Isabel E. Allen

Derivation and validation of two decision instruments for selective chest CT in blunt trauma: a multicenter prospective observational study (NEXUS Chest CT).

Background Unnecessary diagnostic imaging leads to higher costs, longer emergency department stays, and increased patient exposure to ionizing radiation. We sought to prospectively derive and validate two decision instruments (DIs) for selective chest computed tomography (CT) in adult blunt trauma patients. Methods and Findings From September 2011 to May 2014, we prospectively enrolled blunt trauma patients over 14 y of age presenting to eight US, urban level 1 trauma centers in this observational study. During the derivation phase, physicians recorded the presence or absence of 14 clinical criteria before viewing chest imaging results. We determined injury outcomes by CT radiology readings and categorized injuries as major or minor according to an expert-panel-derived clinical classification scheme. We then employed recursive partitioning to derive two DIs: Chest CT-All maximized sensitivity for all injuries, and Chest CT-Major maximized sensitivity for only major thoracic injuries (while increasing specificity). In the validation phase, we employed similar methodology to prospectively test the performance of both DIs. We enrolled 11,477 patients—6,002 patients in the derivation phase and 5,475 patients in the validation phase. The derived Chest CT-All DI consisted of (1) abnormal chest X-ray, (2) rapid deceleration mechanism, (3) distracting injury, (4) chest wall tenderness, (5) sternal tenderness, (6) thoracic spine tenderness, and (7) scapular tenderness. The Chest CT-Major DI had the same criteria without rapid deceleration mechanism. In the validation phase, Chest CT-All had a sensitivity of 99.2% (95% CI 95.4%–100%), a specificity of 20.8% (95% CI 19.2%–22.4%), and a negative predictive value (NPV) of 99.8% (95% CI 98.9%–100%) for major injury, and a sensitivity of 95.4% (95% CI 93.6%–96.9%), a specificity of 25.5% (95% CI 23.5%–27.5%), and a NPV of 93.9% (95% CI 91.5%–95.8%) for either major or minor injury. Chest CT-Major had a sensitivity of 99.2% (95% CI 95.4%–100%), a specificity of 31.7% (95% CI 29.9%–33.5%), and a NPV of 99.9% (95% CI 99.3%–100%) for major injury and a sensitivity of 90.7% (95% CI 88.3%–92.8%), a specificity of 37.9% (95% CI 35.8%–40.1%), and a NPV of 91.8% (95% CI 89.7%–93.6%) for either major or minor injury. Regarding the limitations of our work, some clinicians may disagree with our injury classification and sensitivity thresholds for injury detection. Conclusions We prospectively derived and validated two DIs (Chest CT-All and Chest CT-Major) that identify blunt trauma patients with clinically significant thoracic injuries with high sensitivity, allowing for a safe reduction of approximately 25%–37% of unnecessary chest CTs. Trauma evaluation protocols that incorporate these DIs may decrease unnecessary costs and radiation exposure in the disproportionately young trauma population.

Neurologic signs and symptoms frequently manifest in acute HIV infection

Objective: To determine the incidence, timing, and severity of neurologic findings in acute HIV infection (pre–antibody seroconversion), as well as persistence with combination antiretroviral therapy (cART). Methods: Participants identified with acute HIV were enrolled, underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks. Concurrent brain MRIs and both viral and inflammatory markers in plasma and CSF were obtained. Results: Median estimated HIV infection duration was 19 days (range 3–56) at study entry for the 139 participants evaluated. Seventy-three participants (53%) experienced one or more neurologic findings in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barré syndrome). A total of 245 neurologic findings were noted, reflecting cognitive symptoms (33%), motor findings (34%), and neuropathy (11%). Nearly half of the neurologic findings (n = 121, 49%) occurred at diagnosis, prior to cART initiation, and most of these (n = 110, 90%) remitted concurrent with 1 month on treatment. Only 9% of neurologic findings (n = 22) persisted at 24 weeks on cART. Nearly all neurologic findings (n = 236, 96%) were categorized as mild in severity. No structural neuroimaging abnormalities were observed. Participants with neurologic findings had a higher mean plasma log10 HIV RNA at diagnosis compared to those without neurologic findings (5.9 vs 5.4; p = 0.006). Conclusions: Acute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in treated acute HIV.

Correlation between pubic hair grooming and STIs: results from a nationally representative probability sample

Objective STIs are the most common infections among adults. Concurrently, pubic hair grooming is prevalent. Small-scale studies have demonstrated a relationship between pubic hair grooming and STIs. We aim to examine this relationship in a large sample of men and women. Design We conducted a probability survey of US residents aged 18–65 years. The survey ascertained self-reported pubic hair grooming practices, sexual behaviours and STI history. We defined extreme grooming as removal of all pubic hair more than 11 times per year and high-frequency grooming as daily/weekly trimming. Cutaneous STIs included herpes, human papillomavirus, syphilis and molluscum. Secretory STIs included gonorrhoea, chlamydia and HIV. We analysed lice separately. Results Of 7580 respondents who completed the survey, 74% reported grooming their pubic hair, 66% of men and 84% of women. After adjusting for age and lifetime sexual partners, ever having groomed was positively associated with a history of self-reported STIs (OR 1.8; 95% CI 1.4 to 2.2), including cutaneous STIs (OR 2.6; CI 1.8 to 3.7), secretory STIs (OR 1.7; CI 1.3 to 2.2) and lice (OR 1.9; CI 1.3 to 2.9). These positive associations were stronger for extreme groomers (OR 4.4; CI 2.9 to 6.8) and high-frequency groomers (OR 3.5; CI 2.3 to 5.4) with cutaneous STIs, and for non-extreme groomers (OR 2.0; CI 1.3 to 3.0) and low-frequency groomers (OR 2.0; CI 1.3 to 3.1) with lice. Conclusions Among a representative sample of US residents, pubic hair grooming was positively related to self-reported STI history. Further research is warranted to gain insight into STI risk-reduction strategies.

Association of Sleep-Disordered Breathing With Cognitive Function and Risk of Cognitive Impairment: A Systematic Review and Meta-analysis

Importance Growing evidence suggests an association between sleep-disordered breathing (SDB) and cognitive decline in elderly persons. However, results from population-based studies have been conflicting, possibly owing to different methods to assess SDB or cognitive domains, making it difficult to draw conclusions on this association. Objective To provide a quantitative synthesis of population-based studies on the relationship between SDB and risk of cognitive impairment. Data Sources PubMed, EMBASE, and PsychINFO were systematically searched to identify peer-reviewed articles published in English before January 2017 that reported on the association between SDB and cognitive function. Study Selection We included cross-sectional and prospective studies with at least 200 participants with a mean participant age of 40 years or older. Data Extraction and Synthesis Data were extracted independently by 2 investigators. We extracted and pooled adjusted risk ratios from prospective studies and standard mean differences from cross-sectional studies, using random-effect models. This meta-analysis followed the PRISMA guidelines and also adhered to the MOOSE guidelines. Main Outcomes and Measures Cognitive outcomes were based on standard tests or diagnosis of cognitive impairment. Sleep-disordered breathing was ascertained by apnea-hypopnea index or clinical diagnosis. Results We included 14 studies, 6 of which were prospective, covering a total of 4 288 419 men and women. Pooled analysis of the 6 prospective studies indicated that those with SDB were 26% (risk ratio, 1.26; 95% CI, 1.05-1.50) more likely to develop cognitive impairment, with no evidence of publication bias but significant heterogeneity between studies. After removing 1 study that introduced significant heterogeneity, the pooled risk ratio was 1.35 (95% CI, 1.11-1.65). Pooled analysis of the 7 cross-sectional studies suggested that those with SDB had slightly worse executive function (standard mean difference, −0.05; 95% CI, −0.09 to 0.00), with no evidence of heterogeneity or publication bias. Sleep-disordered breathing was not associated with global cognition or memory. Conclusions and Relevance Sleep-disordered breathing is associated with an increased risk of cognitive impairment and a small worsening in executive function. Further studies are required to determine the mechanisms linking these common conditions and whether treatment of SDB might reduce risk of cognitive impairment.

ApoE ε4 Is Associated With Cognition, Brain Integrity, and Atrophy in HIV Over Age 60.

Background:There are contradicting reports on the associations between Apolipoprotein E4 (ApoE &egr;4) and brain outcomes in HIV with some evidence that relationships may be greatest in older age groups. Methods:We assessed cognition in 76 clinically stable HIV-infected participants over age 60 and genotyped ApoE. Sixty-one of these subjects underwent structural brain magnetic resonance imaging and diffusion tensor imaging. Results:The median age of the participants was 64 years (range: 60–84) and the median estimated duration of HIV infection was 22 years. Apo &egr;4 carriers (n = 19) were similar to noncarriers (n = 57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE &egr;4 carriers demonstrated greater deficits in cognitive performance in the executive domain (P = 0.045) and had reduced fractional anisotropy and increased mean diffusivity throughout large white matter tracts within the brain compared with noncarriers. Tensor-based morphometry analyses revealed ventricular expansion and atrophy in the posterior corpus callosum, thalamus, and brainstem among HIV-infected ApoE &egr;4 carriers compared with &egr;4 noncarriers. Conclusions:In this sample of older HIV-infected individuals, having at least 1 ApoE &egr;4 allele was associated with decreased cognitive performance in the executive functioning domain, reduced brain white matter integrity, and brain atrophy. Brain atrophy was most prominent in the posterior corpus callosum, thalamus, and brainstem. This pattern of cognitive deficit, atrophy, and damage to white matter integrity was similar to that described in HIV, suggesting an exacerbation of HIV-related pathology; although emergence of other age-associated neurodegenerative disorders cannot be excluded.

Effect of Tamsulosin on Stone Passage for Ureteral Stones: A Systematic Review and Meta-analysis

Study objective: Tamsulosin is recommended for patients receiving a diagnosis of a ureteral stone less than 10 mm who do not require immediate urologic intervention. Because of conflicting results from recent meta‐analyses and large randomized controlled trials, the efficacy of tamsulosin is unclear. We perform a systematic review and meta‐analysis to investigate the effect of tamsulosin on stone passage in patients receiving a diagnosis of ureteral stone. Methods: MEDLINE, EMBASE, and CENTRAL databases were searched without language restriction through November 2015 for studies assessing the efficacy of tamsulosin and using a double‐blind, randomized, controlled trial design. Meta‐analysis was conducted with a random‐effects model and subgroup analyses were conducted to determine sources of heterogeneity. Results: Eight randomized controlled trials (N=1,384) contained sufficient information for inclusion. The pooled risk of stone passage in the tamsulosin arm was 85% versus 66% in the placebo arm, but substantial heterogeneity existed across trials (I2=80.2%; P<.001). After stratifying of studies by stone size, the meta‐analysis of the large stone subgroup (5 to 10 mm; N=514) indicated a benefit of tamsulosin (risk difference=22%; 95% confidence interval 12% to 33%; number needed to treat=5). The meta‐analysis of the small stone subgroup (<4 to 5 mm; N=533) indicated no benefit (risk difference=–0.3%; 95% confidence interval –4% to 3%). Neither meta‐analysis for the occurrence of dizziness or hypotension showed a significant effect. Conclusion: Tamsulosin significantly improves stone passage in patients with larger stones, whereas the effect of tamsulosin is diminished in those with smaller stones, who are likely to pass their stone regardless of treatment.

Cognitive-behavioral changes in amyotrophic lateral sclerosis: Screening prevalence and impact on patients and caregivers.

Abstract Our objective was to evaluate the association between cognitive-behavioral deficits and patient quality of life (QoL), caregiver burden, and disease stage in a population of patients with amyotrophic lateral sclerosis (ALS). We administered the ALS Cognitive-Behavioral Screen™ to 86 patients with ALS. Multiple regression was used to evaluate the association between cognitive or behavioral deficits and disease stage, patient QoL, and caregiver burden while controlling for clinically important variables. Of 86 participants enrolled, 53 (62%) had some degree of cognitive impairment, 32 (37%) were behaviorally impaired and four met both cognitive and behavioral screening criteria for frontotemporal dementia (FTD). The severity of cognitive-behavioral deficits was not associated with patient QoL. More pronounced cognitive deficits (beta = –1.4, p = 0.04) and behavioral symptoms (–0.69, p < 0.001) predicted higher caregiver burden. Self-reported QoL was lower in patients with more depressive symptoms (beta = –0.32, p < 0.001) and more advanced disease (beta =0.10, p = 0.01). In conclusion, general QoL for patients with ALS is not associated with cognitive or behavioral deficits. More severe cognitive deficits and caregiver-reported behavioral symptoms predict higher caregiver burden. Routine cognitive-behavioral screening can identify patients who require full neuropsychological examination, inform patient counseling, and identify caregivers in need of early, targeted interventions.

Sex differences in soluble markers vary before and after the initiation of antiretroviral therapy in chronically HIV-infected individuals

Objective: To evaluate differences in soluble inflammatory markers between chronically HIV-infected men and women, with or without cognitive impairment, and in response to treatment. Design: Soluble biomarkers were measured in cryopreserved plasma and cerebrospinal fluid (CSF) of 60 treatment-naïve individuals (25 men and 35 women) with chronic HIV infection and 18 HIV-uninfected controls (9 men and 9 women) from Thailand. Following enrollment, participants began combination antiretroviral therapy and were evaluated for expression of these markers after 48 weeks. Methods: Plasma and CSF levels of 19 soluble biomarkers (IFN-&ggr;, TNF&agr;, TNF-RII, IL-1&agr;, IL-1&bgr;, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-15, MCP-1, t-Tau, IP-10, neopterin, IFN&agr;, I-FABP, and sCD14) were measured using either a multiparameter or standard ELISA assay. Results: Prior to combination antiretroviral therapy, women with impaired cognition had elevated levels of neopterin and TNF-RII compared with women with normal cognition in both the plasma and CSF; however, levels did not differ between cognitively impaired or normal men. In a secondary outcome-hypothesis generating analysis, sex differences were also pronounced in plasma levels of MCP-1, IL-10, I-FABP, and sCD14 in response to treatment. Neopterin, IP-10, TNF&agr;, TNF-RII, IFN&agr;, MCP-1, IL-8, I-FABP, and sCD14 plasma levels remained elevated following 48 weeks of therapy in both sexes compared with uninfected controls. Conclusion: We provide evidence of sustained immune activation after 48 weeks of treatment and identify possible sex differences in biomarkers previously linked to cognitive impairment, chronic inflammation, and gut integrity that may contribute to immunological differences between sexes in relationship to disease progression and response to therapy.

Risk of serious adverse events in hypertensive patients receiving isradipine: a meta-analysis

A meta-analysis was performed to compare the risk of serious adverse events associated with the use of all formulations of isradipine, when used as monotherapy in hypertension, to active drug or placebo controls. Eligible studies totalled 65 published and unpublished randomised controlled trials involving 9903 subjects and 10 675 treatment exposures: 4492 to isradipine, 1473 to isradipine sustained release, 2768 to other active drugs, and 1942 to placebo. Mortality, cardiovascular outcomes, other serious incident illnesses, such as cancer, and withdrawals were sought. Seventy-five per cent of the isradipine exposures were to standard-release formulations and 25% were to sustained-release formulations. Overall, isradipine therapy shows no difference in risk of major adverse events or withdrawals compared to other active controls or placebo (odds ratios [OR] 0.9; 95% CI 0.7–1.46 and 0.5; 95% CI 0.2–1.3). These major adverse events included angina, fatal and non-fatal myocardial infarction, stroke and overall mortality. Isradipine sustained release could be compared only to placebo, based on available data, and shows a lower risk of withdrawals (OR 0.5; 95% CI 0.3–0.9), and a similar trend was observed for major adverse events, (OR 0.8; 95% CI 0.3–2.5). Published and unpublished randomised controlled trials were analysed in separate meta-analyses and later combined when this sensitivity analysis of risk showed no differences between the groups. In conclusion, we find no evidence for increased risk of serious adverse events in patients receiving isradipine as monotherapy for hypertension.

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years

Background: Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants. Methods: We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24). Results: The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. Conclusions: Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.