Benzodiazepine and Unhealthy Alcohol Use Among Adult Outpatients

OBJECTIVES: Concomitant excessive alcohol consumption and benzodiazepine use is associated with adverse health outcomes. We examined associations of unhealthy alcohol use and other patient characteristics with benzodiazepine use. STUDY DESIGN: A cross-sectional analysis of 2,089,525 Kaiser Permanente of Northern California outpatients screened for unhealthy alcohol use in primary care between November 1, 2014, and December 31, 2016. METHODS: We fit multivariable generalized linear models to estimate the associations between unhealthy alcohol use and benzodiazepine dispensation and, among patients who were dispensed a benzodiazepine, mean doses (in mean lorazepam-equivalent daily doses [LEDDs]) and prescription durations. We controlled for patient sex, age, race/ethnicity, estimated household income, Charlson Comorbidity Index (CCI) score, anxiety disorder, alcohol use disorder, insomnia, musculoskeletal pain, and epilepsy. RESULTS: In the 12 months centered around (6 months before and 6 months after) the first alcohol-screening visit, 7.5% of patients used benzodiazepines. The following characteristics were independently associated with higher rates of benzodiazepine use, higher LEDD, and longer prescription duration: older age, white race/ethnicity, lower estimated household income, higher CCI score, and the presence of an anxiety disorder, insomnia, musculoskeletal pain, or epilepsy. Women and patients with an alcohol use disorder or unhealthy alcohol use, compared with men and patients with low-risk drinking or abstinence, were more likely to use a benzodiazepine; however, their LEDDs were lower and their prescription durations were shorter. CONCLUSIONS: Benzodiazepine use in primary care was associated with older age, female sex, white race/ethnicity, lower socioeconomic status, and unhealthy alcohol use. These findings may be applied to develop policies and interventions to promote judicious benzodiazepine use

Using concurrent EEG and fMRI to probe the state of the brain in schizophrenia

Perceptional abnormalities in schizophrenia are associated with hallucinations and delusions, but also with negative symptoms and poor functional outcome. Perception can be studied using EEG-derived event related potentials (ERPs). Because of their excellent temporal resolution, ERPs have been used to ask when perception is affected by schizophrenia. Because of its excellent spatial resolution, functional magnetic resonance imaging (fMRI) has been used to ask where in the brain these effects are seen. We acquired EEG and fMRI data simultaneously to explore when and where auditory perception is affected by schizophrenia. Thirty schizophrenia (SZ) patients and 23 healthy comparison subjects (HC) listened to 1000 Hz tones occurring about every second. We used joint independent components analysis (jICA) to combine EEG-based event-related potential (ERP) and fMRI responses to tones. Five ERP-fMRI joint independent components (JIC) were extracted. The “N100” JIC had temporal weights during N100 (peaking at 100 ms post-tone onset) and fMRI spatial weights in superior and middle temporal gyri (STG/MTG); however, it did not differ between groups. The “P200” JIC had temporal weights during P200 and positive fMRI spatial weights in STG/MTG and frontal areas, and negative spatial weights in the nodes of the default mode network (DMN) and visual cortex. Groups differed on the “P200” JIC: SZ had smaller “P200” JIC, especially those with more severe avolition/apathy. This is consistent with negative symptoms being related to perceptual deficits, and suggests patients with avolition/apathy may allocate too few resources to processing external auditory events and too many to processing internal events

Did I Do That? Abnormal Predictive Processes in Schizophrenia When Button Pressing to Deliver a Tone

Motor actions are preceded by an efference copy of the motor command, resulting in a corollary discharge of the expected sensation in sensory cortex. These mechanisms allow animals to predict sensations, suppress responses to self-generated sensations, and thereby process sensations efficiently and economically. During talking, patients with schizophrenia show less evidence of pretalking activity and less suppression of the speech sound, consistent with dysfunction of efference copy and corollary discharge, respectively. We asked if patterns seen in talking would generalize to pressing a button to hear a tone, a paradigm translatable to less vocal animals. In 26 patients [23 schizophrenia, 3 schizoaffective (SZ)] and 22 healthy controls (HC), suppression of the N1 component of the auditory event-related potential was estimated by comparing N1 to tones delivered by button presses and N1 to those tones played back. The lateralized readiness potential (LRP) associated with the motor plan preceding presses to deliver tones was estimated by comparing right and left hemispheres' neural activity. The relationship between N1 suppression and LRP amplitude was assessed. LRP preceding button presses to deliver tones was larger in HC than SZ, as was N1 suppression. LRP amplitude and N1 suppression were correlated in both groups, suggesting stronger efference copies are associated with stronger corollary discharges. SZ have reduced N1 suppression, reflecting corollary discharge action, and smaller LRPs preceding button presses to deliver tones, reflecting the efference copy of the motor plan. Effects seen during vocalization largely extend to other motor acts more translatable to lab animals

Abnormal coupling between DMN and delta and beta band EEG in psychotic patients

Common-phase synchronization of neuronal oscillations is a mechanism by which distributed brain regions can be integrated into transiently stable networks. Based on the hypothesis that schizophrenia is characterized by deficits in functional integration within neuronal networks, this study aimed to explore whether psychotic patients exhibit differences in brain regions involved in integrative mechanisms. We report an EEG-informed fMRI analysis of eyes-open resting state data collected from patients and healthy controls at two study sites. Global field synchronization (GFS) was chosen as an EEG measure indicating common-phase synchronization across electrodes. Several brain clusters appeared to be coupled to GFS differently in patients and controls: Activation in brain areas belonging to the default mode network (DMN) were negatively associated to GFS delta (1 - 3.5Hz) and positively to GFS beta (13 - 30Hz) bands in patients, whereas controls showed an opposite pattern for both GFS frequency bands in those regions; activation in extrastriate visual cortex was inversely related to GFS alpha1 (8.5 - 10.5Hz) band in healthy controls, while patients had a tendency towards a positive relationship. Taken together, the GFS measure might be useful for detecting additional aspects of deficient functional network integration in psychosis

Abnormal Coupling Between Default Mode Network and Delta and Beta Band Brain Electric Activity in Psychotic Patients

Common-phase synchronization of neuronal oscillations is a mechanism by which distributed brain regions can be integrated into transiently stable networks. Based on the hypothesis that schizophrenia is characterized by deficits in functional integration within neuronal networks, this study aimed to explore whether psychotic patients exhibit differences in brain regions involved in integrative mechanisms. We report an electroencephalography (EEG)-informed functional magnetic resonance imaging analysis of eyes-open resting-state data collected from patients and healthy controls at two study sites. Global field synchronization (GFS) was chosen as an EEG measure indicating common-phase synchronization across electrodes. Several brain clusters appeared to be coupled to GFS differently in patients and controls. Activation in brain areas belonging to the default mode network was negatively associated to GFS delta (1-3.5 Hz) and positively to GFS beta (13-30 Hz) bands in patients, whereas controls showed an opposite pattern for both GFS frequency bands in those regions; activation in the extrastriate visual cortex was inversely related to GFS alpha1 (8.5-10.5 Hz) band in healthy controls, while patients had a tendency toward a positive relationship. Taken together, the GFS measure might be useful for detecting additional aspects of deficient functional network integration in psychosis

Healthcare utilization of individuals with substance use disorders following Affordable Care Act implementation in a California healthcare system.

BackgroundPractitioners expected the Affordable Care Act (ACA) to increase availability of health services and access to treatment for Americans with substance use disorders (SUDs). Yet research has not examined the associations among ACA enrollment mechanisms, deductibles, and the use of SUD treatment and other healthcare services. Understanding these relationships can inform future healthcare policy.MethodsWe conducted a longitudinal analysis of patients with SUDs newly enrolled in the Kaiser Permanente Northern California health system in 2014 (N = 6957). Analyses examined the likelihood of service utilization (primary care, specialty SUD treatment, psychiatry, inpatient, and emergency department [ED]) over three years after SUD diagnosis, and associations with enrollment mechanisms (ACA Exchange vs. other), deductibles (none, $1-$999 [low] and ≥$1000 [high]), membership duration, psychiatric comorbidity, and demographic characteristics. We also evaluated whether the enrollment mechanism moderated the associations between deductible limits and utilization likelihood.ResultsService utilization was highest in the 6 months after SUD diagnosis, decreased in the following 6 months, and remained stable in years 2-3. Relative to patients with no deductible, those with a high deductible had lower odds of using all health services except SUD treatment; associations with primary care and psychiatry were strongly negative among Exchange enrollees. Among non-Exchange enrollees, patients with deductibles were more likely than those without deductibles to receive SUD treatment. Exchange enrollment compared to other mechanisms was associated with less ED use. Psychiatric comorbidity was associated with greater use of all services. Nonwhite patients were less likely to initiate SUD and psychiatry treatment.ConclusionsHigher deductibles generally were associated with use of fewer health services, especially in combination with enrollment through the Exchange. The role of insurance factors, psychiatric comorbidity and race/ethnicity in health services for people with SUDs are important to consider as health policy evolves

Healthcare utilization of individuals with substance use disorders following Affordable Care Act implementation in a California healthcare system.

BackgroundPractitioners expected the Affordable Care Act (ACA) to increase availability of health services and access to treatment for Americans with substance use disorders (SUDs). Yet research has not examined the associations among ACA enrollment mechanisms, deductibles, and the use of SUD treatment and other healthcare services. Understanding these relationships can inform future healthcare policy.MethodsWe conducted a longitudinal analysis of patients with SUDs newly enrolled in the Kaiser Permanente Northern California health system in 2014 (N = 6957). Analyses examined the likelihood of service utilization (primary care, specialty SUD treatment, psychiatry, inpatient, and emergency department [ED]) over three years after SUD diagnosis, and associations with enrollment mechanisms (ACA Exchange vs. other), deductibles (none, $1-$999 [low] and ≥$1000 [high]), membership duration, psychiatric comorbidity, and demographic characteristics. We also evaluated whether the enrollment mechanism moderated the associations between deductible limits and utilization likelihood.ResultsService utilization was highest in the 6 months after SUD diagnosis, decreased in the following 6 months, and remained stable in years 2-3. Relative to patients with no deductible, those with a high deductible had lower odds of using all health services except SUD treatment; associations with primary care and psychiatry were strongly negative among Exchange enrollees. Among non-Exchange enrollees, patients with deductibles were more likely than those without deductibles to receive SUD treatment. Exchange enrollment compared to other mechanisms was associated with less ED use. Psychiatric comorbidity was associated with greater use of all services. Nonwhite patients were less likely to initiate SUD and psychiatry treatment.ConclusionsHigher deductibles generally were associated with use of fewer health services, especially in combination with enrollment through the Exchange. The role of insurance factors, psychiatric comorbidity and race/ethnicity in health services for people with SUDs are important to consider as health policy evolves

Manganese exposure and working memory-related brain activity in smallholder farmworkers in Costa Rica: Results from a pilot study

Main sources of manganese (Mn) in the general population are diet and drinking water. Mn is also found in ethylene bisdithiocarbamate (EBDC) fungicides used in agriculture or emitted into the air by ferromanganese plants and welding fumes, which can be additional environmental and occupational sources of exposure. High occupational Mn exposure has been linked with motor, behavioral, and cognitive impairment, but its effects on neural function remain poorly understood. We conducted a functional neuroimaging study in a sample of 48 farmworkers in Zarcero County, Costa Rica, an agricultural region where EBDC fungicides are sprayed. We measured Mn concentrations in farmworkers' toenails (n = 40 farmworkers) and hair (n = 33 farmworkers), and recorded brain activity in the dorsolateral prefrontal cortex during a letter-retrieval working memory task using functional near-infrared spectroscopy (fNIRS). We estimated exposure-outcome associations using multivariable linear regression models adjusted for age and education level. Geometric mean (geometric standard deviation) toenail and hair Mn concentrations were 0.40 μg/g (3.52) and 0.24 μg/g (3.54), respectively. We did not find strong evidence that Mn concentrations were associated with working memory-related brain activity in this sample of farmworkers; we also found null associations between working memory task accuracy and brain activity. However, our small sample size may have limited our ability to detect small effect sizes with statistical precision. Our study demonstrates that fNIRS can be a useful and feasible tool in environmental epidemiology for examining the effects of toxicants, like Mn, on neural function. This may prove to be important for elucidating neuropathological pathways that underlie previously reported associations of elevated Mn exposure with neurotoxic effects

Associations between alcohol brief intervention in primary care and drinking and health outcomes in adults with hypertension and type 2 diabetes: a population-based observational study

Objectives To evaluate associations between alcohol brief intervention (BI) in primary care and 12-month drinking outcomes and 18-month health outcomes among adults with hypertension and type 2 diabetes (T2D).Design A population-based observational study using electronic health records data.Setting An integrated healthcare system that implemented system-wide alcohol screening, BI and referral to treatment in adult primary care.Participants Adult primary care patients with hypertension (N=72 979) or T2D (N=19 642) who screened positive for unhealthy alcohol use between 2014 and 2017.Main outcome measures We examined four drinking outcomes: changes in heavy drinking days/past 3 months, drinking days/week, drinks/drinking day and drinks/week from baseline to 12-month follow-up, based on results of alcohol screens conducted in routine care. Health outcome measures were changes in measured systolic and diastolic blood pressure (BP) and BP reduction ≥3 mm Hg at 18-month follow-up. For patients with T2D, we also examined change in glycohaemoglobin (HbA1c) level and ‘controlled HbA1c’ (HbA1c<8%) at 18-month follow-up.Results For patients with hypertension, those who received BI had a modest but significant additional −0.06 reduction in drinks/drinking day (95% CI −0.11 to −0.01) and additional −0.30 reduction in drinks/week (95% CI −0.59 to −0.01) at 12 months, compared with those who did not. Patients with hypertension who received BI also had higher odds for having clinically meaningful reduction of diastolic BP at 18 months (OR 1.05, 95% CI 1.00 to 1.09). Among patients with T2D, no significant associations were found between BI and drinking or health outcomes examined.Conclusions Alcohol BI holds promise for reducing drinking and helping to improve health outcomes among patients with hypertension who screened positive for unhealthy drinking. However, similar associations were not observed among patients with T2D. More research is needed to understand the heterogeneity across diverse subpopulations and to study BI’s long-term public health impact

Manganese exposure and working memory-related brain activity in smallholder farmworkers in Costa Rica : Results from a pilot study

Main sources of manganese (Mn) in the general population are diet and drinking water. Mn is also found in ethylene bisdithiocarbamate (EBDC) fungicides used in agriculture or emitted into the air by ferromanganese plants and welding fumes, which can be additional environmental and occupational sources of exposure. High occupational Mn exposure has been linked with motor, behavioral, and cognitive impairment, but its effects on neural function remain poorly understood. We conducted a functional neuroimaging study in a sample of 48 farmworkers in Zarcero County, Costa Rica, an agricultural region where EBDC fungicides are sprayed. We measured Mn concentrations in farmworkers' toenails (n = 40 farmworkers) and hair (n = 33 farmworkers), and recorded brain activity in the dorsolateral prefrontal cortex during a letter-retrieval working memory task using functional near-infrared spectroscopy (fNIRS). We estimated exposure-outcome associations using multivariable linear regression models adjusted for age and education level. Geometric mean (geometric standard deviation) toenail and hair Mn concentrations were 0.40 μg/g (3.52) and 0.24 μg/g (3.54), respectively. We did not find strong evidence that Mn concentrations were associated with working memory-related brain activity in this sample of farmworkers; we also found null associations between working memory task accuracy and brain activity. However, our small sample size may have limited our ability to detect small effect sizes with statistical precision. Our study demonstrates that fNIRS can be a useful and feasible tool in environmental epidemiology for examining the effects of toxicants, like Mn, on neural function. This may prove to be important for elucidating neuropathological pathways that underlie previously reported associations of elevated Mn exposure with neurotoxic effects