ISCEV standard for clinical pattern electroretinography -- 2007 update The pattern electroretinogram -LRB- PERG -RRB- is a retinal response evoked by viewing a temporally alternating pattern , usually a black and white checkerboard or grating . The PERG is important in clinical and research applications because it provides information both about retinal ganglion cell function and , because the stimulus is customarily viewed with central fixation , the function of the macula . The PERG can therefore facilitate interpretation of an abnormal pattern VEP by revealing the retinal responses to a similar stimulus to that used for the VEP . However , practitioners may have difficulty choosing between the different techniques for recording the PERG that have been described in the literature . The International Society for Clinical Electrophysiology of Vision published a standard for clinical PERG recording in 2000 to assist practitioners in obtaining good quality reliable responses and to facilitate inter-laboratory communication and comparison . This document is the scheduled revision of that standard . Introduction The pattern electroretinogram -LRB- PERG -RRB- is a retinal biopotential evoked when a temporally modulated patterned stimulus -LRB- checkerboard or grating -RRB- of constant mean luminance is viewed . The PERG is most often evoked by alternating contrast-reversal of a black and white square checkerboard pattern with central fixation . It may be altered in dysfunction confined to the macula or to the retinal ganglion cells , which do not significantly affect the a - and b-waves of the conventional full-field ERG , and thus the PERG receives clinical and research attention in both neurological and ophthalmological practice . Clinically , the PERG can be used in a patient with an abnormal visual evoked potential to establish whether a retinal -LRB- macular -RRB- disorder is present , and thus differentiate between macular and optic nerve dysfunction as a cause for the VEP abnormality . It can also directly demonstrate retinal ganglion cell dysfunction . However , the PERG is a very small signal , typically in the region of 2 -- 8 μV across a normal population , and PERG recording is technically more demanding than standard flash ERGs . The amplitude values recorded will depend upon stimulus characteristics and the electrodes being used . The recordings published in the literature vary considerably in technique and technical quality ; this document is intended to guide new or existing users to the most appropriate techniques for recording a standard clinical PERG . The International Society for Clinical Electrophysiology of Vision -LRB- ISCEV -RRB- initially published `` PERG Guidelines '' -LSB- 1 -RSB- , intended as a guide to practice and to assist in interpretation of PERGs . Those guidelines were subsequently revised to a PERG standard -LSB- 2 -RSB- and the present document is the scheduled revision of that standard . The standard PERG represents a minimum protocol for recording a PERG with straightforward technical procedures that should allow reproducible responses to be recorded under defined conditions . As a minimum , it is intended that the standard method and responses be widely used , but in addition to rather than to the exclusion of other paradigms . Common additional PERG techniques are also briefly described in this document , and individual laboratories are encouraged to use additional stimuli and protocols tailored to their own requirements . The standard is based upon equipment and analytic capabilities currently available in most neurophysiological or ophthalmological electrodiagnostic clinics . This document addresses recording conditions and technology specific to the PERG , and presumes that the reader already has basic understanding and skills in clinical electrophysiology . Although much of the document will apply equally to adults and children , the standard is not necessarily appropriate to paediatric applications . The standard will be reviewed by ISCEV in a further four years . Waveform nomenclature and measurement The waveform of the PERG evoked by pattern-reversal stimuli depends on the temporal frequency of the stimulus . By convention , positivity is displayed upward . Transient PERG The ISCEV standard PERG is a transient response i.e. a response that is effectively complete before the next contrast reversal . Transient recording allows separation of the PERG components . At low temporal frequencies -LRB- < 6 reversals per second -LRB- rev/s -RRB- ; equivalent to < 3 Hz -RRB- transient PERGs are obtained -LRB- Fig. 1 -RRB- . The PERG waveform in normal subjects usually consists of a small initial negative component with a peak time of approximately 35 ms , N35 , which is followed at 45 -- 60 ms by a much larger positive component -LRB- P50 -RRB- . This positive component is followed by a larger negative component at 90 -- 100 ms -LRB- N95 -RRB- . Fig. 1A normal PERG . The amplitude of P50 in a normal subject is usually between 2.0 and 4.0 μV For the transient PERG , amplitude measurements are made between peaks and troughs : the P50 amplitude is measured from the trough of N35 to the peak of P50 . In some patients the N35 is poorly defined ; in these cases N35 is replaced by the average baseline between time zero and the onset of P50 . The N95 amplitude is measured from the peak of P50 to the trough of N95 . It should be recognised that measured in this way , N95 amplitude includes the P50 amplitude and P50 that of N35 . It can be argued that baseline to peak measurements may be more meaningful . However , the P50 and N95 components may not be independent . At the time of writing there are no peer-reviewed data attempting to resolve these issues , and given the wealth of data already published using peak-to-peak measures , they remain the standard measures for PERG amplitudes . The times to peaks in the waveform -LRB- implicit time -RRB- should be measured from the onset of the contrast-reversal to the peak of the component concerned ; it should be noted that the highest absolute amplitude point on a waveform will not always be appropriate for the definition of the peak if there is contamination from muscle activity or other artifacts . The peak should be designated where it would appear on a smoothed or idealised waveform -LRB- see Fig. 1 -RRB- . The peak times or implicit times are often -LRB- erroneously -RRB- referred to as latencies . Correctly , latency refers to the delay prior to the onset of a response , not to the maximum activity of a peak . Basic technology Standard equipment for visual stimulus generation , amplification of physiological signals , and the recording and storing of electrophysiological data , is required for PERG testing . Information about the calibration of equipment and measurement of the parameters specified in this standard appears in the ISCEV Calibration Guidelines -LSB- 3 -RSB- . Electrodes Recording electrodes Clinical ERG electrodes that contact the cornea or nearby bulbar conjunctiva should be used as the active electrodes to record standard PERGs . Electrodes that degrade image quality on the retina -LRB- this includes all contact lens electrodes -RRB- must not be used . Thin conductive fibres and foils can usually be positioned without topical anaesthesia . Electrode integrity should be checked prior to insertion , to meet guidelines for each electrode type . It is recommended not to measure impedance in situ unless explicitly specified by the particular equipment manufacturer . Electrodes should be carefully positioned to minimise instability -LRB- a major source of artifact or interference -RRB- . Those who perform the test should be aware of possible causes of artifact.Fibre electrodes are best positioned in relation to the upper margin of the lower eyelid . Some place the electrode in the lower conjunctival fornix -LRB- under the lower eyelid -RRB- ; such a position may reduce trial-to-trial variability but will also result in a lower amplitude PERG . Optimum stability is achieved by tethering the electrode at the nasal canthus.Foil electrodes should be positioned directly under the centre of the pupil so that there is minimal or no movement of the electrode when the patient blinks . This is best achieved by having the foil curve over the lower eyelashes without contacting them , and then tethering the lead to the cheek . The junction of the electrode and lead should form as straight a line as possible and the junction should not touch the skin.Loop electrodes should be hooked into the lower fornix . Loops should be folded so that the contact windows on otherwise insulated wire are positioned on the bulbar conjunctiva , about 5 mm under the limbus . Loop electrodes should not touch the cornea . To achieve this , the limbs of the loop should diverge widely -LRB- 15 -- 20 mm -RRB- before entering the fornix . The lead is then taped to the cheek . The appropriate techniques for individual electrode types are very important to achieve stable and reproducible PERG recordings . Additional sources should be consulted in relation to the specific electrode used . Surface -LRB- skin -RRB- active electrodes should not routinely be used for recording the standard PERG ; a surface electrode positioned on the lower eyelid will record PERGs of lower amplitude than those recorded from an electrode in contact with the eye . Surface electrode recordings may however be useful when a corneal electrode is contraindicated or in paediatric practice . The use of a surface electrode to record the PERG is a variation from the standard and should be noted in the report . Reference electrodes Separate surface reference electrodes should be placed on the skin near the ipsilateral outer canthus of each eye . Mastoid , earlobe or forehead locations may result in contamination of the PERG from cortical potentials or the fellow eye . If monocular PERG recording is performed , the electrode in the occluded eye may be used as a reference . Ground electrodes A separate surface electrode should be attached and connected to the amplifier `` ground input '' ; the forehead would be a typical location , but other locations are acceptable as the location of the ground electrode should not affect the standard PERG . Surface electrodes The skin should be prepared with a suitable cleaning agent , and a suitable conductive paste used to ensure good electrical connection . The impedance between the skin electrodes used for reference and ground , measured on the subject , should be less than 5 kΩ . Since the electrode in the eye will have very low impedance , a low impedance of the reference electrode is also important to obtain recordings as free as possible from mains -LRB- line frequency -RRB- interference . Electrode cleaning and sterilisation Electrodes should be cleaned and sterilised according to local health and safety regulations . The ISCEV Standard for full-field flash ERGs describes the appropriate care of ERG electrodes -LSB- 4 -RSB- . Stimulus parameters This standard specifies the protocol for basic clinical PERG recording . Laboratories may choose to test more conditions or parameters than are described herein . Field and check size A black and white reversing checkerboard should be used for the standard PERG . It is not necessary to use a square stimulus field , but the aspect ratio between the width and the height of the stimulus field should not exceed 4:3 . The mean of the width and the height of the stimulus field should be 15 ° -LRB- ± 3 ° -RRB- with a check size of 0.8 ° -LRB- ± 0.16 ° -RRB- . Luminance PERGs are difficult to record with low stimulus luminance , and a photopic luminance level for the white areas of greater than 80 cd · m − 2 is required . The mean luminance of the stimulus screen must be constant during checkerboard reversals -LRB- i.e. no transient luminance change -RRB- . Contrast The contrast between black and white squares should be maximal -LRB- close to 100 % -RRB- for the standard PERG and not less than 80 % . The contrast and luminance used should be reported . Frame rate Raster-based CRTs are typically used to present the pattern stimuli . The frame rate of the CRT is a significant stimulus parameter for PERGs , and a frequency of 75 Hz or greater should be used . Background illumination The luminance of the background beyond the checkerboard field is not critical when using the standard PERG technique providing dim or ordinary room lighting is used ; ambient lighting should be the same for all recordings . Care should be taken to keep bright lights out of the subjects ' direct view . Pupil diameter should be recorded . Reversal rate The standard transient PERG should be obtained using a reversal rate of 4 rev/s ± 0.8 rev/s -LRB- i.e. 2 Hz ± 0.4 Hz -RRB- . Calibration All stimulus parameters including luminance and contrast should be calibrated either locally or by the manufacturer and regular recalibration is advised -LSB- 3 -RSB- . Recording equipment Amplification systems AC-coupled amplifiers with a minimum input impedance of 10 MΩ should be used . Amplification systems must be electrically isolated from the patient according to the current safety standards for medical recording systems . The frequency response of bandpass amplifiers should include the range from 1 -- 100 Hz ; analogue notch filters -LRB- that suppress signals at the alternating current line frequency -RRB- should not be used . Some users may encounter severe electromagnetic interference from the stimulus display that makes it difficult to obtain satisfactory recordings with these filter settings . Ideally , such interference should be eliminated by shielding or modifying the equipment ; rearranging the electrode leads may be of benefit . Averaging and signal analysis Signal averaging is necessary because of the small amplitude of the PERG . The analysis period -LRB- sweep time -RRB- for the standard PERGs should be 150 ms or greater . Some laboratories assess baseline stability by displaying two successive responses on the same trace . Artefact rejection Computerised artifact rejection is essential . The limits for rejection should be set at no higher than ± 50 μV , and preferably lower . The amplifiers must return to baseline rapidly following artifactual signals to avoid inadvertent storage of non-physiological data . Sampling rate A minimum sampling rate of 1,000 Hz -LRB- 1 ms per point -RRB- is recommended . See the calibration standard -LRB- 3 -RRB- for further information . Data display systems Display systems must have adequate resolution to represent accurately the characteristics of this small amplitude signal . Ideally the recording system provides simultaneous display of the input signal and the accumulating average . In the absence of a simultaneous display , the system should allow a rapid alternation between displaying the input signal and displaying the current average so that the quality of the input signal can be adequately monitored . Even with a computerised artifact rejection system , it is important that the input signal be continuously monitored for baseline stability and the absence of amplifier blocking . Clinical protocol Preparation of the patient Positioning The patient should be as comfortable as possible with their head in a stable position against a head-rest . A chin rest is inappropriate and should not be used . Pupils The PERG should be recorded without dilatation of the pupils , to preserve accommodation and thus retinal image quality . Fixation A fixation mark in the centre of the screen at a node of the checkerboard is essential . If there are any doubts about the quality of fixation in an individual patient , an effective method is to give the patient a -LRB- laser -RRB- pointer and have them point at the middle of the screen throughout . Excessive blinking during recording should be discouraged , pauses may be advantageous . Refraction Because of the nature of the stimulus , PERG examination should be performed with optimal visual acuity at the testing distance . Patients should wear the appropriate optical correction for the test distance . Monocular and binocular recording Proper positioning of recording and reference electrodes will permit either monocular or binocular recording of the PERG . Binocular recording is recommended for the standard PERG because it is generally more stable , it reduces examination time and it allows fixation by the better eye in cases of asymmetric visual loss . Monocular stimulation is required to record the PERG and the VEP simultaneously . Recording A minimum of 100 artefact-free sweeps should be collected and averaged for a standard PERG . More sweeps , perhaps as many as 300 , will be needed when the PERG is small or undetectable or in a `` noisy '' subject . At least two trials for each stimulus condition should be obtained to confirm reproducibility -LRB- i.e. at least one replication -RRB- . It may be beneficial to superimpose repeated PERG recordings to evaluate quality and reproducibility . PERG reporting Reporting It is recommended that all reports contain measurements of P50 and N95 amplitude -LRB- see above -RRB- , and P50 peak time -LRB- the peak of N95 is often rather broad precluding accurate peak time measurement of this component -RRB- . All reports should also contain the stimulus parameters -LRB- luminance , contrast , and field size -RRB- , and normal ranges for the laboratory concerned . Pupil size should be noted . Whenever practical , reporting of PERG results should include representative waveforms with appropriate amplitude and time calibrations , marks for the N35 , P50 and N95 components , and should show replications . Normative data/reference ranges At present there are no standard international reference ranges for PERG measurements . Each laboratory should establish normal values for its own equipment and patient population . It should be noted that there are PERG changes with age . Additional tests Large field PERGs For some applications , such as glaucoma assessment , a larger field , such as 30 ° , may be more appropriate . Further , some practitioners find the improved signal-to-noise ratio obtained with a larger field may have advantages ; users may wish to consider recording a large field PERG in addition to the standard response . Steady-state PERG At higher temporal frequencies , i.e. above 10 rev/s -LRB- 5 Hz -RRB- , the successive waveforms overlap and a `` steady-state '' PERG is evoked . There are situations in which the steady-state PERG is useful and some laboratories favour it for glaucoma studies . Since little extra time is required , laboratories may wish to consider recording it in addition to the transient response . For steady-state PERG , a reversal rate of approximately 16 rev/s -LRB- 8 Hz -RRB- is recommended . The steady-state PERG waveform is roughly sinusoidal , and interpretation of steady-state PERGs requires measurement of amplitude and phase shift -LRB- relative to the stimulus -RRB- of the second harmonic by Fourier analysis . The presence of a significant first harmonic indicates technical problems . For correct interpretation the analysis period must be an integer number of stimulus cycles , preferably greater than 6 . Steady-state PERG recording without the capability for such analysis is not recommended . Reporting of steady-state PERGs should include the amplitude and phase shift of the PERG at the reversal rate -LRB- i.e. at the second harmonic of the stimulus rate in Hz -RRB- .

O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

clinical electrophysiology
electroretinogram
retina
macula


Increasing

overall

physical

activity

and

aerobic

fitness

is

associated

with

improvements

in

metabolic

risk

cohort

analysis

of

the

ProActive

trial

Aims/hypothesis

Our

aim

was

to

examine

the

association

between

change

in

physical

activity

energy

expenditure

-LRB-

PAEE

-RRB-

total

body

movement

-LRB-

counts

per

day

-RRB-

and

aerobic

fitness

-LRB-

maximum

oxygen

consumption

-LSB-

-RSB-

-RRB-

over

year

and

metabolic

risk

among

individuals

with

a

family

history

of

diabetes

Introduction

The

metabolic

syndrome

has

been

defined

as

a

cluster

of

closely

related

cardiovascular

risk

factors

including

visceral

obesity

insulin

resistance

hyperglycaemia

hypertension

hypertriacylglycerolaemia

and

low

HDL-cholesterol

-LSB-

-RSB-

The

combination

of

these

risk

factors

has

been

shown

to

predict

type

diabetes

cardiovascular

disease

and

all-cause

mortality

-LSB-

-RSB-

with

physical

inactivity

identified

as

a

major

underlying

risk

factor

Given

the

rising

prevalence

of

obesity

and

type

diabetes

the

metabolic

syndrome

represents

a

potentially

large

public

health

burden

-LSB-

-RSB-

Previous

research

has

shown

that

low

levels

of

physical

activity

are

associated

with

the

metabolic

syndrome

-LSB-

-RSB-

and

that

objectively

measured

physical

activity

energy

expenditure

-LRB-

PAEE

-RRB-

predicts

progression

towards

the

metabolic

syndrome

independently

of

obesity

-LSB-

-RSB-

with

some

evidence

of

interaction

by

cardiorespiratory

fitness

-LSB-

-RSB-

Additionally

lifestyle

interventions

targeting

physical

activity

as

a

modifiable

risk

factor

have

shown

positive

effects

upon

various

metabolic

components

-LSB-

-RSB-

However

physical

activity

remains

poorly

measured

in

most

epidemiological

studies

with

many

relying

on

self-reporting

-LSB-

-RSB-

Furthermore

it

is

unclear

whether

metabolic

risk

is

most

effectively

reduced

by

increases

in

overall

energy

expenditure

-LRB-

EE

-RRB-

fitness

or

total

body

movement

A

better

understanding

of

these

relationships

would

inform

the

development

and

targeting

of

individual

and

population-based

interventions

to

reduce

risk

of

diabetes

and

related

metabolic

disorders

The

ProActive

-LRB-

UK

-RRB-

trial

is

an

explanatory

trial

of

a

theory-based

intervention

to

promote

physical

activity

among

individuals

reporting

low

levels

of

activity

and

who

are

at

increased

risk

of

the

consequences

of

a

sedentary

lifestyle

due

to

their

family

history

of

type

diabetes

The

main

trial

results

are

presented

elsewhere

-LSB-

-RSB-

We

recently

observed

a

cross-sectional

association

between

total

body

movement

and

clustered

metabolic

risk

in

this

cohort

-LSB-

-RSB-

and

are

now

extending

these

observations

to

examine

the

association

between

change

in

objectively

measured

PAEE

-LRB-

measured

by

individually

calibrated

heart

rate

-LSB-

HR

-RSB-

monitoring

-RRB-

physical

activity

-LRB-

total

body

movement

measured

by

accelerometry

-RRB-

and

aerobic

fitness

and

clustered

metabolic

risk

in

the

ProActive

trial

cohort

over

a

period

of

year

Methods

The

ProActive

trial

Full

details

of

the

study

have

been

reported

elsewhere

-LSB-

-RSB-

In

brief

ProActive

aimed

to

evaluate

the

efficacy

of

a

theoretical

evidence

and

family-based

intervention

programme

to

increase

physical

activity

among

individuals

defined

as

high-risk

through

having

a

parental

history

of

type

diabetes

Potential

participants

were

identified

via

diabetes

registers

and

medical

records

of

family

history

in

general

practices

in

the

East

Anglia

region

of

the

UK

Three

hundred

and

sixty-five

individuals

aged

years

and

reporting

low

levels

of

activity

were

randomly

assigned

to

one

of

three

interventions

brief

written

advice

-LRB-

control

group

-RRB-

or

a

behavioural-change

programme

at

two

levels

of

intensity

delivered

either

by

telephone

-LRB-

distance

-RRB-

or

face-to-face

in

the

family

home

The

theory-based

intervention

programme

-LSB-

-RSB-

was

delivered

by

trained

facilitators

and

aimed

to

support

increases

in

physical

activity

through

the

introduction

and

facilitation

of

a

range

of

self-regulatory

skills

Main

trial

results

indicated

no

significant

difference

in

the

year

change

in

objectively

measured

daytime

physical

activity

expressed

as

a

ratio

to

resting

EE

between

the

three

trial

arms

-LSB-

-RSB-

Consequently

the

three

trial

arms

were

pooled

and

a

cohort

analysis

conducted

Complete

data

on

PAEE

aerobic

fitness

anthropometry

and

biochemistry

were

available

in

participants

at

baseline

and

participants

at

follow-up

in

addition

to

socio-demographic

information

Total

body

movement

measured

by

accelerometry

was

also

assessed

in

a

subsample

of

participants

-LRB-

n

-RRB-

at

baseline

and

follow-up

and

the

data

were

included

in

these

analyses

The

measure

of

socioeconomic

status

-LRB-

SES

-RRB-

was

based

on

age

at

finishing

full-time

education

-LRB-

above

or

below

years

-RRB-

Ethics

approval

was

obtained

from

the

Eastern

England

Multi-centre

Research

Committee

-LRB-

MREC

-RRB-

and

all

participants

gave

written

informed

consent

Anthropometric

and

metabolic

tests

Participants

attended

the

study

centre

after

an

overnight

fast

and

a

sample

of

venous

blood

was

taken

Fasting

plasma

glucose

serum

insulin

levels

and

lipid

profiles

-LRB-

cholesterol

triacylglycerol

HDL

and

LDL-cholesterol

-RRB-

were

measured

using

the

hexokinase

method

and

standard

enzymatic

methods

as

described

previously

-LSB-

-RSB-

Weight

was

measured

on

standard

calibrated

scales

and

height

was

measured

using

a

rigid

stadiometer

BMI

was

calculated

as

weight

-LRB-

kg

-RRB-

divided

by

height

-LRB-

m

-RRB-

squared

Waist

circumference

-LRB-

cm

-RRB-

was

measured

over

light

indoor

clothing

as

the

mid-point

between

the

lower

costal

margin

and

the

level

of

the

anterior

superior

iliac

crests

Body

fat

percentage

was

measured

by

bio-electrical

impedance

-LRB-

Bodystat

Isle

of

Man

UK

-RRB-

and

systolic

and

diastolic

blood

pressures

were

measured

using

an

automated

Accutorr

sphygmomanometer

-LRB-

Accutorr

Cambridge

UK

-RRB-

Assessment

of

aerobic

fitness

PAEE

and

total

body

movement

Aerobic

fitness

-LRB-

maximum

oxygen

consumption

-LSB-

-RSB-

-RRB-

was

predicted

as

oxygen

uptake

at

maximal

HR

-LRB-

minus

age

-LSB-

years

-RSB-

-RRB-

by

extrapolation

of

the

regression

line

established

during

the

individual

calibration

for

the

relationship

between

oxygen

consumption

and

HR

during

a

submaximal

graded

treadmill

exercise

test

uptake

and

production

was

measured

continuously

by

indirect

calorimetry

throughout

the

test

-LRB-

Vista

XT

metabolic

system

Vacumed

Ventura

CA

USA

-RRB-

Resting

EE

-LRB-

REE

-RRB-

was

calculated

by

the

Weir

formula

-LSB-

-RSB-

using

and

measurements

obtained

in

the

fasting

state

after

approximately

min

of

supine

rest

using

the

same

indirect

calorimetry

system

as

previously

described

PAEE

was

measured

using

the

flex

HR

method

-LSB-

-RSB-

Flex

HR

was

calculated

as

the

mean

of

the

highest

resting

HR

and

the

lowest

HR

while

exercising

This

point

was

used

in

the

analysis

of

free-living

minute-by-minute

HR

data

to

discriminate

between

rest

and

exercise

Below

the

flex

HR

point

EE

was

assumed

to

be

equivalent

to

REE

EE

above

the

flex

point

was

predicted

from

the

individual

HR

EE

regression

line

Participants

wore

HR

monitors

-LRB-

Polar

Electro

Kemple

Finland

-RRB-

continuously

during

the

waking

hours

over

the

following

days

PAEE

was

calculated

by

subtracting

REE

from

the

estimated

average

daily

EE

and

thereafter

averaged

over

the

day

period

PAEE

is

body

size

dependent

e.g.

it

requires

more

energy

to

move

a

heavier

body

Similarly

aerobic

fitness

is

highly

correlated

with

body

size

or

mass

e.g.

larger

individuals

have

a

higher

absolute

aerobic

capacity

Therefore

body

size

is

a

confounding

factor

that

needs

to

be

normalised

for

when

analysing

associations

between

EE

variables

and

metabolic

outcomes

-LSB-

-RSB-

As

such

both

baseline

and

follow-up

measures

of

aerobic

fitness

and

PAEE

were

expressed

relative

to

fat-free

mass

-LRB-

FFM

kJ

kg

FFM

min

-RRB-

to

adjust

for

between-individual

differences

in

body

size

-LSB-

-RSB-

Free-living

total

body

movement

was

assessed

with

an

MTI

Actigraph

-LRB-

formerly

known

as

the

CSA

activity

monitor

-RRB-

model

-LRB-

Manufacturing

Technology

Fort

Walton

Beach

FL

USA

-RRB-

The

accelerometer

was

worn

over

the

same

day

period

as

the

HR

monitor

Participants

who

did

not

manage

to

record

at

least

min/day

of

activity

for

at

least

days

were

excluded

from

analyses

A

customised

program

was

used

for

data

reduction

and

further

analyses

-LRB-

MAHUffe

-RRB-

The

outcome

variable

derived

from

accelerometry

presented

in

this

study

is

total

body

movement

-LRB-

counts

per

day

-RRB-

adjusted

for

monitored

time

which

is

an

indicator

of

the

overall

level

of

physical

activity

Calculation

of

the

metabolic

syndrome

z

score

A

summary

score

of

clustered

metabolic

risk

based

on

WHO

criteria

-LSB-

-RSB-

was

calculated

by

summing

standardised

values

for

waist

circumference

triacylglycerol

fasting

insulin

and

glucose

systolic

blood

pressure

and

the

inverse

of

HDL-cholesterol

-LSB-

-RSB-

Variables

were

standardised

by

subtracting

the

sample

mean

from

the

individual

mean

and

dividing

by

the

SD

Baseline

and

follow-up

z

scores

were

computed

with

the

same

transformation

e.g.

using

the

mean

and

SD

of

baseline

values

This

continuously

distributed

metabolic

risk

variable

-LRB-

zMS

-RRB-

was

also

calculated

without

the

adiposity

component

-LRB-

i.e.

waist

circumference

zMS-ob

-RRB-

This

clustered

metabolic

risk

score

increases

statistical

power

as

variables

were

not

dichotomised

and

includes

a

continuous

measure

of

glycaemia

-LRB-

unlike

some

other

measures

of

vascular

risk

-LSB-

-RSB-

-RRB-

Additionally

the

International

Diabetes

Federation

criteria

were

used

to

define

metabolic

syndrome

as

a

dichotomous

variable

-LSB-

-RSB-

This

score

predicts

hard

clinical

endpoints

-LSB-

-RSB-

Statistical

analyses

Descriptive

summary

statistics

were

calculated

separately

for

men

and

women

using

means

and

SDs

at

baseline

and

follow-up

t

tests

were

used

to

examine

whether

there

were

any

differences

in

baseline

characteristics

between

those

with

and

without

follow-up

data

as

well

as

those

with

missing

accelerometer

data

Fasting

insulin

and

triacylglycerol

values

were

log

transformed

-LRB-

ln

-RRB-

due

to

their

non-normal

distribution

In

order

to

characterise

change

in

physical

activity

and

fitness

in

the

ProActive

cohort

we

described

the

association

between

exposure

variables

using

correlation

coefficients

We

then

examined

the

proportion

of

metabolic

syndrome

and

the

mean

clustered

metabolic

risk

score

among

participants

who

increased

and

decreased

their

PAEE

fitness

and

total

body

movement

over

year

We

used

linear

regression

to

model

change

in

PAEE

and

fitness

-LRB-

both

per

unit

FFM

-RRB-

and

total

body

movement

-LRB-

-LSB-

total

counts

per

day

-RSB-

adjusted

for

monitored

time

-RRB-

against

individual

subcomponents

of

the

clustered

metabolic

risk

score

at

follow-up

-LRB-

waist

circumference

blood

pressure

fasting

triacylglycerol

insulin

and

glucose

and

the

inverse

of

HDL-cholesterol

-RRB-

These

models

were

adjusted

for

age

sex

waist

circumference

-LRB-

except

when

waist

circumference

was

modelled

as

the

outcome

-RRB-

smoking

status

SES

-LRB-

assessed

by

self-reporting

-RRB-

and

baseline

phenotype

and

were

presented

as

standardised

β-coefficients

We

then

tested

whether

change

in

PAEE

fitness

and

total

body

movement

was

associated

with

the

clustered

metabolic

risk

score

at

follow-up

The

first

model

-LRB-

obesity

dependent

-RRB-

included

all

metabolic

subcomponents

-LRB-

zMS

-RRB-

and

was

adjusted

for

age

sex

smoking

status

SES

and

baseline

zMS

while

the

second

model

excluded

waist

circumference

from

the

zMS

-LRB-

obesity

independent

zMS-ob

-RRB-

and

was

adjusted

for

age

sex

smoking

status

SES

baseline

zMS-ob

and

waist

circumference

Finally

we

examined

whether

there

was

evidence

of

interaction

between

change

in

PAEE

total

body

movement

and

aerobic

fitness

and

clustered

metabolic

risk

as

well

as

interaction

by

age

and

sex

All

data

were

analysed

in

continuous

form

although

some

data

were

dichotomised

for

illustrative

purposes

All

analyses

were

completed

using

Stata

Version

-LRB-

STATA

College

Station

TX

USA

-RRB-

Results

Table

shows

the

anthropometric

and

metabolic

characteristics

of

participants

with

complete

data

for

baseline

and

follow-up

-LRB-

n

-RRB-

stratified

by

sex

More

women

met

the

inclusion

criteria

and

agreed

to

take

part

in

the

study

than

men

Participants

with

missing

data

at

follow-up

were

slightly

shorter

than

those

with

complete

data

-LRB-

difference

cm

p

-RRB-

but

not

significantly

different

for

all

other

baseline

variables

There

were

also

no

significant

differences

in

baseline

characteristics

between

participants

with

and

without

accelerometer

data

-LRB-

data

not

shown

-RRB-

In

general

men

were

significantly

taller

and

heavier

than

women

but

had

a

lower

percentage

body

fat

at

baseline

In

terms

of

the

six

metabolic

syndrome

subcomponents

waist

circumference

systolic

blood

pressure

triacylglycerol

fasting

glucose

and

insulin

were

all

significantly

higher

in

men

while

HDL-cholesterol

was

significantly

higher

in

women

Statistically

significant

differences

were

also

observed

for

PAEE

-LRB-

kJ

kg

FFM

min

-RRB-

and

-LRB-

ml

kg

FFM

min

-RRB-

with

men

achieving

higher

levels

of

physical

activity

and

fitness

even

after

adjustment

for

FFM

There

were

no

significant

differences

in

total

body

movement

between

men

and

women

at

baseline

Table

and

metabolic

characteristics

of

ProActive

participants

with

complete

baseline

and

follow-up

data

-LRB-

n

-RRB-

stratified

by

sex

MenWomenBaseline

-LRB-

n

-RRB-

Follow-up

-LRB-

n

-RRB-

Baseline

-LRB-

n

-RRB-

Follow-up

-LRB-

n

-RRB-

Age

-LRB-

years

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

N/AHeight

-LRB-

cm

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

cWeight

-LRB-

kg

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

BMI

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

dBody

fat

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Waist

circumference

-LRB-

cm

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

cSystolic

blood

pressure

-LRB-

mmHg

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

cDiastolic

blood

pressure

-LRB-

mmHg

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

cTriacylglycerol

-LRB-

mmol/l

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Total

cholesterol

-LRB-

mmol/l

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

HDL-cholesterol

-LRB-

mmol/l

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Fasting

plasma

insulin

-LRB-

mmol/l

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Fasting

plasma

glucose

-LRB-

mmol/l

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

dPAEE

-LRB-

kJ

kg

FFM

min

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

ml

kg

FFM

min

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Daily

physical

activity

-LRB-

total

count

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Data

are

means

-LRB-

SD

-RRB-

ap

bp

for

women

vs

men

at

baseline

cp

dp

for

baseline

vs

follow-up

-LRB-

separately

in

men

and

women

-RRB-

eThese

values

are

based

on

data

from

n

ProActive

participants

for

whom

accelerometer

data

were

available

at

baseline

and

follow-up

For

men

there

were

no

significant

differences

in

mean

height

weight

BMI

body

fat

waist

circumference

triacylglycerol

HDL-cholesterol

fasting

insulin

and

glucose

from

baseline

to

follow-up

The

only

metabolic

subcomponent

that

changed

significantly

over

time

was

systolic

blood

pressure

which

reduced

from

to

mmHg

In

terms

of

the

activity

variables

men

significantly

increased

their

physical

activity

-LRB-

PAEE

-RRB-

from

to

kJ

kg

FFM

min

but

increases

in

fitness

and

total

body

movement

did

not

achieve

statistical

significance

For

women

there

were

no

significant

differences

in

mean

weight

body

fat

triacylglycerol

total

cholesterol

HDL-cholesterol

and

fasting

insulin

from

baseline

to

follow-up

Mean

height

decreased

very

slightly

while

BMI

increased

from

to

and

waist

circumference

increased

from

to

cm

Values

for

both

diastolic

and

systolic

pressure

decreased

significantly

while

fasting

plasma

glucose

increased

slightly

from

to

mmol/l

Increases

over

the

year

in

PAEE

total

body

movement

and

fitness

did

not

reach

statistical

significance

There

was

no

significant

change

in

the

use

of

cardiovascular

therapies

during

follow-up

-LRB-

data

not

shown

-RRB-

There

was

no

evidence

for

a

correlation

between

change

in

fitness

and

change

in

PAEE

-LRB-

r

-RRB-

or

total

body

movement

-LRB-

r

-RRB-

There

was

limited

evidence

for

a

positive

correlation

between

change

in

PAEE

and

total

body

movement

-LRB-

r

-RRB-

The

overall

prevalence

of

metabolic

syndrome

was

at

both

baseline

and

follow-up

although

there

was

some

movement

between

groups

The

proportion

of

metabolic

syndrome

at

follow-up

was

higher

among

participants

who

failed

to

increase

their

PAEE

fitness

and

total

body

movement

over

year

-LRB-

Fig.

-RRB-

Similarly

clustered

metabolic

risk

scores

were

lower

among

individuals

who

managed

to

increase

their

PAEE

fitness

and

total

body

movement

during

follow-up

-LRB-

Fig.

-RRB-

of

the

differences

between

these

groups

reached

statistical

significance

but

were

in

the

expected

direction

of

effect

Fig.

Proportion

of

ProActive

participants

with

metabolic

syndrome

at

year

follow-up

by

those

who

increased

and

decreased

their

PAEE

fitness

and

total

body

movement

b

Mean

metabolic

summary

score

for

ProActive

participants

at

year

follow-up

by

those

who

increased

and

decreased

their

PAEE

fitness

and

total

body

movement

-LRB-

bars

represent

CIs

-RRB-

Table

shows

the

crude

and

adjusted

associations

between

change

in

PAEE

-LRB-

kJ

kg

FFM

min

-RRB-

-LRB-

ml

kg

FFM

min

-RRB-

and

total

body

movement

-LRB-

-LSB-

counts

per

day

-RSB-

-RRB-

with

standardised

subcomponents

of

the

clustered

metabolic

risk

score

and

the

whole

score

-LRB-

zMS

-RRB-

at

follow-up

As

all

outcomes

are

expressed

in

the

same

unit

-LRB-

SD

-RRB-

it

is

possible

to

directly

compare

the

magnitude

of

associations

between

the

different

components

of

activity

with

each

of

the

outcomes

assuming

they

are

measured

with

the

same

degree

of

measurement

error

In

adjusted

analyses

fasting

glucose

insulin

and

HDL-cholesterol

at

follow-up

were

significantly

associated

with

a

change

in

fitness

over

time

on

average

individuals

who

increased

their

fitness

had

reduced

levels

of

glucose

and

insulin

and

increased

levels

of

HDL-cholesterol

at

follow-up

Similarly

fasting

glucose

and

insulin

were

associated

with

change

in

total

body

movement

over

time

All

other

subcomponents

of

the

clustered

metabolic

risk

score

failed

to

show

an

association

with

change

in

either

physical

activity

fitness

or

total

body

movement

In

adjusted

analyses

change

in

fitness

but

not

change

in

PAEE

was

associated

with

clustered

metabolic

risk

at

follow-up

with

-LRB-

zMS

p

-RRB-

and

without

the

obesity

component

-LRB-

zMS-ob

p

-RRB-

In

addition

change

in

total

body

movement

from

baseline

to

follow-up

was

associated

with

clustered

metabolic

risk

in

both

the

overall

-LRB-

zMS

p

-RRB-

and

obesity-independent

score

-LRB-

zMS-ob

p

-RRB-

Table

and

adjusted

associations

-LRB-

standardised

β-coefficients

-RRB-

between

change

in

PAEE

and

total

body

movement

with

standardised

subcomponents

of

the

metabolic

summary

score

and

the

whole

score

-LRB-

zMS

-RRB-

at

follow-up

in

the

ProActive

cohort

over

yearOutcome

-LRB-

SD

-RRB-

Standardised

β-coefficient

-LRB-

CI

-RRB-

Change

in

PAEE

-LRB-

n

-RRB-

Change

in

-LRB-

n

-RRB-

Change

in

total

body

movement

-LRB-

n

-RRB-

CrudeAdjustedaCrudeAdjustedaCrudeAdjustedaWaist

circumference

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Systolic

blood

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Logged

triacylglycerol

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Logged

fasting

insulin

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

b

-LRB-

-RRB-

-LRB-

-RRB-

bFasting

plasma

glucose

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

b

-LRB-

-RRB-

b

-LRB-

-RRB-

-LRB-

-RRB-

bHDL-cholesterol

-LRB-

inverse

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

b

-LRB-

-RRB-

b

-LRB-

-RRB-

-LRB-

-RRB-

zMS

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

b

-LRB-

-RRB-

b

-LRB-

-RRB-

-LRB-

-RRB-

bzMS-ob

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

b

-LRB-

-RRB-

b

-LRB-

-RRB-

-LRB-

-RRB-

baAll

coefficients

adjusted

for

age

sex

smoking

status

SES

waist

circumference

and

baseline

phenotype

except

for

waist

circumference

which

was

adjusted

for

age

sex

smoking

status

SES

and

baseline

phenotypebp

There

was

no

evidence

of

interaction

between

change

in

EE

and

aerobic

fitness

-LRB-

p

-RRB-

EE

and

total

body

movement

-LRB-

p

-RRB-

and

aerobic

fitness

and

total

body

movement

-LRB-

p

-RRB-

with

clustered

metabolic

risk

at

follow-up

While

there

was

no

evidence

of

a

significant

interaction

between

age

or

sex

and

change

in

the

activity

variables

the

β-coefficients

for

change

in

PAEE

appeared

stronger

in

men

than

in

women

and

also

in

older

rather

than

younger

individuals

Discussion

Our

results

suggest

that

small

increases

in

physical

activity

measured

using

accelerometry

and

aerobic

fitness

were

associated

with

improvement

in

clustered

metabolic

risk

over

a

year

period

in

middle-aged

individuals

at

high

risk

of

developing

type

diabetes

Our

results

were

independent

of

age

sex

smoking

status

socioeconomic

group

and

baseline

phenotype

This

confirms

our

earlier

cross-sectional

result

-LSB-

-RSB-

in

a

prospective

analysis

which

provides

stronger

inferential

evidence

for

the

association

between

total

body

movement

and

metabolic

risk

Further

this

result

is

supported

by

our

finding

that

the

proportion

of

metabolic

syndrome

at

follow-up

was

higher

albeit

non-significantly

among

groups

who

failed

to

increase

their

PAEE

fitness

and

total

body

movement

over

year

Although

PAEE

was

not

significantly

associated

with

clustered

metabolic

risk

in

our

analyses

we

were

able

to

demonstrate

an

association

between

overall

body

movement

-LRB-

i.e.

physical

activity

-RRB-

assessed

by

accelerometry

and

clustered

metabolic

risk

This

is

a

novel

finding

given

that

previous

prospective

associations

between

objectively

measured

physical

activity

and

metabolic

risk

were

observed

in

a

population

of

healthy

middle-aged

Europids

-LSB-

-RSB-

rather

than

the

overweight

sedentary

younger

adults

with

a

high

risk

of

developing

type

diabetes

described

in

this

cohort

We

also

observed

that

the

benefits

of

increased

fitness

and

total

body

movement

acted

primarily

through

changes

in

serum

glucose

insulin

and

HDL-cholesterol

which

may

suggest

that

blood

pressure

is

less

sensitive

to

changes

in

activity

and

fitness

In

a

comparable

study

Ekelund

et

al.

-LSB-

-RSB-

observed

that

an

increase

in

activity

was

associated

with

fasting

insulin

triacylglycerol

h

glucose

and

clustered

metabolic

risk

but

not

with

systolic

or

diastolic

blood

pressure

Contrary

to

our

findings

previous

literature

has

shown

an

association

between

PAEE

and

clustered

metabolic

risk

both

cross-sectionally

-LSB-

-RSB-

and

prospectively

over

a

period

of

years

independently

of

fitness

-LSB-

-RSB-

This

apparent

discrepancy

might

be

explained

in

a

number

of

ways

First

while

the

trial

was

powered

to

detect

a

difference

in

physical

activity-related

EE

between

trial

arms

equivalent

to

metabolic

energy

equivalent

-LRB-

MET

-RRB-

h/day

or

approximately

min

of

brisk

walking

the

sample

size

was

relatively

small

for

a

cohort

analysis

and

may

not

have

been

large

enough

to

detect

smaller

but

still

biologically

important

differences

Nonetheless

all

the

PAEE

β-coefficients

were

in

the

same

direction

of

effect

as

those

for

the

accelerometry

data

but

they

did

not

reach

statistical

significance

Second

the

precision

in

the

methods

we

used

to

assess

PAEE

and

body

movement

may

affect

the

observed

associations

PAEE

from

individually

calibrated

HR

monitoring

is

an

integrated

measure

of

EE

above

rest

calculated

from

free-living

HR

data

In

sedentary

populations

much

of

the

daytime

is

spent

in

the

region

around

the

flex

HR

which

is

used

to

discriminate

between

rest

and

physical

activity

The

association

between

HR

and

EE

is

less

precise

in

this

region

which

may

influence

the

accuracy

of

predicted

PAEE

on

an

individual

level

Furthermore

the

flex

HR

method

may

be

sensitive

to

the

fitness

level

of

the

people

under

investigation

-LSB-

-RSB-

In

contrast

accelerometry

measures

the

vertical

accelerations

of

the

body

i.e.

physical

work

and

is

likely

to

be

less

sensitive

to

the

characteristics

of

the

population

in

terms

of

a

sedentary

lifestyle

and

fitness

level

If

most

of

the

activities

performed

are

locomotor

activities

such

as

walking

measurement

of

body

movement

by

accelerometry

may

be

superior

to

HR

monitoring

when

examining

associations

with

disease

risk

Ideally

the

two

different

measurement

techniques

should

be

combined

into

one

single

piece

instrument

-LSB-

-RSB-

Finally

by

standardising

the

clustered

metabolic

risk

score

we

assumed

each

component

made

an

equal

contribution

towards

defining

metabolic

risk

It

is

unlikely

that

each

component

is

equally

strongly

associated

with

metabolic

risk

and

some

variables

will

be

more

important

that

others

in

different

populations

It

would

therefore

be

ideal

to

weight

each

component

of

the

score

but

data

are

currently

unavailable

Our

results

suggest

that

small

feasible

changes

in

physical

activity

-LRB-

total

body

movement

-RRB-

and

fitness

in

an

at-risk

population

may

prevent

progression

towards

the

metabolic

syndrome

This

supports

previous

literature

which

has

demonstrated

an

inverse

relationship

between

fitness

physical

activity

and

risk

of

developing

metabolic

syndrome

in

a

number

of

settings

-LSB-

-RSB-

At

a

population

level

our

findings

have

important

implications

This

group

of

middle-aged

slightly

overweight

individuals

identified

through

primary

care

registers

via

their

first

degree

family

history

of

diabetes

represents

an

accessible

population

who

might

benefit

from

increased

physical

activity

and

fitness

levels

Primary

care

or

public

health

practitioners

might

target

this

group

for

preventive

action

Findings

can

also

be

extrapolated

to

inform

the

characteristics

of

public

health

initiatives

Increasing

total

body

movement

can

be

achieved

through

small

changes

in

lifestyle

activity

such

as

taking

the

stairs

and

parking

the

car

further

away

from

work

which

may

be

more

palatable

to

sedentary

and

at-risk

populations

than

targeting

changes

in

moderate

to

vigorous

intensity

activities

Regular

physical

activity

participation

also

has

multiple

positive

effects

upon

other

diseases

in

addition

to

metabolic

syndrome

such

as

stroke

coronary

heart

disease

and

cancer

-LSB-

-RSB-

However

currently

there

is

limited

evidence

regarding

the

effectiveness

of

lifestyle

interventions

for

individuals

at-risk

groups

or

populations

in

the

treatment

and

prevention

of

metabolic

syndrome

and

this

is

an

area

of

research

that

warrants

further

investigation

It

is

important

to

clarify

whether

metabolic

risk

is

most

effectively

reduced

by

increases

in

overall

EE

fitness

or

total

body

movement

to

inform

the

development

and

nature

of

preventive

interventions

This

study

had

several

methodological

strengths

The

ProActive

trial

allowed

objective

measurement

of

several

components

of

physical

activity

and

fitness

over

a

period

of

months

in

a

well-defined

group

of

individuals

accessed

through

primary

care

who

were

at

risk

of

diabetes

There

was

a

high

follow-up

rate

-LRB-

-RRB-

and

standardised

measures

were

used

throughout

We

used

objective

measures

of

physical

activity

which

reduces

the

error

and

bias

commonly

associated

with

self-report

measures

and

our

objective

measures

of

EE

physical

activity

-LRB-

PAEE

total

body

movement

-RRB-

and

fitness

have

been

extensively

validated

in

the

laboratory

and

during

free-living

conditions

-LSB-

-RSB-

In

conclusion

small

increases

in

physical

activity

assessed

by

accelerometry

and

in

aerobic

fitness

were

associated

with

improved

metabolic

risk

over

year

Further

research

is

needed

to

clarify

the

relationship

between

physical

activity

EE

fitness

and

metabolic

risk

to

inform

advice

and

intervention

development

We

may

need

even

more

precise

methods

of

measurement

to

capture

the

true

dose

effect

of

such

relationships

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O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B I O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O B O O O O O O O O O O O O O O O O O O O O O O B I O O O O B I O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B I O B O O O O O O O O O O O B O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O B I O O O O O O O O O O O O O O B I O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B O O O O O O O O O B I O O O O O O O O O O O O O B O B I O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O 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fitness
metabolic risk
metabolic syndrome
physical activity


Fiberoptic endoscopic evaluation of swallowing in intensive care unit patients Aspiration in critically ill patients frequently causes severe co-morbidity . We evaluated a diagnostic protocol using routine FEES in critically ill patients at risk to develop aspiration following extubation . We instructed intensive care unit physicians on specific risk factors for and clinical signs of aspiration following extubation in critically ill patients and offered bedside FEES for such patients . Over a 45-month period , we were called to perform 913 endoscopic examinations in 553 patients . Silent aspiration or aspiration with acute symptoms -LRB- cough or gag reflex as the bolus passed into the trachea -RRB- was detected in 69.3 % of all patients . Prolonged non-oral feeding via a naso-gastric tube was initiated in 49.7 % of all patients . In 13.2 % of patients , a percutaneous endoscopic gastrostomy was initiated as a result of FEES findings , and in 6.3 % an additional tracheotomy to prevent aspiration had to be initiated . In 59 out of 258 patients -LRB- 22.9 % -RRB- , tracheotomies were closed , and 30.7 % of all 553 patients could be managed with the immediate onset of an oral diet and compensatory treatment procedures . Additional radiological examinations were not required . FEES in critically ill patients allows for a rapid evaluation of deglutition and for the immediate initiation of symptom-related rehabilitation or for an early resumption of oral feeding . Introduction Pulmonary aspiration is a serious cause of morbidity and mortality in patients with a depressed sensorium , patients with neuromuscular discoordination , or patients having structural disorders of the upper aerodigestive tract . It is a leading cause of nosocomial infection in the intensive care unit -LRB- ICU -RRB- . The most common manifestations of pulmonary aspiration are pneumonia , pleuropulmonary infection , and acute airway obstruction -LSB- 1 -RSB- . Hospital-acquired pneumonia is the second most common nosocomial infection in the critically ill patient and is associated with the greatest mortality and increased morbidity and cost of care . Incidence of HAP varies in different populations of critically ill patients and generally ranges from 9 to 20 % . The etiologic agents differ according to the population studied , duration of hospital stay , time after intubation , and prior antimicrobial therapy -LSB- 2 -RSB- . Risk factors include nonmodifiable factors like age , chronic obstructive pulmonary disease , severe head trauma , and multiple trauma , and modifiable factors like large-volume gastric aspiration , duration of mechanical ventilation , elevated gastric pH , histamine type two blocker therapy , ventilator circuit change frequency , self-extubation , and silent aspiration following scheduled extubation -LSB- 2 -RSB- . When patients are admitted to the ICU , they are at increased risk of more frequent aspiration events because of a variety of factors , including depressed level of consciousness -LRB- often caused by excess analgesia and sedation -RRB- , forced supine position , and the presence of nasogastric or endotracheal tubes -LSB- 3 -RSB- . There is a growing body of evidence suggesting that intubation for longer than 48 h may cause at least transient injury to the larynx with a subsequent reduction in the protective mechanism and increased incidence of oropharyngeal secretions once the patient is extubated . The presence of an orotracheal tube has been shown to alter the mechanoreceptors and chemoreceptors of the pharyngeal and laryngeal mucosa , causing dysfunction of the swallowing reflex . The prevalence of swallowing dysfunction post-extubation has been reported to occur in between 20 and 83 % of those patients intubated longer than 48 h . This wide range of estimate has partly been attributed to the variation in the diagnostic tools -LSB- 4 -RSB- . The impact that diagnosis using invasive diagnostic techniques may have on the epidemiological characteristics of HAP in critically ill patients is unknown , but may potentially improve aspiration-related specific therapy and ultimately clinical outcome . Based on these considerations , we prospectively evaluated a diagnostic protocol using routine fiberoptic endoscopic evaluation of swallowing -LRB- FEES -RRB- in critically ill patients at risk to develop aspiration following temporary transnasal intubation or tracheotomy and tried to define the impact of post-extubation FEES on the initiation of aspiration-related treatment . Material and methods We conducted a prospective , interventional , clinical study at Klagenfurt General Hospital . The hospital is a 1,400-bed tertiary referral centre that serves a population of approximately 1,000,000 and runs seven ICUs -LRB- paediatrics and neonatology , 1 ; neurology , 1 ; neurosurgery , 1 ; cardiology , 1 ; general internal medicine , 1 ; and anaesthesiology , 2 -RRB- with a total of 84 beds . We offered a standardized endoscopy protocol for critically ill patients considered to be at risk for silent aspiration following transnasal intubation or tracheotomy for ventilation . Patient selection for endoscopic assessment of swallowing was done by ICU physicians using a protocol that we designed to help in the early recognition of risk factors for , or overt signs of , aspiration . This protocol included a taxonomic summary of symptoms and clinical signs potentially related to aspiration . Rating was applied after the stop of mechanical ventilation . Symptoms were defined as : Weight loss , unexplained fever > 38.0 ° centigrade , coughing , bronchitis/pneumonitis , impaired voice , witnessed regurgitation/aspiration event at the bedside accompanied by coughing , choking , and/or expectoration of material , prolonged oral feeding , aversion for oral intake of liquids and solids , disturbance of bolus transport , frequent postural changes during oral intake , andregurgitation.If such conditions were observed in previously intubated patients following extubation , or in patients with tracheotomies , physicians at ICUs were encouraged to request endoscopic assessment of swallowing . The FEES procedure was consequently provided by staff members of the department of Oto-Rhino-Laryngology , Head and Neck Surgery . The team consisted of a laryngologist and a nurse who had both previously gone through a specialized training in performing FEES procedures in patients with deglutition disorders . Over the 45-month period from 1 January 2002 to 30 September 2005 , we were called to perform 913 endoscopic examinations in 553 patients treated in one of the ICUs . Four hundred and 46 patients underwent one single endoscopy , and 107 had repeated examinations . Two hundred and 95 patients had shortly before been extubated after transnasal tracheal intubation , and 258 patients had indwelling tracheotomies . For further data interpretation , patients were sub-grouped according to their route of ventilation -LRB- transoral/transnasal intubation vs. tracheotomy -RRB- . Findings and recommendations from the initial FEES procedure in all 553 patients were accumulated for this study . The results of 360 control procedures were not further analyzed . Details of the FEES procedure have previously been described in detail . Therefore , only a short summary of the procedure shall be given here : The FEES procedure is a portable examination , easily taken to bedside in ICUs . Since our patients were usually bedridden , we performed the examination in a in bed with the head of bed elevated to approximately 70 ° with the bend of the bed is at the patient 's lower back -LRB- 904/913 patients , i.e. , 99 % -RRB- . In four patients -LRB- 0.4 % -RRB- , the examination was carried out with the patient in reverse Trendelenberg at 30 ° -- 45 ° , and five patients -LRB- 0.6 % -RRB- were able to sit on a chair during the procedure . A fiberoptic laryngoscope was passed transnasally to the oropharynx , where the larynx and surrounding structures could then be visualized . Patients were led through various tasks to evaluate the sensory and motor status of the pharyngeal and laryngeal mechanism . Stained liquid and semi-liquid boluses were then given to determine the integrity of pharyngeal deglutition . The interior larynx and airway were examined for evidence of food penetration within the laryngeal vestibule and aspiration of food below the true vocal folds before and after each swallow . In each case , the nasogastric tube was removed prior to the procedure . We assessed structural changes of the larynx and pharynx , timing and direction of movement of the bolus through the pharynx , the ability to protect the airway and to uphold airway protection for a some seconds , the capability to clear the bolus during deglutition , presence of pooling and residue of material in the hypopharynx , and timing of bolus flow and laryngeal closure . Aspiration was defined as the entry of material into the airway below the levels of the true vocal cords . Silent aspiration was defined as aspiration occurring in the absence of acute symptoms -LRB- i.e. , lack of cough or gag reflex as the food or liquid bolus passed into the trachea -RRB- . Findings were documented in a standardized form to allow for monitoring therapeutic interventions over time , and for later data analysis and evaluation . Results Over a 45-month period , we were called to perform 913 endoscopic examinations in 553 patients . Of these , 295 patients had previously been extubated , and 258 patients had indwelling tracheotomies . Silent aspiration or aspiration with acute symptoms -LRB- cough or gag reflex as the bolus passed into the trachea -RRB- was detected in 383 -LRB- 69.3 % -RRB- of all patients during initial FEES . Prolonged non-oral feeding via a naso-gastric tube was initiated in 49.7 % of all patients . In 13.2 % of patients , a percutaneous endoscopic gastrostomy was initiated as a result of FEES findings , and in 6.3 % an additional tracheotomy to prevent aspiration had to be set off . In 59 out of 258 patients -LRB- 22.9 % -RRB- , tracheotomies were closed , and 30.7 % of 553 patients could be managed with the immediate onset of an oral diet ± compensatory treatment procedures without further diagnostic evaluation . Logopedic instruction of the patient and/or rehabilitation using compensatory strategies to reduce the risk of aspiration were an integral part of our rehabilitation program and included one or more of the following : Modifications in volume and tempo of food presentationoral feeding with consistency modificationshead rotationholding the chin down during deglutition to narrow the airway entrancesupraglottic swallow : This technique uses simultaneous swallowing and breath-holding , closing the vocal cords and protecting the airway.One hundred and seven patients were scheduled for repeated FEES , usually to assess the progress of the rehabilitation program . Signs and symptoms encountered during initial FEES are condensed in Table 1 . Table 2 stratifies the route of feeding in the two subgroups of our study population . Table 3 classifies the type of aspiration detected during FEES . Table 4 summarizes the recommendations derived from our endoscopic findings for the further management of patients with aspiration . Table 1Symptoms of aspiration in 553 patientsPatients after transnasal tracheal intubation -LRB- n = 295 -RRB- Patients with indwelling tracheotomies -LRB- n = 258 -RRB- Unexplained fever17 -LRB- 5.8 % -RRB- 39 -LRB- 15.1 % -RRB- Coughing68 -LRB- 23.1 % -RRB- 31 -LRB- 12.0 % -RRB- Bronchitis/pneumonitis57 -LRB- 19.32 % -RRB- 39 -LRB- 15.1 % -RRB- Impaired voice57 -LRB- 19.32 % -RRB- 0 -LRB- 0 % -RRB- Witnessed regurgitation/aspiration event 74 -LRB- 25.1 % -RRB- 149 -LRB- 57.8 % -RRB- Others16 -LRB- 5.4 % -RRB- 23 -LRB- 8.9 % -RRB- No data69 -LRB- 23.3 % -RRB- 19 -LRB- 7.4 % -RRB- Since more than one symptom or sign could apply per patient , results sum up to more than 100 % Table 2Route of feeding for 553 patients on initial FEESPatients after transnasal tracheal intubation -LRB- n = 295 -RRB- Patients with indwelling tracheotomies -LRB- n = 258 -RRB- Nasogastric tube224 -LRB- 75.9 % -RRB- 186 -LRB- 72.1 % -RRB- PEG15 -LRB- 5.1 % -RRB- 59 -LRB- 22.9 % -RRB- Parenteral12 -LRB- 4.1 % -RRB- 5 -LRB- 1.9 % -RRB- Oral diet44 -LRB- 14.9 % -RRB- 8 -LRB- 3.1 % -RRB- PEG percutaneous endoscopic gastrostomyTable 3Classification of aspiration for 553 patients on initial FEESPatients after transoral or transnasal tracheal intubation -LRB- n = 295 -RRB- Patients with indwelling tracheotomies -LRB- n = 258 -RRB- Silent aspiration51 -LRB- 17.3 % -RRB- 95 -LRB- 36.8 % -RRB- Aspiration115 -LRB- 39.0 % -RRB- 126 -LRB- 48.8 % -RRB- No aspiration129 -LRB- 43.7 % -RRB- 37 -LRB- 14.4 % -RRB- Aspiration = inhalation of material into the airway below the level of the true vocal cords , with acute symptoms -LRB- cough or gag reflex as the bolus passed into the trachea -RRB- , silent aspiration = aspiration occurring in the absence of acute symptomsTable 4Recommendation for further treatment in 553 patients after initial FEESPatients after transoral or transnasal tracheal intubation -LRB- n = 295 -RRB- Patients with indwelling tracheotomies -LRB- n = 258 -RRB- Non-oral feeding -LRB- naso-gastric tube -RRB- ± logopedic -LRB- functional -RRB- therapy144 -LRB- 48.8 % -RRB- 131 -LRB- 50.8 % -RRB- Indication for PEG27 -LRB- 9.1 % -RRB- 46 -LRB- 17.8 % -RRB- Indication for non-oral feeding plus tracheotomy35 -LRB- 11.9 % -RRB- NAOral feeding ± logopedic -LRB- functional -RRB- therapy89 -LRB- 30.2 -RRB- 22 -LRB- 8.5 % -RRB- Decannulation and oral feeding ± logopedic -LRB- functional -RRB- therapyNA59 -LRB- 22.9 % -RRB- PEG percutaneous endoscopic gastrostomy , NA not applicable Discussion Aspiration is a common event . The North American Summit on Aspiration in the Critically Ill Patient , in a consensus statement published in 2002 -LSB- 5 -RSB- , estimates the frequency of aspiration in various patient populations is as follows : 45 % in normal individuals during sleep70 % in patients with impaired consciousness0 -- 40 % in patients on ETF50 -- 75 % in patients with endotracheal tubesWhat determines the clinical consequences of an aspiration event are host factors -LRB- age , immune status , underlying disease process , and comorbidities -RRB- and the nature of the aspirate . The morbidity and mortality associated with aspiration -LRB- with or without subsequent pneumonia -RRB- is difficult to ascertain and may vary greatly depending on the patient population that is under study -LSB- 5 -RSB- . Despite these general considerations , aspiration is generally accepted as a leading cause of nosocomial pulmonary infection in the ICU -LSB- 6 -RSB- . Ajemian reported a 56 % -LRB- 27/48 -RRB- incidence of swallowing dysfunction following prolonged intubation ; 12 -LRB- 25 % -RRB- of 48 patients were silent aspirators -LSB- 7 -RSB- . In a study by Leder et al. -LSB- 8 -RSB- , FEES demonstrated swallowing dysfunction in 33 % of critically ill trauma patients after prolonged intubation , with 20 % having silent aspiration . In a recent study by El Solh and co-workers , aspiration was documented in 52 % of ICU patients aged over 65 years and in 36 % of those up to age 65 . No significant difference in the co-morbidity index and the length of mechanical ventilation was found between aspirators and non-aspirators -LSB- 4 -RSB- . Non-specific methods to monitor for and detect aspiration are usually subjective , not standardized or validated , and inaccurate , and there are few outcome valid data . Blue dye has been commonly used to color the feeding solutions , but this method is insensitive and non-specific for assessing aspiration and pneumonia . Testing of pharyngeal secretions with glucose oxidase strips also is not standardized and is too insensitive and non-specific to test for aspiration of feeding solution . The best single test for aspiration remains undetermined to date . Therefore , clinical studies are needed to determine the potential role of particular tests suited for specific indications -LSB- 9 -RSB- . Video-fluoroscopy has traditionally been accepted as the `` gold standard '' for evaluation of a swallowing disorder for the comprehensive information it provides . However , it is not very efficient and accessible in certain clinical and practical situations . This is particularly true for critically ill patients treated at ICUs , who are almost invariably bedridden . FEES has been shown to be safe and effective for assisting in swallowing evaluation , and in therapy as a visual display to help patients learn various swallowing manoeuvres . -LSB- 4 , 10 -- 13 -RSB- . It can be used in a wide variety of settings , ranging from office evaluation of swallowing , inpatient and outpatient services to critically ill patient treated at the ICU -LSB- 14 -- 20 -RSB- . FEES is not just a screening procedure , it can achieve a complete assessment of the pharyngeal stage of swallowing . It includes five components : assessment of structural changes in the larynx and pharynx , assessment of movement and sensation , assessment of secretions management , direct visualization of swallowing function for food and liquid , and response to therapeutic interventions -LSB- 12 -- 15 , 17 -RSB- . Aviv and co-workers suggested combining FEES with sensory testing of the laryngeal and pharyngeal mucosa using discrete pulses of air delivered to the epithelium innervated by the internal branch of the superior laryngeal nerve -LRB- FEESST : Fiberoptic endoscopic evaluation of swallowing with sensory testing -RRB- . They performed 1,340 consecutive FEESST procedures on 1,076 adult patients with dysphagia , among them 172 examinations in critically ill patients at the ICU -LRB- mostly following cardiac surgery -RRB- . The authors concluded that FEESST for the purpose of swallowing function can be done safely and yields a 96.5 % success rate in terms of completed examinations -LSB- 19 , 21 -RSB- . Our experience suggests that FEES can be performed easily at the bedside of ICU patients . It is associated with minimal complications for those patients recently liberated from mechanical ventilation , and for patients with indwelling tracheotomy treated at the ICU . However , we can not determine from our data whether adopting FEES prevented aspiration pneumonia . Barquist et al. -LSB- 22 -RSB- conducted a randomized , prospective clinical trial of FEES versus routine clinical management in 70 patients after prolonged intubation . The addition of a FEES examination did not change the incidence of aspiration or postextubation pneumonia . Larger prospective randomized trials of FEES versus conventional patient management will be required to determine whether a difference in the rate of post-extubation pneumonia can be demonstrated . However , in our study , the observations recorded during FEES had immediate impact on the further treatment of patients : prolonged non-oral feeding via a naso-gastric tube was initiated in 49.7 % of patients , percutaneous endoscopic gastrostomy in 13.2 % , and an additional tracheotomy to prevent aspiration in 6.3 % . On the other hand , 81 out of 258 pre-existing tracheotomies were immediately closed , and 30.7 % of all 553 patients with endoscopy-proven aspiration could be treated with the immediate onset of an oral diet and compensatory treatment procedures . After assessing the critically ill patient for risk of aspiration , the clinician still must decide if the patient is ready to be fed . The goal is to identify critically ill patients who are likely to tolerate enteral nutrition and attempt to minimize complications -LSB- 23 -RSB- . FEES is certainly a versatile tool in achieving timely and appropriate clinical decisions in patients at risk for aspiration-related morbidity . In contrast to most of the recently published material on FEES in critically ill patients , we report our observation in a large proportion of patients with indwelling tracheotomies -LRB- 258 out of 553 , i.e. , 46.7 % -RRB- at the time of the examination . Tracheotomy is a commonly performed procedure in ventilator dependent patients . Many critical care practitioners believe that performing a tracheostomy early in the postinjury period decreases the length of ventilator dependence as well as having other benefits such as better patient tolerance and lower respiratory dead space -LSB- 24 -RSB- . Table 4 demonstrates that silent aspiration as well as clinically overt aspiration was more frequently encountered in patients with tracheotomies as compared to those that had previously been intubated via an oral or transnasal route . However , the clinical impressions that a tracheotomy or tracheotomy tube increases aspiration risk or that decannulation results in improved swallowing function have not been supported by a recent study . Rather , the need for a tracheotomy indicated comorbidities -LRB- e.g. respiratory failure , trauma , stroke , advanced age , reduced functional reserve , and medications used to treat the critically ill -RRB- that by themselves predispose patients for dysphagia and aspiration -LSB- 25 -RSB- . These data confirmed similar findings previously published by same authors : Neither the presence of a tracheotomy tube nor decannulation affected aspiration status in early , postsurgical head and neck cancer patients . In the acute care setting , no causal relationship between tracheotomy and aspiration status was exhibited -LSB- 26 -RSB- . Our results allow no conclusion regarding the impact of tracheotomies on deglutition , since the initial decision to perform a tracheotomy had not been randomly assigned to patients in our two subgroups . The decision to perform tracheotomies was not consistent over different ICUs and largely depended on the anticipated length of assisted ventilation . In our study , FEES was used to determine the need for maintaining tracheotomy , and was accepted by ICU physicians as an important criterion in deciding to close tracheotomies following assisted ventilation . Conclusion After the introduction of a standardized endoscopy protocol for critically ill patients considered being at risk for silent aspiration , ICU physicians soon requested FEES routinely for their patients . FEES in critically ill patients allows for a rapid evaluation of deglutition , for targeted further diagnostic procedures if needed , and for the immediate initiation of symptom-related rehabilitation or for an early resumption of oral feeding . FEES is now accepted at our institution as an important tool in achieving timely and appropriate clinical decisions for ICU-patients at risk for aspiration-related morbidity . Laryngologists should be encouraged to offer FEES procedures to responsible coordinators of ICUs .

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aspiration deglutition swallowing dysphagia tracheotomy rehabilitation endoscopy