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As the opioid epidemic evolves, it is vital to identify changes in the geographical distribution of opioid-related deaths, and the specific opioids to which those deaths are attributed, to ensure that federal and state public health interventions remain appropriately targeted. To identify changes in the geographical distribution of opioid-related mortality across the United States by opioid type. Cross-sectional study using joinpoint modeling and life table analysis of individual-level data from the National Center for Health Statistics on 351 630 US residents who died from opioid-related causes from January 1, 1999, to December 31, 2016, for all of the United States and the District of Columbia. The analysis was conducted from September 6 to November 23, 2018. Deaths involving any opioid, heroin, synthetic opioids, and natural and semisynthetic opioids. Opioid-related mortality rate, annual percent change in the opioid-related mortality rate, and life expectancy lost at age 15 years by state and opioid type. From 1999 to 2016, a total of 231 264 men and 120 366 women died from opioid-related causes across the whole United States. Sixty-six observations were removed owing to missing data on age; therefore, 351 564 US residents were included in this study. The mean (SD) age at death was 39.8 (12.5) years for men and was 43.5 (12.9) years from women. Opioid-related mortality rates, especially from synthetic opioids, rapidly increased in all of the eastern United States. In most states, mortality associated with natural and semisynthetic opioids (ie, prescription painkillers) remained stable. In contrast, 28 states had mortality rates from synthetic opioids that more than doubled every 2 years (ie, annual percent change, ≥41%), including 12 with high mortality rates from synthetic opioids (>10 per 100 000 people). Among these 28 states, the mortality rate from natural and semisynthetic opioids ranged from 2.0 to 18.7 per 100 000 people (with a mean mortality rate of 6.0 per 100 000 people). The District of Columbia had the fastest rate of increase in mortality from opioids, more than tripling every year since 2013 (annual percent change, 228.3%; 95% CI, 169.7%-299.6%; P < .001), and a high mortality rate from synthetic opioids in 2016 (18.8 per 100 000 people); the mortality rate from natural and semisynthetic opioids was 6.9 per 100 000 people. Nationally, overall opioid-related mortality resulted in 0.36 years of life expectancy lost in 2016, which was 14% higher than deaths due to firearms and 18% higher than deaths due to motor vehicle crashes; 0.17 years of the life expectancy lost was due specifically to synthetic opioids. In 2016, New Hampshire and West Virginia lost more than 1 year of life expectancy due to opioid-related mortality. Opioid-related mortality, particularly mortality associated with synthetic opioids, has increased in the eastern United States. These findings indicate that policies focused on reducing opioid-related deaths may need to prioritize synthetic opioids and rapidly expanding epidemics in northeastern states and consider the potential for synthetic opioid epidemics outside of the heroin supply.

Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia). We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon’s preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72–96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects. Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112–228 v. 242.4 mg, IQR 166.8–352) with and without RSC, respectively (p = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications. The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings. La pancréatoduodénectomie est la seule option à visée curative pour les personnes atteintes d’un cancer du pancréas; toutefois, la douleur postopératoire reste un problème de taille. Étant donné que de nombreux centres abandonnent peu à peu l’analgésie épidurale, il est nécessaire d’explorer d’autres modalités d’épargne opiacée pour l’analgésie postopératoire. Nous avons voulu vérifier si le bloc de gaine des grands droits (BGD) exerçait un effet analgésique et un impact sur l’épargne opiacée, comparativement aux soins standard seuls (analgésie opiacée). Nous avons procédé à une étude de cohorte rétrospective préet postintervention regroupant des personnes soumises à une pancréatoduodénectomie dans 1 seul centre hospitalier universitaire de soins tertiaires à Toronto, au Canada, entre avril 2018 et décembre 2019. Toutes les personnes soumises à une pancréatoduodénectomie étaient admissibles. Parmi les 101 cas identifiés, 84 (61 témoins, 23 BGD) ont été analysés après application de critères d’exclusion (analgésie épidurale, admission à l’unité des soins intensifs, intubation ou réintubation au cours des 96 premières heures). Le groupe pré-intervention a reçu un protocole semi-standardisé d’analgésiques, incluant de l’hydromorphone IV, de l’acétaminophène, de la kétamine avec ou sans anti-inflammatoires non stéroïdiens, et avec ou sans lidocaïne intraveineuse; ces 2 derniers agents étaient administrés à la discrétion des services d’anesthésiologie et de chirurgie. Pour le groupe post-intervention, le même cycle d’analgésiques a été utilisé avec le BGD. Le cathéter de BGD était inséré en fin d’intervention avec une dose de charge de ropivacaïne, suivie d’une série de bolus intermittents programmés sur une période de 72–96 heures. Le paramètre principal était le volume total d’opiacés postopératoires administrés (en équivalence de morphine orale). Les paramètres secondaires incluaient les scores d’évaluation de la douleur (échelle numérique) et les effets indésirables des traitements. La prise d’opiacés (en équivalence de morphine orale) au bout de 96 heures était significativement moindre avec le BGD (médiane 188 mg, éventail interquartile [ÉI] 112–228 c. 242,4 mg, ÉI 166,8–352) avec et sans BGD, respectivement (p = 0,01). Le groupe sous BGD a effectivement utilisé significativement moins d’opiacés à chaque étape de mesure à partir de 24 heures suivant l’intervention, sans différence significative quant aux scores d’évaluation de la douleur entre les groupes ni complications notables liées au cathéter. L’utilisation du BGD a été associée à des réductions significatives de la consommation postopératoire d’opiacés. Étant donné que le BGD est facile à installer et à gérer et qu’il donne lieu à peu de complications, il gagnerait à être intégré aux protocoles d’analgésie postopératoire multimodale. La réalisation d’un grand essai randomisé et contrôlé permettrait d’explorer la question plus avant.

Underground labs in China are devising potent new opiates faster than U.S. and Chinese authorities can respond. Fentanyl, a synthetic opiate about 100 times more potent than morphine, and its analogs are new faces of a worsening addiction scourge in the United States. In 2015, opiates factored in 33,091 U.S. deaths, up more than 4000 from the previous year. The opium poppy is no longer the starting point for many of the opiates on the street. The new compounds, often sold mixed with heroin, originate in illicit labs in China. In underground Chinese labs, unscrupulous chemists have created new, unregulated fentanyl variants, some of them even more potent than the original. The fentanyl derivatives not only allow makers and dealers to elude law enforcement; they blindside public health authorities and they make addiction even riskier.

BackgroundPost-operative ileus and delayed return of gastrointestinal function are complications seen frequently in patients undergoing colorectal surgery. Many enhanced recovery after surgery protocols include alvimopan to inhibit the effects of opiates in the gastrointestinal tract and lidocaine to augment analgesics. Limited data exist regarding alvimopan’s efficacy in opiate-sparing regimens.MethodsThis single-center, retrospective cohort analysis was conducted in a randomly selected population of adult patients undergoing colorectal resection between February 2018 and October 2019. Patients meeting inclusion criteria were divided into four groups dependent upon whether or not they received alvimopan (A or a) and/or lidocaine (L or l). The primary endpoint in this study was median time to first bowel movement or discharge, whichever came first. Our secondary endpoint was length of stay.ResultsOf the 430 patients evaluated, a total of 192 patients were included in the final evaluation in the following groups: AL (n = 93), Al (n = 34), aL (n = 44), and al (n = 21). A significant difference was found among the groups for the primary outcome of median time to bowel movement or discharge (p = 0.001). Three subsequent pair-wise comparisons resulted in a significant difference in the primary outcome: group AL 39.4 h vs. group aL 54.0 h (p = 0.003), group AL 39.4 h vs. group al 55.4 h (p = 0.001), and group Al 44.9 h vs. group al 55.4 h (p = 0.01). Length of stay was significantly reduced by 1.8 days in groups AL and Al compared to group aL (p < 0.001).ConclusionTreatment with alvimopan resulted in a significant improvement in time to GI recovery and decreased length of stay in an established ERAS program. While lidocaine’s reduction in opiates was minimal, the group receiving both alvimopan and lidocaine had the greatest reduction in time to GI recovery and length of stay.

Background The collective cognitive and motor deficits known as HIV-associated neurocognitive disorders (HAND) remain high even among HIV+ individuals whose antiretroviral therapy is optimized. HAND is worsened in the context of opiate abuse. The mechanism of exacerbation remains unclear but likely involves chronic immune activation of glial cells resulting from persistent, low-level exposure to the virus and viral proteins. We tested whether signaling through C-C chemokine receptor type 5 (CCR5) contributes to neurotoxic interactions between HIV-1 transactivator of transcription (Tat) and opiates and explored potential mechanisms. Methods Neuronal survival was tracked in neuronal and glial co-cultures over 72 h of treatment with HIV-1 Tat ± morphine using cells from CCR5-deficient and wild-type mice exposed to the CCR5 antagonist maraviroc or exogenously-added BDNF (analyzed by repeated measures ANOVA). Intracellular calcium changes in response to Tat ± morphine ± maraviroc were assessed by ratiometric Fura-2 imaging (analyzed by repeated measures ANOVA). Release of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF from CCR5-deficient and wild-type glia was measured by ELISA (analyzed by two-way ANOVA). Levels of CCR5 and μ-opioid receptor (MOR) were measured by immunoblotting (analyzed by Student’s t test). Results HIV-1 Tat induces neurotoxicity, which is greatly exacerbated by morphine in wild-type cultures expressing CCR5. Loss of CCR5 from glia (but not neurons) eliminated neurotoxicity due to Tat and morphine interactions. Unexpectedly, when CCR5 was lost from glia, morphine appeared to entirely protect neurons from Tat-induced toxicity. Maraviroc pre-treatment similarly eliminated neurotoxicity and attenuated neuronal increases in [Ca 2+ ] i caused by Tat ± morphine. proBDNF/BDNF ratios were increased in conditioned media from Tat ± morphine-treated wild-type glia compared to CCR5-deficient glia. Exogenous BDNF treatments mimicked the pro-survival effect of glial CCR5 deficiency against Tat ± morphine. Conclusions Our results suggest a critical role for glial CCR5 in mediating neurotoxic effects of HIV-1 Tat and morphine interactions on neurons. A shift in the proBDNF/BDNF ratio that favors neurotrophic support may occur when glial CCR5 signaling is blocked. Some neuroprotection occurred only in the presence of morphine, suggesting that loss of CCR5 may fundamentally change signaling through the MOR in glia.

Background and Aims Multiple medications are associated with an increased risk of incident hepatic encephalopathy. Despite this known risk, medications such as opioids, benzodiazepines, gabapentin/pregabalin, and/or proton pump inhibitors are increasingly prescribed to persons with cirrhosis. Deprescribing is a promising intervention to reduce the burden of hepatic encephalopathy. Given that deprescribing has not been trialed in cirrhosis, we evaluated the barriers and facilitators to safe and successful deprescribing in cirrhosis. Methods We conducted, transcribed, and analyzed semi‐structured interviews using qualitative methodology with 22 subjects. This included eight patients with cirrhosis and recent use of opiates, benzodiazepines, gabapentin/Lyrica, and/or proton pump inhibitors as well as 14 providers (primary care, transplant surgery, transplant hepatology). Interviews explored opinions, behaviors, and understanding surrounding the risks and benefits of deprescribing. Results Major provider‐specific barriers included deferred responsibility of the deprescribing process, knowledge gaps regarding the risk of hepatic encephalopathy associated with medications (e.g., proton pump inhibitors) as well as the safe method of deprescription (i.e., benzodiazepines), and time constraints. Patient‐specific barriers included knowledge gaps regarding the cirrhosis‐specific risks of their medications and anxiety about the recurrence of symptoms after medication discontinuation. Patients uniformly reported trust in their provider's opinions on risks and wished for more comprehensive education during or after visits. Providers uniformly reported support for deprescription resources including pharmacist or nurse outreach. Conclusion Given knowledge of medication risks related to hepatic encephalopathy in patients with cirrhosis, deprescribing is universally seen as important. Knowledge gaps, inaction, and uncertainty regarding feasible alternatives prevent meaningful implementation of deprescription. Trials of protocolized pharmacy‐based deprescribing outreach and patient‐facing education on risks are warranted. Key Summary Summarize the established knowledge on this subject Hepatic encephalopathy (HE) is a morbid complication of cirrhosis. The risk of HE may be increased by psychoactive medications and proton pump inhibitors. Deprescribing is felt to be a promising approach to HE prevention. What are the significant and/or new findings of this study? Patients are unaware of how their medications influence the risk of HE. Patients are willing to follow physician recommendations regarding deprescribing but are afraid of worsening symptoms. Physicians do not feel comfortable deprescribing opioids or benzodiazepines. Physicians do not feel responsible or equipped with the resources for deprescribing.

A 31-year-old woman receiving total parenteral nutrition after small-bowel resection presented with progressive exertional dyspnea. CT and lung biopsy confirmed a diagnosis of pulmonary foreign-body granulomatosis due to parenteral injection of oral opiates.

Abstract Urine drug testing is an essential component in the evaluation and management of individuals with opioid use disorders, including those on buprenorphine or methadone maintenance therapies. Notwithstanding its centrality in adherence monitoring, studies have shown that clinicians have important knowledge deficiencies regarding the ordering and interpretation of drug tests. In this review, we discuss the scope and frequency of testing, the advantages and disadvantages of immunoassay- (presumptive) and liquid chromatograph-mass spectrometry- (definitive) based techniques, indications for definitive testing, medical necessity, and other considerations. Optimal use of urine drug testing depends on collaboration between clinicians and laboratory scientists.

ObjectivesIncreased rates of illicit drug inhalation are thought to expose opiate misusers (OMUs) to an enhanced risk of respiratory health problems. This pilot study aimed to determine the feasibility of undertaking respiratory screening of OMUs in a community clinic.SettingSingle-centre UK community substance misuse clinic.ParticipantsAll clinic attendees receiving treatment for opiate misuse were eligible to participate. 36 participants (mean age=37) were recruited over a 5-week period. The sample included 26 males and 10 females.Outcome measuresSpirometry without bronchodilation; health related quality of life EQ-5D-3L; Asthma Control Test; Mini Asthma Quality of Life; Clinical COPD Questionnaire and the Treatment Outcome Profile were used to assess the respiratory health of participants. Findings were discussed with staff and service users in 2 patient and public involvement events and feedback was analysed thematically.Results34 participants reported that they had smoked heroin. 8 participants diagnosed with asthma, scored under 13 on the Asthma Control Test, suggesting poorly controlled asthma. Participants (n=28), without a diagnosis of asthma completed the Lung Function Questionnaire. Of these, 79% produced scores under 18, indicating symptoms associated with the development of chronic obstructive pulmonary disease. Spirometry showed 14% of all participants had forced expiratory volume in 1 s/forced vital capacity <0.7 (without bronchodilator), indicating potential obstructive lung disease. Feedback from service users and staff suggested a willingness and capacity to deliver respiratory health screening programmes. Insight towards the difficulties service users have in accessing services and the burden of respiratory health was also provided.ConclusionsIt is feasible to undertake respiratory health screening of OMUs in a community clinic. Larger screening studies are warranted to determine the prevalence of respiratory health problems in this population. Research regarding asthma medicines adherence and access to healthcare among OMUs is also required.