The Opioid Crisis

Opioid use and addiction have reached epidemic proportions in Philadelphia, making drug overdose involving opioids a leading cause of death. Both pharmaceutical and illicit opioids contribute to this crisis. Opioid sales in Philadelphia more than doubled between 2000 and 2012, and health care providers continue to prescribe opioid pain medication in greater quantities than medically appropriate. The peak age group for overdoses is 45-54, an older age group than previously seen. Over-prescribing of opioids contributes to the recruitment of adults into drug dependence. While use of opioid pain medications usually does not lead to opioid use disorder, four out of five heroin users nationwide transitioned from original use of prescription medications. Heroin is easy to obtain, potent and cheap compared to prescription pain medications. There are estimated to be at least 70,000 heroin users in Philadelphia.https://repository.upenn.edu/publichealth_databriefs/1003/thumbnail.jp

Effect of membrane exposure on guided bone regeneration: A systematic review and metaâ analysis

AimsThis review aimed at investigating the effect of membrane exposure on guided bone regeneration (GBR) outcomes at periâ implant sites and edentulous ridges.Material and MethodsElectronic and manual literature searches were conducted by two independent reviewers using four databases, including MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, for articles up to February 2017. Articles were included if they were human clinical trials or case series reporting outcomes of GBR procedures with and without membrane exposure. A randomâ effects metaâ analysis was conducted, and the weighted mean difference (WMD) between the two groups and 95% confidence interval (CI) were reported.ResultsOverall, eight articles were included in the quantitative analysis. The WMD of the horizontal bone gain at edentulous ridges was â 76.24% (95% CI = â 137.52% to â 14.97%, p = .01) between sites with membrane exposure and without exposure. In addition, the WMD of the dehiscence reduction at periâ implant sites was â 27.27% (95% CI of â 45.87% to â 8.68%, p = .004). Both analyses showed significantly favorable outcomes at the sites without membrane exposure.ConclusionBased on the findings of this study, membrane exposure after GBR procedures has a significant detrimental influence on the outcome of bone augmentation. For the edentulous ridges, the sites without membrane exposure achieved 74% more horizontal bone gain than the sites with exposure. For periâ implant dehiscence defects, the sites without membrane exposure had 27% more defect reduction than the sites with exposure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142961/1/clr13121.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142961/2/clr13121_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142961/3/clr13121-sup-0003-checklist.pd

Significance of Keratinized Mucosa in Maintenance of Dental Implants With Different Surfaces

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142329/1/jper1410.pd

Drug-Resistant Tuberculosis among HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

Objective: To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa. Design Cross-sectional cohort study. Methods Consecutive HIV-infected adults (≥18y/o) initiating HIV care were enrolled from May 2007–May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed. Results: 1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42–150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0–12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9–30.5) compared to 5.2% (95% CI 2.1–8.9) among those with no prior TB. 5.1% (95% CI 2.4–9.5) had rifampin or rifampin plus INH resistance. Conclusions: The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence

The Prescription Drug Monitoring Program in a Multifactorial Approach to the Opioid Crisis: PDMP Data, Pennsylvania, 2016–2020

Background: Prescription opioids remain an important contributor to the United States opioid crisis and to the development of opioid use disorder for opioid-naïve individuals. Recent legislative actions, such as the implementation of state prescription drug monitoring programs (PDMPs), aim to reduce opioid morbidity and mortality through enhanced tracking and reporting of prescription data. The primary objective of our study was to describe the opioid prescribing trends in the state of Pennsylvania (PA) as recorded by the PA PDMP following legislative changes in reporting guidelines, and discuss the PDMP\u27s role in a multifactorial approach to opioid harm reduction. Methods: State-level opioid prescription data summaries recorded by the PA PDMP for each calendar quarter from August 2016 through March 2020 were collected from the PA Department of Health. Data for oxycodone, hydrocodone, and morphine were analyzed by quarter for total prescription numbers and refills. Prescription lengths, pill quantities, and average morphine milliequivalents (MMEs) were analyzed by quarter for all 14 opioid prescription variants recorded by the PA PDMP. Linear regression was conducted for each group of variables to identify significant differences in prescribing trends. Results: For total prescriptions dispensed, the number of oxycodone, hydrocodone, and morphine prescriptions decreased by 34.4, 44.6, and 22.3% respectively (p \u3c 0.0001). Refills fluctuated less consistently with general peaks in Q3 of 2017 and Q3 of 2018 (p = 0.2878). The rate of prescribing for all opioid prescription lengths decreased, ranging in frequency from 22 to 30 days (47.5% of prescriptions) to 31+ days of opioids (0.8% of prescriptions) (p \u3c 0.0001). Similarly, decreased prescribing was observed for all prescription amounts, ranging in frequency from 22 to 60 pills (36.6% of prescriptions) to 60-90 pills (14.2% of prescriptions) (p \u3c 0.0001). Overall, the average MME per opioid prescription decreased by 18.9%. Conclusions: Per the PA PDMP database, opioid prescribing has decreased significantly in PA from 2016 to 2020. The PDMP database is an important tool for tracking opioid prescribing trends in PA, and PDMPs structured similarly in other states may enhance our ability to understand and influence the trajectory of the U.S. opioid crisis. Further research is needed to determine optimal PDMP policies and practices nationwide

Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors

The mammalian target of rapamycin (mTOR) regulates cell growth by integrating nutrient and growth factor signaling and is strongly implicated in cancer. But mTOR is not an oncogene, and which tumors will be resistant or sensitive to new ATP-competitive mTOR inhibitors now in clinical trials remains unknown. We screened a panel of over 600 human cancer cell lines to identify markers of resistance and sensitivity to the mTOR inhibitor PP242. RAS and PIK3CA mutations were the most significant genetic markers for resistance and sensitivity to PP242, respectively; colon origin was the most significant marker for resistance based on tissue type. Among colon cancer cell lines, those with KRAS mutations were most resistant to PP242, while those without KRAS mutations most sensitive. Surprisingly, cell lines with co-mutation of PIK3CA and KRAS had intermediate sensitivity. Immunoblot analysis of the signaling targets downstream of mTOR revealed that the degree of cellular growth inhibition induced by PP242 was correlated with inhibition of phosphorylation of the translational repressor 4E-BP1, but not ribosomal protein S6. In a tumor growth inhibition trial of PP242 in patient-derived colon cancer xenografts, resistance to PP242 induced inhibition of 4E-BP1 phosphorylation and xenograft growth was again observed in KRAS mutant tumors without PIK3CA co-mutation, compared to KRAS WT controls. We show that, in the absence of PIK3CA co-mutation, KRAS mutations are associated with resistance to PP242 and that this is specifically linked to changes in the level of phosphorylation of 4E-BP1

The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics From 10-100 AU

We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semi-major axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M $>$ 1.5 $M_\odot$ more likely to host planets with masses between 2-13 M$_{\rm Jup}$ and semi-major axes of 3-100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semi-major axis (a) for planet populations around high-mass stars (M $>$ 1.5M$_\odot$) of the form $\frac{d^2 N}{dm da} \propto m^\alpha a^\beta$, finding $\alpha$ = -2.4 $\pm$ 0.8 and $\beta$ = -2.0 $\pm$ 0.5, and an integrated occurrence rate of $9^{+5}_{-4}$% between 5-13 M$_{\rm Jup}$ and 10-100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with 0.8$^{+0.8}_{-0.5}$% of stars hosting a brown dwarf companion between 13-80 M$_{\rm Jup}$ and 10-100 au. Brown dwarfs also appear to be distributed differently in mass and semi-major axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the RV method, our results are consistent with a peak in occurrence of giant planets between ~1-10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability.Comment: 52 pages, 18 figures. AJ in pres

An Updated Visual Orbit of the Directly Imaged Exoplanet 51 Eridani b and Prospects for a Dynamical Mass Measurement with \u3ci\u3eGaia\u3c/i\u3e

We present a revision to the visual orbit of the young, directly imaged exoplanet 51 Eridani b using four years of observations with the Gemini Planet Imager. The relative astrometry is consistent with an eccentric (e= 0.53-0.13+0.09) orbit at an intermediate inclination (i= 13611+10°), although circular orbits cannot be excluded due to the complex shape of the multidimensional posterior distribution. We find a semimajor axis of 11.1-1.3+4.2 au and a period of 28.1-4.9+17.2 yr, assuming a mass of 1.75 M· for the host star. We find consistent values with a recent analysis of VLT/SPHERE data covering a similar baseline. We investigate the potential of using the absolute astrometry of the host star to obtain a dynamical mass constraint for the planet. The astrometric acceleration of 51 Eri derived from a comparison of the Hipparcos and Gaia catalogs was found to be inconsistent at the 2ω-3ω level with the predicted reflex motion induced by the orbiting planet. Potential sources of this inconsistency include a combination of random and systematic errors between the two astrometric catalogs and the signature of an additional companion within the system interior to current detection limits. We also explored the potential of using Gaia astrometry alone for a dynamical mass measurement of the planet by simulating Gaia measurements of the motion of the photocenter of the system over the course of the extended 8 yr mission. We find that such a measurement is only possible (\u3e98% probability) given the most optimistic predictions for the Gaia scan astrometric uncertainties for bright stars and a high mass for the planet (≳3.6 MJup)