Preimplantation Genetic Testing for Aneuploidy in In Vitro Fertilization Using Comprehensive Chromosome Screening: A Systematic Review and Meta-Analysis.

The utility of pre-implantation genetic testing (PGT-A) is controversial, with older meta-analyses demonstrating improved pregnancy outcomes, while newer trials have not shown benefit. Therefore, we performed a meta-analysis which aimed to evaluate the benefits of PGT-A using comprehensive chromosome screening (CCS) and its effects on in vitro fertilization (IVF) outcomes among randomized controlled trials (RCTs). We conducted a systematic search to identify RCTs comparing women undergoing PGT-A with CSS with women not undergoing PGT-A, from inception to December 2020. Random effects meta-analysis was utilized to calculate average odds ratios (OR) for clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and miscarriage rate (MR). The heterogeneity of exposure was assessed using Forest plots and I2 statistics. Publication bias was evaluated using Egger's test. Among 1251 citations, seven RCTs met the inclusion criteria. Biopsies of embryos were carried out at various developmental stages, including polar body, day 3, and day 5-6 of culture. Data was analyzed as all studies and blastocyst only. Meta-analysis failed to show improvement in OPRs using PGT-A in the all ages, <35 years old and ≥35 years old age groups. There was also no significant difference in CPRs in any group. The MR decreased with the use of PGT-A (among all biopsy types and among blastocyst biopsies) in the all-ages group, but not when stratifying according to patient age <35 and ≥35 years old. More data regarding the risks and advantages of PGT-A are needed to make a final decision on the value of this intervention in clinical practice. The exact magnitude of the benefit of PGT-A selection cannot be correctly determined until multiple standardized protocol IVF PGT-A trials are conducted.

Lacking evidence for the association between frequent urine drug screening and health outcomes of persons on opioid agonist therapy.

BACKGROUND: Opioid agonist therapy (OAT) is a first-line treatment for opioid use disorder (OUD); however, the efficacy and role of urine drug screening (UDS) in OAT has received little research attention. Prior evidence suggests that UDS frequency reflects philosophy and practice context rather than differences in patient characteristics or clinical need. Therefore, we reviewed the literature on the effect of and recommendations for the frequency of UDS on health outcomes for persons with OUD who receive OAT. METHODS: We searched Medline and EMBASE for articles published from 1995-2017. Search results underwent double, independent review with discrepancies resolved through discussion with a third reviewer, when necessary. Additional articles were identified through snowball searching, hand searching (Google Scholar), and expert consultation. The Cochrane tool was used to assess risk of bias. RESULTS: Of the 60 potentially eligible articles reviewed, only one three-arm randomized open-label trial, comparing weekly and monthly UDS testing with take-home OAT doses, met our inclusion criteria. CONCLUSIONS: Our review identified an urgent gap in research evidence underpinning an area of clinical importance and that is routinely reported by patients as an area of concern.

Large Variation in Provincial Guidelines for Urine Drug Screening during Opioid Agonist Treatment in Canada.

Urine drug screening (UDS) is commonly used to detect or validate self-reported substance use, particularly when beginning and maintaining opioid agonist therapy (OAT). However, there is currently no summary of the published clinical practice guidelines for UDS in Canada, and no measure of the consistency with which different provinces suggest administering UDS. Therefore, we conducted a policy scan of UDS guidelines, examining the published clinical practice guidelines for each Canadian province and extracting all relevant data in March 2017. Our Canadian guideline and policy scan found that UDS frequency recommendations vary greatly among Provinces for persons receiving OAT for opioid use disorder.

Combination Therapies for Smoking Cessation: A Hierarchical Bayesian Meta-Analysis.

CONTEXT: Treatment guidelines recommend the use of combination therapies for smoking cessation, particularly behavioral therapy (BT) as an adjunct to pharmacotherapy. However, these guidelines rely on previous reviews with important limitations. This study's objective was to evaluate the efficacy of combination therapies compared with monotherapies, using the most rigorous data available. EVIDENCE ACQUISITION: A systematic review and meta-analysis of RCTs of pharmacotherapies, BTs, or both were conducted. The Cochrane Library, Embase, PsycINFO, and PubMed databases were systematically searched from inception to July 2015. Inclusion was restricted to RCTs reporting biochemically validated abstinence at 12 months. Direct and indirect comparisons were made in 2015 between therapies using hierarchical Bayesian models. EVIDENCE SYNTHESIS: The search identified 123 RCTs meeting inclusion criteria (60,774 participants), and data from 115 (57,851 participants) were meta-analyzed. Varenicline with BT increased abstinence more than other combinations of a pharmacotherapy with BT (varenicline versus bupropion: OR=1.56, 95% credible interval [CrI]=1.07, 2.34; varenicline versus nicotine patch: OR=1.65, 95% CrI=1.10, 2.51; varenicline versus short-acting nicotine-replacement therapies: OR=1.68, 95% CrI=1.15, 2.53). Adding BT to any pharmacotherapy compared with pharmacotherapy alone was inconclusive, owing to wide CrIs (OR=1.17, CrI=0.60, 2.12). Nicotine patch with short-acting nicotine-replacement therapy appears safe and increases abstinence versus nicotine-replacement monotherapy (OR=1.63, CrI=1.06, 3.03). Data are limited concerning other pharmacotherapy combinations and their safety and tolerability. CONCLUSIONS: Evidence suggests that combination therapy benefits may be less than previously thought. Combined with BT, varenicline increases abstinence more than other pharmacotherapy with BT combinations.

Mesocortical Dopamine Phenotypes in Mice Lacking the Sonic Hedgehog Receptor Cdon.

Motivated behaviors and many psychopathologies typically involve changes in dopamine release from the projections of the ventral tegmental area (VTA) and/or the substantia nigra pars compacta (SNc). The morphogen Sonic Hedgehog (Shh) specifies fates of midbrain dopamine neurons, but VTA-specific effects of Shh signaling are also being uncovered. In this study, we assessed the role of the Shh receptor Cdon in the development of VTA and SNc dopamine neurons. We find that Cdon is expressed in the proliferating progenitor zone of the embryonic ventral midbrain and that the number of proliferating cells in this region is increased in mouse Cdon(-/-) embryos. Consistent with a role of Shh in the regulation of neuronal proliferation in this region, we find that the number of tyrosine hydroxylase (TH)-positive neurons is increased in the VTA of Cdon(-/-) mice at birth and that this effect endures into adulthood. In contrast, the number of TH-positive neurons in the SNc is not altered in Cdon(-/-) mice at either age. Moreover, adult Cdon(-/-) mice have a greater number of medial prefrontal cortex (mPFC) dopamine presynaptic sites, and increased baseline concentrations of dopamine and dopamine metabolites selectively in this region. Finally, consistent with increased dopamine function in the mPFC, we find that adult Cdon(-/-) mice fail to exhibit behavioral plasticity upon repeated amphetamine treatment. Based on these data, we suggest that Cdon plays an important role encoding the diversity of dopamine neurons in the midbrain, influencing both the development of the mesocortical dopamine pathway and behavioral outputs that involve this neural circuitry.