Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Unsupervised remote digital cognitive assessment makes frequent testing feasible and allows for measurement of learning across days on participants’ own devices. More rapid detection of diminished learning may provide a potentially valuable metric that is sensitive to cognitive change over short intervals. In this study we examine feasibility and predictive validity of a novel digital assessment that measures learning of the same material over 7 days in older adults.

The Boston Remote Assessment for Neurocognitive Health (BRANCH) (Papp et al., 2021) is a web-based assessment administered over 7 consecutive days repeating the same stimuli each day to capture multi-day-learning slopes. The assessment includes Face-Name (verbal-visual associative memory), Groceries-Prices (numeric-visual associative memory), and Digits-Signs (speeded processing of numeric-visual associations). Our sample consisted of200 cognitively unimpaired older adults enrolled in ongoing observational studies (mean age=74.5, 63% female, 87% Caucasian, mean education=16.6) who completed the tasks daily, at home, on their own digital devices. Participants had previously completed in-clinic paper-and-pencil tests to compute a Preclinical Alzheimer’s Cognitive Composite (PACC-5). Mixed-effects models controlling for age, sex, and education were used to observe the associations between PACC-5 scores and both initial performance and multi-day learning on the three BRANCH measures.

Adherence was high with 96% of participants completing all seven days of consecutive assessment; demographic factors were not associated with differences in adherence. Younger participants had higher Day 1 scores all three measures, and learning slopes on Digit-Sign. Female participants performed better on Face-Name (T=3.35, p<.001) and Groceries-Prices (T=2.00, p=0.04) on Day 1 but no sex differences were seen in learning slopes; there were no sex differences on Digit-Sign. Black participants had lower Day 1 scores on Face-Name (T=-3.34, p=0.003) and Digit Sign (T=3.44, p=0.002), but no racial differences were seen on learning slopes for any measure. Education was not associated with any measure. First day performance on Face-Name (B=0.39, p<.001), but not learning slope B=0.008, p=0.302) was associated with the PACC5. For Groceries-Prices, both Day 1 (B=0.27, p<.001) and learning slope (B=0.02, p=0.03) were associated with PACC-5. The Digit-Sign scores at Day 1 (B=0.31, p<.001) and learning slope (B=0.06, p<.001) were also both associated with PACC-5.

Seven days of remote, brief cognitive assessment was feasible in a sample of cognitively unimpaired older adults. Although various demographic factors were associated with initial performance on the tests, multi-day-learning slopes were largely unrelated to demographics, signaling the possibility of its utility in diverse samples. Both initial performance and learning scores on an associative memory and processing speed test were independently related to baseline cognition indicating that these tests’ initial performance and learning metrics are convergent but unique in their contributions. The findings signal the value of measuring differences in learning across days as a means towards sensitively identifying differences in cognitive function before signs of frank impairment are observed. Next steps will involve identifying the optimal way to model multi-day learning on these subtests to evaluate their potential associations with Alzheimer’s disease biomarkers.

Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions.

A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP.

In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3.

History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

To examine differences in surgical practices between salaried and fee-for-service (FFS) surgeons for two common degenerative spine conditions. Surgeons may offer different treatments for similar conditions on the basis of their compensation mechanism.

The study assessed the practices of 63 spine surgeons across eight Canadian provinces (39 FFS surgeons and 24 salaried) who performed surgery for two lumbar conditions: stable spinal stenosis and degenerative spondylolisthesis. The study included a multicenter, ambispective review of consecutive spine surgery patients enrolled in the Canadian Spine Outcomes and Research Network registry between October 2012 and July 2018. The primary outcome was the difference in type of procedures performed between the two groups. Secondary study variables included surgical characteristics, baseline patient factors, and patient-reported outcome.

For stable spinal stenosis (n = 2234), salaried surgeons performed statistically fewer uninstrumented fusion (p < 0.05) than FFS surgeons. For degenerative spondylolisthesis (n = 1292), salaried surgeons performed significantly more instrumentation plus interbody fusions (p < 0.05). There were no statistical differences in patient-reported outcomes between the two groups.

Surgeon compensation was associated with different approaches to stable lumbar spinal stenosis and degenerative lumbar spondylolisthesis. Salaried surgeons chose a more conservative approach to spinal stenosis and a more aggressive approach to degenerative spondylolisthesis, which highlights that remuneration is likely a minor determinant in the differences in practice of spinal surgery in Canada. Further research is needed to further elucidate which variables, other than patient demographics and financial incentives, influence surgical decision-making.

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.