Applying narrative medicine to prepare empathetic healthcare providers in undergraduate pharmacy education in Singapore: a mixed methods study.

BACKGROUND: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. METHODS: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. RESULTS: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. CONCLUSION: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.

The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study.

OBJECTIVES: There is limited evidence supporting the widespread use of α2 agonists (clonidine and dexmedetomidine) in pediatric critical care sedation. This study sought to test the association between the use of α2 agonists and enhanced sedation. DESIGN: A retrospective observational cohort study was conducted. Noninferiority of time adequately sedated (COMFORT Behavior Score 11-16) while mechanically ventilated was assessed. Secondarily, dosing of opioids and benzodiazepines was examined. SETTING: Two tertiary PICUs. PATIENTS: Children were classified into an exposed group, who received an α2 agonist as part of their sedation regimen, and an unexposed group. Groups were matched using propensity score analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand eighty-five patients were included. The exposed group were adequately sedated 74% (95% CI, 72-75%) of the study time compared with the unexposed group at 70% (95% CI, 67-72%) giving a ratio of 1.06 (95% CI, 1.02-1.10) and a noninferior time adequately sedated. A decrease in time oversedated was observed with 8.1% (95% CI, 4.3-11.9%) less time classified as oversedated in the exposed group. Reduction in morphine use of 0.25 µg/kg/hr (95% CI, -0.68 to 1.18 µg/kg/hr) was not statistically significant. Midazolam use did not decrease and was statistically higher. CONCLUSIONS: Use of α2 agonists was associated with similar time adequately sedated as a matched unexposed group although no reduction in morphine or benzodiazepine coadministration was observed. There was a shift toward lighter sedation with α2 agonist use.

Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study.

BACKGROUND: Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilized in clinical practice and in research studies. Within these studies, clonidine has inconsistently shown useful sedation properties. One of the reasons attributed to the inconsistent signs of efficacy is suboptimal clonidine dosing. AIMS: This study aims to propose a target plasma concentration and simulate clonidine pharmacokinetics (PK) in a cohort of mechanically ventilated children to evaluate the adequacy of clonidine dosage regimens used in clinical practice and research studies. METHODS: A literature search was undertaken to identify a clonidine pharmaockinetic-pharmacodynamics (PKPD) model, from which a target concentration for sedation was defined. Using a previously published PK model, the projected plasma concentrations of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed. RESULTS: A target plasma concentration of above 2 µg/L was proposed. Nine dosage regimens (four intravenous boluses, four intravenous infusions, and one nasogastric route boluses) were evaluated ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Regimens with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score appear most suitable. Doses should be halved in neonates. CONCLUSION: The variety of dosage regimens in the previous studies of clonidine along with difficulties in the conduct of interventional studies may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by higher than current practice maintenance dose infusion is required to achieve adequate steady-state concentrations early in treatment. Further PKPD studies will aid in the determination of the optimal clonidine dosage regimen.

Efficacy of α2-Agonists for Sedation in Pediatric Critical Care: A Systematic Review.

OBJECTIVE: Children in PICUs normally require analgesics and sedatives to maintain comfort, safety, and cooperation with interventions. α2-agonists (clonidine and dexmedetomidine) have been described as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. This systematic review aimed to determine whether α2-agonists were effective in maintaining patients at a target sedation score over time compared with a comparator group. We also aimed to determine whether concurrent use of α2-agonists provided opioid-sparing effects. DATA SOURCES: A systematic search was performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, and LILACS. STUDY SELECTION: We included randomized controlled trials of children in PICU treated with clonidine or dexmedetomidine for the indication of sedation. DATA EXTRACTION: Two authors independently screened articles for inclusion. DATA SYNTHESIS: Six randomized controlled trials with sufficient data were identified and critically appraised. Three clonidine trials (two vs placebo and one vs midazolam) and three dexmedetomidine trials (two vs fentanyl, one vs midazolam) were included. Due to study heterogeneity it was not possible to pool studies. A narrative synthesis is provided. CONCLUSIONS: Reporting of study results using the outcome "time maintained at target sedation score' for clonidine or dexmedetomidine was poor. Only one trial compared clonidine with midazolam using a sedation score outcome. This study was underpowered to demonstrate equivalence to midazolam as a sedative. The adjunctive use of clonidine demonstrated significant decreases in opioid use in neonates but not in older groups. Clonidine dose was inconsistent between studies. Dexmedetomidine demonstrated an opioid-sparing effect in two small trials. Further studies, including dose-finding studies and studies with sedation score-based outcomes, are needed.

The fox and the grapes: an Anglo-Irish perspective on conscientious objection to the supply of emergency hormonal contraception without prescription.

Emergency hormonal contraception (EHC) has been available from pharmacies in the UK without prescription for 11 years. In the Republic of Ireland this service was made available in 2011. In both jurisdictions the respective regulators have included 'conscience clauses', which allow pharmacists to opt out of providing EHC on religious or moral grounds providing certain criteria are met. In effect, conscientious objectors must refer patients to other providers who are willing to supply these medicines. Inclusion of such clauses leads to a cycle of cognitive dissonance on behalf of both parties. Objectors convince themselves of the existence of a moral difference between supply of EHC and referral to another supplier, while the regulators must feign satisfaction that a form of regulation lacking universality will not lead to adverse consequences in the long term. We contend that whichever of these two parties truly believes in that which they purport to must act to end this unsatisfactory status quo. Either the regulators must compel all pharmacists to dispense emergency contraception to all suitable patients who request it, or a pharmacist must refuse either to supply EHC or to refer the patient to an alternative supplier and challenge any subsequent sanctions imposed by their regulator.

Transforming pharmaceutical education: A needs-based global analysis for policy development.

Background: A needs-based approach is desirable for the transformation of pharmaceutical education, and to link pharmaceutical education with the health needs of populations and national priorities. There are varying levels of data in the literature on the status of pharmaceutical education in all six World Health Organization (WHO) regions, especially in the context of needs identification and evidence-based policy interventions. The framework for this study was the FIP Development Goals. Objectives: The aim of the study was to develop evidence-based policies through a needs-based approach for pharmaceutical education transformation nationally, regionally and globally by addressing the following objectives: 1. Identify global and regional needs in pharmaceutical education, through a regional SWOT analysis and prioritization of FIP development goals; 2. Develop valid and credible regional roadmaps for pharmaceutical education advancement according to the identified prioritized goals and 3. Develop a global call to action as a policy intervention for advancing pharmaceutical education. Methods: This study was conducted between 2020 and 2021 using a mixed methods approach. Surveys of higher education institutions and a series of qualitative interviews were conducted with national professional leadership organizations, with further regional workshops having 284 participants recruited from the International Pharmaceutical Federation (FIP) membership base, spanning all six WHO regions. Results: Eleven out of 21 FIP DGs were identified as priorities for regional roadmaps and FIP DG 1 (Academic capacity) was identified as a priority in four regions. All regions had distinctive results with an area of commonality between them. There were common weaknesses in the adoption of competency-based education and inter-professional education. Conclusions: It is critical for every country and region to develop needs- and evidence-based policies for the transformation of pharmaceutical education, for which FIP DGs provide a systematic framework.

The application of high-content analysis in the study of targeted particulate delivery systems for intracellular drug delivery to alveolar macrophages.

With an ever increasing number of particulate drug delivery systems being developed for the intracellular delivery of therapeutics a robust high-throughput method for studying particle-cell interactions is urgently required. Current methods used for analyzing particle-cell interaction include spectrofluorimetry, flow cytometry, and fluorescence/confocal microscopy, but these methods are not high throughput and provide only limited data on the specific number of particles delivered intracellularly to the target cell. The work herein presents an automated high-throughput method to analyze microparticulate drug delivery system (DDS) uptake byalveolar macrophages. Poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared in a range of sizes using a solvent evaporation method. A human monocyte cell line (THP-1) was differentiated into macrophage like cells using phorbol 12-myristate 13-acetate (PMA), and cells were treated with microparticles for 1 h and studied using confocal laser scanning microscopy (CLSM), spectrofluorimetry and a high-content analysis (HCA). PLGA microparticles within the size range of 0.8-2.1 µm were found to be optimal for macrophage targeting (p < 0.05). Uptake studies carried out at 37 °C and 4 °C indicated that microparticles were internalized in an energy dependent manner. To improve particle uptake, a range of opsonic coatings were assessed. Coating PLGA particles with gelatin and ovalbumin was found to significantly increase particle uptake from 2.75 ± 0.98 particles per cell for particles coated with gelatin. Opsonic coating also significantly increased particle internalization into primary human alveolar macrophages (p < 0.01) with a 1.7-fold increase in uptake from 4.19 ± 0.48 for uncoated to 7.53 ± 0.88 particles per cell for coated particles. In comparison to techniques such as spectrofluorimetry and CLSM, HCA provides both qualitative and quantitative data on the influence of carrier design on cell targeting that can be gathered in a high-throughput format and therefore has great potential in the screening of intracellularly targeted DDS.

Methadone and perinatal outcomes: a retrospective cohort study.

OBJECTIVE: The purpose of this study was to examine the relationship among methadone maintenance treatment, perinatal outcomes, and neonatal abstinence syndrome. STUDY DESIGN: This was a retrospective cohort study of 61,030 singleton births at a large maternity hospital from 2000-2007. RESULTS: There were 618 (1%) women on methadone at delivery. Methadone-exposed women were more likely to be younger, to book late for antenatal care, and to be smokers. Methadone exposure was associated with an increased risk of very preterm birth <32 weeks of gestation (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.40-4.34), being small for gestational age <10th percentile (aOR, 3.27; 95% CI, 2.49-4.28), admission to the neonatal unit (aOR, 9.14; 95% CI, 7.21-11.57), and diagnosis of a major congenital anomaly (aOR, 1.94; 95% CI, 1.10-3.43). There was a dose-response relationship between methadone and neonatal abstinence syndrome. CONCLUSION: Methadone exposure is associated with an increased risk of adverse perinatal outcomes, even when known adverse sociodemographic factors have been accounted for. Methadone dose at delivery is 1 of the determinants of neonatal abstinence syndrome.

Medication use in early pregnancy-prevalence and determinants of use in a prospective cohort of women.

PURPOSE: To examine the extent, nature and determinants of medication use in early pregnancy. METHODS: We reviewed early pregnancy medication use, as reported to a midwife at the booking interview, in women delivering between 2000 and 2007 in a large maternity hospital in Dublin, Ireland (n = 61 252). RESULTS: Excluding folic acid, at least one medication was reported in 23 989 (39.2%) pregnancies. Over the counter (OTC) medications were reported in 11 970 (19.5%) pregnancies, illicit drugs or methadone in 545 (0.9%) and herbal medicines/supplements in 352 (0.58%). FDA category D and X medications were reported by 1532 (2.5%) and 1987 (3.2%) women. Asthma, depression and hypertension were among the most commonly reported chronic medical disorders. Medications with potential for foetal harm were reported by 86 (15.7%) women treated for depression and 68 (20%) women treated for hypertension. Factors associated with reporting the use of medications with potential for foetal harm included unplanned pregnancy (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.12-1.52), booking at less than 12 weeks gestation (aOR 1.83, 95%CI 1.58-2.13), being above 25 years of age, unemployed (aOR 2.58, 95%CI 2.03-3.29), nulliparous (aOR 1.41; 95%CI 1.22-1.63), single (aOR 1.28; 95%CI 1.06-1.54) or smoking during pregnancy (aOR 1.96, 95%CI 1.67-2.28). CONCLUSIONS: Women frequently report medication use in early pregnancy. Women and prescribers need to be aware of the lack of pregnancy safety data for many medications, and the need for pre-pregnancy planning. Prescribers should ensure that optimal medications are used when treating women of childbearing potential with chronic medical disorders.

'Both useful in their own way': Video podcasts and typed solutions as feedback on undergraduate pharmaceutical calculations skills assessment.

INTRODUCTION: Accurately completing pharmaceutical calculations is a core professional skill for pharmacists. To date, few studies have focused on to providing feedback on calculations, or the role of technology in feedback provision. This study aimed to develop a theory-informed video podcast-based method of providing formative feedback and evaluate student perceptions. METHODS: First-year pharmacy students (n = 53) completed a formative pharmaceutical calculations assessment. Two forms of feedback were designed and evaluated; typed solutions (traditional format commonly used/seen in textbooks) and video podcasts informed by instructional design theory (novel format). RESULTS: A survey was completed by 70% (37/53) of students. Specific features of video podcasts reported useful included hearing reasoning, and the ability to pause and rewind. Most (76%) reported positive attitudes towards video podcasts, considered them useful (75%) and helpful for learning (79%). A comparable number (76% and 71% respectively) felt positively about typed solutions. The majority (51%) preferred to receive both types rather than podcasts alone (24%), or typed solutions alone (8%). Free-text responses indicated both were used in different ways; typed solutions for quick verification and video podcasts for clarification. CONCLUSIONS: Video podcasts appear to be a potentially helpful additional method of delivering feedback that afford specific advantages. They can be readily developed by faculty with minimal expense/difficulty. However, as respondents indicated that they used both kinds of feedback in different ways to support their learning, and indicated a preference to receive both types, they should be considered an addition rather than replacement for typed solutions.

Consensus validation of the POSAMINO (POtentially Serious Alcohol-Medication INteractions in Older adults) criteria.

OBJECTIVES: Older adults are particularly vulnerable to adverse effects from concurrent alcohol and medication use. However, there is limited evidence regarding the prevalence of these adverse outcomes among older adults, and there is a lack of consensus regarding what constitutes an alcohol-interactive medicine. The objective of this study was to develop an explicit list of potentially serious alcohol-medication interactions for use in older adults. DESIGN: Following a systematic review, review of drug compendia and clinical guidance documents, a two-round Delphi consensus method was conducted. SETTING: Ireland and the United Kingdom (UK), primary care and hospital setting. PARTICIPANTS: The Project Steering Group developed a list of potentially serious alcohol-medication interactions. The Delphi panel consisted of 19 healthcare professionals (general practitioners, geriatricians, hospital and community pharmacists, clinical pharmacologists and pharmacists, and physicians specialising in substance misuse). RESULTS: An inventory of 52 potentially serious alcohol-medication interactions was developed by the Project Steering Group. British National Formulary black dot warnings (n=8) were included in the final criteria as they represent 'potentially serious' interactions. The remaining 44 criteria underwent a two-round Delphi process. In the first round, 13 criteria were accepted into the POtentially Serious Alcohol-Medication INteractions in Older adults (POSAMINO) criteria. Consensus was not reached on the remaining 31 criteria; 9 were removed and 8 additional criteria were included following a review of panellist comments. The remaining 30 criteria went to round 2, with 17 criteria reaching consensus, providing a final list of 38 potentially serious alcohol-medication interactions: central nervous system (n=15), cardiovascular system (n=9), endocrine system (n=5), musculoskeletal system (n=3), infections (n=3), malignant disease and immunosuppression (n=2), and respiratory system (n=1). CONCLUSIONS: POSAMINO is the first set of explicit potentially serious alcohol-medication interactions for use in older adults. Following future validation studies, these criteria may allow for the risk stratification of older adults at the point of prescribing.

Design and Evaluation of Video Podcasts for Providing Online Feedback on Formative Pharmaceutical Calculations Assessments.

Objective. To evaluate worked example video podcasts as a method of providing feedback to pharmacy interns for an online and formative pharmaceutical calculations assessment. Methods. A theory-informed approach based on multimedia learning theory was used to design video podcasts as feedback on a calculations examination. A mixed-methods evaluation completed by pharmacy interns enrolled in Ireland's National Pharmacy Internship Programme was used to establish cognitive and affective attitudes toward video podcasts compared with conventional written solutions. Results. The majority of students found video podcasts were clear, helpful for learning, easy to understand, and useful as a method of feedback. Majority reported that they felt positively about standard written solutions. The evaluation suggested distinct benefits for each kind of feedback, something that has not been previously reported. Thematic analysis of qualitative data indicated useful features of video podcasts, including clear explanation, step-by-step approach, and synchronization of audio and visual information. Conclusion. Respondents reported positive cognitive and affective attitudes toward video podcasts as online feedback. Video podcasts are a helpful and novel way of providing feedback on pharmaceutical calculations. A similar opinion of traditional written solutions suggests that students may benefit from both forms of feedback. Further study is required to identify the particular benefits associated with both kinds.

Effectiveness of α2agonists for sedation in paediatric critical care: study protocol for a retrospective cohort observational study.

INTRODUCTION: Mechanically ventilated children in paediatric intensive care units are commonly administered analgesics and sedative agents to minimise pain and distress and facilitate cooperation with medical interventions. Opioids and benzodiazepines are the most common analgesic and sedative agents but have safety concerns. The α2 agonists clonidine and dexmedetomidine are alternative sedatives in use despite neither having robust evidence to support their use. Studies evaluating effectiveness of α2 agonists to date have not focused on sedation-based outcomes instead focusing on opioid-sparing properties and ventilation outcomes. The aim of this study is to evaluate if an opioid-based sedation regimen, with an α2 agonist adjunct (clonidine or dexmedetomidine), produces a non-inferior proportion of time adequately sedated compared with a control group without an α2 agonist adjunct, while conferring potential additional benefits such as reduced opioid administration and less exposure to potential additional agents such as benzodiazepines. METHODS AND ANALYSIS: We will conduct a retrospective cohort study in two Irish paediatric intensive care units using clinical information on patient characteristics, sedation scores and drug use. Eligible children admitted between January 2014 and June 2016 who were mechanically ventilated and received an opioid infusion will be included. Patients will be categorised into two exposure categories (received an α2 agonist or did not receive an α2 agonist) and the time adequately sedated (measured using the COMFORT Behaviour Score) will be calculated using interpolation of nursing sedation scores at each recorded time point. At least 150 per group is planned for inclusion to ensure adequate study power. Propensity score matching will be used in analysis to account for potential confounding by indication. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of both hospitals. Dissemination will occur via local, national and international presentations for academic and healthcare audiences as well as through peer reviewed publications.

Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co-Glycolic Acid) Microparticles Drives NFκB and Autophagy Dependent Bacillary Killing.

The emergence of multiple-drug-resistant tuberculosis (MDR-TB) has pushed our available repertoire of anti-TB therapies to the limit of effectiveness. This has increased the urgency to develop novel treatment modalities, and inhalable microparticle (MP) formulations are a promising option to target the site of infection. We have engineered poly(lactic-co-glycolic acid) (PLGA) MPs which can carry a payload of anti-TB agents, and are successfully taken up by human alveolar macrophages. Even without a drug cargo, MPs can be potent immunogens; yet little is known about how they influence macrophage function in the setting of Mycobacterium tuberculosis (Mtb) infection. To address this issue we infected THP-1 macrophages with Mtb H37Ra or H37Rv and treated with MPs. In controlled experiments we saw a reproducible reduction in bacillary viability when THP-1 macrophages were treated with drug-free MPs. NFκB activity was increased in MP-treated macrophages, although cytokine secretion was unaltered. Confocal microscopy of immortalized murine bone marrow-derived macrophages expressing GFP-tagged LC3 demonstrated induction of autophagy. Inhibition of caspases did not influence the MP-induced restriction of bacillary growth, however, blockade of NFκB or autophagy with pharmacological inhibitors reversed this MP effect on macrophage function. These data support harnessing inhaled PLGA MP-drug delivery systems as an immunotherapeutic in addition to serving as a vehicle for targeted drug delivery. Such "added value" could be exploited in the generation of inhaled vaccines as well as inhaled MDR-TB therapeutics when used as an adjunct to existing treatments.

Methadone dosing and prescribed medication use in a prospective cohort of opioid-dependent pregnant women.

AIMS: This study aimed to (i) describe methadone dosing before, during and after pregnancy, (ii) to compare the incidence of neonatal abstinence syndrome (NAS) between those with dose decreases and those with steady or increasing doses and (iii) to describe prescribed medication use among opioid-dependent pregnant women. DESIGN: Prospective cohort study. SETTING: Two Irish tertiary care maternity hospitals. PARTICIPANTS: A total of 117 pregnant women on methadone maintenance treatment (MMT) recruited between July 2009 and July 2010. MEASUREMENTS: Electronic dispensing records from addiction clinics and the Primary Care Reimbursement Service were used to determine methadone doses and dispensed medications in the year preceding and the month following delivery. The Finnegan score was used to determine need for medical treatment of NAS. FINDINGS: Of the 117 participants, sufficient dosing data were available for 89 women treated with MMT throughout pregnancy; 36 (40.4%) had their dose decreased from a mean pre-pregnancy dose of 73.3 mg [standard deviation (SD) 25.5] to a third-trimester dose of 58.0 mg (SD 26.0). The corresponding figures for those with increased doses (n = 31, 34.8%) were 70.7 mg (SD 25.3) and 89.7 mg (SD 21.0), respectively. The incidence of medically treated NAS did not differ between dosage groups. Antidepressants were dispensed for 29 women (25.7%) during pregnancy, with the rate decreasing from pre-pregnancy to postpartum. Benzodiazepines were prescribed for 43 women (38.0%). CONCLUSION: In the Irish health service, opioid-dependent women frequently have their methadone dose decreased during pregnancy but this does not appear to affect the incidence of the neonatal abstinence syndrome in their babies.

Methadone and perinatal outcomes: a prospective cohort study.

AIMS: Methadone use in pregnancy has been associated with adverse perinatal outcomes and neonatal abstinence syndrome (NAS). This study aimed to examine perinatal outcomes and NAS in relation to (i) concomitant drug use and (ii) methadone dose. DESIGN: Prospective cohort study. SETTING: Two tertiary care maternity hospitals. PARTICIPANTS: A total of 117 pregnant women on methadone maintenance treatment recruited between July 2009 and July 2010. MEASUREMENTS: Information on concomitant drug use was recorded with the Addiction Severity Index. Perinatal outcomes included pre-term birth (<37 weeks' gestation), small-for-gestational-age (<10th centile) and neonatal unit admission. NAS outcomes included: incidence of medically treated NAS, peak Finnegan score, cumulative dose of NAS treatment and duration of hospitalization. FINDINGS: Of the 114 liveborn infants 11 (9.6%) were born pre-term, 49 (42.9%) were small-for-gestational-age, 56 (49.1%) had a neonatal unit admission and 29 (25.4%) were treated medically for NAS. Neonates exposed to methadone-only had a shorter hospitalization than those exposed to methadone and concomitant drugs (median 5.0 days versus 6.0 days, P = 0.03). Neonates exposed to methadone doses ≥80 mg required higher cumulative doses of morphine treatment for NAS (median 13.2 mg versus 19.3 mg, P = 0.03). The incidence and duration of NAS did not differ between the two dosage groups. CONCLUSIONS: The incidence and duration of the neonatal abstinence syndrome is not associated with maternal methadone dose, but maternal opiate, benzodiazepine or cocaine use is associated with longer neonatal hospitalization.

Methadone dose and neonatal abstinence syndrome-systematic review and meta-analysis.

AIM: To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS). METHODS: PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966-2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut-off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta-analysis. Sensitivity analyses explored the impact of limiting meta-analyses to prospective studies or studies using an objective scoring system to diagnose NAS. RESULTS: A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta-analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non-significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS. CONCLUSIONS: Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.