Self-injurious unnatural death among Veterans with HIV: a nested case-control study.

OBJECTIVE: People living with HIV (PWH) are at increased risk of suicide and death from unintentional causes compared with people living without HIV. Broadening the categorization of death from suicide to self-injurious unnatural death (SIUD) may better identify a more complete set of modifiable risk factors that could be targeted for prevention efforts among PWH. DESIGN: We conducted a nested case-control study using data from the Veterans Aging Cohort Study (VACS), a longitudinal, observational cohort of Veterans from 2006-2015. A total of 5,036 Veterans with HIV, of whom 461 died by SIUD, were included in the sample. METHODS: SIUD was defined using the International Classification of Disease 10th revision cause of death codes. Cases (n = 461) included individuals who died by SIUD (intentional, unintentional, and undetermined causes of death). Controls (n = 4,575) were selected using incidence density sampling, matching on date of birth ± one year, race, sex, and HIV status. SIUD and suicide was estimated using conditional logistic regression. RESULTS: A previous suicide attempt, a diagnosis of an affective disorder, recent use of benzodiazepines, psychiatric hospitalization, and living in the western US significantly increased the risk of suicide and SIUD. Risk factors that appear more important for SIUD than for suicide included a drug use disorder, alcohol use disorder, Hepatitis C, VACS Index 2.0, current smoking, and high pain levels (7-10). CONCLUSION: Limiting studies to known suicides obscures the larger public health burden of excess deaths from self-injurious behavior. Our findings demonstrate the benefit of expanding the focus to SIUD for the identification of modifiable risk factors that could be targeted for treatment.

Temporal Considerations in Brain Metastases Radiation Therapy: The Intersection of Chronobiology and Patient Profiles.

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017-2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival analyses utilized Kaplan-Meier curves. This was a single-institution study involving patients receiving whole-brain radiotherapy. Demographic, disease, and socioeconomic parameters from electronic medical records were collected. Morning treatment (n = 158) showed a trend toward improved overall survival vs. afternoon (n = 79); the median survival was 158 vs. 79 days (p = 0.20, HR = 0.84, CI95% 0.84-0.91). Subgroup benefits for morning treatment in females (p = 0.04) and trends in controlled primary disease (p = 0.11) and breast cancer metastases (p = 0.08) were observed. Black patients exhibited diminished circadian influence. The present study emphasized chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlated with improved survival, particularly in specific subgroups. Potential circadian influence disparities were identified, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

Risk factors for suicide among veterans living with and without HIV: a nested case-control study.

The rate of suicide among people with HIV (PWH) remains elevated compared to the general population. The aim of the study was to examine the association between a broad range of risk factors, HIV-specific risk factors, and suicide. We conducted a nested case-control study using data from the Veterans Aging Cohort Study (VACS) between 2006 and 2015. The risk of suicide was estimated using conditional logistic regression and models were stratified by HIV status. Most risk factors associated with suicide were similar between PWH and people without HIV; these included affective disorders, use of benzodiazepines, and mental health treatment. Among PWH, HIV-specific risk factors were not associated with suicide. A multiplicative interaction was observed between a diagnosis of HIV and a previous suicide attempt. Among PWH, a high prevalence of psychiatric, substance use disorders and multimorbidity contribute to the risk of suicide.

RESUMEN: La tasa de suicidio entre las personas con VIH (PWH) sigue siendo elevada en comparación con la población general. El objetivo del estudio fue examinar la asociación entre un amplio rango de factores de riesgo, los riesgos específicos del VIH y el suicidio. Realizamos un estudio anidado de casos y controles usando datos del Veterans Aging Cohort Study (VACS) entre 2006­2015. El riesgo de suicidio fue estimado mediante regresión logística condicional y los modelos se estratificaron por estado serológico. La mayoría de los factores de riesgo asociados con el suicidio fueron similares entre las PWH y las personas sin VIH; estos incluyeron trastornos afectivos, uso de benzodiazepinas y tratamiento de salud mental. Entre las PWH, los factores de riesgo específicos del VIH no se asociaron con el suicidio. Se observó una interacción multiplicativa entre un diagnóstico de VIH y un intento de suicidio previo. Entre las PWH, una alta prevalencia de trastornos psiquiátricos, por consumo de sustancias y multimorbilidad contribuyen al riesgo de suicidio.

A social media analysis of kratom use to discontinue stimulants.

BACKGROUND: While FDA-approved treatments exist for opioid use disorder, none are available for stimulant use disorder. Kratom (Mitragyna speciosa), an unregulated plant-derived substance with known opioid- and stimulant-like effects, has been used to self-treat opioid use disorder; however, its use in relation to stimulant use disorder has not been described. OBJECTIVE: To understand whether and how individuals use kratom to self-treat stimulant use disorder. METHODS: Using a commercially available social listening platform, 3,820 publicly available social media posts published between January 1, 2020, and June 21, 2021, were reviewed for relevance to kratom and stimulant discontinuation. Manual qualitative thematic analysis was conducted on relevant data. RESULTS: Among the 398 relevant posts that discussed using kratom to discontinue stimulants, motivations and methods varied considerably. Posts predominantly identified benefits but also negative outcomes of kratom use. Some justified it as necessary despite consequences, while others reported a desire to quit. CONCLUSIONS: Although there is some awareness that kratom is used to self-treat opioid use disorder, its use to treat stimulant use disorder is more novel. In the absence of approved treatments, kratom was viewed as a natural and safe way to quit stimulants. Despite some reported success, this study shows self-treatment may pose significant risks, including kratom addiction and physical dependence. Healthcare practitioners, researchers, and public health professionals may benefit from understanding motivations for kratom use, associated benefits and risks, and the importance of discussing kratom use with patients/clients who have stimulant use disorder.

Physician Perceptions on Cancer Screening for LGBTQ+ Patients.

The LGBTQ+ community experiences cancer disparities due to increased risk factors and lower screening rates, attributable to health literacy gaps and systemic barriers. We sought to understand the experiences, perceptions, and knowledge base of healthcare providers regarding cancer screening for LGBTQ+ patients. A 20-item IRB-approved survey was distributed to physicians through professional organizations. The survey assessed experiences and education regarding the LGBTQ+ community and perceptions of patient concerns with different cancer screenings on a 5-point Likert scale. Complete responses were collected from 355 providers. Only 100 (28%) reported past LGBTQ+-related training and were more likely to be female (p = 0.020), have under ten years of practice (p = 0.014), or practice family/internal medicine (p < 0.001). Most (85%) recognized that LGBTQ+ subpopulations experience nuanced health issues, but only 46% confidently understood them, and 71% agreed their clinics would benefit from training. Family/internal medicine practitioners affirmed the clinical relevance of patients' sexual orientation (94%; 62% for medical/radiation oncology). Prior training affected belief in the importance of sexual orientation (p < 0.001), confidence in understanding LGBTQ+ health concerns (p < 0.001), and willingness to be listed as "LGBTQ+-friendly" (p = 0.005). Our study suggests that despite a paucity of formal training, most providers acknowledge that LGBTQ+ patients have unique health needs. Respondents had a lack of consensus regarding cancer screenings for lesbian and transgender patients, indicating the need for clearer screening standards for LGBTQ+ subpopulations and educational programs for providers.

Human spinal cord tissue is an underutilised resource in degenerative cervical myelopathy: findings from a systematic review of human autopsies.

STUDY DESIGN: Systematic review. BACKGROUND: Although degenerative cervical myelopathy (DCM) is the most prevalent spinal cord condition worldwide, the pathophysiology remains poorly understood. Our objective was to evaluate existing histological findings of DCM on cadaveric human spinal cord tissue and explore their consistency with animal models. METHODS: MEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in human cadaveric spinal cord tissue. Data was extracted using a piloted proforma. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Findings were compared to a systematic review of animal models (Ahkter et al. 2020 Front Neurosci 14). RESULTS: The search yielded 4127 unique records. After abstract and full-text screening, 19 were included in the final analysis, reporting on 150 autopsies (71% male) with an average age at death of 67.3 years. All findings were based on haematoxylin and eosin (H&E) staining. The most commonly reported grey matter findings included neuronal loss and cavity formation. The most commonly reported white matter finding was demyelination. Axon loss, gliosis, necrosis and Schwann cell proliferation were also reported. Findings were consistent amongst cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Cavitation was notably more prevalent in human autopsies compared to animal models. CONCLUSION: Few human spinal cord tissue studies have been performed. Neuronal loss, demyelination and cavitation were common findings. Investigating the biological basis of DCM is a critical research priority. Human spinal cord specimen may be an underutilised but complimentary approach.

Predictive Risk Model for Serious Falls Among Older Persons Living With HIV.

BACKGROUND: Older (older than 50 years) persons living with HIV (PWH) are at elevated risk for falls. We explored how well our algorithm for predicting falls in a general population of middle-aged Veterans (age 45-65 years) worked among older PWH who use antiretroviral therapy (ART) and whether model fit improved with inclusion of specific ART classes. METHODS: This analysis included 304,951 six-month person-intervals over a 15-year period (2001-2015) contributed by 26,373 older PWH from the Veterans Aging Cohort Study who were taking ART. Serious falls (those falls warranting a visit to a health care provider) were identified by external cause of injury codes and a machine-learning algorithm applied to radiology reports. Potential predictors included a fall within the past 12 months, demographics, body mass index, Veterans Aging Cohort Study Index 2.0 score, substance use, and measures of multimorbidity and polypharmacy. We assessed discrimination and calibration from application of the original coefficients (model derived from middle-aged Veterans) to older PWH and then reassessed by refitting the model using multivariable logistic regression with generalized estimating equations. We also explored whether model performance improved with indicators of ART classes. RESULTS: With application of the original coefficients, discrimination was good (C-statistic 0.725; 95% CI: 0.719 to 0.730) but calibration was poor. After refitting the model, both discrimination (C-statistic 0.732; 95% CI: 0.727 to 0.734) and calibration were good. Including ART classes did not improve model performance. CONCLUSIONS: After refitting their coefficients, the same variables predicted risk of serious falls among older PWH nearly and they had among middle-aged Veterans.

Diabetes: the role of continuous glucose monitoring.

Diabetes mellitus is a chronic condition affecting 1 out of every 11 people worldwide. Monitoring of blood glucose allows for therapeutic lifestyle and pharmacotherapy changes to reduce the occurrence of hyperglycaemia and hypoglycaemia. Advancements in technology over the past two decades have increased patient and clinician access to glucose data and trends with continuous glucose monitoring (CGM) systems. This narrative review seeks to investigate the efficacy and safety of CGM for the management of diabetes. In type 1 diabetes (T1DM) and type 2 diabetes, efficacy studies of real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) have shown a decrease in HbA1C (0.3-0.6%) over traditional self-monitoring blood glucose. Percent time in the target glucose range also improved (6.8-17.6%). Rates of hypoglycaemia, including severe hypoglycaemia, decreased in studies of rtCGM and isCGM with most available data in T1DM. In pregnant women with T1DM, rtCGM has shown modest improvements in HbA1C and time in target glucose range and decreased risk of neonatal complications. Multiple studies have shown that the use of rtCGM or isCGM increased diabetes treatment satisfaction amongst patients. Head-to-head studies of rtCGM and isCGM are limited but one study indicates that a CGM system with alarms may be preferred in T1DM to reduce the risk of hypoglycaemia. Selection of a CGM device should depend on patient-specific factors and insurance coverage. The results of one study show that the benefits of CGM device use were not sustained after discontinuing use. Increasing widespread and long-term access to CGM devices is necessary to improve the management of diabetes amongst the greater population.

Vastus lateralis versus rectus femoris muscle flaps for recalcitrant hip joint infection: An anatomical study comparing the effectiveness of acetabular dead space control.

Eliminating recalcitrant prosthetic hip joint infections remains one of the greatest challenges in orthopedic surgery. In such cases, the salvage procedure of femoral head excision (the Girdlestone procedure) is often performed. There has been emerging surgical interest in filling the resulting acetabular dead space with a pedicled muscle flap, to enable antibiotic delivery. Both vastus lateralis (VL) and rectus femoris (RF) muscle flaps have been described for this purpose with good success. This study is the first anatomical investigation comparing VL and RF as candidates for interposition myoplasty following hip joint excision. Following standard surgical technique, the Girdlestone procedure and interposition myoplasty of both RF and VL were performed on 10 cadavers. The primary aim was to determine which muscle flap eliminated a greater volume of acetabular dead space. Secondary aims were to characterize the blood supply to RF and assess additional metrics indicative of the likelihood of flap success. The VL flap eliminated more dead space than RF. However, the use of the RF flap was feasible in all cases and has several benefits, including ease of harvest, mobility, and aesthetics. The location of the inferior vascular pedicle into RF was relatively consistent and the most effective predictor of flap success. Both VL and RF are effective in reducing acetabular dead space. While VL can fill a greater volume, the RF flap has technical advantages, related to the predictability of the blood supply.

Effects of a National Campaign on Youth Beliefs and Perceptions About Electronic Cigarettes and Smoking.

INTRODUCTION: Our study assesses the relationship between the exposure of youth to the US Food and Drug Administration's national tobacco public education campaign, The Real Cost, and changes in campaign-focused risk perceptions and beliefs. METHODS: A nationally representative cohort study of youth was conducted from June 2018 to July 2019, consisting of a baseline and one follow-up survey. We performed logistic regressions to examine the association between campaign exposure and beliefs. Exposure was measured by self-report as the frequency of exposure to individual campaign advertisements about the health consequences of e-cigarette use and of smoking cigarettes. RESULTS: We found that increased levels of exposure to campaign advertising was associated with a significant increase in the odds of reporting agreement with campaign-specific beliefs. Positive patterns of findings were found across multiple items selected by specific advertisements, whereas unrelated beliefs were not associated with advertisement exposure. CONCLUSION: A sustained national tobacco public education campaign can change beliefs about the harms of e-cigarette use and cigarette smoking among youth. Combined with other findings from The Real Cost evaluation, results indicate that prevention mass media campaigns continue to be an effective and cost-efficient approach to reduce the health and financial cost of tobacco use in the US.

Predictive validity of the original and expanded susceptibility scales for smokeless tobacco.

BACKGROUND: This study seeks to validate the original and expanded susceptibility scales for smokeless tobacco (SLT) use among a longitudinal sample of rural male youth. We also compare the predictive validity of both scales for SLT. METHODS: Data are from a five-wave longitudinal sample of rural males in the Unites States aged 11-16 at baseline. Data were collected from January 2016 to December 2018. We used a series of logistic regressions to identify whether individual demographic variables, the original (use SLT soon, in next year, if friend offers), or the expanded (original plus curiosity) susceptibility scales predicted experimentation with SLT by 2018. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both scales were also calculated to determine reliability. All analyses were limited to 2016 never SLT users. RESULTS: Both susceptibility scales were significant predictors of SLT initiation by follow-up. Susceptible youth had three times the odds of SLT initiation by follow-up compared to youth who were non-susceptible. Both scales have high specificity, identifying a large proportion of never users as non-susceptible. Sensitivity for the original scale was 37.0% and increased to 44.2% for the expanded scale. The PPV was approximately 20% for both the original and expanded scales. CONCLUSIONS: The SLT susceptibility scales are valid for predicting future SLT initiation; however, there remains room for improvement as the sensitivity of both scales is relatively low compared to the smoking scale. Future research should examine additional methods to identify youth at risk of SLT initiation.

A Systematic Review of Risk Factors for Suicide Among Persons Living with HIV (1996-2020).

Persons living with HIV (PWH) are at elevated risk for suicide. We conducted a systematic literature review following PRISMA-P guidelines to examine risk factors associated with suicide as a cause of morbidity among PWH. We searched six electronic databases using search terms (suicide, suicide attempt, self-harm, self-injurious behavior, HIV, AIDS, PWH). We focused on factors that were specific to HIV infection (CD4 count, HIV-1 RNA, and antiretroviral therapy [ART]). The initial search yielded N = 2657 studies. Eligible studies included suicide as an outcome, quantitative study design, and publication in peer-reviewed journals from 1996 through 2020. Fourteen studies met inclusion criteria. PWH share risk factors for suicide found in the general population: psychiatric illness, previous suicide attempt, drug and alcohol misuse. PWH also have HIV-specific risk factors for suicide. HIV diagnosis in the past two years and transmission related to injection drug use were associated with increased risk; HIV-1 RNA, ART, and AIDS-defining illness were not.

RESUMEN: Las personas viviendo con VIH (PVV) tienen riesgo elevado de suicidio. Realizamos un examen sistemático de la bibliografía, siguiendo las pautas PRISMA-P para examinar los factores de riesgo asociados con suicidio como la causa de morbilidad entre PVV. Realizamos búsquedas en seis bases de datos electrónicas mediante el uso de términos de búsqueda (suicidio, intento de suicidio, autolesiones, comportamiento autolesivo, VIH, AIDS). Nos hemos centrado en factores que eran específicos de la infección por VIH (recuento de CD4, ARN del VIH-1 y la terapia antirretroviral). La búsqueda inicial arrojó N = 2657 estudios. Los estudios seleccionados según criterio incluyeron muerte por suicidio, que el diseño del estudio fuera cuantitativo, y la publicación haya sido entre 1996 y 2020. 14 estudios cumplieron estos criterios de inclusión para el estudio. PVV comparten los mismos factores de riesgo de suicidio que se encuentran en la población general: enfermedad psiquiátrica, intento previo de suicidio, abuso de drogas y alcohol. PVV también poseen factores de riesgo de suicidio propios del VIH. El diagnóstico de VIH en los últimos dos años y la transmisión relacionada con el uso de drogas inyectables se asociaron con un mayor riesgo; mientras que el ARN del VIH-1, la terapia antirretroviral y las enfermedades definidas del SIDA no fueron asociadas con un mayor riesgo de suicidio.

Chronoradiobiology of Breast Cancer: The Time Is Now to Link Circadian Rhythm and Radiation Biology.

Circadian disruption has been linked to cancer development, progression, and radiation response. Clinical evidence to date shows that circadian genetic variation and time of treatment affect radiation response and toxicity for women with breast cancer. At the molecular level, there is interplay between circadian clock regulators such as PER1, which mediates ATM and p53-mediated cell cycle gating and apoptosis. These molecular alterations may govern aggressive cancer phenotypes, outcomes, and radiation response. Exploiting the various circadian clock mechanisms may enhance the therapeutic index of radiation by decreasing toxicity, increasing disease control, and improving outcomes. We will review the body's natural circadian rhythms and clock gene-regulation while exploring preclinical and clinical evidence that implicates chronobiological disruptions in the etiology of breast cancer. We will discuss radiobiological principles and the circadian regulation of DNA damage responses. Lastly, we will present potential rational therapeutic approaches that target circadian pathways to improve outcomes in breast cancer. Understanding the implications of optimal timing in cancer treatment and exploring ways to entrain circadian biology with light, diet, and chronobiological agents like melatonin may provide an avenue for enhancing the therapeutic index of radiotherapy.

Perceived Message Effectiveness and Campaign-Targeted Beliefs: Evidence of Reciprocal Effects in Youth Tobacco Prevention.

Perceived message effectiveness (PE) has been widely used in campaign formative research and evaluation. The relationship between PE and actual message effectiveness (AE) is often assumed to be causal and unidirectional, but careful conceptualization and empirical testing of this and other causal possibilities are generally lacking. In this study, we investigated the potential reciprocity in the relationship between PE and AE in the context of a national youth tobacco education campaign. In so doing, we also sought to generate much needed evidence on PE's utility to predict campaign-targeted outcomes in youth tobacco prevention. Using five waves of campaign evaluation data (N = 1,128), we found significant lagged associations between PE and campaign-targeted beliefs, and vice versa. These results suggest a dynamic, mutually influencing relationship between PE and AE and call for greater attention to such dynamics in campaign research.

"The Real Cost" Smokeless campaign: changes in beliefs about smokeless tobacco among rural boys, a longitudinal randomized controlled field trial.

BACKGROUND: The prevalence of current smokeless tobacco (SLT) use in 2019 among high school students was 4.8%, and the overall rate of SLT use was higher among high school boys (7.5%) than girls (1.8%). The U.S. Food and Drug Administration (FDA) launched "The Real Cost" Smokeless media campaign in April 2016 to educate rural youth about the dangers of SLT use. In this study, we evaluate the effectiveness of "The Real Cost" Smokeless campaign. METHODS: We use a 3-year (Jan 2016 - Dec 2018) randomized controlled longitudinal field trial that consists of a baseline survey of boys and a parent/guardian and four follow-up surveys of the boys. The cohort includes 2200 boys who were 11 to 16 years old at baseline and lived in the rural segments of 30 media markets (15 treatment markets and 15 control). "The Real Cost" Smokeless campaign targets boys who are 12 to 17 years old in 35 media markets. It focuses primarily on graphic depictions of cosmetic and long-term health consequences of SLT use. The key outcome measures include beliefs and attitudes toward SLT that are targeted (explicitly or implicitly) by campaign messages. RESULTS: Using multivariate difference-in-difference analysis (conducted in 2019 and 2020), we found that agreement with 4 of the 11 explicit campaign-targeted belief and attitude measures increased significantly from baseline to post-campaign launch among boys 14 to 16 years old in treatment vs. control markets. Agreement did not increase for boys 11-13 years old in treatment vs. control markets and only increased for one targeted message for the overall sample. CONCLUSIONS: These findings suggest that "The Real Cost" Smokeless campaign influenced beliefs and attitudes among older boys in campaign markets and that a campaign focused on health consequences of tobacco use can be targeted to rural boys, influence beliefs about SLT use, and potentially prevent SLT use.

Brief Report: Are Serious Falls Associated With Subsequent Fragility Fractures Among Veterans Living With HIV?

BACKGROUND: The extensive research on falls and fragility fractures among persons living with HIV (PWH) has not explored the association between serious falls and subsequent fragility fracture. We explored this association. SETTING: Veterans Aging Cohort Study. METHODS: This analysis included 304,951 6-month person- intervals over a 15-year period (2001-2015) contributed by 26,373 PWH who were 50+ years of age (mean age 55 years) and taking antiretroviral therapy (ART). Serious falls (those falls significant enough to result in a visit to a health care provider) were identified by the external cause of injury codes and a machine learning algorithm applied to radiology reports. Fragility fractures were identified using ICD9 codes and included hip fracture, vertebral fractures, and upper arm fracture and were modeled with multivariable logistic regression with generalized estimating equations. RESULTS: After adjustment, serious falls in the previous year were associated with increased risk of fragility fracture [odds ratio (OR) 2.10; 95% confidence interval (CI): 1.83 to 2.41]. The use of integrase inhibitors was the only ART risk factor (OR 1.17; 95% CI: 1.03 to 1.33). Other risk factors included the diagnosis of alcohol use disorder (OR 1.49; 95% CI: 1.31 to 1.70) and having a prescription for an opioid in the previous 6 months (OR 1.40; 95% CI: 1.27 to 1.53). CONCLUSIONS: Serious falls within the past year are strongly associated with fragility fractures among PWH on ART-largely a middle-aged population-much as they are among older adults in the general population.

The sputum microbiome and clinical outcomes in patients with bronchiectasis: a prospective observational study.

BACKGROUND: Infection is a key component of bronchiectasis pathophysiology. Characterisation of the microbiome offers a higher degree of sensitivity and resolution than does traditional culture methods. We aimed to evaluate the role of the microbiome in determining the risk of exacerbation and long-term outcomes, including all-cause mortality, in bronchiectasis. METHODS: We did a prospective observational cohort study of patients with bronchiectasis from eastern Scotland. Patients were enrolled from Sept 11, 2012, to Dec 21, 2015, and followed until Jan 8, 2019, for long-term outcomes. Patients were included if they were aged 18 years or older, and had a high-resolution CT-confirmed diagnosis of bronchiectasis and clinical symptoms consistent with the disease. Sputum samples were obtained when patients were clinically stable. Repeat sputum samples were taken at stable and exacerbation visits during follow-up. The V3-V4 region of the bacterial 16S rRNA gene was sequenced using the Illumina MiSeq platform. The dominant bacterial genus in each sample was assigned on the basis of a previously published method. Microbiome characteristics were analysed for their association with measures of clinical disease severity and long-term outcomes using PERMANOVA, random forest, and survival analyses. FINDINGS: Sequencing data were obtained from the sputum samples of 281 patients with bronchiectasis who were included in the stable baseline cohort. 49 (17%) of 281 patients provided more than one sample when clinically stable and were included in the longitudinal analysis. 64 (23%) patients provided both stable and exacerbation samples. In both stable bronchiectasis and during exacerbations, a sputum microbiome dominated by Proteobacteria and Firmicutes was observed. Individual patients' microbiome profiles were relatively stable over time, during exacerbations and at disease stability. Lower microbiome diversity, measured using the Shannon-Wiener diversity index, was associated with more severe bronchiectasis defined by the bronchiectasis severity index, lower FEV1, and more severe symptoms. Random forest analysis of baseline samples identified Pseudomonas, Enterobacteriaceae, and Stenotrophomonas as being associated with severe bronchiectasis (bronchiectasis severity index ≥9) and greater lung inflammation and Pseudomonas and Enterobacteriaceae with more frequent exacerbations. Patients in whom Pseudomonas was dominant (n=35) were at increased risk of all-cause mortality (hazard ratio 3·12, 95% CI 1·33-7·36; p=0·0091) and had more frequent exacerbations (incident rate ratio 1·69, 95% CI 1·07-2·67; p=0·024) during follow-up compared with patients with other dominant genera (n=246). INTERPRETATION: A reduction in microbiome diversity, particularly one associated with dominance of Pseudomonas, is associated with greater disease severity, higher frequency and severity of exacerbations, and higher risk of mortality. The microbiome might therefore identify subgroups of patients at increased risk of poor outcomes who could benefit from precision treatment strategies. Further research is required to identify the mechanisms of reduced microbiome diversity and to establish whether the microbiome can be therapeutically targeted. FUNDING: British Lung Foundation and European Respiratory Society EMBARC2 consortium.

Serious Falls in Middle-Aged Veterans: Development and Validation of a Predictive Risk Model.

BACKGROUND/OBJECTIVES: Due to high rates of multimorbidity, polypharmacy, and hazardous alcohol and opioid use, middle-aged Veterans are at risk for serious falls (those prompting a visit with a healthcare provider), posing significant risk to their forthcoming geriatric health and quality of life. We developed and validated a predictive model of the 6-month risk of serious falls among middle-aged Veterans. DESIGN: Cohort study. SETTING: Veterans Health Administration (VA). PARTICIPANTS: Veterans, aged 45 to 65 years, who presented for care within the VA between 2012 and 2015 (N = 275,940). EXPOSURES: The exposures of primary interest were substance use (including alcohol and prescription opioid use), multimorbidity, and polypharmacy. Hazardous alcohol use was defined as an Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) score of 3 or greater for women and 4 or greater for men. We used International Classification of Diseases, Ninth Revision (ICD-9), codes to identify alcohol and illicit substance use disorders and identified prescription opioid use from pharmacy fill-refill data. We included counts of chronic medications and of physical and mental health comorbidities. MEASUREMENTS: We identified serious falls using external cause of injury codes and a machine-learning algorithm that identified serious falls in radiology reports. We used multivariable logistic regression with general estimating equations to calculate risk. We used an integrated predictiveness curve to identify intervention thresholds. RESULTS: Most of our sample (54%) was aged 60 years or younger. Duration of follow-up was up to 4 years. Veterans who fell were more likely to be female (11% vs 7%) and White (72% vs 68%). They experienced 43,641 serious falls during follow-up. We identified 16 key predictors of serious falls and five interaction terms. Model performance was enhanced by addition of opioid use, as evidenced by overall category-free net reclassification improvement of 0.32 (P < .001). Discrimination (C-statistic = 0.76) and calibration were excellent for both development and validation data sets. CONCLUSION: We developed and internally validated a model to predict 6-month risk of serious falls among middle-aged Veterans with excellent discrimination and calibration.

Severe Maternal Morbidity Among a Cohort of Post-9/11 Women Veterans.

Background: Maternal morbidity and mortality are key indicators of women's health status and quality of care. Maternal morbidity and mortality are high and rising in the United States. There has been no evaluation of severe maternal morbidity and mortality among veteran women, although population characteristics suggest that they may be at risk. This study aimed to evaluate a surveillance methodology at the U.S. Department of Veterans Affairs (VA) and describe the characteristics of women veterans who experienced severe maternal morbidity events. Materials and Methods: The study sample derived from a national sample of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans who were enrolled for care at the VA. The surveillance methodology followed a recommended process of case identification and chart review following a standardized guide. Centers for Disease Control and Prevention (CDC) International Classification of Diseases codes for maternal morbidity were applied to billing, inpatient, and outpatient data for 9,829 pregnancies among 91,061 veteran women between January 1, 2014 and December 31, 2016. Descriptive statistics is reported. Results: One hundred twenty-seven pregnancies with severe maternal morbidity events were identified, 66 of which were confirmed after chart review. The positive predictive value of CDC indicators to identify cases was 0.52. High rates of mental health problems, obesity, rurality, maternal conditions, and racial discrepancies were noted among veterans who experienced severe maternal morbidity events. Conclusions: Severe maternal morbidity affects a significant number of veteran women. Systematic reporting of pregnancy outcomes and a multidisciplinary review committee would improve surveillance and case management at the VA. The VA is uniquely positioned to develop innovative comanagement strategies, especially in the area of perinatal mental health.