Automated spike and seizure detection: Are we ready for implementation?

OBJECTIVE: Automated detection of spikes and seizures has been a subject of research for several decades now. There have been important advances, yet automated detection in EMU (Epilepsy Monitoring Unit) settings has not been accepted as standard practice. We intend to implement this software at our EMU and so carried out a qualitative study to identify factors that hinder ('barriers') and facilitate ('enablers') implementation. METHOD: Twenty-two semi-structured interviews were conducted with 14 technicians and neurologists involved in recording and reporting EEGs and eight neurologists who receive EEG reports in the outpatient department. The study was reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ). RESULTS: We identified 14 barriers and 14 enablers for future implementation. Most barriers were reported by technicians. The most prominent barrier was lack of trust in the software, especially regarding seizure detection and false positive results. Additionally, technicians feared losing their EEG review skills or their jobs. Most commonly reported enablers included potential efficiency in the EEG workflow, the opportunity for quantification of EEG findings and the willingness to try the software. CONCLUSIONS: This study provides insight into the perspectives of users and offers recommendations for implementing automated spike and seizure detection in EMUs.

Automated spike detection: Which software package?

PURPOSE: We assessed three commercial automated spike detection software packages (Persyst, Encevis and BESA) to see which had the best performance. METHODS: Thirty prolonged EEG records from people aged at least 16 years were collected and 30-minute representative epochs were selected. Interictal epileptiform discharges (IEDs) were marked by three human experts and by all three software packages. For each 30-minutes selection and for each 10-second epoch we measured whether or not IEDs had occurred. We defined the gold standard as the combined detections of the experts. Kappa scores, sensitivity and specificity were estimated for each software package. RESULTS: Sensitivity for Persyst in the default setting was 95% for 30-minute selections and 82% for 10-second epochs. Sensitivity for Encevis was 86% (30-minute selections) and 61% (10-second epochs). The specificity for both packages was 88% for 30-minute selections and 96%-99% for the 10-second epochs. Interrater agreement between Persyst and Encevis and the experts was similar than between experts (0.67-0.83 versus 0.63-0.67). Sensitivity for BESA was 40% and specificity 100%. Interrater agreement (0.25) was low. CONCLUSIONS: IED detection by the Persyst automated software is better than the Encevis and BESA packages, and similar to human review, when reviewing 30-minute selections and 10-second epochs. This findings may help prospective users choose a software package.

Automated seizure detection in an EMU setting: Are software packages ready for implementation?

PURPOSE: We assessed whether automated detection software, combined with live observation, enabled reliable seizure detection using three commercial software packages: Persyst, Encevis and BESA. METHODS: Two hundred and eighty-six prolonged EEG records of individuals aged 16-86 years, collected between August 2019 and January 2020, were retrospectively processed using all three packages. The reference standard included all seizures mentioned in the clinical report supplemented with true detections made by the software and not previously detected by clinical physiologists. Sensitivity was measured for offline review by clinical physiologists and software seizure detection, both in combination with live monitoring in an EMU setting, for all three software packages at record and seizure level. RESULTS: The database contained 249 seizures in 64 records. The sensitivity of seizure detection was 98% for Encevis and Persyst, and 95% for BESA, when a positive results was defined as detection at least one of the seizures occurring within an individual record. When positivity was defined as recognition of all seizures, sensitivity was 93% for Persyst, 88% for Encevis and 84% for BESA. Clinical physiologists' review had a sensitivity of 100% at record level and 98% at seizure level. The median false positive rate per record was 1.7 for Persyst, 2.4 for BESA and 5.5 for Encevis per 24 h. CONCLUSION: Automated seizure detection software does not perform as well as technicians do. However, it can be used in an EMU setting when the user is aware of its weaknesses. This assessment gives future users helpful insight into these strengths and weaknesses. The Persyst software performs best.

TREX1 mutations are not associated with sporadic inclusion body myositis.

BACKGROUND: Sporadic inclusion body myositis (sIBM) is the most frequent acquired myopathy above the age of fifty. The exact mechanism causing this disease is not known, but immune-mediated features are prominent and are probably to play a role in its pathogenesis. TREX1 gene mutations are associated with a large range of autoimmune diseases, such as systemic lupus erythematosus. We investigated whether mutations in the TREX1 gene were associated with sIBM. METHODS: Fifty-four patients with sIBM were tested for TREX1 mutations by direct sequencing. RESULTS: All 54 patients tested negative for pathogenic mutations in the TREX1 gene. One presumed non-pathogenic polymorphism was found in 42 out of 54 patients. CONCLUSION: TREX1 mutations do not play a role in the pathogenesis of sIBM.

Detecting dysphagia in inclusion body myositis.

Dysphagia is an important yet inconsistently recognized symptom of inclusion body myositis (IBM). It can be disabling and potentially life-threatening. We studied the prevalence and symptom-sign correlation of dysphagia. Fifty-seven IBM patients were interviewed using a standard questionnaire for dysphagia and 43 of these underwent swallowing videofluoroscopy (VFS). Symptoms of dysphagia were present in 37 of 57 patients (65%). Nevertheless, only 17 of these patients (46%) had previously and spontaneously complained about swallowing to their physicians. Both symptoms of impaired propulsion (IP) (59%) and aspiration-related symptoms (52%) were frequently mentioned. Swallowing abnormalities on VFS were present in 34 of 43 patients (79%) with IP of the bolus in 77% of this group. The reported feeling of IP was confirmed by VFS in 92% of these patients. Dysphagia in IBM is common but underreported by the vast majority of patients if not specifically asked for. In practice, two questions reliably predict the presence of IP on VFS: 'Does food get stuck in your throat' and 'Do you have to swallow repeatedly in order to get rid of food'. These questions are an appropriate means in selecting IBM patients for further investigation through VFS and eventual treatment.

Selective coating of holes in microstructured optical fiber and its application to in-fiber absorptive polarizers.

An interesting feature of microstructured optical fibers (MOFs) is that their properties can be adjusted by filling or coating of the holes. Some applications require selective filling or coating, which has proved experimentally demanding. We demonstrate selective coating of MOFs with metal and use it to fabricate an in-fiber absorptive polarizer.

[A man with the combination of dry and wet beriberi]. / Een man met de combinatie van droge en natte beriberi.

A 34-year-old alcoholic man had neurological and cardiac symptoms. The patient was admitted to the hospital for acute painful sensory disturbances and severe weakness of the feet. Neurological and electrophysiological investigation revealed axonal sensorimotor polyneuropathy that was most prominent in the legs. Cardiac assessment showed signs and symptoms of heart failure due to a high-output state. Blood analysis showed a low thiamine concentration of 58 nmol/l (lower reference limit: 80). Therefore, a diagnosis of combined wet beriberi with cardiomyopathy and dry beriberi with axonal polyneuropathy was made. The treatment of beriberi is simple and effective and consists of thiamine supplementation in conjunction with diuretic treatment. With this approach, the patient recovered fully. Patients with beriberi have a good prognosis, particularly when the diagnosis is made at an early stage.

Liquid-filled hollow core microstructured polymer optical fiber.

Guidance in a liquid core is possible with microstructured optical fibers, opening up many possibilities for chemical and biochemical fiber-optic sensing. In this work we demonstrate how the bandgaps of a hollow core microstructured polymer optical fiber scale with the refractive index of liquid introduced into the holes of the microstructure. Such a fiber is then filled with an aqueous solution of (-)-fructose, and the resulting optical rotation measured. Hence, we show that hollow core microstructured polymer optical fibers can be used for sensing, whilst also fabricating a chiral optical fiber based on material chirality, which has many applications in its own right.

Relationship between quality of life and clinical status in asthma: a factor analysis.

Many studies have shown that correlation between clinical asthma status and asthma-specific quality of life is only weak to moderate. However, this relationship has never been explored to determine whether the weakness is due to noise of measurement or whether quality of life is a distinct component of asthma health status. With a database from three clinical trials (n = 763), factor analysis was used to explore the relationships between quality of life, measured by the Asthma Quality of Life Questionnaire (AQLQ), and conventional measures of asthma clinical status (symptoms, airway calibre and rescue beta2-agonist use). The analysis revealed that although patients with severe, poorly controlled asthma tend to have worse quality of life than milder, well-controlled patients, overall asthma health status has four components (factors): asthma-specific quality of life; airway calibre; daytime symptoms and daytime beta2-agonist use, and night-time symptoms and night-time beta2-agonist use. The clean loading of all 21 outcomes onto four distinct and clinically identifiable factors suggests that, although some weakness of correlation between clinical indices and quality of life may be due to noise of measurement, it is mainly attributable to asthma health status being composed of distinct components.

Comparison of the standard gamble, rating scale, AQLQ and SF-36 for measuring quality of life in asthma.

With interest in health economics growing, there is a demand for valid methods for measuring health-related quality of life (HRQL) in asthma using utilities. The aims of this study were to develop disease-specific versions of the standard gamble and rating scale, to compare their measurement properties with those of the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Survey Short-Form 36 (SF-36), as well as to determine their validity for assessing asthma-specific quality of life. Forty adults with symptomatic asthma participated in a 9-week observational study. Participants completed the standard gamble, rating scale, AQLQ, SF-36 and other measures of clinical asthma status at baseline and after 1, 5 and 9 weeks. In patients whose asthma was stable between assessments, reliability was good for the rating scale (intraclass correlation coefficient (ICC)=0.89) and the AQLQ (ICC=0.95) but more modest for the SF-36 mental score (ICC=0.68), SF-36 physical score (ICC=0.65) and standard gamble (ICC=0.59). The responsiveness index was highest in the AQLQ (1.35), followed by the rating scale (0.74), the physical score of the SF-36 (0.61) and the standard gamble (0.31). Construct validity (correlation with other indices of health status) was strongest for the AQLQ and the rating scale. In conclusion, both the disease-specific rating scale and the Asthma Quality of Life Questionnaire have strong measurement properties for measuring asthma-specific quality of life; the Short-Form 36 health survey physical summary score has more modest properties. Although the disease-specific standard gamble has acceptable discriminative properties, its evaluative properties are too inadequate for it to be used in cost/utility analyses. Poor correlation between the standard gamble and the rating scale indicates that utilities cannot be derived from rating scale data.

Economic burden of influenza-like illness in long-term-care facilities.

Direct medical costs and medically related transportation costs incurred by patients in long-term-care facilities (LTCFs) as a result of influenza-like illness (ILI) were studied. The study was conducted from the payer's perspective. Charts were reviewed retrospectively for all patients who were residents of four Richmond, Virginia, LTCFs between January 1 and May 31, 1999. Consultant pharmacists gathered data on patient demographics, ILI status, vaccination for influenza and streptococcal pneumonia, diagnosis of asthma or chronic obstructive pulmonary disease, and utilization of health care services related to ILI. Services included the use of antimicrobials, antivirals, and respiratory drugs; emergency room visits; diagnostic tests; hospitalizations; and medically related transportation. Costs were based on average wholesale prices (for drugs) and Medicare or Medicaid reimbursement rates. Data were collected for 551 patients. Of these, 112 patients had been diagnosed with 128 cases of ILI during the study period. Twenty-two patients with ILI had 28 visits to emergency rooms, and 30 patients with ILI had 36 hospitalizations. The mean +/- S.D. cost per case of ILI was $1341 +/- $2063; inpatient hospital costs accounted for 84% of this amount. Centers for Disease Control and Prevention criteria for ILI provided a lower incidence of ILI and, consequently, a lower mean +/- S.D. cost of $968 +/- $1806 per case. ILI in patients in four LTCFs in Richmond, Virginia, generated substantial costs, the bulk of which resulted from hospitalization. A substantial percentage of the patients apparently were not immunized.

Cost of treating influenza in emergency department and hospital settings.

OBJECTIVES: To provide an estimate of the costs of treating influenza in emergency department and hospital settings. STUDY DESIGN: Retrospective, descriptive study using patient-level data from the Perspective Comparative Database. PATIENTS AND METHODS: We analyzed clinical and cost data obtained from 75 of the 169 hospitals in the database. These hospitals were located throughout the United States. Patients were included in the study if they visited the emergency department between January 1, 1997, and June 30, 1998, and had a primary diagnosis of influenza. RESULTS: A total of 1362 patients with influenza visited the emergency department during the study period. Of these, 333 (24.4%) required hospitalization. The mean cost of treatment for patients discharged directly from the emergency department was $141.89; the mean cost of treatment for hospitalized patients was $3251.04. The mean length of stay for hospitalized patients was 4.3 days. Compared with younger patients, elderly patients were more likely to be hospitalized and incur higher costs. Thirty-eight percent of hospitalized patients for whom drug data were available received either amantadine or rimantadine during their stay. CONCLUSIONS: Few data are available documenting resource utilization and associated costs for patients with influenza treated in the emergency department or hospital. Our results represent a significant addition to the identification of the costs associated with the treatment of influenza. This suggests early intervention care aimed at minimizing the impact of influenza, especially in the elderly, could result in decreased hospitalizations and substantial cost savings to managed care.

Development and validation of the Mini Asthma Quality of Life Questionnaire.

The 32-item Asthma Quality of Life Questionnaire (AQLQ) has shown good responsiveness, reliability and construct validity; properties that are essential for use in clinical trials, clinical practice and surveys. However, to meet the needs of large clinical trials and long-term monitoring, where efficiency may take precedent over precision of measurement, the 15-item self-administered MiniAQLQ has been developed. The MiniAQLQ was tested in a 9-week observational study of 40 adults with symptomatic asthma. Patients completed the MiniAQLQ, the AQLQ, the Short Form (SF)-36, the Asthma Control Questionnaire and spirometry at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability was very acceptable for the MiniAQLQ (intraclass correlation coefficient (ICC)=0.83), but not quite as good as for the AQLQ (ICC=0.95). Similarly, responsiveness in the MiniAQLQ (p=0.0007) was good but not quite so good as for the AQLQ (p<0.0001). Construct validity (correlation with other indices of health status) was strong for both the MiniAQLQ and the AQLQ. Criterion validity showed that there was no bias between the instruments (p=0.61) and the correlation between them was high (r=0.90). The Mini Asthma Quality of Life Questionnaire has good measurement properties but they are not quite as strong as those of the original Asthma Quality of Life Questionnaire. The choice of questionnaire should depend on the task at hand.

Validation of a standardized version of the Asthma Quality of Life Questionnaire.

BACKGROUND: In the original 32-item Asthma Quality of Life Questionnaire (AQLQ), five activity questions are selected by patients themselves. However, for long-term studies and large clinical trials, generic activities may be more appropriate. METHODS: For the standardized version of the AQLQ, the AQLQ(S), we formulated five generic activities (strenuous exercise, moderate exercise, work-related activities, social activities, and sleep) to replace the five patient-specific activities in the AQLQ. In a 9-week observational study, we compared the AQLQ with the AQLQ(S) and examined their measurement properties. Forty symptomatic adult asthma patients completed the AQLQ(S), the AQLQ, the Medical Outcomes Survey Short Form 36, the Asthma Control Questionnaire, and spirometry at baseline, 1, 5, and 9 weeks. RESULTS: Activity domain scores (mean +/- SD) were lower with the AQLQ (5.7 +/- 0.9) than with the AQLQ(S) (5.9 +/- 0.8; p = 0.0003) and correlation between the two was moderate (r = 0.77). However, for overall scores, there was minimal difference (AQLQ, 5.4 +/- 0.8; AQLQ(S), 5.5 +/- 0.8; r = 0.99). Reliability (AQLQ intraclass correlation coefficient, 0.95; AQLQ(S) intraclass correlation coefficient, 0.96) and responsiveness (AQLQ, p < 0.0001; AQLQ(S), p < 0.0001) were similar for the two instruments. Construct validity (correlation with other measures of health status and clinical asthma) was also similar for the two instruments. CONCLUSIONS: The AQLQ(S) has strong measurement properties and is valid for measuring health-related quality of life in asthma. The choice of instrument should depend on the task at hand.

Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids. Salmeterol Quality of Life Study Group.

BACKGROUND: Traditional clinical outcomes have demonstrated that salmeterol improves pulmonary function and reduces asthma symptoms. However, they do not evaluate how patients perceive the effect of therapeutic intervention on day-to-day functioning and well-being. OBJECTIVE: We sought to evaluate the impact of salmeterol on disease-specific quality of life with the Asthma Quality-of-Life Questionnaire, as well as the efficacy and safety of salmeterol in patients with stable asthma who were symptomatic despite daily use of inhaled corticosteroids. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group study of 506 patients. Patients were treated with 42 microg salmeterol or placebo twice daily for 12 weeks delivered through a metered dose inhaler. RESULTS: Mean change from baseline in asthma quality-of-life scores was significantly greater (p < or = 0.006) after 12 weeks of treatment with salmeterol compared with placebo ("as-needed" albuterol) in global scores (1.08 vs 0.61) and individual domains (activity limitations, 0.91 vs 0.54; asthma symptoms, 1.28 vs 0.71; emotional function, 1.17 vs 0.65; and environmental exposure, 0.84 vs 0.47). Patients treated with salmeterol experienced significantly greater improvements from baseline to week 12 compared with placebo in FEV1 (0.42 L vs 0.15 L, p < 0.001), morning peak expiratory flow (47 L/min vs 14 L/min, p < 0.001), evening peak expiratory flow (29 L/min vs 11 L/min, p < 0.001), and asthma symptom scores (daytime scores reduced by 0.55 vs 0.30, p < 0.001). Patients treated with salmeterol used significantly less supplemental albuterol (reduced by 3 puffs/day vs 1 puff/day, p < 0.001). CONCLUSION: Salmeterol provided significantly greater improvement in quality-of-life outcomes in patients whose asthma symptoms are not well controlled with inhaled corticosteroids. These results demonstrate that the benefits of salmeterol are not limited to conventional clinical measures of efficacy.

Salmeterol versus theophylline in the treatment of asthma.

BACKGROUND: Although theophylline is recommended by current guidelines for the management of asthma in patients with persistent symptoms, theophylline has a narrow therapeutic index, requiring individual dose titration and regular monitoring of serum theophylline concentrations to avoid adverse effects. OBJECTIVE: To compare the inhaled long-acting bronchodilator, salmeterol, with the oral bronchodilator, theophylline, in the maintenance treatment of asthma. METHODS: In two multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group studies, patients received salmeterol aerosol 42 micrograms, extended-release theophylline capsules, or placebo twice daily for 12 weeks. RESULTS: Of 638 adult and adolescent patients with moderate asthma who entered the prebaseline theophylline titration period, 154 were withdrawn prior to randomization (71 due to theophylline-related adverse effects); 484 patients comprised the intent-to-treat population. The mean serum theophylline concentration measured approximately seven hours postdose during the titration period in the theophylline group was 12.7 mg/L (70 mumol/L). The same dose during the treatment period resulted in a mean serum theophylline concentration between 7.6 to 7.9 mg/L (42-44 mumol/L) when measured approximately 12 hours postdose. Salmeterol was significantly more effective than theophylline or placebo in improving mean morning PEF over the entire 12 weeks (P < or = .02). Mean predose FEV1 improved significantly with salmeterol compared with placebo (P < .001); there was no difference between theophylline and placebo. Salmeterol was also significantly more effective than theophylline or placebo (P < .02) in improving asthma symptoms, reducing nighttime awakenings, and reducing the daily use of albuterol. After 12 weeks of treatment, patients in the salmeterol group expressed significantly greater overall satisfaction with their asthma medication than did patients who received theophylline (P < .01). Patients in the theophylline group experienced more gastrointestinal adverse events than did patients in the salmeterol group (P < .05). CONCLUSION: Salmeterol, 42 mg twice daily, was better tolerated and significantly more effective than extended-release theophylline twice daily in the maintenance treatment of asthma.

Economic impact with home delivery of chemotherapy to pediatric oncology patients.

OBJECTIVE: To examine the economic impact of a home chemotherapy program (HCP) for pediatric oncology patients. RATIONALE: Factors that led to initiation of an HCP included availability of specially trained nurses and programmable ambulatory infusion devices at local home care agencies, routine central venous catheter placement, inpatient bed space shortages, and the availability of ondansetron. SETTING: Chemotherapy delivery in the home setting from June 1991 through June 1994. DESIGN: Charge data and nausea and vomiting severity data were collected for patients treated through the HCP. METHODS: Economic impact was calculated by incorporating and summing all charge categories associated with hospital admission for chemotherapy (HAC) versus delivery by the HCP. All data were adjusted for 1993 dollars, and reflect changes for the average patient size (1 m2). Charge data for each chemotherapy protocol delivered in the home were analyzed by calculating the differences between HAC and HCP charges using the following formula: charge difference (HAC - HCP) per protocol times the number of courses. Total economic impact was calculated by summing the differences in charges for each protocol. RESULTS: A total of 262 chemotherapy courses were given to 44 patients (mean age 9.5 +/- 5.1 y) through the HCP, which represented 1012 patient care days and 24 different chemotherapy protocols. Monetary savings from the HCP ranged from $5180 per course of ifosfamide plus etoposide to $367 per course for high-dose methotrexate. Total monetary savings from the HCP during the 3-year period was $640,793. Successful control of nausea and vomiting with a combination of ondansetron plus methylprednisolone was achieved in approximately 80% of the patients receiving highly emetogenic chemotherapy protocols. CONCLUSIONS: HCP for pediatric oncology patients results in substantial monetary savings to payors. Effective control of nausea and vomiting can be accomplished at home in the majority of patients with an ondansetron-based antiemetic regimen.

An industry survey of current lower limits of detection for various radionuclides.

The results of a survey to assess detection limits of various radionuclides and their associated costs is presented herein. Included among the radionuclides of interest are mixed fission products, mixed activation products, actinides and transuranics, plus tritium (3H) and 14C. The survey encompassed commercial analytical radiochemistry services and nuclear instrument suppliers in the United States. In the study, a simple soil sample was defined as the object of consideration with no requirements for any special quality control/assurance. Standard procedures and instrumentation were requested, as were standard prices/costs required for the various analyses. The minimum detectable level for most isotopes using standard procedures was on the order of 0.0037 to 0.037 Bq g-1 (0.1 to 1.0 pCi g-1). The analytical costs varied by factors of 2 to 4 over a range of 0.0037 to 0.37 Bq g-1 (0.1 to 10.0 pCi g-1). While the ability to detect below 0.0037 Bq g-1 (0.1 pCi g-1) is possible, the required detection times were considered prohibitive for a commercial laboratory.