Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

BACKGROUND: Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. METHODS: A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. RESULTS: In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. CONCLUSIONS: As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

Psychological treatments for early psychosis can be beneficial or harmful, depending on the therapeutic alliance: an instrumental variable analysis.

BACKGROUND: The quality of the therapeutic alliance (TA) has been invoked to explain the equal effectiveness of different psychotherapies, but prior research is correlational, and does not address the possibility that individuals who form good alliances may have good outcomes without therapy. METHOD: We evaluated the causal effect of TA using instrumental variable (structural equation) modelling on data from a three-arm, randomized controlled trial of 308 people in an acute first or second episode of a non-affective psychosis. The trial compared cognitive behavioural therapy (CBT) over 6 weeks plus routine care (RC) v. supportive counselling (SC) plus RC v. RC alone. We examined the effect of TA, as measured by the client-rated CALPAS, on the primary trial 18-month outcome of symptom severity (PANSS), which was assessed blind to treatment allocation. RESULTS: Both adjunctive CBT and SC improved 18-month outcomes, compared to RC. We showed that, for both psychological treatments, improving TA improves symptomatic outcome. With a good TA, attending more sessions causes a significantly better outcome on PANSS total score [effect size -2.91, 95% confidence interval (CI) -0.90 to -4.91]. With a poor TA, attending more sessions is detrimental (effect size +7.74, 95% CI +1.03 to +14.45). CONCLUSIONS: This is the first ever demonstration that TA has a causal effect on symptomatic outcome of a psychological treatment, and that poor TA is actively detrimental. These effects may extend to other therapeutic modalities and disorders.

Negative cognition, affect, metacognition and dimensions of paranoia in people at ultra-high risk of psychosis: a multi-level modelling analysis.

BACKGROUND: Paranoia is one of the commonest symptoms of psychosis but has rarely been studied in a population at risk of developing psychosis. Based on existing theoretical models, including the proposed distinction between 'poor me' and 'bad me' paranoia, we aimed to test specific predictions about associations between negative cognition, metacognitive beliefs and negative emotions and paranoid ideation and the belief that persecution is deserved (deservedness). METHOD: We used data from 117 participants from the Early Detection and Intervention Evaluation for people at risk of psychosis (EDIE-2) trial of cognitive­behaviour therapy, comparing them with samples of psychiatric in-patients and healthy students from a previous study. Multi-level modelling was utilized to examine predictors of both paranoia and deservedness, with post-hoc planned comparisons conducted to test whether person-level predictor variables were associated differentially with paranoia or with deservedness. RESULTS: Our sample of at-risk mental state participants was not as paranoid, but reported higher levels of 'bad-me' deservedness, compared with psychiatric in-patients. We found several predictors of paranoia and deservedness. Negative beliefs about self were related to deservedness but not paranoia, whereas negative beliefs about others were positively related to paranoia but negatively with deservedness. Both depression and negative metacognitive beliefs about paranoid thinking were specifically related to paranoia but not deservedness. CONCLUSIONS: This study provides evidence for the role of negative cognition, metacognition and negative affect in the development of paranoid beliefs, which has implications for psychological interventions and our understanding of psychosis.

Cognitive-self consciousness and metacognitive beliefs: Stress sensitization in individuals at ultra-high risk of developing psychosis.

OBJECTIVE: Metacognitive beliefs (MCB) may guide information and attention processes, increasing affective and symptomatic reactions to stressful events. Cognitive self-consciousness (CSC; i.e., a preoccupation with one's thoughts) may increase awareness of MCB, potentially triggering the onset of psychotic symptoms. This study tested the hypotheses that (1), MCB would moderate affective and symptomatic reactions to stress in individuals at ultra-high risk (UHR) of developing psychosis, and (2), greater CSC would precede worsening in psychotic symptoms in individuals with strong MCB. METHOD: Twenty-seven individuals at UHR of developing psychosis completed a self-report diary when prompted by an electronic wristwatch several times each day for 6 days (experience sampling). RESULTS: MCB moderated the association between affective, but not symptomatic, responses to social stress. CSC preceded the subsequent occurrence of hallucinations in individuals who reported strong beliefs about the need to control their thoughts. CONCLUSIONS: The data suggest that MCB sensitize an individual to social stressors. CSC may represent times where an individual is aware that their thoughts are uncontrollable, and therefore contradicting their MCB, motivating them to make an external attribution. The findings have implications for improving the effectiveness of interventions for people experiencing hallucinations.

Emotional and symptomatic reactivity to stress in individuals at ultra-high risk of developing psychosis.

BACKGROUND: The stress-vulnerability model of psychosis continues to be influential. The aim of this study was to compare emotional and symptomatic responses to stress in individuals at ultra-high risk (UHR) of developing psychosis, in age- and gender-matched healthy controls, and in patients with non-affective psychosis. METHOD: A total of 27 UHR, 27 psychotic and 27 healthy individuals completed the experience sampling method, an ambulant diary technique, where they were required to fill in self-assessment questions about their emotions, symptoms and perceived stress at semi-random times of the day for 6 days. Quesionnaire and interview assessments were also completed. RESULTS: Multilevel regression analyses showed that individuals at UHR of developing psychosis reported greater negative emotions in response to stress than the healthy individuals. Against the initial hypotheses, the UHR individuals also experienced greater emotional reactivity to stress when compared with the patient group. No significant differences were observed between the patients and the non-clinical sample. Stress measures significantly predicted the intensity of psychotic symptoms in UHR individuals and patients, but the extent of this did not significantly differ between the groups. CONCLUSIONS: Individuals at UHR of developing psychosis may be particularly sensitive to everyday stressors. This effect may diminish after transition to psychosis is made and in periods of stability. Subtle increases in psychotic phenomena occur in response to stressful events across the continuum of psychosis.

Affective variability predicts suicidal ideation in individuals at ultra-high risk of developing psychosis: an experience sampling study.

OBJECTIVE: There is a suggestion in the literature that more variable affect increases suicidal ideation through the repeated re-activation of latent suicidal cognitions. The hypothesis that affective variability would be a better predictor of suicidal ideation and related behaviour than affect level was tested in individuals at ultra-high risk of developing psychosis. This study also examined the prediction that affective variability is a suicide-specific mechanism and would not predict levels of attenuated psychotic phenomena. METHOD: Twenty-seven ultra-high risk individuals were required to complete ambulant ratings of their affect when prompted by an electronic wristwatch for six days (the experience sampling method). In the debriefing session, participants were assessed with a semi-structured interview (the Comprehensive Assessment of At-Risk Mental State), which assessed the severity and frequency of suicidality and psychosis-related phenomena. RESULTS: The variability of negative and positive affect was predictive of the frequency of suicidal thoughts and behaviour. More variable negative, but not positive affect, was also associated with more severe suicidal ideation and related behaviour. Affect variability was not significantly related to the severity of attenuated psychotic phenomena. CONCLUSION: Affective variability appears to be a specific risk factor for suicidal ideation in individuals at ultra-high risk of developing psychosis. Early intervention should focus on providing individuals with skills for regulating their own affect.

Experience sampling research in individuals with mental illness: reflections and guidance.

OBJECTIVE: The experience sampling method (ESM) represents a valuable way of assessing clinical phenomena in real world settings and across time. Despite its theoretical advantages, using this methodology in psychiatric populations is challenging. This paper acts as a guide to researchers wishing to employ this approach when investigating mental illness. METHOD: The contents represent the opinions of researchers around the United Kingdom and the Netherlands who are experienced at using the ESM. RESULTS: In ESM studies, participants are required to fill in questions about their current thoughts, feelings and experiences when prompted by an electronic device (e.g. a wristwatch, PDA). Entries are typically made at fixed or random intervals over 6 days. This article outlines how to design and validate an ESM diary. We then discuss which sampling procedure to use and how to increase compliance through effective briefing and telephone sessions. Debriefing, data management and analytical issues are considered, before suggestions for future clinical uses of the ESM are made. CONCLUSION: The last decade has seen an increase in the number of studies employing the ESM in clinical research. Further research is needed to examine the optimal equipment and procedure for different clinical groups.

The role of metacognitive beliefs in stress sensitisation, self-esteem variability, and the generation of paranoia.

INTRODUCTION. Stress sensitisation may play a key role in the formation of psychosis. The authors examined whether metacognitive beliefs and self-esteem moderate affective response to stress, and whether subtle fluctuations in self-esteem act as a mediator between stress and attenuated psychotic phenomena. METHOD. 70 healthy volunteers completed two conditions of the same experimental tasks, which were designed to be either neutral or stress inducing. Ambulant assessments of negative affect, self-esteem, and suspicious thoughts were taken before and after each task, and standardised questionnaires were completed at the beginning or end of each session. RESULTS. Metacognitive belief subscales, but not self-esteem, moderated the association between stress and resultant negative affect, and negative affect and suspicious thinking. Individuals who placed greater emphasis on controlling their thoughts had greater variability in their self-esteem during the stress condition, which in turn predicted the severity of their attenuated psychotic phenomena. DISCUSSION. Metacognitive beliefs may sensitise an individual to minor stressors, by increasing affective reactivity and causing subtle shifts in appraisals of self-worth. Psychosocial intervention may wish to target these beliefs in order to desensitise an individual to negative events.

Effects of cognitive therapy on the longitudinal development of psychotic experiences in people at high risk of developing psychosis.

BACKGROUND: There have been recent advances in the identification of people at high risk of psychosis and psychological treatments have shown promise for prevention. AIMS: To compare the longitudinal course of psychotic experiences and emotional dysfunction in high-risk participants receiving cognitive therapy with those receiving treatment as usual. METHOD: Data from a recent randomised controlled trial of cognitive therapy for people at risk of developing psychosis were utilised to examine three different statistical models that were based on 432 measurements of psychotic experiences and 421 of emotional dysfunction (anxiety-depression) contributed by 57 participants across the 13 measurement occasions (monthly monitoring for a year). RESULTS: Psychotic experiences and emotional dysfunction were correlated and decreased significantly over the course of the study, with most improvement in the early months. The reduction in positive symptoms, but not emotional dysfunction, was enhanced by allocation to cognitive therapy. CONCLUSIONS: Psychotic experiences and emotional dysfunction appear to interact in people at risk of developing psychosis. There appears to be a specific benefit of cognitive therapy.

Fundamental studies of the adhesion of explosives to textile and non-textile surfaces.

This paper describes the use of atomic force microscopy (AFM) to investigate the interactions between explosives crystals and different surfaces. Crystals of TNT, PETN and RDX were mounted onto tipless AFM cantilevers and repeatedly brought into contact with a range of surfaces (n=15), including textile and non-textile surfaces. The adhesion force during each contact was measured, and the results are presented in this work. The results suggest that explosives crystals display a higher adhesion to smoother, non-textile surfaces, particularly glass. This finding may be of use for forensic explosives investigators when deciding the best types of debris to target for explosives recovery.

The stability of TNT, RDX and PETN in simulated post-explosion soils: Implications of sample preparation for analysis.

Explosives residues in soils may be a useful source of evidence following the detonation of an improvised explosive device (IED), such as a vehicle-borne IED. Soil samples collected from the vicinity of an explosion scene will often be stored for some time prior to analysis, yet explosives residues in soil samples are susceptible to rapid degradation or transformation. Although some research has assessed the use of different storage temperatures with a view to reducing explosives' degradation over time, further research examining the degradation of explosives in soil when stored under a variety of storage conditions is crucial to determine the optimal sample collection and storage procedures for soil containing explosives residues. In this work, three different soils were spiked with solutions of TNT, RDX and PETN and stored either at room temperature, refrigerated or frozen. Samples were extracted over 6 weeks, with additional samples gamma-irradiated or nitrogen purged prior to storage. Experimental results indicate that TNT underwent very rapid degradation at room temperature, attributed to microbial action, whereas PETN and RDX proved to be more stable. Gamma irradiation and nitrogen purging proved of some benefit for mitigating TNT degradation, with lower storage temperatures ultimately proving the most effective method of mitigating degradation.

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment.

OBJECTIVES: To determine the clinical and cost-effectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to, or having unacceptable side-effects from, their current medication. DESIGN: Two pragmatic, randomised controlled trials (RCTs) were undertaken. The first RCT (band 1) compared the class of older, inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders, whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects. The second RCT (band 2) compared the new (non-clozapine) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs. Both RCTs were four-centre trials with concealed randomisation and three follow-up assessments over 1 year, blind to treatment. SETTING: Adult mental health settings in England. PARTICIPANTS: In total, 227 participants aged 18-65 years (40% of the planned sample) were randomised to band 1 and 136 (98% of the planned sample) to band 2. INTERVENTIONS: Participants were randomised to a class of drug. The managing clinician selected the individual drug within that class, except for the clozapine arm in band 2. The new atypical drugs included risperidone, olanzapine, quetiapine and amisulpride. The conventional drugs included older drugs, including depot preparations. As in routine practice, clinicians and participants were aware of the identity of the prescribed drug, but clinicians were asked to keep their participating patient on the randomised medication for at least the first 12 weeks. If the medication needed to be changed, the clinician was asked to prescribe another drug within the same class, if possible. MAIN OUTCOME MEASURES: The primary outcome was the Quality of Life Scale (QLS). Secondary clinical outcomes included symptoms [Positive and Negative Syndrome Scale (PANSS)], side-effects and participant satisfaction. Economic outcomes were costs of health and social care and a utility measure. RESULTS: Recruitment to band 1 was less than anticipated (40%) and diminished over the trial. This appeared largely due to loss of perceived clinical equipoise (clinicians progressively becoming more convinced of the superiority of new atypicals). Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75% power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks. The recruitment to band 2 was approximately as planned. Follow-up assessments were completed at week 52 in 81% of band 1 and 87% of band 2 participants. Band 1 data showed that, on the QLS and symptom measures, those participants in the conventional arm tended towards greater improvements. This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample. Participants reported no clear preference for either class of drug. There were no statistically significant differential outcomes for participants entering band 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance. Net costs over the year varied widely, with a mean of 18,850 pounds sterling in the conventional drug group and 20,123 pounds sterling in the new atypical group, not a statistically significant difference. Of these costs, 2.1% and 3.8% were due to antipsychotic drug costs in the conventional and atypical group, respectively. There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year. The results for band 2 showed an advantage for commencing clozapine in quality of life (QLS) at trend level (p = 0.08) and in symptoms (PANSS), which was statistically significant (p = 0.01), at 1 year. Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects. Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals (p < 0.05). Net costs of care varied widely, but were higher than in band 1, with a mean of 33,800 pounds sterling in the clozapine group and 28,400 pounds sterling in the new atypical group. Of these costs, 4.0% and 3.3%, respectively, were due to antipsychotic drug costs. The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug. There was a trend towards higher mean participant utility scores in the clozapine group. CONCLUSIONS: For band 1, there is no disadvantage in terms of quality of life and symptoms, or associated costs of care, over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs. Conventional drugs were associated with non-significantly better outcomes and lower costs. Drug costs represented a small proportion of the overall costs of care (<5%). For band 2, there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs, but with increased associated costs of care. The results suggest that conventional antipsychotic drugs, which are substantially cheaper, still have a place in the treatment of patients unresponsive to, or intolerant of, current medication. Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance, valid measures of utility in serious mental illness, low-dose 'conventional' treatment in first episode schizophrenia, QLS validity and determinants of QLS score in schizophrenia, and into the possible financial and other mechanisms of rewarding clinician participation in trials.

Investigation into the temporal stability of aqueous standard solutions of psilocin and psilocybin using high performance liquid chromatography.

This paper reports an investigation into the temporal stability of aqueous solutions of psilocin and psilocybin reference drug standards over a period of fourteen days. This study was performed using high performance liquid chromatography utilising a (95:5% v/v) methanol: 10 mM ammonium formate, pH 3.5 mobile phase and absorption detection at 269 nm. It was found that the exclusion of light significantly prolonged the useful life of standards, with aqueous solutions of both psilocin and psilocybin being stable over a period of seven days.

Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.

BACKGROUND: Previous twin studies have supported a genetic contribution to the major categories of psychotic disorders, but few of these have employed operational diagnostic criteria, and no such study has been based on a sample that included the full range of functional psychotic disorders. METHODS: A total of 224 twin probands (106 monozygotic, 118 dizygotic) with a same-sex co-twin and a lifetime history of psychosis was ascertained from the service-based Maudsley Twin Register in London, England. Research Diagnostic Criteria psychotic diagnoses were made on a lifetime-ever basis. Main-lifetime diagnoses of DSM-III-R and International Statistical Classification of Diseases, 10th Revision schizophrenia were also made. Probandwise concordance rates and correlations in liability were calculated, and biometrical model fitting applied. RESULTS: A substantial genetic contribution to variance in liability was confirmed for the major diagnostic categories except Research Diagnostic Criteria depressive psychosis and unspecified functional psychosis, where familial transmission was confirmed, but the relative contribution of genetic and common environmental factors was unclear. Heritability estimates for Research Diagnostic Criteria schizophrenia, schizoaffective disorder, mania, DSM-III-R schizophrenia, and International Statistical Classification of Diseases, 10th Revision schizophrenia were all between 82% and 85%. None of the estimates differed significantly from any other. CONCLUSIONS: Heritability estimates for schizophrenia, schizoaffective disorder, and mania were substantial and similar. Population morbid risk estimates were inferred rather than directly measured, but the results were very similar to those from studies where morbid risks were directly estimated.

Investigations into the initial composition of latent fingermark lipids by gas chromatography-mass spectrometry.

A more comprehensive understanding of the variability of latent fingermark composition is essential to improving current fingermark detection capabilities in an informed manner. Gas chromatography-mass spectrometry was used to examine the composition of the lipid fraction of latent fingermarks collected from a population of over 100 donors. Variations in the appearances of chromatograms from different donors were apparent in the relative peak sizes of compounds including free fatty acids, squalene, cholesterol and wax esters. Principal component analysis was used as an exploratory tool to explore patterns in this variation, but no correlation to donor traits could be discerned. This study also highlights the practical and inherent difficulties in collecting reproducible samples.

Hand preference in psychotic twins.

In an attempt to replicate the influential study of Boklage (1977), hand preference for writing was examined in a new series of 30 monozygotic (MZ) and 30 dizygotic (DZ) twin pairs in whom the proband had suffered a functional psychosis. In contrast to the original report, no increased rate of left-handedness was found in MZ compared to DZ twins, or psychotic compared with nonpsychotic twins. In particular, no relationship between within-pair left-handedness and discordance for psychosis emerged. Possible reasons for the disagreement between the two studies are examined.

Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders.

OBJECTIVE: Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome. Methodologically sound studies investigating treatment approaches for patients with these disorders are rare, although recommendations for integrated and comprehensive treatment programs abound. This study investigates the relative benefit of adding an integrated psychological and psychosocial treatment program to routine psychiatric care for patients with schizophrenia and substance use disorders. METHOD: The authors conducted a randomized, single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family or caregiver intervention. RESULTS: The integrated treatment program resulted in significantly greater improvement in patients' general functioning than routine care alone at the end of treatment and 12 months after the beginning of the study. Other benefits of the program included a reduction in positive symptoms and in symptom exacerbations and an increase in the percent of days of abstinence from drugs or alcohol over the 12-month period from baseline to follow-up. CONCLUSIONS: These findings demonstrate the effectiveness of a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family intervention over routine psychiatric care alone for patients with comorbid schizophrenia and alcohol or drug abuse or dependence.

Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley Family Study.

OBJECTIVE: Family studies have shown that abnormalities of smooth pursuit eye movement are increased in the adult relatives of schizophrenic probands as well as in the probands themselves. More recently, an inability of schizophrenic subjects to inhibit reflexive saccades reliably has been shown. This study aimed to test the hypothesis that the latter dysfunction is part of the extended schizophrenia phenotype. METHOD: With the use of infrared oculography, measurements of reflexive saccades and antisaccades were undertaken in 29 probands with schizophrenia, 50 of their nonpsychotic first-degree relatives, and 38 unrelated healthy volunteers. RESULTS: Probands, relatives, and healthy subjects showed no overall differences in the generation of reflexive saccades. However, in the antisaccade task, probands showed more saccadic distractibility when they were required to inhibit reflexive saccades. Analysis of corrective saccades showed that this was not due to failed comprehension or motivation. Relatives of the probands with high saccadic distractibility showed a higher distractibility rate than relatives of the probands with normal distractibility. Across all subjects, females showed a higher rate of distractibility errors than males. CONCLUSIONS: The ability to suppress reflexive saccades is an objective neurocognitive measure that is impaired in schizophrenic patients and in a proportion of their biological relatives. This antisaccade abnormality may be a vulnerability marker in a subset of schizophrenic patients and their families.

The prognosis of patients with chronic obstructive pulmonary disease after hospitalization for acute respiratory failure.

We followed the course of 36 consecutive patients hospitalized with chronic obstructive pulmonary disease and acute respiratory failure due to exacerbation of chronic bronchitis in order to clarify the prognosis in this common group of patients. All of the patients had spirometric evidence of severe, poorly reversible airflow limitation and all had a similar cause of acute respiratory failure. In addition, all received similar treatment during hospitalization and follow-up. Patients wtih asthma and pneumonia were excluded by clinical, spirometric, and roentgenographic criteria. Hospital survival was 94 percent, and only one patient required intubation. Two-year survival was 72 percent, and none of the patients died during a readmission for acute respiratory failure. This prognosis is much better than commonly recognized and compares favorably to that of stable outpatients with similar degrees of airflow limitation. An episode of acute respiratory failure, triggered by an exacerbation of chronic bronchitis, does not necessarily alter the prognosis of patients with COPD.

Prolonged respiratory paralysis in wound botulism.

Two patients had wound botulism with longer duration of respiratory paralysis than previously described. Each sustained extensive trauma to soft tissues and grossly contaminated wounds when thrown from a vehicle in a rural area. Progressive muscular weakness and respiratory distress occurred 8 and 13 days after injury, in the presence of infected wounds and clinical and laboratory findings characteristic of botulism. Spontaneous vital capacity and inspiratory effort served as bedside indicators of ventilatory function throughout 11 weeks of ventilatory support in each case and paralleled other clinical assessments of progress and recovery. Wound botulism may result in neuromuscular paralysis for a prolonged period. These cases illustrate the primary role of scrupulous nursing and respiratory care throughout such a period of ventilatory insufficiency.