ResearchPad - opioids https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Recreational drug use among Nigerian university students: Prevalence, correlates and frequency of use]]> https://www.researchpad.co/article/elastic_article_15734 Given the paucity of data on recreational drug use and the recent media attention on the abuse of drugs such as codeine cough syrups and tramadol, in Nigeria, our study examined the prevalence and frequency of recreational drug use among young adults from two Nigerian universities. We drew from the Socio-ecological Model to examine the influence of factors at the individual and family level on recreational drug use among adolescents and young adults.MethodsThis cross-sectional study was conducted between February and March 2018 among a final sample of 784 male and female university students selected using stratified random sampling. Binary logistic regression was used to identify significant predictors of ever use and current use of drugs.ResultsOur analyses showed that 24.5% of students had ever used drugs for recreational purposes, and 17.5% are current users. The median drug use frequency over the past month was six days among current users (n = 137). In the multivariable analyses, living in the same household as one's mother (AOR 0.28 95% CI 0.16–0.49), adequate family support (AOR 0.48 95% CI 0.26–0.89) and frequent attendance of religious fellowships (AOR 0.13 95% CI 0.07–0.25) were significantly associated with a lower likelihood of recreational drug use. However, male sex (AOR 1.52 95% CI 1.05–2.21) was associated with higher odds of recreational drug use.ConclusionThe family should be considered as an important unit to sensitize young people on the harmful effects of drug use. It is also vital that religious leaders speak against drug use in their various fellowships. There is a need to address recreational drug use on Nigerian campuses by educating students about its adverse impacts. ]]> <![CDATA[Medications for opioid use disorder among pregnant women referred by criminal justice agencies before and after Medicaid expansion: A retrospective study of admissions to treatment centers in the United States]]> https://www.researchpad.co/article/elastic_article_15710 There has been a 4-fold increase in the number of pregnant women with opioid use disorder (OUD). Medications such as methadone and buprenorphine are standard of care for OUD and are recommended during pregnancy, but only 50% of pregnant women receive such medication.Pregnant women with OUD who are involved in the criminal justice system are at high risk of poor outcomes, but data regarding the use of medications for OUD in this population are limited.What did the researchers find?From 1992 to 2017, pregnant women in the US who were referred to treatment for OUD by a criminal justice agency (versus other referral sources) were half as likely to receive medication as part of their treatment plan.After implementation of the Affordable Care Act’s Medicaid expansion, medication for OUD increased significantly more among pregnant women referred to treatment by criminal justice agencies in Medicaid expansion states compared with nonexpansion states.What do these findings mean?Pregnant women referred to treatment for OUD by criminal justice agencies were consistently less likely to receive evidence-based treatment, which increases their risk of overdose and poor maternal and neonatal outcomes.Improving access to Medicaid for justice-involved individuals may increase the rate at which pregnant women receive evidence-based treatment for OUD. ]]> <![CDATA[Exploring stress, cognitive, and affective mechanisms of the relationship between interpersonal trauma and opioid misuse]]> https://www.researchpad.co/article/elastic_article_14719 People with a history of interpersonal trauma, including intimate partner violence, sexual assault, and adverse childhood experiences, are disproportionately affected by the current opioid epidemic. Interpersonal trauma has been shown to increase risk for chronic pain conditions, prescription opioid use, and opioid misuse. Stress, cognition, and affective function have been examined as potential mechanisms that may influence opioid misuse among individuals with a history of interpersonal trauma. However, no studies have examined these factors simultaneously, despite their interrelatedness.ObjectiveThe purpose of this study was to 1) examine perceived stress, perceived cognitive function, depressive symptoms, and PTSD symptoms as potential mechanisms of opioid misuse among individuals with a history of interpersonal trauma, 2) examine the types of interpersonal trauma that are associated with opioid misuse, and 3) assess the mediating role of pain and opioid prescription.MethodsA cross-sectional, observational study design was conducted. Data were collected through a confidential self-report online survey using validated instruments (n = 230). A series of regression analyses were conducted to identify mechanistic factors and interpersonal trauma types associated with opioid misuse, opioid prescription, and pain intensity. Structural equation modeling was used to examine mediating effects of pain intensity and opioid prescription.ResultsOpioid prescription, depressive symptoms, and intimate partner violence increased the odds of reporting opioid misuse. Pain intensity and adverse childhood experiences increased the odds of opioid prescription. Higher levels of perceived stress and depressive symptoms were associated with increased pain intensity. Pain intensity emerged as a mediator of the relationship between depressive symptoms and opioid misuse.ConclusionsOur work shows that there are likely several pathways through which interpersonal trauma can lead to opioid misuse. Interventions aimed at improving depressive symptoms and coping with traumatizing events should be included as part of comprehensive trauma-informed pain management practices. ]]> <![CDATA[Retention of patients in opioid substitution treatment: A systematic review]]> https://www.researchpad.co/article/elastic_article_14597 Retention in opioid substitution (OST) treatment is associated with substantial reductions in all cause and overdose mortality. This systematic review aims to identify both protective factors supporting retention in OST, and risk factors for treatment dropout.MethodsA systematic search was performed using MEDLINE, Embase, PsycInfo, CINAHL and Web of Science (January 2001 to October 2019). Randomised controlled trials (RCTs) and observational cohort studies reporting on retention rates and factors associated with retention in OST were included. Factors associated with treatment retention and dropout were explored according to the Maudsley Addiction Profile. A narrative synthesis is provided.Results67 studies were included in this review (4 RCTs and 63 observational cohort studies; N = 294,592), all assessing factors associated with retention in OST or treatment dropout. The median retention rate across observational studies was approximately 57% at 12 months, which fell to 38.4% at three years. Studies included were heterogeneous in nature with respect to treatment setting, type of OST, risk factor assessment, ascertainment of outcome and duration of follow-up. While the presence of such methodological heterogeneity makes it difficult to synthesise results, there is limited evidence to support the influence of a number of factors on retention, including age, substance use, OST drug dose, legal issues, and attitudes to OST.ConclusionsYounger age, substance use particularly cocaine and heroin use, lower doses of methadone, criminal activity/incarceration, and negative attitudes to MMT appear to be associated with reduced retention in OST. A consensus definition of retention is required to allow for comparability across future studies. ]]> <![CDATA[Oxycodone versus morphine for cancer pain titration: A systematic review and pharmacoeconomic evaluation]]> https://www.researchpad.co/article/N5c0f7a4c-4090-42ec-ba95-57e120b0c99c

Objective

To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release Tablets (SR morphine) for moderate to severe cancer pain titration.

Methods

Randomized controlled trials meeting the inclusion criteria were searched through Medline, Cochrane Library, Pubmed, EMbase, CNKI,VIP and WanFang database from the data of their establishment to June 2019. The efficacy and safety data were extracted from the included literature. The pain control rate was calculated to eatimate efficacy. Meta-analysis was conducted by Revman5.1.4. A decision tree model was built to simulate cancer pain titration process. The initial dose of CR oxycodone and SR morphine group were 20mg and 30mg respectively. Oral immediate-release morphine was administered to treat break-out pain. The incremental cost-effectiveness ratio was performed with TreeAge Pro 2019.

Results

19 studies (1680 patients)were included in this study. Meta-analysis showed that the pain control rate of CR oxycodone and SR morphine were 86% and 82.98% respectively. The costs of CR oxycodone and SR morphine were $23.27 and $13.31. The incremental cost-effectiveness ratio per unit was approximate $329.76. At the willingness-to-pay threshold of $8836, CR oxycodone was cost-effective, while the corresponding probability of being cost-effective at the willingness-to-pay threshold of $300 was 31.6%. One-way sensitivity analysis confirmed robustness of results.

Conclusions

CR oxycodone could be a cost-effective option compared with SR morphine for moderate to severe cancer pain titration in China, according to the threshold defined by the WHO.

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<![CDATA[Proteomic analysis of protein composition of rat hippocampus exposed to morphine for 10 days; comparison with animals after 20 days of morphine withdrawal]]> https://www.researchpad.co/article/N2838fdc6-dc33-429a-ba0d-e2e831e6a950

Opioid addiction is recognized as a chronic relapsing brain disease resulting from repeated exposure to opioid drugs. Cellular and molecular mechanisms underlying the ability of organism to return back to the physiological norm after cessation of drug supply are not fully understood. The aim of this work was to extend our previous studies of morphine-induced alteration of rat forebrain cortex protein composition to the hippocampus. Rats were exposed to morphine for 10 days and sacrificed 24 h (groups +M10 and −M10) or 20 days after the last dose of morphine (groups +M10/−M20 and −M10/−M20). The six altered proteins (≥2-fold) were identified in group (+M10) when compared with group (−M10) by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). The number of differentially expressed proteins was increased to thirteen after 20 days of the drug withdrawal. Noticeably, the altered level of α-synuclein, β-synuclein, α-enolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also determined in both (±M10) and (±M10/−M20) samples of hippocampus. Immunoblot analysis of 2D gels by specific antibodies oriented against α/β-synucleins and GAPDH confirmed the data obtained by 2D-DIGE analysis. Label-free quantification identified nineteen differentially expressed proteins in group (+M10) when compared with group (−M10). After 20 days of morphine withdrawal (±M10/−M20), the number of altered proteins was increased to twenty. We conclude that the morphine-induced alteration of protein composition in rat hippocampus after cessation of drug supply proceeds in a different manner when compared with the forebrain cortex. In forebrain cortex, the total number of altered proteins was decreased after 20 days without morphine, whilst in hippocampus, it was increased.

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<![CDATA[Prescription medication use during pregnancies that resulted in births and abortions (2001-2013): A retrospective population-based study in a Canadian population]]> https://www.researchpad.co/article/5c897711d5eed0c4847d23a9

We aimed to describe medication use in pregnancies that resulted in births and abortions, as well as use after a pregnancy-related visit to characterize the receipt of medication after knowledge of pregnancy. Abortions included both spontaneous and induced abortions. Rates of medication use among women with a pregnancy outcome (2001–2013) were described using the Manitoba Population Research Data Repository at the Manitoba Centre for Health Policy. Use was determined as ≥ 1 prescription filled during pregnancies that resulted in births (livebirth/stillbirth) and abortions. Rates were calculated at any time during pregnancy and after a pregnancy-related visit. Rates were additionally characterized by risk in pregnancy using Briggs classification (2017). Of 174,848 birth pregnancies, overall 64.9% filled ≥ 1 prescription during pregnancy (a significant increase from 62.3% to 68.8% from 2001–2013, p<0.0001); 55.4% filled ≥ 1 prescription after a pregnancy-related visit. Of 71,967 abortions, 44.7% filled ≥ 1 prescription (a significant increase from 42.6% to 46.8% from 2001–2013, p<0.0001). Only 3.7% of birth pregnancies had at least one prescription for a contraindicated medication (according to Briggs classification), whereas 10.8% of abortions filled a prescription for a contraindicated medication. The most common drugs used in pregnancy were amoxicillin, doxylamine, codeine combinations, nitrofurantoin, cephalexin, salbutamol and ranitidine. Fewer women filled prescriptions for undesirable medications according to Briggs classification during pregnancy after a pregnancy-related visit.

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<![CDATA[Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study]]> https://www.researchpad.co/article/5c6f14fad5eed0c48467abf4

In recent years, low dose naltrexone (LDN) has been used as an off-label therapy for several chronic diseases. Results from small laboratory and clinical studies indicate some beneficial effects of LDN in autoimmune diseases, but clinical research on LDN in rheumatic disease is limited. Using a pharmacoepidemiological approach, we wanted to test the hypothesis that starting LDN leads to reduced dispensing of medicines used in the treatment of rheumatic disease. We performed a controlled before-after study based on the Norwegian Prescription Database (NorPD) to compare prescriptions to patients one year before and one year after starting LDN in 2013. The identified patients (n = 360) were stratified into three groups based on LDN exposure. Outcomes were differences in dispensing of medicines used in rheumatic disease. In persistent LDN users, there was a 13% relative reduction in cumulative defined daily doses (DDD) of all medicines examined corresponding to -73.3 DDD per patient (95% CI -120,2 to -26.4, p = 0.003), and 23% reduction of analgesics (-21.6 DDD (95% CI -35.5 to -7.6, p<0.009)). There was no significant DDD change in patients with lower LDN exposure. Persistent LDN users had significantly reduced DDDs of NSAID and opioids, and a lower proportion of users of DMARDs (-6.7 percentage points, 95% CI -12.3 to-1.0, p = 0.028), TNF-α antagonists and opioids. There was a decrease in the number of NSAID users among patients with the least LDN exposure. Important limitations are that prescription data are proxies for clinical effects and that a control group unexposed to LDN is lacking. The results support the hypothesis that persistent use of LDN reduces the need for medication used in the treatment of rheumatic and seropositive arthritis. Randomised clinical trials on LDN in rheumatic disease are warranted.

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<![CDATA[Evaluating the pharmacological response in fluorescence microscopy images: The Δm algorithm]]> https://www.researchpad.co/article/5c6dca2ed5eed0c48452a88e

Current drug discovery procedures require fast and effective quantification of the pharmacological response evoked in living cells by agonist compounds. In the case of G-protein coupled receptors (GPCRs), the efficacy of a particular drug to initiate the endocytosis process is related to the formation of endocytic vesicles or endosomes and their subsequent internalisation within intracellular compartments that can be observed with high spatial and temporal resolution by fluorescence microscopy techniques. Recently, an algorithm has been proposed to evaluate the pharmacological response by estimating the number of endosomes per cell on time series of images. However, the algorithm was limited by the dependence on some manually set parameters and in some cases the quality of the image does not allow a reliable detection of the endosomes. Here we propose a simple, fast and automated image analysis method—the Δm algorithm- to quantify a pharmacological response with data obtained from fluorescence microscopy experiments. This algorithm does not require individual object detection and computes the relative increment of the third order moment in fluorescence microscopy images after filtering with the Laplacian of Gaussian function. It was tested on simulations demonstrating its ability to discriminate different experimental situations according to the number and the fluorescence signal intensity of the simulated endosomes. Finally and in order to validate this methodology with real data, the algorithm was applied to several time-course experiments based on the endocytosis of the mu opioid receptor (MOP) initiated by different agonist compounds. Each drug displayed a different Δm sigmoid time-response curve and statistically significant differences were observed among drugs in terms of efficacy and kinetic parameters.

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<![CDATA[Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia]]> https://www.researchpad.co/article/5c6f14b9d5eed0c48467a745

Objective

Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.

Study design

Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008–2010 (SHIVER) and 2010–2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.

Results

244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C– 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C– 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia.

Conclusions

Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.

Trial registration

www.trialregister.nl NTR2529.

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<![CDATA[Psychological distress mediated the effects of self-stigma on quality of life in opioid-dependent individuals: A cross-sectional study]]> https://www.researchpad.co/article/5c648cd9d5eed0c484c8193c

Background

Both stigma and psychological distress affect quality of life (QOL). This study is an attempt to determine the effects of these two factors on QOL and to explore possible mediation effects between psychological distress and self-stigma in opioid-dependent individuals.

Methods

This cross-sectional study comprised 268 consecutive, treatment-seeking opioid-dependent individuals who were interviewed using the brief version of the World Health Organization Quality of Life instrument (WHOQOL-BREF), the Self-Stigma Scale-Short (SSS-S), the Chinese Health Questionnaire-12 (CHQ-12), and the Opiate Treatment Index (OTI). A series of regression models were constructed to determine if the SSS-S and CHQ-12 predict the WHOQOL-BREF scores. Moreover, a comparison of the potential mediation effects of psychological distress (as assessed by the CHQ-12) was made between the SSS-S and the WHOQOL-BREF using the Baron and Kenny procedure (including three separate regressions), along with the Sobel test.

Results

The CHQ-12 score was predictive of the scores for the four domains and almost all facets of the WHOQOL-BREF except the item, “Dependence on medical aids.” Nonetheless, the SSS-S score predicted three of the four facets of the social QOL after adjustment of the CHQ-12 score. Psychological distress completely mediated the relation between self-stigma and the physical, psychological, and environmental domains, and partially mediated the relationship between self-stigma and social QOL (two-tailed Sobel test: p = 0.02 for each domain).

Conclusions

Psychological distress has a significant impact on the QOL of treated opioid users. It appears to be a core element in reducing the negative effects of self-stigma on aspects of QOL.

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<![CDATA[Predicting inadequate postoperative pain management in depressed patients: A machine learning approach]]> https://www.researchpad.co/article/5c648d07d5eed0c484c81d9a

Widely-prescribed prodrug opioids (e.g., hydrocodone) require conversion by liver enzyme CYP-2D6 to exert their analgesic effects. The most commonly prescribed antidepressant, selective serotonin reuptake inhibitors (SSRIs), inhibits CYP-2D6 activity and therefore may reduce the effectiveness of prodrug opioids. We used a machine learning approach to identify patients prescribed a combination of SSRIs and prodrug opioids postoperatively and to examine the effect of this combination on postoperative pain control. Using EHR data from an academic medical center, we identified patients receiving surgery over a 9-year period. We developed and validated natural language processing (NLP) algorithms to extract depression-related information (diagnosis, SSRI use, symptoms) from structured and unstructured data elements. The primary outcome was the difference between preoperative pain score and postoperative pain at discharge, 3-week and 8-week time points. We developed computational models to predict the increase or decrease in the postoperative pain across the 3 time points by using the patient’s EHR data (e.g. medications, vitals, demographics) captured before surgery. We evaluate the generalizability of the model using 10-fold cross-validation method where the holdout test method is repeated 10 times and mean area-under-the-curve (AUC) is considered as evaluation metrics for the prediction performance. We identified 4,306 surgical patients with symptoms of depression. A total of 14.1% were prescribed both an SSRI and a prodrug opioid, 29.4% were prescribed an SSRI and a non-prodrug opioid, 18.6% were prescribed a prodrug opioid but were not on SSRIs, and 37.5% were prescribed a non-prodrug opioid but were not on SSRIs. Our NLP algorithm identified depression with a F1 score of 0.95 against manual annotation of 300 randomly sampled clinical notes. On average, patients receiving prodrug opioids had lower average pain scores (p<0.05), with the exception of the SSRI+ group at 3-weeks postoperative follow-up. However, SSRI+/Prodrug+ had significantly worse pain control at discharge, 3 and 8-week follow-up (p < .01) compared to SSRI+/Prodrug- patients, whereas there was no difference in pain control among the SSRI- patients by prodrug opioid (p>0.05). The machine learning algorithm accurately predicted the increase or decrease of the discharge, 3-week and 8-week follow-up pain scores when compared to the pre-operative pain score using 10-fold cross validation (mean area under the receiver operating characteristic curve 0.87, 0.81, and 0.69, respectively). Preoperative pain, surgery type, and opioid tolerance were the strongest predictors of postoperative pain control. We provide the first direct clinical evidence that the known ability of SSRIs to inhibit prodrug opioid effectiveness is associated with worse pain control among depressed patients. Current prescribing patterns indicate that prescribers may not account for this interaction when choosing an opioid. The study results imply that prescribers might instead choose direct acting opioids (e.g. oxycodone or morphine) in depressed patients on SSRIs.

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<![CDATA[The characteristics and patterns of utilization of healthcare services among Omanis with substance use disorders attending therapy for cessation]]> https://www.researchpad.co/article/5c5ca288d5eed0c48441e5a3

Background

It is indicated that Oman is witnessing an increase in issues pertinent to alcohol and psychoactive substance use.

Aim

The aim of this study was to identify the characteristics of Omanis with substance use disorder attending a specialized hospital in Oman and the pattern of their utilization of healthcare services. A related aim was to ascertain the age group most vulnerable to alcohol and substance use in Oman.

Method

A cross-sectional study was conducted in a tertiary care center specialized for treatment of those engaging in substance use in Oman. The participants in the study were selected from a convenience sample among patients seeking consultation at the center for alcohol and substance use. A six-part questionnaire was designed to obtain information regarding socio-demographic background, clinical history, healthcare utilization and perceived hurdles to access. Chi-square analyses were used to evaluate the significance of differences among categorical data. Logistic regression modelling was used to obtain measures of association after adjusting for confounding factors.

Results

Among the patients (n = 293) seeking cessation therapy, 99% were male and less than 30 years of age. Peer influences on the initiation of substance use were significant. Most patients had a history of polysubstance use, including intravenous substance use. Cannabis and alcohol were the first substances consumed by most patients and Hepatitis C and psychiatric disorders were found to be the most common co-morbidities. The participants that reported use of cannabis and benzodiazepines were more likely to perceive “improvement” upon receiving treatment.

Conclusion

This study indicated that males below 30 years of age with a history of polysubstance use were likely to attend a hospital specialized in treating substance use disorder in Oman. This study identified information regarding socio-demographic background, risk factors and perceived hurdles to healthcare that could serve as groundwork for further studies conducted on newly emerging issues of substance use in Oman.

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<![CDATA[Associations between the use of specific psychotropic drugs and all-cause mortality among older adults in Germany: Results of the mortality follow-up of the German National Health Interview and Examination Survey 1998]]> https://www.researchpad.co/article/5c466516d5eed0c48451754a

Background

Use of psychotropic drugs is common among older adults. Population-based studies on the associations of psychotropic drug use with mortality are sparse.

Objectives

To investigate the associations between the use of specific psychotropic drug groups (opioids, antipsychotics, antidepressants and benzodiazepines) and all-cause mortality among community-dwelling older adults in Germany.

Methods

Participants of the German National Health Interview and Examination Survey 1998 were followed up for mortality from 1997 to 2011. Persons aged 60–79 years with complete data on psychotropic drug use at baseline and on mortality follow-up were considered as study population (N = 1,563). Associations between the use of opioids, antipsychotics, antidepressants and benzodiazepines and all-cause mortality were examined by Cox proportional hazards models adjusted for sociodemographics (sex, age, community size, region, socioeconomic status), life style (smoking, sports, risky alcohol drinking) and health conditions (obesity, disability, history of cardiovascular diseases, diabetes, hyperlipidemia, hypertension, any cancers, any mental disorders) at baseline.

Results

After a median follow-up of 11.4 years, 21, 18, 23 and 26 deaths were documented among those who used at baseline opioids (n = 39), antipsychotics (n = 30), antidepressants (n = 53) and benzodiazepines (n = 54) with an unadjusted mortality rate (MR) of 57.7, 59.1, 44.6 and 53.7 per 1000 person-years, respectively. Meanwhile, 400 deaths were documented among 1,406 nonusers of any of the above mentioned psychotropic drugs with a MR of 26.7 per 1000 person-years. The age and sex adjusted mortality rate ratios in comparison with nonusers were 2.20 (95% confidence intervals 1.42–3.41), 1.66(1.03–2.70), 1.56(1.06–2.28), and 1.57(1.07–2.31) for the use of opioids, antipsychotics, antidepressants and benzodiazepines, respectively. In the fully adjusted Cox models, use of opioids (hazardous ratio 2.04, 95% confidence intervals 1.07–3.89), antipsychotics (2.15, 1.11–4.15) and benzodiazepines (1.76, 1.09–2.82), but not antidepressants, were significantly associated with an increased risk of mortality.

Conclusions

Use of opioids, antipsychotics, benzodiazepines is significantly associated with an increased risk of all-cause mortality among community-dwelling older adults in Germany. Clinicians should be careful in prescribing these psychotropic drugs to older adults while patients already under psychotropic therapy should well balance the risks and benefits of drug use. Further studies with a larger sample size and information on specific indications for psychotropic drug use and mental comorbidities are required to confirm the findings of the present study.

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<![CDATA[Developing key performance indicators for prescription medication systems]]> https://www.researchpad.co/article/5c478c87d5eed0c484bd2e34

Objective

To develop key performance indicators that evaluate the effectiveness of a prescription medication system.

Methods

A modified RAND/UCLA appropriateness method was used to develop key performance indicators (KPIs) for a prescription medication system. A broad list of potential KPIs was compiled. A multidisciplinary group composed of 21 experts rated the potential KPIs. A face-to-face meeting was held following the first rating exercise to discuss each potential KPI individually. The expert panel undertook a final rating of KPIs. The final set of KPIs were those indicators where at least 80 percent of experts rated the indicator highly i.e. rating of ≥ 7 on a scale from 1 to 9.

Results

292 KPIs were identified from the published literature. After removing duplicates and combining similar indicators 71 KPIs were included. The final ranking resulted in six indicators being ranked 7 or higher by 80% of the respondents and an additional seven indicators being ranked 7 or higher by ≥70 but ≤80% of respondents. The six selected indicators include four specific disease areas, measure structural and process aspects of health service delivery, and assessed three of the domains of healthcare quality: efficiency, effectiveness, and safety.

Conclusions

These indicators are recommended as a starting point to assess the current performance of prescription medication systems. Consideration should be given to developing indicators in additional disease areas as well as indicators that measure the domains of timeliness and patient–centeredness. Future work should focus on the feasibility of measuring these indicators.

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<![CDATA[Cross-sectional survey of off-label and unlicensed prescribing for inpatients at a paediatric teaching hospital in Western Australia]]> https://www.researchpad.co/article/5c3e4f70d5eed0c484d754d2

Objectives

To evaluate the prevalence of off-label and unlicensed prescribing in inpatients at a major paediatric teaching hospital in Western Australia and to identify which drugs are commonly prescribed off-label or unlicensed, including factors influencing such prescribing.

Methods

A retrospective cross-sectional study was conducted in June, 2013. Patient and prescribing data were collected from 190 inpatient medication chart records which had been randomly selected from all admissions during the second week of February 2013. Drugs were categorised as licensed, off-label or unlicensed, according to their approved Australian registration product information (PI). All drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code.

Results

There were 120 male and 70 female inpatients. The average age was 6.0 years (± 4.7). The study included 1160 prescribed drugs suitable for analysis. The number of drugs prescribed per patient ranged from 1 to 25 with an average of 6.1 (± 4.3). More than half (54%) were prescribed off-label. Oxycodone, clonidine, parecoxib and midazolam were always prescribed off-label. The most common off-label drugs were ondansetron (18.5%), fentanyl (12.9%), oxycodone (8.8%) and paracetamol (6.1%). Many ATC classifications included high off-label proportions especially the genitourinary system and sex hormones, respiratory system drugs, systemic hormonal preparations and alimentary tract and metabolism drugs.

Conclusions

This study highlights that prescribing of paediatric drugs needs to be better supported by existing and new evidence. Incentives should be established to foster the conduct of evidence-based studies in the paediatric population. The current level of off-label prescribing raises issues of unexpected toxicity and adverse drug effects in children that are in some cases severely ill.

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<![CDATA[Dexamethasone added to local anesthetics in ultrasound-guided transversus abdominis plain (TAP) block for analgesia after abdominal surgery: A systematic review and meta-analysis of randomized controlled trials]]> https://www.researchpad.co/article/5c3e509dd5eed0c484d838d6

Objective

To evaluate the analgesic efficacy of dexamethasone added to local anesthetics in ultrasound-guided transversus abdominis plane (TAP) block for the patients after abdominal surgery.

Methods

PubMed, CENTRAL, EMBASE, Web of science were searched to identify eligible randomized controlled trials (RCTs) that compared dexamethasone added to local anesthetics in ultrasound-guided TAP block with control for postoperative analgesia in adult patients undergoing abdominal surgery. Primary outcomes included postoperative pain intensity, the time to the first request for additional analgesics, and opioid consumption over 24 h after surgery. Secondary outcome was the incidence of postoperative nausea and vomiting. Analysis was performed by RevMan 5.3 software and the quality of evidence was rated using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Results

Nine RCTs involving 575 patients were included. Compared to the control, dexamethasone added to local anesthetics in ultrasound-guided TAP block significantly decreased visual analogue scale (VAS) scores at rest at 4h (mean difference [MD] = -1.01; 95% confidence intervals [CI], -1.29 to -0.73; P<0.00001; moderate quality of evidence), 6h (MD = -1.21; 95% CI, -1.74 to -0.69; P<0.00001; low quality of evidence), and 12h after surgery (MD = -0.79; 95% CI, -0.97 to -0.60; P<0.00001; moderate quality of evidence). No difference was found at 2h (MD = -0.64; 95% CI, -1.35 to 0.08; P = 0.08; low quality of evidence) and 24 h (MD = -0.41; 95% CI, -0.91 to 0.09; P = 0.11; moderate quality of evidence) in VAS scores. The time to the first request for additional analgesics was prolonged in the dexamethasone group (MD = 3.08; 95% CI, 2.37 to 3.78; P<0.00001; moderate quality of evidence). Opioid consumption over 24 h after surgery was also reduced (MD = -5.42; 95% CI, -8.20 to -2.63; P = 0.0001; low quality of evidence). Meanwhile, the incidence of postoperative nausea and vomiting was significantly decreased in the dexamethasone group (risk ratios [RR] = 0.40; 95% CI, 0.28 to 0.58; P<0.00001; high quality of evidence). No complications were reported in all the included studies.

Conclusions

Dexamethasone added to local anesthetics in ultrasound-guided TAP block was a safe and effective strategy for postoperative analgesia in adult patients undergoing abdominal surgery.

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<![CDATA[Early life adversity diminishes the cortisol response to opioid blockade in women: Studies from the Family Health Patterns project]]> https://www.researchpad.co/article/5bca48d940307c0516656414

Early life adversity (ELA) contributes to behavioral impulsivity along with risk for substance use disorders, both accompanied by blunted stress-axis reactivity. However, the biological contributors to blunted stress reactivity are not known. We took advantage of the fact that women have significant opioid inhibition of cortisol output by using the opioid antagonist, naltrexone, to unmask opioid interactions due to ELA. We administered 50 mg of naltrexone or placebo to 72 healthy women (23 years of age) in a double-blind crossover study and observed deviations in cortisol secretion from placebo over the next 180 minutes. ELA was assessed by reported exposure to physical and sexual abuse or neglect and low socioeconomic status and scored as Low, Medium, or High (0, 1–2, and 3+). The ELA groups all had identical placebo-day cortisol secretion, indicating normal basal regulation of the hypothalamic-pituitary-adrenocortical axis. Cortisol rises to naltrexone were largest in the Low-ELA group and strongly blunted in the High-ELA group (F = 3.51, p = 0.035), indicating a lack of opioid function in women with high degrees of ELA. The Low-ELA women reported dysphoric responses to naltrexone (F = 4.05, p = .022) indicating a mild opioid withdrawal, an effect that was absent in the High-ELA group. Women exposed to ELA have blunted cortisol responses to naltrexone, indicating reduced opioid regulation of the stress axis. Central opioid changes may be one pathway linking ELA to blunted stress reactivity in adulthood.

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<![CDATA[Preventing dispensing errors by alerting for drug confusions in the pharmacy information system—A survey of users]]> https://www.researchpad.co/article/5b28b137463d7e116be9c9a6

Introduction

Drug confusion is thought to be the most common type of dispensing error. Several strategies can be implemented to reduce the risk of medication errors. One of these are alerts in the pharmacy information system.

Objective

To evaluate the experiences of pharmacists and pharmacy technicians with alerts for drug name and strength confusion.

Methods

In May 2017, a cross-sectional survey of pharmacists and pharmacy technicians was performed in community pharmacies in the Netherlands using an online questionnaire.

Results

Of the 269 respondents, 86% (n = 230) had noticed the alert for drug name confusion, and 26% (n = 67) for drug strength confusion. Of those 230, 9% (n = 20) had experienced that the alert had prevented dispensing the wrong drug. For drug strength confusion, this proportion was 12% (n = 8). Respondents preferred to have an alert for drug name and strength confusion in the pharmacy information system. ‘Alert fatigue’ was an important issue, so alerts should only be introduced for frequent confusions or confusions with serious consequences.

Conclusion

Pharmacists and pharmacy technicians were positive about having alerts for drug confusions in their pharmacy information system and experienced that alerts contributed to the prevention of dispensing errors. To prevent alert fatigue, it was considered important not to include all possible confusions as a new alert: the potential contribution to the prevention of drug confusion should be weighed against the risk of alert fatigue.

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<![CDATA[Analogosedation during flexible bronchoscopy using a combination of midazolam, propofol and fentanyl – A retrospective analysis]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc7c6

Background

According to current guidelines flexible bronchoscopy is usually performed under sedation. Previously it has been demonstrated that combined sedation with e. g. the combination of midazolam and propofol or an opioid might have several advantages over sedation with just one sedative drug. However, little is known about the efficacy and safety of combined sedation with midazolam, fentanyl and propofol (MFP) compared to sedation with midazolam and fentanyl (MF) or midazolam and propofol (MP).

Methods

We carried out a retrospective analysis of bronchoscopies performed under triple (MFP) or double sedation (MF and MP) in an academic hospital. 1392 procedures were analyzed (MFP: n = 824; MF: n = 272; MP: n = 296). In particular, we compared the occurrence of complications and the dosage of administered sedative drugs between the groups.

Results

The occurrence of adverse events (MFP vs. MF: odds ratio (OR) 1.116 [95% CI 0.7741 to 1.604]; MFP vs. MP: OR 0.8296 [95% CI 0.5939 to 1.16] and severe adverse events (MFP vs. MF: OR 1.581 [95% CI 0.5594 to 4.336]; MFP vs. MP: OR 3.47 [95% CI 0.908 to 15.15]; all p>0.05) was similar in all groups. The dosage of midazolam was lower in the MFP compared to the MF or MP group (MFP vs. MF: Cohen’s d 0.075; MFP vs. MP: Cohen’s d 0.225; all p<0.001). In addition patients in the MFP group received significantly less propofol compared to the MP group (Cohen’s d 1.22; p<0.001).

Conclusions

In summary we were able to demonstrate that triple sedation can safely be administered during flexible bronchoscopy and is associated with a reduced dosage of midazolam and propofol.

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