We used 20 de novo genome assemblies to probe the speciation history and architecture of gene flow in rapidly radiating
butterflies. Our tests to distinguish incomplete lineage sorting from ...introgression indicate that gene flow has obscured several ancient phylogenetic relationships in this group over large swathes of the genome. Introgressed loci are underrepresented in low-recombination and gene-rich regions, consistent with the purging of foreign alleles more tightly linked to incompatibility loci. Here, we identify a hitherto unknown inversion that traps a color pattern switch locus. We infer that this inversion was transferred between lineages by introgression and is convergent with a similar rearrangement in another part of the genus. These multiple de novo genome sequences enable improved understanding of the importance of introgression and selective processes in adaptive radiation.
Aims
To estimate the influence of non‐medical use of prescription opioids (NMUPO) on heroin initiation among US veterans receiving medical care.
Design
Using a multivariable Cox regression model, we ...analyzed data from a prospective, multi‐site, observational study of HIV‐infected and an age/race/site‐matched control group of HIV‐uninfected veterans in care in the United States. Approximately annual behavioral assessments were conducted and contained self‐reported measures of NMUPO and heroin use.
Setting
Veterans Health Administration (VHA) infectious disease and primary care clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh and Washington, DC.
Participants
A total of 3396 HIV‐infected and uninfected patients enrolled into the Veterans Aging Cohort Study who reported no life‐time NMUPO or heroin use, had no opioid use disorder diagnoses at baseline and who were followed between 2002 and 2012.
Measurements
The primary outcome measure was self‐reported incident heroin use and the primary exposure of interest was new‐onset NMUPO. Our final model was adjusted for socio‐demographics, pain interference, prior diagnoses of post‐traumatic stress disorder and/or depression and self‐reported other substance use.
Findings
Using a multivariable Cox regression model, we found that non‐medical use of prescription opioids NMUPO was associated positively and independently with heroin initiation adjusted hazard ratio (AHR) = 5.43, 95% confidence interval (CI) = 4.01, 7.35.
Conclusions
New‐onset non‐medical use of prescription opioids (NMUPO) is a strong risk factor for heroin initiation among HIV‐infected and uninfected veterans in the United States who reported no previous history of NMUPO or illicit opioid use.
•Urine drug testing is recommended for all patients receiving opioid therapy.•Whites are at higher risk of opioid overdose.•Yet blacks are more likely to receive urine drug testing (UDT).•Blacks are ...more likely to have opioids discontinued following a positive UDT.•A more universal approach to urine drug testing is needed.
Among patients prescribed long-term opioid therapy (LTOT) for chronic pain, no study has yet examined how clinicians respond to evidence of illicit drug use and whether the decision to discontinue opioids is influenced by a patient’s race.
Among outpatients of black and white race initiating LTOT through the VA between 2000 and 2010, we reviewed electronic medical records to determine whether opioids were discontinued within 60 days of a positive urine drug test. Logistic regression was used to examine differences by race.
Among 15,366 patients of black (48.1%) or white (51.9%) race initiating LTOT from 2000 to 2010, 20.5% (25.5% of blacks vs. 15.8% of whites, P <. 001) received a urine drug test within the first 6 months of treatment; 13.8% tested positive for cannabis and 17.4% for cocaine. LTOT was discontinued in 11.4% of patients who tested positive for cannabis and in 13.1% of those who tested positive for cocaine. Among patients testing positive for cannabis, blacks were 2.1 times more likely than whites to have LTOT discontinued (adjusted odds ratio AOR 2.06, 95% confidence interval CI 1.04–4.08). Among patients testing positive for cocaine, blacks were 3.3 times more likely than whites to have LTOT discontinued (AOR 3.30, CI 1.28–8.53).
Among patients testing positive for illicit drug use while receiving LTOT, clinicians are substantially more likely to discontinue opioids when the patient is black. A more universal approach to administering and responding to urine drug testing is urgently needed.
Opioid prescribing remains common despite known overdose-related harms. Less is known about links to nonoverdose morbidity. We determined the association between prescribed opioid receipt with ...incident cardiovascular disease (CVD) using data from the Veterans Aging Cohort Study, a national prospective cohort of Veterans with/without Human Immunodeficiency Virus (HIV) receiving Veterans Health Administration care. Selected participants had no/minimal prior exposure to prescription opioids, no opioid use disorder, and no severe illness 1 year after the study start date (baseline period). We ascertained prescription opioid exposure over 3 years after the baseline period using outpatient pharmacy fill/refill data. Incident CVD ascertainment began at the end of the prescribed opioid exposure ascertainment period until the first incident CVD event, death, or September 30, 2015. We used adjusted Cox proportional hazards regression models with matching weights using propensity scores for opioid receipt to estimate CVD risk. Among 49,077 patients, 30% received opioids; the median age was 49 years, 97% were male, 49% were Black, and 47% were currently smoking. Prevalence of hypertension, diabetes, current smoking, alcohol and cocaine use disorder, and depression was higher in patients receiving opioids versus those not but were well-balanced by matching weights. Unadjusted CVD incidence rates per 1,000-person-years were higher among those receiving opioids versus those not: 17.4 (95% confidence interval CI, 16.5-18.3) versus 14.7 (95% CI, 14.2-15.3). In adjusted analyses, those receiving opioids versus those not had an increased hazard of incident CVD (adjusted hazard ratio 1.16 95% CI, 1.08-1.24). Prescribed opioids were associated with increased CVD incidence, making opioids a potential modifiable CVD risk factor. PERSPECTIVE: In a propensity score weighted analysis of Veterans Administration data, prescribed opioids compared to no opioids were associated with an increased hazard of incident CVD. Higher opioid doses compared with lower doses were associated with increased hazard of incident CVD. Opioids are a potentially modifiable CVD risk factor.
Increased long-term prescription of opioids and/or benzodiazepines necessitates evaluating risks associated with their receipt. We sought to evaluate the association between long-term opioids and/or ...benzodiazepines and mortality in HIV-infected patients receiving antiretroviral therapy and uninfected patients.
Prospective analysis of all-cause mortality using multivariable methods and propensity score matching among HIV-infected patients receiving antiretroviral therapy and uninfected patients.
Of 64,602 available patients (16,989 HIV-infected and 47,613 uninfected), 27,128 (exposed and unexposed to long-term opioids and/or benzodiazepines) were 1:1 matched by propensity score. The hazard ratio for death was 1.40 95% confidence interval (CI): 1.22 to 1.61 for long-term opioid receipt, 1.26 (95% CI: 1.08 to 1.48) for long-term benzodiazepine receipt, and 1.56 (95% CI: 1.26 to 1.92) for long-term opioid and benzodiazepine receipt. There was an interaction (P = 0.01) between long-term opioid receipt and HIV status with mortality. For long-term opioid receipt, the hazard ratio was 1.46 (95% CI: 1.15 to 1.87) among HIV-infected patients, and 1.25 (95% CI: 1.05 to 1.49) among uninfected patients. Mortality risk was increased for patients receiving both long-term opioids and benzodiazepines when opioid doses were ≥ 20 mg morphine-equivalent daily dose and for patients receiving long-term opioids alone when doses were ≥ 50 mg morphine-equivalent daily dose.
Long-term opioid receipt was associated with an increased risk of death; especially with long-term benzodiazepine receipt, higher opioid doses, and among HIV-infected patients. Long-term benzodiazepine receipt was associated with an increased risk of death regardless of opioid receipt. Strategies to mitigate risks associated with these medications, and caution when they are coprescribed, are needed particularly in HIV-infected populations.
Harms of opioid analgesics, especially high-dose therapy among individuals with comorbidities and older age, are increasingly recognized. However, trends in opioid receipt among HIV-infected patients ...are not well characterized. We examined trends, from 1999 to 2010, in any and high-dose (≥120 mg/day) opioid receipt among patients with and without HIV, by age strata, controlling for demographic and clinical correlates. Of 127,216 patients, 64 % received at least one opioid prescription. Opioid receipt increased substantially among HIV-infected and uninfected patients over the study; high-dose therapy was more prevalent among HIV-infected patients. Trends in high-dose receipt stratified by three age groups revealed an increasing trend in each age strata, higher among HIV-infected patients. Correlates of any opioid receipt included HIV, PTSD and major depression. Correlates of high-dose receipt included HIV, PTSD, major depression and drug use disorders. These findings suggest a need for appropriate balance of risks and benefits, especially as these populations age.
Antisaccade and prosaccade (PS) performance were studied in a large cohort of females (age range 42-74 yr). Antisaccade performance was assessed in two variants of the task, a "traditional" ...antisaccade (TA) task, in which no visual stimuli were present at the saccade goal, and a visually guided antisaccade (VGA) task, in which small visual stimuli were present at the possible saccade goals prior to the imperative visual stimulus. Directional error frequency was similar in the two antisaccade tasks. However, reaction time (RT) was ∼33 ms longer in the VGA task than in the TA task. Across participants, the average saccade amplitudes of prosaccades and TAs were both correlated with those of VGAs but not with each other. TAs had a hypermetria that increased with age. Saccade amplitude variability was much higher for TAs than for PSs and VGAs. Saccade polar angle variability was low for all three tasks. Age diminished performance with modest task dependence, except for an increase in TA hypermetria. These results suggest that the generation of antisaccade directional errors does not depend on visual target presence at the saccade goal, that antisaccade RT can be affected by target presence, that age can increase saccade hypermetria in the absence of visual guidance, and that visually guided antisaccades are governed by distinct voluntary and visually guided saccade mechanisms. Moreover, these results suggest that an understanding of human motor performance benefits from the use of a participant pool with a larger age range than that used in most studies.
This study uses a visually guided antisaccade (VGA) task to determine whether poor performance in a large middle-aged participant pool on an antisaccade task results from problems with executive control or voluntary saccade generation. Spatial and temporal attributes of saccade performance as a function of task and age are analyzed comprehensively. Correlational analysis is used to determine how VGAs are governed jointly by voluntary and visually guided movement mechanisms.
Cognitive dysfunction has been observed consistently in a subset of breast cancer survivors. Yet, the precise physiological and processing origins of dysfunction remain unknown. The current study ...examined the utility of methods and procedures based on cognitive neuroscience to study cognitive change associated with cancer and cancer treatment.
We used electroencephalogram and behavioral measures in a longitudinal design to investigate pre- versus post-treatment effects on attention performance in breast cancer patients (n = 15) compared with healthy controls (n = 24), as participants completed the revised Attention Network Test, a cognitive measure of alerting, orienting, and inhibitory control of attention.
We found no group differences in behavioral performance from pretest to posttest, but significant event-related potential effects of cancer treatment in processing cue validity: After treatment, patients revealed decreased N1 amplitude and increased P3 amplitude, suggesting a suppressed early (N1) response and an exaggerated late (P3) response to invalid cues.
The results suggest that treatment-related attentional disruption begins in early sensory/perceptual processing and extends to compensatory top-down executive processes.
•Opioid use was strongly associated with overdose death among HIV- individuals.•Opioid use was not associated with overdose death among people with HIV.•Caution is needed when interpreting cause of ...death data among people with HIV.
Ascertainment of unnatural and overdose death may be unreliable among individuals with life-limiting conditions such as HIV infection. We sought to determine whether the relationship between opioid use and unnatural death differs among decedents with HIV (DWH) and those without.
Decedents in the Veterans Aging Cohort Study (VACS) from 2002 to 14 were linked to the National Death Index cause of death file. Deaths were classified as unnatural, overdose (a subset of unnatural), or other. We defined opioid use as self-reported illicit use or receipt of prescribed opioids. Treating unnatural and overdose deaths as outcomes, we calculated odds ratios for opioid exposure by HIV status, with and without adjustment for disease severity using VACS Index.
Among 561 decedents without HIV (DWOH) and 884 DWH, 11 % and 8 % respectively were classified as unnatural deaths and 4 % and 2 % were classified as overdose deaths. Among DWOH, opioid use was associated with 2-fold greater odds of unnatural (OR 2.3; 95 % CI 1.3–4.0) and 4-fold greater odds of overdose death (OR 4.5; 95 % CI 1.5–13.7); in adjusted analyses, opioid use was associated with unnatural death (OR 2.6; 95 % CI 1.3–4.9) and with overdose (OR 4.2; 95 % CI 1.4–12.7). Opioid use was not associated with unnatural or overdose death among DWH.
Opioid use was strongly associated with unnatural and overdose death among DWOH but not among DWH suggesting potential differential misclassification. Caution should be used in interpreting prevalence, incidence and risk factors for unnatural and overdose cause of death among patients with life-limiting conditions such as HIV.
•Examined incident nonmedical use of prescription opioids (NMUPO) among veterans.•Among veterans prescribed opioids, 15% reported incident NMUPO.•Duration of prescription opioid receipt was a risk ...factor for incident NMUPO.
Although nonmedical use of prescription opioids (NMUPO) is a public health problem, few studies have examined the new-onset NMUPO in clinical populations. We estimated NMUPO incidence among veterans in medical care who had received prescription opioid medication and examined correlates of new-onset NMUPO.
Prospective cohort study.
Veterans Health Administration primary care and infectious disease clinics in Atlanta, Baltimore, Bronx, Houston, Los Angeles, Manhattan, Pittsburgh, and Washington, DC.
Patients enrolled in the Veterans Aging Cohort Study wave 3 (2005–2007) who received prescription opioids in the previous year and without lifetime NMUPO were followed at waves 4 and 5 (2008–2011).
Cox proportional hazards regression was used to examine the relationship between duration of prescription opioid receipt and incident NMUPO, adjusting for demographics, alcohol and tobacco use, substance use disorders, psychiatric and medical diagnoses, and medication-related characteristics.
Among eligible participants (n = 815), the median age was 52 (IQR = 47–58) and 498 (59.8%) were Black; 122 (15.0%) reported new-onset NMUPO, for an incidence rate of 5.0 per 100 person-years. In a multivariable Cox model, compared to <30 days, receipt of prescription opioids for 30–180 days (adjusted hazard ratio AHR = 1.65 95% CI: 1.06, 2.58) or >180 days (AHR = 1.99, 95% CI: 1.21, 3.29) was associated with incident NMUPO.
Duration of prescription opioid receipt is a risk factor for incident NMUPO among veterans receiving medical care. Providers who prescribe opioids should monitor for NMUPO, especially among those with a longer duration of opioid therapy.
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