Prescription Drug Monitoring Program: Access in the First Year.

BACKGROUND AND OBJECTIVES: Prescription Drug Monitoring Programs (PDMP) detect high-risk prescribing and patient behaviors. This study describes the characteristics associated with documented PDMP access when prescribing opioids. METHODS: Retrospective chart review of 695 opioid prescriptions written from inpatient and outpatient medical and psychiatric settings. Data were abstracted and analyzed to identify characteristics associated with documented PDMP access. RESULTS: One-third of the charts had PDMP access documented within the week of opioid prescription; 12% showed PDMP consultation on the same day. Services varied greatly from 10.5% (inpatient medicine) to 57% (inpatient psychiatry) with regard to same-day PDMP access (P < .0001). Patient characteristics associated with PDMP access include having acute pain, current mental health treatment, and current and past substance use disorders (all P < .05). Logistic regression modeling identified three variables associated with the odds of PDMP access (c-statistic = 0.66): if the prescription originated from the inpatient medicine unit (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.32, 0.68), or if the patient received a prescription for an opioid in the past 30 days (OR = 0.30, 95% CI = 0.10, 0.90) or had a urine toxicology screen in the past year (OR = 2.00, 95% CI = 1.40, 2.90). DISCUSSION AND CONCLUSIONS: Utilization of the PDMP varied by specialty and setting. SCIENTIFIC SIGNIFICANCE: This study is among the first to compare rates of PDMP access in a large sample by specialty and practice setting in a healthcare system with a policy requiring its access and appropriate documentation. With less than one-third adherence to the policy, additional steps to increase consistent PDMP access are warranted. (Am J Addict 2021;00:00-00).

Adherence to extended release naltrexone: Patient and treatment characteristics.

BACKGROUND AND OBJECTIVES: Despite the promise of extended release naltrexone in the treatment of the opioid and alcohol use disorders, challenges with initiation and subsequent adherence have limited its potential. The purpose of this study is to identify the patient and treatment characteristics associated with adherence to extended release naltrexone. METHODS: Retrospective cohort study of 155 veterans who initiated the medication in FY 2014 and FY2015. Medical records were abstracted for patient and treatment data including preferred drug and utilization of substance use treatment in the year before and after medication initiation. RESULTS: Sample characteristics include 94% male, 70% domiciled, 60% without current legal problems, 30% employed, and preferred drug being opioids for 55% and alcohol for 45%. The mean of five extended release naltrexone injections did not differ by preferred drug. Treatment variables associated with medication adherence included concurrent substance use residential, individual, group, and psychiatric therapies (all p < .05) with inpatient detoxification admissions halved afterward (p < .0001) . DISCUSSION AND CONCLUSIONS: Whereas most studies of extended release naltrexone have focused on patients with either alcohol or opioid use disorders for 6 months, this study allowed for a direct comparison of adherence in both groups over a year. The average treatment persistence in this veteran sample is greater than described in other public sector studies and may illustrate the importance of concurrent psychosocial therapies. SCIENTIFIC SIGNIFICANCE: Results extend the findings of other studies and add to an emerging appreciation of the factors associated with treatment retention for extended release naltrexone. (Am J Addict 2018;27:524-530).

Myo/Nog cell regulation of bone morphogenetic protein signaling in the blastocyst is essential for normal morphogenesis and striated muscle lineage specification.

Cells that express MyoD mRNA, the G8 antigen and the bone morphogenetic protein (BMP) inhibitor noggin (Nog) are present in the epiblast before gastrulation. Ablation of "Myo/Nog" cells in the blastocyst results in an expansion of canonical BMP signaling and prevents the expression of noggin and follistatin before and after the onset of gastrulation. Once eliminated in the epiblast, they are neither replaced nor compensated for as development progresses. Older embryos lacking Myo/Nog cells exhibit severe axial malformations. Although Wnts and Sonic hedgehog are expressed in ablated embryos, skeletal muscle progenitors expressing Pax3 are missing in the somites. Pax3+ cells do emerge adjacent to Wnt3a+ cells in vitro; however, few undergo skeletal myogenesis. Ablation of Myo/Nog cells also results in ectopically placed cardiac progenitors and cardiomyocytes in the somites. Reintroduction of Myo/Nog cells into the epiblast of ablated embryos restores normal patterns of BMP signaling, morphogenesis and skeletal myogenesis, and inhibits the expression of cardiac markers in the somites. This study demonstrates that Myo/Nog cells are essential regulators of BMP signaling in the early epiblast and are indispensable for normal morphogenesis and striated muscle lineage specification.

Rhabdomyosarcoma and Wilms tumors contain a subpopulation of noggin producing, myogenic cells immunoreactive for lens beaded filament proteins.

Myo/Nog cells are identified by their expression of the skeletal muscle specific transcription factor MyoD and the bone morphogenetic protein inhibitor noggin, and binding of the G8 monoclonal antibody. Their release of noggin is critical for morphogenesis and skeletal myogenesis. In the adult, Myo/Nog cells are present in normal tissues, wounds and skin tumors. Myo/Nog cells in the lens give rise to myofibroblasts that synthesize skeletal muscle proteins. The purpose of this study was to screen human lens tissue, rhabdomyosarcoma cell lines, and tissue sections from rhabdomyosarcoma, Wilms and tumors lacking features of skeletal muscle for co-localization of antibodies to Myo/Nog cell markers and the lens beaded filament proteins filensin and CP49. Immunofluorescence localization experiments revealed that Myo/Nog cells of the lens bind antibodies to beaded filament proteins. Co-localization of antibodies to G8, noggin, filensin and CP49 was observed in most RC13 and a subpopulation of RD human rhabdomyosarcoma cell lines. Western blotting with beaded filament antibodies revealed bands of similar molecular weights in RC13 and murine lens cells. Human alveolar, embryonal, pleomorphic and spindle cell rhabdomyosarcomas and Wilms tumors contained a subpopulation of cells immunoreactive for G8, noggin, MyoD and beaded filaments. G8 was also co-localized with filensin mRNA. Staining for beaded filament proteins was not detected in G8 positive cells in leiomyosarcomas, squamous and basal cell carcinomas, syringocarciomas and malignant melanomas. Lens beaded filament proteins were thought to be present only in the lens. Myo/Nog-like cells immunoreactive for beaded filaments may be diagnostic of tumors related to the skeletal muscle lineage.

Issues related to sex differences in antipsychotic treatment.

PURPOSE OF REVIEW: The effectiveness, side-effect profiles, and numerous other characteristics of antipsychotic medications have been extensively studied. However, the majority of publications do not address the many potential sex differences in efficacy and doses of medications, as well as other sex-specific considerations. RECENT FINDINGS: Of studies that exist, some suggest that female patients respond to lower doses of antipsychotic medications than males and that side-effect profiles vary between the sexes. However, the majority of preclinical trials use only male laboratory animals, and human clinical trials consist of too few women to analyze their response as a separate group. SUMMARY: Although changes in hormone production occurring at multiple stages throughout a women's life (such as during pregnancy, breast feeding, menopause, and postmenopausal) are presented as too complex to deal with in clinical trials, they could instead be embraced as clinical dilemmas that require additional study and consideration. We suggest that a focus should be made to reanalyze data from existing major treatment trials of antipsychotics to determine what medications specifically provide the most efficacy for female patients and at what dose range. In addition, new prospective studies are needed to specifically address appropriate adjustments in psychopharmacologic treatment for female patients during pregnancy, and when postmenopausal. More studies of the effects of antipsychotics on male and female fetuses in utero and during breast feeding are also needed to better manage women with schizophrenia and their offspring on a long-term basis in the community. There is currently too little known about sex differences in neuropharmacology. With the new USA National Institutes of Health policy to include sex in all new proposals, the time has come to close this gap in knowledge.

Myo/Nog cells: targets for preventing the accumulation of skeletal muscle-like cells in the human lens.

Posterior capsule opacification (PCO) is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow regions of the human lens, cornea and ciliary processes. In anterior lens tissue removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha smooth muscle actin (α-SMA) was detected in a subpopulation of Myo/Nog cells. Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog cells. Some of these cell free areas contained a wrinkle in the capsule. Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins in 5-day cultures but did not affect cells immunoreactive for beaded filament proteins that accumulate in differentiating lens epithelial cells. Transforming growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition, did not induce the expression of skeletal muscle proteins in lens cells following Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior lens tissue removed from cataract patients have undergone a partial differentiation to skeletal muscle. Myo/Nog cells appear to be the source of skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog cells with the G8 antibody during cataract surgery may reduce the incidence of PCO.