Effects of Occupational and Leisure-Time Physical Activity on the Risk of Dementia: Results From the Copenhagen City Heart Study.

Leisure-time physical activity (LTPA) decreases the risk of dementia, whereas occupational physical activity (OPA) possibly increases the risk. Yet, previous findings are mixed. We therefore aimed to investigate the effect of LTPA and OPA, respectively, on dementia among men and women. In this observational, longitudinal study, we used data from the second wave of a population-based cohort from the municipality of Copenhagen as baseline. Data were collected in 1981-1983, and 10 343 participants were followed until the end of 2016. LTPA and OPA were self-reported, and information on dementia diagnoses and redemption of dementia medication was obtained at an individual level from national health registers. We used Poisson regression to analyze the association between LTPA/OPA and dementia and adjusted for self-reported age, socioeconomic factors, stress, and cardiovascular risk factors (smoking, alcohol, body mass index, and blood pressure). A higher level of LTPA was associated with a lower dementia risk among men, but we found no clear association among women. OPA and dementia were not associated among men, but occupationally active women who reported OPA in terms of walking, lifting, and heavy work had a higher risk of dementia than women with sedentary jobs. This study supported earlier findings of a protective effect of LTPA on dementia among men. Women in physically demanding jobs possibly have a higher risk of dementia, yet this finding warrants further investigation in future studies.

The association between migraine and dementia - a national register-based matched cohort study.

OBJECTIVES: Migraine and dementia, two major public health challenges, are associated, but more knowledge is needed to understand their relationship. Objectives of this study were to investigate 1) the association between non-self-reported measures of migraine and dementia, and whether dementia was associated with 2) migraine without aura (MO) and with aura (MA) in combination with migraine medication use, and 3) migraine severity operationalized as the number of migraine prescriptions. STUDY DESIGN: Matched cohort study. METHODS: National register data were obtained from individuals born between 1934 and 1958. Migraine cases (aged 25-58 years) were identified by migraine diagnoses and redeemed migraine medication. Migraine cases were matched with non-cases (N = 340,850) and date of diagnosis or medication redemption was defined as index year. Dementia was identified by dementia diagnoses and redeemed dementia medication. RESULTS: We observed a 1.46 (95% CI: 1.26-1.69) times higher dementia rate in individuals with a migraine diagnosis and a 0.86 (95% CI: 0.76-0.97) times lower rate when using migraine medication. We found the highest dementia rate among individuals with MA, who also used migraine medication (HR = 2.23; 95% CI: 1.19-4.17), and the lowest rate among individuals with MO, who also used medication (HR = 1.25; 95% CI: 0.75-2.10). The number of migraine medication prescriptions was not associated with dementia. CONCLUSIONS: Being registered with a migraine diagnosis was associated with a higher dementia rate, while use of prescribed migraine medication was not. The differences in the dementia rate among migraine cases identified via diagnoses versus medications warrants further investigation.

Accuracy of CD64 expression on neutrophils and monocytes in bacterial infection diagnosis at pediatric intensive care admission.

The CD64 receptor has been described as an interesting bacterial infection biomarker. Its expression has not been studied in previously healthy children admitted to pediatric critical care unit (PICU). Our objective was firstly to describe the CD64 expression and secondly study its diagnostic accuracy to discriminate bacterial versus viral infection in this children. We made a prospective double-blind observational study (March 2016-February 2018). A flow cytometry (FC) was done from peripheral blood at PICU admission. We studied the percentage of CD64+ neutrophils and the CD64 mean fluorescence intensity (MFI) on neutrophils (nCD64) and monocytes (mCD64). Statistical analyses were performed with non-parametric tests (p < 0.05). Twenty children in the bacterial infection group (BIG) and 25 in the viral infection group (VIG). Children in BIG showed higher values of CD64+ neutrophils (p = 0.000), nCD64 (p = 0.001), and mCD64 (p = 0.003). In addition, CD64+ neutrophils and nCD64 expression have positive correlation with procalcitonin and C reactive protein. The nCD64 area under the curve (AUC) was 0.83 (p = 0.000). The %CD64+ neutrophils showed an AUC of 0.828 (p = 0.000). The mCD64 AUC was 0.83 (p = 0.003). The nCD64 and %CD64+ neutrophils also showed higher combined values of sensitivity (74%) and specificity (90%) than all classical biomarkers.In our series CD64 expression allows to discriminate between bacterial and viral infection at PICU admission. Future studies should confirm this and be focused in the study of CD64 correlation with clinical data and its utility as an evolution biomarker in critical care children.

Patient and health care professional perspectives on using telehealth to deliver pulmonary rehabilitation.

The objective of this study was to identify the necessary features of pulmonary telerehabilitation (P-TR) from the perspectives of individuals living with chronic lung disease and health care professionals (HCPs) who deliver pulmonary rehabilitation (PR). Focus groups were carried out with patients ( n = 26) and HCPs ( n = 26) to elicit and explore their opinions about the critical elements of in-person PR and ideas for how these elements could be supported using technology. A questionnaire was used to assess technology use, PR experience, and general health status. Four key elements of PR were identified as critical to P-TR: the social aspect of PR; communicating with HCPs for education and support; using biosensors for monitoring and promoting self-knowledge; and the evolution of support with progress over time. A range of technology-enabled devices and programs were suggested as means to recreate aspects of these integral elements. Consultations with patients and HCPs suggest that users are interested in technology and want to ensure it recreates the important aspects of PR. Patients and HCPs identified similar key elements for P-TR. The opinions and suggestions of patients and HCPs should be the driving force of innovation if P-TR is to succeed in improving health outcomes.

External ophthalmomyiasis: a case series.

Oestrus ovis or 'sheep botfly' causes common ophthalmomyiasis in warm climates. It is a self-limited infestation with symptoms such as foreign body sensation and/or tearing. The larvae can be observed in the conjunctiva and should be extracted with forceps. The development of larvae beyond the first stage does not occur in healthy humans, although they may penetrate the ocular globe, causing so-called internal myiasis. External ophthalmomyiasis is typical of rural areas, but it may be observed occasionally in urban environments.

Early prognostic factors for morbidity and mortality in severe traumatic brain injury. Experience in a child polytrauma unit.

OBJECTIVE: To identify early prognostic factors that lead to an increased risk of unfavorable prognosis. DESIGN: Observational cohort study from October 2002 to October 2017. SETTING AND PATIENTS: Patients with severe TBI admitted to intensive care were included. VARIABLES AND INTERVENTIONS: Epidemiological, clinical, analytical and therapeutic variables were collected. The functional capacity of the patient was assessed at 6 months using the Glasgow Outcome Scale (GOS). An unfavorable prognosis was considered a GOS less than or equal to 3. A univariate analysis was performed to compare the groups with good and bad prognosis and their relationship with the different variables. A multivariate analysis was performed to predict the patient's prognosis. RESULTS: 98 patients were included, 61.2% males, median age 6.4 years (IQR 2.49-11.23). 84.7% were treated by the out-of-hospital emergency services. At 6 months, 51% presented satisfactory recovery, 26.5% moderate sequelae, 6.1% severe sequelae, and 2% vegetative state. 14.3% died. Statistical significance was found between the score on the prehospital Glasgow coma scale, pupillary reactivity, arterial hypotension, hypoxia, certain analytical and radiological alterations, such as compression of the basal cisterns, with an unfavorable prognosis. The multivariate analysis showed that it is possible to make predictive models of the evolution of the patients. CONCLUSIONS: it is possible to identify prognostic factors of poor evolution in the first 24 h after trauma. Knowledge of them can help clinical decision-making as well as offer better information to families.

Early prognostic factors for morbidity and mortality in severe traumatic brain injury. Experience in a child polytrauma unit. / Factores pronósticos precoces de morbimortalidad en el traumatismo craneoencefálico grave en niños. Experiencia en una unidad de politraumatismo infantil.

OBJECTIVE: To identify early prognostic factors that lead to an increased risk of unfavorable prognosis. DESIGN: Observational cohort study from October 2002 to October 2017. SETTING AND PATIENTS: Patients with severe TBI admitted to intensive care were included. VARIABLES AND INTERVENTIONS: Epidemiological, clinical, analytical and therapeutic variables were collected. The functional capacity of the patient was assessed at 6 months using the Glasgow Outcome Scale (GOS). An unfavorable prognosis was considered a GOS ≤3. A univariate analysis was performed to compare the groups with good and bad prognosis and their relationship with the different variables. A multivariate analysis was performed to predict the patient's prognosis. RESULTS: A total of 98 patients were included, 61.2% males, median age 6.4years (IQR 2.49-11.23). 84.7% were treated by the out-of-hospital emergency services. At 6 months, 51% presented satisfactory recovery, 26.5% moderate sequelae, 6.1% severe sequelae, and 2% vegetative state. 14.3% died. Statistical significance was found between the score on the prehospital Glasgow coma scale, pupillary reactivity, arterial hypotension, hypoxia, certain analytical and radiological alterations, such as compression of the basal cisterns, with an unfavorable prognosis. The multivariate analysis showed that it is possible to make predictive models of the evolution of the patients. CONCLUSIONS: It is possible to identify prognostic factors of poor evolution in the first 24hours after trauma. Knowledge of them can help clinical decision-making as well as offer better information to families.

Respiratory and pharmacological management in severe acute bronchiolitis: Were clinical guidelines not written for critical care?

PURPOSE: The treatment applied for children admitted to the pediatric intensive care unit (PICU) for severe acute bronchiolitis may differ from general recommendations. The first objective of our study was to describe the treatments offered to these children in a Spanish tertiary PICU. The second objective was to analyse the changes in management derived from the publication of the American Academy of Pediatrics (AAP) bronchiolitis guideline in 2014. METHODS: This was a retrospective-prospective observational study conducted during two epidemic waves (2014-2015 and 2015-2016). The AAP guidelines were distributed and taught to PICU staff between both epidemic waves. RESULTS: A total of 138 children were enrolled (78 male). In the first period, 78 children were enrolled. The median age was 1.8 months (IQR 1.1-3.6). There were no differences between the management in the two periods, except for the use of high-flow oxygen therapy (HFOT); its use increased in the second period. Overall, 83% of patients received non-invasive ventilation or HFOT. Children older than 12 months received HFOT exclusively. In comparison, continuous positive airway pressure and bi-level positive airway pressure were used less during the period 2015-2016 (P=0.036). Regarding pharmacological therapy, 70% of patients received antibiotics, 23% steroids, 33% salbutamol, 31% adrenaline, and 7% hypertonic saline. The mortality rate was zero. CONCLUSIONS: Our PICU did not follow the AAP recommendations. There were no differences between the two periods, except in the use of HFOT. All children older than 12 months received HFOT exclusively. The rate of using invasive mechanical ventilation was also low.

Effects of lifestyle factors on concentrations of salivary cortisol in healthy individuals.

OBJECTIVE: Salivary cortisol is widely used in occupational health research. However, many ordinary daily activities can influence the concentrations of cortisol and the interpretation of field studies. The aim of the present study was to evaluate the effect of lifestyle factors on salivary cortisol in everyday settings. MATERIAL AND METHODS: Healthy employees participated in one or more sub-studies on the effect of eating a vegetable salad versus protein-rich mid-day meal (n = 40), drinking coffee and smoking (n = 12), drinking alcohol (n = 32), awakening at different times (n = 29) and exercising (n = 21). Cortisol in saliva was measured by radioimmunoassay (RIA). RESULTS: When eating a mid-day meal, salivary cortisol was increased by 10 % (CI -1 % to 24 %) 1 h after eating compared to before eating in the case of both types of meal. Salivary cortisol increased by 80 % (CI 9 % to 199 %) after exercising compared to before exercise. The relative awakening response was approximately 100 % when using an alarm clock on both work-days and days off. However, the awakening response was 39 % (CI 10 % to 75 %) on a day off with spontaneous awakening. No effects of alcohol, coffee or smoking were observed. DISCUSSION: In field studies, the biological variation in salivary cortisol may be reduced by restricting physical exercise and in collecting pre-meal samples. However, the protein content of food and moderate consumption of alcohol had no effect on concentrations of cortisol. Differences in relative awakening responses on work-days and days off are related to time and mode of awakening.

Airflow from nasal pulse oximetry in the screening of obstructive sleep apnea.

Obstructive Sleep Apnea (OSA) is recognized as an increasing health risk, leading to daytime sleepiness and various medical conditions, such as hypertension and heart failure. Polysomnography (PSG), the gold standard to diagnose OSA, is a resource-intensive and expensive investigation confined to the hospital.Portable home monitoring, i.e. pulse oximetry, may become an acceptable OSA screening method. The novel nasal pulse oximeter sensor (Xhale Alar) adds the possibility of combining pulse oximetry (SpO2) with airflow analysis by an integrated thermistor, which might increase the diagnostic accuracy.In the Alar pilot study, 39 adults were measured during an overnight PSG recording together with the Alar sensor. This study aims to investigate the additional value of an airflow signal compared to SpO2 analysis in OSA screening. Both time and spectral features were extracted from SpO2 and airflow signals recorded with the Alar sensor. Leave one out cross-validation was used to develop Random Forest models in screening for apnea-hypopnea index (AHI) thresholds 5 and 10. Using both AHI ≥ 5 and AHI ≥ 10 as the diagnostic cutoff, the airflow signal shows respectively an AUC of 89% and 80% compared to 78% and 77% with SpO2 analysis, showing a higher performance using an airflow signal in screening adults for OSA.

A smartphone oximeter with a fingertip probe for use during exercise training: usability, validity and reliability in individuals with chronic lung disease and healthy controls.

BACKGROUND AND AIM: Telehealth is a strategy to expand the reach of pulmonary rehabilitation (PR). Smartphones can monitor and transmit oxygen saturation (SpO2) and heart rate (HR) data to ensure patient safety during home-based or other exercise. The purpose of this study was to evaluate the usability, validity and reliability of a Kenek O2 pulse oximeter and custom prototype smartphone application (smartphone oximeter) during rest and exercise in healthy participants and those with chronic lung disease. METHODS: Fifteen individuals with chronic lung disease and 15 healthy controls were recruited. SpO2 and HR were evaluated at rest and during cycling and walking. SpO2 was valid if the mean bias was within +±2%, the level of agreement (LoA) was within ±4%; HR was valid if the mean bias was within ±5 beats per min (bpm), LoA was within ±10bpm. Usability was assessed with a questionnaire and direct observation. RESULTS: The smartphone oximeter was deemed easy to use. At rest, SpO2 measures were valid in both groups (bias <2%, lower bound LoA -2 to 3%). During exercise, SpO2 measurement did not meet validity and reliability thresholds in the patients with chronic lung disease, but was accurate for the healthy controls. HR recording during exercise or rest was not valid (LoA>10bpm) in either group. CONCLUSIONS: The smartphone oximeter did not record HR or SpO2 accurately in patients with chronic lung disease during exercise, although SpO2 was valid at rest. During exercise, patients with chronic lung disease should pause to ensure greatest accuracy of SpO2 and HR measurement.

Time-varying signal analysis to detect high-altitude periodic breathing in climbers ascending to extreme altitude.

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30-120 min in duration, high values of mean power (MP(VE)) and slope (MSlope(VE)) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89%, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MP(VE)) and cardiac (MP(LF)(HR) ) oscillations and cardiorespiratory coherence (MP(LF)(Coher)), but reduced ventilation entropy (SampEn(VE)), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.

An easy microtiter assay for quantitation of cytokine induction by lipopolysaccharide (LPS) and activity of LPS-binding serum components.

Lipopolysaccharide (LPS, endotoxin) is a major inducer of cytokines, such as interleukin 1 (IL1), IL6, IL8 and tumor necrosis factor (TNF). A convenient microtiter assay was developed to measure such activity. LPS coated onto a plastic surface was used to stimulate purified human mononuclear cells (MNC) in microtiter plates. Following stimulation the supernatants were assayed for presence of TNF by ELISA. Purified rough and smooth LPS from Pseudomonas aeruginosa gave a dose-dependent TNF release over a range of 0.1-1.0 microgram LPS/well. The assay was subsequently used to investigate the biological activity of anti-LPS antibodies and other LPS-specific serum components in sera from patients with cystic fibrosis (CF). As a group, sera from 10 CF patients chronically infected with P. aeruginosa did not affect the LPS-induced TNF release, while sera from normal controls inhibited this biological activity. When individual CF patients with or without chronic lung infection are considered, the antibodies appear to either enhance or inhibit the LPS-stimulated TNF release (range: 73-120%), while all antibodies from healthy controls inhibit the activity of LPS (range: 76-97%). Only a weak correlation (rho = 0.491, p = 0.037, n = 19) was found between the antibody titer in ELISA and the biological activity of sera. This new assay is suggested for convenient measurement of interference with cytokine induction from human MNC by patient or therapeutic anti-LPS antibodies and other LPS-specific serum components.

Seasonal and biological variation of urinary epinephrine, norepinephrine, and cortisol in healthy women.

BACKGROUND: There is a significant circadian and seasonal periodicity in various endocrine functions. The present study describes the within-day and seasonal fluctuation for urinary catecholamines and cortisol and estimates the within- (CV(i)) and between-subject (CV(g)) coefficients of variation for healthy women undertaking their routine work. In addition, index of individuality (I(i)) and power calculations were derived. METHODS: Eleven healthy females undertaking their routine life-style at work participated in the study. Each subject collected six samples during 24 h 15 days over a year, giving a total number of 990 samples. Using a random effect analysis of variance, we estimated CV(g) and total within-subject variation (CV(ti)), i.e. combined within-subject and analytical variation, from logarithmically transformed data. Analytical variation was subtracted from CV(ti) to give CV(i). CV(i) was estimated from samples collected monthly during 1 year (CV(iy)), weekly during 1 month (CV(im)), and six to eight times/day (CV(id)). RESULTS: A seasonal variation was demonstrated for excretion of epinephrine, norepinephrine, and cortisol standardized with creatinine. Concentrations of urinary epinephrine were higher during June and July compared to the rest of the year, whereas concentrations of urinary cortisol were higher during December and January compared to the rest of the year. Excretion of norepinephrine was lower during working hours and higher during hours off work for June and July compared to the rest of the year. There was a high within- and between-subject variation, which could not be explained by menstrual cycle, behavioral, emotional, or cognitive stress reactions. CONCLUSIONS: Despite high biological variation a reasonably low sample size, e.g. 10-50 individuals, is adequate for practical applicability, i.e. studying differences above 150%. The present study recommends to include the sampling time in the statistical evaluation of data and to be aware of the changes in diurnal variations over seasons. When single measurements are to be evaluated, reference intervals are recommended.

Reference interval and subject variation in excretion of urinary metabolites of nicotine from non-smoking healthy subjects in Denmark.

BACKGROUND: Passive smoking has been found to be a respiratory health hazard in humans. The present study describes the calculation of a reference interval for urinary nicotine metabolites calculated as cotinine equivalents on the basis of 72 non-smokers exposed to tobacco smoke less than 25% of the day. METHODS: Twenty subjects (passive smokers) exposed to tobacco smoke more than 25% of the day (subjectively assessed) and 32 smokers were used to validate the estimated reference interval. Urine samples were collected three times during the day approximately at 06.30, 17.00 and 22.45 h. RESULTS: Within-subject variation was found to be 89.4, 72.6, and 79.2% and between-subject variation was found to be 64.5, 64.2, and 36.1%. No gender difference could be demonstrated. In general all subjects showed increased concentrations in the afternoon and evening samples compared to the morning samples. Parametric reference interval for excretion of nicotine metabolites in urine from non-smokers was established according to International Union of Pure and Applied Chemistry (IUPAC) and International Federation for Clinical Chemistry (IFCC) for use of risk assessment of exposure to tobacco smoke. The reference interval for urinary cotinine was estimated to be 1.1-90.0 micromol/mol creatinine in morning samples from non-smokers. An intercomparison between the radioimmunoassay (RIA) method used for determination of nicotine metabolites and a gas chromatography-mass spectrometry (GC-MS) method for determination of cotinine was carried out on 27 samples from non-smokers and smokers. Results obtained from the RIA method showed 2.84 [confidence interval (CI): 2.50; 3.18] times higher results compared to the GC-MS method. A linear correlation between the two methods was demonstrated (rho=0.96). CONCLUSION: The RIA method is rapid and adequate for clinical use in the assessment of exposure to tobacco smoke, i.e. ratio between CV(a)/CV(ti) was<0.50.

Physiological responses to four hours of low-level repetitive work.

OBJECTIVES: The study investigated physiological responses to 4 hours of standardized low-level repetitive work. It was hypothesized that accumulative effects not observed after 1 hour could be found after 4 hours of repetitive work. METHODS: Ten healthy women performed intermittent (5 seconds + 5 seconds) handgrip contractions at 10% of the maximal voluntary contraction combined with mental demands for concentration and attention. Muscle activity in the working forearm muscles, cardiovascular responses, and concentrations of biomarkers in biological fluids were recorded along with exerted force, performance, and ratings of perceived physical exertion (RPE), and perceived mental exertion. RESULTS: The urinary epinephrine, norepinephrine, and cortisol concentrations were higher during the repetitive task than on a reference day, but only the norepinephrine concentrations increased progressively during the 4 hours. In accordance, the RPE recorded for the hand, forearm, and shoulder regions increased progressively. For the remaining physiological measures, no accumulative changes were found. Forearm muscle activity was higher during a mental reference task with lower exerted force than during the repetitive task. The variation in exerted force was higher during the repetitive task than during a force reference task without mental demands. CONCLUSIONS: The urinary biomarkers were increased during the repetitive task. However, only norepinephrine increased progressively during the 4 hours. Forearm muscle activity during a mental reference task with low exerted force indicated attention-related muscle activity. Finally, it was indicated that repetitive work including high demands for attention is performed at the expense of the precision of the exerted force.