To examine whether mental health problems predict incident use of 12 different tobacco products in a nationally representative sample of youth and young adults.
This study analyzed Wave (W) 1 and W2 ...data from 10,533 12- to 24-year-old W1 never tobacco users in the Population Assessment of Tobacco and Health (PATH) Study. Self-reported lifetime internalizing and externalizing symptoms were assessed at W1. Past 12-month use of cigarettes, electronic nicotine delivery systems (ENDS), traditional cigars, cigarillos, filtered cigars, pipe, hookah, snus pouches, other smokeless tobacco, bidis and kreteks (youth only), and dissolvable tobacco was assessed at W2.
In multivariable regression analyses, high-severity W1 internalizing (adjusted odds ratio AOR = 1.5, 95% CI = 1.3-1.8) and externalizing (AOR = 1.3, 95% CI = 1.1-1.5) problems predicted W2 onset of any tobacco use compared to no/low/moderate severity. High-severity W1 internalizing problems predicted W2 use onset across most tobacco products. High-severity W1 externalizing problems predicted onset of any tobacco (AOR = 1.6, 95% CI = 1.3-1.8), cigarettes (AOR = 1.4, 95% CI = 1.0-2.0), ENDS (AOR = 1.8, 95% CI = 1.5-2.1), and cigarillos (AOR = 1.5, 95% CI = 1.0-2.1) among youth only.
Internalizing and externalizing problems predicted onset of any tobacco use. However, findings differed for internalizing and externalizing problems across tobacco products, and by age, gender, and race/ethnicity. In addition to screening for tobacco product use, health care providers should screen for a range of mental health problems as a predictor of tobacco use. Interventions addressing mental health problems may prevent youth from initiating tobacco use.
Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including ...cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients.
This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index.
A total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6).
Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts.
Despite widespread use of formalin-fixed, paraffin-embedded (FFPE) tissue in clinical and research settings, potential effects of variable tissue processing remain largely unknown.
To elucidate ...molecular effects associated with clinically relevant preanalytical variability, the National Cancer Institute initiated the Biospecimen Preanalytical Variables (BPV) program.
The BPV program, a well-controlled series of systematic, blind and randomized studies, investigated whether a delay to fixation (DTF) or time in fixative (TIF) affects the quantity and quality of DNA and RNA isolated from FFPE colon, kidney, and ovarian tumors in comparison to case-matched snap-frozen controls.
DNA and RNA yields were comparable among FFPE biospecimens subjected to different DTF and TIF time points. DNA and RNA quality metrics revealed assay- and time point-specific effects of DTF and TIF. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was superior when assessing RNA quality, consistently detecting differences between FFPE and snap-frozen biospecimens and among DTF and TIF time points. RNA Integrity Number and DV
(representing the percentage of RNA fragments longer than 200 nucleotides) displayed more limited sensitivity. Differences in DNA quality (Q-ratio) between FFPE and snap-frozen biospecimens and among DTF and TIF time points were detected with a qPCR-based assay.
DNA and RNA quality may be adversely affected in some tumor types by a 12-hour DTF or a TIF of 72 hours. Results presented here as well as those of additional BPV molecular analyses underway will aid in the identification of acceptable delays and optimal fixation times, and quality assays that are suitable predictors of an FFPE biospecimen's fit-for-purpose.
Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal ...mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.
The Restoring Insulin Secretion (RISE) Adult Medication Study compared pharmacological approaches targeted to improve β-cell function in individuals with impaired glucose tolerance (IGT) or ...treatment-naive type 2 diabetes of <12 months duration.
A total of 267 adults with IGT (
= 197, 74%) or recently diagnosed type 2 diabetes (
= 70, 26%) were studied. Participants were randomized to receive 12 months of metformin alone, 3 months of insulin glargine with a target fasting glucose <5 mmol/L followed by 9 months of metformin, 12 months of liraglutide combined with metformin, or 12 months of placebo. β-Cell function was assessed using hyperglycemic clamps at baseline, 12 months (on treatment), and 15 months (3 months off treatment). The primary outcome was β-cell function at 15 months compared with baseline.
All three active treatments produced on-treatment reductions in weight and improvements in HbA
compared with placebo; the greatest reductions were seen in the liraglutide plus metformin group. At 12 months, glucose-stimulated C-peptide responses improved in the three active treatment groups and were greatest in the liraglutide plus metformin group, but the arginine-stimulated incremental C-peptide response was reduced in the liraglutide plus metformin group. Despite on-treatment benefits, 3 months after treatment withdrawal there were no sustained improvements in β-cell function in any treatment group.
In adults with IGT or recently diagnosed type 2 diabetes, interventions that improved β-cell function during active treatment failed to produce persistent benefits after treatment withdrawal. These observations suggest that continued intervention may be required to alter the progressive β-cell dysfunction in IGT or early type 2 diabetes.
Within recent years, public health interventions have become technology based to reflect the digital age we currently live in and appeal to the public in innovative and novel ways. The Internet ...breaks down boundaries distance imposes and increases our ability to reach and connect with people. Internet-based interventions have the potential to expand access to effective behavioral interventions (EBIs). The US National HIV/AIDS Strategy states that people living with HIV should have access to EBIs such as healthy relationships (HR) to help them develop safe sex and disclosure skills. However, access to HR is limited across the country, especially for people in remote or rural areas. Internet-based healthy relationships video groups (HR-VG) delivered at home or community-based organizations (CBOs) can possibly expand access. This study assesses the preferences of women living with HIV (WLH) for participation in HR-VG among 21 WLH who participated in a randomized control trial (RCT) testing HR-VG and completed open-ended semi-structured telephone interviews. Transcripts were thematically analyzed to determine advantages and disadvantages of home or CBO delivery of HR-VG. Themes relating to convenience, technology access, privacy, distractions, HIV serostatus disclosure, and social opportunities were identified as advantages or disadvantages to participating in HR-VG at each location. Overall, privacy was the most salient concern of accessing HR-VG at home or at a CBO. Considering the concerns expressed by WLH, further studies are needed to assess how an Internet-based intervention delivered at home for WLH can maintain privacy while being cost effective.
Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 ...vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development.
Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose ‘ChAd’ (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or ‘BNT’ (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8–12 weeks later with either the homologous vaccine, or ‘Mod’ (mRNA-1273, Spikevax, Moderna) or ‘NVX’ (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration.
In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N = 540, 45% female) or BNT (N = 532, 39% female) as part of the national vaccination programme.
In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95% CI (confidence interval): 8.2, 11.5) at D28 to 6.2 (95% CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95% CI:2.5,3.5) to 2.4 (95% CI:1.9, 3.0).
In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The adjusted GMR (aGMR) for BNT/Mod compared with BNT/BNT increased from 1.36 (95% CI: 1.17, 1.58) at D28 to 1.52 (95% CI: 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95% CI: 0.47, 0.64) at day 28 and 0.62 (95% CI: 0.49, 0.78) at day 196.
Heterologous ChAd-primed schedules produced and maintained the largest T-cell responses until D196. Immunisation with BNT/NVX generated a qualitatively different antibody response to BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels of neutralising antibodies.
Heterologous ChAd-primed schedules remain more immunogenic over time in comparison to ChAd/ChAd. BNT-primed schedules with a second dose of either mRNA vaccine also remain more immunogenic over time in comparison to BNT/NVX. The emerging data on mixed schedules using the novel vaccine platforms deployed in the COVID-19 pandemic, suggest that heterologous priming schedules might be considered as a viable option sooner in future pandemics. ISRCTN:27841311 EudraCT:2021-001275-16.
•Heterologous versus homologous AZ-primed schedules retain higher antibodies over time.•Priming schedules with two mRNA vaccine doses remain the most humorally immunogenic.•Neutralising antibody response is proportionally greater in Pfizer/Novavax.•Novavax-boosted regimens are less immunogenic in participants with greater BMI.•Heterologous priming schedules should be considered sooner in future pandemics.
On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated ...with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.
Abstract Background Childhood abuse and neglect have been linked with alcohol disorders in adulthood yet less is known about the potential of early trauma to influence transitions in stages of ...alcohol involvement among women. Study aims were to (1) identify stages of women's alcohol involvement, (2) examine the probability of transitions between stages, and (3) investigate the influence of four domains of childhood abuse and neglect (sexual abuse, physical abuse, neglect, and witness to domestic violence), assessed individually and as poly-victimization, on transitions. Methods The sample consisted of 11,750 adult female current drinkers identified in Wave 1 (2001–2002) and re-interviewed in Wave 2 (2004–2005) of the National Epidemiological Survey on Alcohol and Related Conditions. Results Three stages of alcohol involvement emerged from latent class analysis of 11 DSM-IV abuse/dependence criteria: severe (1.5% at Wave 1, 1.9% at Wave 2), hazardous (13.6% at Wave 1, 16.0% at Wave 2), and non-problem drinking (82.1% at Wave 1, 84.5% at Wave 2). Adjusted latent transition analyses determined transition probabilities between stages across waves. Women reporting any childhood abuse and neglect were more likely to advance from the non-problem drinking class at Wave 1 to severe (AOR = 3.90, 95% CI = 1.78–8.53) and hazardous (AOR = 1.56, 95% CI = 1.22–2.01) drinking classes at Wave 2 relative to women without this history. Associations were also observed between individual domains and transition from no problems to severe alcohol stage. Conclusions Results suggest a long-term impact of childhood abuse and neglect as drivers of progression in women's alcohol involvement.
Routine laboratory studies are often obtained daily after total joint arthroplasty (TJA) regardless of medical management. The purpose of this study was to investigate the utility of routine basic ...metabolic panel (BMP) tests after TJA. Furthermore, the goal was to identify factors that may predispose patients to abnormal laboratory values that require medical intervention.
A retrospective review was performed on 767 patients who underwent primary TJA at a single institution. Preoperative and postoperative potassium, sodium, creatinine, and glucose values were collected along with demographic data, comorbidities, and procedural characteristics. Multivariable logistic regression models were used to determine independent risk factors for abnormal postoperative laboratory values.
Diabetes was associated with abnormal glucose (odds ratio OR 23.4, 95% confidence interval CI 10.7-51.0, P < .001), while chronic kidney disease was associated with abnormal creatinine (OR 3.1, 95% CI 1.7-5.8, P < .001) and potassium (OR 1.8, 95% CI 1.1-2.8, P = .014) requiring medical intervention. An abnormal preoperative laboratory value was also associated with medical treatment for each of sodium, potassium, and creatinine (all P < .001). Average number of BMP tests collected for patients who did not receive medical intervention was 2.8. This equated to $472,372.56 in total hospital charges.
Cost containment while maintaining high-quality patient care is critical. Routine postoperative BMP tests in patients with normal preoperative values without major medical comorbidities do not contribute to actionable information. Patients with diabetes, chronic kidney disease, or with abnormal preoperative values should obtain a BMP after TJA.
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