Initial Stage of Disease Similar for White and Black Patients With Early-Onset Colorectal Cancer at a Safety-Net Hospital.

BACKGROUND: Non-Hispanic Black (NHB) patients with early-onset colorectal cancer (EOCRC) are more likely to present with advanced-stage disease than their Non-Hispanic White (NHW) counterparts. To further elucidate whether differences in tumor biology or disparities in access to care may be responsible, we examined the association between race/ethnicity and initial stage of disease, time to diagnosis, and tumor characteristics among NHW and NHB patients with EOCRC cared for in a safety-net health care setting. METHODS: We performed a retrospective cohort study of NHW and NHB patients diagnosed with primary EOCRC who received care at Boston Medical Center between January 2000 and May 2020. We compared demographics, risk factors, presenting signs/symptoms, time to diagnosis, health care utilization, and tumor characteristics (stage, grade, location, and mutational status). RESULTS: We identified 103 patients (mean age 41.5±7.2 y, 53.4% men), including 40 NHWs and 63 NHBs, with EOCRC. NHB and NHW patients were similar with respect to demographics, presenting signs/symptoms, and risk factor distribution. There were also no significant differences between NHWs and NHBs with respect to the advanced stage of disease at presentation (45.0% vs. 42.9%, P =0.83), the median time to diagnosis [152 d (IQR, 40 to 341) vs. 160 d (IQR, 61 to 312), P =0.79] or tumor characteristics, except for a predilection for proximal disease among NHBs (30.2% vs. 15.0%). CONCLUSIONS: NHB patients were no more likely than NHW patients to present with advanced-stage disease, aggressive tumor histology, or experience delays in diagnosis within a safety-net health care system.

Heavy Alcohol Use and HIV Outcomes: The Moderating Role of Pain.

Pain and heavy alcohol consumption are prevalent among people living with HIV/AIDS (PLWH), each contributing to impaired functioning and diminished quality of life. Each of these conditions may have negative effects on the HIV care continuum, but less is known about their combined influences. The current study examined how heavy drinking and pain were associated with HIV viral suppression and CD4 cell count among participants receiving antiretroviral therapy (ART). The study sample consisted of 220 PLWH with past 12-month substance dependence or ever injection drug use enrolled in a large HIV cohort study. Logistic regression analyses showed an interaction between pain level (no/mild pain vs moderate/severe) and heavy drinking on viral suppression such that heavy drinking was a significant predictor of poorer viral suppression only for those who experienced moderate/severe pain. We also examined whether ART adherence differentially mediated the association between heavy drinking and HIV viral suppression by level of pain. Although there was a significant indirect effect of heavy drinking on viral suppression among those with moderate/severe pain, moderated mediational analyses did not indicate that the indirect effect of heavy drinking on viral suppression through ART adherence differed significantly by level of pain. Pain level did not significantly moderate the association between heavy drinking and CD4 cell count. We conclude that heavy drinking may be particularly likely to be associated with poorer HIV viral suppression among PLWH with moderate or severe pain. Providers should routinely address comorbid heavy drinking and pain to improve HIV outcomes.

Self-medication of pain and discomfort with alcohol and other substances by people with HIV infection and substance use disorder: preliminary findings from a secondary analysis.

There is a limited literature regarding factors associated with self-medication of pain and discomfort using alcohol, non-prescription substances or overuse of prescription medications among people living with Human Immunodeficiency Virus (HIV). This cross-sectional analysis used data from the Boston ARCH Cohort among participants with HIV infection and a history of alcohol or other substance use. Among 248 participants, 37% were female, 50% Black, 25% Latinx; 36% reported fair to poor health and 89% had CD4 cell counts >200/mm3. Half reported self-medication and of those, 8.8% reported doing so only with alcohol, 48.8% only with other substances and 42.4% with both alcohol and other substances. Those reporting self-medication were significantly (p < .05) younger (mean 47 vs 50 years), less employed (11% vs 21%), and less likely to have HIV viral suppression (60% vs. 80%). Depression, anxiety, and HIV symptoms were associated with significantly greater odds of self-medicating, as were substance dependence, recent injection substance use, heavy alcohol use, cocaine use, opioid use, sedative use, and cannabis use. Self-medication, highly prevalent and associated with worse mental health symptoms, greater substance use, and lesser HIV disease control, should be explored by HIV clinicians caring for people who use substances.

Burden of Chronic Obstructive Pulmonary Disease Attributable to Tuberculosis: A Microsimulation Study.

Tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD), but COPD is also a predictor of TB. The excess life-years lost to COPD caused by TB can potentially be saved by screening for and treating TB infection. We examined the number of life-years that could be saved by preventing TB and TB-attributable COPD. We compared the observed (no intervention) and counterfactual microsimulation models constructed from observed rates in the Danish National Patient Registry (covering all Danish hospitals between 1995 and 2014). In the Danish population of TB and COPD-naive individuals (n = 5,206,922), 27,783 persons (0.5%) developed TB. Among those who developed TB, 14,438 (52.0%) developed TB with COPD. Preventing TB saved 186,469 life-years overall. The excess number of life-years lost to TB alone was 7.07 years per person, and the additional number of life-years lost among persons who developed COPD after TB was 4.86 years per person. The life-years lost to TB-associated COPD are substantial, even in regions where TB can be expected to be identified and treated promptly. Prevention of TB could prevent a substantial amount of COPD-related morbidity; the benefit of screening and treatment for TB infection is underestimated by considering morbidity from TB alone.

Quantitative MRI Characterization of the Extremely Preterm Brain at Adolescence: Atypical versus Neurotypical Developmental Pathways.

Background Extremely preterm (EP) birth is associated with higher risks of perinatal white matter (WM) injury, potentially causing abnormal neurologic and neurocognitive outcomes. MRI biomarkers distinguishing individuals with and without neurologic disorder guide research on EP birth antecedents, clinical correlates, and prognoses. Purpose To compare multiparametric quantitative MRI (qMRI) parameters of EP-born adolescents with autism spectrum disorder, cerebral palsy, epilepsy, or cognitive impairment (ie, atypically developing) with those without (ie, neurotypically developing), characterizing sex-stratified brain development. Materials and Methods This prospective multicenter study included individuals aged 14-16 years born EP (Extremely Low Gestational Age Newborns-Environmental Influences on Child Health Outcomes Study, or ELGAN-ECHO). Participants underwent 3.0-T MRI evaluation from 2017 to 2019. qMRI outcomes were compared for atypically versus neurotypically developing adolescents and for girls versus boys. Sex-stratified multiple regression models were used to examine associations between spatial entropy density (SEd) and T1, T2, and cerebrospinal fluid (CSF)-normalized proton density (nPD), and between CSF volume and T2. Interaction terms modeled differences in slopes between atypically versus neurotypically developing adolescents. Results A total of 368 adolescents were classified as 116 atypically (66 boys) and 252 neurotypically developing (125 boys) participants. Atypically versus neurotypically developing girls had lower nPD (mean, 557 10 × percent unit [pu] ± 46 [SD] vs 573 10 × pu ± 43; P = .04), while atypically versus neurotypically developing boys had longer T1 (814 msec ± 57 vs 789 msec ± 82; P = .01). Atypically developing girls versus boys had lower nPD and shorter T2 (eg, in WM, 557 10 × pu ± 46 vs 580 10 × pu ± 39 for nPD [P = .006] and 86 msec ± 3 vs 88 msec ± 4 for T2 [P = .003]). Atypically versus neurotypically developing boys had a more moderate negative association between T1 and SEd (slope, -32.0 msec per kB/cm3 [95% CI: -49.8, -14.2] vs -62.3 msec per kB/cm3 [95% CI: -79.7, -45.0]; P = .03). Conclusion Atypically developing participants showed sexual dimorphisms in the cerebrospinal fluid-normalized proton density (nPD) and T2 of both white matter (WM) and gray matter. Atypically versus neurotypically developing girls had lower WM nPD, while atypically versus neurotypically developing boys had longer WM T1 and more moderate T1 associations with microstructural organization in WM. © RSNA, 2022 Online supplemental material is available for this article.

Systemic Inflammation in the First 2 Weeks after Birth as a Determinant of Physical Growth Outcomes in Hospitalized Infants with Extremely Low Gestational Age.

OBJECTIVE: To examine associations of systemic inflammation with growth outcomes at neonatal intensive care unit discharge or transfer among infants with extremely low gestational ages. STUDY DESIGN: We studied 850 infants at born at 23-27 weeks of gestation. We defined inflammatory protein elevation as the highest quartile of C-reactive protein (CRP), Interleukin (IL)-6, tumor necrosis factor-∝, or IL-8 on postnatal days 1, 7, and 14. We compared z-scores of weight, length, and head circumference at neonatal intensive care unit discharge or transfer between infants with vs without inflammatory protein elevation, adjusting in linear regression for birth size z-score, sex, gestational age, diet, comorbidities, medications, and length of hospitalization. RESULTS: The mean gestational age was 25 weeks (range, 23-27 weeks) and birth weight z-score 0.14 (range, -2.73 to 3.28). Infants with a high CRP on day 7 had lower weights at discharge or transfer (-0.17 z-score; 95% CI, -0.27 to -0.06) than infants without CRP elevation, with similar results on day 14. Infants with CRP elevation on day 14 were also shorter (-0.21 length z-scores; 95% CI, -0.38 to -0.04), and had smaller head circumferences (-0.18 z-scores; 95% CI, -0.33 to -0.04) at discharge or transfer. IL-6 elevation on day 14 was associated with lower weight (-0.12; 95% CI, -0.22 to -0.02); IL-6 elevation on day 7 was associated with shorter length (-0.27; 95% CI, -0.43 to -0.12). Tumor necrosis factor-∝ and IL-8 elevation on day 14 were associated with a lower weight at discharge or transfer. CONCLUSIONS: Postnatal systemic inflammation may contribute to impaired nutrient accretion during a critical period in development in infants with extremely low gestational ages.

Alcohol and falls among people with HIV infection: A view from Russia and the United States.

BACKGROUND: Both human immunodeficiency virus (HIV) infection and alcohol use predispose to autonomic/sensory neuropathy, imbalance symptoms, and cognitive impairment-conditions associated with a greater risk of falls-yet it is unclear how to identify people with HIV (PWH) whose drinking is associated with falls. Research on alcohol and falls using the same instruments in different countries could help to specify the level of alcohol use associated with fall risk. We examined whether a consumption-based measure (the Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]) and/or a symptom-based measure (DSM-5 criteria for alcohol use disorder [AUD]) are associated with sustaining a fall among PWH in St Petersburg, Russia and Boston, Massachusetts in the United States. METHODS: Separate multivariate logistic regressions were used for each cohort to examine cross-sectional associations for each alcohol measure predicting fall. Potential confounders included physical functioning, depressive symptoms, and other substance use (measured with the Addiction Severity Index). RESULTS: A fall was reported by 35% (87/251) of the sample in Boston and 12% (46/400) in St Petersburg. Each additional AUD criterion-but not higher AUDIT-C score-was significantly associated with a fall in both Boston (odds ratio [OR] = 1.10; 95% confidence interval [CI] 1.02, 1.18) and St Petersburg (adjusted OR AOR = 1.10; 95% CI 1.02, 1.18). Heavy alcohol use (>6 drinks/occasion, any vs. none) was associated with more than twice the odds of a fall (AOR = 2.24; 95% CI 1.21, 4.13) in Boston. CONCLUSIONS: These findings suggest that while fall risk may vary by setting and population, heavy alcohol use and AUD symptom severity are potential targets for interventions to prevent falls. Studies in diverse global settings advance our understanding of the relationship between alcohol and falls in PWH.

Health symptom trajectories and neurotoxicant exposures in Gulf War veterans: the Ft. Devens cohort.

BACKGROUND: Thirty years ago, Gulf War (GW) veterans returned home with numerous health symptoms that have been associated with neurotoxicant exposures experienced during deployment. The health effects from these exposures have been termed toxic wounds. Most GW exposure-outcome studies utilize group analyses and thus individual fluctuations in symptoms may have been masked. This study investigates health symptom trajectories in the same veterans over 25 years. METHODS: Veterans were categorized into 5 a priori trajectory groups for each health symptom and Chronic Multisymptom Illness (CMI) clinical case status. Multinomial logistic regression models were used to investigate associations between these trajectories and neurotoxicant exposures. RESULTS: Results indicate that more than 21 Pyridostigmine Bromide (PB) pill exposure was associated with consistent reporting of fatigue, pain, and cognitive/mood symptoms as well as the development of six additional symptoms over time. Chemical weapons exposure was associated with both consistent reporting and development of neurological symptoms over time. Reported exposure to tent heater exhaust was associated with later development of gastrointestinal and pulmonary symptoms. Veterans reporting exposure to more than 21 PB pills were more than 8 times as likely to consistently meet the criteria for CMI over time. CONCLUSION: This study highlights the importance of the continued documentation of the health impacts experienced by GW veterans', their resulting chronic health symptoms, and the importance of exposure-outcome relationships in these veterans now 30 years post-deployment.

The impact of neurotoxicant exposures on posttraumatic stress disorder trajectories: The Ft. Devens Gulf War Veterans Cohort.

Gulf War veterans (GWVs) were exposed to neurotoxicants, including sarin nerve gas, anti-nerve agent pills, pesticides, oil well fires, and fumes from unvented tent heaters, all of which have been associated with subsequent adverse health. Posttraumatic stress disorder (PTSD) symptoms have also been associated with GW deployment; however, associations between exposures and PTSD symptoms have not been investigated. We assessed PTSD symptom trajectories and associations with neurotoxicant exposures in Ft. Devens Cohort (FDC) veterans (N = 259) who endorsed trauma exposure during deployment and completed the PTSD Checklist at three follow-ups (1992-1993, 1997-1998, 2013-2017). Results indicate that among veterans with more severe initial PTSD symptoms, symptoms remained significantly higher across follow-ups, Bs = -1.489-1.028, whereas among those with low initial PTSD symptoms, symptom severity increased significantly over time, Bs = 1.043-10.304. Additionally, neurotoxicant exposure was associated with a significant increase in PTSD symptoms, Bs = -1.870-9.003. Significant interactions between time and exposures were observed for PTSD symptom clusters, suggesting that among participants with high initial PTSD symptom, unexposed veterans experienced symptom alleviation, whereas exposed veterans' PTSD symptoms remained high. In GWVs with low initial PTSD symptoms, both unexposed and exposed veterans experienced PTSD symptom exacerbations over time; however, this occurred at a faster rate among exposed veterans. These findings suggest that in the years following deployment, GWVs who were exposed to both traumatic events and neurotoxicants may experience more severe and chronic PTSD symptoms than those without neurotoxicant exposures.

Variation in United States COVID-19 newborn care practices: results of an online physician survey.

BACKGROUND: Newborn care practices that best promote the health and well-being of mother-infant dyads after birth while minimizing transmission of COVID-19 were uncertain at the onset of the COVID-19 pandemic. OBJECTIVE: Examine variation in COVID-19 newborn care practices among U.S. birth hospitals and by hospital characteristics (U.S. census region, highest level of neonatal level of care, and Baby-Friendly hospital status). STUDY DESIGN: We surveyed physicians via American Academy of Pediatrics email listservs and social media between 5/26/2020-6/8/2020. Physicians identified the birth hospital in which they provided newborn care and their hospital's approach to obstetrical and newborn care related to COVID-19. Chi-square tests were used to examine variation in hospital practices by U.S. census region, highest level of neonatal care, and Baby-Friendly hospital status. RESULTS: Four hundred thirty three physicians responded from 318 hospitals across 46 states. Variation in care of SARS-CoV-2 positive mother-infant dyads was greatest for approaches to location of newborn care (31% separation, 17% rooming-in, and 51% based on shared-decision making), early skin-to-skin care (48% prohibited/discouraged, 11% encouraged, and 40% based on shared-decision making) and direct breastfeeding (37% prohibited/discouraged, 15% encouraged, and 48% based on shared-decision making). Among presumed uninfected dyads, 59% of hospitals discharged at least some mother-infant dyads early. We found variation in practices by U.S. census region. CONCLUSION: Approaches to newborn care and breastfeeding support for mother-infant dyads with positive SARS-CoV-2 testing differed across U.S. birth hospitals during the COVID-19 pandemic. Early discharge of presumed uninfected mother-infant dyads was common.

Associations of spousal and non-spousal caregiving with six-year trajectories of depressive symptoms among older women in the Caregiver-Study of Osteoporotic Fractures study.

Objectives:Caregiving and becoming widowed are risk factors for depression in older adults, but few studies have examined their combined effect on depressive symptom trajectories. In a cohort of older women (mean age = 80.7 years) from the Caregiver-Study of Osteoporotic Fractures, we used latent class growth curve modeling to identify trajectories of depressive symptoms over approximately six years.Method:We used multinomial logistic regression to assess the relative odds of four depressive symptom trajectories (consistently low, consistently moderate, moderate/increasing, and consistently high), among three groups: spousal caregivers (n = 149), non-spousal caregivers (n = 157), and non-caregivers (n = 422). We also repeated this analysis with combined caregiving status and widowhood as the exposure.Results:Compared to non-caregivers, spousal caregivers had greater relative odds of consistently high versus consistently low depressive symptoms (adjusted odds ratio [aOR] = 3.6, 95% confidence interval [CI]: 1.9, 6.5). Non-spousal caregivers did not differ from non-caregivers in depressive trajectories. Compared to non-caregivers who did not become widowed, both widowed and non-widowed spousal caregivers had greater relative odds of consistently high versus consistently low depressive symptoms (aOR = 4.9, 95% CI: 1.9, 12.7 and aOR = 3.0, 95% CI: 1.5, 6.0, respectively). Non-widowed spousal caregivers, but not widowed spousal caregivers, had a non-statistically-significant trend toward increased relative odds of moderate/increasing depressive symptoms (aOR = 1.5, 95% CI: 0.7, 3.4).Conclusion:Spousal caregiving and widowhood, but not non-spousal caregiving, are associated with trajectories reflecting greater depressive symptoms over time. Informal caregiving is common among older women, and women caring for spouses should be monitored for depression, both during caregiving and after spousal loss.Supplemental data for this article can be accessed online at https://doi.org/10.1080/13607863.2021.1950611.

Food insecurity and substance use in people with HIV infection and substance use disorder.

BACKGROUND: Food insecurity and substance use are common among people living with HIV (PLWH). Substance use may help people cope with hunger and thus be associated with food insecurity, but the association is uncertain. This study assessed whether, in PLWH and substance dependence, if there was an association between food insecurity and substance use.Methods: We studied adults with HIV and current substance dependence or ever injection drug use interviewed at 12 and 24 months after enrollment in a prospective cohort study. The presence of food insecurity (insufficient food quantity or quality, or anxiety about its availability) was assessed using the Household Food Insecurity Assessment Scale questionnaire (HFIAS). Unhealthy alcohol use was assessed with the Alcohol Use Disorder Identification Test - Consumption (AUDIT-C) and past 30-day other drug use with the Addiction Severity Index. Associations using repeat cross-sectional data from each of two time-points, 12 months apart, from the same participants were tested using generalized estimating equations logistic regressions.Results: The 233 participants had a mean age of 50 years and 65% were male. At the first interview, 44% reported food insecurity, 40% unhealthy alcohol use, 25% past 30-day cocaine use, and 17% past 30-day illicit opioid use. In analyses adjusted for demographics, social factors, physical and mental health function, and substance use related variables, there was no significant association between food insecurity and unhealthy alcohol use (adjusted odds ratio (aOR) = 1.06 (95% CI: 0.59, 1.87)). Those with food insecurity had higher odds of illicit opioid use (aOR = 2.5 (95% CI: 1.12, 5.58)) and cocaine use (aOR = 1.95 (CI 95%: 1.00, 3.81)).Conclusion: Food insecurity was not associated with unhealthy alcohol use but was associated with cocaine and illicit opioid use. Given the prevalence and impact substance use has on PLWH, food insecurity should be identified and addressed.

Trends in Cannabis Involvement and Risk of Alcohol Involvement in Motor Vehicle Crash Fatalities in the United States, 2000‒2018.

Objectives. To assess cannabis and alcohol involvement among motor vehicle crash (MVC) fatalities in the United States. Methods. In this repeated cross-sectional analysis, we used data from the Fatality Analysis Reporting System from 2000 to 2018. Fatalities were cannabis-involved if an involved driver tested positive for a cannabinoid and alcohol-involved based on the highest blood alcohol concentration (BAC) of an involved driver. Multinomial mixed-effects logistic regression models assessed cannabis as a risk factor for alcohol by BAC level. Results. While trends in fatalities involving alcohol have remained stable, the percentage of fatalities involving cannabis and cannabis and alcohol increased from 9.0% in 2000 to 21.5% in 2018, and 4.8% in 2000 to 10.3% in 2018, respectively. In adjusted analyses, fatalities involving cannabis had 1.56 (95% confidence interval [CI] = 1.48, 1.65), 1.62 (95% CI = 1.52, 1.72), and 1.46 (95% CI = 1.42, 1.50) times the odds of involving BACs of 0.01% to 0.049%, 0.05% to 0.079%, and 0.08% or higher, respectively. Conclusions. The percentage of fatalities involving cannabis and coinvolving cannabis and alcohol doubled from 2000 to 2018, and cannabis was associated with alcohol coinvolvement. Further research is warranted to understand cannabis- and alcohol-involved MVC fatalities. (Am J Public Health. 2021;111(11):1976-1985. https://doi.org/10.2105/AJPH.2021.306466).

Alcohol policies, firearm policies, and suicide in the United States: a lagged cross-sectional study.

BACKGROUND: Alcohol and firearms are commonly involved in suicide in the United States. State alcohol and firearm policies may impact alcohol and firearm related suicide, yet little is known about these relationships. This study examines relationships between state alcohol and firearm policies and suicides involving alcohol, guns, or both, and explores interactive policy associations. METHODS: Alcohol policies were assessed with the Alcohol Policy Scale. Firearm policies were assessed using the Gun Law Scorecard from Giffords Law Center. Suicide data from the National Violent Death Reporting System in 2015 covered 22 states. State- and individual-level GEE Poisson and logistic regression models assessed relationships between policies and firearm- and/or alcohol-involved suicides with a 1-year lag. RESULTS: In 2015, there were 8996 suicide deaths with blood alcohol concentration test results in the 22 included states. Of those deaths, alcohol and/or firearms were involved in 5749 or 63.9%. Higher alcohol and gun law scores were associated with reduced incidence rates and odds of suicides involving either alcohol or firearms (adjusted incidence rate ratios [IRR] 0.72 (95% CI 0.63, 0.83) for alcohol policies, 0.86 (95% CI 0.82, 0.90) for firearm policies). Relationships were similar for suicides involving both alcohol and firearms, and there was an interactive effect, such that states with restrictive policies for both had the lowest rates of suicides involving alcohol or guns. CONCLUSIONS: More restrictive alcohol and firearm policies are associated with lower rates and odds of suicides involving alcohol or firearms, and alcohol and firearms, and may be a promising means by which to reduce suicide.

Alterations in high-order diffusion imaging in veterans with Gulf War Illness is associated with chemical weapons exposure and mild traumatic brain injury.

The complex etiology behind Gulf War Illness (GWI) has been attributed to the combined exposure to neurotoxicant chemicals, brain injuries, and some combat experiences. Chronic GWI symptoms have been shown to be associated with intensified neuroinflammatory responses in animal and human studies. To investigate the neuroinflammatory responses and potential causes in Gulf War (GW) veterans, we focused on the effects of chemical/biological weapons (CBW) exposure and mild traumatic brain injury (mTBI) during the war. We applied a novel MRI diffusion processing method, Neurite density imaging (NDI), on high-order diffusion imaging to estimate microstructural alterations of brain imaging in Gulf War veterans with and without GWI, and collected plasma proinflammatory cytokine samples as well as self-reported health symptom scores. Our study identified microstructural changes specific to GWI in the frontal and limbic regions due to CBW and mTBI, and further showed distinctive microstructural patterns such that widespread changes were associated with CBW and more focal changes on diffusion imaging were observed in GW veterans with an mTBI during the war. In addition, microstructural alterations on brain imaging correlated with upregulated blood proinflammatory cytokine markers TNFRI and TNFRII and with worse outcomes on self-reported symptom measures for fatigue and sleep functioning. Taken together, these results suggest TNF signaling mediated inflammation affects frontal and limbic regions of the brain, which may contribute to the fatigue and sleep symptoms of the disease and suggest a strong neuroinflammatory component to GWI. These results also suggest exposures to chemical weapons and mTBI during the war are associated with different patterns of peripheral and central inflammation and highlight the brain regions vulnerable to further subtle microscale morphological changes and chronic signaling to nearby glia.

Alcohol and Bone Turnover Markers among People Living with HIV and Substance Use Disorder.

BACKGROUND: Although unhealthy alcohol use and low bone density are prevalent among people living with HIV (PLWH), it is not clear whether alcohol use is associated with bone turnover markers (BTMs), and if so, at what quantity and frequency. The study objective was to examine the association between alcohol and BTMs in PLWH with substance use disorder. METHODS: We studied a prospective cohort recruited from 2 HIV clinics who met criteria for DSM-IV substance dependence or reported ever injection drug use. Outcomes were BTM of (i) bone formation (serum procollagen type 1 N-terminal propeptide [P1NP]) and (ii) bone resorption (serum C-telopeptide type 1 collagen [CTx]). Alcohol consumption measures included (i) mean number of drinks/d (Timeline Follow-Back [TLFB]) (primary predictor), (ii) any alcohol use on ≥20 of the past 30 days, and phosphatidylethanol (PEth), a biomarker of recent alcohol consumption. Linear regression analysis examined associations between (i) each alcohol measure and each BTM and (ii) change in alcohol and change in BTM over 12 months. RESULTS: Among 198 participants, baseline characteristics were as follows: The median age was 50 years; 38% were female; 93% were prescribed antiretroviral medications; 13% had ≥20 drinking days/month; mean drinks/day was 1.93 (SD 3.89); change in mean drinks/day was -0.42 (SD 4.18); mean P1NP was 73.1 ng/ml (SD 34.5); and mean CTx was 0.36 ng/ml (SD 0.34). Higher drinks/day was significantly associated with lower P1NP (slope -1.09 ng/ml; 95% confidence interval [CI] -1.94, -0.23, per each additional drink). On average, those who drank on ≥ 20 days/month had lower P1NP (-15.45 ng/ml; 95% CI: -26.23, -4.67) than those who did not. Similarly, PEth level ≥ 8ng/ml was associated with lower P1NP. An increase in drinks/d was associated with a decrease in P1NP nonsignificantly (-1.14; 95% CI: -2.40, +0.12; p = 0.08, per each additional drink). No significant associations were detected between either alcohol measure and CTx. CONCLUSIONS: In this sample of PLWH with substance use disorder, greater alcohol consumption was associated with lower serum levels of bone formation markers.

The Effects of a Health Care-Based Brief Intervention on Dating Abuse Perpetration: Results of a Randomized Controlled Trial.

Dating abuse (DA) is prevalent and consequential, yet there are no evidence-based interventions for the health care setting that prevent perpetration. The current study's purpose was to test a one-session brief motivational interview-style intervention to decrease DA perpetration. We conducted a two-arm RCT of the Real Talk intervention with follow-up at 3 and 6 months. Participants were 172 youth ages 15-19 years old, recruited from the pediatric emergency department or outpatient care services of an urban hospital in the USA in 2014-2017. The primary outcome was change in self-reported DA perpetration, including subtypes of DA such as physical, sexual, psychological, and cyber DA. Youth in both intervention and control arms reduced DA perpetration over time. GEE models indicated no overall intervention effects for any, physical, sexual, or psychological DA. There were overall effects for cyber DA (RR 0.49, 95% CI 0.27, 0.87). There were also effects at 3 months for psychological DA (RR 0.24, 95% CI 0.06, 0.93) and cyber DA (RR 0.39, 95% CI 0.19, 0.79). Analyses stratified by gender also found overall effects for males for any DA (RR 0.20, 95% CI 0.07, 0.55), physical DA (RR 0.30, 95% CI 0.10, 0.89), and cyber DA (RR 0.04, 95% CI 0.01, 0.27). For males, intervention effects on any DA persisted to 6 months (RR 0.13, 95% CI 0.02, 1.01). This health care-based one-session DA intervention is a potentially promising approach to reduce DA perpetration among adolescents.Clinical trial registration: This study is registered at www.clinicaltrials.gov NCT02080923.

Assessing the Role of Selection Bias in the Protective Relationship Between Caregiving and Mortality.

Caregivers have lower mortality rates than noncaregivers in population-based studies, which contradicts the caregiver-stress model and raises speculation about selection bias influencing these findings. We examined possible selection bias due to 1) sampling decisions and 2) selective participation among women (baseline mean age = 79 years) in the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF) (1999-2009), an ancillary study to the Study of Osteoporotic Fractures (SOF). Caregiver-SOF includes 1,069 SOF participants (35% caregivers) from 4 US geographical areas (Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley, Pennsylvania; and Portland, Oregon). Participants were identified by screening all SOF participants for caregiver status (1997-1999; n = 4,036; 23% caregivers) and rescreening a subset of caregivers and noncaregivers matched on sociodemographic factors 1-2 years later. Adjusted hazard ratios related caregiving to 10-year mortality in all women initially screened, subsamples representing key points in constructing Caregiver-SOF, and Caregiver-SOF. Caregivers had better functioning than noncaregivers at each screening. The association between caregiving and mortality among women invited to participate in Caregiver-SOF (41% died; adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI): 0.61, 0.88) was slightly more protective than that in all initially screened women (37% died; aHR = 0.83, 95% CI: 0.73, 0.95), indicating little evidence of selection bias due to sampling decisions, and was similar to that in Caregiver-SOF (39% died; aHR = 0.71, 95% CI: 0.57, 0.89), indicating no participation bias. These results add to a body of evidence that informal caregiving may impart health benefits.

Association of Circulating Proinflammatory and Anti-inflammatory Protein Biomarkers in Extremely Preterm Born Children with Subsequent Brain Magnetic Resonance Imaging Volumes and Cognitive Function at Age 10 Years.

OBJECTIVES: To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition. STUDY DESIGN: We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10 years of age (73 males; 93 females). Top quartile levels on ≥2 days for ≥3 inflammation-related proteins and for ≥4 neurotrophic proteins defined exposure. We examined associations among protein levels, brain Magnetic Resonance Imaging volumes, and cognition with multiple linear and logistic regressions. RESULTS: Analyses were adjusted for gestational age at birth and sex. Children with ≥3 elevated inflammation-related proteins had smaller grey matter, brain stem/cerebellar, and total brain volumes than those without elevated inflammation-related proteins, adjusted for neurotrophic proteins. When adjusted for inflammation-related proteins, children with ≥4 neurotrophic proteins, compared with children with no neurotrophic proteins, had larger grey matter and total brain volumes. Higher grey matter, white matter, and cerebellum and brainstem volumes were significantly correlated with higher IQ. Grey and white matter volumes were correlated with each other (r = -0.18; P = .021), and cerebellum and brainstem was highly correlated with grey matter (r = 0.55; P < .001) and white matter (r = 0.29; P < .001). Adjusting for other brain compartments, cerebellum and brainstem was associated with IQ (P = .016), but the association with white matter was marginally significant (P = .051). Grey matter was not associated with IQ. After adjusting for brain volumes, elevated inflammation-related proteins remained significantly associated with a lower IQ, and elevated neurotrophic proteins remained associated with a higher IQ. CONCLUSIONS: Newborn inflammatory and neurotrophin protein levels are associated with later brain volumes and cognition, but their effects on cognition are not entirely explained by altered brain volumes.

Comparison of novel methods in two-way enriched clinical trial design.

Two-way enriched design (TED) is a novel approach addressing placebo response in clinical trials. It is a two-stage, randomized, placebo-controlled trial design with enrichment in placebo non-responders and treatment responders at the second stage. All data from the first stage and data from placebo non-responders and treatment responders in the second stage are used for the final analysis of the treatment effect. The existing methods for the analysis of TED data include score tests with one, two, and three degrees of freedom. All these methods are only applicable to binary outcomes. However, there is an interest in continuous outcomes in clinical trials in psychiatry. In this manuscript, we apply some novel methods, including a repeated measures model, a weighted repeated measures model with weights from propensity score, and weights from K-means clustering, to analyze TED data for both binary outcomes and continuous outcomes. The simulation study indicates that the repeated measures model performs consistently well in preserving the type I error and achieving the minimum mean standard error as well as a higher power. The performance of the weighted repeated measures model with weights from K-means clustering improves with increasing sample size. Investigators can choose from these analytic approaches under different scenarios.