Validation of the Diagnostic Accuracy Levels of International Classification of Diseases, 10th Revision Codes for Diabetic Ketoacidosis: A Multicentre, Cross-sectional Study of Adults.

OBJECTIVES: International Classification of Diseases (ICD) codes are commonly used to identify cases of diabetic ketoacidosis (DKA) in health services research, but they have not been validated. Our aim in this study was to assess the accuracy of ICD, 10th revision (ICD-10) diagnosis codes for DKA. METHODS: We conducted a multicentre, cross-sectional study using data from 5 hospitals in Ontario, Canada. Each hospitalization event has a single most responsible diagnosis code. We identified all hospitalizations assigned diagnosis codes for DKA. A true case of DKA was defined using laboratory values (serum bicarbonate ≤18 mmol/L, arterial pH ≤7.3, anion gap ≥14 mEq/L, and presence of ketones in urine or blood). Chart review was conducted to validate DKA if laboratory values were missing or the diagnosis of DKA was unclear. Outcome measures included positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of ICD-10 codes in patients with laboratory-defined DKA. RESULTS: We identified 316,517 hospitalizations. Among these, 312,948 did not have an ICD-10 diagnosis code for DKA and 3,569 had an ICD-10 diagnosis code for DKA. Using a combination of laboratory and chart review, we identified that the overall PPV was 67.0%, the NPV was 99.7%, specificity was 99.6%, and sensitivity was 74.9%. When we restricted our analysis to hospitalizations in which DKA was the most responsible discharge diagnosis (n=3,374 [94.5%]), the test characteristics were PPV 69.8%, NPV 99.7%, specificity 99.7%, and sensitivity 71.9%. CONCLUSION: ICD-10 codes can identify patients with DKA among those admitted to general internal medicine.

Press Releases of Drug-Related Randomized Trial Results Prior to Publication in High-Impact Journals: an Observational Study.

IMPORTANCE: Results from high-profile randomized controlled trials (RCTs) are routinely reported through press release months prior to peer-reviewed publication. There are potential benefits to press releases (e.g., knowledge dissemination, ensuring regulatory compliance), but also potential drawbacks (e.g., selective reporting, positive "spin"). OBJECTIVE: To characterize the practice of press release predating the publication of a drug-related RCT in a peer-reviewed journal ("preemptive press release"), including factors associated with this practice. DESIGN, SETTING, AND PARTICIPANTS: We systematically reviewed all RCTs of medications published between 2015 and 2019 in the New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and Lancet. Press releases were identified using a systematic search of the grey literature (e.g., press release databases, study sponsor websites). An RCT was considered to have a preemptive press release if the press release was published at least three months (90 days) prior to the date of publication in a peer-reviewed journal. MAIN OUTCOMES AND MEASURES: Presence of preemptive press release, defined as a press-release at least 90 days prior to the date of publication in a peer-reviewed journal. As secondary measures for dissemination, we also assessed citation count and Altmetric score. RESULTS: We identified 988 RCTs, of which 172 (17%) had a press release published at least 90 days before the date of peer-reviewed publication. Press releases were published a median of 246 days (interquartile range [IQR] 169-366 days) before publication in a peer-reviewed journal. In the multivariable logistic regression model, the strongest predictor of having a preemptive press release was funding by a pharmaceutical company (odds ratio 13, 95% CI 7, 25). Approximately 85% of RCTs with preemptive press releases had a positive primary outcome and, concordantly, 81% of the corresponding press releases had a positive headline. Multivariable regression models identified studies with a preemptive press release had a similar Altmetric score (median - 15, 95% CI - 33, 12) and higher median citation count (median 22 [95% CI 10 to 33] compared to studies without a preemptive press release. CONCLUSIONS AND RELEVANCE: Preemptive press releases were common, most often issued for trials funded by a pharmaceutical company, and typically preceded publication in a peer-reviewed journal by approximately eight months.

Comparison of Medical and Mental Health Sequelae Following Hospitalization for COVID-19, Influenza, and Sepsis.

Importance: People who survive hospitalization for COVID-19 are at risk for developing new cardiovascular, neurological, mental health, and inflammatory autoimmune conditions. It is unclear how posthospitalization risks for COVID-19 compare with those for other serious infectious illnesses. Objective: To compare risks of incident cardiovascular, neurological, and mental health conditions and rheumatoid arthritis in 1 year following COVID-19 hospitalization against 3 comparator groups: prepandemic hospitalization for influenza and hospitalization for sepsis before and during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study included all adults hospitalized for COVID-19 between April 1, 2020, and October 31, 2021, historical comparator groups of people hospitalized for influenza or sepsis, and a contemporary comparator group of people hospitalized for sepsis in Ontario, Canada. Exposure: Hospitalization for COVID-19, influenza, or sepsis. Main Outcome and Measures: New occurrence of 13 prespecified conditions, including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis, within 1 year of hospitalization. Results: Of 379 366 included adults (median [IQR] age, 75 [63-85] years; 54% female), there were 26 499 people who survived hospitalization for COVID-19, 299 989 historical controls (17 516 for influenza and 282 473 for sepsis), and 52 878 contemporary controls hospitalized for sepsis. Hospitalization for COVID-19 was associated with an increased 1-year risk of venous thromboembolic disease compared with influenza (adjusted hazard ratio, 1.77; 95% CI, 1.36-2.31) but with no increased risks of developing selected ischemic and nonischemic cerebrovascular and cardiovascular disorders, neurological disorders, rheumatoid arthritis, or mental health conditions compared with influenza or sepsis cohorts. Conclusions and Relevance: In this cohort study, apart from an elevated risk of venous thromboembolism within 1 year, the burden of postacute medical and mental health conditions among those who survived hospitalization for COVID-19 was comparable with other acute infectious illnesses. This suggests that many of the postacute consequences of COVID-19 may be related to the severity of infectious illness necessitating hospitalization rather than being direct consequences of infection with SARS-CoV-2.

Association Between Diabetes and Mortality Among Adult Patients Hospitalized With COVID-19: A Cohort Study of Hospitalized Adults in Ontario, Canada, and Copenhagen, Denmark.

OBJECTIVES: Diabetes has been reported to be associated with an increased risk of death among patients with COVID-19. However, the available studies lack detail on COVID-19 illness severity and measurement of relevant comorbidities. METHODS: We conducted a multicentre, retrospective cohort study of patients 18 years of age and older who were hospitalized with COVID-19 between January 1, 2020, and November 30, 2020, in Ontario, Canada, and Copenhagen, Denmark. Chart abstraction emphasizing comorbidities and disease severity was performed by trained research personnel. The association between diabetes and death was measured using Poisson regression. The main outcome measure was in-hospital 30-day risk of death. RESULTS: Our study included 1,133 hospitalized patients with COVID-19 in Ontario and 305 in Denmark, of whom 405 and 75 patients, respectively, had pre-existing diabetes. In both Ontario and Denmark, patients with diabetes were more likely to be older; have chronic kidney disease, cardiovascular disease, and higher troponin levels; and be receiving antibiotics, when compared with adults without diabetes. In Ontario, 24% (n=96) of adults with diabetes died compared with 15% (n=109) of adults without diabetes. In Denmark, 16% (n=12) of adults with diabetes died in hospital compared with 13% (n=29) of those without diabetes. In Ontario, the crude mortality ratio among patients with diabetes was 1.60 (95% confidence interval [CI], 1.24 to 2.07) and in the adjusted regression model it was 1.19 (95% CI, 0.86 to 1.66). In Denmark, the crude mortality ratio among patients with diabetes was 1.27 (95% CI, 0.68 to 2.36) and in the adjusted model it was 0.87 (95% CI, 0.49 to 1.54). Meta-analysis of the 2 rate ratios from each region resulted in a crude mortality ratio of 1.55 (95% CI, 1.22 to 1.96) and an adjusted mortality ratio of 1.11 (95% CI, 0.84 to 1.47). CONCLUSION: The presence of diabetes was not strongly associated with in-hospital COVID-19 mortality independent of illness severity and other comorbidities.

Impact of presentation at conference with timed release of academic publication.

Fast-tracking publication of original research to coincide with a conference presentation ("coordinated publication") is a mechanism of rapidly disseminating new data. How often this occurs, whether its frequency is changing, and the impact of this approach on information dissemination, is unknown. Our objective was to describe the characteristics of coordinated publications, how the practice has changed over time, and evaluate its potential impact on dissemination of study results. We conducted a cross-sectional study of randomized controlled trials published in NEJM, Lancet, and JAMA between January 1, 2015, and December 31, 2019. Among the 1533 included randomized controlled trials, 502 (33%) had coordinated publications. Coordinated publications increased from 30% [n = 94] in 2015 to 37% [n = 136] in 2019. Coordinated publications were more likely to be unblinded (61% [n = 305] vs. 52% [n = 532]) and more likely to be funded by industry (50% [n = 249] vs. 30% [n = 311]). The strongest predictor of a coordinated publication was cardiovascular disease subspecialty (OR = 3.96, 95% CI [2.95, 5.36]). The median number of citations (188 vs. 98) and the median Altmetric score (318 vs. 182) were higher for coordinated publications than non-coordinated publications. These differences persisted in a multivariable regression model. Coordinated publication is increasingly common. While coordinated publications may generate greater attention, they were observed to be more likely to be unblinded and more likely to be funded by industry, raising questions about the value and intentions of such promotion.

Older Age is Associated With Lower Utilization of Living Donor Kidney Transplant.

Introduction: Older adults (65 years or older) constitute a substantial and increasing proportion of patients with kidney failure, potentially needing kidney replacement therapy. Living donor kidney transplant (LDKT) offers superior outcomes for suitable patients of all ages. However, exploring LDKT and finding a living donor could be challenging for older adults. Here, we assessed the association between age and utilization of LDKT and assessed effect modification of key variables such as ethnicity and language. Methods: This is a retrospective cohort study of patients with kidney failure referred for kidney transplant (KT) assessment in Toronto between January 2006 and December 2013. The association between age and having a potential living donor identified was assessed using logistic regression and the association between age and the receipt of LDKT was assessed using Cox proportional hazards models. Results: Of the 1617 participants, 50% were middle-aged (45-64 years old), and 17% were ≥65 years old. In our final multivariable adjusted models, compared to young adults, middle-aged and older adults had lower odds of having a potential living donor identified (odds ratio [OR], 0.47; confidence interval [CI], [0.35-0.63]; OR, 0.30; CI, [0.20-0.43]; P < 0.001, for middle-aged and older adults, respectively), and were less likely to receive LDKT (hazard ratio [HR], 0.79; CI, [0.63-0.99]; P = 0.04; HR, 0.47; CI, [0.30-0.72]; P = 0.001, for middle-aged and older adults, respectively.). Conclusion: Age is an independent predictor of receiving LDKT. Considering that nearly 90% of patients with kidney failure in Canada are >45 years of age, these results point to important and potentially modifiable age-related barriers to LDKT.

Osmotic Demyelination Syndrome in Patients Hospitalized with Hyponatremia.

BACKGROUND: Osmotic demyelination syndrome (ODS) is a rare but potentially devastating neurologic complication of hyponatremia. The primary objective of this study was to identify the proportion of patients who developed ODS in a large, contemporary, multicenter cohort of patients admitted to the hospital with hyponatremia. METHODS: We conducted a multicenter cohort study of patients admitted with hyponatremia at five academic hospitals in Toronto, Ontario, Canada, between April 1, 2010, and December 31, 2020. All adult patients presenting with hyponatremia (serum sodium level 8 mmol/l in any 24-hour period). RESULTS: Our cohort included 22,858 hospitalizations with hyponatremia. Approximately 50% were women, the average age was 68 years, and mean initial serum sodium was 125 mmol/l (standard deviation, 4.6), including 11.9% with serum sodium from 110 to 119 mmol/l and 1.2% with serum sodium less than 110 mmol/l. Overall, rapid correction of serum sodium occurred in 3632 (17.7%) admissions. Twelve patients developed ODS (0.05%). Seven (58%) patients who developed ODS did not have rapid correction of serum sodium. CONCLUSIONS: In this large multicenter study of patients with hyponatremia, rapid correction of serum sodium was common (n=3632 [17.7%]), but ODS was rare (n=12 [0.05%]). Future studies with a higher number of patients with ODS are needed to better understand potential causal factors for ODS.

Actigraphic detection of periodic limb movements: development and validation of a potential device-independent algorithm. A proof of concept study.

STUDY OBJECTIVES: We propose a unique device-independent approach to analyze long-term actigraphy signals that can accurately quantify the severity of periodic limb movements in sleep (PLMS). METHODS: We analyzed 6-8 hr of bilateral ankle actigraphy data for 166 consecutively consenting patients who simultaneously underwent routine clinical polysomnography. Using the proposed algorithm, we extracted 14 time and frequency features to identify PLMS. These features were then used to train a Naïve-Bayes learning tool which permitted classification of mild vs. severe PLMS (i.e. periodic limb movements [PLM] index less than vs. greater than 15 per hr), as well as classification for four PLM severities (i.e. PLM index < 15, between 15 and 29.9, between 30 and 49.9, and ≥50 movements per hour). RESULTS: Using the proposed signal analysis technique, coupled with a leave-one-out cross-validation method, we obtained a classification accuracy of 89.6%, a sensitivity of 87.9%, and a specificity of 94.1% when classifying a PLM index less than vs. greater than 15 per hr. For the multiclass classification for the four PLM severities, we obtained a classification accuracy of 85.8%, with a sensitivity of 97.6%, and a specificity of 84.8%. CONCLUSIONS: Our approach to analyzing long-term actigraphy data provides a method that can be used as a screening tool to detect PLMS using actigraphy devices from various manufacturers and will facilitate detection of PLMS in an ambulatory setting.

Integrated Signal Encoding and Analysis System for Actigraphy-based Long-term Monitoring of Periodic Limb Movements in Sleep.

There has been a boom in the development of wearable devices for wellness and healthcare applications. Numerous studies have been conducted on the utility of employing wearable devices for the long-term monitoring of biosignals. Despite their efficacy, the potential for practical implementation faces many hurdles such as memory usage, power consumption, denoising, and efficient data transmission. Of the many wearables being used, the actigraph has been a popular choice amongst experts for identifying motion abnormalities such as periodic leg movements (PLMs) in sleep and the activities of patients suffering from various medical illnesses. In this paper, we present an efficient pulse code modulation based, 3-bit, signal encoding technique, which when applied to long-term (6-8 hours), 16-bit sleep actigraphy signals, generates 3-bit encoded, accelerometry data with an average compression ratio of 92%, an average increase in the signal-to-noise (SNR) ratio by 20 dB and an average reduction of memory usage by 92%. The proposed technique also eliminates the need to apply filters for denoising, by retaining only characteristic signal information in the quantized version. The proposed technique, in general, could be applied to accelerometer-based wearables and has the potential to provide efficient memory and power usage in long-term monitoring applications.

A Modified Definition for Obstructive Sleep Apnea in Home Sleep Apnea Testing after Stroke or Transient Ischemic Attack.

BACKGROUND: Home sleep apnea testing (HSAT) underestimates obstructive sleep apnea (OSA) severity. Overnight oxygen desaturation has been shown to be a strong predictor of incident stroke, and may be helpful in determining which patients with lower apnea-hypopnea indices (AHIs) should be offered treatment. OBJECTIVES: To examine whether a modified definition for OSA that uses oxygen desaturation (i.e., AHI 5-14.9 per hour and lowest O2 desaturation ≤88%), as compared to an AHI ≥ 15 per hour, would impact: (1) changes in Epworth Sleepiness Scale scores post-continuous positive airway pressure (CPAP) initiation; (2) CPAP compliance rates; and (3) the accuracy of automated versus manual scoring of HSAT. METHODS: One hundred and six patients with a prior stroke or transient ischemic attack (TIA) underwent HSAT. Epworth Sleepiness Scale and CPAP compliance were measured at baseline and 3-6 months. RESULTS: Median age was 67.5 years, 57.5% male, and 76.4% presented with stroke. Fifty-nine patients were diagnosed with OSA; of these 54.2% met criteria for the "modified definition" for OSA (AHI 5-14.9 per hour with oxygen desaturation) and 45.8% met criteria for the "classic definition" for OSA (AHI ≥15). The modified (versus classic) definition had: (1) a greater decrease in ESS (P = .05) post-CPAP initiation; (2) comparable CPAP compliance rates; and (3) comparable automatically versus manually scored AHIs (Spearman's rho = .96, Cohen's Kappa ≥ .75 for both definitions, P < .001). CONCLUSIONS: Using a modified definition of OSA that uses a lower AHI cutoff and includes an oxygen desaturation cutoff in the setting of HSAT for stroke or transient ischemic attack (TIA) patients may improve daytime sleepiness post-CPAP initiation, while not significantly affecting CPAP compliance rates nor the accuracy of automated scoring.

Advanced signal analysis for the detection of periodic limb movements from bilateral ankle actigraphy.

Actigraphy can assist in the detection of periodic limb movements in sleep. Although several actigraphs have been previously reported to accurately detect periodic limb movements, many are no longer available; of the existing actigraphs, most sample too infrequently to accurately detect periodic limb movements. The purpose of this study was to use advanced signal analysis to validate a readily available actigraph that has the capability of sampling at relatively high frequencies. We simultaneously recorded polysomnography and bilateral ankle actigraphy in 96 consecutive patients presenting to our sleep laboratory. After pre-processing and conditioning, the bilateral ankle actigraphy signals were then analysed for 14 simple time, frequency and morphology-based features. These features reduced the signal dimensionality and aided in better representation of the periodic limb movement activity in the actigraph signals. These features were then processed by a Naïve-Bayes binary classifier for distinguishing between normal and abnormal periodic limb movement indices. We trained the Naïve-Bayes classifier using a training set, and subsequently tested its classification accuracy using a testing set. From our experiments, using a periodic limb movement index cut-off of 5, we found that the Naïve-Bayes classifier had a correct classification rate of 78.9%, with a sensitivity of 80.3% and a specificity of 73.7%. The algorithm developed in this study has the potential of facilitating identification of periodic limb movements across a wide spectrum of patient populations via the use of bilateral ankle actigraphy.