Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The Olfactory Cleft Endoscopy Scale: a multi-institutional validation study in chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction (OD) associated with chronic rhinosinusitis (CRS) remains quite challenging. Instruments to precisely assess olfactory cleft anatomy and their association with olfaction are needed. METHODS: The olfactory cleft endoscopy scale (OCES) was used to assess the olfactory cleft in healthy control subjects and a cohort of patients with CRS. Psychophysical and psychosocial olfactory function were assessed and correlations with OCES scores were measured. RESULTS: Control subjects and subjects with CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) were enrol- led. OCES correlated with both psychophysical and psychosocial olfaction, as measured by threshold, discrimination and identi- fication (TDI) scores and Questionnaire on Olfactory Disorders (QOD-NS) scores for all case and control subjects combined. OCES improved in both CRS groups postoperatively with the highest correlation seen in postoperative olfaction in CRSwNP patients. CRS patients who achieve near perfect OCES and sinus endoscopy scores after surgery have olfactory metrics that are indistin- guishable from controls regardless of polyp status. CONCLUSIONS: The OCES is a valid olfactory-specific measure that demonstrates strong validity and provides complimentary infor- mation to traditional sinus endoscopy to aid in our understanding of OD associated with CRS.

Lack of impact of radiologic septal measurements upon patient symptoms and performance of septoplasty during endoscopic sinus surgery.

BACKGROUND: Recent literature suggests that concurrent septoplasty during endoscopic sinus surgery (ESS) improves patient outcomes, however, the underlying indications for performing concurrent septoplasty are unknown. The objective of this study was to investigate the relationship between objective radiologic measures of nasal septal deviation with preoperative patient symptomatology and measures of CRS disease severity. We also sought to understand the association of objective radiologic measurements with surgeon performance of concurrent septoplasty during ESS. METHODOLOGY: Seventy-four patients with CRS undergoing ESS were prospectively enrolled. Angles of septal deviation, intranasal areas and volumes were assessed on preoperative computed tomography (CT) scans and correlated with a robust battery of patient reported outcomes measures (PROMs), objective measures of CRS severity including olfaction scores, radiologic and endoscopic staging, and performance of septoplasty. RESULTS: Intranasal areas and volumes demonstrated only weak linear associations with patient-reported nasal congestion, however, angles of septal deviation alone did not correlate with congestion or any other PROM measure. Meanwhile, radiologic septal-related measurements did not correlate with objective measures of CRS disease severity or the performance of a concurrent septoplasty. CONCLUSIONS: Though prior studies demonstrate improved patient outcomes in the setting of concurrent septoplasty during ESS, this study failed to establish an association between preoperative radiologic septal-related measurements and patient symptomatology or surgeon decision to perform septoplasty. Although objective factors to identify patients most likely to benefit from concurrent septoplasty remain unidentified, the potential improvement of surgical recommendations and patient outcomes makes this an important area of continued investigation.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma: preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates.

Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D(KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.

An AAVP-based solid-phase transducing matrix for transgene delivery: potential for translational applications.

A hybrid vector of adeno-associated virus and phage (termed AAVP) has been introduced as a platform for systemic ligand-directed delivery of transgenes to tumors over the past decade. A series of studies have evaluated the AAVP platform for potential theranostic or purely therapeutic applications in several tumor models. Sufficient ligand-directed tumor targeting consistently resulted in specific molecular-genetic imaging and/or anti-tumor responses to 'suicide' transgene delivery. However, efforts to optimize transduction efficiency are still ongoing. Here, we set out to expand the translational utility of AAVP by combining it with gold (Au) nanoparticles in order to generate a 'transducing matrix' for improved targeted gene delivery in solid phase. Targeted AAVP-based solid-phase transduction is superior to conventional transduction in soluble (aqueous) environments. This transducing matrix is stable and can be further modified with additional attributes (for example, magnetization) for targeted imaging and therapeutic gene delivery. Notably, it spontaneously assembles around cells in vitro to markedly enhance transduction capabilities compared with AAVP alone. This versatile nanoplatform may enable new applications of AAVP for transgene delivery in translational settings including, for example, efforts toward complex tissue patterning.

Asthma quality of life and control after sinus surgery in patients with chronic rhinosinusitis.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) often have comorbid asthma. Prior studies have not examined the impact of CRS or endoscopic sinus surgery (ESS) upon asthma quality of life (QOL) and asthma control using validated outcome metrics. METHODS: Patients with CRS, both with and without polyps, and comorbid asthma completed the Mini Asthma QOL Questionnaire (miniAQLQ) and Asthma Control Test (ACT) at baseline and 6 months postoperatively as part of a multi-institutional, prospective study. RESULTS: Baseline metrics were available on 86 patients. Patients undergoing ESS reported improved miniAQLQ [0.5 (SD ±1.1), 95% CI: 0.2-0.7; P = 0.002] and ACT scores [1.3 (±4.1), 95% CI: 0.2-2.4; P = 0.025]. Uncontrolled baseline asthma (ACT < 20) was present in 51% of patients undergoing ESS. In uncontrolled patients, ESS resulted in a minimal clinically important difference 57% of the time for miniAQLQ scores (≥0.5 points) and 50% of the time for ACT scores (≥3.0 points). After adjustment with linear regression, baseline miniAQLQ scores were worse in patients with comorbid allergy (P = 0.045) and chronic obstructive pulmonary disease (COPD; P = 0.015). Adjusted baseline ACT scores were worse in patients with COPD (P = 0.004). Covariates associated with changes in miniAQLQ scores after ESS were pre-operative corticosteroid dependency (P = 0.011) and change in total SNOT-22 score (P = 0.010). Covariate associated with significantly less improvement in ACT scores was obstructive sleep apnea (P = 0.016). CONCLUSIONS: Patients with CRS often present with uncontrolled asthma, and ESS improves both miniAQLQ and ACT. Approximately half of patients with uncontrolled asthma improve after ESS, yet there are few CRS-specific factors associated with asthma QOL or control or ESS outcomes.

A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa.

BACKGROUND: The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' cognitive-behavioral therapy (CBT-E). METHOD: Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). RESULTS: Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. CONCLUSIONS: ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.

Review of brucellosis cases from laboratory exposures in the United States in 2008 to 2011 and improved strategies for disease prevention.

Five laboratory-acquired brucellosis (LAB) cases that occurred in the United States between 2008 and 2011 are presented. The Centers for Disease Control and Prevention (CDC) reviewed the recommendations published in 2008 and the published literature to identify strategies to further prevent LAB. The improved prevention strategies are described.

A 90-day adaptation to a high glycaemic diet alters postprandial lipid metabolism in non-obese horses without affecting peripheral insulin sensitivity.

High glycaemic feeds are associated with the development of insulin resistance in horses. However, studies that evaluated the effect of high glycaemic feeds used horses that either ranged in body condition from lean to obese or were fed to increase body condition over a period of months; thus, the ability of high glycaemic feeds to induce insulin resistance in lean horses has not been determined. This study evaluated the insulin sensitivity of 18 lean horses fed a 10% (LO; n = 6), 20% (MED; n = 6) or 60% (HI; n = 6) non-structural carbohydrate complementary feed for 90 days. Although both the MED and HI diets increased insulinaemic responses to concentrate feeding in relation to the LO diet (p > 0.05), neither induced insulin resistance, as assessed by glucose tolerance test, following the 90-day feeding trial. Interestingly, the post-feeding suppression of plasma non-esterified fatty acids was less pronounced in HI-fed horses (p = 0.054) on days 30 and 90 of the study, potentially indicating that insulin-induced suppression of adipose tissue lipolysis was reduced. As insulin-resistant animals often have elevated plasma lipid concentrations, it is possible that altered lipid metabolism is an early event in the development of insulin resistance. The effects of high glycaemic feeds that are fed for a longer duration of time, on glucose and lipid metabolism, should be investigated further.

Dietary supplementation with short-chain fructo-oligosaccharides improves insulin sensitivity in obese horses.

Obesity and insulin resistance are risk factors for laminitis in horses and ponies, and diet can play an important role in modulating these risk factors. Dietary supplementation with prebiotic fibers, such as short-chain fructo-oligosaccharides (scFOS), has resulted in improvement of insulin sensitivity in obese dogs and rodents. Thus, we hypothesized that scFOS may reduce insulin resistance in obese horses and designed a study to evaluate the effect of dietary supplementation with scFOS on insulin sensitivity. Eight mature Arabian geldings (BW = 523.0 ± 56.5 kg) with an average BCS of 8 were included in a crossover study. In each period, 4 horses were provided 45 g/d per horse of maltodextrin (control) and 4 horses received the same amount of scFOS for 6 wk, with a 3-wk washout between periods. Resting plasma concentrations of glucose, insulin, triglycerides, and leptin were measured. Minimal model analysis of a frequently sampled intravenous glucose tolerance test was used to evaluate insulin sensitivity, glucose effectiveness, acute insulin response to glucose, and disposition index. Without affecting BW and BCS, dietary supplementation with scFOS increased (P < 0.05) insulin sensitivity and reduced (P < 0.05) acute insulin response to glucose in comparison with maltodextrin but did not alter (P > 0.05) glucose effectiveness and disposition index. Resting serum insulin concentration also was reduced (P < 0.05) by scFOS supplementation but not by maltodextrin (P > 0.05). There was no effect (P > 0.05) of scFOS supplementation on plasma glucose or serum triglyceride and leptin concentrations. This study demonstrated that scFOS can moderately improve insulin sensitivity of obese horses, a finding that has potential relevance to the dietary management of obese, insulin-resistant horses at increased risk for laminitis.

Inactivation of the p16 cyclin-dependent kinase inhibitor in high-grade canine non-Hodgkin's T-cell lymphoma.

The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL.

Survey of the migration of melamine and formaldehyde from melamine food contact articles available on the UK market.

The migration of melamine and formaldehyde, monomers used in the production of melamine-ware food contact articles, has been determined from 50 retail articles purchased in the UK. The food simulant 3% aqueous acetic acid was used as this is the most aggressive simulant towards melamine plastics. The test conditions used were repeated exposure to the simulant for 2 hours at 70 degrees C, since the articles were all intended for general use including contact with hot foods and beverages. Melamine migrated from 43 of the 50 samples tested and formaldehyde migrated from all 50 samples. Directive 2002/72/EC specifies migration limits for both of these monomers in foods and food simulants. Melamine is restricted by a specific migration limit (SML) of 30 mg/kg (equivalent to 5 mg/dm(2)) and formaldehyde, along with hexamethylenetetramine expressed as formaldehyde, is restricted by a total (T) SML(T) of 15 mg/kg (equivalent to 2.5 mg/dm(2)). In all cases the migration of melamine was much lower than the SML for this monomer. The migration of formaldehyde exceeded the SML(T) for 5 of the 50 samples tested. The failure to comply with the SML(T) was accompanied by a number of visible surface effects including discolouration and/or pitting of the simulant contact surface and cracking of the articles. Similar surface effects were observed when one of the samples was exposed to fruit juice which confirmed the suitability of the exposure conditions and 3% acetic acid as a simulant for the articles tested. The ratio of specific migration to overall migration was consistent with, but did not prove, the hypothesis that high formaldehyde migration could be due to the use of excessive hexamethylenetetramine in the polymer formulation. All illegal products were voluntarily removed from the market by the product suppliers.

Expression of sigma 1 receptor in human breast cancer.

The sigma 1 receptor (S1R) represents a unique drug-binding site that is distinct from any other receptors. We examined S1R expression in human breast cancer and assessed the activity of S1R ligands in breast cancer cell lines. One-hundred nine breast specimens from normal breast, benign breast disease and cancer were examined with immunohistochemistry or RT-PCR and six different cell lines were also evaluated. S1R mRNA overexpression was detected in 64% of breast cancers compared to normal breast tissue. Immunohistochemistry showed positive epithelial cell staining in 60% of invasive and 41% of in situ cancers, 75% of ductal hyperplasia and in 33% of normal breast. The pattern of expression was more diffuse in invasive breast carcinoma compared to other conditions (p = 0.02). S1R expression was neither a prognostic nor a predictive factor for efficacy of adjuvant chemotherapy but the study only included 58 cancer patients and therefore the statistical power is limited. MDA-MB-361, MDA-MB-435, BT20 and MCF7 cells all expressed S1R protein by Western blot. The non-specific S1R ligands haloperidol, reduced haloperidol and progesterone produced a dose-dependent inhibition of the growth at high (>10 microM) concentrations. Reduced haloperidol also showed additive cytotoxic effects when combined with doxorubicin, vinorelbine , paclitaxel and docetaxel in vitro. The S1R-specific ligand, SKF 10047 demonstrated the least growth inhibitory activity and showed no interaction with chemotherapy. These results demonstrate that some normal and most neoplastic breast epithelial cells and cell lines commonly express S1R. High concentrations of haloperidol inhibit the growth of these cells and potentiate the effect of chemotherapy in vitro.

Predicting spasticity after stroke in those surviving to 12 months.

OBJECTIVE: To measure muscle tone in a cohort of patients 12 months after stroke and develop a preliminary model, using data recorded routinely after stroke, to predict who will develop spasticity. DESIGN: A cohort study. SETTING: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, United Kingdom. SUBJECTS: One hundred and six consecutively presenting stroke patients surviving to 12 months. MAIN OUTCOME MEASURES: Spasticity measured at a range of joints using the Tone Assessment Scale. RESULTS: The Tone Assessment Scale revealed spasticity in 38 (36%) patients and more severe spasticity in 21 (20%) of the 106 patients. Logistic regression analysis revealed that lower day 7 Barthel Index score and early arm or leg weakness were significant predictors of abnormal muscle tone; and lower day 7 Barthel Index score, left-sided weakness and ever smoked to be significant predictors of more severe muscle tone. CONCLUSIONS: Using the models, it may be possible to predict whether or not spasticity will develop in patients 12 months after stroke. The utility of the models is aided by their use of predictor variables that are routinely collected as part of stroke care in hospital and which are easy to measure. The models need testing prospectively in a new cohort of patients in order to test their validity, reliability and utility and to determine if other data could improve their efficiency.

A 5-year prospective evaluation of DSM-IV alcohol dependence with and without a physiological component.

BACKGROUND: The DSM-III-R removed tolerance and withdrawal as required elements for a diagnosis of alcohol dependence. Although this practice was continued in DSM-IV, the more recent manual asked clinicians to note whether physiological aspects of withdrawal (tolerance and withdrawal) had ever been experienced. Few studies have determined the prognostic meaning of a history of a physiological component to DSM-IV alcohol dependence. METHODS: Face-to-face structured interviews were used to evaluate the course of alcohol, drug, and psychiatric problems during the subsequent 5 years for 1094 alcohol-dependent men and women. These subjects had been classified into subgroups at the time of initial interview regarding evidence of tolerance or withdrawal, and all evaluations were based on DSM-IV criteria. At baseline, the application of DSM-IV diagnostic guidelines resulted in 649 (59.3%) individuals having a history of an alcohol withdrawal syndrome, with or without tolerance (group 1); 391 (35.7%) with histories of tolerance but not withdrawal (group 2); and 54 (4.9%) with no lifetime histories of tolerance or withdrawal (group 3). RESULTS: During the 5-year follow-up, both the broad (group 1 plus 2 versus group 3) and narrow (group 1 versus group 2 plus group 3) definitions of physiological dependence were associated with more alcohol and drug problems. However, for most items, this differential primarily reflected differences between groups 1 and 3, with a less impressive effect by group 2. Although no group differences were noted for the rate of independent major depressive episodes, substance-induced depressions did differentiate among groups, a finding also most closely related to the distinction between groups 1 and 3. CONCLUSIONS: These data support the prognostic importance of noting the presence of a physiological component in alcohol dependence and indicate the potential relevance of limiting the definition of a physiological component to withdrawal.

A five-year prospective study of diagnostic orphans for alcohol use disorders.

OBJECTIVE: One consequence of the DSM-IV diagnostic system for substance abuse and dependence is that there are individuals who might endorse one or two of the criterion items for dependence but not meet criteria for abuse. These persons have been referred to as "diagnostic orphans." The aim of the analyses presented here is to further understanding about this potentially important group. METHOD: The DSM-IV categorical approach was used to determine alcohol-related diagnoses for 439 young adult men. Structured face-to-face follow-up interviews were administered 5 years later. RESULTS: At the beginning of the evaluation period, 14.6% (n = 64) of the men were alcohol dependent, 18.2% (n = 80) fulfilled criteria for alcohol abuse, 16.4% (n = 72) did not meet criteria for an alcohol use disorder but endorsed one or two of the dependence criteria and 50.8% (n = 223) reported none of the dependence items. At the initial interview, and again 5 years later, the diagnostic orphans reported alcohol and drug use histories that fell between the histories of those with dependence and those with no alcohol-related difficulties. The orphans were most similar to the men with abuse, although they had lower quantities and frequencies of alcohol use, endorsed fewer additional alcohol-related problems and reported less involvement with drugs compared with that group. CONCLUSIONS: Although the diagnostic orphans were more similar to the subjects with alcohol abuse than they were to those with dependence or no diagnosis, the data do not necessarily support combining the orphans with those with abuse. These diagnostic orphans do, however, constitute an important group that carries an enhanced risk for alcohol use disorders and should be closely followed.

Prevalence of spasticity post stroke.

OBJECTIVES: To establish the prevalence of spasticity 12 months after stroke and examine its relationship with functional ability. DESIGN: A cohort study of prevalence of spasticity at 12 months post stroke. SETTING: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, UK. SUBJECTS: One hundred and six consecutively presenting stroke patients surviving to 12 months. MAIN OUTCOME MEASURES: Muscle tone measured at the elbow using the Modified Ashworth Scale and at several joints, in the arms and legs, using the Tone Assessment Scale; functional ability using the modified Barthel Index. RESULTS: Increased muscle tone (spasticity) was present in 29 (27%) and 38 (36%) of the 106 patients when measured using the Modified Ashworth Scale and Tone Assessment Scale respectively. Combining the results from both scales produced a prevalence of 40 (38%). Those with spasticity had significantly lower Barthel scores at 12 months (p < 0.0001). CONCLUSION: When estimating the prevalence of spasticity it is essential to assess both arms and legs, using both scales. Despite measuring tone at several joints, spasticity was demonstrated in only 40 (38%) patients, lower than previous estimates.

A comparison of alcohol-induced and independent depression in alcoholics with histories of suicide attempts.

OBJECTIVE: Alcohol-dependent men and women are at high risk for two types of major depressive episodes and for suicide attempts. The aim of this study is to compare the characteristics of two groups: (1) alcohol-dependent subjects with histories of suicide attempts and independent mood disorders and (2) a similar population of alcoholics with histories of self harm but who have only experienced alcohol-induced depressions. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism (COGA), semistructured detailed interviews were administered to 371 alcohol-dependent individuals (62% women) with histories of suicide attempts and major mood disorders. Of the total, 145 (39.1%) had ever had an independent depressive episode and 226 (60.9%) had experienced only alcohol-induced depressions. Information was obtained about socioeconomic characteristics, suicidal behavior, independent and induced psychiatric conditions, and aspects of alcohol dependence. RESULTS: Univariate and multivariate comparisons revealed that alcohol-dependent individuals with a history of suicide attempts and independent depression had a higher number of suicide attempts, were less likely to have been drinking during their most severe attempt, and were more likely to have an independent panic disorder. Univariate analyses indicated that these subjects reported a less severe history of alcohol dependence. CONCLUSIONS: The results indicate that a distinction between independent and alcohol-induced mood disorders in alcoholics with a history of suicide attempts may be useful.

Mood and anxiety symptoms among 140 children from alcoholic and control families.

OBJECTIVE: Children of alcoholics have been reported to have elevated levels of internalizing symptoms, including anxiety and depression. However, many studies have not adequately controlled for the influence of independent (i.e. not substance-induced) parental mood or anxiety disorders and other factors. The present evaluations assess the relationships of the family histories of alcohol use disorders and independent mood and anxiety disorders to internalizing symptoms in children of alcoholic and nonalcoholic subjects. METHOD: A behavioral checklist and a structured interview were administered to the parents of 140 children aged 7-18 years. The fathers of these offspring had been recruited 15 years previously from a university population to participate in a prospective study of 453 men from alcoholic and nonalcoholic families. RESULTS: While a higher score for one of four measures of internalizing symptoms in the children was found to relate to a higher density of alcoholic relatives, this pattern was more robust in children of parents with mood or anxiety disorders. In a hierarchical regression, the family history of alcohol use disorders did not add significantly to the prediction of any of the four internalizing scores in the children after considering the impact of a family history of independent mood and anxiety disorders. CONCLUSIONS: The results indicate that internalizing symptoms in children of alcoholics were more strongly influenced by a positive family history of mood and anxiety disorders than the family history of alcohol use disorders.