How to Combat the Global Opioid Crisis.

Since 2000 there have been 915,515 people who have died from a drug overdose in the United States (US). This number continues to increase and in 2021 drug overdose deaths reached a record high of 107,622, and opioids specifically were responsible for 80,816 of those deaths. This unprecedented rate of drug overdose deaths is the direct result of increasing rates of illicit drug use in the US. It was estimated that in the US in 2020, approximately 59.3 million individuals had used illicit drugs, 40.3 million had a substance use disorder (SUD), and 2.7 million had opioid use disorder (OUD). Typical treatment for OUD involves an opioid agonist (i.e., buprenorphine or methadone) along with a variety of psychotherapeutic interventions (i.e., motivational interviewing, cognitive-behavioral therapy (CBT), behavioral family counseling, mutual help groups, etc.). In addition to the aforementioned treatment options, there is an urgent need for new therapies and screening methods that are reliable, safe, and effective. Similar to the concept of prediabetes is the novel concept of "preaddiction." Preaddiction is defined as individuals with mild to moderate SUD or those at risk for developing a severe SUD/addiction. Screening for preaddiction could be achieved through genetic testing (i.e., the genetic addiction risk severity (GARS) test) and/or through other neuropsychiatric testing (i.e., Memory (CNSVS), Attention (TOVA), Neuropsychiatric (MCMI-III), Neurological Imaging (qEEG/P300/EP)). The concept of preaddiction, when used in conjunction with standardized and objective diagnostic screening/testing, would halt the rise of SUD and overdoses with early detection and treatment.

Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants.

Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of selection along a transmission chain. While increased force of infection, receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here we compare the transmission bottleneck of non-VOC SARS-CoV-2 lineages to those of Alpha, Delta, and Omicron. We sequenced viruses from 168 individuals in 65 households. Most virus populations had 0-1 single nucleotide variants (iSNV). From 64 transmission pairs with detectable iSNV, we identify a per clade bottleneck of 1 (95% CI 1-1) for Alpha, Delta, and Omicron and 2 (95% CI 2-2) for non-VOC. These tight bottlenecks reflect the low diversity at the time of transmission, which may be more pronounced in rapidly transmissible variants. Tight bottlenecks will limit the development of highly mutated VOC in transmission chains, adding to the evidence that selection over prolonged infections may drive their evolution.

Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids.

In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids.

Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants.

Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of natural selection along a transmission chain. Many viruses exhibit tight bottlenecks, and studies of early SARS-CoV-2 lineages identified a bottleneck of 1-3 infectious virions. While increased force of infection, host receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here, we compare the transmission bottleneck of non-variant-of-concern (non-VOC) SARS-CoV-2 lineages to those of the Alpha, Delta, and Omicron variants. We sequenced viruses from 168 individuals in 65 multiply infected households in duplicate to high depth of coverage. In 110 specimens collected close to the time of transmission, within-host diversity was extremely low. At a 2% frequency threshold, 51% had no intrahost single nucleotide variants (iSNV), and 42% had 1-2 iSNV. In 64 possible transmission pairs with detectable iSNV, we identified a bottleneck of 1 infectious virion (95% CI 1-1) for Alpha, Delta, and Omicron lineages and 2 (95% CI 2-2) in non-VOC lineages. The latter was driven by a single iSNV shared in one non-VOC household. The tight transmission bottleneck in SARS-CoV-2 is due to low genetic diversity at the time of transmission, a relationship that may be more pronounced in rapidly transmissible variants. The tight bottlenecks identified here will limit the development of highly mutated VOC in typical transmission chains, adding to the evidence that selection over prolonged infections in immunocompromised patients may drive their evolution.

Predictors of depressive symptoms in patients with COPD and health impact.

While depression is a common co-morbid condition among patients with COPD, little is known about predictors or health impact of depression among these patients. To address these gaps in knowledge we conducted a cross-sectional survey of 207 patients with COPD cared for in a network of primary care clinics affiliated with an urban academic health center. A standardized questionnaire was used to measure demographic characteristics, smoking status, co-morbid medical conditions, current medications, self-efficacy, social support, illness intrusiveness, and self-reported health care utilization during the previous 6 months. Depressive symptoms were assessed using the Centers for Epidemiologic Studies-Depression scale. Overall, the prevalence of moderate to high levels of depressive symptoms was 60.4%. In a multivariate analysis independent predictors of depressive symptoms were being a former smoker (OR = 0.41 (95% CI 0.19-0.89)), higher self-efficacy (OR = 0.42 (0.28-0.64)), higher social support (OR = 0.72 (0.52-0.99)), and higher perceived illness intrusiveness (OR = 1.05 (1.02-1.08)). Depressive symptoms were associated with increased physician visits, emergency room visits, and hospitalizations for lung disease. In conclusion, depressive symptoms are common among patients with COPD and associated with an increase in healthcare utilization. These findings suggest that the identification of risk factors for depressive symptoms (e.g., continued smoking) may increase detection and improve management of depression and health outcomes among patients with COPD.

Pharmacy discount card programs: catching up with the health markets.

Pharmacy costs continue to rise, as does the number of senior citizens. One of the ways of containing costs may be the pharmacy discount drug card program, for both seniors and the general population.