The effect of the infusion connection point on intravenous multi-infusion drug delivery to premature neonates - Use of standard concentration infusions of critical medications.

BACKGROUND: Sick neonates with haemodynamic instability often require complex medication regimens, which may result in the connection of a catecholamine infusion distally. This increases the dead volume of the infusion system, extending the time to medication delivery. This study evaluated the effects of body weight, and infusion connection point on the delivery rate of two medications infused through a multi-infusion system at infusion rates suitable for extremely and very low birth weight (ELBW and VLBW) neonates. METHODS: An infusion system consisting of six infusions was used to investigate time to delivery, drug concentration at time to delivery and quantity of adrenaline and dopamine administered by intravenous infusions at infusion rates suitable for premature neonates. RESULTS: In an ELBW neonate model, the measured adrenaline and dopamine concentration at 12 T was higher than expected (66.7 (7.5)% (mean (SD)) and 68.0 (4.4)%, respectively, P < 0.001). At the calculated time to delivery, neither drug reached target concentration. In a VLBW neonate model, the measured adrenaline and dopamine concentration at 12 T was higher than expected (92.2 (7.1)% and 97.1 (3.1)%, respectively, P < 0.001). Adrenaline reached target concentration at 27 (11) min and dopamine at 56 (12) min, times significantly shorter than calculated. The measured quantity of adrenaline and dopamine delivered was lower (P < 0.001) than calculated in all tested combinations except adrenaline at proximal connection (97.2 (3.4)%, P = 0.097) in the VLBW neonate model CONCLUSIONS: Using the most proximal available infusion connection considerably improves drug delivery times and drug doses delivered, which is critical during the administration of short-acting cardiovascular medications.

Pharmacokinetic-pharmacodynamic modelling and simulation of methotrexate dosing in patients with rheumatoid arthritis.

AIMS: To develop a non-linear mixed-effects population pharmacokinetic and pharmacodynamic (PK-PD) model describing the change in the concentration of methotrexate polyglutamates in erythrocytes (ery-MTX-PGn with "n" number of glutamate, representing PK component) and how this relates to modified 28-joint Disease Activity Score incorporating erythrocyte sedimentation rate (DAS-28-3) for rheumatoid arthritis (RA), representing PD component. METHODS: An existing PK model was fitted to data from a study consisting of 117 RA patients. The estimation of population PK-PD parameters was performed using stochastic approximation expectation maximisation algorithm in Monolix 2021R2. The model was used to perform Monte Carlo simulations of a loading dose regimen (50mg subcutaneous methotrexate as loading doses, then 20mg weekly oral methotrexate) compared to a standard dosing regimen (10mg weekly oral methotrexate for 2 weeks, then 20mg weekly oral methotrexate). RESULTS: Every 40 nmol/L increase in ery-MTX-PG3-5 total concentration correlated with 1-unit reduction in DAS-28-3. Significant covariate effects on the therapeutic response of methotrexate included the use of prednisolone in the first 4 weeks (positive use correlated with 25% reduction in DAS-28-3 when other variables were constant) and patient age (every 10-year increase in age correlated with 3.4% increase in DAS-28-3 when other variables were constant). 4 methotrexate loading doses led to a higher percentage of patients achieving a good/moderate response compared to the standard regimen (Week 4: 87.6% vs. 39.8%; Week 10: 64.7% vs. 57.0%). CONCLUSIONS: A loading dose regimen was more likely to achieve higher ery-MTX-PG concentration and better therapeutic response after 4 weeks of methotrexate treatment.

Evaluation and implementation of optimized antimicrobial dosing strategies in obese and underweight patients.

PURPOSE: We aimed to develop and implement dosing recommendations for antimicrobials in obese and underweight patients within an academic hospital, and assess their impact on antibiotic prescribing. METHODS: A multi-step approach project was performed. First, obese and underweight patient prevalence and antimicrobial prescription frequency was determined in a point prevalence study. Second and third, a literature review and e-survey provided dosing evidence. Fourth, a consensus meeting was organized to formulate dosing recommendations. Fifth, these were implemented in our clinical validation service as six clinical rules continuously screening patients' records for potentially inappropriate prescriptions (PIPs). Uptake was evaluated by documenting the number of advices and acceptance rate. Last, an interrupted time series analysis (ITS) compared pre- and post-implementation periods to measure the impact of the intervention on residual PIPs/day. A residual PIP was defined as a PIP which persisted up to 48 h. RESULTS: First, 41% of 15.896 hospitalized patients received antimicrobials over 20 days; of which 12% were obese and 9% underweight. Antibiotics were predominantly prescribed according to standard dosing regimens, adjusted to renal function. Next, six dosing recommendations, derived from literature, survey, and consensus, were implemented. In the fifth step, during an 18-week period, 219 advices were given, with 86% acceptance rate. Last, in the ITS analysis, at preintervention, a median of 75% residual PIPs/day existed, reduced to 0% postintervention. Use of clinical rules resulted in a significant immediate 84% relative reduction in residual PIPs (95% CI 0.55-0.94). CONCLUSION: After conducting a literature review, e-survey, and seeking consensus from a panel of experts, dosing recommendations for antimicrobial treatment in both obese and underweight patients were developed. These recommendations have been successfully implemented into clinical practice, addressing the specific needs of these patient populations.

Unpredictable supplementation of vitamin D to infants in the neonatal intensive care unit: An experimental study.

AIM: Extremely premature infants receive nutrition and medication through nasogastric tubes. Breastmilk given accordingly is subject to fat loss. This study aimed to investigate whether this could also apply to vitamin D. METHODS: A questionnaire investigated vitamin D administration at a level III neonatal intensive care unit in Sweden in 2021. Feeding simulations with breastmilk and various vitamin D mixtures were done accordingly. After administration, vitamin D3 concentration was analysed using chromatography with mass spectrometry, followed by repeated simulations with vitamin D mixtures without breastmilk in 2023. RESULTS: The questionnaire was completed by 10 persons. Vitamin D was administered as drops using an enteral syringe and a nasogastric tube in conjunction with a breastmilk meal. In the feeding simulations, vitamin D3 concentration after administration was significantly higher using a syringe alone compared to standard administration. When vitamins were administered according to standard but without breastmilk, 100% of the vitamin D and 40% of the multivitamins were lost. The vitamins adhered to the material, mainly in the nasogastric tube. CONCLUSION: Our findings indicate that standard vitamin D supplementation in the neonatal intensive care unit may be unpredictable when administered by enteral syringe and nasogastric tube. We suggest using direct oral administration whenever possible.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Here, we quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022. We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR: 1.66; 95% CI: 1.07, 2.59; p = 0.02) after the first dose. Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Mind the Decimal Point: A Case of Diazoxide Overdose-Induced Ileus.

Diazoxide is the only medication approved by the United States Food and Drug Administration for the treatment of hyperinsulinism-induced hypoglycemia. Overdose is infrequently reported. This case describes a preterm four-week-old male who was prescribed diazoxide and chlorothiazide for perinatal stress-induced hyperinsulinism. The patient presented to the emergency department with feeding intolerance and abdominal distension following an accidental 10-fold diazoxide overdose. On presentation, vital signs were remarkable for tachycardia and intermittent tachypnea. Physical exam revealed a grossly distended abdomen. Laboratory abnormalities included a glucose of 216 mg/dL, sodium of 132 mmol/L, and chloride of 98 mmol/L. Abdominal X-ray interpretation found moderate gaseous distension suggestive of generalized ileus. The patient was admitted to the neonatal intensive care unit (NICU), and a nasogastric tube was placed. He received intravenous dextrose fluids, and enteral feeds were resumed as serial X-rays showed interval improvement. The patient remained in the NICU for several days to monitor bowel movements and resolution of ileus and he was discharged after improvement. While diazoxide overdose is rarely reported, and ileus due to such is documented even less frequently, 10-fold medication dose errors are common among infants. The source of the 10-fold mistake is often decimal points, leading zeros, or trailing zeros. Utilizing the smallest possible syringe for the prescribed dose may reduce the incidence of medication errors.

Practical considerations in the management of patients treated with bosutinib for chronic myeloid leukemia.

Bosutinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML), and for patients with Ph + chronic phase, accelerated phase, or blast phase CML resistant or intolerant to prior therapy. As is the case for all TKIs approved for treatment of CML, bosutinib is associated with adverse events (AEs) that require appropriate management to ensure adherence to treatment and optimized outcomes. The aim of this review is to provide physicians with updated practical information for the prevention and management of AEs occurring during treatment with bosutinib, including dosing strategies, based on the latest published evidence and clinical experience. Clinical studies and real-world evidence have shown bosutinib has a generally favorable safety profile, which has remained consistent across lines of therapy and in long-term reports. Adjusting the starting dose and/or modifying the dose during treatment with bosutinib are important strategies to manage AEs and improve tolerability, which are recognized within the label and in treatment guidelines. Dosing adjustment strategies to manage AEs are a recognized management approach for other TKIs in the treatment of CML and are not exclusive to bosutinib. In summary, long-term results from clinical trials and emerging real-world evidence demonstrate bosutinib has a safety profile that can largely be managed with treatment modifications and/or supportive care. Increased experience in managing toxicities and by using a personalized dosing approach may further improve adherence and outcomes with bosutinib.

Impact of dosing schedules on performance of rotavirus vaccines in Ghana.

Background: Available live-oral rotavirus vaccines are associated with low to moderate performance in low- and middle-income settings. There is limited evidence relating to how the vaccine dosing schedule might be adjusted to improve vaccine performance in these settings. Methods: We used mathematical models fitted to rotavirus surveillance data for children <5 years of age from three different hospitals in Ghana (Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi and War Memorial Hospital in Navrongo) to project the impact of rotavirus vaccination over a 10-year period (April 2012-March 2022). We quantified and compared the impact of the previous vaccination program in Ghana to the model-predicted impact for other vaccine dosing schedules across the three hospitals and the entire country, under different assumptions about vaccine protection. To project the rotavirus vaccine impact over Ghana, we sampled from the range of model parameters for Accra and Navrongo, assuming that these two settings represent the "extremes" of rotavirus epidemiology within Ghana. Results: For the previously implemented 6/10-week monovalent Rotarix vaccine (RV1) schedule, the model-estimated average annual incidence of moderate-to-severe rotavirus-associated gastroenteritis (RVGE) ranged between 1,151 and 3,002 per 100,000 people per year over the 10-year period for the three sites. Compared to no vaccination, the model-estimated median percentage reductions in RVGE ranged from 28-85% and 12-71% among children <1 year and <5 years of age respectively, with the highest and lowest percentage reductions predicted using model parameters estimated for Accra and Navrongo, respectively. The median predicted reductions in RVGE for the whole country ranged from 57-66% and 35-45% among children <1 year and <5 years of age, respectively. The 1/6/10- and 6/10/14-week schedules provided the best and comparable reductions in RVGE compared to the original 6/10-week schedule, whereas there was no improvement in impact for the 10/14-week schedule. Conclusions: We found that administering an additional dose of RV1 might be an effective strategy to improve rotavirus vaccine impact, particularly in settings with low vaccine effectiveness. The results could be extrapolated to other countries using a 2-dose vaccine schedule with low to moderate vaccine performance.

Practical management of oral treprostinil in patients with pulmonary arterial hypertension: Lessons from ADAPT, EXPEDITE, and expert consensus.

BACKGROUND: Oral treprostinil is a prostacyclin analogue approved to treat pulmonary arterial hypertension (PAH) by delaying disease progression and improving exercise capacity. Higher doses of oral treprostinil correlate with increased treatment benefit. Titrations may be challenging due to common side effects of prostacyclin-class therapies. STUDY DESIGN AND METHODS: The multicenter, prospective, real-world, observational ADAPT Registry study followed adult patients with PAH for up to 78 weeks after initiating oral treprostinil (NCT03045029). Dosing, titration, and transitions of oral treprostinil were at the discretion of the prescriber. Patient-reported incidence and treatment of common side effects were collected to understand side effect management and tolerability. Insights from literature and expert recommendations were added to provide a consolidated resource for oral treprostinil use. RESULTS: In total, 139 participants in ADAPT completed ≥1 weekly survey; (median age 60.0 years, 76 % female). Median treatment duration of oral treprostinil was 13.1 months. During early therapy (Months 1-5), 62 % (78/126) of patients reported headache and diarrhea, and 40 % (50/126) reported nausea. At Month 6, many patients who reported side effects during early therapy reported an improvement (61 % headache, 44 % diarrhea, 70 % nausea). Common side effect treatments, including acetaminophen, loperamide, and ondansetron, were effective. Approximately one-quarter of patients reporting the most common side effects were untreated at Month 6. CONCLUSION: Patient selection for, and initiation and titration of, oral treprostinil should be individualized and may include parenteral treprostinil induction-transition for faster titration. Assertive side effect management may help patients reach higher and more efficacious doses of oral treprostinil.

A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease.

OBJECTIVES: Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase. METHODS: We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect. RESULTS: Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients. CONCLUSION: This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.

Comparative pharmacokinetics of a single oral dose of meloxicam in the California sea lion (Zalophus californianus) and Pacific harbor seal (Phoca vitulina richardii).

Pharmacokinetics studies have investigated meloxicam, a non-steroidal anti-inflammatory drug, dosing strategies in a wide variety of non-domestic animals; however, there is no prior study examining well-founded dosing for pinnipeds. To develop dosing protocols, pharmacokinetic information is needed, with an examination of differences between pinniped species. Apparently, healthy California sea lions (Zalophus californianus: CSL; n = 13) and Pacific harbor seals (Phoca vitulina richardii: PHS; n = 17) that had completed rehabilitation were enrolled into a population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg, and two blood samples were collected from each animal at varying intervals during a 96-h study period. Plasma concentrations of meloxicam were determined by high-pressure liquid chromatography. Data were analyzed with nonlinear mixed effects modeling (Phoenix® NLME™, Certara, St. Louis, MO 63105, USA). The results indicated that in PHS, peak plasma concentration (Cmax) was 0.33 µg/mL with an elimination half-life (Ke t½) of 31.53 h. In CSL, Cmax was 0.17 µg/mL with Ke t½ of 32.71 h. All animals enrolled completed the study without outward adverse clinical signs. The elimination half-life was longer than previously recommended dosing intervals for pinnipeds; however, we cannot speculate in the optimum clinical dose from these results.

Virtual Job Interview Training: A Dose Response to Improve Employment for Transition-Age Youth With Disabilities.

Virtual Interview Training for Transition Age Youth and Virtual Reality Job Interview Training are job interview simulators with demonstrated effectiveness in randomized controlled trials. We evaluated their dose responses via secondary data analysis of 558 transition-age youth with disabilities in 47 schools where the simulators were implemented in quasi-experimental studies. Cut-point analyses determined dosing efficiency and efficacy to optimize competitive employment. The most efficient dose when accounting for the balance between dose and employment was completing nine virtual interviews. The most efficacious dose to maximize the likelihood of successful employment was 38, but varied across race, IQ, IDEA categories and employment history. This study provides a novel approach to inform implementation guidelines for virtual interview training in pre-employment transition services. Limitations and implications for research and practice are discussed.

Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri®) Dosing: NOVA Phase IIIb Extension Study (Part 2).

INTRODUCTION: Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration. METHODS: In part 2, participants received natalizumab (Tysabri®) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa). The primary endpoint was the proportion of participants who indicated a preference for natalizumab SC administration on the Patient Preference Questionnaire. RESULTS: A total of 153 participants were randomized in NOVA part 2. Of 123 with patient preference data, 108 (87.8%) preferred the SC route of administration for natalizumab over the IV route; 102 (82.9%) specified "requires less time in the clinic" as the reason for the SC preference. CONCLUSION: In NOVA (part 2), most participants on Q6W dosing of natalizumab preferred SC administration versus IV administration. CLINICALTRIALS: GOV: NCT03689972. INFOGRAPHIC.

Vincristine exposure in Kenyan children with cancer: CHAPATI feasibility study.

The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

Comprehensive Review on the Use of Oral Cholera Vaccine (OCV) in Ethiopia: 2019 to 2023.

BACKGROUND: Cholera outbreaks in Ethiopia necessitate frequent mass oral cholera vaccine (OCV) campaigns. Despite this, there is a notable absence of a comprehensive summary of these campaigns. Understanding national OCV vaccination history is essential to design appropriate and effective cholera control strategies. Here, we aimed to retrospectively review all OCV vaccination campaigns conducted across Ethiopia between 2019 and 2023. METHODS: The OCV request records from 2019 to October 2023 and vaccination campaign reports for the period from 2019 to December 2023 were retrospectively accessed from the Ethiopia Public Health Institute (EPHI) database. Descriptive analysis was conducted using the retrospective data collected. RESULTS: From 2019 to October 2023, Ethiopian government requested 32 044 576 OCV doses (31 899 576 doses to global stockpile; 145 000 doses to outside of stockpile). Around 66.3% of requested doses were approved; of which 90.4% were received. Fifteen OCV campaigns (12 reactive and 3 pre-emptive) were conducted, including five two-dose campaigns with varying dose intervals and single-dose campaigns partially in 2019 and entirely in 2021, 2022 and 2023. Overall vaccine administrative coverage was high; except for Tigray region (41.8% in the 1st round; 2nd round didn't occur). The vaccine administrative coverage records were documented, but no OCV coverage survey data was available. CONCLUSIONS: This study represents the first comprehensive review of OCV campaigns in Ethiopia spanning the last five years. Its findings offer valuable insights into informing future cholera control strategies, underscoring the importance of monitoring and evaluation despite resource constraints. Addressing the limitations in coverage survey data availability is crucial for enhancing the efficacy of future campaigns.

Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo.

PURPOSE: The CYP2D6 gene exhibits significant polymorphism, contributing to variability in responses to drugs metabolized by CYP2D6. While CYP2D6*2 and CYP2D6*35 are presently designated as alleles encoding normal metabolism, this classification is based on moderate level evidence. Additionally, the role of the formerly called "enhancer" single nucleotide polymorphism (SNP) rs5758550 is unclear. In this study, the impacts of CYP2D6*2, CYP2D6*35 and rs5758550 on CYP2D6 activity were investigated using risperidone clearance as CYP2D6 activity marker. METHODS: A joint parent-metabolite population pharmacokinetic model was used to describe 1,565 serum concentration measurements of risperidone and 9-hydroxyrisperidone in 512 subjects. Risperidone population clearance was modeled as the sum of a CYP2D6-independent clearance term and the partial clearances contributed from each individually expressed CYP2D6 allele or haplotype. In addition to the well-characterized CYP2D6 alleles (*3-*6, *9, *10 and *41), *2, *35 and two haplotypes assigned as CYP2D6*2-rs5758550G and CYP2D6*2-rs5758550A were evaluated. RESULTS: Each evaluated CYP2D6 allele was associated with significantly lower risperidone clearance than the reference normal function allele CYP2D6*1 (p < 0.001). Further, rs5758550 differentiated the effect of CYP2D6*2 (p = 0.005). The haplotype-specific clearances for CYP2D6*2-rs5758550A, CYP2D6*2-rs5758550G and CYP2D6*35 were estimated to 30%, 66% and 57%, respectively, relative to the clearance for CYP2D6*1. Notably, rs5758550 is in high linkage disequilibrium (R2 > 0.85) with at least 24 other SNPs and cannot be assigned as a functional SNP. CONCLUSION: CYP2D6*2 and CYP2D6*35 encode reduced risperidone clearance, and the extent of reduction for CYP2D6*2 is differentiated by rs5758550. Genotyping of these haplotypes might improve the precision of genotype-guided prediction of CYP2D6-mediated clearance.

Efficacy, effectiveness and immunogenicity of reduced HPV vaccination schedules: A review of available evidence.

Background: Current National Advisory Committee on Immunization (NACI) guidance recommends human papillomavirus (HPV) vaccines be administered as a two or three-dose schedule. Recently, several large clinical trials have reported the clinical benefit of a single HPV vaccine dose. As a result, the World Health Organization released updated guidance on HPV vaccines in 2022, recommending a two-dose schedule for individuals aged 9-20 years, and acknowledging the use of an alternative off-label single dose schedule. Objective: The objective of this overview is to provide a detailed account of the available evidence comparing HPV vaccination schedules, which was considered by NACI when updating recommendations on HPV vaccines. Methods: To identify relevant evidence, existing systematic reviews were leveraged where possible. Individual studies were critically appraised, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence. Results: Available evidence suggests that a one, two, or three-dose HPV vaccine schedule may provide similar protection from HPV infection. While antibody levels against HPV vaccine types were statistically significantly lower with a single dose schedule compared to two or three doses, titres were sustained for up to 16 years. The clinical significance of lower antibody titres is unknown, as there is no established immunologic correlate of protection. Conclusion: While the available evidence on single-dose HPV vaccination schedules shows a one-dose schedule is highly effective, continued follow-up of single-dose cohorts will be critical to understanding the relative duration of protection for reduced dose schedules and informing future NACI guidance on HPV vaccines.

Assessing predictors of adequate individual buprenorphine maintenance dosage for the treatment of opioid use disorder: Listening to the patient.

OBJECTIVE: Dose optimization plays a key role in determining clinical outcomes in patients on opioid agonist treatment (OAT). The objective of this study was to identify the variables independently associated with buprenorphine/naloxone (B/N) dose adequacy in patients with opiate use disorder (OUD). METHOD: Cross-sectional study of a convenience sample of patients with OUD treated with B/N (n = 315) in four regions in Spain. The Opiate Dosage Adequacy Scale (ODAS) was used to determine B/N dose adequacy. The ODAS evaluate the six components of the "dose adequacy" construct, as follows: continued use of heroin; narcotic blockade or crossed tolerance; objective opioid withdrawal symptoms (OWS); subjective OWS; craving for heroin; and overmedication. A binomial logistic regression analysis was performed to identify the variables associated with the condition "ODAS Adequate B/N dose". Participants completed a battery of instruments to assess sociodemographic, substance use, clinical, and treatment variables. RESULTS: The B/N dose was considered adequate in 231 of the 315 participants (73.3 %). Two variables, satisfaction with B/N as a medication (OR=5.764, 95 % CI=2.211-15.030) and patient-perceived participation in B/N dose decisions (OR=1.790, 95 % CI=1221-2623), were independently, significantly, and positively associated with the "ODAS Adequate B/N dose" condition. While the severity of heroin dependence was significantly associated with buprenorphine dose adequacy in the bivariate analyses, significance was lost in the full regression model. CONCLUSION: Satisfaction with B/N as a medication and patient-perceived involvement in the dose decision are associated with clinician-assessed dose adequacy. In the context of good clinical practice, it is important to take into account both of these variables to individualize the prescribed dose through a shared decision-making process.