Individual Baseline Data Research Articles

Machine learning application: A kind of prostate disease early warning model

Prostate Diseases pose significant health risks, and the author has developed an integrated machine learning model using a medical indicator dataset of prostate patients. The article introduces seven different machine learning algorithms for classification tasks. The approach involved detailed exploratory data analysis, descriptive statistics, feature engineering, and data visualization. Additionally, data preprocessing was performed by addressing missing values and eliminating non-numeric characters. During the model training process, cross-validation techniques are employed to determine the optimal model parameters, ensuring the accuracy of the training. Furthermore, the training performance of the seven models is assessed through histograms and ROC curves. Based on their performance, three models are selected for ensemble modeling, aiming to further enhance training accuracy and improve precision. Conclusively, the findings indicate that the likelihood of prostate diseases correlates significantly with the medical indicator generated through feature engineering, specifically PSA (free)/PSA (Total), aligning with clinical guidelines for diagnosing prostate diseases. Furthermore, individual baseline data indicators such as body weight have a crucial impact on the likelihood of prostate disease, with obesity serving as a significant risk factor. Among the individual models, the k-Nearest Neighbors (KNN) model achieved the highest accuracy, while the ensemble model further improved accuracy. In summary, the work effectively alerts individuals to the potential occurrence of prostate cancer and hyperplasia by evaluating medical indicators. Ultimately, this initiative aims to raise awareness of maintaining good health and reducing the risk of prostate diseases.

[Translated article] Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation

IntroductionThe incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. MethodsREGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. ResultsA total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. ConclusionsThe distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento

IntroductionThe incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. MethodsREGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. ResultsA total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. ConclusionsThe distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

The Finnegan Score for Neonatal Opioid Withdrawal Revisited With Routine Electronic Data: Retrospective Study.

The severity of neonatal abstinence syndrome (NAS) may be assessed with the Finnegan score (FS). Since the FS is laborious and subjective, alternative ways of assessment may improve quality of care. In this pilot study, we examined associations between the FS and routine monitoring data obtained from the electronic health record system. The study included 205 neonates with NAS after intrauterine (n=23) or postnatal opioid exposure (n=182). Routine monitoring data were analyzed at 60±10 minutes (t-1) and 120±10 minutes (t-2) before each FS assessment. Within each time period, the mean for each variable was calculated. Readings were also normalized to individual baseline data for each patient and parameter. Mixed effects models were used to assess the effect of different variables. Plots of vital parameters against the FS showed heavily scattered data. When controlling for several variables, the best-performing mixed effects model displayed significant effects of individual baseline-controlled mean heart rate (estimate 0.04, 95% CI 0.02-0.07) and arterial blood pressure (estimate 0.05, 95% CI 0.01-0.08) at t-1 with a goodness of fit (R2m) of 0.11. Routine electronic data can be extracted and analyzed for their correlation with FS data. Mixed effects models show small but significant effects after normalizing vital parameters to individual baselines.

A Comparison of Normalization Techniques for Individual Baseline-Free Estimation of Absolute Hypovolemic Status Using a Porcine Model.

Hypovolemic shock is one of the leading causes of death in the military. The current methods of assessing hypovolemia in field settings rely on a clinician assessment of vital signs, which is an unreliable assessment of hypovolemia severity. These methods often detect hypovolemia when interventional methods are ineffective. Therefore, there is a need to develop real-time sensing methods for the early detection of hypovolemia. Previously, our group developed a random-forest model that successfully estimated absolute blood-volume status (ABVS) from noninvasive wearable sensor data for a porcine model (n = 6). However, this model required normalizing ABVS data using individual baseline data, which may not be present in crisis situations where a wearable sensor might be placed on a patient by the attending clinician. We address this barrier by examining seven individual baseline-free normalization techniques. Using a feature-specific global mean from the ABVS and an external dataset for normalization demonstrated similar performance metrics compared to no normalization (normalization: R2 = 0.82 ± 0.025|0.80 ± 0.032, AUC = 0.86 ± 5.5 × 10-3|0.86 ± 0.013, RMSE = 28.30 ± 0.63%|27.68 ± 0.80%; no normalization: R2 = 0.81 ± 0.045, AUC = 0.86 ± 8.9 × 10-3, RMSE = 28.89 ± 0.84%). This demonstrates that normalization may not be required and develops a foundation for individual baseline-free ABVS prediction.

Generalizability of clinical trial efficacy results to a real-world population: An example in migraine prevention.

Health care decision makers are often concerned about the external validity of randomized controlled trials (RCTs), as their results may not apply to certain patients in the real world who intend to receive treatment. To demonstrate a methodology for assessing the generalizability of clinical trial results to a real-world population, before sufficient and appropriate real-world effectiveness data are available, using individual patient-level data from an RCT and aggregated baseline data from a real-world French registry in migraine. The analyses were conducted in 2 steps. First, individual patient-level baseline data from the multinational CONQUER RCT were weighted to match aggregated real-world InovPain registry patient characteristic data. Matched patient characteristics were sex, age, migraine type and duration, number of monthly migraine headache days, and number of monthly headache days at baseline. Second, the weighted CONQUER patient data were used to reanalyze the primary endpoint of CONQUER (least squares mean change from baseline in the number of monthly migraine headache days during the 3-month double-blind treatment phase) using predefined methodology. Sensitivity analyses were conducted to assess the robustness of findings. A total of 462 patients with migraine were randomized and treated with galcanezumab or placebo in CONQUER; aggregated InovPain data were available from 130 patients with migraine. We identified no important differences in baseline patient characteristics between the 2 prespecified populations, suggesting good external validity for CONQUER. Although this limited the extent of observed differences between the original and matched CONQUER populations, weighting of CONQUER data did help harmonize the 2 datasets and allow the results obtained in CONQUER to be generalized to patients more representative of the real-world French population with migraine. Results of weighted analyses suggested that galcanezumab would be superior to placebo for reducing monthly migraine headache days in a clinical trial in patients with episodic or chronic migraine who reflected the characteristics of patients eligible to receive the drug in France. Findings suggest that our methods may be helpful for assessing the generalizability of clinical trial results to a real-world population before the availability of substantial real-world clinical data.

Confirmation of Sgr A* Using the Event Horizon Telescope Data as Extreme Binary of the Supermassive Black Holes Concluded by Decameter Radio Wave Pulse Observations

We analyzed the time variation of the visibilities in the publicly released event horizon telescope (EHT) data provided by the EHT Collaboration, who carried out observations of Sgr A* on April 6 and 7, 2017. The EHT consists of the 1.3 mm wavelength very long baseline interferometry (VLBI) system associated with globally distributed six stations with eight antennas. The analyses were not intended to make image of Sgr A*; instead, we searched for periodic time variations in the observed individual baseline data of the EHT by applying a method to compare with the model visibility, for 1.3 mm VLBI detection that was constructed to reflect the effects of the supermassive black hole binary (SMBHB) concluded from the study on the observation of the decameter radio wave pulses from Sgr A*. The SMBHB, orbiting with a period of 2200 ± 50 sec and an orbit size of 4.1×107 km, is observable with an observation angle width of 32.6 μas in a plane nearly parallel to the Galactic equatorial plane. After confirming the possible correspondence between the visibilities of EHT data and constructed model via direct comparison in real-time space, we applied the modified Fourier transformation to confirm the coincidence between observation data and model visibilities. The modified Fourier transformation was uniquely restructured in this paper to eliminate the artificially modulated data sampling time interval by utilizing Fourier transformation of the random noises distributed over time synchronized with data sample timing of the EHT data. We identified significant periodic time variations in the radiation within a range below 70 μas with an orbiting period of 2193.3±27.5 sec that is associated with an eclipse cycle period of 1096.5 sec caused by the SMBHB orbiting motion.

Predicted impact of atrial flow regulator on survival in heart failure with reduced and preserved ejection fraction.

We aim to assess the theoretical impact of the atrial flow regulator (AFR) on survival in heart failure. The prospective, multicentre, open-label, non-randomised PRELIEVE study (NCT03030274) assessed the safety and efficacy of the Occlutech AFR device in patients with symptomatic heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction (LVEF)≥15% and <40%) or heart failure with preserved ejection fraction (HFpEF) (LVEF ≥40% and <70%) and elevated PCWP (≥15mmHg at rest or ≥25mmHg during exercise). In this analysis, after the first 60 patients completed 12months of follow-up, the theoretical impact of AFR implantation on survival was assessed by comparing the observed mortality rate with the median predicted probability for one-year mortality. Each subject's risk of mortality was predicted from individual baseline data using the Meta-Analysis Global Group in Chronic HF (MAGGIC) prognostic model. A total of 87 patients (46% female, median age 69years [IQR 62-74]) had undergone successful device implantation for the treatment of HFrEF (53%) and HFpEF (47%). Sixty patients had a complete 12month follow-up. The median follow-up was 351days (interquartile range [IQR] 202-370). Six (7%) patients died during follow-up (8.6 deaths per 100 patient-years; 95% confidence interval [CI] 2.7 to 15.5), all of which had HFrEF. The median predicted mortality rate for the overall study population was 12.2 deaths per 100 patient-years (95% CI 10.2 to 14.7). While the observed mortality rate (0 deaths per 100 patient-years) was significantly lower than the median predicted mortality rate (9.3 deaths per 100 patient-years; 95% CI 8.4 to 11.1) in patients with HFpEF (-9.3 deaths per 100 patient-years; 95% CI -11.1 to -8.4), there was no difference in patients with HFrEF (-3.6 deaths per 100 patient-years; 95% CI -9.5 to 3.0). Four deaths were HF-related deaths (5.7 HF-related deaths per 100 patient-years; 95% CI 1.4 to 11.9; 10.8 HF-related deaths per 100 patient-years; 95% CI 2.5 to 23.1 in the HFrEF subgroup). In patients with HFpEF, the mortality rate following AFR implantation was lower than the predicted mortality rate. Dedicated randomised, controlled trials are needed - and currently ongoing - to investigate whether the AFR improves mortality.

Where Is the Geography? A Study of the Predictors of Obesity Using UK Biobank Data and Machine Learning

In this study, we adopted individual baseline data from the UK Biobank cohort of participants aged 40–69 across the UK to explore whether there is evidence of the geography related to health disparities in obesity. First, we used multilevel models to decompose the variation in body mass index (BMI) values to examine the presence of spatial clustering patterns of individual BMI values at various geographic scales. Next, we looked at whether key predictors of obesity, such as physical activities and dietary habits, differ across 6 cities in England by using a machine learning approach. To do this, we trained random forest models in one city, and we used them to predict BMI values in other cities to see if the models were spatially transferable. Subsequently, we turned to explore socio-economic status, which is one of the direct interests in the literature with obesity and used those in combination with multilevel models to check for the existence of spatially varying effects. The results of the multilevel null models indicate that most of the variance of BMI is due to individual variation, suggesting little evidence of geographical clustering at any geographical scales. The machine learning prediction results show that the effects of the main identified risk factors for obesity are stable (spatially stationary) across cities, based on approximately the same predictive power and broadly constant effect sizes of main factors. Multilevel models taking socio-economic status into account further support that individual and neighbourhood deprivation levels display limited geographical variation in their effects on obesity across the study areas. Contrary to our expectations, the models together suggest the limited association of geographical context with obesity, among the UK Biobank participants.

Impact of atrial flow regulator implantation on survival in patients with heart failure with reduced and preserved ejection fraction: a post-hoc analysis of the PRELIEVE study

Abstract Purpose This analysis aims to assess the theoretical impact of atrial flow regulator implantation on mortality by comparing the observed survival rate with the median predicted probability for one-year survival. Methods The prospective, multicentre, open-label, non-randomised PRELIEVE study assessed the safety and efficacy of the atrial flow regulator in patients with symptomatic HFrEF (left ventricular ejection fraction (LVEF) ≥15% and &amp;lt;40%) or HFpEF (LVEF ≥40% and &amp;lt;70%) and elevated PCWP (≥15mmHg at rest or ≥25mmHg during exercise). In this analysis, after the first 60 patients completed twelve months of follow-up, the theoretical impact of atrial flow regulator implantation on survival was assessed by comparing the observed mortality rate with the median predicted probability for one-year mortality. Each subject's risk of mortality was predicted from individual baseline data using the Meta-Analysis Global Group in Chronic HF (MAGGIC) prognostic model. Results A total of 87 patients had undergone successful device implantation for the treatment of HFrEF (53%) and HFpEF (47%). Sixty patients had a complete twelve-month follow-up. The median follow-up was 351 days (interquartile range [IQR] 202–370). A total of six (7%) patients died during follow-up (8.6 deaths per 100 patient-years; 95% confidence interval [CI] 2.7 to 15.5), all of which had HFrEF. The median predicted mortality rate for the overall study population was 12.2 deaths per 100 patient-years (95% CI 10.2 to 14.7). While the observed mortality rate (0 deaths per 100 patient-years) was significantly lower than the median predicted mortality rate (9.3 deaths per 100 patient-years; 95% CI 8.4 to 11.1) in patients with HFpEF (−9.3 deaths per 100 patient-years; 95% CI −11.1 to −8.4), there was no difference in patients with HFrEF (−3.6 deaths per 100 patient-years; 95% CI −9.5 to 3.0) (Figure 1). Four deaths were HF-related deaths (5.7 HF-related deaths per 100 patient-years; 95% CI 1.4 to 11.9; 10.8 HF-related deaths per 100 patient-years; 95% CI 2.5 to 23.1 in the HFrEF subgroup). Conclusion In patients with HFpEF, the mortality rate following atrial flow regulator implantation was lower than the predicted mortality rate. These findings need to be confirmed by larger randomised, controlled trials. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Occlutech International AB

A concentration-QTc analysis of vericiguat

Abstract Introduction Vericiguat is a soluble guanylate cyclase stimulator developed for the treatment of symptomatic chronic heart failure (HF) in patients with ejection fraction less than 45% who had a previous decompensation event. A dedicated, randomised, Phase Ib, QT study of vericiguat (NCT03504982) in 74 adult patients with stable coronary artery disease demonstrated no clinically significant prolongation of the time-matched, placebo-adjusted change from baseline in the Fridericia-corrected QT interval (QTcF) after vericiguat 10 mg once daily at steady state. Purpose We conducted a concentration–QTc (C-QTc) modelling analysis, on data from the QT study, to investigate the potential effect of vericiguat on QTcF and define the vericiguat plasma concentration window within which a relevant prolongation in QTcF can be excluded. Methods In the QT study, the effect of vericiguat once daily (2.5 mg titrated to 5 mg and then to 10 mg [treatments A, B, C] over 42±9 days) on the QT interval was investigated. The positive control was a single dose of moxifloxacin 400 mg (treatment D) on Day 8 or Day 50 (7 days before the first vericiguat dose or 7 days after the last vericiguat dose), depending on the treatment sequence (Figure 1). Baseline electrocardiogram assessments were performed 24 h before the start of treatment (“baseline”) and at follow-up (“back-up baseline”; Figure 1). Time-matched, baseline- and placebo-adjusted QTcF (ΔΔQTc) mean values and 90% confidence intervals (CIs) were calculated. Two analytical approaches were used to calculate ΔΔQTc. The first one (“single baseline ΔΔQTc” approach) was data-driven, where ΔΔQTc was adjusted with placebo- and either “baseline” or “back-up baseline”. The second one (“modelled baseline ΔΔQTc”) accounted for individual baseline and placebo effects, such as diurnal time course, used linear mixed effects and integrated all individual baseline and placebo data. Calculated ΔΔQTc values were then related to observed vericiguat concentrations in the C-QTc modelling step, performed with linear mixed effects implemented in R (R, the R Foundation for Statistical Computing, version 3.2.5). Results The C-QTc modelling of ΔΔQTc calculated with the “single baseline ΔΔQTc” approach indicated a positive, but non-significant, slope (Figure 2A). The “modelled baseline ΔΔQTc” approach indicated a positive and statistically significant slope (Figure 2B). In both cases, the upper limits of the 90% CI were below the threshold of clinical relevance of 10 ms within the investigated exposure range (up to 745 μg/l). Conclusion Based on the presented analysis, a clinically meaningful QT prolongation was robustly excluded within the plasma concentration range associated with the recommended target dose of vericiguat 10 mg. The C-QTc analysis supports the conclusion of the primary study statistical analysis that administration of vericiguat between 2.5 and 10 mg is not associated with a clinically meaningful QTc prolongation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Funding was provided by Bayer AG, Berlin, Germany and Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA Figure 1Figure 2

Tuberculosis recurrence over a 7-year follow-up period in successfully treated patients in a routine program setting in China: a prospective longitudinal study

To determine tuberculosis (TB) recurrence in previously successfully treated patients in a routine program setting and baseline characteristics associated with TB recurrence. A prospective longitudinal study in Jiangxi Province, China. Patients, ≥14 years old, were consecutively registered and were followed up for seven years to assess TB recurrence against a patients' individual baseline data that had been entered into a database at TB registration. There were 800 TB patients registered at baseline, and 634 (79.2%) of them completed anti-TB treatments. Fifty-nine (9.3%) died, and 21 (3.3%) were lost to follow-up over the follow-up period. There were 96 patients with recurrent episodes (total incidence 15.2% or annual incidence 2,200/100,000). Of the recurrent cases, 53 (55.2%) happened within 2-year after completion of anti-TB treatments. After controlling confounding factors, the risk of TB recurrence was significantly higher in the age range 34-73 years (P<0.01) and current smokers (P<0.01). Overall recurrence rate among previously treated TB patients was much higher than the initial incidence in the same population (61-98/100,000) and settings with similar TB incidence. TB programs should consider closer monitoring of these patients for early detection of recurrence. Particular attention should be given to those between 34-73 years and those who use tobacco products.

Interpreting Clinical Reaction Time Change and Recovery After Concussion: A Baseline Versus Norm-Based Cutoff Score Comparison.

Preseason testing can be time intensive and cost prohibitive. Therefore, using normative data for postconcussion interpretation in lieu of preseason testing is desirable. To establish the recovery trajectory for clinical reaction time (RTclin) and assess the usefulness of changes from baseline (comparison of postconcussion scores with individual baseline scores) and norm-based cutoff scores (comparison of postconcussion scores with a normative mean) for identifying impairments postconcussion. Case-control study. Multisite clinical setting. An overlapping sample of 99 participants (age = 19.0 ± 1.1 years) evaluated within 6 hours postconcussion, 176 participants (age = 18.9 ± 1.1 years) evaluated at 24 to 48 hours postconcussion, and 214 participants (age = 18.9 ± 1.1 years) evaluated once they were cleared to begin a return-to-play progression were included. Participants with concussion were compared with 942 control participants (age = 19.0 ± 1.0 years) who did not sustain a concussion during the study period but completed preseason baseline testing at 2 points separated by 1 year (years 1 and 2). At each time point, follow-up RTclin (ie, postconcussion or year 2) was compared with the individual year 1 preseason baseline RTclin and normative baseline data (ie, sex and sport specific). Receiver operating characteristic curves were calculated to compare the sensitivity and specificity of RTclin change from baseline and norm-based cutoff scores. Clinical reaction time performance declined within 6 hours (18 milliseconds, 9.2% slower than baseline). The decline persisted at 24 to 48 hours (15 milliseconds, 7.6% slower than baseline), but performance recovered by the time of return-to-play initiation. Within 6 hours, a change from baseline of 16 milliseconds maximized combined sensitivity (52%) and specificity (79%, area under the curve [AUC] = 0.702), whereas a norm-based cutoff score of 19 milliseconds maximized combined sensitivity (46%) and specificity (86%, AUC = 0.700). At 24 to 48 hours, a change from baseline of 2 milliseconds maximized combined sensitivity (64%) and specificity (61%, AUC = 0.666), whereas a norm-based cutoff score of 0 milliseconds maximized combined sensitivity (63%) and specificity (62%, AUC = 0.647). Norm-based cutoff scores can be used for interpreting RTclin scores postconcussion in collegiate athletes when individual baseline data are not available, although low sensitivity and specificity limit the use of RTclin as a stand-alone test.

Clinical Reaction Time After Concussion: Change From Baseline Versus Normative-Based Cutoff Scores.

Pre-season testing is often used to establish baseline scores for post-concussion interpretation. However, pre-season testing can be time-intensive and cost-prohibitive, in which case normative data may be used for post-injury interpretation. To compare change from baseline and normative-based cutoff scores in interpreting clinical reaction time (RTclin) following concussion. Prospective case-control study. Multi-site study with testing completed in university athletic training rooms. An overlapping sample of 99 participants (age=19.0±1.1 years) evaluated within 6 hours post injury, 176 participants (age 18.9±1.1 years) evaluated 24-48 hours post injury, and 214 participants (18.9±1.1 years) evaluated at the time they were cleared to begin a return-to-play progression. Concussion participants were compared to 942 control participants (age=19.0±1.0 years) who did not sustain a concussion during the study period but completed preseason baseline testing one year apart. At each time point, follow-up RTclin (i.e., post injury or year 2) was compared to individualized year 1 preseason baseline RTclin and to normative baseline data (i.e., sex- and sport-specific). Receiver operating characteristic curves were used to compare sensitivity and specificity of RTclin change from baseline and normative-based cutoff scores. Within 6h, change from baseline of 16ms maximized combined sensitivity (52%) and specificity (78%, AUC=0.702), while normative-based cutoff scores of 19ms maximized combined sensitivity (45%) and specificity (86%, AUC=0.700). At 24-48h, change from baseline of 2ms maximized combined sensitivity (64%) and specificity (61%, AUC=0.666), while normative-based cutoff scores of 0ms maximized combined sensitivity (63%) and specificity (62%, AUC=0.647). Normative-based cutoff scores can be used for interpreting RTclin scores following concussion when individualized baseline data is not available, although low sensitivity and specificity may limit clinical use as a stand-alone test.

Sensitivity and specificity of EEG biomarkers of AD at the preclinical stage

AbstractBackgroundCognitive reserve (CR) is present in Alzheimer’s disease (AD) seniors with high education attainment making them clinically resilient to extended brain neuropathology and neurodegeneration. Here we tested whether subjective memory complaint (SMC) seniors with AD neuropathology and high education attainment may present abnormal eyes‐closed resting state posterior electroencephalographic (rsEEG) rhythms around individual alpha frequency peak (IAFp), typically altered in AD patients with mild cognitive impairment and dementia.MethodWe selected all individual baseline data of the prospective INSIGHT‐preAD cohort (Paris) including mini mental state examination score ≥ 28, artifact‐free markers of 18F‐florbetapir positron emission tomography (amyPET), structural magnetic resonance imaging, and rsEEG rhythms (e.g., 172 SMC seniors). Delta, theta, alpha1, alpha2, and alpha3 bands were determined on individual basis based on IAFp, while beta1 (14‐20 Hz), beta2 (20‐30 Hz), and gamma (30‐40 Hz) were standard fixed bands.ResultThe SMC participants negative to amyPET AD markers (SMCneg) with high (over low‐moderate) education level showed higher posterior alpha 2 power density (possibly “neuroprotective”). Furthermore, amyPET‐positive SMC (SMCpos) participants with high (over low‐moderate) education level showed higher temporal alpha 3 power density (possibly “neuroprotective”) and lower posterior alpha 2 power density (possibly “compensatory”; Figure 1). This effect may reflect CR as no differences in brain gray‐white matter and cognitive functions were observed between these SMCpos/SMCneg sub‐groups.ConclusionPreclinical Alzheimer’s neuropathology may interact with education attainment and neurophysiological mechanisms generating cortical alpha rhythms around IAFp (i.e., alpha 2 and 3) in quiet wakefulness.

Predicting Subjective Recovery from Lower Limb Surgery Using Consumer Wearables

Introduction: A major challenge in the monitoring of rehabilitation is the lack of long-term individual baseline data which would enable accurate and objective assessment of functional recovery. Consumer-grade wearable devices enable the tracking of individual everyday functioning prior to illness or other medical events which necessitate the monitoring of recovery trajectories. Methods: For 1,324 individuals who underwent surgery on a lower limb, we collected their Fitbit device data of steps, heart rate, and sleep from 26 weeks before to 26 weeks after the self-reported surgery date. We identified subgroups of individuals who self-reported surgeries for bone fracture repair (n = 355), tendon or ligament repair/reconstruction (n = 773), and knee or hip joint replacement (n = 196). We used linear mixed models to estimate the average effect of time relative to surgery on daily activity measurements while adjusting for gender, age, and the participant-specific activity baseline. We used a sub-cohort of 127 individuals with dense wearable data who underwent tendon/ligament surgery and employed XGBoost to predict the self-reported recovery time. Results: The 1,324 study individuals were all US residents, predominantly female (84%), white or Caucasian (85%), and young to middle-aged (mean age 36.2 years). We showed that 12 weeks pre- and 26 weeks post-surgery trajectories of daily behavioral measurements (steps sum, heart rate, sleep efficiency score) can capture activity changes relative to an individual’s baseline. We demonstrated that the trajectories differ across surgery types, recapitulate the documented effect of age on functional recovery, and highlight differences in relative activity change across self-reported recovery time groups. Finally, using a sub-cohort of 127 individuals, we showed that long-term recovery can be accurately predicted, on an individual level, only 1 month after surgery (AUROC 0.734, AUPRC 0.8). Furthermore, we showed that predictions are most accurate when long-term, individual baseline data are available. Discussion: Leveraging long-term, passively collected wearable data promises to enable relative assessment of individual recovery and is a first step towards data-driven intervention for individuals.

The Ability of Baseline and Normative Neurocognitive Testing to Identify Cognitive Impairments Following Concussion: A Critically Appraised Topic

Focused Clinical Question: In a high school, college, and professional athletic population, does individualized baseline tests increase the diagnostic accuracy (e.g., sensitivity and specificity) of identifying cognitive impairments when utilizing neurocognitive testing compared to normative data? Clinical Bottom Line: There was insufficient evidence to definitively suggest the use of individualized baseline data over the use of normative data during a postinjury assessment.

Concussion History’s Impact On Instrumented Bess Scores In Division I Contact-Sport Athletes

PURPOSE: The purpose of this study was to determine if concussion history has an impact on sway velocity. A concussion injury can disrupt proper functioning of the vestibular system, and chronic disruption of this system can increase the chances of subsequent musculoskeletal or concussive injury. Athletes with a history of concussion injury who present with balance deficits, should be targeted for interventions to decrease the risk of sustaining a musculoskeletal or concussive injury. METHODS: 175 healthy Division I football & men’s lacrosse players (age = 19.8 ± 1.2; ht = 71.9 ± 2.2”; wt = 202.1 ± 33.9 lbs) participated in this study. Players were provided with a brief, 1-on-1, concussion discussion and then answered the questions “have you ever sustained a concussion? If yes, how many?”. All players underwent a balance assessment as part of their preseason screening and were medically cleared to participate in sports. Players performed the BESS test (double leg, single leg, & tandem) on firm & foam surfaces while standing on the VSR SportTM force plate by NeuroCom®. RESULTS: No difference was found between those with and without a previous concussion injury on any of the instrumented BESS stances (Table 1). To further analyze the data, a Spearman Rho correlation determined there was a smaller than typical correlation between number of concussions sustained and sway velocity measurements; double leg firm (rs = 0.02), single leg firm (rs = 0.09), tandem firm (rs = 0.08), double leg foam (rs = 0.01), single leg foam (rs = 0.01), tandem foam (rs = 0.02), & composite (rs = 0.06). CONCLUSION: Concussion history does not appear to have an impact on sway velocity measurements in contact sport athletes. The vestibulospinal system may be resilient to long-term deficits associated with concussion injury. In the absence of individualized baseline data, normative data may be used to determine balance deficits in those with a suspected concussion, regardless of previous concussion history.

Hyperhydration using different hydration agents does not affect the haematological markers of the athlete biological passport in euhydrated volunteers

ABSTRACT Athlete Biological Passport (ABP) is an indirect approach, implemented by WADA, aimed at detecting blood manipulation based on abnormal changes in haematological markers. Cases report the use of hyperhydration as masking method during anti-doping urine sample collection which could potentially mask suspicious fluctuations on ABP profiles. This study investigated the hyperhydration effect on haemoglobin concentration, reticulocyte percentage and OFF-hr score (an algorithm based on haemoglobin concentration and reticulocyte percentage), with and without recombinant human erythropoietin (rHuEPO) administration. A five-week clinical study performed; Baseline and rHuEPO Phase. Water and a sports drink were used as hyperhydration agents. To examine the hyperhydration effect on the normal ABP profile per volunteer, hyperhydration was implemented at 0, 24 and 48 hours during the baseline. During the rHuEPO phase, volunteers received Epoetin beta (3000 IU) with hyperhydration to be implemented at 0, 24 and 48 hours after drug administration. Blood and urine samples were collected and analysed according to WADA guidelines. No significant effect on ABP markers was observed due to hyperhydration at any time during the study. Pre- and post-hyperhydration data were not statistically different compared to individual baseline data. In conclusion, hyperhydration does not affect the ABP haematological markers under the examined conditions.

Unfavourable treatment outcomes in tuberculosis patients with different vitamin D status and blood glucose levels in a programme setting in China.

Tuberculosis (TB) treatment success rates are high in China, but there are still a considerable number of cases who have unfavourable treatment outcomes (UTO). We aimed to determine the proportion of TB patients with UTO and to assess whether baseline characteristics that included glycaemic status [normal fasting blood glucose (FBG), transient hyperglycaemia and diabetes mellitus (DM)] and vitamin D status were associated with UTO. Prospective cohort study conducted between November 2015 and July 2016 at six clinics within routine TB services in Jilin province, where persons with TB were consecutively recruited. Data analysis was performed using the chi-squared test and multivariate logistic regression. Of the306 recruited TB patients, 96 (31.4%) had smear-positive pulmonary TB, 187 (61.1%) had smear-negative pulmonary TB and 23 (7.5%) had extrapulmonary TB (EPTB). Of these, 95 (31.1%) had normal blood glucose, 83 (27.1%) had transient hyperglycaemia and 128 (41.8%) had DM. 227 (74.2%) patients had vitamin D deficiency/severe deficiency. There were 125 (40.8%) patients with UTO of whom the majority were lost to follow-up (57.6%) or not evaluated (28.8%). UTO was significantly associated with smear-negative pulmonary TB (P=0.009), EPTB (P<0.001) and DM (P=0.007). The proportion of TB patients with UTO increased with smear-negative pulmonary TB, EPTB and DM. TB programmes need to pay more attention to these issues and ensure intensive patient support to those at risk and early detection of DM.