Drug addiction continues to be an important public health problem, with an estimated 22.6 million current illicit drug users in the United States alone. For many addictions, including cocaine, ...methamphetamine, and marijuana addiction, there are no approved pharmacological treatments. Behavioral treatments are effective but effects vary widely across individuals. Treatments that are effective across multiple addictions are greatly needed, and accumulating evidence suggests that one such approach may be pharmacological or behavioral interventions that enhance executive inhibitory control in addicts. Current evidence indicates that most forms of chronic drug use may be associated with significant cognitive impairments, especially in attention, working memory, and response inhibition functions. In some studies, these impairments predict poor treatment retention and outcome. A number of cognitive enhancing agents, including galantamine, modafinil, atomoxetine, methylphenidate, and guanfacine, have shown promising findings in human studies. Specific behavioral interventions, including cognitive remediation, also show promise. However, whether improvement of selective cognitive functions reduces drug use behavior remains to be determined. Cognitive enhancement to improve treatment outcomes is a novel strategy worthy of future research, as are related questions such as whether these approaches may be broadly beneficial to most addicts or best reserved for substance users with specific demonstrated cognitive impairments.
This article is part of a Special Issue entitled ‘Cognitive Enhancers’.
► Long-term drug use is associated with a wide-range of cognitive impairments. ► Cognitive impairments are potential targets for the treatment of addictive disorders. ► These impairments can be targeted by both medications and behavioral approaches. ► Cognitive enhancement to improve treatment outcomes is a novel strategy.
Objectives To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009. Methods Mortality and cancer incidence ...were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias. Results Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques. Conclusions Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.
ObjectivesTo examine exposure–response relationships between surrogates of firefighting exposure and select outcomes among previously studied US career firefighters.MethodsEight cancer and four ...non-cancer outcomes were examined using conditional logistic regression. Incidence density sampling was used to match each case to 200 controls on attained age. Days accrued in firefighting assignments (exposed-days), run totals (fire-runs) and run times (fire-hours) were used as exposure surrogates. HRs comparing 75th and 25th centiles of lagged cumulative exposures were calculated using loglinear, linear, log-quadratic, power and restricted cubic spline general relative risk models. Piecewise constant models were used to examine risk differences by time since exposure, age at exposure and calendar period.ResultsAmong 19 309 male firefighters eligible for the study, there were 1333 cancer deaths and 2609 cancer incidence cases. Significant positive associations between fire-hours and lung cancer mortality and incidence were evident. A similar relation between leukaemia mortality and fire-runs was also found. The lung cancer associations were nearly linear in cumulative exposure, while the association with leukaemia mortality was attenuated at higher exposure levels and greater for recent exposures. Significant negative associations were evident for the exposure surrogates and colorectal and prostate cancers, suggesting a healthy worker survivor effect possibly enhanced by medical screening.ConclusionsLung cancer and leukaemia mortality risks were modestly increasing with firefighter exposures. These findings add to evidence of a causal association between firefighting and cancer. Nevertheless, small effects merit cautious interpretation. We plan to continue to follow the occurrence of disease and injury in this cohort.
The increasing use of mass cytometry for analyzing clinical samples offers the possibility to perform comparative analyses across public datasets. However, challenges in batch normalization and data ...integration limit the comparison of datasets not intended to be analyzed together. Here, we present a data integration strategy, CytofIn, using generalized anchors to integrate mass cytometry datasets from the public domain. We show that low-variance controls, such as healthy samples and stable channels, are inherently homogeneous, robust against stimulation, and can serve as generalized anchors for batch correction. Single-cell quantification comparing mass cytometry data from 989 leukemia files pre- and post normalization with CytofIn demonstrates effective batch correction while recapitulating the gold-standard bead normalization. CytofIn integration of public cancer datasets enabled the comparison of immune features across histologies and treatments. We demonstrate the ability to integrate public datasets without necessitating identical control samples or bead standards for fast and robust analysis using CytofIn.
Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and ...Drug Administration for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% to 73%, with the most common being mood disorders (13% to 64%) and anxiety disorders (21% to 50%), as well as non-substance-induced psychotic disorders (<10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible transdiagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and include cholinesterase inhibitors (e.g., galantamine, rivastigmine) and monoamine transporter inhibitors (e.g., modafinil, methylphenidate). Cognitive behavioral therapy and cognitive rehabilitation also enhance executive control, while cognitive bias modification targets impairments associated with automatic processes. Cognitive enhancement to improve treatment outcomes is a novel and promising strategy, but its clinical value for the treatment of stimulant use disorder, with or without other psychiatric comorbidities, remains to be determined in future studies.
Chronic cocaine users are known to have cognitive deficits that are predictive of poor treatment response. Whether these deficits improve with medications targeting specific cognitive functions has ...not been examined in previous studies. The goal of this study was to evaluate galantamine's efficacy on selected cognitive outcomes, including measures of sustained attention, response inhibition, and attentional bias in recently abstinent cocaine users. Galantamine, a reversible and competitive inhibitor of acetylcholinesterase, is used clinically in the treatment of Alzheimer's dementia. In a randomized, double-blind, parallel-group study, 34 participants were randomized to galantamine (8 mg/day) or placebo treatment for 10 days. Cognitive and self-report mood measures were obtained at baseline and on Days 5 and 10 after the initiation of treatment. Galantamine treatment, compared to placebo, improved the reaction time,
F
(2, 50) = 8.6,
p
< .01, detection sensitivity (A'),
F
(2, 50) = 4.9,
p
< .03, number of hits,
F
(2, 50) = 4.2,
p
< .04, and number of correct rejections,
F
(2, 50) = 5.6,
p
< .02, on the Rapid Visual Information Processing task. With the exception of speeding the reaction time on the Stroop, galantamine did not affect performance on other tasks, (
p
> .05). These results demonstrate that medications can enhance cognitive function (e.g., sustained attention) in abstinent cocaine users. The potential efficacy of galantamine as a treatment for cocaine abuse needs to be further evaluated in clinical trials.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Objective To follow-up on earlier studies of the leukaemogenicity of occupational ionising radiation exposure. Methods We conducted a nested case-control analysis of leukaemia mortality in a pooled ...cohort of US nuclear workers followed through 2005. Each case was matched to four controls on attained age. Exposures were estimated from available records. General relative risk models were used to estimate the excess relative risk (ERR) of leukaemia, excluding chronic lymphocytic (CLL), acute myeloid leukaemia, chronic myeloid leukaemia and CLL while controlling for potential confounders. Preferred exposure lags and time-windows of risks were calculated using joint maximum likelihood. Dose-response was also examined using linear, linear-quadratic, categorical and restricted cubic spline models. Results There were 369 leukaemia deaths in 105 245 US nuclear workers. The adjusted ERR for non-CLL leukaemia was 0.09 (95% CI −0.17 to 0.65) per 100 mGy. Elevated non-CLL risks were observed from exposures occurring 6–14 years prior to attained age of cases (ERR per 100 mGy=1.9; 95% CI <0 to 8.0). Lagged models indicated non-linearity of risk at very low (<10 mGy) and high (>100 mGy) doses, which contributed to the imprecision of results in linear models. Similar risk attenuation was not evident in time-windows-based models. Conclusions Risk estimates were in reasonable agreement with previous estimates, with the temporality of non-CLL leukaemia risk as a dominant factor in dose-response analyses. Future research should focus on methods that improve evaluations of the dose-response, particularly in the low-dose range.
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