Automated femoral version estimation without the distal femur.

Femoral version impacts the long-term functioning of the femoroacetabular joint. Accurate measurements of version are thus required for success in total hip arthroplasties and hip reconstructive surgeries. These are impossible to obtain without visualization of the distal femur, which is often unavailable preoperatively as the majority of imaging scans are isolated to the pelvis and proximal femur. We developed an automated algorithm for identifying the major landmarks of the femur. These landmarks were then used to identify proximal axes and create a statistical shape model of the proximal femur across 144 asymptomatic femora. With six proximal axes selected, and 200 parameters (distances and angles between points) from the shape model measured, the best-fitting linear correlation was found. The difference between true version and version predicted by this model was 0.00 ± 5.13° with a maximum overestimation and underestimation of 11.80 and 15.35°, respectively. The mean absolute difference was 4.14°. This model and its prediction of femoral version are a substantial improvement over pre-operative 2D or intra-operative visual estimation measures. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3161-3168, 2018.

Usefulness of a Nonsuture Closure Device in Patients Undergoing Diagnostic Coronary and Peripheral Angiography.

Vascular access site complications can follow diagnostic coronary and peripheral angiography. We compared the complication rates of the Catalyst vascular closure device, with the complication rates after manual compression in patients undergoing diagnostic angiographic procedures via femoral access. We studied 1,470 predominantly male patients undergoing diagnostic coronary and peripheral angiography. Catalyst closure devices were used in 436 (29.7%) patients and manual compression was used in 1,034 (70.3%) patients. The former were allowed to ambulate after 2 hours, while the latter were allowed to ambulate after 6 hours. Major complications occurred in 4 (0.9%) patients who had a Catalyst device and in 14 (1.4%) patients who had manual compression (odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.22-2.1, p = 0.49). Any complications occurred in 51 (11.7%) patients who had a Catalyst closure device and in 64 (6.2%) patients who had manual compression (OR: 2, CI: 1.4-3, p < 0.01). After adjustment for other variables and for a propensity score reflecting the probability to receive the closure device, the association of major complications with the use of the closure device remained not significant (OR: 0.54, 95% CI: 0.17-1.7, p = 0.29), while the association of any complications with the use of the Catalyst device remained significant (OR: 1.9, 95% CI: 1.3-2.9, p < 0.01). The Catalyst device was not associated with an increased risk of major groin complications but was associated with an increased risk of any complications compared with manual compression. Patients receiving the closure device ambulated sooner.

Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial.

BACKGROUND: Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clinical trial will evaluate the clinical effectiveness of pre-hospital plasma administration compared with standard- of-care crystalloid resuscitation in severely-injured patients with major traumatic haemorrhage. METHODS/DESIGN: This is a prospective, randomized, open-label, non-blinded trial to determine the effect of pre-hospital administration of thawed plasma (TP) on mortality, morbidity, transfusion requirements, coagulation, and inflammatory response in severely-injured bleeding trauma patients. Two hundred and ten eligible adult trauma patients will be randomised to receive either two units of plasma, to be administered in-field, vs standard of care normal saline (NS). Main analyses will compare subjects allocated to TP to those allocated to NS, on an intention-to-treat basis. Primary outcome measure is all-cause 30-day mortality. Secondary outcome measures include coagulation and lipidomic/pro-inflammatory marker responses, volume of resuscitation fluids (crystalloid, colloid) and blood products administered, and major hospital outcomes (e.g. incidence of MSOF, length of ICU stay, length of hospital stay). DISCUSSION: This study is part of a US Department of Defense (DoD)-funded multi-institutional investigation, conducted independently of, but in parallel with, the University of Pittsburgh and University of Denver. Demonstration of significant reductions in mortality and coagulopathic/inflammatory-related morbidities as a result of pre-hospital plasma administration would be of considerable clinical importance for the management of haemorrhagic shock in both civilian and military populations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02303964 on 28 November 2014.

Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

Prophylactic dressing application to reduce pressure ulcer formation in cardiac surgery patients.

PURPOSE: The study was designed to determine if application of a self-adherent silicone border foam dressing would reduce pressure ulcer incidence when compared to standard preventive interventions among patients managed in a cardiac surgery intensive care unit (CSICU). SUBJECTS AND SETTING: One hundred consecutive patients in the CSICU at Virginia Commonwealth University Medical Center in Richmond participated in the study. Fifteen were subsequently excluded due to incomplete data or failure to remain in the CSICU for at least 48 hours. Of the 100 subjects consecutively enrolled, 56 subjects were assigned to the intervention group with attrition of 6 subjects (6/56), and 39 were assigned to the standard care comparison group with attrition of 4 subjects (4/39). Five study forms were lost and the group assignment of those subjects is unknown. METHODS: Patients admitted to the CSICU were assigned to either standard treatment or an intervention group consisting of standard preventive care plus application of the silicone border foam dressing. The assignment of subjects to these groups was done in a nonrandom manner, via prestudy room designation (7 intervention rooms/7 standard practice rooms) and room availability on call from the operating room. The charge nurse and bed management staff were unaware of room designation, and staff did not know which group the subjects were assigned to until they admitted the patient and opened the bedside chart that indicated group assignment. Twenty-one covariates were compared between the 2 groups. A Cox proportional hazards model was computed to compare the hazard (risk per unit time) of developing a pressure ulcer between these groups. Propensity score covariate adjustment was performed to adjust for any imbalance between the groups. RESULTS: Nine pressure ulcers developed during the course of the study. Eight pressure ulcers developed in 4 out of 35 patients who received standard preventive care; 5 were classified as suspected deep tissue injuries and 3 were classified as stage II pressure ulcers. One pressure ulcer developed in 1 out of 50 patients in the intervention group; it was classified as suspected deep tissue injury. No statistically significant difference in any covariate was found between the groups (all P > .058). The group that received standard care had a hazard ratio of 3.6 in relation to the intervention group, but this difference was not statistically significant (P = .3). CONCLUSION: Pressure ulcer incidence was lower than anticipated over the study period for both groups. No statistically significant difference in pressure ulcer incidence between the intervention and control groups was found. A randomized controlled trial based on a power analysis is needed to more precisely determine the efficacy of a silicone border foam dressing for prevention of pressure ulcers in the intensive care unit.

Vestibular dysfunction in DFNB1 deafness.

Mutations of GJB2 and GJB6 (connexin-26 and 30) at the DFNB1 locus are the most common cause of autosomal recessive, nonsyndromic deafness. Despite their widespread expression throughout the vestibular system, vestibular dysfunction has not been widely recognized as a commonly associated clinical feature. The observations of vertigo accompanying DFNB1 deafness in several large families prompted our hypothesis that vestibular dysfunction may be an integral, but often overlooked, component of DFNB1 deafness. Our aim was to define the prevalence of vestibular dysfunction in Cases of DFNB1 deafness and Controls with other forms of deafness. We developed and used a survey to assess symptoms of vestibular dysfunction, medical, and family history was distributed to Cases with deafness due to pathogenic GJB2 and/or GJB6 mutations and deaf Controls without DFNB1 deafness. Our results showed: Surveys were returned by 235/515 Cases (46%) with DFNB1 mutations and 121/321 Controls (38%) without these mutations. The mean age of Cases (41) was younger than Controls (51; P < 0.001). Vestibular dysfunction was reported by 127 (54%) of Cases and was present at significantly higher rates in Cases than in deaf Controls without DFNB1 deafness (P < 0.03). Most (63%) had to lie down in order for vertigo to subside, and 48% reported that vertigo interfered with activities of daily living. Vertigo was reported by significantly more Cases with truncating than non-truncating mutations and was also associated with a family history of dizziness. We conclude that vestibular dysfunction appears to be more common in DFNB1 deafness than previously recognized and affects activities of daily living in many patients.

Variables associated with odds of finishing and finish time in a 161-km ultramarathon.

We sought to determine the degree to which age, sex, calendar year, previous event experience and ambient race day temperature were associated with finishing a 100-mile (161-km) trail running race and with finish time in that race. We computed separate generalized linear mixed-effects regression models for (1) odds of finishing and (2) finish times of finishers. Every starter from 1986 to 2007 was used in computing the models for odds of finishing (8,282 starts by 3,956 individuals) and every finisher in the same period was included in the models for finish time (5,276 finishes). Factors associated with improved odds of finishing included being a first-time starter and advancing calendar year. Factors associated with reduced odds of finishing included advancing age above 38 years and warmer weather. Beyond 38 years of age, women had worse odds of finishing than men. Warmer weather had a similar effect on finish rates for men and women. Finish times were slower with advancing age, slower for women than men, and less affected by warm weather for women than for men. Calendar year was not associated with finish time after adjustment for other variables.

Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy.

BACKGROUND & AIMS: Patients with cirrhosis and minimal hepatic encephalopathy (MHE) have driving difficulties but the effects of therapy on driving performance is unclear. We evaluated whether performance on a driving simulator improves in patients with MHE after treatment with rifaximin. METHODS: Patients with MHE who were current drivers were randomly assigned to placebo or rifaximin groups and followed up for 8 weeks (n = 42). Patients underwent driving simulation (driving and navigation tasks) at the start (baseline) and end of the study. We evaluated patients' cognitive abilities, quality of life (using the Sickness Impact Profile), serum levels of ammonia, levels of inflammatory cytokines, and model for end-stage-liver disease scores. The primary outcome was the percentage of patients who improved in driving performance, calculated as follows: total driving errors = speeding + illegal turns + collisions. RESULTS: Over the 8-week study period, patients given rifaximin made significantly greater improvements than those given placebo in avoiding total driving errors (76% vs 31%; P = .013), speeding (81% vs 33%; P = .005), and illegal turns (62% vs 19%; P = .01). Of patients given rifaximin, 91% improved their cognitive performance, compared with 61% of patients given placebo (P = .01); they also made improvements in the psychosocial dimension of the Sickness Impact Profile compared with the placebo group (P = .04). Adherence to the assigned drug averaged 92%. Neither group had changes in ammonia levels or model for end-stage-liver disease scores, but patients in the rifaximin group had increased levels of the anti-inflammatory cytokine interleukin-10. CONCLUSIONS: Patients with MHE significantly improve driving simulator performance after treatment with rifaximin, compared with placebo.

Similar progression of fibrosis between HIV/HCV-infected and HCV-infected patients: Analysis of paired liver biopsy samples.

BACKGROUND & AIMS: Fibrosis progression might be accelerated in patients who are coinfected with human immunodeficiency virus (HIV) and HCV (HIV/HCV). However, no studies have directly compared fibrosis progression by paired liver biopsy between patients infected with HIV and HCV versus those infected with only HCV. METHODS: Liver biopsy samples were collected from patients with HIV/HCV (n = 306) and those with HCV; biopsies from 59 without a sustained virologic response (SVR) or cirrhosis were matched with those from patients with only HCV (controls) for initial fibrosis stage, demographics, and HCV treatment. For HIV/HCV patients, categorical variables at baseline and the area under the curve of continuous variables per unit time were analyzed for associations with fibrosis progression. RESULTS: Liver biopsies from HIV/HCV patients had more piecemeal necrosis than controls (P = .001) and increased lobular inflammation (P = .002); HIV/HCV patients also had shorter intervals between liver biopsies (4.7 vs 5.9 years, P < .0001). Between the first and second biopsies, fibrosis remained unchanged or progressed 1 or 2 units in 55%, 18%, and 18% of HIV/HCV patients, respectively, compared with 45%, 30%, and 9% of controls. The fibrosis progression rate was similar between HIV/HCV and control patients (0.12 ± 0.40 vs 0.091 ± 0.29 units/y; P = .72). In paired biopsies from 66 patients, including those with SVR, there were no associations between fibrosis progression and demographics; numbers of CD4+ T cells; levels of aspartate aminotransferase or alanine aminotransferase; use of highly active antiretroviral therapy; response to HCV therapy (no treatment, SVR, or non-response); baseline levels of FIB-4; or histologic features including inflammation, fibrosis, or steatosis. CONCLUSIONS: On the basis of analysis of liver biopsy samples, fibrosis progression was similar between HIV/HCV-infected and HCV-infected patients; no clinical or laboratory parameters predicted disease progression.

Anxiety disorders in rural primary care: use of the MINI to estimate prevalence in clinic patients.

Anxiety disorders are a common problem, but there are few estimates of their prevalence in rural areas. The purpose of the present study was to determine the prevalence of anxiety disorders in rural Northern California and compare the rural rates with those nationally and at urban primary care clinics. The Mini-International Neuropsychiatric Interview was administered to patients seeking care at rural primary care clinics in Northern California as a psychiatric screening tool. Over three years, 3,462 patients were screened at five clinics, and the prevalence was compared with published primary care prevalences.1 The observed rate of panic disorder was 9.5%, social phobia was 8.5%, and generalized anxiety disorder (GAD) was 21.9%. Compared with population estimates, these rates are unusually high. This apparent difference may reflect socio-demographic characteristics of rural primary care populations. The prevalence of anxiety disorders in rural primary care clinics may have implications for clinical care and service delivery systems.

Lagtime in psychosomatic medicine consultations for cognitive-disorder patients: association with length of stay.

BACKGROUND: Utilization studies in inpatient psychosomatic medicine have focused on patterns of consultation requests, timing of consultation requests relative to date of hospital admission, and the association between time to initial psychiatric consultation and length of stay. OBJECTIVE: The authors studied the association of time to initial psychosomatic medicine consultation and length of stay for inpatients with cognitive disorders. METHOD: The authors reviewed 157 charts, analyzing effects of age, gender, days from admission until consultation (REFLAG), and length of stay (LOS). Two values were computed: referral lag divided by LOS (REFLAG/LOS) and log(REFLAG)/log(LOS). RESULTS: Mean REFLAG was 8.13; mean LOS was 18.6 days; mean REFLAG/LOS was 0.466; and mean log(REFLAG)/log (LOS) was 0.596. REFLAG and log (REFLAG)/log(LOS) correlated significantly with LOS. CONCLUSION: REFLAG is significantly associated with increased LOS. Referring services may need to consider earlier consultation requests.

The Western States 100-Mile Endurance Run: participation and performance trends.

PURPOSE: Examine changes in demographics of participants and performance trends at the Western States 100-Mile Endurance Run (WSER) since its inception in 1974. METHODS: Name, age, sex, and finish information was obtained on runners in the WSER from 1974 to 2007. Linear regression analyses, ANOVA, and t-tests were used to examine participation and performance trends. RESULTS: The mean age of participants increased (P < 0.001) to around 45 yr, with men being an average of 3 yr older (P < 0.001) than women. The increase in average age of starters was accounted for by the growth in participation among women >or=40 yr and men >or=50 yr, and by the decreasing participation among men <50 yr. Between 1986 and 2007, there was an increasing participation among women to around 20% of all starters. With this came improved (P < 0.01) finish times for the top 5 overall women and the top 5 women in the 30-39 and 40-49 yr age groups, whereas performances among the men did not improve over this time span. Average ages of the top performers increased (P

The utility of the model for end-stage liver disease score: a reliable guide for liver transplant candidacy and, for select patients, simultaneous hospice referral.

Patients with chronic liver disease are referred late to hospice or never referred. There are several barriers to timely referral. First, liver transplantation (LT) and hospice care have always been perceived as mutually exclusive. Yet the criteria for hospice referral and for LT are more similar than different (for example, advanced liver disease and imminent death). Second, physicians, patients, and families have not had a reliable metric to guide referral. However, many patients wait for transplantation but never receive an organ. We hypothesized that the Model for End-Stage Liver Disease (MELD) score already in use to prioritize LT could be used in selected patients for concurrent hospice referral. Furthermore, we hypothesized that patients awaiting LT can receive hospice care and remain eligible for transplantation. Patients with advanced or end-stage liver disease were referred to the University of California Davis Health System hospice program. We correlated the MELD score at admission to length of stay (LOS) in hospice. A total of 157 end-stage liver disease patients were admitted to the hospice service. At the time of hospice admission the mean MELD score was 21 (range, 6-45). The mean length of hospice stay was 38 days (range, 1-329 days). A significant correlation was observed between hospice LOS and MELD score at hospice admission (P < 0.01). Six patients were offered a liver graft while on the combined (LT and hospice) program. MELD can be used to guide clinician recommendation to families about hospice care, achieving one of the national benchmark goals of increasing hospice care duration beyond the current median of 2-3 weeks. A higher MELD score might augment physician judgment as to hospice referral. Hospice care for selected patients may be an effective strategy to improve the care of end-stage liver disease patients waiting for LT.

Variable cortisol circadian rhythms in children with autism and anticipatory stress.

OBJECTIVE: Autism is characterized by impairment in communication and social interaction, by repetitive behaviours and by difficulty in adapting to novel experiences. The objective of the current investigation was to replicate and extend our previous findings showing variable circadian rhythm and significant elevations in cortisol following exposure to a novel stimulus (mock magnetic resonance imaging [MRI]). METHODS: Circadian rhythms of cortisol were estimated in 22 children with and 22 children without autism via analysis of salivary samples collected in the morning, afternoon and evening over 6 separate days. We assessed hypothalamic-pituitary-adrenal (HPA) responsiveness by examining changes in salivary cortisol in response to a mock MRI. One-half of the children were re-exposed to the MRI environment. RESULTS: Children with autism showed a decrease in cortisol in the morning over 6 days while maintaining higher evening values. Children with autism also showed more within-and between-subject variability in circadian rhythms. Although the cortisol values tended to be higher in some of the children with autism, a statistically significant elevation in cortisol in response to the initial mock MRI was not observed. Rather, both groups showed heightened cortisol at the arrival to the second visit to the imaging centre, suggesting an anticipatory response to the re-exposure to the mock MRI. CONCLUSION: Children with autism showed dysregulation of the circadian rhythm evidenced by variability between groups, between children and within individual child comparisons. Both groups demonstrated increased salivary cortisol in anticipation of re-exposure to the perceived stressor.

Early acceleration of head circumference in children with fragile x syndrome and autism.

OBJECTIVE: Head circumference (HC) growth has been shown in several studies to be accelerated early in life in both fragile X syndrome (FXS) and autism spectrum disorders (ASDs), but the rates of growth have not been compared between those with only FXS and those with FXS and ASD (FXS + ASD). METHODS: We hypothesized that individuals with FXS + ASD would have significantly larger HCs from individuals with only FXS and that there would be an early acceleration of HC in both the FXS-only and FXS + ASD groups. HC measurements were available retrospectively for 44 males, five and younger, with FXS, of whom 22 also had ASD. Measurements over time were available for 24 of the 44 children. HC percentiles were compared between the groups in two ways: by focusing on cross-sectional subsamples and by fitting hierarchical linear models to the full sample. RESULTS: Neither group differed significantly from the norm in the first year of life (p > 0.2). At 30 months, the FXS + ASD group was 27 percentile points above the norm (p = .0125), whereas the FXS-only group did not differ from the norm. At 60 months, the FXS-only group was 21 percentile points above the norm (p = .029), whereas the FXS + ASD group did not differ from the norm. CONCLUSION: The group difference in HC growth rate may differentiate brain development in individuals with FXS-only versus those with FXS + ASD.

Endophthalmitis after uncomplicated cataract surgery with the use of fourth-generation fluoroquinolones: a retrospective observational case series.

OBJECTIVE: To estimate the rate of acute postoperative endophthalmitis after uncomplicated cataract surgery in patients treated before and after surgery with 1 of 2 different fourth-generation fluoroquinolone ophthalmic drops for surgical prophylaxis. DESIGN: Retrospective, multicenter, observational case series. PARTICIPANTS: Included in this study were 20,013 patients from 9 cataract surgery centers in 7 states in the United States. METHODS: Patients who had undergone uncomplicated phacoemulsification who received preoperative and postoperative topical fourth-generation fluoroquinolones for surgical prophylaxis between March 2003 and July 2005 were included in the study. The files of patients in whom acute endophthalmitis developed were reviewed and analyzed. MAIN OUTCOME MEASURES: Number and rate of endophthalmitis cases after uncomplicated cataract surgery. RESULTS: During the study period, the participating surgeons performed 20,013 uncomplicated surgeries. Of these, 16,209 patients (81%) received topical gatifloxacin and 3804 patients (19%) were treated with topical moxifloxacin as antiinfective prophylaxis. A total of 14 patients experienced endophthalmitis. The overall rate of endophthalmitis was 0.07%. There were 9 endophthalmitis patients in the gatifloxacin group and 5 endophthalmitis patients in the moxifloxacin group. The rate of endophthalmitis in the gatifloxacin group was 0.06% and the rate in the moxifloxacin group was 0.1%. The difference in the rate of endophthalmitis between the 2 groups was not statistically significant. In 10 of the patients, vitreous culture results were positive. Coagulase-negative staphylococci, followed by streptococci, species were the most commonly isolated organisms in the culture-positive patients. CONCLUSIONS: The overall rate of endophthalmitis after uncomplicated cataract surgery in patients treated with topical fourth-generation fluoroquinolones as antiinfective prophylaxis was 0.07%. This rate was within the range of previously reported rates of endophthalmitis in the literature. The difference in the observed rate of postoperative endophthalmitis in patients treated with moxifloxacin versus gatifloxacin was not statistically significant.

Cognitive-disorder diagnoses in inpatient psychosomatic-medicine consultations: associations with age and length of stay.

Authors reviewed consecutive charts of 155 cognitive-disorder patients from a psychosomatic medicine service in 2001, analyzing factors of age, cognitive-disorder diagnosis, and length of stay. Mean length of stay for this cohort exceeded the typical hospital length of stay, and decreased with age. Increased age was associated with a decreased probability of a delirium-only diagnosis, and was strongly associated with an increased probability of a dementia diagnosis. Among those with dementia, the probability of having an additional diagnosis of delirium was unrelated to age. The case-mix of cognitive disorders differs with age, whereas cognitive disorders are associated with increased length of stay for adult patients of all ages.

Cortisol circadian rhythms and response to stress in children with autism.

BACKGROUND: Autism is a severe neurodevelopmental disorder characterized by impairment in communication, social interaction, repetitive behaviors and difficulty adapting to novel experiences. The Hypothalamic-Pituitary-Adrenocortical (HPA) system responds consistently to perceived novel or unfamiliar situations and can serve as an important biomarker of the response to a variety of different stimuli. Previous research has suggested that children with autism may exhibit dysfunction of the HPA system, but it is not clear whether altered neuroendrocrine regulation or altered responsiveness underlies the differences between children with and without autism. In order to provide preliminary data concerning HPA regulation and responsiveness, we compared circadian rhythms and response to a non-social, environmental stressor in children with and without autism. METHODS: Circadian rhythms of cortisol were estimated in children with (N=12) and without (N=10) autism via analysis of salivary samples collected in the morning, afternoon and evening on 2 consecutive days. HPA responsiveness was assessed by examining the time course of changes in salivary cortisol in response to a mock MRI. RESULTS: Both groups showed expected circadian variation with higher cortisol concentration in morning than in the evening samples. The children with autism, but not typical children, showed a more variable circadian rhythm as well as statistically significant elevations in cortisol following exposure to a novel, nonsocial stimulus. CONCLUSIONS: The results suggest that children with autism process and respond idiosyncratically to novel and threatening events resulting in an exaggerated cortisol response.

Abnormal elevation of FMR1 mRNA is associated with psychological symptoms in individuals with the fragile X premutation.

Until recently, individuals with premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene were believed to be psychologically unaffected. However, the recent documentation of abnormal elevation of FMR1 mRNA, discovery of fragile X-associated tremor/ataxia syndrome (FXTAS), and reports of psychiatric disorders in children and adults with the premutation have suggested a pathogenic gene-brain-behavior mechanism. In a large collaborative study, 68 men and 144 women with the FMR1 premutation completed a psychological symptoms checklist and FMR1 genetic testing, including determination of CGG repeat size, percentage of FMR1 protein (FMRP)-positive lymphocytes, and FMR1 mRNA levels. Relative to published norms, men and women with FXTAS symptoms reported higher levels of several types of psychological symptoms. In addition, men and women with the premutation and no overt evidence of FXTAS reported higher levels of obsessive-compulsive symptoms. Elevated FMR1 mRNA, but not CGG repeat size or reduced FMRP (as measured by immunocytochemistry), was significantly associated with increased psychological symptoms, predominantly obsessive-compulsive symptoms and psychoticism, in premutation men with and without FXTAS symptoms. There was no relationship between CGG repeat size, FMR1 mRNA or FMRP and psychological symptoms in premutation women unless the sample was restricted to those with skewed X-activation ratio toward >50% active premutation alleles. The results of this study support the hypothesis that FMR1 function is associated with psychological difficulties in individuals with the premutation, and provide evidence concordant with an RNA toxic gain-of-function model in a neuropsychiatric phenotype.

The impact of psychiatric diagnosis on length of stay in a university medical center in the managed care era.

Inpatient use data were examined for fiscal years 1999-2001. Patients with and without psychiatric diagnoses were compared for length of hospital stay and complexity of illness. Patients with psychiatric disorders represented 33%-35% of total cases. Substance use (9,824 cases), mood disorders (2,524 cases), and cognitive disorders (2,362 cases) were the most common psychiatric illnesses. Patients with substance use disorders or no psychiatric diagnosis had the shortest adjusted length of stay, whereas the small number with adjustment disorders (N=147) had the longest. Other psychiatric patients had lengths of stay between these extremes. Excepting substance use disorders, increased lengths of stay with psychiatric comorbidity have persisted into the managed care era.