First Human Case of Fungal Keratitis Caused by a Putatively Novel Species of Lophotrichus

We report an aggressive fungal keratitis caused by a putatively novel species of Lophotrichus in a patient with traumatic injury to the cornea from a dog paw. The organism was isolated from the patient''s necrotic cornea, which perforated despite coverage with hourly fortified broad-spectrum topical antibiotic therapy. This report represents the first case of human infection caused by this species.     

Waiting for a Pediatric Chronic Pain Clinic Evaluation: A Prospective Study Characterizing Waiting Times and Symptom Trajectories

Chronic pain during childhood is prevalent and costly, but the access to interdisciplinary pain care is limited. Studies investigating adults waiting for pain clinic evaluation found that symptoms and quality of life deteriorate over the waiting period, but little is known about the experience of adolescents. Therefore, we aimed to determine wait list times and the longitudinal trends of pain and physical, mental, and social health over a 12-week period. In total, 97 adolescents, aged 10 to 18 years (M?=?14.7 years, 82% female), waiting for evaluation at an interdisciplinary pediatric pain clinic completed assessments at enrollment and at 4-, 8-, and 12-week follow-up. We performed a review of the medical record of attendance patterns 12 months later. Twelve adolescents and their parents also completed qualitative interviews, describing their experience of waiting for evaluation. Wait times averaged 197.5 days (range?=?69–758 days) from the time of referral to the first-attended appointment, and 86.6% of youths completed appointments. Longitudinal repeated measures analyses demonstrated little improvement in pain or other domains of functioning over the 12-week period. In qualitative interviews, families described anxious anticipation for the upcoming appointment, combined with frustration in waiting. Findings highlight the need to consider approaches to reduce wait times and provide early intervention for youths awaiting pain clinic evaluation.Perspective: This study extends the literature on the characteristics and symptom trajectories of adolescents during the wait period for interdisciplinary pain clinic evaluation, described previously only in adults with chronic pain. Findings demonstrated an average wait time of 6.5 months, during which youths’ pain and physical and social health remained impaired.     

The time-course changes of NT-proBNP and tissue Doppler indices in patients undergoing mitral valve replacement

Background: In severe mitral regurgitation, a subset of patients who are asymptomatic may develop left ventricular decompensation before changes in echocardiographic parameters become evident. Since N-terminal brain natriuretic peptide (NT-proBNP) is used to detect early heart failure, we hypothesised that NT-proBNP would be activated in patients with mitral regurgitation. Methods: Patients submitted to surgery were prospectively evaluated over eight months in the Department of Cardiology at Inkosi Albert Luthuli Central Hospital. Control patients with severe mitral regurgitation were obtained from the outpatient clinic. In order to define their value in identifying left ventricular decompensation, NT-proBNP levels and tissue Doppler imaging (TDI) indices were simultaneously measured and compared with conventional echocardiographic indices at baseline and this was repeated at one week and at six weeks after valve replacement. Results: Mean NT-proBNP levels were markedly elevated pre-operatively in all surgical cases compared to controls (p = 0.0001). The diastolic E-mitral/E-annulus ratio, measured using TDI, was higher in the study group, indicating higher left ventricular filling pressure present in the study group. NT-proBNP levels increased further at one week after surgery and subsided at the six-week follow-up visit to levels similar to the control group. The TDI diastolic ratio also decreased at one week, and increased slightly again at the six-week follow up. These changes were accompanied by significant reduction in left atrium and left ventricular chamber dimensions with an increase in the ejection fraction from one to six weeks. Conclusion: Marked differences in mean NT-proBNP levels and TDI ratios between the study and control groups suggest that using TDI and NT-proBNP assays may detect covert left ventricular decompensation.     

A Randomized Controlled Trial of IVR-Based Alcohol Brief Intervention to Promote Patient–Provider Communication in Primary Care

BACKGROUND

Brief interventions for unhealthy drinking in primary care settings are efficacious, but underutilized. Efforts to improve rates of brief intervention though provider education and office systems redesign have had limited impact. Our novel brief intervention uses interactive voice response (IVR) to provide information and advice directly to unhealthy drinkers before a physician office visit, with the goals of stimulating in-office dialogue about drinking and decreasing unhealthy drinking. This automated approach is potentially scalable for wide application.

OBJECTIVE

We aimed to examine the effect of a pre-visit IVR-delivered brief alcohol intervention (IVR-BI) on patient–provider discussions of alcohol during the visit.

DESIGN

This was a parallel group randomized controlled trial with two treatment arms: 1) IVR-BI or 2) usual care (no IVR-BI).

PARTICIPANTS

In all, 1,567 patients were recruited from eight university medical center-affiliated internal medicine and family medicine clinics.

INTERVENTIONS

IVR-BI is a brief alcohol intervention delivered by automated telephone. It has four components, based on the intervention steps outlined in the National Institute of Alcohol Abuse and Alcoholism guidelines for clinicians: 1) ask about alcohol use, 2) assess for alcohol use disorders, 3) advise patient to cut down or quit drinking, and 4) follow up at subsequent visits.

MAIN MEASURES

Outcomes were patient reported: patient–provider discussion of alcohol during the visit; patient initiation of the discussion; and provider’s recommendation about the patient’s alcohol use.

KEY RESULTS

Patients randomized to IVR-BI were more likely to have reported discussing alcohol with their provider (52 % vs. 44 %, p?=?0.003), bringing up the topic themselves (20 % vs. 12 %, p?<?0.001), and receiving a recommendation (20 % vs. 14 %, p?<?0.001). Other predictors of outcome included baseline consumption, education, age, and alcohol use disorder diagnosis.

CONCLUSIONS

Providing automated brief interventions to patients prior to a primary care visit promotes discussion about unhealthy drinking and increases specific professional advice regarding changing drinking behavior.

     

Sex-specific and non-sex-specific quantitative trait loci contribute to normal variation in bone mineral density in men

INTRODUCTION: A major determinant of osteoporotic fracture is peak bone mineral density (BMD). In women peak BMD is highly heritable and several quantitative trait loci (QTL) have been reported. There are few comparable data in men. This study in men aimed to establish the heritability of peak BMD, identify QTL contributing to normal variation in BMD, and determine which QTL might be sex specific. METHODS: BMD at the spine and hip were measured in 323 pairs of brothers aged 18-61 yr (264 white pairs; 59 black pairs). Heritability was calculated and linkage analysis performed with spine and hip BMD phenotypes. RESULTS: Heritability estimates ranged from 0.61 to 0.87 and were not significantly different between white and black men. A 9-cM genome-wide scan followed by genotyping with more closely spaced markers identified suggestive QTL (logarithm of the odds > 2.2) for BMD on chromosomes 1q (spine), 2p (spine), 2q (hip), 14p (spine), 18 (hip), and 21 (hip). Comparison with published data in 774 pairs of premenopausal sisters suggested that the QTL on 1q (spine), 2q (hip), 14p (spine), and 21q (hip) were male specific, whereas those on 2p (spine) and 18 (hip) were not sex specific. CONCLUSIONS: This study demonstrates that BMD in healthy men is highly heritable with similar estimates of the genetic contribution to BMD in both whites and blacks. Of the six QTL identified, three were specific for spine BMD and three were specific for hip BMD. When compared with published QTL for peak BMD in women from the same geographical region, four of the QTL appeared to be male specific. The occurrence of sex-specific genes in humans for BMD has potentially important implications for the pathogenesis and treatment of osteoporosis.     

Nitrate-based vasodilators inhibit multiple vascular aldehyde dehydrogenases

Nitrate-based vasodilators (NBVs) are commonly used to treat multiple sequelae of atherosclerosis. A commonly used NBV, glyceryl trinitrate (GTN) is bioactivated by mitochondrial, class 2 aldehyde dehydrogenase (ALDH2). ALDH2 and other ALDHs are NAD(P)⁺-dependent enzymes critical to the detoxification of cytotoxic lipid-aldehydes elevated in atherosclerotic lesions, such as trans-4-hydroxy-2-nonenal (HNE). The GTN bioactivation step, however, inactivates ALDH2 and may alter the metabolism of these aldehydes. In this study, we tested the hypothesis that multiple ALDH enzymes are inhibited by different NBVs. ALDH2, ALDH3A, and ALDH5A were present in aorta with ALDH2 and ALDH3A localized to the smooth muscle layers. GTN (1 μM) inhibited ALDH2 activity (55±6% of control) and ablated ALDH3 activity. In contrast, isosorbide-2,5-dinitrate (ISDN, 1 μM) inhibited ALDH3 activity (1.1±0.4% of control) but did not inhibit ALDH2 activity even up to 50 μM ISDN. In homogenates of rat aorta, GTN (1 μM) inhibited the NAD⁺-dependent (41±5% of control) and NADP⁺-dependent (25±6% of control) detoxification of HNE. The inhibition of ALDH3A, but not ALDH2, could be prevented by the addition of dithiothreitol. These studies demonstrate that GTN and ISDN possess selectivity for ALDH inactivation with different mechanisms of inactivation.     

Iteratively Developing an mHealth HIV Prevention Program for Sexual Minority Adolescent Men

Five activities were implemented between November 2012 and June 2014 to develop an mHealth HIV prevention program for adolescent gay, bisexual, and queer men (AGBM): (1) focus groups to gather acceptability of the program components; (2) ongoing development of content; (3) Content Advisory Teams to confirm the tone, flow, and understandability of program content; (4) an internal team test to alpha test software functionality; and (5) a beta test to test the protocol and intervention messages. Findings suggest that AGBM preferred positive and friendly content that at the same time, did not try to sound like a peer. They deemed the number of daily text messages (i.e., 8–15 per day) to be acceptable. The Text Buddy component was well received but youth needed concrete direction about appropriate discussion topics. AGBM determined the self-safety assessment also was acceptable. Its feasible implementation in the beta test suggests that AGBM can actively self-determine their potential danger when participating in sexual health programs. Partnering with the target population in intervention development is critical to ensure that a salient final product and feasible protocol are created.     

Factor Structure of the Children's Depression Inventory in a Multisite Sample of Children and Adolescents With Chronic Pain

This study examined the factor structure of the Children's Depression Inventory (CDI) among children and adolescents with chronic pain using exploratory and confirmatory factor analysis in a large, multisite sample of treatment-seeking youth. Participants included 1,043 children and adolescents (ages 8–18) with a range of chronic pain complaints who presented for initial evaluation at 1 of 3 tertiary care pediatric chronic pain clinics across the United States. They completed the CDI and reported on pain intensity and functional disability. Factor analysis was conducted using a 2-step (exploratory and confirmatory) approach. Results supported a 5-factor model for the CDI with good fit to the data. The distribution and item-total correlations of the somatic items (eg, pain complaints, fatigue) were explored in this sample. Results indicate that the CDI is a useful tool for assessing depressive symptoms in youth with chronic pain, but some caution is warranted in interpreting the clinical significance of scores in light of the overlap of specific symptoms common to both pain and depression.PerspectiveThe CDI can be considered a valid tool for assessing mood symptoms in children with chronic pain. Caution is encouraged when interpreting the clinical significance of scores due to symptom overlap between chronic pain and depression.