SciCombinator

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Concept: Withdrawal

232

Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome that occurs primarily among opioid-exposed infants shortly after birth, often manifested by central nervous system irritability, autonomic overreactivity, and gastrointestinal tract dysfunction (1). During 2000-2012, the incidence of NAS in the United States significantly increased (2,3). Several recent publications have provided national estimates of NAS (2,3); however, data describing incidence at the state level are limited. CDC examined state trends in NAS incidence using all-payer, hospital inpatient delivery discharges compiled in the State Inpatient Databases of the Healthcare Cost and Utilization Project (HCUP) during 1999-2013. Among 28 states with publicly available data in HCUP during 1999-2013, the overall NAS incidence increased 300%, from 1.5 per 1,000 hospital births in 1999, to 6.0 per 1,000 hospital births in 2013. During the study period, significant increases in NAS incidence occurred in 25 of 27 states with at least 3 years of data, with annual incidence rate changes ranging from 0.05 (Hawaii) to 3.6 (Vermont) per 1,000 births. In 2013, NAS incidence ranged from 0.7 cases per 1,000 hospital births (Hawaii) to 33.4 cases per 1,000 hospital births (West Virginia). The findings underscore the importance of state-based public health programs to prevent unnecessary opioid use and to treat substance use disorders during pregnancy, as well as decrease the incidence of NAS.

Concepts: Nervous system, Childbirth, United States, Addiction, Heroin, Withdrawal, Benzodiazepine, Benzodiazepine withdrawal syndrome

197

Nicotine is known as the drug that is responsible for the addicted behaviour of tobacco users, but it has poor reinforcing effects when administered alone. Tobacco product design features enhance abuse liability by (A) optimising the dynamic delivery of nicotine to central nervous system receptors, and affecting smokers' withdrawal symptoms, mood and behaviour; and (B) effecting conditioned learning, through sensory cues, including aroma, touch and visual stimulation, to create perceptions of pending nicotine reward. This study examines the use of additives called ‘pyrazines’, which may enhance abuse potential, their introduction in ‘lights’ and subsequently in the highly market successful Marlboro Lights (Gold) cigarettes and eventually many major brands.

Concepts: Central nervous system, Nervous system, Tobacco, Cigarette, Nicotine, Drug addiction, Addiction, Withdrawal

150

Dexmedetomidine (DEX) is a centrally acting alpha-2-adrenoceptor agonist that has potential in the management of alcohol withdrawal syndrome (AWS) owing to its ability to produce arousable sedation and to inhibit the adrenergic system without respiratory depression. The objective of this randomized controlled study was to evaluate whether addition of DEX to benzodiazepine (BZD) therapy is effective and safe for AWS patients in the intensive care unit (ICU).

Concepts: Addiction, Physical dependence, Withdrawal, Benzodiazepine, Delirium tremens, Alcohol withdrawal syndrome, Benzodiazepine withdrawal syndrome

71

We identified anti-obesity medications withdrawn since 1950 because of adverse drug reactions after regulatory approval, and examined the evidence used to support such withdrawals, investigated the mechanisms of the adverse reactions, and explored the trends over time.

Concepts: Pharmacology, Medicine, Addiction, Heroin, Adverse drug reaction, Pharmaceutical drug, Withdrawal, Benzodiazepine

67

Cigarette smoking is the leading cause of preventable disease and death in the United States, with more persons dying from nicotine addiction than any other preventable cause of death. Even though smoking cessation incurs multiple health benefits, the abstinence rate remains low with current medications. Here we show that the AMP-activated protein kinase (AMPK) pathway in the hippocampus is activated following chronic nicotine use, an effect that is rapidly reversed by nicotine withdrawal. Increasing pAMPK levels and, consequently, downstream AMPK signaling pharmacologically attenuate anxiety-like behavior following nicotine withdrawal. We show that metformin, a known AMPK activator in the periphery, reduces withdrawal symptoms through a mechanism dependent on the presence of the AMPKα subunits within the hippocampus. This study provides evidence of a direct effect of AMPK modulation on nicotine withdrawal symptoms and suggests central AMPK activation as a therapeutic target for smoking cessation.

Concepts: Medicine, Smoking, Tobacco, Cigarette, Nicotine, Smoking cessation, Addiction, Withdrawal

65

In a landmark judgment in the English Court of Protection, the judge (Charles J) found it to be in the best interests of a minimally conscious patient for clinically assisted nutrition and hydration (CANH) to be withdrawn, with the inevitable consequence that the patient would die. In making this judgment, it was accepted that the patient’s level of consciousness - if CANH were continued and rehabilitation provided - might improve, and that he might become capable of expressing emotions and making simple choices. The decision to withdraw treatment relied on a best interests decision, which gave great weight to the patient’s past wishes, feelings, values and beliefs, and brought a ‘holistic’ approach to understanding what this particular patient would have wanted. We draw on our own experience of supporting families, advocating for patients and training healthcare professionals in similar situations to consider the implications of the published judgment for policy and practice with patients in prolonged disorders of consciousness and their families.

Concepts: Health care provider, Patient, Illness, Decision theory, Patience, Consciousness, Choice, Withdrawal

59

Modern turtles are composed of two monophyletic groups, notably diagnosed by divergent neck retraction mechanisms. Pleurodires (side-necked turtles) bend their neck sideways and protect their head under the anterior margin of the carapace. Cryptodires (hidden-necked turtles) withdraw their neck and head in the vertical plane between the shoulder girdles. These two mechanisms of neck retraction appeared independently in the two lineages and are usually assumed to have evolved for protective reasons. Here we describe the neck of Platychelys oberndorferi, a Late Jurassic early stem pleurodire, and find remarkable convergent morphological and functional similarities with modern cryptodires. Partial vertical neck retraction in this taxon is interpreted to have enabled fast forward projection of the head during underwater prey capture and offers a likely explanation to the functional origin of neck retraction in modern cryptodires. Complete head withdrawal for protection may therefore have resulted from an exaptation in that group.

Concepts: Protection, Withdrawal

46

Background Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown. Methods We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital. The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0.2 mg per deciliter per hour for infants up to 72 hours of age or a decrease in total serum bilirubin for infants older than 72 hours of age who received at least 5 hours of phototherapy; we prespecified a noninferiority margin of 10% for the difference in efficacy rates between groups. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn. Results We enrolled 447 infants and randomly assigned 224 to filtered sunlight and 223 to conventional phototherapy. Filtered sunlight was efficacious on 93% of treatment days that could be evaluated, as compared with 90% for conventional phototherapy, and had a higher mean level of irradiance (40 vs. 17 μW per square centimeter per nanometer, P<0.001). Temperatures higher than 38.0°C occurred in 5% of the infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy (P<0.001), but no infant met the criteria for withdrawal from the study for reasons of safety or required an exchange transfusion. Conclusions Filtered sunlight was noninferior to conventional phototherapy for the treatment of neonatal hyperbilirubinemia and did not result in any study withdrawals for reasons of safety. (Funded by the Thrasher Research Fund, Salt Lake City, and the National Center for Advancing Translational Sciences of the National Institutes of Health; Clinical Trials.gov number, NCT01434810 .).

Concepts: Infant, Randomized controlled trial, Bilirubin, Efficacy, Pediatrics, Withdrawal, Neonatal jaundice, Crigler-Najjar syndrome

40

The safety profile of Puritane™, a closed system electronic vapour product (EVP), was evaluated when used by smokers of conventional cigarettes (CCs) for 24 months in a real-life setting. The study was a two-centre ambulatory clinical study with 209 healthy volunteers. Outcome measures included adverse events (AEs), vital signs, electrocardiogram, lung function tests, exposure to nicotine and selected smoke constituents, nicotine withdrawal effects and smoking desire. No serious AEs related to EVP use were observed. The most frequently reported AEs were headache, nasopharyngitis, sore throat and cough, reported by 28.7%, 28.7%, 19.6% and 16.7% of subjects, respectively, which dissipated over time. Small decreases in lung function were not considered clinically relevant. No clinically relevant findings were observed in the other safety parameters. From Month 2, nicotine withdrawal symptoms decreased. Smoking desire and CC consumption steadily decreased over time in all subjects. EVP use was associated with reduced exposure to cigarette smoke constituents, whereas urinary nicotine levels remained close to baseline. Body weight did not increase in CC subjects switching to the EVP. In conclusion, the aerosol of the EVP at study was well tolerated and not associated with any clinically relevant health concerns after usage for up to 24 months.

Concepts: Pulmonology, Asthma, Smoking, Tobacco smoking, Cigarette, Nicotine, Addiction, Withdrawal

40

There have been no studies of the patterns of post-marketing withdrawals of medicinal products to which adverse reactions have been attributed. We identified medicinal products that were withdrawn because of adverse drug reactions, examined the evidence to support such withdrawals, and explored the pattern of withdrawals across countries.

Concepts: Pharmacology, Systematic review, Drug addiction, Addiction, Heroin, Adverse drug reaction, Withdrawal, Benzodiazepine