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BACKGROUND AND PURPOSE This study evaluates the incidence, prevalence and survival trends of motor neurone disease (MND) in Northern Ireland from 2015 to 2019. METHODS A capture-recapture analysis was performed using five independent data sources. Incidence and prevalence rates were standardized to the European Standard Population. Survival outcomes were analysed using Kaplan-Meier curves and Cox regression analysis. RESULTS Amongst 254 total cases of MND, capture-recapture analysis estimated three missing cases (case ascertainment 98.8%). Age standardized incidence of captured cases was 3.12 per 100,000 (2.73, 3.50) and standardized prevalence ranged from 9.45 to 6.49 per 100,000 from 2015 to 2019. Standardized incidence and prevalence rates in 2006 were 1.4 and 3.3 per 100,000 respectively. Of identified cases, 133 (52.4%) were male; 94.5% had amyotrophic lateral sclerosis; median age of onset was 67 years; median time to diagnosis was 12 months (95% confidence interval 11.2, 12.8); survival from diagnosis was 12 months (95% confidence interval 10.6, 15.4); 25 (9.8%) reported a family history of MND or frontotemporal dementia; and a known MND-associated genetic mutation was identified in 7.9% of total cases, of which the most common was C9orf72 (5.7% of all patients). Factors associated with improved survival were younger age at onset, longer time to diagnosis, attendance at regional MND clinic, and initial neurology presentation as outpatient (all p

Objective: Physician-rating websites have exploded in popularity in recent years. Consequently, these sites have garnered attention from researchers interested in factors influencing patient satisfaction. A doctor's earnings might reflect practice patterns that could influence their patients' perceptions. We sought to explore any association between physicians' earnings and their online ratings.Methods: The names and billings of 500 physicians from British Columbia, Canada were randomly extracted from the 2016-17 BC Blue Book and matched to their profiles on RateMDs.com. Physicians' earnings were compared to their global ratings and to their Staff, Punctuality, Helpfulness, and Knowledge scores. Earnings and ratings were also compared between men and women, as well as between family medicine, surgical, and internal medicine and subspecialties cohorts.Results: We found no significant correlation between physicians' earnings and their global online ratings (p = 0.304). Weak negative correlations existed between earnings and Staff and Helpfulness ratings (Spearman's rho = −0.055, p < 0.001; rho = −0.033, p < 0.028). Online ratings were largely favorable (mean MD rating of 3.85/5. Male physicians earned significantly more than their female colleagues ($371,734.85 and $261,590.82, respectively; p < 0.001), but no significant difference existed between men and women with regards to online ratings (mean 3.87 and 3.81, respectively, p = 0.191). Surgical and Family Medicine specialties showed a negative correlation between income and ratings; no relationship was seen in the internal medicine and subspecialties cohort.Conclusions: No meaningful association was found between physicians' earnings and their online ratings, although there is an impact of specialty grouping. Patients tend to review doctors favorably online; these data add to the discussion of whether male and female doctors are differentially rated. Trends toward increased transparency in health care systems may help to elucidate how doctors' earnings influence patients' perception of and satisfaction with the care they receive.

Exercise programs have shown great potential for both the prevention and treatment of substance use disorder (SUD). As exercise has been shown to have potent effects on physical and psychological health, it is reasonable to examine the mechanism of how exercise can be used as an adjunct treatment for addiction. The present study examined the effects of chronic aerobic (treadmill) exercise on both GABA(a) and mu-opioid receptor levels in the brains of male and female rats. GABA(a) receptor binding, measured by [3H] Flunitrazepam, was increased in the cingulate cortex following exercise, but only in females. Mu-opioid receptor expression, measured by [3H] ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin) (DAMGO), showed no effect of exercise while showing an effect of sex, with increased [3H] DAMGO binding in the brains of sedentary males compared to that of sedentary females. Our findings support the potential role for GABA(a) signaling in the cingulate cortex as part of the mechanism of action of aerobic exercise. These data, along with prior reports, aid our understanding of the neurochemical impact and mechanism of chronic aerobic exercise on neuropsychiatric disease, particularly regarding addiction.

Reduced social motivation is hypothesised to underlie social behavioural symptoms of Autism Spectrum Disorder (ASD). The extent to which rewarding social stimuli are granted privileged access to awareness in ASD is currently unknown. We use continuous flash suppression to investigate whether individuals with and without ASD show privileged access to awareness for social over nonsocial rewarding scenes that are closely matched for stimulus features. Strong evidence for a privileged access to awareness for rewarding social over nonsocial scenes was observed in neurotypical adults. No such privileged access was seen in ASD individuals, and moderate support for the null model was noted. These results suggest that the purported deficits in social motivation in ASD may extend to early processing mechanisms.

Individuals with low empathy often show reduced attention towards social stimuli. A limitation of this literature is the lack of empirical work that has explicitly characterized how this relationship manifests itself over time. We investigate this issue by analysing data from two large eye-tracking datasets (total n = 176). Via growth-curve analysis, we demonstrate that self-reported empathy (as measured by the empathy quotient—EQ) predicts the temporal evolution of gaze behaviour under conditions where social and non-social stimuli compete for attention. In both datasets, we found that EQ not only predicted a global increase in social attention, but predicted a different temporal profile of social attention. Specifically, we detected a reliable effect of empathy on gaze towards social images after prolonged viewing. An analysis of switch latencies revealed that low-EQ observers switched gaze away from an initially fixated social image more frequently and at earlier latencies than high-EQ observers. Our analyses demonstrate that modelling these temporal components of gaze signals may reveal useful behavioural phenotypes. The explanatory power of this approach may provide enhanced biomarkers for conditions marked by deficits in empathy-related processes.

OBJECTIVES: We used an unbiased proteomics approach to identify candidate urine biomarkers (CUBMs) predictive of LN chronicity and pursued their validation in a larger cohort. METHODS: In this cross-sectional pilot study, we selected urine collected at kidney biopsy from 20 children with varying levels of LN damage (discovery cohort) and performed proteomic analysis using isobaric tags for relative and absolute quantification (iTRAQ). We identified differentially excreted proteins based on degree of LN chronicity and sought to distinguish markers exhibiting different relative expression patterns using hierarchically clustered log10-normalized relative abundance data with linked and distinct functions by biological network analyses. For each CUBM, we performed specific ELISAs on urine from a validation cohort (n = 41) and analysis of variance to detect differences between LN chronicity, with LN activity adjustment. We evaluated for CUBM expression in LN biopsies with immunohistochemistry. RESULTS: iTRAQ detected 112 proteins in urine from the discovery cohort, 51 quantifiable in all replicates. Simple analysis of variance revealed four differentially expressed, chronicity-correlated proteins (P-values < 0.05). Further correlation and network analyses led to selection of seven CUBMs for LN chronicity. In the validation cohort, none of the CUBMs distinguished LN chronicity degree; however, urine SERPINA3 demonstrated a moderate positive correlation with LN histological activity. Immunohistochemistry further demonstrated SERPINA3 staining in proximal tubular epithelial and endothelial cells. CONCLUSION: We identified SERPINA3, a known inhibitor of neutrophil cathepsin G and angiotensin II production, as a potential urine biomarker to help quantify LN activity.

Objective In certain cases, the recurrent laryngeal nerve (RLN) has to be sacrificed. This often results in an inadequate length of residual RLN to be used in a reinnervation procedure. We investigated the length of the distal stump of the RLN from the inferior border of the inferior pharyngeal constrictor muscle (IPCM), where it is frequently compromised, to its entrance into the larynx. Our objective was to determine whether this residual nerve stock was sufficient for margin clearance and neurorrhaphy. Study design Cadaveric study Methods Recurrent laryngeal nerves were identified in fresh frozen cadavers. The IPCM was divided, revealing the distal stump of the RLN, which was measured. Results Dissection was performed in 20 cadavers (40 nerves). The average length of the right RLN and the left RLN from the IPCM until it entered the larynx was 15 mm and 14 mm, respectively. All residual RLN remnants were of sufficient length for neurorrhaphy. Conclusion Concomitant RLN reinnervation procedures in the setting of nerve sacrifice are not well described. A barrier to reinnervation in this setting may be insufficient residual nerve length for a neurorrhaphy. Often, when the RLN is sacrificed intraoperatively either iatrogenically or due to tumor invasion, it is close to the cricoarytenoid joint, at the inferior border of the IPCM. This study demonstrates that by splitting the IPCM, sufficient length can be obtained for neurorrhaphy.

Background: Former prison inmates experience high rates of hospitalizations and death during the transition from prison to the community, particularly from drug-related causes and early after release. The authors designed a randomized controlled trial (RCT) of patient navigation to reduce barriers to health care and hospitalizations for former prison inmates. Methods: Forty former prison inmates with a history of drug involvement were recruited and randomized within 15 days after prison release. Participants were randomized to receive 3 months of patient navigation (PN) with facilitated enrollment into an indigent care discount program (intervention) or facilitated enrollment into an indigent care discount program alone (control). Structured interviews were conducted at baseline, 3 months, and 6 months. Outcomes were measured as a change in self-reported barriers to care and as the rate of health service use per 100 person-days. Results: The mean number of reported barriers to care was reduced at 3 and 6 months in both groups. At 6 months, the rate of emergency department/urgent care visits per 100 person-days since baseline was 1.1 among intervention participants and 0.5 among control participants ( P = .04), whereas the rate of hospitalizations per 100 person-days was 0.2 in intervention participants and 0.6 in control participants ( P = .04). Conclusions: Recruitment of former inmates into an RCT of patient navigation was highly feasible, but follow-up was limited by rearrests. Results suggest a significantly lower rate of hospitalizations among navigation participants, although the rate of emergency department/urgent care visits was not improved. Patient navigation is a promising, pragmatic intervention that may be effective at reducing high-cost health care utilization in former prison inmates.

Introduction The purpose of our study was to describe a novel technique for reconstruction of orbital defects after maxillectomy using a non-anatomic titanium mesh suspension of orbital contents for both support and volume correction. This construct is then articulated with a layered fibula osteocutaneous free flap that restores orbital rim, zygoma, and maxillary alveolus. We herein present our application of this technique, including refinements over time and long-term outcomes. Methods A retrospective review was performed on 12 patients who underwent reconstruction of Brown class III orbitopalatomaxillary defects with extensive orbital involvement (at minimum complete orbital floor and rim absent) with titanium mesh sling and a layered fibula free flap. Results Primary reconstruction was accomplished in all 12 patients. The mean postoperative length of stay was 8 days (6-14 days). There were no free flap failures or perioperative re-explorations. Patients were routinely extubated on postoperative day #1 and began oral intake by postoperative day #3. At a mean follow-up length of 48 months, unrestricted eye function was accomplished in all patients. Midfacial symmetry was accomplished in 10 of 12 patients; 2 patients had moderate asymmetry due to extirpation of facial musculature and/or soft tissue. Minor revisions were necessary for lower lid ectropion and exposure of the titanium plate. Two patients required adipofascial free flap coverage of exposed intraoral bone after radiation therapy. Conclusions This technique provides excellent restoration of eye position and function and also allows for implant-based prosthetic rehabilitation. It has become our procedure of choice for orbitomaxillary reconstruction.

Humans generally prefer social over nonsocial stimuli from an early age. Reduced preference for social rewards has been observed in individuals with autism spectrum conditions (ASC). This preference has typically been noted in separate tasks that measure orienting toward and engaging with social stimuli. In this experiment, we used two eye-tracking tasks to index both of these aspects of social preference in in 77 typical adults. We used two measures, global effect and preferential looking time. The global effect task measures saccadic deviation toward a social stimulus (related to ‘orienting’), while the preferential looking task records gaze duration bias toward social stimuli (relating to ‘engaging’). Social rewards were found to elicit greater saccadic deviation and greater gaze duration bias, suggesting that they have both greater salience and higher value compared to nonsocial rewards. Trait empathy was positively correlated with the measure of relative value of social rewards, but not with their salience. This study thus elucidates the relationship of empathy with social reward processing.

Inferior turbinate surgery for nasal obstruction can be performed in a variety of ways. Only a few of these methods produce tissue that can be sent for pathologic analysis. According to the College of American Pathologists, turbinate tissues are not exempt from requisite pathologic evaluation. Our objectives were to evaluate the clinical value and cost implications of routine pathological examination of turbinate specimens.Case series with chart review.Academic tertiary care medical center.Charts of patients who underwent an inferior turbinate procedure for nasal obstruction between January 2008 and August 2011 were reviewed.Thirteen hundred consecutive cases from 17 surgeons were identified. Among these patients, 223 (17%) underwent an isolated turbinate reduction procedure and 779 (59%) underwent a reduction procedure in conjunction with a septoplasty. The remaining patients had a turbinate procedure in addition to another head and neck procedure. Only 591 (45%) turbinate reduction procedures were performed by methods that were tissue producing, and of these, 137 (23%) were sent for pathologic analysis. All submitted specimens received a gross examination and 123 (90%) also underwent histologic analysis. No abnormalities were reported.At our institution, most surgeons did not submit turbinate tissues for pathologic examination even when a specimen was produced. Of the specimens sent, no abnormal pathologic results were identified. Our results suggest that routine pathologic evaluation of inferior turbinate specimens may not contribute to patient care and perhaps represents an unnecessary cost.

Objectives/Hypothesis To evaluate the endoscopic surgical management of adult subglottic stenosis and describe treatment outcomes. Study Design Retrospective review. Methods Ten-year review of adult patients with subglottic stenosis. Results Ninety-two adults (23 male, 69 female) with subglottic stenosis underwent 247 endoscopic dilations between 2001 and 2010. The mean age was 48 years at time of first surgery. Etiology was GPA (granulomatosis with polyangiitis, formerly Wegener's granulomatosis) (45%), intubation (25%), or idiopathic (33%). Forty-one patients (45%) underwent a single procedure; 51 patients (55%) required multiple surgeries. The average interval for patients requiring a subsequent procedure was 13.7 months. Variations in surgical technique did not show differences in time to next procedure, and the use of mitomycin-C did not result in longer intervals between procedures. No significant complications were encountered after dilation. Conclusions Subglottic stenosis remains a treatment challenge. Although patients are often symptomatically improved after endoscopic dilation, recurrence rates remain high. Level of Evidence 4. Laryngoscope, 124:736–741, 2014

Background In clinical practice, α2-adrenoceptor agonists have been adjunctively administered with psychostimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD). Two studies have examined the adjunctive use of guanfacine extended release (GXR, Intuniv®; Shire Development LLC, Wayne, PA, USA) with psychostimulants in children and adolescents with a suboptimal response to psychostimulant treatment. However, the potential for pharmacokinetic drug–drug interactions (DDIs) between GXR and lisdexamfetamine dimesylate (LDX, Vyvanse®; Shire US LLC, Wayne, PA, USA) has not been thoroughly evaluated. Objective The primary objective of this study was to examine the pharmacokinetics of GXR 4 mg and LDX 50 mg given as single doses alone and in combination. Study Design This was an open-label, randomized, three-period crossover, DDI study. Setting The study was conducted in a single clinical research center. Participants Forty-two healthy adults were randomized in this study. Interventions Subjects were administered single oral doses of GXR 4 mg, LDX 50 mg, or GXR and LDX in combination. Main Outcome Measures Blood samples collected predose and up to 72 h postdose assessed guanfacine, LDX, and d-amphetamine levels. Bioequivalence was defined as the 90 % confidence intervals (CIs) of the geometric mean ratios of the area under the plasma concentration–time curve extrapolated to infinity (AUC0–∞) and maximum plasma concentration (Cmax) falling within the bioequivalence reference interval (0.80–1.25). Safety measures included adverse events, vital signs, and electrocardiograms (ECGs). Results Forty subjects completed the study. Following administration of LDX alone or in combination with GXR, the statistical comparisons of the AUC0–∞ and Cmax of d-amphetamine fell entirely within the reference interval. For guanfacine, the 90 % CI of the geometric mean ratio of AUC∞ for the two treatments was within the bioequivalence criteria, but for Cmax the upper bound of the 90 % CI exceeded the standard range for bioequivalence by 7 %. This relatively small change is unlikely to be clinically meaningful. Treatment-emergent adverse events (TEAEs) were reported by 42.9 % of subjects; the most commonly reported TEAEs included dizziness (5.0, 7.3, and 7.3 %) and headache (7.5, 4.9, and 7.3 %) following administration of GXR, LDX, and GXR and LDX in combination, respectively. Clinically significant ECG abnormalities occurred in one subject following administration of LDX and in one subject following coadministration of GXR and LDX. Conclusions In healthy adults, coadministration of GXR and LDX did not result in a clinically meaningful pharmacokinetic DDI compared with either treatment alone. No unique TEAEs were observed with coadministration of GXR and LDX compared with either treatment alone.

Background Lisdexamfetamine dimesylate (LDX), a prodrug consisting of d-amphetamine and l-lysine, is being studied in clinical trials of major depressive disorder. Additional drug-drug interaction studies were warranted. Objective This study aimed to describe the pharmacokinetics and safety of LDX and venlafaxine extended-release (VXR), alone or combined. Study Design The study was an open-label, two-arm, single-sequence crossover investigation with randomization to treatment sequence. Setting and Participants The study was conducted at two clinical study centres and included healthy adult males and females (18–45 years of age). Intervention The study included two single-sequence crossover designs: LDX alone followed by LDX + VXR (Treatment Arm A); and VXR alone followed by VXR + LDX (Treatment Arm B). Drug treatment was initiated on day 1 with once-daily LDX or VXR alone with 15 days’ titration to final dose (LDX 30, 50 and 70 mg for 5 days each; VXR 75, 150 and 225 mg for 5 days each). On days 16–30, VXR, titrated to a final dose of 225 mg, or LDX, titrated to a final dose of 70 mg, was coadministered for participants in Treatment Arm A or B, respectively. On days 31–38, VXR doses were tapered. Main Outcome Measures On days 1–2, 15–16 and 30–31, safety evaluations and blood samples were obtained pre-dose through 24 h post-dose for analysis of LDX, d-amphetamine, venlafaxine (VEN), and O-desmethylvenlafaxine (ODV). Combination treatment was considered bioequivalent to single treatment if 90 % confidence intervals (CIs) for geometric mean ratios (GMRs) of analytes fell within the interval 0.80–1.25 based on maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) from time zero to time of last measurable concentration (AUCτ). Safety assessments included treatment-emergent adverse events (TEAEs), pulse rate and blood pressure (BP), clinical laboratory assessments, and 12-lead electrocardiograms (ECG). Results Among 80 enrolled subjects, 77 were included in pharmacokinetic and safety analyses. Combination LDX + VXR was bioequivalent to LDX alone, based on exposure to d-amphetamine (GMR [95 % CI], Cmax (ng/mL): 0.97 [0.82, 1.14], AUCτ: 0.95 [0.81, 1.12]). Exposure to VEN with LDX + VXR (vs. VXR alone) was increased (Cmax: 1.10 [0.88, 1.38], AUCτ: 1.13 [0.88, 1.45]) and ODV decreased (Cmax: 0.91 [0.77, 1.06], AUCτ: 0.83 [0.71, 0.96]), whereas composite VEN + ODV was bioequivalent to VXR alone (Cmax: 0.96 [0.84, 1.09], AUCτ: 0.98 [0.85, 1.13]). TEAEs with LDX or LDX + VXR were similar. Maximum mean increases from baseline were: pulse rate, +8.73 to 12.76 beats/min with either treatment alone and +17.67 to 20.85 beats/min with LDX + VXR; systolic BP, +4.32 to 6.56 mmHg with either treatment alone and +12.96 to 13.78 mmHg with LDX + VXR; diastolic BP, +5.39 to 5.74 mmHg with either treatment alone and +12.09 to 12.46 mmHg with LDX + VXR. One participant was withdrawn due to a serious TEAE (presyncope). No unexpected, clinically meaningful trends or changes from baseline in mean laboratory or ECG parameters were observed during the trial. Conclusion In healthy adults, combination LDX + VXR (vs. LDX alone) did not alter exposure to d-amphetamine. Although small changes in exposure to VEN (increased) and ODV (decreased) were seen with combination treatment, total VEN + ODV exposure showed no change (vs. VEN alone). LDX + VXR led to increases in BP and pulse rate, supporting existing recommendations for vital sign monitoring when using these medications.

Objective The best imaging study for evaluation of pediatric hearing loss is debated and it is well known magnetic resonance imaging is more costly than computed tomography. The objective of this study is to evaluate charges of computed tomography temporal bone (CTTB) versus magnetic resonance imaging brain, internal auditory canal/cerebellopontine angle (MRI IAC/CPA), with and without sedation in the pediatric population in order to assess to what extent the charges for the procedure are increased. In addition, differences in need for sedation and duration of sedation will be evaluated. Methods All patients, 0–18 years that underwent CTTB or MRI IAC/CPA, between January 2013 through December 2014 within department of otolaryngology. Results 120 CTTBs (118 non-sedated and 2 sedated) and 51 MRI IAC/CPAs (32 non-sedated and 19 sedated) were performed. Average charge for non-sedated CTTB was $1856. CTTB scan under sedation incurred total additional charges of $2385. Average charges for non-sedated MRI IAC/CPA was $3770. Technical charges for sedated MRI IAC/CPA was $151 lower ($2858) but had additional sedation charges of $2256, a recovery room charge of $250, and additional professional fees of $1496 for total charges of $7621. 37% of MRI IAC/CPAs needed sedation to be completed in comparison to 1.6% of CTTB. Conclusion MRI IAC/CPAs are, on average, twice as costly as CTTBs. Almost 40% of patients need sedation to complete MRI IAC/CPA. These considerations may factor into decision making when choosing imaging modality in evaluation of pediatric hearing loss.

Morphological features of coronary arteries and incidental lesions are reported from hearts in five species of sharks, the shortfin mako shark, Isurus oxyrhinchus Rafinesque, thresher shark Alopias vulpinus (Bonaterre), blue shark, Prionace glauca L., the smooth dogfish, Mustelus canis (Mitchill), and spiny dogfish, Squalus acanthias L. Sharks were collected from the northwestern Atlantic between June and August from 1996 to 2010. They were necropsied dockside and the hearts were preserved in buffered formalin. Routine sections including ventricle/conus arteriosus and the atrio-ventricular junctions were embedded in paraffin, stained with common histological and immunohistochemical methods and examined by brightfield microscopy. Myointimal hyperplasia, medial myo-myxomatous hyperplasia and bifurcation pads were observed commonly, and medial muscle reorientation and epicardial myeloid tissues were rare. All the above features differed in severity, prevalence and distribution depending on anatomical site and shark species/size. Morphometric analysis indicated that myomyxomatous hyperplasia is associated with luminal narrowing of blood vessels. As suggested previously, the described morphological features are most likely physiological responses to blood flow characteristics. Vascular and cardiac lesions were uncommon and included, granulomatous proliferative epicarditis with fibroepitheliomas, myxomatous epicardial expansions, medial arterial vacuolation, myocardial fibrosis, acute ventricular emboli and parasitic granulomas. The lesions of embolism, proliferative and granulomatous epicarditis and myocardial fibrosis were in all sharks associated with capture events including retained fishing hooks. The significance and aetiopathogenesis of medial vacuolation and epicardial myxomatous expansions remains unclear.

Objectives/Hypothesis: The use of topical drug delivery through nasal irrigations can minimize systemic side effects and deliver higher concentrations of drugs directly to diseased sinus mucosa. Complications related to this popular method of treatment are not well described. We present our experience with paranasal sinus exostosis (PSE), a new diagnostic entity that appears to be a complication of cold nasal irrigations. Study Design: Retrospective chart review. Methods: Retrospective chart reviews were performed on patients within the Cleveland Clinic Foundation from 2005 to 2011. Six patients were identified with sinus exostoses. A literature review for “sinonasal exostoses” and “paranasal sinus exostoses” was performed using PubMed. Results: Six patients with PSE were identified at the Cleveland Clinic Foundation between 2005 and 2011. All patients had undergone sinus surgery, and none had documented evidence of PSE prior to surgery. There was no evidence of worsening PSE once the cold irrigations were stopped. No patients showed any resolution of PSE over time. None of our patients has progressed to have disease burden significant enough to require intervention. Conclusions: PSE is a rare condition that mirrors a well-described otologic process; exostoses of the external auditory canal. PSE appears to be a complication of cold nasal irrigations. It does not resolve with the halting of cold irrigations, but does not appear to progress further after intervention. PSE only affects postoperative patients. With the evolving trend to treat postoperative sinus disease topically, the clinician should be aware of the dangers of cold irrigations, and patients should be counseled accordingly.

Data on pharmacokinetic parameters of the prodrug stimulant lisdexamfetamine dimesylate via alternate routes of administration are limited. The pharmacokinetics of d-amphetamine derived from lisdexamfetamine dimesylate after single oral (PO) versus intranasal (IN) administration of lisdexamfetamine dimesylate were compared.In this randomized, two-period, crossover study, healthy men without a history of substance abuse were administered single PO or IN (radiolabelled with ≤100 μCi (99m)Tc-diethylenetriamine-pentaacetic acid and confirmed by scintigraphy) lisdexamfetamine dimesylate 50 mg ≥7 days apart. Serial blood samples were drawn to measure d-amphetamine and intact lisdexamfetamine at 0 (pre-dose), 15, 30 and 45 minutes and at 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose for PO administration and at 0 (pre-dose), 5, 10, 15, 20, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose for IN administration. Treatment-emergent adverse events (TEAEs) were assessed.Eighteen subjects were enrolled and completed the study. The mean ± SD maximum observed plasma concentration (C(max)) and area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUC(last)) of d-amphetamine following PO administration of lisdexamfetamine dimesylate were 37.6 ± 4.54 ng/mL and 719.1 ± 157.05 ng · h/mL, respectively; after IN administration, these parameters were 35.9 ± 6.49 ng/mL and 690.5 ± 157.05 ng · h/mL, respectively. PO and IN administration demonstrated similar median time to reach C(max) (t(max)) for d-amphetamine: 5 hours for PO administration versus 4 hours for IN administration. Mean ± SD elimination half-life (t(1/2)) values were also similar for PO (11.6 ± 2.8 hours) and IN (11.3 ± 1.8 hours) lisdexamfetamine dimesylate. TEAEs after PO and IN administration were reported by 27.8% of subjects (5/18) and 38.9% of subjects (7/18), respectively; all AEs were mild or moderate in severity, and TEAEs such as anorexia, dry mouth, headache and nausea were consistent with known amphetamine effects.IN administration of lisdexamfetamine dimesylate resulted in d-amphetamine plasma concentrations and systemic exposure to d-amphetamine comparable to those seen with PO administration. Subject variability for d-amphetamine pharmacokinetic parameters was low. Both PO and IN lisdexamfetamine dimesylate demonstrated a tolerability profile similar to that of other long-acting stimulants.

To evaluate the pharmacokinetics of lisdexamfetamine dimesylate (LDX), a long-acting prodrug stimulant, and mixed amphetamine salts extended-release (MAS XR), alone or with omeprazole, a proton pump inhibitor (PPI).This open-label, randomized, 4-period crossover study enrolled healthy adults (18-45 years). Subjects alternately received single doses of LDX 50 mg and MAS XR 20 mg at 4-day intervals. Following washout, subjects received omeprazole (40 mg/day x 14 days), with alternate single doses of LDX 50 mg or MAS XR 20 mg added on days 7 and 11. Blood samples were collected predose and 0 to 96 hours postdose for pharmacokinetic analysis. Safety assessments included adverse events (AEs).Overall, 24 subjects were randomized; 21 completed the study. For LDX monotherapy, d-amphetamine mean (SD) exposure was 45.0 (13.97) ng/mL and 713.0 (134.75) ng . h/mL; when coadministered with omeprazole it was 46.3 (9.71) ng/mL and 761.6 (191.13) ng . h/mL, for Cmax and AUCinf, respectively. The median Tmax was 3 hours with and without omeprazole. For MAS XR monotherapy, total amphetamine mean (SD) exposure was 36.6 (9.19) ng/mL and 640.8 (95.66) ng . h/mL; when coadministered with omeprazole it was 38.1 (7.35) ng/mL and 643.9 (143.16) ng . h/mL, for Cmax and AUCinf, respectively. The median Tmax was 5 hours and 2.75 hours without and with omeprazole, respectively; 57.1% to 61.9% of subjects receiving MAS XR and 25% receiving LDX showed an earlier (or= 1 hour) Tmax with omeprazole. Both medications had AEs consistent with amphetamine use.Total exposure was unaffected by omeprazole for both compounds. However, approximately 50% of subjects receiving MAS XR showed an earlier Tmax while on omeprazole, indicating unpredictable release of active drug by the second bead of MAS XR, most likely related to reduced stomach acid while on a PPI compromising the pulsed delivery of MAS XR. No clear trend was observed for LDX.

This study reports urinalysis values for three species of captive rhinoceros (Rhinoceros unicornis, Dicerorhinus sumatrensis, and Diceros bicornis) and evaluates individual and species differences. Repeated urinalysis was conducted on 11 individuals to establish normal reference ranges. Although no individual or species differences existed in urinary values for pH, all species differed in specific gravity. Rhinoceros urine demonstrated many physical and chemical properties similar to that of the horse, but reliability of this comparison was limited. Urinary pH in the rhinoceros was within range of that established for the horse and other large herbivores. However, all rhinoceros species exhibited urinary specific gravities below the lower limit of the normal equine reference range. Comparative urinalysis using an outside laboratory source confirmed the results of this study and illustrated the value of conducting in-house analysis. These results are the first data available on reference ranges for urine parameters in the greater one-horned, Sumatran, and African black rhinoceros and provide a useful diagnostic tool for the veterinary care of individuals in captivity.

Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.

Minimizing morbidity when performing free flap reconstruction of the head and neck is important in the overall reconstructive paradigm.To examine the indications and success rates of free tissue transfer using small-caliber facial recipient vessels and minimal access incisions.Retrospective medical record review of patients with head and neck defects undergoing free tissue transfer from May 2010 to June 2013 at 2 tertiary care academic medical centers.Free tissue transfer using small-caliber recipient vessels and minimal access approaches.Postoperative complications, including flap failure, requirement for revision surgery, and nerve dysfunction.Eighty-nine flaps in 86 patients met inclusion criteria. Fifty flaps used the facial artery and vein distal to the facial notch, and 33 flaps used the superficial temporal vascular system. Six flaps used the angular artery and vein. A variety of flap donor sites were included. In most cases, free tissue transfer was indicated for the reconstruction of defects secondary to extirpation of malignant neoplasia. Overall success rate was 97.7% with 2 instances of total flap loss and 1 partial loss. One patient had transient nerve weakness (frontal branch), which resolved during a follow-up of 9 months.Free tissue reconstruction of head and neck defects can be safely and reliably accomplished using small-caliber recipient vessels, such as the superficial temporal, distal facial, and angular vessels. Minimal access approaches for microvascular anastomosis may be performed with excellent cosmesis and minimal morbidity.4.

This study describes a reliable technique for mucosal reconstruction of large defects using components of a common free flap technique.To review the harvest technique and the varied scenarios in which the anterolateral thigh adipofascial flap (ALTAF) can be used for mucosal restoration in oral cavity and nasal reconstruction.A retrospective review of the medical records of 51 consecutive patients was conducted. The patients had undergone ALTAF head and neck reconstruction between January 2009 and June 2013. Each case was reviewed, and flap survival and goal-oriented results were evaluated.Thirty patients met the inclusion criteria and were included in the analysis. The mean patient age was 60.6 years. Reconstruction sites included the tongue, palate, gingiva, floor of the mouth, and nasal mucosa. All mucosal reconstructions maintained function and form of replaced and preserved tissues. One patient (3%) experienced flap failure that was reconstructed with a contralateral adipofascial flap with excellent outcome. Three patients (10%) required minor flap revisions. There were no other complications.The ALTAF is a versatile flap easily harvested for use in several types of mucosal reconstructions.

Background A 10- to 15-mm L-strut in the dorsal and caudal areas of the nasal septum is preserved during septoplasty to maintain structural stability and prevent external deformity. However, during endoscopically performed septoplasty the surgeon has a very different perspective, which may create a more challenging situation to ensure adequate strut preservation. No reliable intranasal landmarks have been established. We establish intranasal landmarks that may be used during endoscopic septoplasty (ES) to safely maintain sufficient caudal and dorsal support. A cadaveric anatomic study was performed. Methods Measurements were made using calipers in 15 human cadavers (8 male and 7 female subjects), totaling 30 nasal passages. The caudal strut distance was measured from the inferior concha to the caudal aspect of the quadrangular cartilage. The dorsal strut height was measured from a line parallel to the nasal dorsum that extended from the middle turbinate (MT) axilla to the nasal vestibule (termed the “axillary line”). Results Using the inferior concha and the vertical MT attachment as endoscopic landmarks, the average caudal and dorsal struts measured 18.9 and 16.4 mm, respectively. Strut size was larger in male subjects than female subjects; however, dimensions remained >10 mm in all cadavers, establishing these landmarks as safe and effective for determining extent of cartilage resection. Conclusion The inferior turbinate and vertical MT attachment may be used to guide extent of cartilage resection during ES. Use of the described conchal and axillary lines as landmarks allow for preservation of an adequate L-strut during ES and may reduce support related complications.

IMPORTANCE The vascular supply of anterolateral thigh (ALT) free flaps is variable, and the pedicle length and ability to capture perforators to the flap may be limited by the anatomic configuration. We describe the reasoning behind performing the auto flow-through procedure, as well as the steps to carry this procedure out. OBSERVATIONS A retrospective medical chart review was performed within our health care system database to identify patients in whom the auto flow-through technique was used during reconstruction with an ALT free flap. The auto flow-through technique was applied to 3 separate ALT free flaps to incorporate perforators from 2 separate vascular systems. This technique allowed for more robust vascularity of the flap and/or optimized pedicle length that would have otherwise necessitated vein grafts. All patients had successful ALT free flap reconstruction and went on to have good functional results. CONCLUSIONS AND RELEVANCE The auto flow-through technique is an adaptation of the flow-through flap, which allows for capture of vascular perforators from separate sources when this configuration is present in the ALT free flap. This technique is especially useful when operating in a vessel-depleted neck or when maximizing pedicle reach is necessary. This technique allows the ALT to be used in challenging reconstruction cases regardless of the vascular branching pattern of the pedicle. LEVEL OF EVIDENCE 4.

Objectives This study is a review of our series of pediatric patients with unilateral sensorineural hearing loss (USNHL) to report abnormalities on imaging studies, review genetic and ophthalmologic results, and survey audiometric findings. Methods This study is a retrospective chart review of all pediatric patients with USNHL seen between 1/1/03 and 12/31/08 at our institution. The study was approved by the institutional review board. Results Eighty-nine cases were identified with audiometric findings confirming unilateral hearing thresholds greater than 20 dBHL with no conductive component. There were 48 males and 41 females. Average age of diagnosis was 7 years. One audiogram showed low-frequency loss, 17 mid-frequency, 29 high-frequency, and 32 flat. Ten patients were diagnosed by auditory brainstem response testing at another institution, with thresholds not available for review. Eleven percent of patients progressed to bilateral loss. Sixty-one patients underwent computed tomography of temporal bones (CTTB). Twenty of 61 scans identified 34 anomalies including 15 enlarged vestibular aqueducts (EVAs), 8 Mondini, and 3 superior semicircular canal dehiscences (SSCDs). Thirty-one of 89 patients underwent magnetic resonance imaging (MRI). Three of these 31 patients had positive findings including 1 EVA, 1 Mondini, and 1 asymmetric internal auditory canal. When CTTB was positive, no additional lesions were detected on MRI. When CTTB was negative and MRI was done in 20 patients, 2 additional lesions were detected by MRI. Fourteen patients had genetics evaluation of which 6 had positive findings, including CHARGE, VACTERL, Goldenhar, and 3 were heterozygous for a Connexin mutation. Conclusions CTTB is an effective diagnostic tool for USNHL. MRI should be considered in patients with negative CTTB. Genetics and ophthalmologic evaluations are recommended for patients with risk factors or an abnormal clinical examination. Close follow-up is essential due to high rate of hearing loss progression.

Autism Spectrum Conditions (ASC) are associated with diminished responsiveness to social stimuli, and especially to social rewards such as smiles. Atypical responsiveness to social rewards, which reinforce socially appropriate behavior in children, can potentially lead to a cascade of deficits in social behavior. Individuals with ASC often show diminished spontaneous mimicry of social stimuli in a natural setting. In the general population, mimicry is modulated both by the reward value and the sociality of the stimulus (i.e., whether the stimulus is perceived to belong to a conspecific or an inanimate object). Since empathy and autistic traits are distributed continuously in the general population, this study aimed to test if and how these traits modulated automatic mimicry of rewarded social and nonsocial stimuli. High and low rewards were associated with human and robot hands using a conditioned learning paradigm. Thirty-six participants from the general population then completed a mimicry task involving performing a prespecified hand movement which was either compatible or incompatible with a hand movement presented to the participant. High autistic traits (measured using the Autism Spectrum Quotient, AQ) predicted lesser mimicry of high-reward than low-reward conditioned human hands, whereas trait empathy showed an opposite pattern of correlations. No such relations were observed for high-reward vs. low-reward conditioned robot hands. These results demonstrate how autistic traits and empathy modulate the effects of reward on mimicry of social compared to nonsocial stimuli. This evidence suggests a potential role for the reward system in underlying the atypical social behavior in individuals with ASC, who constitute the extreme end of the spectrum of autistic traits.

The purpose of this work was to assess the pharmacokinetics and safety of lisdexamfetamine dimesylate (LDX) delivered and released regionally in the gastrointestinal (GI) tract. In this open-label, randomized, crossover study, oral capsules and InteliSite delivery capsules containing LDX (50 mg) with radioactive marker were delivered to the proximal small bowel (PSB), distal SB (DSB), and ascending colon (AC) during separate periods. Gamma scintigraphy evaluated regional delivery and GI transit. LDX and d-amphetamine in blood were measured postdose (≤72 h). Treatment-emergent adverse events (TEAEs) were assessed. Healthy males (n = 18; 18-48 years) were enrolled. Mean (S.D.) maximal plasma concentration (C(max)) was 37.6 (4.54), 40.5 (4.95), 38.7 (6.46), and 25.7 (9.07) ng/ml; area under the concentration-time curve to the last measurable time point was 719.1 (157.05), 771.2 (152.88), 752.4 (163.38), and 574.3 (220.65) ng · h · ml⁻¹, respectively, for d-amphetamine after oral, PSB, DSB, and AC delivery of LDX. Median time to C(max) was 5, 4, 5, and 8 h, respectively. Most TEAEs were mild to moderate. No clinically meaningful changes were observed (laboratory, physical examination, or electrocardiogram). LDX oral administration or targeted delivery to small intestine had similar d-amphetamine systemic exposure, indicating good absorption, and had reduced absorption after colonic delivery. The safety profile was consistent with other LDX studies.

Cardiovascular disease (eg, myocardial infarction, ischemic stroke) is the leading cause of death in patients who have metabolic syndrome and diabetes mellitus. By effectively treating the whole patient, however, the risk of death from cardiovascular disease can be reduced or prevented. The author describes clinical approaches for achieving this goal. He reviews information that is useful to know about patients regarding modifiable and potentially modifiable risk factors for cardiovascular disease, including hypertension, hyperlipidemia, smoking, activity levels, dietary habits, obesity, carotid artery stenosis, and atrial fibrillation. He also notes the importance of evaluating patients for relevant psychosocial factors such as depression. Finally, the author analyzes treatment options for patients, including effective medications, dietary modification, and exercise-emphasizing the use of pedometers-as well as participation by patients in weight-control support groups.

The framework of a Canadian-developed parent education program, Nobody's Perfect, was used in the development of a new parent education program offered to parents attending a child nutrition rehabilitation program in the Dominican Republic. While key teaching elements of the original program were retained (e.g., encouraging active participation, emphasizing facilitation over didactic teaching, using experiential learning), locally relevant content was inserted (e.g., diarrhea prevention and treatment strategies). A Canadian team trained a group of Dominicans to deliver the new program to parents of children recovering from malnutrition. This paper describes the development, implementation, and resulting parenting program from this effort. This 8-week program may find use in other settings. In addition, the experience gained from this exportation endeavor may be useful for others undertaking similar initiatives.

Dopexamine hydrochloride is a new synthetic catechol that offers a unique profile of adrenergic and dopaminergic activity. In this multicenter, parallel design, placebo-controlled study, 45 patients with functional class III or IV chronic congestive heart failure were randomized to receive a placebo infusion or one of three different doses of dopexamine. After a 2-h dose titration sequence, patients received a 6-h constant dose infusion. During this 6-h period, dopexamine was infused at rates of 1, 2 and 4 micrograms/kg body weight per min in the low, intermediate and high dose groups, respectively. In patients receiving high dose infusion, dopexamine produced a 78% increase in cardiac index associated with a 43% decrease in systemic vascular resistance and 24% increase in heart rate (p less than 0.05 vs. placebo for all three variables). There was a trend (p = NS) toward a moderate increase in cardiac index at low and intermediate doses. In patients randomized to receive dopexamine, right atrial, systemic arterial, pulmonary artery and pulmonary capillary wedge pressures showed minimal change from baseline and did not differ statistically from the placebo response. Very few patients developed adverse reactions related to dopexamine, although five patients randomized to receive high dose and three patients randomized to receive intermediate dose dopexamine required dose reduction because hemodynamic variables exceeded arbitrary safety limits or the patients developed symptoms related to the study medication. dopexamine in higher doses effectively increases cardiac index in association with a reduction in systemic vascular resistance. Additional clinical studies are indicated to evaluate the merits of dopexamine in comparison with other inotropic and vasodilator medications.

AIMS To compare the efficacy and safety of lanoteplase, a single-bolus thrombolytic drug derived from alteplase tissue plasminogen activator, with the established accelerated alteplase regimen in patients presenting within 6 h of onset of ST elevation acute myocardial infarction. METHODS AND RESULTS 15,078 patients were recruited from 855 hospitals worldwide and randomized in a 2:1 ratio to receive either lanoteplase 120 KU. kg(-1)as a single intravenous bolus, or up to 100 mg accelerated alteplase given over 90 min. The primary end-point was all-cause mortality at 30 days and the hypothesis was that the two treatments would be equivalent. By 30 days, 6.61% of alteplase-treated patients and 6.75% lanoteplase-treated patients had died (relative risk 1.02). Total stroke occurred in 1.53% alteplase- and 1.87% lanoteplase-treated patients (ns); haemorrhagic stroke rates were 0.64% alteplase and 1.12% lanoteplase (P=0.004). The net clinical deficit of 30-day death or non-fatal disabling stroke was 7.0% and 7.2%, respectively. By 6 months, 8.8% of alteplase-treated patients and 8.7% of lanoteplase-treated patients had died. CONCLUSION Single-bolus weight-adjusted lanoteplase is an effective thrombolytic agent, equivalent to alteplase in terms of its impact on survival and with a comparable risk-benefit profile. The single-bolus regimen should shorten symptoms to treatment times and be especially convenient for emergency department or out-of-hospital administration.

In 1986-87, a qualitative research project was conducted in the Dominican Republic, Egypt, Indonesia, and Thailand to expand understanding of the acceptability of NORPLANT contraceptive implants beyond inferences made on the basis of continuation rates. In each of the four study sites, focus group discussions or in-depth interviews were held with potential acceptors, current NORPLANT users, discontinuers, husbands of women in these three groups, and service providers. Nonclinical participants generally had little formal education and lived primarily in urban or semi-urban areas where NORPLANT has been available for at least five years. The study focused on attitudes, perceptions, and experiences of each group regarding NORPLANT implants. Results suggest that factors having an impact on the acceptability of NORPLANT implants fall into three general categories: medical/technical, cultural/religious, and informational/educational. This article discusses each of these categories, including programmatic implications of the findings, and puts forward recommendations for enhancing NORPLANT introduction efforts on the basis of these findings.In 1986-87, a qualitative research project was done in Thailand, Egypt, Indonesia, and the Dominican Republic to expand knowledge of the acceptability of NORPLANT contraceptive implants beyond continuation rates. In each of the 4 studies, in-depth interviews or focus group discussions were held with current NORPLANT users, potential acceptors, discontinuers, husband of women in the 3 groups, and service providers. The 4 countries were chosen because of their diverse cultures and religions. Most participants favored family planning. Many had used other contraceptives. Men and women in all countries were worried that oral female contraceptive agents (the pill) caused cancer. There were many objections to the IUD. In all countries but Thailand, there was little knowledge of NORPLANT. In the Dominican Republic, NORPLANT was used mostly as a child spacing method. In Indonesia, it was used for child spacing and termination of childbearing. Perceived advantages were alike in all countries. Pain during insertion and removal was a big concern of potential users. Men and women in all countries said that religion and traditional beliefs did not influence their family planning decisions. But many said that religion influenced their tolerance of side effects. In Egypt and Indonesia sterilization is unpopular because it is seen as violating Islamic law. Irregular bleeding was the major side effect and the main reason for discontinuation. Many satisfied users felt that the advantaged outweighed the side effects. Primary reasons for removal in all countries were irregular bleeding, amenorrhea, and the desire to give birth. The need for information was mentioned in all countries. In Egypt, Indonesia, and Thailand services providers reported the need for more thorough training in insertion and removal as well as continuing education sessions.

Background α2-Adrenoceptor agonists are used adjunctively to psychostimulants in treating attention-deficit/hyperactivity disorder (ADHD) when psychostimulants alone do not sufficiently reduce symptoms. However, data on the pharmacokinetic profiles and safety of combination treatments in ADHD are needed. Objective The primary objective of this study was to evaluate the pharmacokinetic profiles of guanfacine extended release (GXR) and methylphenidate hydrochloride (MPH) extended release, alone and in combination. Study Design This was an open-label, randomized, three-period crossover, drug–drug interaction study. Setting The study was conducted at a single clinical research center. Participants Thirty-eight healthy adults were randomized in this study. Interventions Subjects were administered single oral doses of GXR (Intuniv®; Shire Development LLC, Wayne, PA, USA) 4 mg, MPH (Concerta®; McNeil Pediatrics, Titusville, NJ, USA) 36 mg, or GXR and MPH combined. Main Outcome Measures Guanfacine, dexmethylphenidate (d-MPH), and l-methylphenidate (l-MPH) levels were measured with blood samples collected predose and up to 72 h postdose. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms (ECGs). Results Thirty-five subjects completed the study. Analyses of the 90 % confidence intervals (CIs) for the geometric mean ratios of the maximum plasma concentration (Cmax) and area under the concentration–time curve extrapolated to infinity (AUC∞) values for guanfacine and d-MPH following administration of GXR or MPH alone or combined met strict bioequivalence criteria (90 % CIs within the interval of 0.80–1.25). Overall, combining GXR and MPH did not alter the pharmacokinetic parameters of either medication. Sixteen subjects (42.1 %) had at least one TEAE. The most commonly reported TEAEs included headache and dizziness following GXR, MPH, and GXR and MPH combined. Two subjects had clinically significant abnormalities in ECG results following coadministration: both events were mild and resolved the same day. Conclusions In this short-term, open-label study of healthy adults, coadministration of GXR and MPH did not result in significant pharmacokinetic drug–drug interactions. No unique TEAEs were observed with coadministration of GXR and MPH compared with either treatment alone.

The short-term effects of omega-3 fatty acids on exercise test parameters in patients with known coronary artery disease are poorly defined. Therefore, we administered a preparation containing 5.4 g of eicosapentaenoic acid and 3.6 g docosahexaenoic acid to 8 patients in a random order, double-blind, crossover design. The patients were given either fish oil or a vegetable oil control for 6 wk and then crossed over to the other treatment for a second 6-wk period, after a 2-wk wash-out interval. Exercise test parameters, angina frequency, and lipoprotein composition were measured at baseline and at the end of each trial phase. No significant changes were found in resting or peak exercise heart rate or double product, exercise duration or ischemic electrocardiographic changes at peak exercise. Angina frequency and sublingual nitroglycerin usage did not change during either the fish oil or the control oil phase. Plasma triglyceride levels decreased significantly with fish oil treatment and HDL cholesterol levels rose slightly. Total and LDL cholesterol levels were unchanged. We conclude that relatively high dose, short-term administration of omega-3 fatty acids does not alter exercise test parameters.