Sarker, A. | bioRxiv Science

bioRxiv2019

Effective buprenorphine use and tapering strategies: Endorsements and insights by people in recovery from opioid use disorder on a Reddit forum

Opioid use disorder (OUD) is a public health emergency in the United States. Over 47,000 overdose-related deaths in 2017 involved opioids. Medication-assisted treatment (MAT), in particular, buprenorphine and buprenorphine combination products such as Suboxone(R), is the most effective, evidence-based treatment for OUD. However, there are a limited number of conclusive scientific studies that provide guidance to medical professionals about strategies for using buprenorphine to achieve stable recovery. In this study, we used data-driven natural language processing methods to mine a total of 16,146 posts about buprenorphine from 1933 unique users on the anonymous social network Reddit. Analysis of a sample of these posts showed that 74% of the posts described users personal experiences and that the top three topics included advice on using Suboxone(R) (55.0%), Suboxone(R) dosage information (35.5%) and information about Suboxone(R) tapering (32.0%). Based on two models, one that incorporated upvoting by other members and one that did not, we found that Reddit users reported more successful recovery with longer tapering schedules, particularly from 2.0 mg to 0.0 mg (median: 93 days; mean: 95 days), as compared to shorter tapering schedules investigated in past clinical trials. Diarrhea, insomnia, restlessness, and fatigue were commonly reported adverse events. Physical exercise, clonidine, and Imodium(R) were frequently reported to help during the recovery process. Due to the difficulties of conducting longer-term clinical trials involving patients with OUD, clinicians should consider other information sources including peer discussions from the abundant, real-time information available on Reddit. Significance StatementOpioid use disorder (OUD) is a national crisis in the United States and buprenorphine is one of the most effective evidence-based treatments. However, few studies have explored successful strategies for using and tapering buprenorphine to achieve stable recovery, particularly due to the difficulties of conducting long-term studies involving patients with OUD. In this study, we show that discussions on the anonymous social network Reddit may be leveraged, via automatic text mining methods, to discover successful buprenorphine use and tapering strategies. We discovered that longer tapering schedules, compared to those investigated in past clinical trials, may lead to (self-reported) sustained recovery. Furthermore, Reddit posts also provide key information regarding buprenorphine withdrawal, cravings, adjunct medications for withdrawal symptoms and relapse prevention strategies.

pharmacology and toxicology↗

bioRxiv2019

Drosophila models of pathogenic copy-number variant genes show global and non-neuronal defects during development

While rare pathogenic copy-number variants (CNVs) are associated with both neuronal and non-neuronal phenotypes, functional studies evaluating these regions have focused on the molecular basis of neuronal defects. We report a systematic functional analysis of non-neuronal defects for homologs of 59 genes within ten pathogenic CNVs and 20 neurodevelopmental genes in Drosophila melanogaster. Using wing-specific knockdown of 136 RNA interference lines, we identified qualitative and quantitative phenotypes in 72/79 homologs, including 21 lines with severe wing defects and six lines with lethality. In fact, we found that 10/31 homologs of CNV genes also showed complete or partial lethality at larval or pupal stages with ubiquitous knockdown. Comparisons between eye and wing-specific knockdown of 37/45 homologs showed both neuronal and non-neuronal defects, but with no correlation in the severity of defects. We further observed disruptions in cell proliferation and apoptosis in larval wing discs for 23/27 homologs, and altered Wnt, Hedgehog and Notch signaling for 9/14 homologs, including AATF/Aatf, PPP4C/Pp4-19C, and KIF11/Klp61F. These findings were further supported by tissue-specific differences in expression patterns of human CNV genes, as well as connectivity of CNV genes to signaling pathway genes in brain, heart and kidney-specific networks. Our findings suggest that multiple genes within each CNV differentially affect both global and tissue-specific developmental processes within conserved pathways, and that their roles are not restricted to neuronal functions. AUTHOR SUMMARYRare copy-number variants (CNVs), or large deletions and duplications in the genome, are associated with both neuronal and non-neuronal clinical features. Previous functional studies for these disorders have primarily focused on understanding the cellular mechanisms for neurological and behavioral phenotypes. To understand how genes within these CNVs contribute to developmental defects in non-neuronal tissues, we assessed 79 homologs of CNV and known neurodevelopmental genes in Drosophila models. We found that most homologs showed developmental defects when knocked down in the adult fly wing, ranging from mild size changes to severe wrinkled wings or lethality. Although a majority of homologs tested showed defects when knocked down specifically in wings and eyes, we found no correlation in the severity of the observed defects in these two tissues. A subset of the homologs showed disruptions in cellular processes in the developing fly wing, including alterations in cell proliferation, apoptosis, and cellular signaling pathways. Furthermore, human CNV genes also showed differences in gene expression patterns and interactions with signaling pathway genes across multiple human tissues. Our findings suggest that genes within CNV disorders affect global developmental processes in both neuronal and non-neuronal tissues.

genomics↗