Identification of a predominant cognitive phenotype in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment occurs frequently in multiple sclerosis (MS). However, the prevalence and clinical characteristics of cognitive MS phenotype are not well established. The aim of the study was to characterize the clinical course and neurocognitive impairment of patients with MS meeting an Expanded Disability Status Scale (EDSS)-defined cognitive phenotype. METHODS: A total of 2302 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study were studied. Predominant cognitive MS phenotype was defined as EDSS Cerebral Functional System (FS) subscore ≥3 and remaining EDSS FS subscores ≤2 on at least one clinical visit. Demographic/clinical characteristics, phenotype stability and neurocognitive domain impairment of these subjects were assessed. RESULTS: A total of 60 of 2302 (2.6%) patients (age 52.8 ± 10.8 years, 68% female, 82% relapsing MS) met criteria for phenotype designation. A total of 29 of 60 (48%) were designated within 10 years of their presenting MS symptom. The mean cohort annualized relapse rate was 0.38 and EDSS score at last clinical assessment was 3.2 ± 1.3. Cognitive phenotype status was poorly sustained, with only 27% of subjects maintaining Cerebral FS score ≥2 throughout all follow-up. However, predominant cognitive phenotype subjects with clinical neuropsychiatric testing [n = 39/60 (65%)] frequently had cognitive impairment (1.5 SD below mean) in ≥1 domain [n = 30/39 (77%) of subjects] affecting memory, attention/executive function and processing speed. A total of 11 of 39 (28%) patients had severe-range cognitive impairment (3.0 SD below mean). Cognitive phenotype designation was associated with low rate of employment at last clinical assessment. CONCLUSION: Predominant cognitive MS phenotype is rare, although an EDSS-based definition identifies patients with multidomain cognitive impairment and may serve as a practical screen for identification of patients who might warrant close monitoring of neurocognitive status.

New IR imaging modalities for cancer detection and for intra-cell chemical mapping with a sub-diffraction mid-IR s-SNOM.

We present two new modalities for generating chemical maps. Both are mid-IR based and aimed at the biomedical community, but they differ substantially in their technological readiness. The first, so-called "Digistain", is a technologically mature "locked down" way of acquiring diffraction-limited chemical images of human cancer biopsy tissue. Although it is less flexible than conventional methods of acquiring IR images, this is an intentional, and key, design feature. It allows it to be used, on a routine basis, by clinical personnel themselves. It is in the process of a full clinical evaluation and the philosophy behind the approach is discussed. The second modality is a very new, probe-based "s-SNOM", which we are developing in conjunction with a new family of tunable "Quantum Cascade Laser" (QCL) diode lasers. Although in its infancy, this instrument can already deliver ultra-detailed chemical images whose spatial resolutions beat the normal diffraction limit by a factor of ∼1000. This is easily enough to generate chemical maps of the insides of single cells for the first time, and a range of new possible scientific applications are explored.

Antidepressant Exposure and DNA Methylation: Insights from a Methylome-Wide Association Study.

Importance: Understanding antidepressant mechanisms could help design more effective and tolerated treatments. Objective: Identify DNA methylation (DNAm) changes associated with antidepressant exposure. Design: Case-control methylome-wide association studies (MWAS) of antidepressant exposure were performed from blood samples collected between 2006-2011 in Generation Scotland (GS). The summary statistics were tested for enrichment in specific tissues, gene ontologies and an independent MWAS in the Netherlands Study of Depression and Anxiety (NESDA). A methylation profile score (MPS) was derived and tested for its association with antidepressant exposure in eight independent cohorts, alongside prospective data from GS. Setting: Cohorts; GS, NESDA, FTC, SHIP-Trend, FOR2107, LBC1936, MARS-UniDep, ALSPAC, E-Risk, and NTR. Participants: Participants with DNAm data and self-report/prescription derived antidepressant exposure. Main Outcomes and Measures: Whole-blood DNAm levels were assayed by the EPIC/450K Illumina array (9 studies, N exposed = 661, N unexposed = 9,575) alongside MBD-Seq in NESDA (N exposed = 398, N unexposed = 414). Antidepressant exposure was measured by self- report and/or antidepressant prescriptions. Results: The self-report MWAS (N = 16,536, N exposed = 1,508, mean age = 48, 59% female) and the prescription-derived MWAS (N = 7,951, N exposed = 861, mean age = 47, 59% female), found hypermethylation at seven and four DNAm sites (p < 9.42x10 -8 ), respectively. The top locus was cg26277237 ( KANK1, p self-report = 9.3x10 -13 , p prescription = 6.1x10 -3 ). The self-report MWAS found a differentially methylated region, mapping to DGUOK-AS1 ( p adj = 5.0x10 -3 ) alongside significant enrichment for genes expressed in the amygdala, the "synaptic vesicle membrane" gene ontology and the top 1% of CpGs from the NESDA MWAS (OR = 1.39, p < 0.042). The MPS was associated with antidepressant exposure in meta-analysed data from external cohorts (N studies = 9, N = 10,236, N exposed = 661, f3 = 0.196, p < 1x10 -4 ). Conclusions and Relevance: Antidepressant exposure is associated with changes in DNAm across different cohorts. Further investigation into these changes could inform on new targets for antidepressant treatments. 3 Key Points: Question: Is antidepressant exposure associated with differential whole blood DNA methylation?Findings: In this methylome-wide association study of 16,536 adults across Scotland, antidepressant exposure was significantly associated with hypermethylation at CpGs mapping to KANK1 and DGUOK-AS1. A methylation profile score trained on this sample was significantly associated with antidepressant exposure (pooled f3 [95%CI]=0.196 [0.105, 0.288], p < 1x10 -4 ) in a meta-analysis of external datasets. Meaning: Antidepressant exposure is associated with hypermethylation at KANK1 and DGUOK-AS1 , which have roles in mitochondrial metabolism and neurite outgrowth. If replicated in future studies, targeting these genes could inform the design of more effective and better tolerated treatments for depression.

Point prevalence and clinical course of proteinuria in dogs with idiopathic non-erosive immune-mediated polyarthritis.

OBJECTIVES: To describe the point prevalence and clinical course of proteinuria in dogs diagnosed with idiopathic non-erosive immune-mediated polyarthritis. MATERIALS AND METHODS: Cases presenting to a single referral centre with a diagnosis of idiopathic non-erosive immune-mediated polyarthritis were retrospectively recruited from January 2009 to August 2018. Data including signalment, urinalysis, clinicopathological results, cytology from arthrocentesis, treatment and long-term follow-up were analysed. Dogs were defined as: non-proteinuric (UPC <0.2), borderline proteinuric (UPC 0.2-0.5) or overtly proteinuric (UPC >0.5). RESULTS: Fifty-eight dogs met the inclusion criteria. Twenty-two dogs were overtly proteinuric (38%), eight dogs were borderline proteinuric (14%) and 28 dogs were non-proteinuric (48%). Repeated urinalysis was performed in nine of 12 dogs with UPC greater than 2.0. The UPC decreased in all nine dogs, with the UPC decreasing to less than 0.5 in 44% of dogs. A greater than 50% decrease in UPC was noted in 44% of dogs, despite seven of nine (77%) receiving prednisolone as either monotherapy or in conjunction with an adjunctive immunosuppressive medication. CLINICAL SIGNIFICANCE: Proteinuria was common in this cohort of dogs diagnosed with primary idiopathic non-erosive immune-mediated polyarthritis. The use of prednisolone does not appear to be contraindicated in proteinuric dogs with idiopathic non-erosive immune-mediated polyarthritis.

Emotion recognition and eye tracking of static and dynamic facial affect: A comparison of individuals with and without traumatic brain injury.

Diminished social functioning is often seen after traumatic brain injury (TBI). Mechanisms contributing to these deficits are poorly understood but thought to relate to impaired ability to recognize facial expressions. Static stimuli are often used to investigate ability post-TBI, and there is less evidence using more real-life dynamic stimuli. In addition, most studies rely on behavioral responses alone. The present study investigated the performance of a TBI group and matched non-TBI group on static and dynamic tasks using eye-tracking technology alongside behavioral measures. This is the first study to use eye tracking methodology alongside behavioral measures in emotion recognition tasks in people with brain injury. Eighteen individuals with heterogeneous TBI and 18 matched non-TBI participants were recruited. Stimuli representing six core emotions (Anger, Disgust, Fear, Happy, Sad, and Surprise faces) were selected from the Amsterdam Dynamic Facial Expression Set (ADFES). Participants were instructed to identify the emotion displayed correctly whilst eye movement metrics were recorded. RESULTS: Results of analyses showed that TBI patients had First Fixation to nose for all emotion stimuli, shorter Fixation Duration and lower Fixation Count to eyes, were generally slower to classify stimuli, and less accurate than non-TBI group for the static task. Those with TBI were also less accurate at identifying Angry, Disgust, and Fear stimulus faces compared to the non-TBI group during the dynamic unfolding of an emotion. CONCLUSION: In the present study, those with TBI had atypical eye scan patterns during emotion identification in the static emotion recognition task compared to the non-TBI group and were associated with lower identification accuracy on behavioral measures in both static and dynamic tasks. Findings suggest potential disruption to oculomotor systems vital for first stage perceptual processing. Arguably, these impairments may contribute to diminished social functioning.

Systematic review of wastewater surveillance of antimicrobial resistance in human populations.

OBJECTIVES: We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) evidence of concordance between wastewater-human AMR prevalence estimates, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin's concordance correlation coefficient (CCC) to quantify concordance between AMR prevalence estimates in wastewater and human compartments (where CCC = 1 reflects perfect concordance), and logistic regression to identify study features (e.g. sampling methods) associated with high agreement studies (defined as >70% of within-study wastewater-human AMR prevalence comparisons within ±10%). RESULTS: Of 8,867 records and 441 full-text methods reviewed, 33 studies were included. AMR prevalence data was extractable from 24 studies conducting phenotypic-only (n = 7), genotypic-only (n = 1) or combined (n = 16) AMR detection. Overall concordance of wastewater-human AMR prevalence estimates was reasonably high for both phenotypic (CCC = 0.85 [95% CI 0.8-0.89]) and genotypic approaches (CCC = 0.88 (95% CI 0.84-0.9)) despite diverse study designs, bacterial species investigated and phenotypic/genotypic targets. No significant relationships between methodological approaches and high agreement studies were identified using logistic regression; however, this was limited by inconsistent reporting of study features, significant heterogeneity in approaches and limited sample size. Based on a secondary, descriptive synthesis, studies conducting composite sampling of wastewater influent, longitudinal sampling >12 months, and time-/location-matched sampling of wastewater and human compartments generally had higher agreement. CONCLUSION: Wastewater-based surveillance of AMR appears promising, with high overall concordance between wastewater and human AMR prevalence estimates in studies irrespective of heterogenous approaches. However, our review suggests future work would benefit from: time-/location-matched sampling of wastewater and human populations, composite sampling of influent, and sampling >12 months for longitudinal studies. Further research and clear and consistent reporting of study methods is required to identify optimal practice.

Complex chronic conditions among children born to women with schizophrenia.

PURPOSE: Maternal schizophrenia is linked to complications in offspring near the time of birth. Whether there is also a higher future risk of the child having a complex chronic condition (CCC) - a pediatric condition affecting any bodily system expected to last at least 12 months that is severe enough to require specialty care and/or a period of hospitalization - is not known. METHODS: In this population-based health administrative data cohort study (Ontario, Canada, 1995-2018), the risk for CCC was compared in 5066 children of women with schizophrenia (the exposed) vs. 2,939,320 unexposed children. Adjusted hazard ratios (aHR) were generated for occurrence of any CCC, by CCC category, and stratified by child sex, and child prematurity. RESULTS: CCC was more frequent in the exposed (7.7 per 1000 person-years [268 children]) than unexposed (4.2 per 100 person-years [124,452 children]) - an aHR of 1.25 (95% CI 1.10-1.41). aHRs were notably higher in 5 of 9 CCC categories: neuromuscular (1.73, 1.28-2.33), cardiovascular (1.94, 1.64-2.29), respiratory (1.83, 1.32-2.54), hematology/immunodeficiency (2.24, 1.24-4.05) and other congenital or genetic defect (1.59, 1.16-2.17). The aHR for CCC was more pronounced among boys (1.32, 1.13-1.55) than girls (1.16, 0.96-1.40), and of similar magnitude in term (1.22, 1.05-1.42) and preterm infants (1.18, 0.95-1.46). CONCLUSIONS: The risk for a CCC appears to be higher in children born to women with schizophrenia. This finding introduces opportunities for targeted preconception counselling, optimization of maternal risk factors, and intervention to support a vulnerable parent population who will experience unique challenges caring for a child with CCCs.

Case report: reconstruction of the distal tibia with porous tantalum spacer after resection for giant cell tumor.

Treatment options for giant cell tumors of the distal tibia include curettage and cement packing, curettage and bone grafting, or resection and reconstruction for aggressive tumors. Curettage of aggressive tumors often leads to severe bone loss requiring reconstruction. Allograft and autograft may be effective options for reconstruction, but each is associated with drawbacks including the possibility of infection and collapse. We present a case of giant cell tumor of the distal tibia treated with curettage and arthrodesis using a porous tantalum spacer. Complete removal of the tumor and successful arthrodesis of the ankle were accomplished using the spacer. The patient returned to pain-free walking along with eradication of the giant cell tumor. We believe porous tantalum spacers are a reasonable option for reconstructing the distal tibia after curettage of a giant cell tumor with extensive bone loss.

Serological markers of gluten sensitivity in Border terriers with gall bladder mucocoeles.

OBJECTIVES: To evaluate serological markers of gluten sensitivity in conjunction with cholecystokinin measurement in Border terriers with gall bladder mucocoeles. MATERIALS AND METHODS: Medical records from two referral hospitals were obtained between 2011 and 2019 to identify Border terriers with gall bladder mucocoeles, non-Border terriers with gall bladder mucocoeles and control Border terriers with non-biliary diseases. Enzyme-linked immunosorbent assays were performed on stored fasted serum samples for anti-gliadin IgG, anti-canine transglutaminase-2-IgA autoantibodies and cholecystokinin. Statistical analysis was performed using the Kruskall-Wallis test to identify differences between the groups. RESULTS: Fifteen Border terriers with gall bladder mucocoeles, 17 non-Border terriers with gall bladder mucocoeles and 14 control Border terriers with non-biliary diseases were recruited. Median transglutaminase-2-IgA autoantibodies in Border terriers with gall bladder mucocoeles was 0.73 (range: 0.18 to 1.67), which was significantly greater than in control Border terriers at 0.41 (0.07 to 1.14). Median cholecystokinin concentration in Border terriers with gall bladder mucocoeles was 13 pg/mL (6 to 45 pg/mL), which was significantly lower than in control Border terriers at 103 pg/mL (9 to 397 pg/mL). There was no difference in the anti-gliadin IgG between these groups. There was no difference observed in the non-Border terriers with gall bladder mucocoeles with either of the other groups. CLINICAL SIGNIFICANCE: Reduced cholecystokinin and increased transglutaminase-2-IgA autoantibodies was detected in Border terriers with gall bladder mucocoeles; which is in part homologous to gall bladder disease identified in human coeliac disease. The results suggest an immunological disease with impaired cholecystokinin release may be affecting gall bladder motility and possibly contributing to mucocoele formation in Border terriers.

Virus-like antigen, antibody, and antigen-antibody complexes in hepatitis measured by complement fixation.

Complement fixation techniques are described for measuring a virus-like antigen associated with viral hepatitis. Antigen was found in the blood of 98 percent of 130 patients, with the serum form of hepatitis, from whom multiple samples were obtained. Antibodies arising during hepatitis are usually combined with antigen and cause anticomplementary activity in the serum, which is reversible with excess antigen or antibody. Tests for antigen and specific anticomplementary activity can be used diagnostically and to screen blood donors for hepatitis carriers.

Pre prosthetic mobility: the amputees' perspectives.

PURPOSE: It is considered good practice that amputees remain in a wheelchair until fitted with a prosthesis. However, this practice is not evidence based. In the first of a series of studies in pre prosthetic mobility, this study will explore the individual amputees' perspective. METHOD: A total of 25 participants from a regional disablement service centre were interviewed focusing on their experiences of getting around the home post discharge. The transcripts were coded for types of mobility methods used and the content analysed. RESULTS: Whilst the wheelchair was the predominant method of mobilizing, this was not viewed positively by amputees. Crutches were frequently used, even if crutches were not provided by therapists. Participants cited space and choice as reasons behind this, in particular the psychological impact of being 'stuck' in a wheelchair. Other methods cited included crawling and bottom shuffling. CONCLUSION: Amputees do not always comply with therapists' advice and frequently use other methods of mobilizing as a matter of choice as well as necessity. The risk factors associated with these methods is a priority for future research.

Diabetes and anxiety in US adults: findings from the 2006 Behavioral Risk Factor Surveillance System.

AIMS: Anxiety disorders may cause substantial impairment in patient functioning and well-being. Little is known about the relationship between diabetes and anxiety. We estimated the prevalence of lifetime diagnosis of anxiety in adults aged > or = 18 years with and without diabetes in the USA. METHODS: We analysed data from the 2006 Behavioral Risk Factor Surveillance System (total, N = 201 575; 20 142 with diabetes; 39.4% men, 77.9% non-Hispanic Whites, 8.1% non-Hispanic Blacks and 7.7% Hispanics; mean age 52.4 years). Diabetes and lifetime diagnosis of anxiety were self-reported. A multivariable log-binomial model was used to estimate prevalence ratios (PR) and associated 95% confidence intervals (CI) of anxiety based on diabetes status. RESULTS: The overall age-adjusted prevalence of lifetime diagnosis of anxiety was 19.5 and 10.9% in people with and without diabetes, respectively. After adjustment for educational level, marital status, employment status, current smoking, leisure-time physical activity and body mass index, people with diabetes had a 20% higher prevalence of lifetime diagnosis of anxiety than those without (PR 1.20; 95% CI 1.12, 1.30). There were no significant differences in the PR by gender (P = 0.06). However, the ratios differed significantly by age (P = 0.04) and by race/ethnicity (P < 0.01), indicating that people aged 18-29 years (PR 1.70; 95% CI 1.19, 2.43) and Hispanics (PR 1.69; 95% CI 1.33, 2.15) had a higher ratio than their counterparts. CONCLUSION: Diabetes was significantly associated with anxiety in adults in this large population-based sample, particularly in Hispanics and young adults.

Overview and quality assurance for the oral health component of the National Health and Nutrition Examination Survey (NHANES), 2003-04.

The 2003-04 National Health and Nutrition Examination Survey (NHANES) was a collaborative effort involving 28 federal funding partners with the National Center for Health Statistics. The collaborators for the 2003-04 NHANES oral health component included the National Institute of Dental and Craniofacial Research and the National Center for Chronic Disease Prevention and Health Promotion, Division of Oral Health. Oral health data are available on 8272 persons aged 2 years or older. This report provides an overview of the 2003-04 oral health component including content descriptions and procedures for oral health assessments conducted for the first time in a national survey in the United States. These assessments include posterior functional contacts, tooth wear, and oral health-related quality of life. This report also provides evaluations of data quality in terms of examiner reliability statistics (percent agreements, kappas, and correlation coefficients) for various NHANES 2003-04 oral health examination components and analytical recommendations for producing 6-year estimates using the previous two NHANES data collection components (1999-2000 and 2001-02).

Effects of short- and long-term exposure of silver nanoparticles and silver ions to Nitrosomonas europaea biofilms and planktonic cells.

The increasing use of silver nanoparticles (AgNPs) in consumer products, and their resulting influx into wastewater, may pose a threat to biological nutrient removal in wastewater treatment plants. Planktonic ammonia-oxidizing bacteria (AOB), which convert ammonia to nitrite in the first step of nitrification, are highly sensitive to AgNPs and their released silver ions (Ag+), but the sensitivity of AOB biofilms to AgNPs and Ag+ is less clear. This study demonstrated that biofilms of Nitrosomonas europaea, a model AOB, were more resistant to both short-term and long-term exposure to AgNP and Ag+ than planktonic cells. The increased resistance of N. europaea biofilms was attributed primarily to the increased biomass and slower growth rates present in the biofilm. Similar inhibition mechanisms were observed for AgNPs and Ag+ in both planktonic cells and biofilms with enzymatic inhibition observed at lower concentrations and cell lysis observed at higher concentrations. Long-term continuous exposure to AgNPs lowered the inhibitory concentration by 1-2 orders of magnitude below that required by short-term exposures. Although the total AgNP load was similar between the short and long-term exposure scenarios, the long-term exposure resulted in an order of magnitude more silver being associated in the biofilms and is the primary reason for the increased sensitivity observed. This suggests that short-term batch toxicity assays may greatly underestimate the sensitivity of biofilm treatment systems to long-term exposures of low concentrations of AgNPs and Ag+.

Legionella indianapolisensis sp. nov., isolated from a patient with pulmonary abscess.

BACKGROUND: To date, at least 50 species of Legionella have been described. These organisms are ubiquitous in nature and have been isolated from diverse ecological environments, including man-made structures such as cooling towers and spas. Legionellae have also been isolated from human and veterinary clinical specimens, and their roles in disease are well-established. This report describes the isolation of a novel Legionella species from a respiratory specimen from a patient with influenza and suspected pulmonary embolus. CASE: A 68-year-old male presented to an Indianapolis-area hospital with pulmonary disease; upon workup, he was found to have influenza A. Bronchoalveolar lavage fluid was also submitted for conventional bacterial culture and Legionella culture. The patient was prescribed a broad-spectrum antibiotic and recovered. RESULTS: A Legionella-like bacterium was isolated on buffered charcoal yeast extract agar, and mass spectrometry and comparative 16S rRNA gene sequencing inconclusively identified the isolate as a Legionella sp. Further analysis of the 16S rRNA gene confirmed the strain to be a new species, related to Legionella hackeliae. Physiochemical and morphological testing were used to confirm the discovery of a novel species, Legionella indianapolisensis sp. nov., type strain SMNF-IS.

Gall bladder mucoceles in Border terriers.

BACKGROUND: Gall bladder mucoceles (GBM) are a leading cause of biliary disease in dogs with several breeds, including the Shetland Sheepdog, American Cocker Spaniel, Chihuahua, Pomeranian, and Miniature Schnauzer apparently predisposed. OBJECTIVE: To determine risk factors, clinical features, and response to treatment of GBM in Border terriers (BT). ANIMALS: Medical records of 99 dogs (including 51 BT) with an ultrasonographic (±histopathologic) diagnosis of GBM from three referral centers in the United Kingdom were collected. A control group of 87 similar-aged BT with no ultrasonographic evidence of gall bladder disease was selected for comparison. METHOD: Retrospective case-control study. Odds ratios were calculated to establish breed predisposition. Signalment, presence of endocrine disease, clinicopathologic results, and outcome were compared between the BT, other breeds, and control BTs. RESULTS: The odds of identifying a GBM in a BT in this hospital population was 85 times that of all other breeds (95% confidence interval 56.9-126.8). BT had similar clinical signs and clinicopathologic changes to other breeds with GBM. There was no evidence that endocrinopathies were associated with GBM in BT. CLINICAL SIGNIFICANCE: A robust breed predisposition to GBM is established for the BT.

Overview and quality assurance for the National Health and Nutrition Examination Survey (NHANES) oral health component, 1999-2002.

The Oral Health Component of the 1999-2002 National Health and Nutrition Examination Survey (NHANES) is a collaborative effort between the National Institute of Dental and Craniofacial Research (NIDCR), the National Center for Chronic Disease Prevention and Health Promotion, Division of Oral Health (NCCDPHP/DOH), and the National Center for Health Statistics (NCHS). The current NHANES is designed as a continuous survey with data released on a 2-year cycle to represent the civilian, non-institutionalized population of the US. Oral health data are currently available for 8082 and 9010 persons aged > or =2 years who participated in the 1999-2000 and 2001-2002 NHANES, respectively. This article provides background information on previous national examination surveys with oral health content. It also provides general analytical considerations, oral health content information, and evaluations of data quality in terms of examiner reliability statistics (percent agreements, kappa, and correlation coefficients) for the 1999-2002 NHANES Oral Health Component.

Oral transmucosal fentanyl citrate versus placebo for painful dressing changes: a crossover trial.

OBJECTIVE: Fentanyl is a potent opioid that is well absorbed via the oral mucosa. It can be given as an oral lozenge. The onset of analgesia is rapid and matches the pain profile observed at dressing changes. METHOD: Patients experiencing pain during daily dressing changes were given entonox plus either placebo or oral transmucosal fentanyl citrate (OTFC) for two consecutive dressing changes in a randomised double-blind placebo-controlled crossover trial. RESULTS: Nine patients were recruited. The mean worst pain score during dressing changes was 7/10 with placebo and 4/10 with OTFC; the reduction in pain achieved with OTFC was significant. The mean number of breaths of entonox taken during the dressing change was 27.67 with placebo and 4.67 with OTFC; the reduction in the number of entonox breaths with OTFC was significant. One patient in the OTFC group suffered nausea. CONCLUSION: Compared with placebo, OTFC improved analgesia during painful dressing changes without an increase in side-effects.

Implicit cognition is impaired and dissociable in a head-injured group with executive deficits.

Implicit or non-conscious cognition is traditionally assumed to be robust to pathology but Gomez-Beldarrain et al. recently showed deficits on a single implicit task after head injury. Laboratory research suggests that implicit processes dissociate. This study therefore examined implicit cognition in 20 head-injured patients and age- and IQ-matched controls using a battery of four implicit cognition tasks: a serial reaction time task (SRT), mere exposure effect task, automatic stereotype activation and hidden co-variation detection. Patients were assessed on an extensive neuropsychological battery, and MRI scanned. Inclusion criteria included impairment on at least one measure of executive function. The patient group was impaired relative to the control group on all the implicit cognition tasks except automatic stereotype activation. Effect size analyses using the control mean and standard deviation for reference showed further dissociations across patients and across implicit tasks. Patients impaired on implicit tasks had more cognitive deficits overall than those unimpaired, and a larger dysexecutive self/other discrepancy (DEX) score suggesting greater behavioural problems. Performance on the SRT task correlated with a composite measure of executive function. Head injury thus produced heterogeneous impairments in the implicit acquisition of new information. Implicit activation of existing knowledge structures appeared intact. Impairments in implicit cognition and executive function may interact to produce dysfunctional behaviour after head injury. Future comparisons of implicit and explicit cognition should use several measures of each function, to ensure that they measure the latent variable of interest.

Hepatitis B virus infection and primary hepatocellular carcinoma.

Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls.