High suicidality predicts overdose events among people with substance use disorder: A latent class analysis.

Introduction: Suicide is the tenth leading cause of death in the United States and continues to be a major public health concern. Suicide risk is highly prevalent among individuals with co-occurring substance use disorders (SUD) and mental health disorders, making them more prone to adverse substance use related outcomes including overdose. Identifying individuals with SUD who are suicidal, and therefore potentially most at risk of overdose, is an important step to address the synergistic epidemics of suicides and overdose fatalities in the United States. The current study assesses whether patterns of suicidality endorsement can indicate risk for substance use and overdose. Methods: Latent class analysis (LCA) was used to assess patterns of item level responses to the Concise Health Risk Tracking Self-Report (CHRT-SR), which measures thoughts and feelings associated with suicidal propensity. We used data from 2,541 participants with SUD who were enrolled across 8 randomized clinical trials in the National Drug Abuse Treatment Clinical Trials Network from 2012 to 2021. Characteristics of individuals in each class were assessed, and multivariable logistic regression was performed to examine class membership as a predictor of overdose. LCA was also used to analyze predictors of substance use days. Results: Three classes were identified and discussed: Class (1) Minimal Suicidality, with low probabilities of endorsing each CHRT-SR construct; Class (2) Moderate Suicidality, with high probabilities of endorsing pessimism, helplessness, and lack of social support, but minimal endorsement of despair or suicidal thoughts; and Class (3) High Suicidality with high probabilities of endorsing all constructs. Individuals in the High Suicidality class comprise the highest proportions of males, Black/African American individuals, and those with a psychiatric history and baseline depression, as compared with the other two classes. Regression analysis revealed that those in the High Suicidality class are more likely to overdose as compared to those in the Minimal Suicidality class (p = 0.04). Conclusion: Suicidality is an essential factor to consider when building strategies to screen, identify, and address individuals at risk for overdose. The integration of detailed suicide assessment and suicide risk reduction is a potential solution to help prevent suicide and overdose among people with SUD.

Untreated substance use disorder affects glycemic control: Results in patients with type 2 diabetes served within a network of community-based healthcare centers in Florida.

Introduction: Patients with diabetes and comorbid substance use disorders (SUD) experience poor diabetes management, increased medical complications and mortality. However, research has documented that patients engaged in substance abuse treatment have better management of their comorbid conditions. The current study examines diabetes management among patients with type 2 diabetes, with and without comorbid SUD, receiving care at Florida-based Federally Qualified Health Centers (FQHC) of Health Choice Network (HCN). Methods: A retrospective analysis was conducted using deidentified electronic health records of 37,452 patients with type 2 diabetes who received care at a HCN site in Florida between 2016 and 2019. A longitudinal logistic regression analysis examined the impact of SUD diagnosis on achievement of diabetes management [HbA1c < 7.0% (53 mmol/mol)] over time. A secondary analysis evaluated, within those with an SUD diagnosis, the likelihood of HbA1c control between those with and without SUD treatment. Results: The longitudinal assessment of the relationship between SUD status and HbA1c control revealed that those with SUD (N = 6,878, 18.4%) were less likely to control HbA1c over time (OR = 0.56; 95% CI = 0.49-0.63). Among those with SUD, patients engaged in SUD treatment were more likely to control HbA1c (OR = 5.91; 95% CI = 5.05-6.91). Discussion: Findings highlight that untreated SUD could adversely affect diabetes control and sheds light on the opportunity to enhance care delivery for patients with diabetes and co-occurring SUD.

Characterization of Virulent T4-Like Acinetobacter baumannii Bacteriophages DLP1 and DLP2.

The world is currently facing a global health crisis due to the rapid increase in antimicrobial-resistant bacterial infections. One of the most concerning pathogens is Acinetobacter baumannii, which is listed as a Priority 1 pathogen by the World Health Organization. This Gram-negative bacterium has many intrinsic antibiotic resistance mechanisms and the ability to quickly acquire new resistance determinants from its environment. A limited number of effective antibiotics against this pathogen complicates the treatment of A. baumannii infections. A potential treatment option that is rapidly gaining interest is "phage therapy", or the clinical application of bacteriophages to selectively kill bacteria. The myoviruses DLP1 and DLP2 (vB_AbaM-DLP_1 and vB_AbaM-DLP_2, respectively) were isolated from sewage samples using a capsule minus variant of A. baumannii strain AB5075. Host range analysis of these phages against 107 A. baumannii strains shows a limited host range, infecting 15 and 21 for phages DLP1 and DLP2, respectively. Phage DLP1 has a large burst size of 239 PFU/cell, a latency period of 20 min, and virulence index of 0.93. In contrast, DLP2 has a smaller burst size of 24 PFU/cell, a latency period of 20 min, and virulence index of 0.86. Both phages show potential for use as therapeutics to combat A. baumannii infections.

Bacteriophage Isolation, Purification, and Characterization Techniques Against Ubiquitous Opportunistic Pathogens.

Healthcare-associated infection with "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) is a global health crisis due to their extensive intrinsic antibiotic resistance and the ability to quickly acquire resistance determinants. Alternative treatment options are required to combat this crisis, and one possibility is the use of bacteriophages, or viruses that strictly infect the pathogenic bacteria. Currently, there is a renaissance in research and development into the use of phages to target multi-, extensively, and pan-resistant bacterial infections in humans, known as phage therapy. Using A. baumannii as an example, this article describes the isolation and purification of bacteriophages from sewage and soil samples, as well as general methods used in phage research such as precipitation of phages using polyethylene glycol, host range analysis, single-cell burst size determination, DNA extraction, and restriction fragment length polymorphism analysis. © 2022 National Research Council Canada. Current Protocols © 2022 Wiley Periodicals LLC. Reproduced with the permission of the Minister of Innovation, Science, and Industry. Basic Protocol 1: Isolation of bacteriophages against A. baumannii from sewage samples Alternate Protocol 1: Isolation of bacteriophages against A. baumannii from soil samples Support Protocol 1: Titering a bacteriophage stock Basic Protocol 2: Purification of phage to an axenic working stock Support Protocol 2: Liquid propagation of bacteriophage Basic Protocol 3: Host range analysis using the spot plate method Basic Protocol 4: Single burst size analysis Alternate Protocol 2: One-step growth curve Basic Protocol 5: Precipitation of bacteriophage using PEG 6000 Basic Protocol 6: DNA extraction from dsDNA bacteriophages Basic Protocol 7: Restriction fragment length polymorphism analysis of novel phage genomes.

Suicidality as a Predictor of Overdose among Patients with Substance Use Disorders.

Increasing rates of overdose and overdose deaths are a significant public health problem. Research has examined co-occurring mental health conditions, including suicidality, as a risk factor for intentional and unintentional overdose among individuals with substance use disorder (SUD). However, this research has been limited to single site studies of self-reported outcomes. The current research evaluated suicidality as a predictor of overdose events in 2541 participants who use substances enrolled across eight multi-site clinical trials completed within the National Drug Abuse Treatment Clinical Trials Network between 2012 to 2021. The trials assessed baseline suicidality with the Concise Health Risk Tracking Self-Report (CHRT-SR). Overdose events were determined by reports of adverse events, cause of death, or hospitalization due to substance overdose, and verified through a rigorous adjudication process. Multivariate logistic regression was performed to assess continuous CHRT-SR score as a predictor of overdose, controlling for covariates. CHRT-SR score was associated with overdose events (p = 0.03) during the trial; the likelihood of overdose increased as continuous CHRT score increased (OR 1.02). Participants with lifetime heroin use were more likely to overdose (OR 3.08). Response to the marked rise in overdose deaths should integrate suicide risk reduction as part of prevention strategies.

The Isolation and Characterization of a Broad Host Range Bcep22-like Podovirus JC1.

Bacteriophage JC1 is a Podoviridae phage with a C1 morphotype, isolated on host strain Burkholderia cenocepacia Van1. Phage JC1 is capable of infecting an expansive range of Burkholderia cepacia complex (Bcc) species. The JC1 genome exhibits significant similarity and synteny to Bcep22-like phages and to many Ralstonia phages. The genome of JC1 was determined to be 61,182 bp in length with a 65.4% G + C content and is predicted to encode 76 proteins and 1 tRNA gene. Unlike the other Lessieviruses, JC1 encodes a putative helicase gene in its replication module, and it is in a unique organization not found in previously analyzed phages. The JC1 genome also harbours 3 interesting moron genes, that encode a carbon storage regulator (CsrA), an N-acetyltransferase, and a phosphoadenosine phosphosulfate (PAPS) reductase. JC1 can stably lysogenize its host Van1 and integrates into the 5' end of the gene rimO. This is the first account of stable integration identified for Bcep22-like phages. JC1 has a higher global virulence index at 37 °C than at 30 °C (0.8 and 0.21, respectively); however, infection efficiency and lysogen stability are not affected by a change in temperature, and no observable temperature-sensitive switch between lytic and lysogenic lifestyle appears to exist. Although JC1 can stably lysogenize its host, it possesses some desirable characteristics for use in phage therapy. Phage JC1 has a broad host range and requires the inner core of the bacterial LPS for infection. Bacteria that mutate to evade infection by JC1 may develop a fitness disadvantage as seen in previously characterized LPS mutants lacking inner core.

Aztreonam Lysine Increases the Activity of Phages E79 and phiKZ against Pseudomonas aeruginosa PA01.

Pseudomonas aeruginosa is a pernicious bacterial pathogen that is difficult to treat because of high levels of antibiotic resistance. A promising alternative treatment option for such bacteria is the application of bacteriophages; the correct combination of phages plus antibiotics can produce synergistic inhibitory effects. In this study, we describe morphological changes induced by sub-MIC levels of the antibiotic aztreonam lysine (AzLys) on P. aeruginosa PA01, which may in part explain the observed phage-antibiotic synergy (PAS). One-step growth curves for phage E79 showed increased adsorption rates, decreased infection latency, accelerated time to lysis and a minor reduction in burst size. Phage E79 plus AzLys PAS was also able to significantly reduce P. aeruginosa biofilm growth over 3-fold as compared to phage treatment alone. Sub-inhibitory AzLys-induced filamentation of P. aeruginosa cells resulted in loss of twitching motility and a reduction in swimming motility, likely due to a reduction in the number of polar Type IV pili and flagella, respectively, on the filamented cell surfaces. Phage phiKZ, which uses Type IV pili as a receptor, did not exhibit increased activity with AzLys at lower sub-inhibitory levels, but still produced phage-antibiotic synergistic killing with sub-inhibitory AzLys. A one-step growth curve indicates that phiKZ in the presence of AzLys also exhibits a decreased infection latency and moderately undergoes accelerated time to lysis. In contrast to prior PAS studies demonstrating that phages undergo delayed time to lysis with cell filamentation, these PAS results show that phages undergo accelerated time to lysis, which therefore suggests that PAS is dependent upon multiple factors, including the type of phages and antibiotics used, and the bacterial host being tested.

Duckweed (Lemna minor) and Alfalfa (Medicago sativa) as Bacterial Infection Model Systems.

Alternative animal host models of bacterial infection have been developed which reproduce some of the disease conditions observed in higher animals. Analogously, plants are useful for modeling bacterial pathogenesis, in some cases revealing broadly conserved infection mechanisms. Similar to animals, plants have been shown to possess innate immune systems that respond to invading viruses, bacteria, and fungi. Plant infection models often yield results faster, are more convenient, and less expensive than many animal infection models. Here, we describe the use of two different plant-based infection models for the discovery of virulence genes and factors involved in bacterial pathogenesis.

Feasibility of Ballistic Strength Training in Subacute Stroke: A Randomized, Controlled, Assessor-Blinded Pilot Study.

OBJECTIVE: To establish the feasibility and effectiveness of a 6-week ballistic strength training protocol in people with stroke. DESIGN: Randomized, controlled, assessor-blinded study. SETTING: Subacute inpatient rehabilitation. PARTICIPANTS: Consecutively admitted inpatients with a primary diagnosis of first-ever stroke with lower limb weakness, functional ambulation category score of ≥3, and ability to walk ≥14 m were screened for eligibility to recruit 30 participants for randomization. INTERVENTIONS: Participants were randomized to standard therapy or ballistic strength training 3 times per week for 6 weeks. MAIN OUTCOME MEASURES: The primary aim was to evaluate feasibility and outcomes included recruitment rate, participant retention and attrition, feasibility of the exercise protocol, therapist burden, and participant safety. Secondary outcomes included measures of mobility, lower limb muscle strength, muscle power, and quality of life. RESULTS: A total of 30 participants (11% of those screened) with mean age of 50 years (SD 18) were randomized. The median number of sessions attended was 15 of 18 and 17 of 18 for the ballistic and control groups, respectively. Earlier than expected discharge to home (n=4) and illness (n=7) were the most common reasons for nonattendance. Participants performed the exercises safely, with no study-related adverse events. There were significant (P<.05) between-group changes favoring the ballistic group for comfortable gait velocity (mean difference [MD] 0.31m/s, 95% confidence interval [CI]: 0.08-0.52), muscle power, as measured by peak jump height (MD 8cm, 95% CI: 3-13), and peak propulsive velocity (MD 64cm/s, 95% CI: 17-112). CONCLUSIONS: Ballistic training was safe and feasible in select ambulant people with stroke. Similar rates of retention and attrition suggest that ballistic training was acceptable to patients. Secondary outcomes provide promising results that warrant further investigation in a larger trial.

Incidence, Morbidity, and Costs of Human Metapneumovirus Infection in Hospitalized Children.

BACKGROUND: Human metapneumovirus (HMPV) causes acute respiratory tract infections in infants and children. We sought to measure the clinical and economic burden of HMPV infection in hospitalized children. METHODS: We conducted a retrospective cohort study from 2007 to 2013 at Primary Children's Hospital in Salt Lake City, Utah. Children <18 years of age with laboratory-confirmed HMPV infection were included. Demographic, clinical, and financial data were abstracted from the electronic medical record. RESULTS: During the study period, 815 children were hospitalized with laboratory-confirmed HMPV infection: 16% <6 months, 50% 6-23 months, 23% 2-4 years, and 11% 5-17 years of age. A complex chronic condition was identified in 453 (56%) children hospitalized with HMPV infection; this proportion increased with increasing age (P < .001). There was marked variation in annual HMPV hospitalization rates, ranging from 9 of 100 000 person-years in 2012-2013 to 79 of 100 000 in 2009-2010. Hospitalization rates were highest among children <2 years (200 of 100 000 person-years) and lowest among children 5-17 years of age (5 of 100 000). Of hospitalized children, 18% were treated in the intensive care unit and 6% required mechanical ventilation. The median length of stay was 2.8 days (interquartile range [IQR], 1.8-4.6) and did not vary by age. The median total hospital cost per patient was $5513 (IQR, $3850-$9946) with significantly higher costs for patients with chronic medical conditions (P < .001). CONCLUSIONS: Human metapneumovirus infection results in a large number of hospitalizations with substantial morbidity, resource utilization, and costs. The development of a safe and effective vaccine could reduce the clinical and economic burden of HMPV.

Outpatient parenteral antimicrobial therapy in pediatrics: an opportunity to expand antimicrobial stewardship.

We reviewed patient discharges with outpatient parenteral antimicrobial therapy (OPAT) to determine whether outpatient parenteral antimicrobial therapy was modifiable or unnecessary at a large tertiary care children's hospital. At least one modification definitely or possibly would have been recommended for 78% of episodes. For more than 40% of episodes, outpatient parenteral antimicrobial therapy was potentially not indicated.