The effect of Huntington's disease on cognitive and physical motivation.

Apathy is one of the most common neuropsychiatric features of Huntington's disease. A hallmark of apathy is diminished goal-directed behaviour, which is characterized by a lower motivation to engage in cognitively or physically effortful actions. However, it remains unclear whether this reduction in goal-directed behaviour is driven primarily by a motivational deficit and/or is secondary to the progressive cognitive and physical deficits that accompany more advanced disease. We addressed this question by testing 17 individuals with manifest Huntington's disease and 22 age-matched controls on an effort-based decision-making paradigm. Participants were first trained on separate cognitively and physically effortful tasks and provided explicit feedback about their performance. Next, they chose on separate trials how much effort they were willing to exert in each domain in return for varying reward. At the conclusion of the experiment, participants were asked to rate their subjective perception of task load. In the cognitive task, the Huntington's disease group were more averse to cognitive effort than controls. Although the Huntington's disease group were more impaired than controls on the task itself, their greater aversion to cognitive effort persisted even after controlling for task performance. This suggests that the lower levels of cognitive motivation in the Huntington's disease group relative to controls was most likely driven by a primary motivational deficit. In contrast, both groups expressed a similar preference for physical effort. Importantly, the similar levels of physical motivation across both groups occurred even though participants with Huntington's disease performed objectively worse than controls on the physical effort task, and were aware of their performance through explicit feedback on each trial. This indicates that the seemingly preserved level of physical motivation in Huntington's disease was driven by a willingness to engage in physically effortful actions despite a reduced capacity to do so. Finally, the Huntington's disease group provided higher ratings of subjective task demand than controls for the cognitive (but not physical) effort task and when assessing the mental (but not the physical) load of each task. Together, these results revealed a dissociation in cognitive and physical motivation deficits between Huntington's disease and controls, which were accompanied by differences in how effort was subjectively perceived by the two groups. This highlights that motivation is the final manifestation of a complex set of mechanisms involved in effort processing, which are separable across different domains of behaviour. These findings have important clinical implications for the day-to-day management of apathy in Huntington's disease.

Prevalence of neurocognitive disorders 5 years after elective orthopaedic surgery.

BACKGROUND: Peri-operative neurocognitive disorders are one of the most common complications affecting older adults after anaesthesia and surgery. It is not clear how exposure to surgery and anaesthesia contributes to the prevalence of long-term neurocognitive disorders. This study aimed to report the prevalence of neurocognitive disorders, and explore pre-operative factors associated with neurocognitive disorders 5 years after elective orthopaedic surgery. METHODS: A prospective, 5-year longitudinal, cohort study was performed recruiting patients (aged ≥ 60 y) undergoing elective orthopaedic surgery and a contemporaneous non-surgical control group. Neurocognitive disorder was evaluated and classified at baseline and 5-year review incorporating: self- and informant-reported cognition; functional participation; and performance on neuropsychological tests. RESULTS: Recruitment at 5-year follow-up included 195 patients and 21 control participants. In the patient cohort the prevalence of neurocognitive disorder was 38.1% (n = 75), with 61 (30.1%) meeting the criteria for mild neurocognitive disorder and 14 (7.1%) for major neurocognitive disorder. At 5-year follow-up, 121 (61.4%) patients were classified with a neurocognitive disorder, with 88 (44.7%) characterised with mild neurocognitive disorder and 33 (16.8%) with major neurocognitive disorder. Age (odds ratio (95%CI) 1.07 (1.02-1.13); p = 0.01) and baseline cognitive impairment (odds ratio (95%CI) 2.1 (1.06-4.15); p = 0.03) were significant predictors of neurocognitive disorder 5 years after surgery. CONCLUSION: More than half of older adult patients had some form of neurocognitive disorder 5 years after elective orthopaedic surgery. Surgery and anaesthesia may be associated with the trajectory of cognitive decline in at-risk older adults, including those with pre-operative cognitive impairment. Cognitive screening should be factored into pre-operative assessments of older adults to inform subsequent care.

Geolocator-tracking seabird migration and moult reveal large-scale, temperature-driven isoscapes in the NE Atlantic.

RATIONALE: By combining precision satellite-tracking with blood sampling, seabirds can be used to validate marine carbon and nitrogen isoscapes, but it is unclear whether a comparable approach using low-precision light-level geolocators (GLS) and feather sampling can be similarly effective. METHODS: Here we used GLS to identify wintering areas of northern gannets (Morus bassanus) and sampled winter grown feathers (confirmed from image analysis of non-breeding birds) to test for spatial gradients in δ13 C and δ15 N in the NE Atlantic. RESULTS: By matching winter-grown feathers with the non-breeding location of tracked birds we found latitudinal gradients in δ13 C and δ15 N in neritic waters. Moreover, isotopic patterns were best explained by sea surface temperature. Similar isotope gradients were found in fish muscle sampled at local ports. CONCLUSIONS: Our study reveals the potential of using seabird GLS and feathers to reconstruct large-scale isotopic patterns.

Examining Subjective Psychological Experiences of Postoperative Delirium in Older Cardiac Surgery Patients.

BACKGROUND: Postoperative delirium (POD) is an acute syndrome including inattention and impaired cognition that affects approximately 42% of older cardiac surgical patients. POD is linked to adverse outcomes including morbidity, mortality, and further cognitive decline. Less is known about the subjective psychological experience of POD and its ongoing impact on well-being. METHODS: We performed a qualitative analysis of the long-term psychological sequelae of older adults who experience POD after cardiac surgery. We sampled 30 patients aged 60 years and older who experienced at least 2 episodes of POD during a prior hospital admission. We administered semistructured interviews with participants via telephone 3 to 5 years postoperatively. Interviews were transcribed and thematically analyzed. Data were interpreted in accordance with the naturalist paradigm. RESULTS: Three overarching themes emerged in our qualitative analysis. The first reflected the multifaceted presentation of POD, including distortion of time and reality; feelings of isolation; and a loss of self, identity, and control. The second theme reflected the psychological challenges associated with functional decline after surgery. Common examples of functional decline included cognitive difficulties, excessive fatigue, and a perceived loss of independence. The final theme captured the emotional sequelae of acute illness, which included low mood, reduced motivation, and social comparisons. CONCLUSIONS: Our findings emphasize the multidimensional experience of POD and long-term effects on psychological wellbeing. Our research highlights the beneficial role multidisciplinary clinicians play in managing POD including strategies that may be embedded into clinical practice and helps anesthesiologists understand why patients who have experienced POD in the past may present with specific concerns should they require subsequent surgery.

Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis.

BACKGROUND: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition. METHODS: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-α), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane. RESULTS: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use. CONCLUSIONS: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect.

Digital clock drawing test metrics in older patients before and after endoscopy with sedation: An exploratory analysis.

BACKGROUND: In the postoperative period, clinically feasible instruments to monitor elderly patients' neurocognitive recovery and discharge-readiness, especially after short-stay procedures, are limited. Cognitive monitoring may be improved by a novel digital clock drawing test (dCDT). We screened for cognitive impairment with the 4 A Test (4AT) and then administered the dCDT pre and post short-stay procedure (endoscopy). The primary aim was to investigate whether the dCDT was sensitive to a change in cognitive status postendoscopy. We also investigated if preoperative cognitive status impacted postendoscopy dCDT variables. METHODS: We recruited 100 patients ≥65 years presenting for endoscopy day procedures at a single metropolitan hospital. Participants were assessed after admission and immediately before discharge from the hospital. We administered the 4AT, followed by both command and copy clock conditions of the dCDT. We analysed the total drawing time (dCDT time), as well as scored the drawn clock against the established Montreal Cognitive Assessment (MoCA) criteria both before and after endoscopy. RESULTS: Linear regression showed higher 4AT test scores (poorer performance) were associated with longer postoperative dCDT time (ß = 5.6, p = 0.012) for the command condition after adjusting for preoperative baseline dCDT metrics, sex, age, and years of education. CONCLUSION: Postoperative dCDT time-based variables slowed in those with baseline cognitive impairment detected by the 4AT, but not for those without cognitive impairment. Our results suggest the dCDT, using the command mode, may help detect cognitive impairment in patients aged >65 years after elective endoscopy.

A novel digital clock drawing test as a screening tool for perioperative neurocognitive disorders: A feasibility study.

BACKGROUND: We developed a digital clock drawing test (dCDT), an adaptation of the original pen and paper clock test, that may be advantageous over previous dCDTs in the perioperative environment. We trialed our dCDT on a tablet device in the preoperative period to determine the feasibility of administration in this setting. To assess the clinical utility of this test, we examined the relationship between the performance on the test and compared derived digital clock measures with the 4 A's Test (4AT), a delirium and cognition screening tool. METHODS: We recruited a sample of 102 adults aged 65 years and over presenting for elective surgery in a single tertiary hospital. Participants completed the 4AT, followed by both command and copy clock conditions of the dCDT. We recorded time-based clock-drawing metrics, alongside clock replications scored using the Montreal Cognitive Assessment (MoCA) clock scoring criteria. RESULTS: The dCDT had an acceptance rate of 99%. After controlling for demographic variables and prior tablet use, regression analyses showed higher 4AT scores were associated with greater dCDT time (seconds) for both command (ß = 8.2, P = .020) and copy clocks (ß = 12, P = .005) and lower MoCA-based clock scores in both command (OR = 0.19, P = .001) and copy conditions (OR = 0.14, P = .012). CONCLUSION: The digital clock drawing test is feasible to administer and is highly acceptable to older adults in a preoperative setting. We demonstrated a significant association between both the dCDT time and clock score metrics, with the established 4AT. Our results provide convergent validity of the dCDT in the preoperative setting.

Integration of light and circadian signals that regulate chloroplast transcription by a nuclear-encoded sigma factor.

We investigated the signalling pathways that regulate chloroplast transcription in response to environmental signals. One mechanism controlling plastid transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light and the circadian clock. However, the extent to which a chloroplast target of SIG5 is regulated by light-induced changes in SIG5 expression is unknown. Moreover, the photoreceptor signalling pathways underlying the circadian regulation of chloroplast transcription by SIG5 are unidentified. We monitored the regulation of chloroplast transcription in photoreceptor and sigma factor mutants under controlled light regimes in Arabidopsis thaliana. We established that a chloroplast transcriptional response to light intensity was mediated by SIG5; a chloroplast transcriptional response to the relative proportions of red and far red light was regulated by SIG5 through phytochrome and photosynthetic signals; and the circadian regulation of chloroplast transcription by SIG5 was predominantly dependent on blue light and cryptochrome. Our experiments reveal the extensive integration of signals concerning the light environment by a single sigma factor to regulate chloroplast transcription. This may originate from an evolutionarily ancient mechanism that protects photosynthetic bacteria from high light stress, which subsequently became integrated with higher plant phototransduction networks.

Physical Therapy Student Attitudes and Beliefs Related to Evidence-Based Practice Following an Integrated Learning Activity.

Evidence-based practice (EBP) is an integral competency for physical therapists; however, a knowledge-to-practice gap exists and best educational practices to facilitate EBP-related behaviors are unclear. This study describes the effects of a multi-semester learning activity on student-reported EBP behaviors. Students (n = 34) in their second and third years of a Doctor of Physical Therapy program participated in a 4-semester learning activity including journal club participation and student research, with integrated learning objectives. The Evidence-Based Practice Profile (EBP2) was administered at the beginning and the end of the learning activity to collect outcomes related to five EBP domains. Significant improvements were observed in four EBP domains, with medium to large effect sizes (relevance 0.63; sympathy 0.18; terminology 1.05; practice 0.94; confidence 0.90). The multi-semester activity described here is generalizable and relevant to a variety of allied health disciplines and shows promise to improve student EBP skills and knowledge.

Cerebrospinal fluid sampling for research of Alzheimer's disease and other neurodegenerative diseases when lumbar punctures are performed by anaesthetists.

Objectives: An increasing number of people are undergoing lumbar puncture (LP) for the purposes of research. Performing LP for research purposes introduces considerations that differ from LP performed for clinical, diagnostic or therapeutic reasons. The demand for research LP will greatly increase as biomarkers are used to both diagnose and monitor disease progression in clinical trials. Minimising adverse events is paramount because research participants receive no clinical benefit and often need repeat procedures. We describe the experience of performing LP for research by anaesthetists. Methods: We reviewed the clinical protocol and incidence of adverse events in 326 research LP in an anaesthesia department. Results: There was a lower incidence of adverse events compared with previous reports when LP was undertaken for clinical reasons. The incidence of severe post-LP headache was 1.3% when an atraumatic spinal needle with a 27 gauge tip and a 22 gauge shaft was used. Conclusions: We describe the practice to sample cerebrospinal fluid (CSF) by LP for research purposes. Specific practices include the sitting position of the participant, aspiration rather than passive CSF withdrawal, attention to the sterility of the procedure, monitoring of vital signs and importantly the use of 22/27 gauge microtip spinal needle. Trial registration numbers: ACTRN12612000493842, NCT04623242.

A qualitative examination of apathy and physical activity in Huntington's and Parkinson's disease.

Aim: In Huntington's disease (HD) and Parkinson's disease (PD), apathy is a frequently cited barrier to participation in physical activity. Current diagnostic criteria emphasize dissociable variants of apathy that differentially affect goal-directed behavior. How these dimensions present and affect physical activity in HD and PD is unknown. Methods: Using a qualitative approach, we examined the experience of apathy and its impact on physical activity in 20 people with early-manifest HD or idiopathic PD. Results: Two major themes emerged: the multidimensionality of apathy, including initiation or goal-identification difficulties, and the interplay of apathy and fatigue; and facilitators of physical activity, including routines, safe environments and education. Conclusion: Physical activity interventions tailored to apathy phenotypes may maximize participant engagement.

Effects of functional electrical stimulation on muscle health after spinal cord injury.

Spinal cord injury is a devastating condition interrupting voluntary movement and motor control. In response to unloading, skeletal muscle undergoes numerous adaptations, including rapid and profound atrophy, intramuscular fat accumulation, impaired muscular glucose metabolism and decreased force generation and muscle performance. Functional electrical stimulation (FES) involves electrically stimulating affected muscles to contract in a coordinated manner to create a functional movement or task. Effects of FES-cycling, rowing and resistance training on muscle health are described here. Briefly, FES-cycling and resistance training may slow muscle atrophy or facilitate muscle hypertrophy, and all modalities benefit muscle composition and performance to some extent. These interventions show promise as future rehabilitative tools after spinal cord injury.

Multidimensional Apathy: The Utility of the Dimensional Apathy Scale in Huntington's Disease.

BACKGROUND: Apathy is a disorder of motivation common to Huntington's disease (HD). Recent conceptual frameworks suggest that apathy is not unitary but consists of discrete subtypes ("dimensions"). Which of the proposed dimensions are preferentially affected in HD, and how these dimensions evolve with disease progression is unknown. OBJECTIVES: The Dimensional Apathy Scale (DAS) separates apathy into Executive, Initiation and Emotional subscales. Using the DAS, we aimed to: 1) Determine the apathy subtypes prevalent in HD; 2) Compare the DAS against a unitary measure of apathy (Apathy Evaluation Scale, AES); 3) Assess the reliability of self- and observer-ratings; and 4) Determine the relationship between the DAS, and disease burden, total functional capacity (TFC) and the AES. METHOD: Fifty pre-manifest, 51 manifest-HD, 87 controls, and 50 HD-observers completed the DAS, AES, and TFC. RESULTS: Manifest-HD participants had the highest levels of apathy across all dimensions (30.4% on Executive subscale, 34.8% on Initiation subscale, and 15.2% on Emotional subscale), relative to pre-manifest and control participants. Self- and observer-ratings on the DAS did not differ. Hierarchical regressions across the entire gene-expanded sample showed that scores on the Initiation subscale correlated with AES scores; higher Executive subscale scores were related to higher disease burden; and Emotional subscale scores with lower total functional capacity. CONCLUSIONS: In this first study of the DAS in HD, manifest-HD participants were more apathetic than pre-manifest and control participants across all apathy subtypes. The DAS may be a useful tool for measuring different aspects of apathy in people with HD.

Preventing Delirium and Promoting Long-Term Brain Health: A Clinical Trial Design for the Perioperative Cognitive Enhancement (PROTECT) Trial.

BACKGROUND: Perioperative neurocognitive disorders (PND), including postoperative delirium (POD), are common in older adults and, for many, precipitate functional decline and/or dementia. OBJECTIVE: In this protocol, we describe a novel multidisciplinary, multicomponent perioperative intervention that seeks to prevent or reduce POD and associated cognitive decline. METHODS: We will conduct a prospective, single-blind, pragmatic, randomized-controlled trial to compare our tailored multi-disciplinary perioperative pathway against current standard of care practices. We will recruit a total of 692 elective surgical patients aged 65 years or more and randomize them in a 1:1 design. Our perioperative intervention targets delirium risk reduction strategies by emphasizing the importance of early mobilization, nutrition, hydration, cognitive orientation, sensory aids, and avoiding polypharmacy. To promote healthy behavior change, we will provide a tailored psychoeducation program both pre- and postoperatively, focusing on cardiovascular and psychosocial risks for cognitive and functional decline. RESULTS: Our primary outcome is the incidence of any PND (encapsulating POD and mild or major postoperative neurocognitive disorder) at three months postoperative. Secondary outcomes include any incidence of POD or neurocognitive disorder at 12 months. A specialized delirium screening instrument, the Confusion Assessment Method (3D-CAM), and a neuropsychological test battery, will inform our primary and secondary outcomes. CONCLUSION: Delirium is a common and debilitating postoperative complication that contributes to the cognitive and functional decline of older adults. By adopting a multicomponent, multidisciplinary approach to perioperative delirium prevention, we seek to reduce the burden of delirium and subsequent dementia in older adults.

Heightened effort discounting is a common feature of both apathy and fatigue.

Apathy and fatigue have distinct aetiologies, yet can manifest in phenotypically similar ways. In particular, each can give rise to diminished goal-directed behaviour, which is often cited as a key characteristic of both traits. An important issue therefore is whether currently available approaches are capable of distinguishing between them. Here, we examined the relationship between commonly administered inventories of apathy and fatigue, and a measure of goal-directed activity that assesses the motivation to engage in effortful behaviour. 103 healthy adults completed self-report inventories on apathy (the Dimensional Apathy Scale), and fatigue (the Multidimensional Fatigue Inventory, and/or Modified Fatigue Impact Scale). In addition, all participants performed an effort discounting task, in which they made choices about their willingness to engage in physically effortful activity. Importantly, self-report ratings of apathy and fatigue were strongly correlated, suggesting that these inventories were insensitive to the fundamental differences between the two traits. Furthermore, greater effort discounting was strongly associated with higher ratings across all inventories, suggesting that a common feature of both traits is a lower motivation to engage in effortful behaviour. These results have significant implications for the assessment of both apathy and fatigue, particularly in clinical groups in which they commonly co-exist.

Dissociable Motivational Deficits in Pre-manifest Huntington's Disease.

Motivation is characterized by a willingness to overcome both cognitive and physical effort costs. Impairments in motivation are common in striatal disorders, such as Huntington's disease (HD), but whether these impairments are isolated to particular domains of behavior is controversial. We ask whether HD differentially affects the willingness of individuals to overcome cognitive versus physical effort. We tested 20 individuals with pre-manifest HD and compared their behavior to 20 controls. Across separate trials, participants made choices about how much cognitive or physical effort they were willing to invest for reward. Our key results were that individuals with pre-manifest HD were less willing than controls to invest cognitive effort but were no different in their overall preference for physical effort. These results cannot be explained by group differences in neuropsychological or psychiatric profiles. This dissociation of cognitive- and physical-effort-based decisions provides important evidence for separable, domain-specific mechanisms of motivation.

Altering Visual Perception Abnormalities: A Marker for Body Image Concern.

The body image concern (BIC) continuum ranges from a healthy and positive body image, to clinical diagnoses of abnormal body image, like body dysmorphic disorder (BDD). BDD and non-clinical, yet high-BIC participants have demonstrated a local visual processing bias, characterised by reduced inversion effects. To examine whether this bias is a potential marker of BDD, the visual processing of individuals across the entire BIC continuum was examined. Dysmorphic Concern Questionnaire (DCQ; quantified BIC) scores were expected to correlate with higher discrimination accuracy and faster reaction times of inverted stimuli, indicating reduced inversion effects (occurring due to increased local visual processing). Additionally, an induced global or local processing bias via Navon stimulus presentation was expected to alter these associations. Seventy-four participants completed the DCQ and upright-inverted face and body stimulus discrimination task. Moderate positive associations were revealed between DCQ scores and accuracy rates for inverted face and body stimuli, indicating a graded local bias accompanying increases in BIC. This relationship supports a local processing bias as a marker for BDD, which has significant assessment implications. Furthermore, a moderate negative relationship was found between DCQ score and inverted face accuracy after inducing global processing, indicating the processing bias can temporarily be reversed in high BIC individuals. Navon stimuli were successfully able to alter the visual processing of individuals across the BIC continuum, which has important implications for treating BDD.

Circadian regulation of chloroplasts.

Circadian rhythms produce a biological measure of time that increases plant performance. The mechanisms that underlie this increase in productivity require investigation to provide information that will underpin future crop improvement. There is a growing body of evidence that a sophisticated signalling network interconnects the circadian oscillator and chloroplasts. We consider this in the context of circadian signalling to chloroplasts and the relationship between retrograde signalling and circadian regulation. We place circadian signalling to chloroplasts by sigma factors within an evolutionary context. We describe selected recent developments in the integration of light and circadian signals that control chloroplast gene expression.

Circadian control of chloroplast transcription by a nuclear-encoded timing signal.

Circadian timekeeping in plants increases photosynthesis and productivity. There are circadian oscillations in the abundance of many chloroplast-encoded transcripts, but it is not known how the circadian clock regulates chloroplast transcription or the photosynthetic apparatus. We show that, in Arabidopsis, nuclear-encoded SIGMA FACTOR5 (SIG5) controls circadian rhythms of transcription of several chloroplast genes, revealing one pathway by which the nuclear-encoded circadian oscillator controls rhythms of chloroplast gene expression. We also show that SIG5 mediates the circadian gating of light input to a chloroplast-encoded gene. We have identified an evolutionarily conserved mechanism that communicates circadian timing information between organelles with distinct genetic systems and have established a new level of integration between eukaryotic circadian clocks and organelles of endosymbiotic origin.

Direct and indirect costs of asthma to an employer.

BACKGROUND: Asthma is a chronic inflammatory condition of the airways that has a significant effect on the use of health care resources. OBJECTIVE: This study is the first of its kind to estimate the overall cost of asthma to a major employer in the United States and to profile the nature of the asthma expenses. METHODS: The annual per capita cost of asthma was determined for beneficiaries of a major employer by analyzing medical, pharmaceutical, and disability claims data. The incremental cost of asthma was determined by using a case-control method matching asthmatic patients to individuals with no record of asthma treatment. RESULTS: The use of health care services, as well as the rate of disability, was substantially higher among asthmatic patients than among control subjects. Annual per capita employer expenditures for asthmatic patients were approximately 2.5 times those for control subjects ($5385 vs. $2121, respectively). Among asthmatic employees with disability claims, total costs were approximately 3 times higher than those among disability claimants in the employee control sample ($14,827 vs. $5280). For asthmatic employees, wage-replacement costs for workdays lost as a result of disability and sporadic absenteeism (40%) accounted for almost as much as did medical care (43%). CONCLUSION: Failure to account fully for the broader consequences of asthma in terms of indirect and comorbid treatment costs would result in a significant underassessment of the cost of asthma to an employer.