Assessing the association between antibody status and symptoms of long COVID: A multisite study.

The association between SARS-CoV-2 humoral immunity and post-acute sequelae of COVID-19 (long COVID) remains uncertain. The objective of this population-based cohort study was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID. English and Spanish-speaking members ≥ 18 years old with SARS-CoV-2 serologic testing conducted prior to August 2021 were recruited from Kaiser Permanente Southern California and Kaiser Permanente Colorado. Between November 2021 and April 2022, participants completed a survey assessing symptoms, physical health, mental health, and cognitive function consistent with long COVID. Survey results were linked to SARS-CoV-2 antibody (Ab) and viral (RNA) lab results in electronic health records. Weighted descriptive analyses were generated for five mutually exclusive patient groups: (1) +Ab/+RNA; (2) +Ab/- or missing RNA; (3) -Ab/+RNA; (4a) -Ab/-RNA reporting no prior infection; and (4b) -Ab/-RNA reporting prior infection. The proportions reporting symptoms between the +Ab/+RNA and -Ab/+RNA groups were compared, adjusted for covariates. Among 3,946 participants, the mean age was 52.1 years old (SD 15.6), 68.3% were female, 28.4% were Hispanic, and the serologic testing occurred a median of 15 months prior (IQR = 12-18). Three quarters (74.5%) reported having had COVID-19. Among people with laboratory-confirmed COVID-19, there was no association between antibody positivity (+Ab/+RNA vs. -Ab/+RNA) and any symptoms, physical health, mental health, or cognitive function. As expected, physical health, cognitive function, and fatigue were worse, and palpitations and headaches limiting the ability to work were more prevalent among people with laboratory-confirmed prior infection and positive serology (+Ab/+RNA) compared to those without reported or confirmed prior infection and negative serology (-Ab/-RNA/no reported COVID-19). Among people with laboratory-confirmed COVID-19, SARS-CoV-2 serology from practice settings were not associated with long COVID symptoms and health status suggesting limited utility of serology testing for long COVID.

Association between severe acute respiratory syndrome coronavirus 2 antibody status and reinfection: A case-control study nested in a Colorado-based prospective cohort study.

The association between the presence of detectable antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 reinfection is not well established. The objective of this study was to determine the association between antibody seronegativity and reinfection. METHODS: Participants in Colorado, USA, were recruited between June 15, 2020, and March 28, 2021, and encouraged to complete SARS-CoV-2 molecular ribonucleic acid (RNA) and serology testing for antibodies every 28 days for 10 months. Participants with reinfections (positive SARS-CoV-2 RNA test ≥ 90 days after the first positive RNA test) were matched to controls without reinfections by age, sex, date of the first positive RNA test, date of the last serology test, and serology test type. Using conditional logistic regression, case patients were compared to control patients on the last serologic test result, with adjustment for demographic and clinical confounders. RESULTS: The cohort (n = 4,235) included 2,033 participants with ≥ 1 positive RNA test, of whom 120 had reinfection. Among the 80 case patients who could be matched, the last serologic test was negative in 12 of the cases (15.0 %) whereas the last serologic test was negative in 77 of 1,034 (7.5 %) controls. Seronegativity (adjusted OR [aOR] 2.24; 95 % CI 1.07, 4.68), Hispanic ethnicity (aOR 1.87; 95 % 1.10, 3.18), and larger household size (aOR 1.15; 95 % 1.01, 1.30 for each additional household member) were associated with reinfection. CONCLUSIONS: Seronegative status, Hispanic ethnicity, and increasing household size were associated with reinfection. Serologic testing could be considered to reduce vaccine hesitancy in higher risk populations.

An individual segmented trajectory approach for identifying opioid use patterns using longitudinal dispensing data.

PURPOSE: The aim of this study is to use electronic opioid dispensing data to develop an individual segmented trajectory approach for identifying opioid use patterns. The resulting opioid use patterns can be used for examining the association between opioid use and drug overdose. METHODS: We retrospectively assembled a cohort of members on long-term opioid therapy (LTOT) between January 1, 2006 and June 30, 2019 who were 18 years and older and enrolled in one of three health care systems in the US. We have developed an individual segmented trajectory analysis for identifying various opioid use patterns by scanning over the follow-up and finding distinct opioid use patterns based on variability measured with coefficient of variation and trends of milligram morphine equivalents levels. RESULTS: Among 31, 865 members who were on LTOT between January 1, 2006 and June 30, 2019, 58.3% were female, and the average age was 55.4 years (STD = 15.4). The study population had 152 557 person-years of follow-up, with an average follow-up of 4.4 years per enrollment per person (STD = 3.4). This novel approach identified up to 13 distinct patterns including 88 756 episodes of "stable" pattern (42.1%) with an average follow-up of 11.2 months, 29 140 episodes of "increasing" pattern (13.8%) with an average follow-up of 6.0 months, 13 201 episodes of ≤10% dose reduction (6.3%) with an average follow-up of 10.4 months, 7286 episodes of 11%-20% dose reduction (3.5%) with an average follow-up of 5.3 months, 4457 episodes of 21%-30% dose reduction (2.1%) with an average follow-up of 4.0 months, and 9903 episodes of >30% dose reduction (4.7%) with an average follow-up of 2.6 months. CONCLUSIONS: A novel approach was developed to identify 13 distinct opioid use patterns using each individual's longitudinal dispensing data and these patterns can be used in examining overdose risk during the time that these patterns are ongoing.

Unveiling the Genetic Symphony: Harnessing CRISPR-Cas Genome Editing for Effective Insect Pest Management.

Phytophagous insects pose a significant threat to global crop yield and food security. The need for increased agricultural output while reducing dependence on harmful synthetic insecticides necessitates the implementation of innovative methods. The utilization of CRISPR-Cas (Clustered regularly interspaced short palindromic repeats) technology to develop insect pest-resistant plants is believed to be a highly effective approach in reducing production expenses and enhancing the profitability of farms. Insect genome research provides vital insights into gene functions, allowing for a better knowledge of insect biology, adaptability, and the development of targeted pest management and disease prevention measures. The CRISPR-Cas gene editing technique has the capability to modify the DNA of insects, either to trigger a gene drive or to overcome their resistance to specific insecticides. The advancements in CRISPR technology and its various applications have shown potential in developing insect-resistant varieties of plants and other strategies for effective pest management through a sustainable approach. This could have significant consequences for ensuring food security. This approach involves using genome editing to create modified insects or crop plants. The article critically analyzed and discussed the potential and challenges associated with exploring and utilizing CRISPR-Cas technology for reducing insect pest pressure in crop plants.

Association Between Opioid Dose Reduction Rates and Overdose Among Patients Prescribed Long-Term Opioid Therapy.

BACKGROUND: Tapering long-term opioid therapy is an increasingly common practice, yet rapid opioid dose reductions may increase the risk of overdose. The objective of this study was to compare overdose risk following opioid dose reduction rates of ≤10%, 11% to 20%, 21% to 30%, and >30% per month to stable dosing. METHODS: We conducted a retrospective cohort study in three health systems in Colorado and Wisconsin. Participants were patients ≥18 years of age prescribed long-term opioid therapy between January 1, 2006, and June 30, 2019. Five opioid dosing patterns and drug overdoses (fatal and nonfatal) were identified using electronic health records, pharmacy records, and the National Death Index. Cox proportional hazard regression was conducted on a propensity score-weighted cohort to estimate adjusted hazard ratios (aHRs) for follow-up periods of 1, 3, 6, 9, and 12 months after a dose reduction. RESULTS: In a cohort of 17 540 patients receiving long-term opioid therapy, 42.7% of patients experienced a dose reduction. Relative to stable dosing, a dose reduction rate of >30% was associated with an increased risk of overdose and the aHR estimates decreased as the follow-up increased; the aHRs for the 1-, 6- and 12-month follow-ups were 5.33 (95% CI, 1.98-14.34), 1.81 (95% CI,1.08-3.03), and 1.49 (95% CI, 0.97-2.27), respectively. The slower tapering rates were not associated with overdose risk. CONCLUSIONS: Patients receiving long-term opioid therapy exposed to dose reduction rates of >30% per month had increased overdose risk relative to patients exposed to stable dosing. Results support the use of slow dose reductions to minimize the risk of overdose.

Insect-pathogen crosstalk and the cellular-molecular mechanisms of insect immunity: uncovering the underlying signaling pathways and immune regulatory function of non-coding RNAs.

Multicellular organisms are constantly subjected to pathogens that might be harmful. Although insects lack an adaptive immune system, they possess highly effective anti-infective mechanisms. Bacterial phagocytosis and parasite encapsulation are some forms of cellular responses. Insects often defend themselves against infections through a humoral response. This phenomenon includes the secretion of antimicrobial peptides into the hemolymph. Specific receptors for detecting infection are required for the recognition of foreign pathogens such as the proteins that recognize glucans and peptidoglycans, together referred to as PGRPs and ßGRPs. Activation of these receptors leads to the stimulation of signaling pathways which further activates the genes encoding for antimicrobial peptides. Some instances of such pathways are the JAK-STAT, Imd, and Toll. The host immune response that frequently accompanies infections has, however, been circumvented by diseases, which may have assisted insects evolve their own complicated immune systems. The role of ncRNAs in insect immunology has been discussed in several notable studies and reviews. This paper examines the most recent research on the immune regulatory function of ncRNAs during insect-pathogen crosstalk, including insect- and pathogen-encoded miRNAs and lncRNAs, and provides an overview of the important insect signaling pathways and effector mechanisms activated by diverse pathogen invaders.

Update of a Multivariable Opioid Overdose Risk Prediction Model to Enhance Clinical Care for Long-term Opioid Therapy Patients.

BACKGROUND: Clinical opioid overdose risk prediction models can be useful tools to reduce the risk of overdose in patients prescribed long-term opioid therapy (LTOT). However, evolving overdose risk environments and clinical practices in addition to potential harmful model misapplications require careful assessment prior to widespread implementation into clinical care. Models may need to be tailored to meet local clinical operational needs and intended applications in practice. OBJECTIVE: To update and validate an existing opioid overdose risk model, the Kaiser Permanente Colorado Opioid Overdose (KPCOOR) Model, in patients prescribed LTOT for implementation in clinical care. DESIGN, SETTING, AND PARTICIPANTS: The retrospective cohort study consisted of 33, 625 patients prescribed LTOT between January 2015 and June 2019 at Kaiser Permanente Colorado, with follow-up through June 2021. MAIN MEASURES: The outcome consisted of fatal opioid overdoses identified from vital records and non-fatal opioid overdoses from emergency department and inpatient settings. Predictors included demographics, medication dispensings, substance use disorder history, mental health history, and medical diagnoses. Cox proportional hazards regressions were used to model 2-year overdose risk. KEY RESULTS: During follow-up, 65 incident opioid overdoses were observed (111.4 overdoses per 100,000 person-years) in the study cohort, of which 11 were fatal. The optimal risk model needed to risk-stratify patients and to be easily interpreted by clinicians. The original 5-variable model re-validated on the new study cohort had a bootstrap-corrected C-statistic of 0.73 (95% CI, 0.64-0.85) compared to a C-statistic of 0.80 (95% CI, 0.70-0.88) in the updated model and 0.77 (95% CI, 0.66-0.87) in the final adapted 7-variable model, which was also well-calibrated. CONCLUSIONS: Updating and adapting predictors for opioid overdose in the KPCOOR Model with input from clinical partners resulted in a parsimonious and clinically relevant model that was poised for integration in clinical care.

Nutritional aspects and dietary benefits of "Silkworms": Current scenario and future outlook.

In the current scenario, it is estimated that by 2050, there will be an additional 2.5 billion people and a 70% increase in food demand. Crop yields are not increasing fast enough to support global needs, and world agriculture is facing several serious challenges. Therefore, insects can be a nutritious alternative to meet the ever-increasing food demand in the present and future. The majority of insect consumption occurs in developing countries, with approximately 1,900 insect species consumed worldwide. Food and feed derived from them are of high quality, have a high feed conversion ratio and emit a low level of greenhouse gases. Among insects silkworms are beneficial to humans, not only because of their high nutritional value, but also because of their several pharmacological properties. Silkworm eggs, larvae, and pupae contains high amount of proteins, oils, minerals, vitamins, and several other beneficial components which are nutritious as well as have positive effect on human health. Studies have shown that silkworm pupae protect the liver, enhance immunity, inhibit apoptosis, inhibit cancer, inhibit tumor growth, inhibit microbial growth, regulate blood glucose and blood lipids, and lower blood pressure. This review paper summerized the nutritional value of different life stages of silkworm, nutritional comparison of silkworm with the major human foods, and the effects of silkworm consumption on human health, thus ittargets to generate interest toward in sericulture and improve human health by using silkworm as a nutritious food and attain sustainability in food and nutritional security.

Opioid Overdose Risk Following Hospital Discharge Among Individuals Prescribed Long-Term Opioid Therapy: a Risk Interval Analysis.

BACKGROUND: Individuals prescribed long-term opioid therapy (LTOT) have increased risk of readmission and death after hospital discharge. The risk of opioid overdose during the immediate post-discharge time period is unknown. OBJECTIVE: To examine the association between time since hospital discharge and opioid overdose among individuals prescribed LTOT. DESIGN: Self-controlled risk interval analysis. PARTICIPANTS: Adults prescribed LTOT with at least one hospital discharge at a safety-net health system and a non-profit healthcare organization in Colorado. MAIN MEASURES: We identified individuals prescribed LTOT who were discharged from January 2006 through June 2019. The outcome was a composite of fatal and non-fatal opioid overdoses during a 90-day post-discharge observation period, identified using electronic health record (EHR) and vital statistics data. Risk intervals included days 0-6 after index and subsequent hospital discharges. Control intervals ranged from days 7 to 89 after index discharge and included all other time during the observation period that did not fall within a risk interval or time readmitted during a subsequent hospitalization, which was excluded. Poisson regression was used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for overdose events during risk in comparison to control intervals. KEY RESULTS: We identified 7695 adults (63.3% over 55 years, 59.4% female, 20.3% Hispanic) who experienced 9499 total discharges during the study period. Twenty-one overdoses occurred during their observation periods (1174 per 100,000 person-years [9 in risk, 12 in control]). Overdose risk was significantly higher during the risk interval in comparison to the control interval (IRR 6.92; 95% CI 2.92-16.43). CONCLUSION: During the first 7 days after hospital discharge, individuals prescribed LTOT appear to be at elevated risk for opioid overdose. Clarifying mechanisms of overdose risk may help inform in-hospital and post-discharge prevention strategies.

Insight into aphid mediated Potato Virus Y transmission: A molecular to bioinformatics prospective.

Potato, the world's most popular crop is reported to provide a food source for nearly a billion people. It is prone to a number of biotic stressors that affect yield and quality, out of which Potato Virus Y (PVY) occupies the top position. PVY can be transmitted mechanically and by sap-feeding aphid vectors. The application of insecticide causes an increase in the resistant vector population along with detrimental effects on the environment; genetic resistance and vector-virus control are the two core components for controlling the deadly PVY. Using transcriptomic tools together with differential gene expression and gene discovery, several loci and genes associated with PVY resistance have been widely identified. To combat this virus we must increase our understanding on the molecular response of the PVY-potato plant-aphid interaction and knowledge of genome organization, as well as the function of PVY encoded proteins, genetic diversity, the molecular aspects of PVY transmission by aphids, and transcriptome profiling of PVY infected potato cultivars. Techniques such as molecular and bioinformatics tools can identify and monitor virus transmission. Several studies have been conducted to understand the molecular basis of PVY resistance/susceptibility interactions and their impact on PVY epidemiology by studying the interrelationship between the virus, its vector, and the host plant. This review presents current knowledge of PVY transmission, epidemiology, genome organization, molecular to bioinformatics responses, and its effective management.

Opioid Dose Trajectories and Associations With Mortality, Opioid Use Disorder, Continued Opioid Therapy, and Health Plan Disenrollment.

Importance: Uncertainty remains about the longer-term benefits and harms of different opioid management strategies, such as tapering and dose escalation. For instance, opioid tapering could help patients reduce opioid exposure to prevent opioid use disorder, but patients may also seek care elsewhere and engage in nonprescribed opioid use. Objective: To evaluate the association between opioid dose trajectories observed in practice and patient outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted in 3 health systems in Colorado and Wisconsin. The study population included patients receiving long-term opioid therapy between 50 and 200 morphine milligram equivalents between August 1, 2014, and July 31, 2017. Follow-up ended on December 31, 2019. Data were analyzed from January 2020 to August 2022. Exposures: Group-based trajectory modeling identified 5 dosing trajectories over 1 year: 1 decreasing, 1 high-dose increasing, and 3 stable. Main Outcomes and Measures: Primary outcomes assessed after the trajectory period were 1-year all-cause mortality, incident opioid use disorder, continued opioid therapy at 1 year, and health plan disenrollment. Associations were tested using Cox proportional hazards regression and log-binomial models, adjusting for baseline covariates. Results: A total of 3913 patients (mean [SD] age, 59.2 [14.4] years; 2767 White non-Hispanic [70.7%]; 2237 female patients [57.2%]) were included in the study. Compared with stable trajectories, the decreasing dose trajectory was negatively associated with opioid use disorder (adjusted hazard ratio [aHR], 0.40; 95% CI, 0.29-0.55) and continued opioid therapy (site 1: adjusted relative risk [aRR], 0.39; 95% CI, 0.34-0.44), but was positively associated with health plan disenrollment (aHR, 1.66; 95% CI, 1.24-2.22). The decreasing trajectory was not associated with mortality (aHR, 1.28; 95% CI, 0.87-1.86). In contrast, the high-dose increasing trajectory was positively associated with mortality (aHR, 2.19; 95% CI, 1.44-3.32) and opioid use disorder (aHR, 1.81; 95% CI, 1.39-2.37) but was not associated with disenrollment (aHR, 0.90; 95% CI, 0.56-1.42) or continued opioid therapy (site 1: aRR, 0.98; 95% CI, 0.94-1.03). Conclusions and Relevance: In this cohort study, decreasing opioid dose was associated with reduced risk of opioid use disorder and continued opioid therapy but increased risk of disenrollment compared with stable dosing, whereas the high-dose increasing trajectory was associated with an increased risk of mortality and opioid use disorder. These findings can inform opioid management decision-making.

Naloxone Co-Dispensing with Opioids: a Cluster Randomized Pragmatic Trial.

BACKGROUND: Although naloxone prevents opioid overdose deaths, few patients prescribed opioids receive naloxone, limiting its effectiveness in real-world settings. Barriers to naloxone prescribing include concerns that naloxone could increase risk behavior and limited time to provide necessary patient education. OBJECTIVE: To determine whether pharmacy-based naloxone co-dispensing affected opioid risk behavior. Secondary objectives were to assess if co-dispensing increased naloxone acquisition, increased patient knowledge about naloxone administration, and affected opioid dose and other substance use. DESIGN: Cluster randomized pragmatic trial of naloxone co-dispensing. SETTING: Safety-net health system in Denver, Colorado, between 2017 and 2020. PARTICIPANTS: Seven pharmacies were randomized. Pharmacy patients (N=768) receiving opioids were followed using automated data for 10 months. Pharmacy patients were also invited to complete surveys at baseline, 4 months, and 8 months; 325 survey participants were enrolled from November 15, 2017, to January 8, 2019. INTERVENTION: Intervention pharmacies implemented workflows to co-dispense naloxone while usual care pharmacies provided usual services. MAIN MEASURES: Survey instruments assessed opioid risk behavior; hazardous drinking; tobacco, cannabis, and other drug use; and knowledge. Naloxone dispensings and opioid dose were evaluated using pharmacy data among pharmacy patients and survey participants. Intention-to-treat analyses were conducted using generalized linear mixed models accounting for clustering at the pharmacy level. KEY RESULTS: Opioid risk behavior did not differ by trial group (P=0.52; 8-month vs. baseline adjusted risk ratio [ARR] 1.07; 95% CI 0.78, 1.47). Compared with usual care pharmacies, naloxone dispensings were higher in intervention pharmacies (ARR 3.38; 95% CI 2.21, 5.15) and participant knowledge increased (P=0.02; 8-month vs. baseline adjusted mean difference 1.05; 95% CI 0.06, 2.04). There was no difference in other substance use by the trial group. CONCLUSION: Co-dispensing naloxone with opioids effectively increased naloxone receipt and knowledge but did not increase self-reported risk behavior. TRIAL REGISTRATION: Registered at ClinicalTrials.gov ; Identifier: NCT03337100.

Combatting insects mediated biotic stress through plant associated endophytic entomopathogenic fungi in horticultural crops.

Horticultural production is a vital catalyst for economic growth, yet insect infestations reduce horticultural crop yield and quality. Pesticides and other pest control methods are used during planting to eliminate pests that cause direct and indirect losses. In such situations, endophytic entomo-pathogenic fungi (EEPF) can act as a potential tools for biological control. They protect plants by boosting growth, nutrition, morpho-physiology and salt or iron tolerance. Antixenosis, antibiosis and plant tolerance change insect performance and preferences. EEPF- plant colonisation slows herbivore development, food consumption, oviposition and larval survival. EEPF changes plant physio-chemical properties like volatile emission profile and secondary metabolite production to regulate insect pest defences. EEPF produces chitinases, laccases, amylases, and cellulases for plant defence. Recent studies focused on EEPF species' significance, isolation, identification and field application. Realizing their full potential is difficult due to insufficient mass production, storage stability and formulation. Genetic-molecular and bioinformatics can help to build EEPF-based biological control systems. Metagenomics helps study microbial EEPF taxonomy and function. Multi-omics and system biology can decode EEPF interactions with host plants and microorganisms. NGS (Next Generation Sequencing), comparative genomics, proteomics, transcriptomics, metabolomics, metatranscriptomics and microarrays are used to evaluate plant-EEPF relationships. IPM requires understanding the abiotic and biotic elements that influence plant-EEPF interaction and the physiological mechanisms of EEPF colonisation. Due to restricted research, there are hundreds of unexplored EEPFs, providing an urgent need to uncover and analyse them.

Moths (Insecta: Lepidoptera) of Delhi, India: An illustrated checklist based on museum specimens and surveys.

BACKGROUND: There have been several recent checklists, books and publications about Indian moths; however, much of this work has focused on biodiversity hotspots such as North-east India, Western Ghats and Western Himalayas. There is a lack of published literature on urban centres in India, despite the increased need to monitor insects at sites with high levels of human disturbance. In this study, we examine the moths of Delhi, the national capital region of India, one of the fastest growing mega-metropolitan cities. We present a comprehensive checklist of 338 moths species using 8 years of light trapping data (2012-2020) and examining about 2000 specimens from historical collections at the National Pusa Collection of ICAR-Indian Agricultural Research Institute, New Delhi (NPC-IARI) spanning over 100 years (1907-2020). The checklist comprises moths from 32 families spanning 14 superfamilies with Noctuoidea (48.5%) and Pyraloidea (20.4%) being the the two most dominant superfamilies. We provide links to images of live individuals and pinned specimens for all moths and provide detailed distribution records and an updated taxonomic treatment. NEW INFORMATION: This is the first comprehensive annotated checklist of the moths of Delhi. The present study adds 234 species to the biodiversity of moths from Delhi that were not reported previously, along with illustrations for 195 species.

Temporal Trends in Undervaccination: A Population-Based Cohort Study.

INTRODUCTION: Monitoring the trends in undervaccination, including that because of parental vaccine refusal or delay, can inform public health responses directed at improving vaccine confidence and vaccination coverage. METHODS: A retrospective cohort study was conducted in the Vaccine Safety Datalink. The cohort included all children born in 2004-2017 with ≥3 well-child visits between ages 2 and 23 months. Using electronic health record-based vaccination data, the average days undervaccinated was calculated for each child. Undervaccination patterns were assessed through age 23 months. Temporal trends were inspected for inflection points and were analyzed using linear regression. Nested within the cohort study, a survey was conducted to compare parent reports of vaccine refusal or delay with observed vaccination patterns. Data were analyzed in 2020. RESULTS: The study cohort consisted of 808,170 children. The percentage of children with average days undervaccinated=0 (fully vaccinated, no delays) rose from a nadir of 47.1% for the birth year 2008 to 68.4% for the birth year 2017 (ptrend<0.001). The percentage with no vaccines rose from 0.35% for the birth year 2004 to 1.28% for the birth year 2017 (ptrend<0.001). Consistent vaccine limiting was observed in 2.04% for the birth year 2017. Omission of measles, mumps, and rubella vaccine peaked at 4.76% in the birth year 2007 and declined thereafter (ptrend<0.001). On the parent survey (response rate 60.2%), a high proportion of parents of the most undervaccinated children reported refusing or delaying vaccines. CONCLUSIONS: In a 14-year cohort study, vaccination timeliness has improved. However, the small but increasing number of children who received no vaccines by age 23 months warrants additional attention.

Addressing logistical barriers to childhood vaccination using an automated reminder system and online resource intervention: A randomized controlled trial.

BACKGROUND: As the rates of vaccination decline in children with logistical barriers to vaccination, new strategies to increase vaccination are needed. The goal of this study was to develop and evaluate the effectiveness of the Vaccines For Babies (VFB) intervention, an automated reminder system with online resources to address logistical barriers to vaccination in caregivers of children enrolled in an integrated healthcare system. Effectiveness was evaluated in a randomized controlled trial. METHODS: Qualitative interviews were conducted with parents of children less than two years old to identify logistical barriers to vaccination that were used to develop the VFB intervention. VFB included automated reminders to schedule the 6- and 12-month vaccine visit linking caregivers to resources to address logistic barriers, sent to the preferred mode of outreach (text, email, and/or phone). Parents of children between 3 and 10 months of age with indicators of logistical barriers to vaccination were randomized to receive VFB or usual well child care (UC). The primary outcome was percentage of days undervaccinated at 2 years of life. A difference in differences analysis was conducted. RESULTS: Qualitative interviews with 6 parents of children less than 2 years of age identified transportation, scheduling challenges, and knowledge of vaccine timing as logistical barriers to vaccination. We enrolled 250 participants in the trial, 45% were loss to follow-up. There were no significant differences in vaccination uptake between those enrolled in UC or the VFB intervention (0.51%, p = 0.86). In Medicaid enrolled participants, there was a modest decrease in percentage of days undervaccinated in the VFB intervention compared to UC (6.3%, p = 0.07). CONCLUSION: Automated Reminders and with links to heath system resources was not shown to increase infant vaccination uptake demonstrating additional resources are needed to address the needs of caregivers experiencing logistical barriers to vaccination.

Web-Based Tailored Messaging to Increase Vaccination: A Randomized Clinical Trial.

BACKGROUND: To increase vaccine acceptance, we created a Web-based the "Vaccines and Your Baby" intervention (VAYB) that provided new parents with vaccine information messages tailored to vaccine beliefs and values. We evaluated the effectiveness of the VAYB by comparing timely uptake of infant vaccines to an untailored version of the intervention (UT) or usual care intervention (UC) only. METHODS: Between April 2016 and June 2019, we conducted a randomized clinical trial. Pregnant women and new parents were randomly assigned to the VAYB, UT, or UC arms. In the VAYB and UT arms, participants were exposed to interventions at 4 time points from pregnancy until their child was 15 months of age. The primary outcome was up-to-date status for recommended vaccines from birth to 200 days of age. A modified intent-to-treat analysis was conducted. Data were analyzed with logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We enrolled 824 participants (276 VAYB, 274 UT, 274 UC), 143 (17.4%) of whom were lost to follow-up. The up-to-date rates in the VAYB, UT, and UC arms were 91.44%, 92.86%, and 92.31%, respectively. Infants in the VAYB arm were not more likely to be up to date than infants in the UC arm (OR = 0.89; 95% CI, 0.45-1.76) or in the UT arm (OR = 0.82; 95% CI, 0.42-1.63). The odds of being up to date did not differ between UT and UC arms (OR = 1.08; 95% CI, 0.54-2.18). CONCLUSIONS: Delivering Web-based vaccine messages tailored to parents' vaccine attitudes and values did not positively impact the timely uptake of infant vaccines.

The Association between Opioid Discontinuation and Heroin Use: A Nested Case-Control Study.

BACKGROUND: Opioid prescribing guidelines recommend reducing or discontinuing opioids for chronic pain if harms of opioid treatment outweigh benefits. As opioid discontinuation becomes more prevalent, it is important to understand whether opioid discontinuation is associated with heroin use. In this study, we sought to assess the association between opioid discontinuation and heroin use documented in the medical record. METHODS: A matched nested case-control study was conducted in an integrated health plan and delivery system in Colorado. Patients receiving opioid therapy in the study period (January 2006-June 2018) were included. Opioid discontinuation was defined as ≥45 days with no opioids dispensed after initiating opioid therapy. The heroin use onset date represented the index date. Case patients were matched to up to 20 randomly selected patients without heroin use (control patients) by age, sex, calendar time, and time between initiating opioid therapy and the index date. Conditional logistic regression models estimated matched odds ratios (mOR) for the association between an opioid discontinuation prior to the index date and heroin use. RESULTS: Among 22,962 patients prescribed opioid therapy, 125 patients (0.54%) used heroin after initiating opioid therapy, of which 74 met criteria for inclusion in the analysis. The odds of opioid discontinuation were approximately two times higher in case patients (n = 74) than control patients (n = 1045; mOR = 2.19; 95% CI 1.27-3.78). CONCLUSIONS: Among patients prescribed chronic opioid therapy, the observed increased risk for heroin use associated with opioid discontinuation should be balanced with potential benefits.

Association of Opioids Prescribed to Family Members With Opioid Overdose Among Adolescents and Young Adults.

Importance: Family members are cited as a common source of prescription opioids used for nonmedical reasons. However, the overdose risk associated with exposure to opioids prescribed to family members among adolescents and young adults is not well established. Objective: To assess the association of opioids prescribed to family members with pharmaceutical opioid overdose among youth. Design, Setting, and Participants: This cohort study included 45 145 family units with a total of 72 040 adolescents and young adults aged 11 to 26 years enrolled in a Kaiser Permanente Colorado health plan in 2006 and observed through June 2018. Exposures: Opioid prescriptions and dosage dispensed to family members and youth in the past month. Main Outcomes and Measures: Fatal pharmaceutical opioid overdoses identified in vital records and nonfatal pharmaceutical opioid overdoses identified in emergency department and inpatient settings. Time to first overdose was modeled using Cox regression. Results: The study population consisted of 72 040 adolescents and young adults (mean [SD] age across follow-up, 19.3 [3.7] years; 36 646 [50.9%] girls and women) nested in 45 145 family units. Youth were more commonly exposed to prescription opioids dispensed to a family member than through their own prescriptions. During follow-up, 26 284 youth (36.5%) filled at least 1 opioid prescription, and 47 461 youth (65.9%) had at least 1 family member with a prescription. Exposure to family members with opioid prescriptions in the past month was associated with increased risk of pharmaceutical opioid overdose (adjusted hazard ratio [aHR], 2.17; 95% CI, 1.24-3.79) independent of opioids prescribed to youth (aHR, 6.62; 95% CI, 3.39-12.91). Concurrent exposure to opioid prescriptions from youth and family members was associated with substantially increased overdose risk (aHR, 12.99; 95% CI, 5.08-33.25). High dosage of total morphine milligram equivalents (MME) prescribed to family members in the past month was associated with youth overdose (0 MME vs >0 to <200 MME: aHR, 1.39; 95% CI, 0.51-3.81; 0 MME vs 200 to <600 MME: aHR, 1.49; 95% CI, 0.59-3.77; 0 MME vs ≥600 MME: aHR, 2.93; 95% CI, 1.55-5.56). Conclusions and Relevance: In this study of youth linked to family members, exposure to family members' prescribed opioids was associated with increased risk of pharmaceutical opioid overdose, independent of opioids prescribed to youth. Further interventions targeting youth and families are needed, including counseling patients about the risks of opioids to youth in their families.

Order of Live and Inactivated Vaccines and Risk of Non-vaccine-targeted Infections in US Children 11-23 Months of Age.

BACKGROUND: Some findings from observational studies have suggested that recent receipt of live vaccines may be associated with decreased non-vaccine-targeted infection risk and mortality. Our objective was to estimate risk of non-vaccine-targeted infections based on most recent vaccine type (live vaccines only, inactivated vaccines only or both concurrently) received in US children 11-23 months of age. METHODS: We conducted a retrospective cohort study within the Vaccine Safety Datalink. We examined electronic health record and immunization data from children born in 2003-2013 who received 3 diphtheria-tetanus-acellular pertussis vaccines before their first birthday. We modeled vaccine type as a time-varying exposure and estimated risk of non-vaccine-targeted infections identified in emergency department and inpatient settings, adjusting for multiple confounders. RESULTS: Among 428,608 children, 48.9% were female, 4.9% had ≥1 immunization visit with live vaccines only and 10.3% had a non-vaccine-targeted infection. In males, lower risk of non-vaccine-targeted infections was observed following last receipt of live vaccines only or live and inactivated vaccines concurrently as compared with last receipt of inactivated vaccines only [live vaccines-only adjusted hazard ratio (aHR) = 0.83, 95% confidence interval (CI): 0.72-0.94; live and inactivated vaccines concurrently aHR: 0.91, 95% CI: 0.88-0.94]. Among females, last receipt of live and inactivated vaccines concurrently was significantly associated with non-vaccine-targeted infection risk (aHR = 0.94, 95% CI: 0.91-0.97 vs. last receipt of inactivated vaccines only). CONCLUSIONS: We observed modest associations between live vaccine receipt and non-vaccine-targeted infections. In this observational study, multiple factors, including healthcare-seeking behavior, may have influenced results.