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Substance abuse among older adults has received little attention in the past, presumably because this population has traditionally accounted for only a small percentage of the drug abuse problem in the United States. The aging of the baby boomer generation (born 1946–1964), however, will soon swell the ranks of older adults and dramatically alter the demography of American society. Several observations suggest that this expansion will likely be accompanied by a precipitous increase in the abuse of drugs, including prescription medications and illicit substances, among older adults. While it is now evident that the brain changes continuously across life, how drugs of abuse interact with these age-related changes remains unclear. The dynamic nature of brain function, however, suggests that substance abuse during older age may augment the risks and require unique considerations for diagnosis and treatment. In addition to describing current and projected prevalence estimates of substance abuse among older adults, the present review discusses how aging affects brain systems involved in drug abuse, and explores the potential impact of drug abuse on the aging brain. Future directions for substance abuse research among older adults will also be considered.

[...] in a Series In 2006, substance dependence or abuse was diagnosed in about 22.6 million persons in the United States.1 Addiction-related morbidity and mortality pose a major burden to society, costing our economy more than $500 billion annually: about $181 billion for illicit drugs,2 $168 billion for tobacco,3 and $185 billion for alcohol. 4 Loss of productivity,broken families, jail time, HIV infection, hepatitis C, and death are common sequelae of drug addiction. Prepotent methamphetamine continues to afflict communities across the country, showing marked increases in abuse consequences and in treatment admissions over the past decade-from about 48,000 admissions a year in 1995 to more than 150,000 a year in 2005.8 Although cocaine use is viewed as having stabilized somewhat, there are still about 2.4 million current cocaine users aged 12 years and older in this country.1 While marijuana use continues to decline among teenagers, it remains the most commonly used illicit drug.1 Outside the illicit drug arena, prescription drug abuse continues to gather momentum; about 7 million US persons report current (in the past month) nonmedical use of prescription drugs, mostly pain relievers-more than the number of persons abusing cocaine, heroin, hallucinogens, and inhalants combined.1 In the more than 30 years since the National Institute on Drug Abuse (NIDA) was established, major strides have been made in understanding addiction as a complex disease of the brain.6 Advances in molecular biology, genetics, and neuroimaging technologies have elucidated the complexity of the opioid, dopaminergic, and other systems, greatly improving our understanding of how the brain responds to and is altered by the acute and long-term use of illicit drugs.

In the ensuing years, advances in molecular biology, genetics, and neuroimaging technologies allowed scientists to begin piecing together the brain's reward pathways, and to elucidate how these pathways are activated and altered by the acute and chronic use of illicit drugs. For example, understanding how the interaction between genetic and environmental factors modulates individual risk of addiction will improve identification of individuals especially vulnerable to the rewarding effects of drugs of abuse.

Neurotoxicity from accumulation of misfolded/mutant proteins is thought to drive pathogenesis in neurodegenerative diseases. Since decreasing levels of proteins responsible for such accumulations is likely to ameliorate disease, a therapeutic strategy has been developed to downregulate almost any gene in the CNS. Modified antisense oligonucleotides, continuously infused intraventricularly, have been demonstrated to distribute widely throughout the CNS of rodents and primates, including the regions affected in the major neurodegenerative diseases. Using this route of administration, we found that antisense oligonucleotides to superoxide dismutase 1 (SOD1), one of the most abundant brain proteins, reduced both SOD1 protein and mRNA levels throughout the brain and spinal cord. Treatment initiated near onset significantly slowed disease progression in a model of amyotrophic lateral sclerosis (ALS) caused by a mutation in SOD1. This suggests that direct delivery of antisense oligonucleotides could be an effective, dosage-regulatable means of treating neurodegenerative diseases, including ALS, where appropriate target proteins are known.

Disordered hemostasis associated with life-threatening hemorrhage commonly afflicts patients in the emergency department, critical care unit, and perioperative settings. Rapid and sensitive hemostasis phenotyping is needed to guide administration of blood components and hemostatic adjuncts to reverse aberrant hemostasis. Here, we report the use of resonant acoustic rheometry (RAR), a technique that quantifies the viscoelastic properties of soft biomaterials, for assessing plasma coagulation in a cohort of 38 bleeding patients admitted to the hospital. RAR captured the dynamic characteristics of plasma coagulation that were dependent on coagulation activators or reagent conditions. RAR coagulation parameters correlated with TEG reaction time and TEG functional fibrinogen, especially when stratified by comorbidities. A quadratic classifier trained on selective RAR parameters predicted transfusion of fresh frozen plasma and cryoprecipitate with modest to high overall accuracy. While these results demonstrate the feasibility of RAR for plasma coagulation and utility of a machine learning model, the relative small number of patients, especially the small number of patients who received transfusion, is a limitation of this study. Further studies are need to test a larger number of patients to further validate the capability of RAR as a cost-effective and sensitive hemostasis assay to obtain quantitative data to guide clinical-decision making in managing severely hemorrhaging patients.

Research to date has not determined a safe level of alcohol or tobacco use during pregnancy. Electroencephalography (EEG) is a noninvasive measure of cortical function that has previously been used to examine effects of in utero exposures and associations with neurodevelopment. To examine the association of prenatal exposure to alcohol (PAE) and tobacco smoking (PTE) with brain activity in newborns. This prospective cohort study enrolled mother-newborn dyads from December 2011 through August 2015, with data analyzed from June 2018 through June 2019. Pregnant women were recruited from clinical sites in Cape Town, South Africa, and the Northern Plains region of the US. Participants were a subset of newborns enrolled in the Safe Passage Study. Exclusions included birth at less than 37 or more than 41 weeks' gestation, multiple birth, or maternal use of psychiatric medication during pregnancy. PAE and PTE groups were determined by cluster analysis. Analyses of covariance were run on EEG spectral power at 12 scalp locations across the frequency spectrum from 1 to 45 Hz in 3-Hz bins by sleep state. The final sample consisted of 1739 newborns (median [interquartile range] gestational age at birth, 39.29 [1.57] weeks; 886 [50.9%] were female; median [interquartile range] newborn age at assessment, 48.53 [44.96] hours). Newborns whose mothers were in the low continuous (95% CI, -0.379 to -0.031; P < .05; 95% CI, -0.379 to -0.045; P < .05), quit (95% CI, -0.419 to -0.127; P < .001; 95% CI, -0.398 to -0.106; P < .005), and moderate or high continuous (95% CI, -0.430 to -0.124; P < .001; 95% CI, -0.420 to -0.119; P < .005) PAE clusters had increased 4- to 6-Hz and 7- to 9-Hz left-temporal EEG power. Newborns with moderate or high continuous PTE had decreased 19- to 21-Hz (95% CI, 0.034 to 0.327; P < .05) and 22- to 24-Hz (95% CI, 0.022 to 0.316; P < .05) right-central EEG compared with newborns with no PTE. Newborns with moderate or high continuous PTE had significantly decreased 22- to 36-Hz right-central EEG power compared with the quit smoking group (22-24 Hz, 95% CI, 0.001 to 0.579; P < .05; 25-27 Hz, 95% CI, 0.008 to 0.586; P < .05; 28-30 Hz, 95% CI, 0.028 to 0.607; P < .05; 31-33 Hz, 95% CI, 0.038 to 0.617; P < .05; 34-36 Hz, 95% CI, 0.057 to 0.636; P < .05). These findings suggest that even low levels of PAE or PTE are associated with changes in offspring brain development.

The efficacy of meropenem was compared to that of the combination of tobramycin plus clindamycin (T/C) in a multiinstitutional clinical trial of treatment for patients suffering intraabdominal infection. Among the 177 patients enrolled and randomized, 127 were clinically evaluable and 86 were microbiologically evaluable. Analysis of data on an intent-to-treat basis for all randomized patients and on the basis of a successful outcome (absence of any infection) for clinically evaluable patients failed to detect any difference in efficacy between the two treatments. Infection was cleared in 92% of meropenem- and 89% of T/C-treated clinically evaluable patients. Eradication of pathogens also was similar in the two treatment groups. Overall, adverse drug experiences were comparable between the two treatment groups, with the exception of an increase in serum creatinine level (which occurred more frequently in patients receiving T/C). Meropenem appears to be efficacious for the treatment of intraabdominal infections.