Clinical decision support systems for opioid prescribing for chronic non-cancer pain in primary care : a scoping review

Background and Objectives: Clinical decision support systems (CDSSs) may help clinicians prescribe opioids for chronic noncancer pain (CNCP) more appropriately. This scoping review determined the extent and range of the current evidence on CDSSs for opioid prescribing for CNCP in primary care, and whether investigators followed best evidence and current guidance in designing, implementing and evaluating these complex interventions. Methods: We searched 9 electronic databases and other data sources for studies from January 1, 2008 to October 11, 2019. Two reviewers independently screened the citations. One reviewer extracted data and a second verified for accuracy. INCLUSION CRITERIA: study of a CDSS for opioid prescribing for CNCP in a primary care clinical setting. We reported quantitative results in tables and qualitative results in narrative form. Results: Our search yielded 5068 records, of which 14 studies met our inclusion criteria. All studies were conducted in the United States. Six studies examined local (eg, health center) CDSSs and 8 examined prescription drug monitoring program CDSSs. Three CDSSs incorporated evidence-based components. Study aims were heterogeneous and study designs included both quantitative and qualitative methodologies. No studies assessed patient health outcomes. Few studies appeared to be following guidance for evaluating complex interventions.  Conclusions: Few studies have rigorously assessed the use of CDSSs for opioid prescribing for CNCP in primary care settings. Going forward, investigators should include evidence-based components into the design of CDSSs and follow guidance for the development and evaluation of complex interventions.PostprintPeer reviewe

Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning

The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma. © 2014 Hum et al

Assembly of Linked Nanocrystal Colloids by Reversible Covalent Bonds

The use of dynamically bonding molecules designed to reversibly link solvent-dispersed nanocrystals (NCs) is a promising strategy to form colloidal assemblies with controlled structure and macroscopic properties. In this work, tin-doped indium oxide NCs are functionalized with ligands that form reversible covalent bonds with linking molecules to drive assembly of NC gels. We monitor gelation using small angle X-ray scattering and characterize how changes in the gel structure affect infrared optical properties arising from the localized surface plasmon resonance of the NCs. The assembly is reversible because of the designed linking chemistry, and we disassemble the gels using two strategies: addition of excess NCs to change the ratio of linking molecules to NCs and addition of a capping molecule that displaces the linking molecules. The assembly behavior is rationalized using a thermodynamic perturbation theory to compute the phase diagram of the NC–linking molecule mixture. Coarse-grained molecular dynamics simulations reveal the competition between loop and bridge linking motifs essential for understanding NC gelation. This combined experimental, computational, and theoretical work provides a platform for controlling and designing the properties of reversible colloidal assemblies that incorporate NC and solvent compositions beyond those compatible with other contemporary (e.g, DNA-based) linking strategies.We would like to acknowledge the UT Mass Spectrometry Facility for their instrumental help and the UT NMR facilities for equipment use and assistance: NIH Grant Number 1 S10 OD021508-01. This work was primarily supported by the National Science Foundation through the Center for Dynamics and Control of Materials: an NSF Materials Research Science and Engineering Center (NSF MRSEC) under Cooperative Agreement DMR-1720595. This work was also supported by NSF Graduate Research Fellowships DGE-1610403 (M.N.D. and S.V.), an Arnold O. Beckman Postdoctoral Fellowship (Z.M.S.), NSF (CHE- 1905263), and the Welch Foundation (F-1848 and F-1696). E.V.A. acknowledges support from the Welch Regents Chair (F-0046). We acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin for providing HPC resources.Center for Dynamics and Control of Material

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

Inadequate harms reporting in randomized control trials of antibiotics for pediatric acute otitis media : a systematic review

INTRODUCTION: Reporting of harms in randomized control trials is often inconsistent and inadequate. OBJECTIVE: To assess the quality of harms reporting in randomized control trials evaluating the efficacy of antibiotics used to treat pediatric acute otitis media and to investigate whether connections to pharmaceutical companies or the publication of the CONSORT-Harms extension influenced the quality of harms reporting. STUDY DESIGN AND SETTING: We considered randomized control trials that evaluated the efficacy and safety of antibiotic treatment for uncomplicated acute otitis media in children aged 0-19. We evaluated the quality of harms reporting using a 19-item checklist addressing the recommendations endorsed in the CONSORT-Harms extension. RESULTS: 160 studies met our inclusion criteria. Overall quality of reporting relating to harms was low; on average studies adhered to 55.2% of the checklist items on the quality of harms reporting. The reporting of methods relating the measurement of harms was particularly lacking; studies adhered to an average of only 33.2% of the checklist items. The overall quality of reporting did not change after the publication of the CONSORT-Harms extension. The overall quality of reporting did not differ significantly in reports with or without declared connections to pharmaceutical companies (mean quality score of 56.8% vs 52.0%, respectively). CONCLUSIONS: Harms reporting in pediatric randomized trials, especially the reporting of methods used to collect harms data, remains inadequate

The stroma of Foxd1DTA mutants is mispatterned.

<p>A–F: E13.5 control (A–C) and Foxd1DTA (D–F) kidney sections stained with renal stromal markers. E13.5 kidneys stained with Meis1/2 (A and D), Tenascin (B and E) and PDGFRB (C and F) show that mutant samples have disorganization with a lack of stromal tissue interdigitating between the nephron progenitor units. G–L: E16.5 control (G–I) and Foxd1DTA (J–L) kidney sections stained with renal stromal markers. The lack of organization is again apparent, with a thickened capsule (concave arrow) and lack of interdigitation (arrow). Low power PDGFRB images show a fused kidney and the lack of stromal organization (I and L). Scale bars A–H and J–K = 100 µm, I and L = 200 µm.</p

Renal stroma ablation causes morphological defects throughout development.

<p>A–B: E11.5 H&E staining shows no renal abnormalities in Foxd1DTA mutants (B) compared to controls (A). C–D: E13.5 H&E staining highlights the absence of the renal stroma in the outer cortex and interdigitating between the caps (black arrows) in mutants (D) compared to controls (C). Early signs of irregular thickening and expansion of the nephron progenitor caps are also present (white arrow). E–G: E16.5 Foxd1DTA mutant kidneys (F,G) are smaller than controls (E) and have severe structural abnormalities such as dysplastic (F) and fused horseshoe (G) kidneys. E′, F′,G′: Close up images of cortical regions of controls (E′) and mutants (F′,G′) show the absence of stroma between renal structures, especially in the spaces between the nephron progenitor caps (black arrows). Furthermore in mutants, the renal structures lack an organized structure in the cortex compared to controls (white arrows). Scale bar = A–B:50 µm; C–D:100 µm; E–G:400 µm; E′–G′:100 µm.</p