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1.  The Effect of Childhood Cow's Milk Intake and HLA-DR Genotype on Risk of Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young (DAISY) 
Pediatric diabetes  2014;16(1):31-38.
Background
Cow's milk intake has been inconsistently associated with islet autoimmunity (IA) and type 1 diabetes (T1D) development. Genetic and environmental factors may modify the effect of cow's milk on IA and T1D risk.
Methods
The Diabetes Autoimmunity Study in the Young (DAISY) follows children at increased T1D risk for IA (presence of autoantibodies to insulin, GAD65 or IA-2 twice in succession) and T1D development. We examined 1,835 DAISY children with data on cow's milk intake: 143 developed IA, 40 subsequently developed T1D. Cow's milk protein and lactose intake were calculated from prospectively collected parent- and self-reported food frequency questionnaires (FFQ). High risk HLA-DR genotype: HLA-DR3/4,DQB1*0302; low/moderate risk: all other genotypes. We examined interactions between cow's milk intake, age at cow's milk introduction, and HLA-DR genotype in IA and T1D development. Interaction models contained the base terms (e.g., cow's milk protein and HLA-DR genotype) and an interaction term (cow's milk protein*HLA-DR genotype).
Results
In survival models adjusted for total calories, FFQ type, T1D family history, and ethnicity, greater cow's milk protein intake was associated with increased IA risk in children with low/moderate risk HLA-DR genotypes (Hazard Ratio (HR): 1.41, 95% Confidence Interval (CI): 1.08–1.84), but not in children with high risk HLA-DR genotypes. Cow's milk protein intake was associated with progression to T1D (HR: 1.59, CI: 1.13–2.25) in children with IA.
Conclusions
Greater cow's milk intake may increase risk of IA and progression to T1D. Early in the T1D disease process, cow's milk intake may be more influential in children with low/moderate genetic T1D risk.
doi:10.1111/pedi.12115
PMCID: PMC4104257  PMID: 24444005
cow's milk protein; childhood diet; HLA-DR genotype; Islet Autoimmunity
2.  Performance Characteristics of Xpert Flu/RSV XC Assay 
Journal of Clinical Microbiology  2015;53(8):2720-2721.
The Xpert Flu/RSV XC assay was compared to laboratory-developed tests (LDTs) (n = 207) and the Xpert Flu assay (n = 147) using archived nasopharyngeal swabs. The percentages of positive agreements with LDTs were 97.8% for influenza A, 97.2% for influenza B, and 89.3% for RSV. The sensitivity of influenza detection was improved with the Xpert Flu/RSV XC assay compared to the Xpert Flu assay.
doi:10.1128/JCM.00972-15
PMCID: PMC4508419  PMID: 26019209
3.  Bartonella spp. Exposure in Northern and Southern Sea Otters in Alaska and California 
Vector Borne and Zoonotic Diseases  2014;14(12):831-837.
Abstract
Since 2002, an increased number of northern sea otters (Enhydra lutris kenyoni) from southcentral Alaska have been reported to be dying due to endocarditis and/or septicemia with infection by Streptococcus infantarius subsp. coli. Bartonella spp. DNA was also detected in northern sea otters as part of mortality investigations during this unusual mortality event (UME) in Kachemak Bay, Alaska. To evaluate the extent of exposure to Bartonella spp. in sea otters, sera collected from necropsied and live-captured northern sea otters, as well as necropsied southern sea otters (Enhydra lutris nereis) unaffected by the UME, were analyzed using an immunofluorescent antibody assay. Antibodies against Bartonella spp. were detected in sera from 50% of necropsied and 34% of presumed healthy, live-captured northern sea otters and in 16% of necropsied southern sea otters. The majority of sea otters with reactive sera were seropositive for B. washoensis, with antibody titers ranging from 1:64 to 1:256. Bartonella spp. antibodies were especially common in adult northern sea otters, both free-living (49%) and necropsied (62%). Adult stranded northern sea otters that died from infectious causes, such as opportunistic bacterial infections, were 27 times more likely to be Bartonella seropositive than adult stranded northern sea otters that died from noninfectious causes (p<0.001; 95% confidence interval 2.62–269.4). Because Bartonella spp. antibodies were detected in necropsied northern sea otters from southcentral (44%) and southwestern (86%) stocks of Alaska, as well as in necropsied southern sea otters (16%) in southcentral California, we concluded that Bartonella spp. exposure is widely distributed among sea otter populations in the Eastern Pacific, providing context for investigating future disease outbreaks and monitoring of Bartonella infections for sea otter management and conservation.
doi:10.1089/vbz.2014.1612
PMCID: PMC4270147  PMID: 25514118
Northern sea otter; Southern sea otter; Bartonella spp; Antibodies; Bartonella washoensis; Alaska
4.  Protracted impairment of impulse control under an acute dose of alcohol: A time course analysis 
Addictive behaviors  2013;39(11):1589-1596.
Alcohol is well-known for impairing impulse control as well as its disruptive effects on other aspects of behavioral functioning, such as motor control. Time-course analyses during a single dose show rapid development of acute tolerance to impairment of motor coordination, reaction time, and levels of subjective intoxication, but no acute tolerance to impairment of the ability to inhibit responses. Evidence for a possible lag in tolerance development to the impairing effects of alcohol on inhibitory control suggests that, as drinkers’ blood alcohol concentration (BAC) declines, they might exhibit prolonged impulsivity despite having an unimpaired ability to initiate action. The present study extended the time-course analysis to examine the recovery of inhibitory control under a dose of alcohol as drinkers’ BAC descended from a peak of 80 mg/100 ml to a zero level. Twenty-four healthy adults were tested following 0.65 g/kg alcohol and a placebo in a counterbalanced order. They performed a cued go/no-go task that measured response inhibition. They also performed tasks that assessed reaction time, motor coordination, and completed ratings of their subjective levels of intoxication. Alcohol initially impaired inhibitory control, response time, and motor coordination and increased subjective ratings of intoxication. However, acute tolerance to the impairing effects of alcohol was observed for measures of response time, motor coordination, and ratings of intoxication and these measures returned to sober (i.e., placebo) levels by the time BAC fell to near zero. By contrast, impairment of inhibitory control showed no acute tolerance and remained impaired even when drinkers’ BAC returned to near zero. Taken together, these results indicate that the disinhibiting effects of alcohol are present even when the impairing effects of alcohol on other aspects of behavior have diminished under the dose. These findings could provide a greater understanding of impulsive behaviors during the descending limb of intoxication.
doi:10.1016/j.addbeh.2013.10.035
PMCID: PMC4014538  PMID: 24286706
Alcohol; Inhibition; Tolerance; Go/No-Go Task
5.  Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa 
Human Reproduction (Oxford, England)  2015;30(12):2737-2746.
STUDY QUESTION
Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success?
SUMMARY ANSWER
Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF.
WHAT IS KNOWN ALREADY
In human spermatozoa, Ca2+ influx induced by progesterone is mediated by CatSper, a sperm-specific Ca2+ channel. A suboptimal Ca2+ influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca2+]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception.
STUDY DESIGN, SIZE, DURATION
Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Samples were primarily screened using the Ca2+ influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca2+ response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a defective Ca2+ response were further examined in order to characterize the potential CatSper abnormalities. In men where there was a consistent and robust failure of calcium signalling, a direct assessment of CatSper function was performed using electrophysiology (patch clamping), and a blood sample was obtained for genetic analysis.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 101/102 (99%) IVF patients and 22/23 (96%) donors exhibited a normal Ca2+ response. The mean (±SD) normalized peak response did not differ between donors and IVF patients (2.57 ± 0.68 [n = 34 ejaculates from 23 different donors] versus 2.66 ± 0.68 [n = 102 IVF patients], P = 0.63). In recall patients, 9/10 (90%) showed a normal Ca2+ response. Three men were initially identified with a defective Ca2+ influx. However, only one (Patient 1) had a defective response in repeat semen samples. Electrophysiology experiments on sperm from Patient 1 showed a near absence of CatSper current and exon screening demonstrated no mutations in the coding regions of the CatSper complex. There was no increase in penetration of viscous media when the spermatozoa were stimulated with progesterone and importantly there was failed fertilization at IVF.
LIMITATIONS, REASONS FOR CAUTION
A key limitation relates to working with a specific functional parameter (Ca2+ influx induced by progesterone) in fresh sperm samples from donors and patients that have limited viability. Therefore, for practical, technical and logistical reasons, some men (∼22% of IVF patients) could not be screened. As such the incidence of significant Ca2+ abnormalities induced by progesterone may be higher than the ∼1% observed here. Additionally, we used a strict definition of a defective Ca2+ influx such that only substantial abnormalities were selected for further study. Furthermore, electrophysiology was only performed on one patient with a robust and repeatable defective calcium response. This man had negligible CatSper current but more subtle abnormalities (e.g. currents present but significantly smaller) may have been present in men with either normal or below normal Ca2+ influx.
WIDER IMPLICATIONS OF THE FINDINGS
These data add significantly to the understanding of the role of CatSper in human sperm function and its impact on male fertility. Remarkably, these findings provide the first direct evidence that CatSper is a suitable and specific target for human male contraception.
STUDY FUNDING/COMPETING INTEREST(S)
Initial funding was from NHS Tayside, Infertility Research Trust, TENOVUS, Chief Scientist Office NRS Fellowship, the Wellcome Trust, University of Abertay. The majority of the data were obtained using funding from a MRC project grant (# 4190). The authors declare that there is no conflict of interest.
TRIAL REGISTRATION NUMBER
Not applicable.
doi:10.1093/humrep/dev243
PMCID: PMC4643530  PMID: 26453676
CatSper; male fertility; sperm motility; ion channels; calcium stores; electrophysiology; failed fertilization; contraception; unexplained infertility; sperm dysfunction
6.  Views on Human Papillomavirus Vaccination: A Mixed-Methods Study of Urban Youth 
Journal of community health  2014;39(5):835-841.
While the human papillomavirus (HPV) vaccine has potential to protect against the majority of HPV-associated cancers, vaccination rates in the United States remain low. Racial/ethnic and economic disparities exist for HPV vaccination completion rates. We conducted a mixed-methods study using the theory of planned behavior framework to explore attitudes and beliefs about HPV vaccination among urban, economically disadvantaged adolescents. Fifty adolescents aged 14-18 years were recruited from community-based organizations to complete a written survey and participate in a focus group. The mean age was 15.5 ± 1.3 years; 98% were African American or mixed race; 64% were female; 52% reported previous sexual intercourse; 40% reported receipt of ≥ 1 HPV vaccine dose. The knowledge deficit about the HPV vaccine was profound and seemed slightly greater among males. Mothers, fathers and grandmothers were mentioned as important referents for HPV vaccination, but peers and romantic partners were not. Common barriers to vaccination were lack of awareness, anticipated side effects (i.e., pain), and concerns about vaccine safety. Characteristics associated with ≥1 vaccine dose were: having heard of the HPV vaccine vs. not (65% vs. 20%, p=0.002) and agreeing with the statement “Most people I know would think HPV vaccine is good for your health” vs. not (67% vs. 27%, p=0.007). Our work indicates a profound lack of awareness about HPV vaccination as well as the important influence of parents among urban, economically-disadvantaged youth. Awareness of these attitudes and beliefs can assist providers and health officials by informing specific interventions to increase vaccine uptake.
doi:10.1007/s10900-014-9858-2
PMCID: PMC4174729  PMID: 24664875
Adolescent; Health promotion; Papillomavirus vaccine; Healthcare disparity
7.  Impact of a Rapid Microarray-Based Assay for Identification of Positive Blood Cultures for Treatment Optimization for Patients with Streptococcal and Enterococcal Bacteremia 
Journal of Clinical Microbiology  2015;53(4):1411-1414.
Implementation of the Verigene Gram-positive blood culture test led to reductions in time to acceptable antibiotic overall (1.9 versus 13.2 h, respectively; P = 0.04) and time to appropriate antibiotic for patients with vancomycin-resistant Enterococcus (4.2 versus 43.7 h; P = 0.006) and viridans group Streptococcus (0.2 versus 7.1 h; P = 0.02).
doi:10.1128/JCM.00104-15
PMCID: PMC4365208  PMID: 25673785
8.  Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold 
TASK-1 is a two-pore domain potassium channel that is important to modulating cell excitability, most notably in the context of neuronal pathways. In order to leverage TASK-1 for therapeutic benefit, its physiological role needs better characterization; however, designing selective inhibitors that avoid the closely related TASK-3 channel has been challenging. In this study, a series of bis-amide derived compounds were found to demonstrate improved TASK-1 selectivity over TASK-3 compared to reported inhibitors. Optimization of a marginally selective hit led to analog 35 which displays a TASK-1 IC50 = 16 nM with 62-fold selectivity over TASK-3 in an orthogonal electrophysiology assay.
doi:10.1016/j.bmcl.2014.06.032
PMCID: PMC4160056  PMID: 25017033
TASK1; KCNK3; selective potassium channel inhibitor; bis-amide
9.  Comparison of the Gen-Probe Aptima HIV-1 and Abbott HIV-1 Qualitative Assays with the Roche Amplicor HIV-1 DNA Assay for Early Infant Diagnosis Using Dried Blood Spots 
Background
The current gold standard for infant diagnosis of HIV-1 is the Roche Amplicor Qualitative DNA assay, but it is being phased out.
Objective
Compare the Abbott qualitative assay and the Gen-Probe Aptima assay to the gold standard Roche DNA assay using dried blood spots (DBS).
Study design
The Gen-Probe Aptima and Abbott qualitative HIV-1 assays were compared to the Roche DNA assay for early infant diagnosis. Specificity and sensitivity were determined for the three assays using DBS from 50 HIV-exposed uninfected infants and 269 HIV-1 infected adults from North Carolina, respectively. All of the negative and 151 of the positive DBS had valid results on the 3 different assays, and an additional 118 positive DBS had valid results on the Roche DNA and Aptima assays.
Results
All three assays were very specific. The Roche DNA assay was the most sensitive (96.7%) over a wide range of HIV PVL, including samples with PVL<400 copies/ml. Restricted to samples with PVL>400 copies/ml, the Gen-Probe Aptima assay had sensitivity (96.5%) comparable to the Roche DNA assay (98.8%). The Abbott Qualitative assay was the least sensitive and only had sensitivity above 95% among samples with PVL over 1000 copies/ml.
Conclusions
The Abbott HIV-1 Qualitative assay was not as sensitive as the comparator assays, so it would not be a useful replacement assay, especially for infants taking antiretroviral prophylaxis. The Gen-Probe Aptima assay is an adequate replacement option for infant diagnosis using DBS.
doi:10.1016/j.jcv.2014.05.012
PMCID: PMC4077672  PMID: 24929752
10.  Xpert MTB/RIF Assay Shortens Airborne Isolation for Hospitalized Patients With Presumptive Tuberculosis in the United States 
First-line Xpert testing on 1, 2, or 3 respiratory specimens significantly decreased airborne isolation duration compared with the 3-smear microscopy strategy in the United States. The 2-specimen Xpert strategy was optimal, capturing all tuberculosis cases while minimizing airborne isolation.
Background. In the United States, individuals with presumptive pulmonary tuberculosis are placed in airborne infection isolation (AII) and assessed by smear microscopy on 3 respiratory specimens collected 8–24 hours apart. Xpert MTB/RIF assay (Xpert) on 1, 2, or 3 specimens may be more efficient for determining AII discontinuation.
Methods. This single-center, observational cohort study of inpatients with presumptive pulmonary tuberculosis enrolled adults with 1 or more sputum specimens submitted for smear microscopy. Smear microscopy and Xpert were performed on each sputum specimen. Clinicians were blinded to Xpert results. The primary endpoint was AII duration. Secondary endpoints were laboratory processing time, strategy-based tuberculosis detection, and sensitivity and specificity.
Results. Among 207 subjects, the median AII duration was 68.0 hours (interquartile range [IQR], 47.1–97.5) for smear microscopy compared with 20.8 hours (IQR, 16.8–32.0) for the 1-specimen Xpert, 41.2 hours (IQR, 26.6–54.8) for the 2-specimen Xpert, and 54.0 hours (IQR, 43.3–80.0) for the 3-specimen Xpert strategies (P ≤ .004). Median laboratory processing time for smear microscopy was 2.5 times as long as Xpert (P < .001). The 2- and 3-specimen Xpert and smear microscopy strategies captured all 6 tuberculosis cases. The 1-specimen Xpert strategy missed 1 case. No difference was observed between smear microscopy and Xpert in sensitivity or specificity for detection of Mycobacterium tuberculosis.
Conclusions. Xpert-based strategies significantly reduced AII duration compared with the smear-based strategy. The 2-specimen Xpert strategy was most efficient in minimizing AII time while identifying all tuberculosis cases among individuals with presumptive tuberculosis in this low-burden setting.
doi:10.1093/cid/ciu212
PMCID: PMC4133562  PMID: 24729506
Xpert; tuberculosis; infection control; United States
11.  Sociotechnical challenges to developing technologies for patient access to health information exchange data 
Background
Providing patients with access to their medical data is widely expected to help educate and empower them to manage their own health. Health information exchange (HIE) infrastructures could potentially help patients access records across multiple healthcare providers. We studied three HIE organizations as they developed portals to give consumers access to HIE data previously exchanged only among healthcare organizations.
Objective
To follow the development of new consumer portal technologies, and to identify barriers and facilitators to patient access to HIE data.
Methods
Semistructured interviews of 15 key informants over a 2-year period spanning the development and early implementation of three new projects, coded according to a sociotechnical framework.
Results
As the organizations tried to develop functionality that fully served the needs of both providers and patients, plans were altered by technical barriers (primarily related to data standardization) and cultural and legal issues surrounding data access. Organizational changes also played an important role in altering project plans. In all three cases, patient access to data was significantly scaled back from initial plans.
Conclusions
This prospective study revealed how sociotechnical factors previously identified as important in health information technology success and failure helped to shape the evolution of three novel consumer informatics projects. Barriers to providing patients with seamless access to their HIE data were multifactorial. Remedies will have to address technical, organizational, cultural, and other factors.
doi:10.1136/amiajnl-2013-002073
PMCID: PMC4078272  PMID: 24064443
Implementation research; Consumer health informatics; Personal health records; Qualitative methods; Electronic health records; Health information exchange
12.  Accessing General and Sexual Healthcare: Experiences of Urban Youth 
Urban adolescents face many barriers to health care that contribute to health disparities in rates of sexually transmitted infections (STIs) and unintended pregnancy. Designing interventions to increase access to health care is a complex process that requires understanding the perspectives of adolescents. We conducted six focus groups to explore the attitudes and beliefs about general and sexual health care access as well as barriers to care among urban, economically disadvantaged adolescents. Participants first completed a written survey assessing health behaviors, health care utilization, and demographics. The discussion guide was based on the Theory of Planned Behavior and its constructs: attitudes, subjective norms, and perceived behavioral control. Transcripts of group discussions were analyzed using directed content analysis with triangulation and consensus to resolve differences. Fifty youth participated (mean age 15.5 years; 64% female; 90% African American). Many (23%) reported missed health care in the previous year. About half (53%) reported previous sexual intercourse; of these, 35% reported no previous sexual health care. Youth valued adults as important referents for accessing care as well as multiple factors that increased comfort such as good communication skills, and an established relationship. However, many reported mistrust of physicians and identified barriers to accessing care including fear and lack of time. Most felt that accessing sexual health care was more difficult than general care. These findings could inform future interventions to improve access to care and care-seeking behaviors among disadvantaged youth.
doi:10.1080/17450128.2014.925170
PMCID: PMC4119761  PMID: 25101138
Adolescent; Health Care Disparities; Health Care Quality; Access; Evaluation
13.  Evidence for a Causal Relationship Between Early Exocrine Pancreatic Disease and Cystic Fibrosis–Related Diabetes: A Mendelian Randomization Study 
Diabetes  2014;63(6):2114-2119.
Circulating immunoreactive trypsinogen (IRT), a biomarker of exocrine pancreatic disease in cystic fibrosis (CF), is elevated in most CF newborns. In those with severe CF transmembrane conductance regulator (CFTR) genotypes, IRT declines rapidly in the first years of life, reflecting progressive pancreatic damage. Consistent with this progression, a less elevated newborn IRT measure would reflect more severe pancreatic disease, including compromised islet compartments, and potentially increased risk of CF-related diabetes (CFRD). We show in two independent CF populations that a lower newborn IRT estimate is associated with higher CFRD risk among individuals with severe CFTR genotypes, and we provide evidence to support a causal relationship. Increased loge(IRT) at birth was associated with decreased CFRD risk in Canadian and Colorado samples (hazard ratio 0.30 [95% CI 0.15–0.61] and 0.39 [0.18–0.81], respectively). Using Mendelian randomization with the SLC26A9 rs7512462 genotype as an instrumental variable since it is known to be associated with IRT birth levels in the CF population, we provide evidence to support a causal contribution of exocrine pancreatic status on CFRD risk. Our findings suggest CFRD risk could be predicted in early life and that maintained ductal fluid flow in the exocrine pancreas could delay the onset of CFRD.
doi:10.2337/db13-1464
PMCID: PMC4030111  PMID: 24550193
14.  Clinical Experience of Life-Threatening Dabigatran-Related Bleeding at a Large, Tertiary Care, Academic Medical Center: a Case Series 
Journal of Medical Toxicology  2014;10(2):223-228.
Introduction
Dabigatran, an oral direct thrombin inhibitor, is FDA approved for the prevention of stroke in patients with nonvalvular atrial fibrillation. No agent exists for the reversal of dabigatran-related major bleeding. Prothrombin complex concentrate (PCC) has been studied in reversal but was not shown to affect the surrogate markers of bleeding such as the thrombin time, ecarin clotting time, or activated partial thromboplastin time (aPTT). Recombinant factor VIIa (rFVIIa) may provide benefit in patients with life-threatening or major bleeding; however, it has not been studied in dabigatran-related bleeding. PCC and rFVIIa are agents utilized at our institution for major bleeding in patients receiving anticoagulant therapy. Due to the high cost and thrombogenic risk of both rVIIa and PCC and lack of a clear reversal strategy, we reviewed the management of all reported cases of dabigatran-related bleeding.
Methods
This was a retrospective chart review of patients admitted to UMass Memorial Medical Center with a bleeding event and also receiving dabigatran therapy.
Results
Eleven patients on dabigatran admitted for bleeding were identified. Seven were admitted for an intracranial hemorrhage (ICH) and four for a gastrointestinal hemorrhage (GIH). The baseline characteristics are as follows: mean age was 74.55 years (range, 63–89), and seven were male. Admission mean hemoglobin was 11.88 g/dl (range, 6.1–18), mean international normalized ratio (INR) was 2.2 (range, 1.1–7.1), and mean aPTT was 42.21 s (range, 36–81.4). Interventions received included fresh frozen plasma (n = 6), platelets (n = 3), packed red blood cells (n = 4), rFVIIa (n = 2), intravenous fluids (n = 10), surgical intervention (n = 3), and dialysis (n = 2). No patients received PCC. Four patients survived in the ICH group, and four patients survived in the GIH group.
Conclusion
Reversal strategies for dabigatran-related bleeding events at our institution are highly variable. Intracranial hemorrhage in patients on dabigatran was associated with 43 % mortality. Patients with severe dabigatran-related bleeding may benefit from a standardized approach to treatment.
doi:10.1007/s13181-013-0364-1
PMCID: PMC4057537  PMID: 24385325
Dabigatran; Reversal; New oral anticoagulant
15.  Issues of Survivorship Are Rarely Addressed during Intensive Care Unit Stays. Baseline Results from a Statewide Quality Improvement Collaborative 
Rationale/Objective: In the context of increasing survivorship from critical illness, many studies have documented persistent sequelae among survivors. However, few evidence-based therapies exist for these problems. Support groups have proven efficacy in other populations, but little is known about their use after an intensive care unit (ICU) stay. Therefore, we surveyed critical care practitioners regarding their hospital’s practice regarding discussing post-ICU problems for survivors with patients and their loved ones, communicating with primary care physicians, and providing support groups for current or former patients and families.
Methods: A written survey was administered to 263 representatives of 73 hospitals attending the January 2013 annual meeting of the Michigan Health and Hospitals Association Keystone ICU initiative, a quality improvement collaborative focused on enhancing outcomes across Michigan ICUs.
Results: There were 174 completed surveys, a 66% response rate. Representatives included staff nurses, nursing leadership, physicians, hospital administrators, respiratory therapists, and pharmacists. Sixty-nine percent of respondents identified at least one issue facing ICU survivors after discharge. The concerns most commonly identified by these ICU practitioners were weakness, psychiatric pathologies, cognitive dysfunction, and transitions of care. However, most respondents did not routinely discuss post-ICU problems with patients and families, and only 20% had a mechanism to formally communicate discharge information to primary care providers. Five percent reported having or being in the process of creating a support group for ICU survivors after discharge.
Conclusions: Despite growing awareness of the problems faced by ICU survivors, in this statewide quality improvement collaborative, hospital-based support groups are rarely available, and deficiencies in transitions of care exist. Practice innovations and formal research are needed to provide ways to translate awareness of the problems of survivorship into improved outcomes for patients.
doi:10.1513/AnnalsATS.201401-007BC
PMCID: PMC4225798  PMID: 24605936
critical illness; intensive care unit; recovery; support groups; disability
16.  Implementing Motivational Interviewing in a Pediatric Hospital 
Missouri medicine  2014;111(3):212-216.
Motivational interviewing is a collaborative style of communication designed to strengthen a person’s own motivation and commitment to change. We report on our ongoing efforts to implement motivational interviewing to address health behavior change among several patient populations in our pediatric hospital, including sexual risk reduction among adolescents, increased self-care for patients with spina bifida, increased adherence for adolescents with Type 1 diabetes, and facilitation with transition from pediatric to adult care among gastroenterology patients.
PMCID: PMC4261616  PMID: 25011343
pediatrics; motivational interviewing; provider-patient communication
17.  When do confounding by indication and inadequate risk adjustment bias critical care studies? A simulation study 
Critical Care  2015;19(1):195.
Introduction
In critical care observational studies, when clinicians administer different treatments to sicker patients, any treatment comparisons will be confounded by differences in severity of illness between patients. We sought to investigate the extent that observational studies assessing treatments are at risk of incorrectly concluding such treatments are ineffective or even harmful due to inadequate risk adjustment.
Methods
We performed Monte Carlo simulations of observational studies evaluating the effect of a hypothetical treatment on mortality in critically ill patients. We set the treatment to have either no association with mortality or to have a truly beneficial effect, but more often administered to sicker patients. We varied the strength of the treatment’s true effect, strength of confounding, study size, patient population, and accuracy of the severity of illness risk-adjustment (area under the receiver operator characteristics curve, AUROC). We measured rates in which studies made inaccurate conclusions about the treatment’s true effect due to confounding, and the measured odds ratios for mortality for such false associations.
Results
Simulated observational studies employing adequate risk-adjustment were generally able to measure a treatment’s true effect. As risk-adjustment worsened, rates of studies incorrectly concluding the treatment provided no benefit or harm increased, especially when sample size was large (n = 10,000). Even in scenarios of only low confounding, studies using the lower accuracy risk-adjustors (AUROC < 0.66) falsely concluded that a beneficial treatment was harmful. Measured odds ratios for mortality of 1.4 or higher were possible when the treatment’s true beneficial effect was an odds ratio for mortality of 0.6 or 0.8.
Conclusions
Large observational studies confounded by severity of illness have a high likelihood of obtaining incorrect results even after employing conventionally “acceptable” levels of risk-adjustment, with large effect sizes that may be construed as true associations. Reporting the AUROC of the risk-adjustment used in the analysis may facilitate an evaluation of a study’s risk for confounding.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-015-0923-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s13054-015-0923-8
PMCID: PMC4432515  PMID: 25925165
18.  High Level Human Herpesvirus-6 Viremia Associated with onset of Stevens-Johnson Syndrome: Report of 2 Cases 
The pathogenesis of Stevens Johnson Syndrome (SJS) remains obscure but it has been associated with various infectious agents, including members of the Herpes virus family. We present the first report of high level human herpesvirus-6 (HHV-6) viremia at the onset of SJS suggesting a possible new association. This finding supports the need for further investigation into the possible relationship between HHV-6 and SJS which may illuminate the pathogenesis of SJS and bring us closer to achieving enhanced prevention and treatment of this rare disease.
doi:10.1097/BCR.0b013e3181d0f48b
PMCID: PMC4396637  PMID: 20182379
Human Herpesvirus-6; HHV-6; Stevens-Johnson Syndrome; Herpes Viruses
19.  Heavy drinking and the role of inhibitory control of attention 
Alcohol can disrupt goal-directed behavior by impairing the ability to inhibit attentional shifts towards salient but goal-irrelevant stimuli. Individuals who are highly sensitive to this effect of the drug may be at increased risk for problematic drinking, especially among those whose attention is drawn to alcohol-related cues in the environment (i.e., attentional bias). The current study examined the acute impairing effect of alcohol on inhibitory mechanisms of attentional control in a group of healthy social drinkers. We then examined whether increased sensitivity to this disinhibiting effect of alcohol was associated with heavy drinking, especially among those who have an attentional bias towards alcohol-related stimuli. Eighty nondependent social drinkers performed a delayed ocular response task that measured their inhibitory control of attention by their ability to suppress attentional shifts to irrelevant stimuli. Attentional bias was measured using a visual probe task. Inhibitory control was assessed following a moderate dose of alcohol (0.64 g/kg) and a placebo. Participants made more inhibitory failures (i.e., premature saccades) following 0.64 g/kg alcohol compared with placebo and the relation of this effect to their drinking habits did depend on the level of the drinker’s attentional bias to alcohol-related stimuli. Among drinkers with higher attentional bias, greater impairment of inhibitory control was associated with heavier drinking. In contrast, drinkers with little or no attentional bias showed no relation between their sensitivity to the disinhibiting effects of alcohol and drinking habits. These findings have implications for understanding how heightened incentive-salience of alcohol cues and impaired attentional control can interactively contribute to excessive alcohol use.
doi:10.1037/a0035317
PMCID: PMC4082663  PMID: 24611837
Inhibitory control; attentional bias; alcohol effects; delayed ocular response task; abuse potential
20.  Providing adolescent sexual health care in the pediatric emergency department: views of health care providers 
Pediatric emergency care  2014;30(2):84-90.
Objective
The purpose of this study was to explore health care providers’ (HCPs) attitudes and beliefs about adolescent sexual health care provision in the emergency department (ED) and to identify barriers to a role of a health educator-based intervention.
Methods
We conducted focused, semi-structured interviews of HCPs from the ED and Adolescent Clinic of a children’s hospital. The interview guide was based on the Theory of Planned Behavior and its constructs: attitudes, subjective norms, perceived behavioral control, and intention to facilitate care. We used purposive sampling and enrollment continued until themes were saturated. Interviews were recorded and transcribed. Transcripts were analyzed using directed content analysis.
Results
Twenty-nine interviews were required for saturation. Participants were 12 physicians, 12 nurses, 3 nurse practitioners and 2 social workers; the majority (83%) were female. Intention to facilitate care was influenced by HCP perception of 1) their professional role, 2) the role of the ED (focused vs. expanded care), and 3) need for patient safety. HCPs identified three practice referents: patients/families, peers and administrators, and professional organizations. HCPs perceived limited behavioral control over care delivery because of time constraints, confidentiality issues, and comfort level. There was overall support for a health educator and many felt the educator could help overcome barriers to care.
Conclusion
Despite challenges unique to the ED, HCPs were supportive of the intervention and perceived the health educator as a resource to improve adolescent care and services. Future research should evaluate efficacy and costs of a health educator in this setting.
doi:10.1097/PEC.0000000000000076
PMCID: PMC4266236  PMID: 24457494
22.  Can the use of multiple stop signals reduce the disinhibiting effects of alcohol? 
Alcoholism, clinical and experimental research  2013;37(11):10.1111/acer.12166.
Background
Research has consistently demonstrated that alcohol impairs the ability to divide attention across two or more stimuli. However, under certain circumstances, the presentation of multiple stimuli can actually facilitate performance. The “redundant signal effect” (RSE) refers to the phenomenon by which individuals respond more quickly and accurately when information is presented as redundant, bimodal stimuli (e.g., visually and aurally), rather than as a single stimulus presented to either modality alone. Recent work has shown that response time (RT) to redundant signals is hastened under alcohol, ameliorating the slowing effects of the drug. However, no research has examined whether RSE can reduce the impairing effects of alcohol on the ability to inhibit behavior.
Methods
This study examined whether the impairing effects of alcohol on inhibitory control might be altered by the presentation of redundant inhibitory signals. Inhibitory control was assessed by a go/no-go task which included single and redundant inhibitory signals. Performance was tested following placebo (0.0 g/kg) and alcohol (0.65 g/kg). The effect of redundant activation signals on alcohol impairment of response activation was also measured.
Results
The results showed evidence for RSE on the activation of behavior, but not for inhibitory control. Compared with placebo, alcohol slowed RT and reduced response inhibition. Redundant signals had a robust speeding effect on RT, even following alcohol. By contrast, redundant signals failed to improve inhibitory control following placebo or alcohol.
Conclusions
These findings have important implications for understanding how drinkers respond to multimodal signals in their everyday environments and highlight the vulnerability of inhibitory control to alcohol’s impairing effects.
doi:10.1111/acer.12166
PMCID: PMC3812342  PMID: 23906541
alcohol; redundant signal effect; inhibitory control; behavioral impairment
23.  Developing Emergency Department–based Education About Emergency Contraception: Adolescent Preferences 
Objectives
The objective was to identify adolescent preferences for emergency department (ED)-based education about emergency contraception.
Methods
This was a cross-sectional computerized survey, using adaptive conjoint analysis (ACA). Patients were eligible if they were females ages 14 through 19 years old and were seeking care in one of two urban EDs. Patients were excluded if they were too ill to participate in the survey or if they were non-English speaking. Participants completed a computerized survey that used ACA, a technique that can be used to assess patients’ relative preferences for services. ACA uses the individual’s answers to update and refine questions through trade-off comparisons, so that each respondent answers a customized set of questions. The survey assessed preferences for the following attributes of emergency contraception education: who should deliver the education, if anyone (e.g., nurse, doctor); how the education should be delivered (e.g., by a person or via video); how often the education should be offered if patients were to frequent the ED (e.g., every time or only when asking for it); length (e.g., 5 minutes, 10 minutes); and chief complaint that would trigger the education (e.g., headache or stomach pain).
Results
A total of 223 patients were enrolled (37.2% at Hospital 1 and 62.8% at Hospital 2). The mean (±SD) age of the participants was 16.1 (±1.3) years. Just over half (55%) reported a history of sexual activity; 8% reported a history of pregnancy. Overall, the participants preferred education that was delivered by a person, specifically a doctor or nurse. They preferred a slightly longer education session and preferred education directed at patients seeking care in the ED for complaints potentially related to sexual activity.
Conclusions
Adolescents have specific preferences for how education about emergency contraception would best serve their needs. This information can inform clinicians as they work to improve adolescents’ knowledge about pregnancy prevention and emergency contraception in particular.
doi:10.1111/acem.12243
PMCID: PMC4047822  PMID: 24238320
24.  Sexual Health Behaviors, Preferences for Care, and Use of Health Services Among Adolescents in Pediatric Emergency Departments 
Pediatric emergency care  2013;29(8):907-911.
Objectives
To describe sexual health behaviors, as well as prior use of and preferences for sexual health services among adolescents in the pediatric Emergency Department (ED).
Methods
In this cross-sectional study, subjects aged 14-19 years who presented to an urban or suburban ED from a single Midwestern area completed a written survey. The survey included questions on previous sexual activity (PSA), high-risk behaviors (1st sex before age 15, no condom at last sex, substance use at last sex, >3 partners in past 3 months, and >4 lifetime partners) and sexual health service use and preferences. Comparisons of responses between subgroups were analyzed using Chi-square test. Multiple logistic regression was used to identify factors associated with high-risk behaviors. Care preferences were scored using a four-point Likert scale; mean scores were ranked.
Results
Subjects included 306 adolescents (85% of approached). The mean age was 15.5 years. Almost half (45%) reported PSA and, of those, 63% reported ≥1 high-risk behavior (most commonly 1st sex before age 15 [43%] and no condom at last sex [29%]). Almost all wanted to prevent pregnancy, but only one-third received birth control counseling before sexual debut and 14% reported no contraception at last sex. Younger age was associated with ≥1 high-risk behavior (odds ratio = 3.7; confidence interval = 1.39-9.84). Preferences for care included caring, knowledgeable providers and low/no cost.
Conclusions
Due to high prevalence of high-risk behaviors among adolescents presenting in the ED, strategies should be developed to link these patients to comprehensive sexual health care.
doi:10.1097/PEC.0b013e31829ec244
PMCID: PMC4184037  PMID: 23903671
adolescent sexual health; health risk behaviors; emergency department
25.  Rickettsia parkeri and Rickettsia montanensis, Kentucky and Tennessee, USA 
Emerging Infectious Diseases  2014;20(10):1750-1752.
We found that 14.3% (15/105) of Amblyomma maculatum and 3.3% (10/299) of Dermacentor variabilis ticks collected at 3 high-use military training sites in west-central Kentucky and northern Tennessee, USA, were infected with Rickettsia parkeri and Rickettsia montanensis, respectively. These findings warrant regional increased public health awareness for rickettsial pathogens and disease.
doi:10.3201/eid2010.140175
PMCID: PMC4193168  PMID: 25271771
Amblyomma maculatum; Dermacentor variabilis; ticks; Rickettsia parkeri; Rickettsia montanensis; rickettsia; bacteria; military training sites; Kentucky; Tennessee

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