Fluent Essays

Requirements Your submission must be your original work. No more than a combined total of 30\% of the submission and no more than a 10\% match to any one individual source can be directly quoted or closely paraphrased from sources, even if cited correctly. An originality report is provided when you submit your task that can be used as a guide. You must use the rubric to direct the creation of your submission because it provides detailed criteria that will be used to evaluate your work. Each requirement below may be evaluated by more than one rubric aspect. The rubric aspect titles may contain hyperlinks to relevant portions of the course. A. Write a summary of the significance and background of a healthcare problem by doing the following: 1. Describe a healthcare problem that can be used to develop a PICO question. Note: You may use the same topic and the same research articles that were used in Task 1 provided they support the proposed intervention. Or you may choose a different topic and select articles focusing on one of the following topics: falls and fall prevention, pain management in children, opioid abuse, hepatitis C, catheter-associated urinary tract infections, and hand hygiene and infections in hospitals. 2. Explain the significance of the problem from part A1. 3. Describe the current healthcare practices related to the problem from part A1. 4. Discuss how the problem affects the organization and patients’ cultural background (i.e., values, health behavior, and preferences). B. Complete a literature review by searching for a total of seven articles consisting of five research articles and two non-research articles related to the healthcare problem from part A1, and describe the search strategy you used to conduct the literature review by doing the following: 1. Discuss two research evidence sources and two nonresearch evidence sources that you considered. Note: Please do not use the same primary author for more than two articles. Articles must not be more than five years old. C. Use your research articles to develop a PICO (patient/population, intervention/indicator, comparison/control, and outcome) question based on the topic. D. Complete the attached “Evidence Matrix,” using the five research evidence sources from scholarly journal sources you located during the literature review in part B. For each article, address the following points: Note: You may submit your completed matrix as a separate attachment to the task, or you may include the matrix within your paper, aligned to APA formatting standards. Note: Upload a copy of the full text of the articles with your submission. • author, journal name, and year of publication • research design (e.g., quantitative, qualitative, mixed design, systematic review) • sample size (e.g., numbers of study participants, number of articles, number of control group participants) • outcome variables measured (e.g., identify what the research is measuring) • quality (using the following scale: A, B, C) • results/author’s conclusions (e.g., briefly summarize the outcome) E. Recommend a practice change that addresses the PICO question, using the evidence collected in the attached “Evidence Matrix.” You must use all five research articles from the “Evidence Matrix” attachment to support this recommendation via in-text citations. F. Describe a process for implementing the practice change from part E in which you do the following: 1. Explain how you would involve three key stakeholders in the decision to implement the recommendation from part E. 2. Describe two specific barriers you may encounter when implementing the practice change from part E in the nursing practice setting. 3. Identify two strategies that could be used to overcome the barriers described in part F2. 4. Identify one indicator to measure the outcome (the O in PICO question) of the recommended change practice from part E. G. Acknowledge sources, using APA-formatted in-text citations and references, for content that is quoted, paraphrased, or summarized. H. Demonstrate professional communication in the content and presentation of your submission. Rubric A1:Healthcare Problems Not Evident A description of a healthcare problem is not provided.  Approaching Competence The described healthcare problem does not contain enough detail that it can be used to develop a PICO question. The described healthcare problem is not one that is currently prioritized in healthcare organizations. Competent The described healthcare problem contains enough detail that it can be used to develop a PICO question. The described healthcare problem is one that is currently prioritized in healthcare organizations. A2:Significance of Problem Not Evident An explanation is not provided. Approaching Competence The explanation does not address the significance of the problem described in part A1. Competent The explanation thoroughly addresses the significance of the problem described in part A1.” The explanation contains enough detail to address the significance of the problem described in part A1. A3:Current Practice Not Evident A description is not provided. Approaching Competence The description does not incorporate specific examples of the current healthcare practices related to the described problem from part A1. Competent The description incorporates specific examples of the current healthcare practices related to the described problem from part A1. A4:Impact on Background Not Evident A discussion is not provided. Approaching Competence The discussion incorporates how the problem affects the organization and patient’s cultural background, but specific details or examples related to the problem are not provided. Competent The discussion incorporates specific details of how the problem affects the organization and specific examples of how the problem impacts the patient’s cultural background. B1:Evidence Sources Not Evident A discussion of 2 research evidence sources and 2 nonresearch evidence sources is not provided. Approaching Competence The discussion of 2 research evidence sources and 2 nonresearch evidence sources does not convey a level of understanding in relation to appropriate scholarly and secular sources. Competent The discussion of 2 research evidence sources and 2 nonresearch evidence sources conveys a level of understanding in relation to appropriate scholarly and secular sources. C:PICO Question Not Evident The question is not provided. Approaching Competence The developed question does not include all elements of PICO (patient/population, intervention/indicator, comparison/control, and outcome), is not based on the topic, or does not use research from part B. Competent The developed question includes all elements of PICO (patient/population, intervention/indicator, comparison/control, and outcome), is based on the topic and uses research from part B. D:Evidence Matrix Not Evident The attachment is not provided. Approaching Competence The “Evidence Matrix” attachment does not include the 5 sources from part B, or the sources are from scholarly journals or are not located in major medical databases. The given points are not all accurately or logically addressed for each source. Competent The “Evidence Matrix” attachment includes the 5 sources from part B, and the scholarly journal sources are located in major medical databases. All of the given points are accurately or logically addressed for each source. E:Recommended Practice Change Not Evident A practice change is not recommended. Approaching Competence The recommended practice change is not a logical outcome of the PICO question or is not supported by the evidence collected in the “Evidence Matrix” attachment. Fewer than 5 research articles from the “Evidence Matrix” attachment are used via in-text citations to support the recommendation. Competent The recommended practice change is an logical outcome of the PICO question and is supported by the evidence collected in the “Evidence Matrix” attachment. All 5 research articles from the “Evidence Matrix” attachment are used via in-text citations to support the recommendation. F1 :Key Stakeholders Not Evident An explanation is not provided. Approaching Competence The explanation does not show an effective way for 3 key stakeholders to be involved in the decision to implement the recommendation from part E. Competent The explanation shows an effective way for 3 key stakeholders to be involved in the decision to implement the recommendation from part E. F2:Barriers Not Evident A description is not provided. Approaching Competence The description does not address 2 plausible barriers that may be encountered when implementing the practice change from part E in a nursing practice setting. Competent The description addresses 2 plausible barriers that may be encountered when implementing the practice change from part E in a nursing practice setting. F3:Strategies for Barriers Not Evident 2 strategies are not identified. Approaching Competence 2 strategies are identified, but both of the identified strategies could not be used to overcome the barriers described in part F2. Competent 2 strategies that could be used to overcome the barriers described in part F2 are identified. F4:Indicator to Measure Outcome Not Evident An indicator is not provided. Approaching Competence 1 indicator is identified, but the identified indicator would not measure the outcome of the recommended practice change from part E. Competent The 1 identified indicator would measure the outcome of the recommended practice change from part E. G:APA Sources Not Evident The submission does not include in-text citations and references according to APA style for content that is quoted, paraphrased, or summarized. Approaching Competence The submission includes in-text citations and references for content that is quoted, paraphrased, or summarized but does not demonstrate a consistent application of APA style. Competent The submission includes in-text citations and references for content that is quoted, paraphrased, or summarized and demonstrates a consistent application of APA style. H:Professional Communication Not Evident Content is unstructured, is disjointed, or contains pervasive errors in mechanics, usage, or grammar. Vocabulary or tone is unprofessional or distracts from the topic. Approaching Competence Content is poorly organized, is difficult to follow, or contains errors in mechanics, usage, or grammar that cause confusion. Terminology is misused or ineffective. Competent Content reflects attention to detail, is organized, and focuses on the main ideas as prescribed in the task or chosen by the candidate. Terminology is pertinent, is used correctly, and effectively conveys the intended meaning. Mechanics, usage, and grammar promote accurate interpretation and understanding. task_2_article_1.pdf task_2_article_2.pdf task_2_article_3.pdf task_2_article_4_non_research.pdf Unformatted Attachment Preview DARU Journal of Pharmaceutical Sciences (2019) 27:423–431 https://doi.org/10.1007/s40199-019-00266-3 REVIEW ARTICLE Therapeutic approaches for neonatal abstinence syndrome: a systematic review of randomized clinical trials Masumeh Ghazanfarpour 1 & Mona Najaf Najafi 2 & Nasibeh Roozbeh 3 & Mohamadghasem Etemadi Mashhadi 4 & Atefeh Keramat-roudi 5 & Bruno Mégarbane 6 & Aristidis Tsatsakis 7 & Mohammad Mobin Miri Moghaddam 8 & Ramin Rezaee 2,9,10,11 Received: 11 January 2019 / Accepted: 11 April 2019 / Published online: 15 May 2019 # Springer Nature Switzerland AG 2019 Abstract Neonatal abstinence syndrome (NAS) which is observed in 55–94\% of the newborns from opioids-taking mothers produces deleterious neurological symptoms. Various pharmacological therapies have been investigated in neonates with NAS. This article reviews all studies on NAS treatment to analyze the duration of treatment, length of hospitalization and possible drug adverse effects. The search was limited to the randomized clinical trials which examined the treatments of neonates with NAS. Scientific databases including PubMed, Cochrane Library, ISI Web of Science, Embase and Scopus were systematically searched. Retrieved articles were reviewed by two researchers and evaluated using the JADAD scoring system. Finally, the treatment duration, hospitalization length and drug side-effects were extracted. Methadone, buprenorphine and clonidine were found more effective than morphine. Diluted tincture of opium (DTO) in combination with phenobarbital or clonidine was significantly more effective than DTO alone. Clonidine was a significantly better adjunctive therapy than phenobarbital in reducing morphine treatment days. No significant difference was observed between morphine and DTO effectiveness. Deciding the optimal regimen to manage symptomatic NAS, as a single or an adjunct therapy is not possible based on the literature, due to the low quality, small size and short-term treatment considered in the published studies. Keywords Neonatal abstinence syndrome . Neonatal withdrawal syndrome . Neonatal passive addiction . Opioid . Opium . Methadone . Morphine . Clonidine . Withdrawal Masumeh Ghazanfarpour and Mona Najaf Najafi contributed equally to this work. Highlights • Although Neonatal abstinence syndrome (NAS) produces deleterious neurological symptoms with considerable emotional and economic burden to the society, no definite approach has been suggested for its treatment. • The effectiveness of methadone, buprenorphine and clonidine was found to be superior to that of morphine in the treatment of NAS. • Diluted tincture of opium (DTO) in combination with either phenobarbital or clonidine was significantly more effective than administered alone. • There were conflicting findings regarding the comparative effectiveness of phenobarbital versus morphine to treat NAS. • Clonidine was significantly better than phenobarbital as adjunctive therapy in reducing morphine treatment days in NAS. • No significant difference was observed between morphine and DTO effectiveness. * Ramin Rezaee raminrezaee1983@gmail.com Extended author information available on the last page of the article Introduction The prevalence of nonmedical use of opioids is increasing. In the US, it is estimated that nearly 1\% of the pregnant women actually use opioids during pregnancy [1]. Neonatal abstinence syndrome (NAS) is defined as “sudden discontinuation of fetal exposure to chemicals/drugs used/abused by the mother during pregnancy”. This syndrome is observed in 55–94\% of infants born from opioid-dependent mothers [2]. Infants with NAS may present deleterious and even life-threatening features including neurological hyperexcitability (insomnia, irritability, hypertonia, hyperreflexia, tremors, and seizures), gastrointestinal symptoms (vomiting, diarrhea, and feeding disturbances) and sympathetic/parasympathetic deregulation (sweating, fever, tachypnea, and congestion) [2]. The time of NAS symptom onset is variable ranging from hours to 8 days post-delivery [3]. NAS is also associated with costly hospitalizations [4]. The majority of symptomatic newborns require pharmacological support for safe opioid weaning [3]. Nevertheless, no 424 single drug has been evidenced as the most appropriate therapy to treat NAS. Although the American Academy of Pediatrics (AAP) has indicated opioids as first-line treatment of NAS, their use remains controversial in the neonate [1]. Alternative therapies include sedative drugs and/or centrally acting α2-agonists such as clonidine. The present article reviews all major studies published in the medical literature on NAS treatment aiming to analyze the duration of treatment, the length of hospitalization and the possible drug adverse effects. DARU J Pharm Sci (2019) 27:423–431 Quality assessment To evaluate the quality of the trials, the Jadad scale which examines three important items [5] namely, randomization (description and adjustment), blinding (description and adjustment), report of withdrawals and the cause of loss to follow up, was used. Total score of Jadad ranges from 3 to 5 points. In the present work, two reviewers independently assessed the articles and calculated Jadad score. Any disagreements were resolved via consensus or by consulting with a third party. Intention-to-treat analysis was also reviewed and reported. Methods Data analysis Search strategy Due to the heterogeneity of the studies, it was not possible to perform meta-analysis and retrieved data were reported using a qualitative approach. The search was limited to the randomized clinical trials which examined the treatments of neonates with NAS. Scientific databases including PubMed, Cochrane Library, ISI Web of Science, Embase and Scopus were systematically searched for articles published until 29 August 2018, using combinations of the following keywords: (“Neonatal Abstinence Syndrome” OR “Neonatal Withdrawal Syndrome” OR “Neonatal Passive Addiction” OR “Opioid” OR “Opiates” OR “Heroin” OR “Hydromorphone” OR “oxycodone” OR “Opium” OR “Methadone” OR “Morphine” OR “Tramadol”) AND (“Management” OR “Therapy” OR “Therapeutics” OR “Treatment” OR “Detoxification). The reference lists of the retrieved publications were thoroughly checked to complete the search. Results We identified 1961 publications in our preliminary search. After excluding duplicate studies, 1011 articles remained. Of them, 963 articles were excluded based on the title and abstract and finally 48 full texts were reviewed. Here, 13 original articles were included in the final review. The PRISMA flow chart of this systematic review is presented in Fig. 1. The quality assessment of these articles is presented in Table 1. Their characteristics including the author’s name, time of study, design (with details), type of opioid exposure in utero, the intervention and control groups, assessment tool of NAS Inclusion/exclusion criteria Randomized Clinical trials that investigated the drug effects on NAS were included in this systematic review. There was no limitation for the control group. Duplicate and non-English articles were excluded. Arcles idenfied through Databases searching (n = 1961) Pubmed: 311 Web of Science: 555 Embase: 265 Scopus: 722 Cochran: 108 Data extraction The articles were reviewed by two researchers. First, related articles were identified based on the title and abstract. Then, full-text articles were downloaded and evaluated independently by two researchers. The references cited in the retrieved articles as well as the review articles published in this field were reviewed to find relevant studies. Outcome measures Outcome measures were the “type of treatment”, “duration of treatment”, “length of hospitalization” and “drug side-effects”. Arcles aer the removing duplicate (n =1011) Full-text arcles assessed in detail (n =48) Arcles excluded aer reading tle and abstract (n =963) Full-text arcles excluded, with following reasons (n =35) Non-pharmacological studies (n=25) Observaonal pharmacological studies (n=7) Non ranomized (n=1) No fulltext (n=2) Trials included in systemac review (n =13) Fig. 1 Process of selecting trials included in the present systematic review + – – + – + – – – – – – + + + + – – – + + + + + – – + + + + + + + + – + + + + – + – – – – + + + – – + +: Present; −: Absent;?: Intention-to-treat not reported Langenfeld,2005 [13] Coyle, 2005 [14] Jackson,2004 [15] Coyle, 2002 [] Kraft, 2008 [12] Agthe, 2009 [2] Kraft, 2011 [11] Brown, 2014 [9] Surran, 2013 [10] Bada, 2015 [1] Nayeri, 2015 [8] + – + + Mention blinding Inappropriate Method Mention randomization appropriate Method Blinding Randomization ClinicalTrials.gov NCT00521248 ClinicalTrials.gov NCT00510016 ClinicalTrials.gov NCT00521248 – ClinicalTrials.gov NCT01958476 ClinicalTrials.gov NCT01452789 IRCT.ir IRCT201406239568N8 ClinicalTrials.gov NCT01734551 – – Davis, 2018 [6] Kraft, 2017 [7] Registration site/ code The quality assessment of included studies in this systematic review First author, year Table 1 + + + + – + – + – + – + + appropriate Method – – – – – – – – – – – – – Inappropriate Method + + + + + + + + + + + + + Report of loss to follow up ? ? ? ? ? + + + ? ? ? + + Intention-to-treat analysis DARU J Pharm Sci (2019) 27:423–431 425 426 severity and the study primary outcome of are shown in Table 2. Methadone vs. morphine Treatment with methadone was associated with 14\% reduction in the mean number of hospitalization days (p = 0.046) and 16\% reduction in the length of treatment (p = 0.02) in comparison to morphine [6]. In another study, methadonecompared to morphine-treated newborns had significantly shorter duration of treatment (p = 0.008) [9]. Phenobarbital vs. morphine No significant differences between oral phenobarbital and morphine were reported in one study regarding the treatment duration (p = 0.9) and hospital length of stay (p = 0.7) [8]. Conversely, shorter treatment duration following oral morphine versus phenobarbital (p = 0.02) was reported in a second study [15]. Interestingly, in both studies, no significant differences in terms of need for adjuvant therapy were observed between the two groups. Morphine vs. diluted tincture of opium (DTO) No significant differences in the treatment duration and hospitalization length were reported between the newborns treated with DTO vs. morphine [13]. Buprenorphine vs. morphine The outcomes of buprenorphine vs. morphine were compared showing significantly shorter length of treatment (p < 0.001) and hospital stay (p < 0.001) in the buprenorphine-treated newborns [7]. Moreover, 15\% versus 23\% of the newborns in the buprenorphine and morphine groups required supplemental phenobarbital, respectively; nonetheless, this difference was not significant (p = 0.36). In another study comparing the same treatments, the durations of treatment (p = 0.01) and hospital stay l (p = 0.05) were significantly shorter in the buprenorphine vs. the morphine group [11]. Besides, 25\% vs. 8.3\% of the newborns in the buprenorphine and morphine groups required phenobarbital, respectively. No statistical comparisons between the groups were performed. Buprenorphine vs. opium solution Sublingual buprenorphine and DTO treatment did not result in significantly different effects on the length of treatment (p = 0.077) and hospital stay (p = 0.068) [12]. DARU J Pharm Sci (2019) 27:423–431 Clonidine vs. morphine The duration of treatment (p = 0.02) and post-discharge treatment (p = 0.005) significantly decreased in the clonidinecompared to the morphine-treated newborns; nevertheless, the length of hospital stay did not vary significantly between the groups [1]. Clonidine /morphine vs. phenobarbital/morphine Clonidine was compared with phenobarbital when coadministered as adjuvant therapy along with morphine to reduce NAS treatment days [10]. Significantly longer duration of treatment (p = 0.037) was observed in the clonidine (18.2 days) compared to phenobarbital group (13.6 days). Clonidine/ DTO vs. placebo/DTO NAS newborns orally received DTO before being randomized to two groups to receive clonidine vs. placebo as adjuvant therapy. In the clonidine group, the median duration of treatment was reduced by 27\% compared to the placebo group (p = 0.02). Importantly, 12.5\% of treatment failure was seen in the placebo group while no treatment failure was observed in the clonidine group (p = 0.05) [2]. DTO vs. DTO/phenobarbital About 48\% decrease in the length of hospital stay (p < 0.001) was reported with DTO/phenobarbital as compared to DTO alone to treat NAS [16]. Additionally, DTO/phenobarbitaltreated newborns spent less time presenting severe withdrawal (p < 0.04). In another study, treatment with DTO alone significantly improved orientation and resulted in smoother movements in comparison to DTO/phenobarbital treatment (p < 0.05) [14]. The newborns were significantly more interactive. Additionally, length of hospital stay was significantly shorter in the DTO/phenobarbital-treated newborns compared to those who received DTO alone (p < 0.01). With respect to the serious adverse effects observed following administration of the above-noted treatments, methadone could induce apnea, lethargy and hypothermia [6]; morphine could induce inguinal hernia [7]; buprenorphine caused supraglottoplasty, reflux/poor feeding (probably not related) [11], and generalized seizures [12]; and clonidine/DTO induced supraventricular tachycardia (SVT). Furthermore, three clonidine/DTO-treated infants died within 2 months after being discharged from the hospital. Deaths were reported to be due to myocarditis, sudden infant death syndrome (SIDS), and methadone overdose; nevertheless, according to the FDA, deaths were not likely caused by clonidine [12]. randomized, double-blind clinical trial Randomized double-blind clinical trial single site, open-label, Randomized, clinical trial Multi centric, double-blind, randomized, clinical trial open-label, randomized, clinical trial Coyle 2002, [16] Jackson, 2004 [15] 17/15 16/17 13/13 40/40 10/10 Methadone/ heroin opioids methadone Morphine/ Methadone opioids Methadone/ Heroin/ Cocaine Buprenorphine/ Methadone Methadone/ Buprenorphine/ Oxycodone 34/34 12/12 sublingual buprenorphine morphine phenobarbital/ DTO* tincture of opium sublingual buprenorphine oral clonidine/ DTO* Sublingual buprenorphine Clonidine+ morphine methadone morphine Opium/heroin/methadone/ Phenobarbital cocaine/methamphetamine Methadone/ buprenorphine Methadone, Buprenorphine, Oxycodone, hydrocodone Benzodiazepines Methadone/ buprenorphine 15/16 Intervention Buprenorphine/Methadone/ methadone opioids for pain decreasing in pregnancy Type of Opioid exposure in uterus 15/16 Double blind, randomized 41/34 clinical trial Coyle, 2005 [14] partially Randomized, clinical trial Langenfeld, 2005 [13] Kraft, 2008 [12] Agthe, 2009 [2] Kraft, 2011 [11] Brown, 2014 [9] single-site, randomized, double-blind clinical trial Surran, 2013 single site, open-label, [10] randomized clinical trial Bada, 2015 [1] single-site, randomized, 33/30 double-blind, clinical trial Nayeri, 2015 [8] Multi centric randomized, 30/30 open-label, clinical trial Kraft, 2017 [7] Multi centric, randomized, 59/59 double-blind, clinical trial Davis, 2018 [6] No. of patients (Int. /Cont.) Study design Systematic review of the randomized studies regarding the neonatal abstinence syndrome Author, year Table 2 0/0 0/0 Placebo/ DTO* 0/0 placebo/ DTO* phenobarbital 0/0 Morphine 8/0 0/0 placebo/DTO* Opium solution 0/0 6/0 0/0 0/0 0/0 9/6.7 1.7/0 Drop out (\%) (Int. /Cont.) Morphine Phenobarbital +morphine morphine clonidine Oral Morphine oral morphine Morphine Control Finnegan Lipsitz Finnegan Finnegan modified Finnegan modified Finnegan MOTHER NAS score Modified Finnegan modified Finnegan Finnegan Finnegan MOTHER NAS scale Finnegan Assessment tool Results Length of treatment (22d Vs. 32d), length of stay (27d Vs. 38d) were not significantly different 1.Length of treatment Length of treatment wasn’t 2.total dose of tincture different significantly of opium needed (26.9 d Vs.29.8 d) infant neurobehaviour improved orientation, during the first quality of movement, three lower total stress/ abstinence weeks of life. score LOS (p < 0.05) Shorter duration in Int. group Vs. control [39.6 ± 25 d Vs. 69.8 ± 31 d (p < 0.01)] Median length of Shorter duration in Int. treatment group Vs. control [8 d vs. 12 d (p = 0.02)] safety, tolerability, methadone was associated with decreased mean number of days for LOS by 14\% (P = .046) Median length of shorter duration in Int. treatment group vs. Cont. group [15 d vs. 28 d(p < 0.001)] Mean length of Non Sig. difference for the treatment duration of treatment between Int. group (8.5 ± 4 d) vs. Cont. (8.5 ± 5 d) (P = 0.9) Median length of Longer duration of treatment Treatment in Int. group (39 d) Vs. Cont. (28 d) (p = 0.02) Median length of shorter duration in Int. opioid treatment group vs. Cont. group [14 d vs. 21 d (p = 0.008)] Median length of Longer duration of treatment morphine treatment in clonidine Vs. Phenobarbital group [18.2 d Vs. 13.6 d, p = 0.037)] shorter duration in Int. group Mean length of treatment vs. Cont. group [23 ± 12 d vs. 38 ± 14 d, (p = 0.01)] median length of shorter duration in Int. group treatment vs. Cont. group [11 d vs. 15 d (p = 0.02)] LOS Primary outcome DARU J Pharm Sci (2019) 27:423–431 427 Non-serious adverse reactions of treatments used against NAS reported by the clinical trials discussed in this systematic review, are shown in Table 3. duration of hospitalization Discussion *DTO: 0.4 mg/mL morphine LOS length of stay, Int. Intervention, Cont. Control, vs. versus, d day, DTO Diluted tincture of opium Phenobarbital/ DTO* partially randomized, clinical trial Study design Author, year Table 2 (continued) No. of patients (Int. /Cont.) Type of Opioid exposure in uterus Intervention Control Drop out (\%) (Int. /Cont.) Assessment tool Primary outcome Shorter duration in Int. group Vs. control [38 d vs. 79 d (P < 0 .001)] DARU J Pharm Sci (2019) 27:423–431 Results 428 In 2005, an estimate of 250,000–300,000 females were reported to be intravenous drug abusers in the US and 75–90\% of these abusers were of child bearing ages [14]. It was also estimated that almost 1\% of the pregnant women take opioids [1]. Interestingly, fetal exposure to methadone during pregnancy poses a 60–80\% risk of NAS development [14]. However, despite the increasing number of NAS in neonates, no optimal therapeutic approach has been established. NAS pathophysiology is complex. The mesolimbic dopaminergic pathway is crucially involved in the development of physical dependency to opioids. In this regard, it was shown that in morphine abstinence syndrome, decrease in serotonin and mesolimbic dopamine lead to continued physical symptoms [17]. Following fetal exposure to opioids, the inhibitory effect of opioids on the noradrenergic neuronal pathways is suddenly abolished at birth, thus augmenting the noradrenergic activities [1]. In the present review article, we found that the efficacy of methadone, buprenorphine and clonidine for NAS treatment was higher than that of morphine. Also, a combination of diluted tincture of opium (DTO) and phenobarbital or clonidine was significantly more effective than DTO alone. Clonidine was a significantly better adjunctive therapy than phenobarbital in reducing morphine treatment days. Nevertheless, no significant difference ... Purchase answer to see full attachment