Motion to Dismiss Appeals as of Right and Brief in Support of Motion to Dismiss and Opposing Motions for Leave to Appeal

Motion to Dismiss Appeals filed as of righ

Distance Traveled and Cross-State Commuting to Opioid Treatment Programs in the United States

This study examined commuting patterns among 23,141 methadone patients enrolling in 84 opioid treatment programs (OTPs) in the United States. Patients completed an anonymous one-page survey. A linear mixed model analysis was used to predict distance traveled to the OTP. More than half (60%) the patients traveled <10 miles and 6% travelled between 50 and 200 miles to attend an OTP; 8% travelled across a state border to attend an OTP. In the multivariate model (n = 17,792), factors significantly (P < .05) associated with distance were, residing in the Southeast or Midwest, low urbanicity, area of the patient's ZIP code, younger age, non-Hispanic white race/ethnicity, prescription opioid abuse, and no heroin use. A significant number of OTP patients travel considerable distances to access treatment. To reduce obstacles to OTP access, policy makers and treatment providers should be alert to patients' commuting patterns and to factors associated with them

The Black Box of Prescription Drug Diversion

A variety of surveys and studies are examined in an effort to better understand the scope of prescription drug diversion and to determine whether there are consistent patterns of diversion among various populations of prescription drug abusers. Data are drawn from the RADARS System, the National Survey of Drug Use and Health, the Delaware School Survey, and a series of quantitative and qualitative studies conducted in Miami, Florida. The data suggest that the major sources of diversion include drug dealers, friends and relatives, smugglers, pain patients, and the elderly, but these vary by the population being targeted. In all of the studies examined, the use of the Internet as a source for prescription drugs is insignificant. Little is known about where drug dealers are obtaining their supplies, and as such, prescription drug diversion is a black box requiring concentrated, systematic study

A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpressed in PDAC tissues and has been correlated to the aggressive nature of these tumors because of its key role in cell cycle progression and resistance to the induction of apoptosis. For these reasons, CDK1 is one of the main causes of chemoresistance, representing a promising pharmacological target. In this study, we report the synthesis of new 1,2,4-oxadiazole compounds and evaluate their ability to inhibit the cell growth of PATU-T, Hs766T, and HPAF-II cell lines and a primary PDAC cell culture (PDAC3). Compound 6b was the most active compound, with IC50 values ranging from 5.7 to 10.7 M. Molecular docking of 6b into the active site of CDK1 showed the ability of the compound to interact effectively with the adenosine triphosphate binding pocket. Therefore, we assessed its ability to induce apoptosis (which increased 1.5- and 2-fold in PATU-T and PDAC3 cells, respectively) and to inhibit CDK1 expression, which was reduced to 45% in Hs766T. Lastly, compound 6b passed the ADME prediction, showing good pharmacokinetic parameters. These data demonstrate that 6b displays cytotoxic activity, induces apoptosis, and targets CDK1, supporting further studies for the development of similar compounds against PDAC

Assessment of Tapentadol API Abuse Liability with the Researched Abuse, Diversion and Addiction-Related Surveillance System

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted

Extremely fast Holocene coastal landscape evolution in the Kachchh Upland (NW India): Clues from a multidisciplinary review

The coastal landscape of the Kachchh Upland (KU) region (NW-India) changed over the last few thousand years from a shallow marine gulf to a salty desert (1-4 meters asl). In this area, bordered to the south by the Northern Hill Range (NHR), the tectonic-climatic interaction triggered the sea level fall from +2/4 m circa (6000-2000 BP) to zero. An ancient river pattern deposited a tidally regulated delta area during the sea level fall that stopped 2000-3000 years ago due to tectonic activity and a dry climate. Deltaic-alluvial fans (DAF) in front of the NHR suggest that the KU's tectonic activity led to fast landscape evolution. We explored such drastic changes by integrating scientific information from a multidisciplinary literature review, identifying terraces and DAFs, and inferring faults through landform recognition, quantitative morphometry, and field surveys. Our interpretation, summarized in a map, provides new information on active processes along the NHR