Prediction of Opioid-Induced Respiratory Depression on Inpatient Wards Using Continuous Capnography and Oximetry: An International Prospective, Observational Trial

Background: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. Methods: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting >30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. Results: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17-26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P < .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44-8.30; P < .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P < .0001) identified using continuous oximetry and capnography monitoring. Conclusions: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor

Prediction of Opioid-Induced Respiratory Depression on Inpatient Wards Using Continuous Capnography and Oximetry: An International Prospective, Observational Trial.

BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting \u3e30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. RESULTS: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17-26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P \u3c .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44-8.30; P \u3c .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P \u3c .0001) identified using continuous oximetry and capnography monitoring. CONCLUSIONS: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

SARS-CoV-2 Vaccination Immune Response

Research Data, SARS-CoV-2 Vaccination Immune Response, for “Humoral and T-Cell Responses to SARS-CoV-2 Vaccination in Multiple Sclerosis Patients Treated with Ocrelizumab” by Katz J.D., Bouley A.J., Jungquist R.M., Douglas E.A., O’Shea I.L., Lathi E.S. Ocrelizumab has been shown to reduce the humoral response to SARS-CoV-2 vaccination, but the T-cell response has not yet been fully characterized. We sought to provide data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in OCR-treated patients, and to determine what variables correlate with vaccine immunogenicity. In this prospective, single center, observational cohort study, we evaluated the humoral response to COVID-19 vaccines 3-4 weeks post-vaccination in adult multiple sclerosis patients treated with OCR, using natalizumab as a real-world comparator. We then assessed the T-cell response for those OCR-treated patients who did not produce detectable antibodies. Participants were multiple sclerosis patients who met revised 2017 McDonald criteria,10 ages 18 to 55 years, with an EDSS of 0 to 5.5, who were treated with either OCR or NTZ for a minimum of 6 months. Upon consent, basic demographic and medical history information was collected from patient medical records (see descriptions below). The primary endpoint of this study was the production of SARS-CoV-2 spike protein antibodies 4 weeks after completion of vaccination. Antibody test results were defined as either positive (≥0.80 U/mL) or negative (<0.80 U/mL) as per the manufacturer’s guidelines. Six (18.2%) of the OCR-treated patients had a positive antibody response. All 15 of the NTZ-treated patients produced a positive response. Of the six OCR-treated patients who produced antibodies, only one had a result that exceeded the upper limit of 250 U/mL, whereas all but one (93.3%) of the NTZ-treated patients exceeded the upper limit. There was no correlation between antibody response and age, sex, BMI, vaccine type, number of infusion cycles, and IgG, CD19, or ALC. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P=0.062). Of the OCR-treated patients that had a negative antibody response, all patients (N=27) had a positive adaptive T-cell response

The Relationship among Chronic Pain, Opiates, and Sleep

Thesis (Ph.D.)--University of Rochester. School of Nursing. Dept. of Nursing, 2008.The overall aim of this study was to examine the relationships among chronic pain, opiates, respiration, and sleep in a sample of subjects referred for assessment of sleep disorders. This study assessed: (a) whether increasing dosages of opiate predict severity of sleep disordered breathing, sleep architecture, sleep continuity abnormalities, and/or excessive daytime sleepiness; (b) whether the study groups ([no pain vs. pain] and [pain minus opiate treatment vs. pain plus opiate treatment]) differed with respect to severity of sleep disordered breathing, sleep architecture, sleep continuity abnormalities; (c) whether the known risk factors for sleep disordered breathing differed for persons with and without chronic pain, and (d) whether intensity of pain predicted severity of sleep disordered breathing. Methods A descriptive cross sectional study was conducted. There were two types of independent variables, (a) risk factors for sleep disordered breathing (BMI, age, gender, number of systems affected by co-morbid diseases, and presence of anatomical abnormalities typical of obstructive sleep apnea), and (b) those that were directly related to the investigational hypothesis (pain incidence and intensity and/or opiate use and dose). Dependent Variables included: measures of sleep disordered breathing (e.g., frequency of central and obstructive events), sleep architecture (e.g., percent of stages 1-4 and REM), and sleep continuity measures (e.g., Sleep Latency, Number of Awakenings, and Total Sleep Time). After orthogonally coding for group membership, regression models were used for statistical analysis. Pain, Opiates and Sleep Results Data was collected on a total of 419 subjects (no pain [n = 171], pain –opiate Tx [n = 187], and pain +opiate Tx [n = 61]). Sample demographic (mean +/- SD) was as follows: age 50 yr + 12.; 51% male; BMI 33.8 + 7; Epworth Sleepiness Scale 10.3 + 5; pain intensity 3.8 + 2 (0-10 scale); morphine equivalent dose 152 + 195 mg; and 98% of subjects with pain had non-malignant chronic pain. Per study hypotheses (a) there was a positive dose response relationship between amount of opiate and frequency of central apneic events and percent of stage 3/4 sleep; (b) the [no pain vs. pain] group comparison revealed that subjects with pain had a lower percent of stage 1 sleep, and the [pain minus opiate vs. pain plus opiate]) group comparison revealed that subjects treated with opiates had significantly more central apneic events, more stage 2 sleep and less REM sleep; (c) the known risk factors for sleep disordered breathing differ in persons with and without chronic pain (chronic pain subjects were older, female and suffered from more comorbidity); (d) there was a relationship between pain intensity and frequency of central apneic events and obstructive apneic events. Greater pain intensity was associated with more frequent central apneic events and fewer obstructive apneic events. Conclusion These data suggest that the management of chronic pain with opiates is not likely to exacerbate obstructive sleep apnea at stable opiate doses; however; central sleep apnea may be worsened. The magnitude of the effect is modest, and the clinical relevance of the effect is unknown. Thus, the potential for marginal respiratory disturbance (an increase of 2.8 central events for every 100 mg. morphine equivalent opiate dose) must be weighed against the therapeutic value of pain management with opiates

Introducing the Sleep Disorders Symptom Checklist-25: A Primary Care Friendly and Comprehensive Screener for Sleep Disorders

Background and Objective With sleep disorders highly prevalent and associated with poor health outcomes, screening for sleep disorders in primary care could reduce the burden of chronic diseases and costs of health care. Currently, a brief comprehensive primary-care-friendly multiple-sleep-disorders screening instrument is not available. The Sleep Disorders Symptom Checklist (SDS-CL)-17, a single-page instrument, was developed to screen for six sleep disorders (insomnia, obstructive sleep apnea, restless legs syndrome/periodic limb movement disorder, circadian rhythm sleep-wake disorders, narcolepsy, and parasomnias) and evaluated psychometrically. SDS-CL-17 psychometrics are reported. The resulting development of a more comprehensive single-page 25-item instrument, the SDS-CL-25, based on validation study results is described. Approaches for clinical use of the SDS-CL-25 are recommended. Methods A cross-sectional study using nested data from two previous research studies (n = 395 sleep clinic referrals and n = 299 community volunteers) was used. SDS-CL-17 subscale scores and physician diagnoses were analysed using receiver operator characteristic curves. Resulting cut-point scores determined sensitivities/specificities. Study subject interview data were used to assess patient-friendliness of the instrument. Results Sensitivities/specificities for the diagnosed sleep disorders ranged from 0.64 to 0.88. Interviewees endorsed the instrument as user-friendly. Conclusions While the SDS-CL-17 is useful, the SDS-CL-25 assesses for a much larger number of sleep disorders yet retains brevity and is therefore recommended for ongoing clinical use. Psychometric evaluation of the SDS-CL-25 continues

Validation of Capturing Sleep Diary Data via a Wrist-Worn Device

Paper sleep diaries are the gold standard for assessment of sleep continuity variables in clinical practice as well as research. Unfortunately, paper diaries can be filled out weekly instead of daily, lost, illegible or destroyed; and are considered out of date according to the newer technology savvy generations. In this study, we assessed the reliability and validity of using a wrist-worn electronic sleep diary. Design. A prospective design was used to compare capturing 14 days of sleep continuity data via paper to a wrist-worn electronic device that also captured actigraphy data. Results. Thirty-five healthy community dwelling adults with mean (sd) age of 36 (15), 80% Caucasians, and 74% females were enrolled. All sleep continuity variables via electronic and paper diary capture methods were significantly correlated with moderate, positive relationships. Assessment of validity revealed that electronic data capture had a significant relationship with objective measure of sleep continuity variables as measured by actigraphy. Paper diary variables were not significantly associated with objective measures. Conclusions. The use of a wrist-worn device to capture daily sleep diary data is as accurate as and for some variables more accurate than using paper diaries