A Meta-Analysis of the Effects of Dietary Yeast Mannan-Rich Fraction on Broiler Performance and the Implication for Greenhouse Gas Emissions from Chicken Production.

Dietary supplementation of yeast-derived mannan-rich fraction (MRF) could improve the gastrointestinal health and production efficiency of broilers, and, consequently, lower the environmental impacts of chicken production. The objective of this meta-analysis was to quantify the retrospective effects of feeding MRF (Actigen®, Alltech Inc., Nicholasville, KY) on the production performance of broilers. The meta-analysis database included 27 studies and consisted of 66 comparisons of MRF-supplemented diets vs. basal (i.e., negative control) and antibiotic-supplemented (i.e., positive control) diets. A total of 34,596 broilers were involved in the comparisons and the average final age of the birds was 35 days. Additionally, the impact of feeding MRF on the carbon footprint (feed and total emission intensities) of chicken production was evaluated using the meta-analysis results of broiler performance (MRF vs. basal diets) to develop a scenario simulation that was analyzed by a life cycle assessment (LCA) model. A database of all trials (MRF vs. basal and antibiotic diets) indicated that feeding MRF increased (p < 0.01) average daily feed intake (ADFI; +3.7%), final body weight (FBW; +3.5%), and average daily gain (ADG; 4.1%) and improved (p < 0.01) feed conversion ratio (FCR; -1.7%) without affecting (p > 0.05) mortality. A subdatabase of MRF vs. basal diets indicated that dietary MRF increased ADFI (+4.5%), FBW (+4.7%), and ADG (+6.3%) and improved FCR (-2.2%) and mortality (-21.1%). For the subdatabase of MRF vs. antibiotic diets, both treatments exhibited equivalent effects (p > 0.05) on broiler performance parameters, suggesting that MRF could be an effective alternative to in-feed antibiotics. Subgroup analysis revealed that different study factors (year of study, breed/strain, production challenges, and MRF feeding duration) influenced the effect of dietary MRF on broiler performance. Simulated life cycle analysis (LCA) indicated that feeding MRF decreased feed and total emission intensities, on average, by -2.4% and -2.1%, respectively. In conclusion, these results demonstrate that dietary MRF is an effective nutritional solution for improving broiler performance, an effective alternative to in-feed antibiotic growth promoters, and reduces the environmental impact of poultry meat production.

If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics.

Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.

Recombinant Lloviu virus as a tool to study viral replication and host responses.

Next generation sequencing has revealed the presence of numerous RNA viruses in animal reservoir hosts, including many closely related to known human pathogens. Despite their zoonotic potential, most of these viruses remain understudied due to not yet being cultured. While reverse genetic systems can facilitate virus rescue, this is often hindered by missing viral genome ends. A prime example is Lloviu virus (LLOV), an uncultured filovirus that is closely related to the highly pathogenic Ebola virus. Using minigenome systems, we complemented the missing LLOV genomic ends and identified cis-acting elements required for LLOV replication that were lacking in the published sequence. We leveraged these data to generate recombinant full-length LLOV clones and rescue infectious virus. Similar to other filoviruses, recombinant LLOV (rLLOV) forms filamentous virions and induces the formation of characteristic inclusions in the cytoplasm of the infected cells, as shown by electron microscopy. Known target cells of Ebola virus, including macrophages and hepatocytes, are permissive to rLLOV infection, suggesting that humans could be potential hosts. However, inflammatory responses in human macrophages, a hallmark of Ebola virus disease, are not induced by rLLOV. Additional tropism testing identified pneumocytes as capable of robust rLLOV and Ebola virus infection. We also used rLLOV to test antivirals targeting multiple facets of the replication cycle. Rescue of uncultured viruses of pathogenic concern represents a valuable tool in our arsenal for pandemic preparedness.

Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer.

People with advanced cancer are at heightened risk of desire for hastened death (DHD), suicidal ideation (SI), and completed suicide. Loss of Meaning (LoM), a component of demoralization, can be elevated by a cancer diagnosis and predicts DHD and SI in this population. We completed a randomized controlled trial in which psilocybin-assisted psychotherapy (PAP) produced rapid and sustained improvements in depression, demoralization, and hopelessness in people with cancer. Converging epidemiologic and clinical trial findings suggests a potential antisuicidal effect of this treatment. To probe our hypothesis that PAP relieves SI through its beneficial impacts on depression and demoralization (LoM in particular), we performed secondary analyses assessing within- and between-group differences with regard to LoM and an SI composite score. Among participants with elevated SI at baseline, PAP was associated with within-group reductions in SI that were apparent as early as 8 h and persisted for 6.5 months postdosing. PAP also produced large reductions in LoM from baseline that were apparent 2 weeks after treatment and remained significant and robust at the 6.5 month and 3.2 and 4.5 year follow-ups. Exploratory analyses support our hypothesis and suggest that PAP may be an effective antisuicidal intervention following a cancer diagnosis due to its positive impact on hopelessness and demoralization and its effects on meaning-making in particular. These preliminary results implicate psilocybin treatment as a potentially effective alternative to existing antidepressant medications in patients with cancer that are also suicidal, and warrant further investigation in participants with elevated levels of depression and suicidality.

Evolution of water conservation in humans.

To sustain life, humans and other terrestrial animals must maintain a tight balance of water gain and water loss each day.1-3 However, the evolution of human water balance physiology is poorly understood due to the absence of comparative measures from other hominoids. While humans drink daily to maintain water balance, rainforest-living great apes typically obtain adequate water from their food and can go days or weeks without drinking4-6. Here, we compare isotope-depletion measures of water turnover (L/d) in zoo- and rainforest-sanctuary-housed apes (chimpanzees, bonobos, gorillas, and orangutans) with 5 diverse human populations, including a hunter-gatherer community in a semi-arid savannah. Across the entire sample, water turnover was strongly related to total energy expenditure (TEE, kcal/d), physical activity, climate (ambient temperature and humidity), and fat free mass. In analyses controlling for those factors, water turnover was 30% to 50% lower in humans than in other apes despite humans' greater sweating capacity. Water turnover in zoo and sanctuary apes was similar to estimated turnover in wild populations, as was the ratio of water intake to dietary energy intake (∼2.8 mL/kcal). However, zoo and sanctuary apes ingested a greater ratio of water to dry matter of food, which might contribute to digestive problems in captivity. Compared to apes, humans appear to target a lower ratio of water/energy intake (∼1.5 mL/kcal). Water stress due to changes in climate, diet, and behavior apparently led to previously unknown water conservation adaptations in hominin physiology.

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.

BACKGROUND: A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses. METHODS: The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration. RESULTS: Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives. CONCLUSION: These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.

Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress.

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960-2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.

Radiological Estimation of Intracranial Blood Volume and Occurrence of Hydrocephalus Determines Stress-Induced Hyperglycemia After Aneurysmal Subarachnoid Hemorrhage.

Acute phase after aneurysmal subarachnoid hemorrhage (aSAH) is associated with several metabolic derangements including stress-induced hyperglycemia (SIH). The present study is designed to identify objective radiological determinants for SIH to better understand its contributory role in clinical outcomes after aSAH. A computer-aided detection tool was used to segment admission computed tomography (CT) images of aSAH patients to estimate intracranial blood and cerebrospinal fluid volumes. Modified Graeb score (mGS) was used as a semi-quantitative measure to estimate degree of hydrocephalus. The relationship between glycemic gap (GG) determined SIH, mGS, and estimated intracranial blood and cerebrospinal fluid volumes were evaluated using linear regression. Ninety-four [94/187 (50.3%)] among the study cohort had SIH (defined as GG > 26.7 mg/dl). Patients with SIH had 14.3 ml/1000 ml more intracranial blood volume as compared to those without SIH [39.6 ml (95% confidence interval, CI, 33.6 to 45.5) vs. 25.3 ml (95% CI 20.6 to 29.9), p = 0.0002]. Linear regression analysis of mGS with GG showed each unit increase in mGS resulted in 1.2 mg/dl increase in GG [p = 0.002]. Patients with SIH had higher mGS [median 4.0, interquartile range, IQR 2.0-7.0] as compared to those without SIH [median 2.0, IQR 0.0-6.0], p = 0.002. Patients with third ventricular blood on admission CT scan were more likely to develop SIH [67/118 (56.8%) vs. 27/69 (39.1%), p = 0.023]. Hence, the present study, using unbiased SIH definition and objective CT scan parameters, reports "dose-dependent" radiological features resulting in SIH. Such findings allude to a brain injury-stress response-neuroendocrine axis in etiopathogenesis of SIH.

Estimating the effects of friends on health behaviors of adolescents.

This paper estimates the effects of friends' smoking and drinking on own behavior while controlling for correlated unobservables between friends. The effect of friends' behaviors is identified by comparing similar individuals who have similar friendship opportunities and make similar friendship choices, exploiting the idea that friendship choice reveals information about unobservables. We combine this identification strategy with an across-cohort within school design so that identification arises in our reduced form estimates from across-grade differences in the clustering of health behaviors. Finally, we use estimated information on correlated unobservables to examine longitudinal data on the onset of health behaviors, where the likelihood of reverse causality should be minimal. We find evidence that this strategy produces somewhat smaller (no more than 16% smaller) friendship effect estimates than the more standard school fixed effect models consistent with at most modest bias from correlated unobservables.

Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy.

A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants' personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient.

Therapeutic Applications of Classic Hallucinogens.

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial.

BACKGROUND: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. METHODS: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. RESULTS: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. CONCLUSIONS: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00957359.

PROSPECTIVE POPULATION MANAGEMENT FOR HEPATITIS B IN THE CHIMPANZEE (PAN TROGLODYTES) SSP® POPULATION.

Hepatitis B virus causes horizontally transmitted infectious hepatopathy of primates and may progress to hepatocellular carcinoma. Historically, a small number of chimpanzees ( Pan troglodytes ) living in accredited North American zoos have been confirmed with positive hepatitis B serology consistent with exposure. However, the overall status for this population and the interpretation of these individual test results have not been established previously. The current U.S. zoo-housed population (n = 259) was assessed serologically for hepatitis B by surface protein antigen (HbsAg) and surface antibodies (anti-Hbs). Signalment, origin, current health status, history of liver disease, and hepatitis B vaccination history were obtained for each animal. Serologic status was measured directly in 86.5% (n = 224) of these individuals, with 2.2% (n = 5) of the study population determined to be chronically infected by positive HbsAg and negative anti-Hbs status. Additionally, 11.6% (n = 26) of the directly measured population tested were HbsAg negative and anti-Hbs positive, which was indicative of viral exposure. No animals were determined to be acutely infected as HbsAg and anti-Hbs positive. Although these results demonstrated a relatively low prevalence of hepatitis B infection among these chimpanzees, the varied serologic results between institutions underscored the importance of routine serologic testing, especially at times of proposed transfers, and consideration of species vaccination protocols.

Evaluating the physiological and behavioral response of a male and female gorilla (Gorilla gorilla gorilla) during an introduction.

Prolonged stress responses can lead to infertility and death; therefore monitoring respective indicators like stress-related hormones and behaviors is an important tool in ensuring the health and well-being among zoo-housed animal populations. Changes in social structure, such as the introduction of a new conspecific, can be a source of stress. In April 2010, a sexually mature female western lowland gorilla (Gorilla gorilla gorilla) was brought to Lincoln Park Zoo (LPZ; Chicago, IL) from the Chicago Zoological Park (Brookfield, IL) for a breeding recommendation from the Gorilla Species Survival Plan. Fecal glucocorticoid metabolites (FGMs) were monitored in two gorillas prior to, during and immediately following the social introduction. Reproduction events, such ovarian cyclicity and pregnancy, were monitored using behavior and fecal progestagen metabolite (FPM; female) and fecal androgen metabolite (FAM; male) analyses. Mean (± standard error) FGM concentrations for the male were elevated (P = 0.002) during the introduction (20.61 ± 0.83 ng/g) compared to the pre- and post-introduction phases (11.31 ± 0.48 ng/g and 12.42 ± 0.65 ng/g, respectively). For the female, mean FGM concentrations were lower (P < 0.001) during the post-introduction (17.91 ± 1.07 ng/g) than during the pre- and introduction phases (30.50 ± 3.42 and 27.38 ± 1.51 ng/g, respectively). The female maintained normal FPM cyclicity throughout the study and became pregnant in the post-introduction phase. These results suggest the importance of both behavioral and physiological monitoring of zoo animals and demonstrate the potential stress that can occur during social introductions. Zoo Biol. 33:394-402, 2014. © 2014 Wiley Periodicals Inc.

Pursuit of quantum monodromy in the far-infrared and mid-infrared spectra of NCNCS using synchrotron radiation.

Quantum monodromy has a dramatic and defining impact on all those physical properties of chain-molecules that depend on a large-amplitude bending coordinate, including in particular the distribution of the ro-vibrational energy levels. As revealed by its pure rotational (a-type) spectrum [B. P. Winnewisser et al., Phys. Chem. Chem. Phys., 2010, 12, 8158-8189] cyanogen iso-thiocyanate, NCNCS, is a particularly illuminating exemplar of quantum monodromy: it clearly shows the distinctive monodromy-induced dislocation of the ro-vibrational energy level pattern for its low-lying bending mode. This dislocation centers on a lattice defect in the energy vs. momentum map of the ro-vibrational levels at the top of the barrier to linearity, and represents an example of an excited state quantum phase transition [D. Larese and F. Iachello, J. Mol. Struct., 2011, 1006, 611-628]. To complete the data, so far limited to ΔJ = +1 transitions, we decided to measure the high-resolution far-infrared band of the large-amplitude bending vibration ν7, and, if possible, mid-infrared bands. This Perspectives article presents our ongoing progress towards this goal, beginning with the description of how to predict line positions and intensities of the a- and b-type bands of the large amplitude bending mode using the Generalized-SemiRigid-Bender (GSRB) Hamiltonian for NCNCS and ab initio dipole moment functions [B. P. Winnewisser et al., Phys. Chem. Chem. Phys., 2010, 12, 8158-8189]. We include background information about synchrotron physics to clarify the advantages and limitations of that radiation source for our experiments. Details of the chemical preparation and sample handling, leading to the realization that NCNCS is 50 kJ mol(-1) lower in energy than its isomer S(CN)2 [Z. Kisiel et al., J. Phys. Chem. A, 2013, 117, 13815-13824] are included. We present the far-infrared and mid-infrared spectrum of NCNCS obtained at the Canadian Light Source synchrotron, using the IFS 125HR Bruker Fourier transform spectrometer. Eight of the fundamental vibrational modes of NCNCS have now been observed at high resolution. Initial analyses of the data confirm band assignments and demonstrate the accuracy of the predictions.

Inviting patients to read their doctors' notes: a quasi-experimental study and a look ahead.

BACKGROUND: Little information exists about what primary care physicians (PCPs) and patients experience if patients are invited to read their doctors' office notes. OBJECTIVE: To evaluate the effect on doctors and patients of facilitating patient access to visit notes over secure Internet portals. DESIGN: Quasi-experimental trial of PCPs and patient volunteers in a year-long program that provided patients with electronic links to their doctors' notes. SETTING: Primary care practices at Beth Israel Deaconess Medical Center (BIDMC) in Massachusetts, Geisinger Health System (GHS) in Pennsylvania, and Harborview Medical Center (HMC) in Washington. PARTICIPANTS: 105 PCPs and 13,564 of their patients who had at least 1 completed note available during the intervention period. MEASUREMENTS: Portal use and electronic messaging by patients and surveys focusing on participants' perceptions of behaviors, benefits, and negative consequences. RESULTS: 11,155 [corrected] of 13,564 patients with visit notes available opened at least 1 note (84% at BIDMC, 82% [corrected] at GHS, and 47% at HMC). Of 5219 [corrected] patients who opened at least 1 note and completed a postintervention survey, 77% to 59% [corrected] across the 3 sites reported that open notes helped them feel more in control of their care; 60% to 78% of those taking medications reported increased medication adherence; 26% to 36% had privacy concerns; 1% to 8% reported that the notes caused confusion, worry, or offense; and 20% to 42% reported sharing notes with others. The volume of electronic messages from patients did not change. After the intervention, few doctors reported longer visits (0% to 5%) or more time addressing patients' questions outside of visits (0% to 8%), with practice size having little effect; 3% to 36% of doctors reported changing documentation content; and 0% to 21% reported taking more time writing notes. Looking ahead, 59% to 62% of patients believed that they should be able to add comments to a doctor's note. One out of 3 patients believed that they should be able to approve the notes' contents, but 85% to 96% of doctors did not agree. At the end of the experimental period, 99% of patients wanted open notes to continue and no doctor elected to stop. LIMITATIONS: Only 3 geographic areas were represented, and most participants were experienced in using portals. Doctors volunteering to participate and patients using portals and completing surveys may tend to offer favorable feedback, and the response rate of the patient surveys (41%) may further limit generalizability. CONCLUSION: Patients accessed visit notes frequently, a large majority reported clinically relevant benefits and minimal concerns, and virtually all patients wanted the practice to continue. With doctors experiencing no more than a modest effect on their work lives, open notes seem worthy of widespread adoption. PRIMARY FUNDING SOURCE: The Robert Wood Johnson Foundation, the Drane Family Fund, the Richard and Florence Koplow Charitable Foundation, and the National Cancer Institute.

Prevalence of prescription opioid-use disorder among chronic pain patients: comparison of the DSM-5 vs. DSM-4 diagnostic criteria.

The authors estimated the prevalence of lifetime prescription opioid-use disorder among outpatients on opioid therapy using criteria from both versions 4 and 5 of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Using electronic records from a large health care system, a random sample of outpatients undergoing long-term opioid therapy for non-cancer pain was identified and 705 participants completed diagnostic interviews. The prevalence of lifetime DSM-5 opioid-use disorder among these patients was 34.9% (95% confidence interval [CI] = 30.5?39.5), similar to the prevalence of DSM-4 opioid dependence (35.5%, 95% CI = 31.1?40.2). The Kappa value between DSM-5 and DSM-4 criteria was high (Kappa = 0.873, p < 0.0001). Logistic regressions suggested DSM-5 opioid-use disorder was associated with age younger than 65 (odds ratio [OR] = 2.25, p = 0.009), history of opioid abuse (OR = 4.94, p < 0.001), higher opioid withdrawal symptoms (OR = 3.01, p = 0.008), and history of substance abuse treatment (OR = 1.62, p = 0.015), similar to DSM-4. Based on DSM-5, 21.7% of patients met criteria for moderate and 13.2% for severe opioid-use disorder, respectively. Given the changes proposed, the finding that the prevalence of and risk factors for DSM-5 opioid-use disorders were similar to DSM-4 were unexpected. Further research is advised.

Symbiotic bacteria induced necrotizing pancreatitis.

CONTEXT: Intestinal flora and anaerobes are frequently implicated in causing infectious necrotizing pancreatitis however Bifidobacterium and Veillonella have rarely been isolated as the causative agents. Bifidobacterium and Veillonella are commensal anaerobes which reside in gastrointestinal tract and help deconjugate bile acids. Bifidobacterium is also frequently used in probiotics. CASE REPORT: We present a 68-year-old man who initially presented with gallstone pancreatitis but eventually developed Bifidobacterium and Veillonella species induced necrotizing pancreatitis and pseudocyst formation. CONCLUSION: Under rare circumstances commensal gut flora can turn pathogenic which can lead to life-threatening morbidity and may even result in mortality.

Pharmacotherapy of addictive disorders.

Substance use disorders are highly prevalent in the United States and cause considerable damage to our society. They are underrecognized and undertreated despite a vast body of literature demonstrating the efficacy of treatment using both psychosocial and psychopharmacological modalities. For the last decade, research and progress into the biological basis of the addictive process has led to a rapidly growing number of pharmacological agents used to interrupt the addictive process at its various stages such as the initiation of substance abuse, the transition from abuse to dependence, and the prevention of drug reinstatement or relapse. Food and Drug Administration-approved medications exist for nicotine, alcohol, and opioid use disorders, and progress is being made to develop agents for stimulant use disorders. Regarding nicotine use disorders, nicotine replacement therapies,bupropion and varenicline, have Food and Drug Administration approval, and future options exist with endocannabinoid antagonists and immune therapy. Aversive agents, opiate antagonists, and glutamate based interventions are currently approved to treat alcohol use disorders with future promise with GABAergic, serotonergic, and endocannabinoid system agents. Opiate addiction is treated by approved agonist and antagonist mu-opioid medications with the future potential for agents that can modulate the stress systems and the iboga alkaloids. Although no pharmacotherapies are currently approved for cocaine addiction, promising lines of research include agents that affect dopaminergic, GABAergic, serotonergic,and glutamatergic systems as well as the promise for immune therapies.