to identify predictors of homicide in this population. During the observation period 160 male patients with schizophrenia and a history of psychiatric admission were convicted of homicide, and they were matched with 542 male control patients who had not been convicted of homicide. Patients who committed homicide were more likely to have a history of violence and comorbid personality disorder or drug misuse. They were more likely to have missed their last contact with services prior to the offence and to have been non-adherent with their treatment plan. Almost all (94%) of homicides were committed by patients who had a history of alcohol or drug misuse and/or who were not in receipt of planned treatment. In England and Wales, homicides by patients with schizophrenia without substance misuse and in receipt of planned care are exceptionally rare. To prevent serious violence, mental health services should focus on drug and alcohol misuse, treatment adherence and maintaining contact with services.

Filling the gaps in the characterization of the clinical management of COVID-19: 30-day hospital admission and fatality rates in a cohort of 118 150 cases diagnosed in outpatient settings in Spain.

BackgroundCurrently, there is a missing link in the natural history of COVID-19, from first (usually milder) symptoms to hospitalization and/or death. To fill in this gap, we characterized COVID-19 patients at the time at which they were diagnosed in outpatient settings and estimated 30-day hospital admission and fatality rates.MethodsThis was a population-based cohort study. Data were obtained from Information System for Research in Primary Care (SIDIAP)—a primary-care records database covering >6 million people (>80% of the population of Catalonia), linked to COVID-19 reverse transcriptase polymerase chain reaction (RT-PCR) tests and hospital emergency, inpatient and mortality registers. We included all patients in the database who were ≥15 years old and diagnosed with COVID-19 in outpatient settings between 15 March and 24 April 2020 (10 April for outcome studies). Baseline characteristics included socio-demographics, co-morbidity and previous drug use at the time of diagnosis, and polymerase chain reaction (PCR) testing and results. Study outcomes included 30-day hospitalization for COVID-19 and all-cause fatality.ResultsWe identified 118 150 and 95 467 COVID-19 patients for characterization and outcome studies, respectively. Most were women (58.7%) and young-to-middle-aged (e.g. 21.1% were 45–54 years old). Of the 44 575 who were tested with PCR, 32 723 (73.4%) tested positive. In the month after diagnosis, 14.8% (14.6–15.0) were hospitalized, with a greater proportion of men and older people, peaking at age 75–84 years. Thirty-day fatality was 3.5% (95% confidence interval: 3.4% to 3.6%), higher in men, increasing with age and highest in those residing in nursing homes [24.5% (23.4% to 25.6%)].ConclusionCOVID-19 infections were widespread in the community, including all age–sex strata. However, severe forms of the disease clustered in older men and nursing-home residents. Although initially managed in outpatient settings, 15% of cases required hospitalization and 4% died within a month of first symptoms. These data are instrumental for designing deconfinement strategies and will inform healthcare planning and hospital-bed allocation in current and future COVID-19 outbreaks.

Removing the stigma of medication for opioid use disorder

Removing the stigma of medication for opioid use disorder

Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis

Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs, i.e., TD-MN, which aims to specifically deliver TAC and DIC to skin and articular cavity, achieving simultaneous alleviation of psoriatic skin and arthritic joint lesions in PsA. In vitro and in vivo skin permeation demonstrated that the inter-layer retained TAC within the skin of ∼100 μm, while the tip-layer delivered DIC up to ∼300 μm into the articular cavity. TD-MN not only efficiently decreased the psoriasis area and severity index scores and recovered the thickened epidermis of imiquimod-induced psoriasis but also alleviated carrageenan/kaolin-induced arthritis even better than DIC injection through reducing joint swelling, muscle atrophy, and cartilage destruction. Importantly, TD-MN significantly inhibited the serum TNF-α and IL-17A in psoriatic and arthritic rats. The results support that this approach represents a promising alternative to multi-administration of different drugs for comorbidity, providing a convenient and effective strategy for meeting the requirements of PsA treatment.

Could aquaporin modulators be employed as prospective drugs for COVID-19 related pulmonary comorbidity?

COVID-19 initially an epidemic caused by SARS-CoV-2 has turned out to be a life- threatening global pandemic with increased morbidity and mortality. The presence of cytokine storm has been linked with the pathogenesis of severe lung injury as evinced in COVID-19. Aquaporins (AQPs) are molecular water channels, facilitating water transport across the cell membrane in response to osmotic gradients. Impairment in alveolar fluid clearance due to altered functional expression of respiratory AQPs highlight their pathophysiological significance in pulmonary edema associated respiratory illness. Therefore, we hypothesize that targeted modulation of AQPs in lungs in the intervening period of time, could diminish the dreadful effects of inflammation- induced comorbidity in COVID-19.

A Mini Review : Clinically Significant Potential Drug-Drug Interactions In COVID-19 and Comorbid Therapy

Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be aggravated by comorbid diseases. In administering COVID-19 therapy, we need to consider potential drug-drug interactions (pDDIs) with comorbid drugs. Most patients with comorbid diseases get polypharmacy, therefore the risk of pDDIs increases. Potential drug-drug interactions can cause unwanted effects such as toxicity to death. There is no on-label therapy for COVID-19 but FDA has Emergency Use Authorization (EUA) for hydroxychloroquine, chloroquine, azithromycin, remdesivir, ritonavir, and lopinavir. Some COVID-19 treatment potential drug-drug interactions have a level of severity C and D, so there is a high need for close monitoring during drug administration or modification therapy.

Remission From Unhealthy Drinking Among Patients With an Alcohol Use Disorder: A Longitudinal Study Using Systematic, Primary Care–Based Alcohol Screening Data

Using electronic health record (EHR) data from a systematic, primary care-based alcohol screening, brief intervention, and referral to treatment (SBIRT) initiative within a health system, we examined correlates of remission from unhealthy drinking among patients with an alcohol use disorder (AUD). We conducted a longitudinal study of 4,078 adults with AUD who screened positive for unhealthy drinking between October 1, 2015, and September 30, 2016. We extracted EHR data up to 3 years after screening until October 1, 2018. We used survival analysis to examine associations between remission (i.e., reporting abstinence or low-risk drinking at a subsequent screening) and patient characteristics, comorbidities, and treatment utilization. The median time to remission from unhealthy drinking was 1.7 years. Factors significantly associated with greater odds of remitting from unhealthy drinking during follow-up were female gender; older age (50-64 years); Black or Latino/Hispanic race/ethnicity; having more medical comorbidities; not having a comorbid drug use disorder; lower alcohol consumption levels; and receiving addiction medicine treatment before the index screening. In the first follow-up year, individuals with mental health comorbidities were more likely to remit, but those in psychiatric treatment were less likely. Receiving addiction treatment during follow-up was not associated with remission. Ethnic minorities and individuals with mental illness were more likely to remit, which is encouraging given the health disparities observed among these clinically important subgroups and warrants further research. Our findings may inform research on AUD recovery and clinical practice, as remission from unhealthy drinking is a crucial component of the early stages of recovery.

Analysis of Potential Interaction between Antiretrovirals and Comorbid Medications of HIV Patients at a Top Referral Hospital in Indonesia

Background: HIV/AIDS usually present with comorbid diseases such as tuberculosis, pneumonia, toxoplasmosis, fungal infections, etc., that need multiple medications. Potential interaction between ARV and comorbid drugs is unavoidable. Objective: This study aimed to investigate the potential interaction between ARV drugs and medications used to treat comorbid diseases among HIV patients at the Dr. Cipto Mangunkusumo Hospital, Jakarta. Methods: This was an observational study using medical record data of 121 HIV/AIDS patients treated at the CM Hospital between January 2016 and July 2017. Potential interaction was classified as “major” if it could lead to increase or decrease of plasma drug levels which potentially result in either drug toxicity or treatment failure, or clinically significant harm to the patient; “moderate” if the interaction is not major, but with the recommendation of close monitoring. National, European, Australian, and Liverpool iChart guidelines were used for the classification of drug interactions. Results: Major interactions were noted in 17 (14.05%)patients. Fourteen of them received rifampicin, which potentially decreases plasma level of nevirapine (9 patients), rilpivirine (1 patient), and lopinavir/ritonavir (4 patients). Potential increase of ARV level was found in 3 patients involving interaction between voriconazole-efavirenz (2) and omeprazole-rilpivirine (1). Moderate interaction with the potential decrease of ARV level occurred in 46 patients (38.01%); consisting of a combination of rifampicin with efavirenz (38 pts), rifampicin with zidovudine (6 pts), and phenytoin with efavirenz or nevirapine (2 patients). Conclusion: Potential major interaction occurred in 17 (14.05%), which mostly attributed to rifampicin use; while moderate interaction occurred in 46 (38.01%) of patients. Although no serious adverse event was observed in this study, special care should be taken when the drugs with potential major interaction are to be administered

Assessment of comorbidities in patients with deranged thyroid hormone levels

Background: There is association of deranged thyroid hormone levels with various co-morbidities. Drugs for comorbidity may interact with each other and affect the outcome of treatment. So, this study was planned to find out comorbidities with deranged thyroid hormone levels and various possible drug interactions.Methods: It was a prospective, observational study carried out at tertiary care hospital from November 2017 to June 2018. Thyroid hormonal levels reports were followed in OPD and online information system facility. Drugs interactions were checked by referring standard pharmacology textbooks, review articles and Medscape drug interaction checker. Approval from the Institutional Ethics Committee was taken before initiation of the study. Patients with deranged thyroid hormone levels were included in the study.Results: Study was conducted in 111 patients of thyroid disorders. Spondylitis, asthma, acne cases were seen in hypothyroid patients whereas hypokalemic periodic paralysis, thyroid ophthalmopathy statistically significantly seen in hyperthyroid patients. Various concurrent medications such as calcium, carbamazepine decreases the effects of levothyroxine. For management of comorbidities various drugs are given which also interact among themselves significantly.Conclusions: Diabetes mellites, obesity, spondylitis, lichen planus were more common in hypothyroidism while comorbidities like hypertension, hypokalemic periodic paralysis, thyroid ophthalmopathy were found to be more in hyperthyroidism. Incidence of drug interactions is found to be more with increased use of medications for comorbidities, so physicians should be careful while prescribing them. Due to drug interactions desired effects of drugs given for thyroid disorders may not be observed.

Drug-Induced Fatty Liver Disease

Drug-induced fatty liver disease (DIFLD) covers a group of adverse drug reactions whose prevalence accounts for about 10% of all adverse reactions. The aim of this review was to analyse and summarise data on medicines that can potentially lead to the development of DIFLD, as well as on the pathophysiological mechanisms of its development, methods of its diagnosis, treatment, and prevention. The analysis of scientifi c literature showed that most often this complication occurred following the use of amiodarone, methotrexate, tamoxifen, valproic acid, and some other medicines. It was demonstrated that the main risk factors for developing DIFLD are comorbidity/polymorbidity and mitochondrial dysfunction. Due to the lack of pathognomonic clinical manifestations of DIFLD the best approach to making diagnosis is to obtain a thorough medical history, including medication history, to use RUCAM and Naranjo scales, to analyse a number of blood chemistry parameters (alanine transaminase, aspartate transaminase, bilirubin, alkaline phosphatase), and, if necessary, to perform liver biopsy. Whenever DIFLD is observed in a patient, it is necessary, if possible, to discontinue the use of the medicine that caused the adverse reaction, or to lower its dose and to exclude the factors that may potentially aff ect the patient’s condition. The following measures will help healthcare professionals to prevent and detect DIFLD in a timely manner: observing the requirements of the patient information leafl et, taking into account any comorbidity and potential adverse drug interactions, as well as regular monitoring of the condition of patients taking medicines with known hepatotoxic eff ects.

HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History.

The fronto-striatal circuitry, involving the nucleus accumbens, ventral tegmental area, and prefrontal cortex, mediates goal-directed behavior and is targeted by both drugs of abuse and HIV-1 infection. Acutely, both drugs and HIV-1 provoke increased dopamine activity within the circuit. However, chronic exposure to drugs or HIV-1 leads to dysregulation of the dopamine system as a result of fronto-striatal adaptations to oppose the effects of repeated instances of transiently increased dopamine. Specifically, chronic drug use leads to reduced dopaminergic tone, upregulation of dopamine transporters, and altered circuit connectivity, sending users into an allosteric state in which goal-directed behaviors are dysregulated (i.e., addiction). Similarly, chronic exposure to HIV-1, even with combination antiretroviral therapy (cART), dysregulates dopamine and dopamine transporter function and alters connectivity of the fronto-striatal circuit, contributing to apathy and clinical symptoms of HIV-1 associated neurocognitive disorders (HAND). Thus, in a drug user also exposed to HIV-1, dysregulation of the fronto-striatal dopamine circuit advances at an exacerbated rate and appears to be driven by mechanisms unique from those seen with chronic drug use or HIV-1 exposure alone. We posit that the effects of drug use and HIV-1 infection on microglia interact to drive the progression of motivational dysfunction at an accelerated rate. The current review will therefore explore how the fronto-striatal circuit adapts to drug use (using cocaine as an example), HIV-1 infection, and both together; emphasizing proper methods and providing future directions to develop treatments for pathologies disrupting goal-directed behaviors and improve clinical outcomes for affected patients. Graphical Abstract Drug use and HIV-1 in the fronto-striatal circuit. Drugs of abuse and HIV-1 infection both target the fronto-striatal circuit which mediates goal-directed behavior. Acutely, drugs and HIV-1 increase dopamine activity; in contrast chronic exposure produces circuit adaptions leading to dysregulation, addiction and/or apathy. Comorbid drug use and HIV-1 infection may interact with microglia to exacerbate motivational dysregulation.

Ethnic inequality in non‐steroidal anti‐inflammatory drug‐associated harm in New Zealand: A national population‐based cohort study

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with many serious complications and they are widely used in New Zealand (NZ). However, differences in NSAID-associated risk for these complications between ethnic groups are largely unknown. We assessed ethnic disparities in risk of hospital admission for upper gastrointestinal bleeding (UGIB), heart failure, and acute kidney failure (AKF) in NZ's primary care population prescribed and dispensed NSAIDs. Retrospective cohort study utilising national pharmaceutical dispensing and hospital admissions data 2007 to 2015. Patient follow-up included 90-day periods following the dispensing of NSAIDs. Risk for each adverse outcome in Maori, Pacific, European, and Asian patients was estimated using multivariable Poisson regression adjusting for age, sex, deprivation, comorbidity and concurrent drug use. 3 023 067 patients were dispensed NSAIDs between 2008 and 2015. Their total intended duration of NSAID treatment encompassed 2 353 140 patient-years. Maori, Pacific and Asian patients were younger than European patients (all P < .001). After adjusting for other risk factors, Maori (rate ratio: 2.54, 95% confidence interval: 2.23-2.90) and Pacific patients (3.17, 2.69-3.74) were more likely to be hospitalised for UGIB than Europeans (reference), and heart failure (Maori: 2.48, 2.24-2.74; Pacific: 1.97, 1.69-2.30). Risk of AKF was higher in Maori (1.46, 1.23-1.74). Higher risk for UGIB and HF in Maori and Pacific patients was most pronounced in males and patients aged <60 years. Inequalities exist in the incidence of serious adverse outcomes experienced by different ethnic groups in NZ while using NSAIDs. Interventions to promote safer use of these medicines are required to reduce this inequity.

Going off pathway: Problem or good care?

7014 Background: Clinical oncology pathways (COP) provide decision support and benchmarking against national standards. Some organizations provide financial incentives for using COP-recommended treatment (on pathway: OnP). Treatment (Rx) other than COP recommended Rx (off pathway: OffP) is appropriate for some cases. There are limited data on the appropriateness of OffP Rx. This study examines rates and reasons for OffP Rx in one cancer center. Methods: All systemic Rx decisions entered in the ClinicalPath COP from 10/1/18 - 9/30/19 were classified as OnP (including Rx on a clinical trial) or OffP and as adjuvant/neoadjuvant therapy (ADJ) or for metastatic cancer (MET). Oncologists must provide free text reasons for OffP Rx. Records of all OffP care were reviewed by a senior nurse-led team and physician to verify and classify OffP reasons. Cases without clear documentation were referred to the treating oncologist and/or multidisciplinary team for review. Justified OffP reasons (R1-6) were classified as: R1. Documented drug toxicity and/or treatment-limiting co-morbidity; R2. Prior treatment precluding pathway Rx; R3. New drug indication or molecular targeted therapy not in COP; R4. Continuation of Rx started prior to referral; R5. Other clearly documented and reviewed provider or multidisciplinary team rationale; and R6. Patient preference. Results: There were 2,997 COP treatment decisions for 2,389 patients. The OnP rate was higher for ADJ than for MET Rx (87% vs. 78%). Non-justified OffP care accounted for 1% of cases. 69% of OffP Rx was because of known drug toxicity, co-morbidity limiting therapy, prior therapy precluding COP choice, and new drug indications (Table). Conclusions: COPs provide decision support and practice benchmarking. Lower OnP rates for MET Rx likely reflect the nuances of Rx for advanced cancer. Most OffP care was justified and appropriate. Financial incentives that focus on the percentage of COP OnP care could paradoxically harm the quality of care, especially given the high percentage of OffP decisions for reasons of drug toxicity, co-morbidity and new drug indications. [Table: see text]