Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Autism and ADHD in the Era of Big Data; An Overview of Digital Resources for Patient, Genetic and Clinical Trials Information

Even in the era of information “prosperity” in the form of databases and registries that compile a wealth of data, information about ASD and ADHD remains scattered and disconnected. These data systems are powerful tools that can inform decision-making and policy creation, as well as advancing and disseminating knowledge. Here, we review three types of data systems (patient registries, clinical trial registries and genetic databases) that are concerned with ASD or ADHD and discuss their features, advantages and limitations. We noticed the lack of ethnic diversity in the data, as the majority of their content is curated from European and (to a lesser extent) Asian populations. Acutely aware of this knowledge gap, we introduce here the framework of the Neurodevelopmental Disorders Database (NDDB). This registry was designed to serve as a model for the national repository for collecting data from Saudi Arabia on neurodevelopmental disorders, particularly ASD and ADHD, across diverse domains

The AfrAbia+plus Parkinson's disease genomic consortium

Many human studies, including those involving genetics, are conducted in people of northern European ancestry. A lack of ancestral representation in genetics makes it harder to understand the underlying biology of disease, results in unsupported generalisation of current genetics to under-represented groups, limits our capacity to deploy precision therapeutics to only those populations that have been studied, and prevents us from accurately mapping genetic loci. Studies in Parkinson's disease have experienced a similar lack of diversity. The Global Parkinson's Genetics Program (GP2) was initiated in 2020 to meet this need for diversity in research. GP2 seeks to improve understanding of the genetic architecture of Parkinson's disease in a global context. A result of this work was the establishment of the AfrAbia Parkinson's Disease Genomic Consortium (AA-PDGC) in 2023

Estimating transfection efficiency in differentiated and undifferentiated neural cells

Abstract Objective Delivery of constructs for silencing or over-expressing genes or their modified versions is a crucial step for studying neuronal cell biology. Therefore, efficient transfection is important for the success of these experimental techniques especially in post-mitotic cells like neurons. In this study, we have assessed the transfection rate, using a previously established protocol, in both primary cortical cultures and neuroblastoma cell lines. Transfection efficiencies in these preparations have not been systematically determined before. Results Transfection efficiencies obtained herein were (10–12%) for neuroblastoma, (5–12%) for primary astrocytes and (1.3–6%) for primary neurons. We also report on cell-type specific transfection efficiency of neurons and astrocytes within primary cortical cultures when applying cell-type selective transfection protocols. Previous estimations described in primary cortical or hippocampal cultures were either based on general observations or on data derived from unspecified number of biological and/or technical replicates. Also to the best of our knowledge, transfection efficiency of pure primary neuronal cultures or astrocytes cultured in the context of pure or mixed (neurons/astrocytes) population cultures have not been previously determined. The transfection strategy used herein represents a convenient, and a straightforward tool for targeted cell transfection that can be utilized in a variety of in vitro applications

Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection

Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS) platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a result, these technologies have become a valuable tool for gene discovery and for clinical diagnostics. The AmpliSeq Inherited Disease Panel (IDP) consists of 328 genes underlying more than 700 inherited diseases. Here, we aimed to assess the performance of the IDP as a sensitive and rapid comprehensive gene panel testing. A total of 88 patients with inherited diseases and causal mutations that were previously identified by Sanger sequencing were randomly selected for assessing the performance of the IDP. The IDP successfully detected 93.1% of the mutations in our validation cohort, achieving high overall gene coverage (98%). The sensitivity for detecting single nucleotide variants (SNVs) and short Indels was 97.3% and 69.2%, respectively. IDP, when coupled with Ion Torrent Personal Genome Machine (PGM), delivers comprehensive and rapid sequencing for genes that are responsible for various inherited diseases. Our validation results suggest the suitability of this panel for use as a first-line screening test after applying the necessary clinical validation

Novel sequence variants detected in this study.

<p>Key: Heterozygous, Het; Homozygous, Homo; Familial, FM; Sporadic, SP; Not available, n.a.</p><p>* Frequency: No. of control carriers/ total No. of controls.</p><p>Novel sequence variants detected in this study.</p

Genetic characterization of <i>PARKIN</i> (p.G409R) and <i>PINK1</i> (p.E195Q) variants and their predicted functional impact.

<p>(A) Pedigree of FM 49 with LOPD. (B) Part of the sequencing chromatogram of <i>PINK1</i> exon 6 showing homozygous c.1225G>A mutation (corresponding to p.G409R substitution) in 49-a and 49-b but not in WT. (C) Part of the sequencing chromatogram of <i>PARKIN</i> exon 5 showing heterozygous c.583G>C variant (corresponding to p.E195Q substitution) in SP-7. (D) Ribbon presentation of PINK1^WT and PINK1^mut structural models. The secondary structures are colored as follows: β-strands (magenta), α-helices (cyan), coils (light pink). (E) PINK1^WT. (F) PINK1^mut. The spatial distance between the P+1 binding motif (cyan) and helix G (blue), measured in Angstrom (Å), is increased in PINK1^mut compared to PINK1^WT. A close-up view of the activation loop (aa 384–417) containing the P+1 binding motif and the helix G is represented [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135950#pone.0135950.ref027" target="_blank">27</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135950#pone.0135950.ref028" target="_blank">28</a>]. (G and H) p.E195Q has a very subtle impact on the protein conformation. Ribbon presentation of PARKIN^WT and PARKIN^mut structural models. The UPD, is shown in (yellow) or (cyan) in PARKIN^WT and PARKIN^mut, respectively. (G) Positions of the missing β-strand and α-helix are indicated by the asterisk and the hash symbols, respectively. (H) Superimposition of PARKIN^WT and PARKIN^mut showing parts of the protein (indicated by a hash symbol) that had lost the β-strand structure and adopted a random coil instead. Age at onset: AAO. Years: y. WT: wild-type.</p