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==== Front
Multimed Tools Appl
Multimed Tools Appl
Multimedia Tools and Applications
1380-7501
1573-7721
Springer US New York
14180
10.1007/s11042-022-14180-5
Article
Adaptive Weiner filtering with AR-GWO based optimized fuzzy wavelet neural network for enhanced speech enhancement
Jadda Amarendra [email protected]
Prabha Inty Santi
grid.411829.7 0000 0004 1775 4749 Department of Electronics and Communication Engineering, Jawaharlal Nehru Technological University, Kakinada, Kakinada, 533 003 Andhra Pradesh India
9 12 2022
125
6 9 2021
17 6 2022
27 10 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Speech signal enhancement is a subject of study in which a large number of researchers are working to improve the quality and perceptibility of speech signals. In the existing Kalman Filter method, the short-time magnitude or power spectrum due to random variations of noise was a serious problem and the signal-to-noise ratio was very low. This issue severely reduced the perceived qualityand intelligibility of enhanced speech. Thus, this paper intent to develop an improved speech enhancement model and it includes“training phase and testing phase”. In the training phase, the input noise corrupted signal is initially fed as input to both STFT-based noise estimation and NMF-based spectrum estimation forestimating the noise spectrum and signal spectrum, respectively. The obtained noise spectrum and the signal spectrum are fed as input to the Wiener filter and these filtered signals are subjected to Empirical Mean Decomposition (EMD).Since, tuning factor η plays a key role in Wiener filter, it has to be determined for each signal and from the denoised signal the bark frequency is evaluated. The computed bark frequency is fed as input to the learning algorithm referred as Fuzzy Wavelet Neural Network (FW-NN)for detecting the suited tuning factor η for the entire input signal in Wiener filter.An Adaptive Randomized Grey Wolf Optimization (AR-GWO) is proposed for proper tuning of the tuning factor η referred as tuned tuning factor (ηtuned). The proposed AR-GWO is the improved version of standard Grey wolf optimization (GWO). In the testing phase, the training is accomplished initially and from which the tuning factor is gathered for each of the relevant input signal. Then, the properly tuned tuning factor (ηtuned) from FW-NN is fed as input to EMD via adaptive wiener filter for decomposing the spectral signal and the output of EMD is denoised enhanced speech signal. At last, the performance of the adopted approach is evaluated to the existing approaches in terms of various metrics. In particular, the computation time of the adopted AR-GWO model is 34.07%, 43.57%, 28.86%, 38.88%, and 16.03% better than the existing GA, ABC, PSO, FF, and GWO approaches respectively.
Keywords
STFT-based noise estimation
NMF-based spectrum estimation
EMD
Weiner filter
FW-NN
==== Body
pmcIntroduction
In the present era, speech enhancement plays a major role in the field of speech processing as it is related to the speaking as well as listening skills. In general, speech enhancement is employed with a desire of processing the noisy speech signals, thereby enhancing human perception [3, 38, 41]. Generally, the quality of the speech is related to the attributes of the speaker, like the naturalness and speaker recognizability, whereas the intelligibility of the speech is related to the meaning or information content that is hidden behind the words [45] [27]. Speech signals are utilized in many purposes and in recent times, COVID-19 [28, 36] has been detected from speech signals. Hence, it is vivid that, the ability to communicate (speak and listen) diminishes in the noisy environment.
The speech enhancement is performed with the intention of reducing the impact of the communication problem [22]. Most of the research proved that, it is a complex task to reduce the noise of the signal without distorting speech and this is the major reason behind the non-availability of an ideal enhancement systems [4, 30]. Beyond this, efforts to enhance the “higher quality and/or intelligibility of noisy speech” will definitely end up with a mass increment in the performance of the speech signal and hence it can be employed in the fields of “speech coding/compression and speech recognition, hearing aids, voice communication systems and so on” [21, 35]. Further, the goal behind each of the speech recognition might be different and they are application based, such as diminishing the listener fatigue, boosting the overall speech quality, enhancing the intelligibility and improving the performance of the voice communication device, etc. But, the major benchmark behind all the research is to diminish the noise level and to enhance the quality as well asthe intelligibility of the signal. Hence,“speech enhancement is necessary to avoid the degradation of speech quality and to overcome the limitations of human auditory systems” [2, 43].
A vast amount of automatic speech processing systems are playing a major role in human life, like the “mobile communication, speech and speaker recognition, hearing impaired and numerous other applications”. Moreover, the quality and intelligibility of speech areof utmost importance with the intention of enhancing the accuracy of information exchange [31]. Beyond this, in the controlled environment, human as well as automatic speech communications are found to be much more effective [5, 47]. The Spectral Subtraction algorithm suffers from the problem of restoration in the basis parameters of the speech like the power spectrum or the magnitude spectrum and here only the additive noise available in the signal can be removed [1]. Then, in the Sub-space analysis algorithm, there was a difficulty in enhancing the noise spectrum and updating the noise spectrum from period to period was a complex task. [46]. Thus, in order to override these entire problems, there is a necessity to have an optimal speech enhancement method.
Nowadays, literature works have come up with several techniques for speech enhancement as relates to speaking as well as listening skills. Tantibundhit et al. [44] proposed JT-FS with the desire of decomposing the speech signal into “transient” as well as “non-transient components” only the basis of the wavelet packets. Lee et al. [30] proffered P-SJL with the intention of enhancing single-channel speech. The phase-related information of the speech signal was represented using PSM which was similar to the T-F mask. Furthermore, the P-ASEalgorithm [48] was formulated on the basis of DNN. Shao and Chang [40] developed a framework of wavelet-based techniques with the intention of enhancing the performance of automatic speech recognition by eliminating the background noise. AKCF algorithm was introduced in [13]with the aim of enhancing speech. The noise as well as the speech parameters was estimated using the Estimate-Maximize (EM) method. Mohammadiha et al. [34] proposed SSD algorithms on the basis of NMF. In addition to this, the Bayesian Formulation of NMF (BNMF) was used for generating the novel speech enhancement method. Additionally, Chazan et al. [6] proposed the S-MSE algorithm in order to enhance the speech signal. Samuiet al. [39] proposed time-frequency masking in the basis of DNN with the intention of enhancing the speech signal and here the pre-training of the signal was accomplished using FRBM. Moreover, the advantages and challenges of the few works are listed in Table 1. These challenges have kept the main stand for motivating and accomplishing the new speech enhancement model. Table 1 Features and Challenges of of the state-of-art Speech Enhancement models
Author [citation] Adopted methodology features Challenges
Tantibundhit et al. [44] JT-FS Algorithm Enhanced the word recognition rate. Low SNR
Increased speech intelligibility in background Noise. No consideration on the constant Or slowly varying frequency information
Lee et al. [30] P-SJL algorithm High SNR Not Applicable to magnitude spectra domain.
Had consideration on the dynamic range of speech and noise spectral Features. Do not solve the phase mismatch problem.
Zheng andZhang [48] P-ASE Algorithm Solved phase wrapping problem Low SNR
Enhanced speech quality and intelligibility. BW is high
Shao and Chang [40] HMM Degraded the residual noise energy. Sensitivity of signal is high
High speech recognition accuracy. SNR is low
Gannot et al. [13] KF algorithm Achieves higher SNR and quality of speech Difficult to construct reliable VAD (Voice Activity Detector)
Applicable to noise sources with fast changing Spectrum
Mohammadiha et al. [34] SSD algorithm Noise classification and speech enhancement were carried out at the same time Highly affected by nonnegative decomposition problem
Solved the mismatch problem
Chazan et al. [6] DNN Preserves the continuity of speech. Do not address the problem of noisy speech received by a single microphone
Reduces the artifacts High distortions in the enhanced speech
Samui et al. [39] Fuzzy based DNN Solves the problem of local optima and total reconstruction error. Not suitable for real-world noise.
Provides good performance under noisy reverberant conditions. Training of the signal is complex
In addition, many optimization algorithms have been introduced recently [8–10, 25] and utilized in many fields for better outcomes [7]. In this research work, a modified version of a popular meta-heuristic algorithm is employed. The major contributions of this research are listed below: In this research work, STFT-based noise estimation and NMF-based spectrum estimation are utilized for the estimation of the noise spectrum and signal spectrum of the noisy signal.
To minimize the error, a Wiener filter is employed and the tuning factor ηof Wiener filter is obtained for different signals.
Introducing a Fuzzy Wavelet Neural Network (FW-NN) for detecting the suited tuning factor η for the entire input signal in Wiener filter.
Proposed an Adaptive Randomized Grey Wolf Optimization (AR-GWO) for proper tuning of the tuning factorηreferred as tuned tuning factor(ηtuned). The proposed AR-GWO algorithm is an improved version of the traditional GWO algorithm.
The rest of the paper is organized as below: Section 2 portrays the proposed architecture of the speech enhancement model. Section 3 depicts the processed steps for enhanced speech enhancement. The results and discussions are exhibited in Section 4, and Section 5 concludes the paper.
Proposed architecture of speech enhancement model
Architectural representation
Figure 1 demonstrates the architecture of the proposed speech enhancement model in which the overall process takes place in “two major phases (i) training phase (ii) testing phase”. In the training phase, initially, the noise corrupted signal is fed as input to STFT-based noise estimation as well as NMF-based spectrum estimation, for estimating the noise spectrum and signal spectrum, respectively. The obtained spectrum (noise and signal) are given as input to the Wiener filter. These, filtered signals are subjected to EMD, from which the denoised signal can be obtained. Since, tuning factor η plays a key role in Wiener filter, it has to be determined for each signals, and is trained in FW-NN. Then, from the denoised signal the bark frequency is evaluated. The computed bark frequency is fed as input to the learning algorithm referred as FW-NNfor detecting the suited tuning factorη for the entire input signal in Weiner filter. The AR-GWO is employed for proper tuning of the tuning factorη. Moreover, in the testing phase of a signal, the training is accomplished initially, from which the tuning factorηis gathered for the corresponding input signal. Then, the properly tuned ηfrom FW-NNis fed as input to EMD via adaptive Wiener filter for decomposing the spectral signal and the output of EMD is denoised signal. Fig. 1 Proposed intelligence architecture for speech enhancement model
Consider the clear signal as T(n), when the noise Wgets corrupted into it, and the signal becomes noisy signal T¯n. This noisy signal is fed as input to the STFT-based noise estimation and NMF-based spectrum estimation, from which the noise spectrum WT and signal spectrum W¯Tare obtained. The obtained noise and signal spectrum are subjected to filtration using Wiener filtering process; at the end of filtration the filtered signal T¯un is generated. Then, T¯un is decomposed using EMD as a result of this, the bark frequency c′(u′) is obtained. This bark frequency is utilized to train FW-NN classifier. From the spectrum WT and W¯T as well as from FW-NN, ‘tuned η’ referred as ηtuned is acquired for all the inputs signals with AR-GWO. In the testing process, the tuned ηtuned is acquired for the corresponding signal with the aid of the AR-GWO; this ηopt is fed as input to the adaptive Wiener filtering process with the intention of tuning the input signal T¯n. The outcomes of the adaptive Wiener filter are the filtered signal Tun¯¯. Again, Tun¯¯ is decomposed using EMD and the result is the enhanced denoised signal Ton¯¯.
Processed steps for enhanced speech enhancement
STFT-based noise estimation
The noise power spectral density estimatorisbased onminimum statistics to track the minima from the noisy signal [26]. The STFT coefficient of the frame γ is depicted as T(γ, p) and their mathematical formula is exhibited in Eq. (1) [14]. 1 Tγp=τγpTγ−1p+1−τγpT(γp)2
Here, the frequency bin is manifested as p. The frequency and time-dependent smoothing parameters is portrayed as τ(γ, p). With the intention of observing the mean power, the bias compensation factor is employed. The variance estimator of the smoothened PSD is represented as var{T(γ, p)} and the function corresponding to the length of minimum search interval is defined by the bias compensation factor Kmin. The variance estimator relating the smoothened PSD is indicated asvar{T(γ, p)} and this assist in evaluating the variance of T(γ, p) by fixing the length of the search interval in the algorithm. Eq. (2) depicts the mathematical formula for evaluating the variance estimator at the frame γ relating the frequency bin p. In Eq. (2), the mean smoothened periodograms is represented as T¯γp, and T2¯αb indicates the first-order recursive average of smoothened periodograms [14]. 2 varTγp=T2¯γp−T¯2γp
This paper deal with STFT-based noise estimation and the graphical representation of the power spectrum corresponding to the noise estimated by FFT as well as STFT is exhibited in Fig. 2. The power spectrum varies by the magnitude of the frequency component. Moreover, in determining the phase content of the signal and varying sine wave frequency that alter over time are predicted using STFT. In general, the time signals which are larger in size are sub-divided into smaller equal size signals and to each of the segments the Fourier transform is employed. In addition, in the filtering process, STFT can also be interpreted. The estimation strategy is satisfied by two major properties viz. magnitude based shift invariance property and LT-FD properties. The noise spectrum WT is obtained as the resultant. Fig. 2 Noise power spectrum (a) estimated by FFT (b) estimated by STFT - minimum statistics
NMF-based Spectrum estimation
In the time-frequency (γ, p) domain, the voicing of the noisy signal T¯n takes place via STFT as per Eq. (3), to enhance the speech signal [42]. In Eq. (3), the STFT of the clear speech T(p, γ), the STFT of the noisy speech T¯pγ and the STFT of the noise signal W(p, γ) are used in pth frequency bin of γ frame. The mathematical formula for “noisy speech’s magnitude spectrum” approximation, which is most commonly, utilized assumption for NMF-based processing of speech and audio signal, is show in Eq. (4) [14]. 3 T¯pγ=Tpγ+Wpγ
4 ∣T¯pγ∣=∣Tpγ∣+∣Wpγ∣
The magnitude spectrum matrices of the varied signal are indicated as per Eq. (5) and magnitude spectral value corresponding to γ frame for the pth bin is depicted as jp, γ. The count of the frequency bins is represented as H and the time frames are indicated as I. 5 J=jp,γ∈N+H×I
For the training data JT∈N+H×ITas well as JW∈N+H×IW, the Eq. (5) is employed separately in the training stage and the outcome of these data is the basis matrices in terms of clear speech FT=rHlT∈N+H×LTand noise FW=rHlW∈N+H×LW, respectively. The count of base vectors is indicated as L. In Eq. (6) ζ represents a H × I matrix, whose entities is equal to one and the transpose of the matrix, is represented as T′. In addition, the basis matrices are fixed in the enhancement stage as FT=FTFW∈N+H×LT+LW.The activation matrix ET^=ETT′EWT′T′∈N+LT+LW×IT^ corresponding to the noisy speech is estimated from JT^∈N+H×IT^ by means of employing the NMF activation update. Further, with the assistance got from the Wiener Filter (WF), the clear speech spectrum is evaluated from the speech signal only after obtaining the activation matrix as per Eq. (7). The estimated PSD matrices corresponding of the clear speech is manifested as V′T = [V′T(p, γ)] and the evaluated PSD matrices corresponding to the noisy signal is represented as V′W=V′Wpγ∈N+H×IT^ in Eq. (7). Further, as per Eqs. (8) and (9) the next solution is obtained via the temporal smoothing of the period grams. The temporal smoothing factor of speech ωT and noise ωW is shown in Eqs. (8) and (9), respectively. 6 F←F⊗J/F.EEζE,E←E⊗FJ/FEFT′ζ
7 Q=V′TV′T+V′W⊗T^
8 V′Tpγ=ρTV′Tpγ−1+1−ρTFTETpγ2
9 V′Wpγ=ρWV′Wpγ−1+1−ρWFWEWpγ2
The signal spectrum W¯Tis obtained as the outcomes.
The obtained noise spectrum WT and signal spectrum W¯Tare subjected to filtration using Wiener filtering process.
WienerFilter
In the signal enhancement technique, the Wiener filter has been employed in large scale [15]. The Wiener filter works on the principle of producing an estimate of the clean signal from the corrupted noise signal. The estimation is accomplished by minimizing MSE in between the desired signal and additive noise corrupted signal. The filter transfer functionis shown in Eq. (10) and it gives the solution to this optimization problem in the frequency domain. This equation is generated by considering the signal spectrum W¯Tand the noise spectrum WT as uncorrelated and stationary signals. The power spectral density of W¯Tis represented as GT(ω) and the power spectral density of WT is depicted as GW(ω). The mathematical formula for SNR is exhibited in Eq. (11) and the SNR formula can be incorporated in the filter transfer function as per Eq. (12). The estimated signal magnitude spectrum is indicated as G^Wω. 10 Fω=GTωGTω+GWω
11 SNR=GTωG^Wω
12 Fω=1+1SNR−1
At the end of filtration the filtered signal T¯un is generated.
The Wiener filteroften fails at all the frequencies due to the drawback of fixed frequency response and requirement of estimating the clean signal and noise signal’s power spectral density prior to filtering.
Empirical model decomposition
EMD [16] was introduced by Huang as an adaptive technique in which small number of orthogonal empirical modes referred as IMF were added to represent the complex data. The symmetric envelope is present in each of the mode in terms of local maximums and minimums. Thus at all locations of the envelope, mean is zero and in the underlying signal, there is no requirement of linearity or time invariance. Further, by the process of shifting, the riding waves are eliminated. The shifting process of EMD algorithm can be depicted as shown below. Two main properties are obeyed by EMD during the splitting of T¯un into its IMF components. They are (a) In between two subsequent zero crossing, the IMF has only one extremum and (b) Mean value of IMF is zero.
The data set T¯un is decomposed into IMFs ye(n) and residue q(n). The mathematical formula corresponding to this decomposition is described in Eq. (13). 13 yn=∑eyen+yn
Furthermore, the detailed steps of EMD are given below. At first, initialization is processed i.e., d ≔ 1,q0(n) = y(n)
As per the following steps, dth IMF is extracted
Set k0(n) ≔ qd − 1(n),m ≔ 1 and local maxima and minima of whole km − 1(n) are identified. Then the envelope UBm − 1(n) for km − 1(n) defined by the maxima and LBm − 1(n) by the minima using the cubic splines interpolation.For both the envelopes belonging to km − 1(n), the mean zm − 1(n) is determined as zm−1n=12UBm−1n−LBm−1n. This running mean is referred as low frequency local trend. Further, via the process of shifting, the evaluation of high- frequency local detail takes place.
Further, the mth component is formed as km(n) ≔ km − 1(n) − zm − 1(n). In case if km(n) is not found to be accordance with whole IMF criteria, then the process of shifting is continued by increasing mm + 1. In case, if all IMF criteria is satisfied by km(n), then set yd(n) ≔ km(n) and qd(n) ≔ qd − 1(n) − yd(n). The shifting process can be stopped, if qd(n) represents a residuum and if not, then continue the shifting process by increasing d, d + 1 and again begin the process.
Further, EMD algorithm achieves the completeness of the decomposition process automatically as yn=∑d=1vyd+q and this represents an identity. The locally orthogonal IMFs are generated by EMD algorithm and lacks to guarantee the global orthogonality, since identical frequencies might be utilized by neighboring IMFs at different time points. As a result of this, the bark frequency c′(u′) is obtained. This bark frequency is utilized to train FW-NN classifier.
Fuzzy wavelet neural network (FW-NN) classifier
Classification is the most frequently used prediction type [37]. Generally, the wavelet functions are combined with neural nets to provide better results [17–19]. In this work, a FW-NN model is employed and it is combination of fuzzy logic concepts and wavelet neural network. In FW-NN, each fuzzy rule corresponds to a WNN comprised of numerous wavelets with changeable translation and dilation parameters. The fuzzy rules are being the consequent part of theFW-NN architecture and it is described only by wavelet functions. The output of WNN is expressed as per Eq. (14). 14 Y=∑j=1kδjκjX
In which κj is jth layers wavelet activation function corresponding to the hidden layer. In addition, δj is the weight between the hidden (hid) and output layer.
The FWNN combines the wavelet functions and the TSK fuzzy system. A MF is shown by each of the region in the TSK fuzzy model. The FWNN has the properties of high precision and fast convergence. The FW-NN has six layers and they are discussed in the below section.
Layer 1 (input layer)
The input signal vector In = (In1, In2, …, Inn) is fed as input to the next layer and the whole FW-NN model is trained with the bark frequency c′(u′).
Layer 2 (fuzzification layer)
The fuzzy MFs are shown by each of the neuron in IF part of the rules. The MFs values are the outcomes’ from this layer. In the first layer there is l1 count of MFs and in the second layer there is l2 count of MFs. For the ith input variable, the Gaussian membership function is shown as per Eq. (15). 15 Ajii=exp−Xi−ϖjiςji2;i=1,2,.,nandji=1,2,…,li
Layer 3 Grey wolf (fuzzy rule layer)
In this layer, each neurons show fuzzy rule. The lth nodes outcome is denoted as per Eq. (2). Here, each of the input MFs based possible combinations describes a fuzzy rule. 16 ηl=∏i=1nAjiiXi
Layer 4 Grey wolf (normalization layer)
Normalization factor is computed for each of the neurons in this layer. The lth nodesnormalization factor is expressed as per Eq. (17). 17 ηl¯=ηl∑j=1mηl
Layer 5
The weighted output value is computed in this layer as per Eq. (18). 18 Fl=ηl¯χl
Layer 6
The overall output is calculated in this layer by summing the previous layers outputs. This is mathematically shown in Eq. (19). 19 Out=∑l=1mFl
During the training phase, the MSE is selected as the performance index and this MSE minimization is being the major objective of the current research work. The mathematical formula for MSE based training is shown in Eq. (20). Here, the actual FWNN outcome is Act and the desired outcome is Pre. 20 Er=1N∑k=1NAct−Pre
Adaptive randomizatized grey wolf algorithm: solution encoding and objective function
Objective function and solution encoding
The major objective of the current research work is to minimize the error Er of the FW-NN. This is expressed mathematically in Eq. (21). 21 Obj=MinEr
The AR-GWO is employed for properly tuning the tuning factor η, which is accomplished by means of optimizing the hidden neurons (hid) of FW-NN. The solution fed as input to AR-GWO is exhibited in Fig. 3. Fig. 3 Solution encoding
Standard GWO
GWO [11, 32] was introduced by Mirjalili on the basis of the natural behavior of the grey wolves and it belongs to the category of swarm intelligence algorithm. Three are four types of grey wolves and these wolves stay in groups. The highest authority among them is the α (alpha) and it has the responsibility of taking decision. The supporter of α in taking decisions is β (beta), the lowest among these wolves is ω (omega) and it has to bow other wolves. The leftovers are referred as δ (delta). The main phases of GWO are “hunting, chasing and approaching the prey, encircling the prey and attacking the prey”. The upcoming section portrays the mathematical model of GWO.
Mathematical model of GWO (i) Search for prey (exploitation): In the search process, the 1st, 2nd and 3rd best solutions are obtained during the search process of unique α, β and δ
(ii) Encircling prey: The mathematical formula for prey encircling during the hunting process is represented in Eqs. (22) and (23). In Eq. (24) the current iteration and the localization of the prey is represented as x&Cg(x). The coefficient vectors are indicated as Y and D. In addition, C(x) represents the position of the grey wolf and the random values are manifested as b1 & b2. In addition Eqs. (24) and (25) are the mathematical formula for calculating the coefficient vectors Y and D, here there is a gradual decrease in the value of c from 2 to 0 over the course of iterations.
22 A=D.Cgx−Cx
23 Cx+1=Cgx−Y.A
24 Y=2.cb1−c
25 D=2.b2
(iii) Hunting the prey: There lacks no information on the location of the prey in the search space. An assumption is made here that a better knowledge on the potential location of prey can be acquired from α, β and δ. This is the reason behind the storage first three results by discarding the others. The mathematical formula for hunting of prey is depicted in Eqs. (26) to (32) [32].
26 Aα=D.Cα−C
27 C1=Cα−Y1.Aα
28 Aβ=D.Cβ−C
29 C2=Cβ−Y2.Aβ
30 Aδ=D.Cβ−C
31 C3=Cδ−Y3.Aδ
32 Cx+1=C1+C2+C33
(iv) (iv) Attacking the prey (exploitation): This is the end process of hunting behaviour of grey wolf and this process take place, when the prey is stationary.
AR-GWO
The conventional GWO suffers from the drawbacks of “bad local searching ability, low solving precision and slow convergence”. So, the AR-GWO is formulated. In the conventional GWO, the random values b1and b2 are within the range [0, 1] and they are utilized to find the coefficient vectors Y and D in Eqs. (24) and (25). But, in the proposed model, instead of random numbers the proposed algorithm determines the random values bi1 and bi2 on the basis the fitness functions. The coefficient vectors are presented as Yi and Di are computed by utilizing Eqs. (33) and (34). Here i denote α, β and δ wolves. Further, the random values bi1 and bi2 are determined by using Eqs. (35) and (36), in which fitness of the best wolves either α, β or δ is represented as Fi, 33 Yi=2.cbi1−c
34 Di=2.bi2
35 bi1=Fi
36 b21=Fi13∑i=α,β,δFi
The resultant from AR-GWO is the properly tuned tuning factor ηtuned, which is fed as input to adaptive Wiener filtering.
Adaptive WienerFiltering
The role of tuning ratio ηtuned is highly substantiated. The estimated tuning ratio by the FW-NN, on the basis of the c′(u′) (bark frequency) of the NMF-based filtered EMD signal T¯on is fine-tuned by AR-GWO. Mathematically, c′(u′) can be expressed as per Eq. (37) 37 c′u′=13arctan0.76u′+3.5arctan0.33u′2
The properly tuned tuning ratio ηtuned acquired from AR- GWO is fed as input to the wiener filter, instead of the constant η. The outcomes of the Adaptive Wiener filter are the filtered signal Tun¯¯. Again, Tun¯¯ is decomposed using EMD and the result is the enhanced denoised signal Ton¯¯.
In the training process, the training library is constructed by giving the known c′(u′) (bark frequency) and tuning ratio ηtuned as inputs. The testing process is said to be the online process, while the training process is an offline process. The appropriate tuning factor for diverse noises are identified in the offline process and with this, the FW-NN is trained. The actual enhancement process takes place in the online mechanism, where the tuning factor is identified with the trained network.
Results and discussion
Experimental setup
The proposed speech enhancement model using GWO with FW-NN was implemented in MATLAB and the resultant of each of the analysis is observed. The data set for the research work is gathered from [23]. In this database, the five noise types, namely, “airport noise, exhibition noise, restaurant noise, station noise and street noise” are added to the speech signals. The performance of the proposed model (AR-GWO) is compared with the extant modelslike GA [29], PSO [20], ABC [24], FF [12] and GWO [14] in terms of “SDR, PESQ, SNR, RMSE, Correlation, ESTOI and CSED”. Also, statistical analysis and computational time analysis are performed. Figure 4 exhibits the noisy and denoised signal for different approaches like GA, PSO, ABC, FF and GWO. Fig. 4 The noisy and denoised signal of various approaches (a) GA (b) ABC (c) PSO (d) FF(e) GWO and (f) AR-GWO
Performce analysis of airport noise
The performance evaluation of the proposed model over the existing model for airport noise at varying SNR levels is shown in Table 2. whenSNR = 0 dB, the SDR of the proposed model is 2.13%, 1.04%, 0.67%, 0.56% and 2.4% superior to the extant models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively.PESQ of the proposed model at SNR = 0 dB exhibits an improvement of 3.7%, 2.6%, 4.5%, 1.3% and 1% over the extant models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively.In airport noise at SNR = 5 dB, RMSE of the proposed model is 3.4%, 2.7%, 1.6%, 3.44% and 0.9% superior to the traditional models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. At SNR = 10 dB, ESTOI of the proposed model is 1.11% better than GA based η tuning, 1.6% better than ABC based η tuning, 2% better than PSO based η tuning, 1.7% better than FF based η tuning and 0.9% better than GWO based η tuning. Further, at SNR = 10 dB, STOI of the proposed model shows an improvement of 0.9%, 1%, 1.2%, 1.1% and 0.7% better than classical model like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. Table 2 Performance evaluation of proposed model over existing for airport noise at varying SNR
Airport Noise at SNR = 0 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 4.7437 1.9181 5.0273 0.024047 0.83179 0.50627 0.7133
ABC [24] based η tuning 4.6986 1.9643 5.165 0.023663 0.82836 0.50418 0.71323
PSO [20] based η tuning 4.6933 1.9661 5.2589 0.023316 0.83346 0.49648 0.70853
FF [12] based η tuning 4.7909 1.9454 5.1998 0.023503 0.829 0.50408 0.71318
GWO [33] based η tuning 4.8551 1.9531 5.1905 0.023567 0.82864 0.50189 0.71254
AR-GWO based η tuning 4.9841 1.9703 5.2668 0.02327 0.82995 0.50845 0.71535
Airport Noise at SNR = 5 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 9.5432 2.3844 8.4923 0.016008 0.92871 0.6604 0.8186
ABC [24] based η tuning 9.71 2.3865 8.5657 0.015902 0.92942 0.66107 0.81988
PSO [20] based η tuning 9.4551 2.4003 8.6167 0.01572 0.93146 0.66148 0.82061
FF [12] based η tuning 9.5676 2.3794 8.5016 0.016011 0.9287 0.66177 0.81667
GWO [33] based η tuning 9.6879 2.3984 8.6911 0.015614 0.93199 0.66267 0.82075
AR-GWO based η tuning 9.746 2.4058 8.7794 0.01546 0.9324 0.66586 0.82486
Airport Noise at SNR = 10 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 12.373 2.7008 10.51 0.012779 0.95782 0.77512 0.88209
ABC [24] based η tuning 12.533 2.7093 10.843 0.01222 0.96042 0.77079 0.88111
PSO [20] based η tuning 12.493 2.7153 10.54 0.01263 0.95905 0.76772 0.87947
FF [12] based η tuning 12.517 2.7075 10.754 0.012384 0.95943 0.76992 0.88066
GWO [33] based η tuning 12.57 2.7293 10.765 0.012342 0.95975 0.77607 0.88368
AR-GWO based η tuning 12.671 2.732 11.128 0.011823 0.96271 0.78377 0.89057
Airport Noise at SNR = 15 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 14.046 2.9512 11.823 0.011128 0.96883 0.83878 0.91063
ABC [24] based η tuning 14.387 2.9856 12.257 0.010448 0.97199 0.84432 0.91623
PSO [20] based η tuning 14.023 2.9525 11.73 0.011077 0.96909 0.83847 0.91185
FF [12] based η tuning 14.37 2.9732 12.34 0.010484 0.97152 0.84457 0.91637
GWO [33] based η tuning 14.303 2.9651 12.18 0.010559 0.9715 0.84048 0.91378
AR-GWO based η tuning 14.616 2.988 12.576 0.010081 0.97384 0.84906 0.9207
Performce analysis of exhibition noise
Table 3 exhibits the performance analysis of the proposed model over exiting for exhibition noise at different SNR levels. At SNR = 0 dB, the proposed model shows an improvement of 10.3%, 3.6% 10.2%, 3.1% and 1.6% over the classical models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectivelyin terms of SNR. Further, RMSE of the proposed model is 5.4%, 2.4%, 6.5%, 2% and 0.9% better than the extant models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively at SNR = 0 dB. For the exhibition noise at SNR = 5 dB, the SDR of the proposed model is improvedover the existing model as 15.7%, 2.16%, 1.2%, 0.86%, and 6.83% by GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. Then, in terms of Correlation at SNR = 10 dB, the proposed model is found to be better than the existing approaches GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. ESTOI of the proposed model is 0.6% better than GA based η tuning, 0.05% better than ABC based η tuning, 0.06% better than PSO based η tuning, 0.3% better than FF based η tuningand 0.15% better than GWO based η tuningat SNR = 10 dB. Table 3 Performance evaluation of proposed model over existing for exhibition noise at varying SNR
Exhibition Noise at SNR = 0 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 4.8816 1.8847 4.9769 0.024181 0.83386 0.5536 0.73186
ABC [24] based η tuning 5.3046 1.9195 5.2921 0.023453 0.83881 0.55774 0.7336
PSO [20] based η tuning 4.934 1.9288 4.9329 0.024466 0.83118 0.5594 0.73382
FF [12] based η tuning 5.3942 1.9284 5.3336 0.023355 0.83972 0.55461 0.73462
GWO [33] based η tuning 5.5763 1.9176 5.404 0.023082 0.84347 0.56018 0.73376
AR-GWO based η tuning 5.6496 1.9372 5.4944 0.022868 0.84495 0.56032 0.73619
Exhibition Noise at SNR = 5 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 8.8427 2.268 8.0345 0.016949 0.9184 0.66867 0.82182
ABC [24] based η tuning 9.2962 2.2925 8.338 0.016348 0.92256 0.67082 0.82384
PSO [20] based η tuning 9.383 2.3008 8.3461 0.016334 0.92438 0.67058 0.81908
FF [12] based η tuning 9.4158 2.3035 8.2985 0.016411 0.92435 0.67239 0.822
GWO [33] based η tuning 8.8893 2.2617 8.3604 0.016278 0.92534 0.67411 0.82333
AR-GWO based η tuning 9.497 2.3164 8.4358 0.016145 0.92541 0.67664 0.82735
Exhibition Noise at SNR = 10 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 12.766 2.6089 10.685 0.012575 0.95814 0.77244 0.88091
ABC [24] based η tuning 12.819 2.626 10.922 0.01215 0.96033 0.77738 0.88182
PSO [20] based η tuning 12.838 2.6333 10.654 0.012527 0.95848 0.77733 0.88133
FF [12] based η tuning 12.791 2.63 10.615 0.012602 0.95782 0.77547 0.88071
GWO [33] based η tuning 12.894 2.6031 10.727 0.012474 0.95847 0.77665 0.88108
AR-GWO based η tuning 12.951 2.6351 11.112 0.011962 0.96048 0.77782 0.88468
Exhibition Noise at SNR = 15 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 15.159 2.8586 12.591 0.010224 0.97272 0.84184 0.91566
ABC [24] based η tuning 15.389 2.9084 12.878 0.00981 0.97467 0.85189 0.92211
PSO [20] based η tuning 15.296 2.9074 12.375 0.01035 0.97274 0.84318 0.91555
FF [12] based η tuning 15.201 2.8987 12.537 0.01017 0.97332 0.84546 0.91675
GWO [33] based η tuning 15.247 2.9056 12.532 0.010191 0.97319 0.84327 0.91605
AR-GWO based η tuning 15.602 2.9094 13.251 0.009483 0.97579 0.85294 0.92215
Performce analysis of restaurant noise
Table 4 portrays the performance evaluation of the proposed model over the existing for restaurant noise at different SNR levels. From, which SDR of the signal at SNR = 0 dB is 8.5%, 5.7%, 9.7%, 5.7% and 4.3% superior to the classical models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning. PESQ of the proposed modelis found to be 1.2%, 0.4% better than GA and ABC, 0.2%, 0.9% and0.7% better than PSO, FF and GWO, respectively at SNR = 0 dB. Then, for SNR = 5 dB, RMSE of the proposed model exhibits superiority to the traditional models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning by 1.54%, 0.04%, 1.2%, 0.7% and 0.09%, respectively. Further, in terms of SNR, there is an improvement of 1.8%, 0.19%, 1.6%, 0.9% and 0.7% in the proposed model over the existing model like GA, ABC, PSO, FF and GWO, respectively at SNR = 5 dB. Moreover, from SNR = 10 dB, STOI of the proposed model is 0.8%, 0.5%, 0.7%, 0.6% and 0.76% better than state-of-art models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning. CSED at SNR = 10 dB is 6.9%, 2%, 6.7%, 5.9% and 5.13% superior to the extant modelsGA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. Table 4 Performance evaluation proposed model over existing for restaurant noise at varying SNR
Restaurant Noise at SNR = 0 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 3.7234 1.9355 4.459 0.025493 0.80808 0.51043 0.70067
ABC [24] based η tuning 3.8386 1.9501 4.5555 0.025202 0.8115 0.51518 0.70489
PSO [20] based η tuning 3.6758 1.9541 4.3721 0.025728 0.8088 0.51486 0.70261
FF [12] based η tuning 3.838 1.9409 4.5605 0.025168 0.81113 0.51307 0.70103
GWO [33] based η tuning 3.8974 1.9553 4.5775 0.025115 0.81268 0.51203 0.70278
AR-GWO based η tuning 4.073 1.9597 4.6674 0.024878 0.81594 0.517 0.7076
Restaurant Noise at SNR = 5 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 8.8132 2.3121 8.1199 0.016642 0.92163 0.65082 0.81008
ABC [24] based η tuning 8.8225 2.316 8.2539 0.016383 0.92313 0.64843 0.80827
PSO [20] based η tuning 8.8684 2.3083 8.137 0.016599 0.92168 0.64538 0.8055
FF [12] based η tuning 8.6289 2.3145 8.2625 0.016515 0.92195 0.64878 0.80944
GWO [33] based η tuning 8.8698 2.3071 8.2049 0.016374 0.92304 0.64866 0.80906
AR-GWO based η tuning 8.9533 2.3219 8.2702 0.01639 0.92368 0.65163 0.81352
Restaurant Noise at SNR = 10 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 11.913 2.6448 10.313 0.013046 0.95504 0.7633 0.87382
ABC [24] based η tuning 12.11 2.6647 10.638 0.012508 0.95762 0.76751 0.87699
PSO [20] based η tuning 11.981 2.6569 10.2 0.013148 0.95455 0.76607 0.87308
FF [12] based η tuning 11.915 2.6478 10.452 0.012784 0.95646 0.76327 0.87696
GWO [33] based η tuning 12.089 2.6708 10.565 0.012615 0.95741 0.76792 0.87634
AR-GWO based η tuning 12.139 2.6774 10.696 0.012403 0.95866 0.7743 0.88253
Restaurant Noise at SNR = 15 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 14.189 2.8967 12.05 0.010765 0.97066 0.84242 0.91343
ABC [24] based η tuning 14.469 2.9243 12.45 0.010169 0.97351 0.84493 0.91598
PSO [20] based η tuning 14.298 2.9281 12.014 0.010704 0.97139 0.84393 0.91434
FF [12] based η tuning 14.268 2.9093 12.153 0.010616 0.97125 0.84181 0.91481
GWO [33] based η tuning 14.281 2.9194 12.14 0.010567 0.97167 0.84285 0.91416
AR-GWO based η tuning 14.617 2.9452 12.676 0.009908 0.9749 0.85112 0.92113
Performce analysis of station noise
From 5 represents the performance analysis of the proposed model over exiting for station noise at different SNR values as (Table 5 shows the performance evaluation of the proposed model over existing model for station noise at varying SNR).. From the table, at SNR = 0 dB, the proposed model overtakes the extant modelsGA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning by 2.6%, 4.5%, 1.2%, 2.7% and 1%, respectively in terms of SDR. Moreover, SEQ of the proposed model at SNR = 0 dB is 3.7%, 1.14%, 2.2%, 1.7% and 1% better than the extant models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. Then, for SNR = 5 dB, the proposed model is better than extant models, 5.4% by GA, 2.4% by ABC, 1.2% by PSO, 3.1% by FF and 1.6% by GWO. SEI of the proposed model at SNR = 10 dB, an improvement of 0.3%, 0.2%, 0.1%, 0.5% and 0.02% over the state-of-art models. Then, atSNR = 15 dB, the proposed model is 0,6%, 0.02%, 0.9%, 0.3% and 0.4% better than extant modelsGA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning in terms of STOI. In terms of CSED at SNR = 15 dB, the proposed model is 9.5%, 4.5%, 10.9%, 9.8% and 7.7% better than the traditional models GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. Table 5 Performance evaluation proposed model over existing for station noise at varying SNR
Station Noise at SNR = 0 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 6.4259 2.037 5.7614 0.022214 0.86557 0.47946 0.70202
ABC [24] based η tuning 6.3054 2.0924 5.6648 0.022488 0.86031 0.4714 0.70522
PSO [20] based η tuning 6.5155 2.0598 5.7821 0.022054 0.86512 0.47993 0.70432
FF [12] based η tuning 6.4156 2.0788 5.8548 0.021868 0.86597 0.47663 0.70174
GWO [33] based η tuning 6.5284 2.0458 5.7819 0.022073 0.86721 0.47881 0.70517
AR-GWO based η tuning 6.5994 2.1167 5.9058 0.021723 0.86727 0.48062 0.70639
Station Noise at SNR = 5 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 9.6888 2.4452 8.168 0.01657 0.92905 0.65479 0.81531
ABC [24] based η tuning 9.8802 2.4501 8.5373 0.015867 0.93236 0.64988 0.81377
PSO [20] based η tuning 9.8902 2.4446 8.356 0.016186 0.93232 0.65575 0.81579
FF [12] based η tuning 9.894 2.4484 8.3898 0.016162 0.93177 0.65616 0.81535
GWO [33] based η tuning 9.924 2.4529 8.4232 0.016112 0.9314 0.65599 0.816
AR-GWO based η tuning 10.04 2.4669 8.6676 0.015649 0.93302 0.6575 0.81666
Station Noise at SNR = 10 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 12.654 2.7153 10.69 0.012513 0.9598 0.76866 0.87386
ABC [24] based η tuning 12.746 2.7219 10.816 0.012267 0.96001 0.76982 0.87447
PSO [20] based η tuning 12.482 2.7009 10.411 0.012815 0.95793 0.76372 0.86911
FF [12] based η tuning 12.647 2.7094 10.755 0.012396 0.95977 0.76721 0.87422
GWO [33] based η tuning 12.654 2.7334 10.744 0.012352 0.96011 0.77175 0.87556
AR-GWO based η tuning 12.758 2.7343 10.988 0.012003 0.9621 0.77158 0.87685
Station Noise at SNR = 15 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 14.281 2.9701 11.881 0.011026 0.96941 0.83574 0.91008
ABC [24] based η tuning 14.569 2.9968 12.436 0.010197 0.97367 0.84294 0.91569
PSO [20] based η tuning 14.096 2.967 11.657 0.011177 0.96897 0.83418 0.90697
FF [12] based η tuning 14.394 2.9911 12.166 0.010578 0.97211 0.83742 0.91285
GWO [33] based η tuning 14.338 2.9964 12.044 0.010711 0.97133 0.83899 0.91214
AR-GWO based η tuning 14.732 2.9993 12.671 0.009969 0.97436 0.84346 0.91593
Performce analysis of street noise
The performance evaluation of the proposed model over the existing model for the street noise is shown in Table 6. For SNR = 0db, the proposed model exhibits an improvement of 1.7%, 0.5%, 1.3%, 1.72% and 1.7% over the classical models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively in terms of CSED. Then, for the same SNR, the STOI of the projected model is 0.4%, 0.3%, 0.9%, 0.7% and 0.3% superior to the state-of-art models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. For SNR = 5 dB, ESTOI of the proposed model is 1.3%, 0.9%, 1.4%, 0.5% and 0.4% superior to the conventional models GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. The correlation of the signal for the same SNR is 0.35%, 0.017%, 0.13%, 0.2% and 0.29% superior to the existing approaches GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. Then, in case of SNR = 15 dB, the PESQ of the proposed model is 1.8%, 0.27%, 0.8%, 0.9% and 0.89% better than GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively. Then, for the same SNR, the proposed model is 2.2%, 0.3%, 2.7%, 1.7% and 2.12% better than the traditional models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively in terms of SDR at 15 dB. Table 6 Performance evaluation proposed model over existing for street noise at varying SNR
Street Noise at SNR = 0 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 6.4479 2.0587 5.8042 0.02216 0.86391 0.51601 0.72324
ABC [24] based η tuning 6.7136 2.1067 5.8664 0.021787 0.86832 0.51561 0.72419
PSO [20] based η tuning 6.3911 2.0922 6.0489 0.021285 0.86341 0.51708 0.71952
FF [12] based η tuning 6.8776 2.0922 5.9977 0.021426 0.86787 0.51849 0.7213
GWO [33] based η tuning 6.7047 2.0819 5.9561 0.021506 0.86648 0.51715 0.72374
AR-GWO based η tuning 6.9113 2.1121 6.0753 0.021276 0.86971 0.51968 0.72652
Street Noise at SNR = 5 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 10.343 2.4608 8.459 0.016038 0.93221 0.65462 0.80808
ABC [24] based η tuning 10.477 2.4569 8.7538 0.015468 0.9354 0.65674 0.81378
PSO [20] based η tuning 10.408 2.4771 8.5652 0.015798 0.9343 0.65378 0.80799
FF [12] based η tuning 10.409 2.4678 8.6381 0.015704 0.9335 0.65946 0.81023
GWO [33] based η tuning 10.378 2.4718 8.5641 0.015827 0.93281 0.6603 0.81101
AR-GWO based η tuning 10.508 2.4865 8.8397 0.015302 0.93556 0.6632 0.81415
Street Noise at SNR = 10 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 13.28 2.759 11.182 0.011819 0.96423 0.75127 0.87123
ABC [24] based η tuning 13.483 2.7811 11.623 0.01118 0.96669 0.75718 0.87601
PSO [20] based η tuning 13.477 2.7518 11.243 0.01165 0.96555 0.75744 0.87482
FF [12] based η tuning 13.473 2.7955 11.401 0.011478 0.96623 0.75838 0.87631
GWO [33] based η tuning 13.451 2.7753 11.307 0.0116 0.96554 0.75485 0.87494
AR-GWO based η tuning 13.619 2.7998 11.643 0.011159 0.96756 0.75995 0.87721
Street Noise at SNR = 15 dB
Approaches SDR PESQ SNR RMSE CORR ESTOI STOI
GA [29] based η tuning 14.94 2.9263 12.472 0.010375 0.97234 0.82301 0.90012
ABC [24] based η tuning 15.24 2.9737 12.86 0.009771 0.97544 0.82681 0.90526
PSO [20] based η tuning 14.869 2.9574 12.26 0.010444 0.97267 0.81959 0.89918
FF [12] based η tuning 15.025 2.9532 12.597 0.010133 0.97394 0.82197 0.9005
GWO [33] based η tuning 14.958 2.9554 12.435 0.010269 0.97339 0.8188 0.89966
AR-GWO based η tuning 15.286 2.982 13.042 0.009615 0.976 0.82982 0.90647
Statistical analysis
The evaluation of statistical analysis of the adopted and existing approaches is depicted in Fig. 5. The outcomes are provided based on the error and thus the proposed model value is lower than the existing works. On considering the results, the best value of the adopted AR-GWO scheme is 9.41%, 3.51%, 8.99%, 3.84%, and 4.53% superior to the existing GA, ABC, PSO, FF, and GWO approaches. Furthermore, in mean case scenario, the suggested approach value is 5.21%, 2.57%, 3.37%, 2.81%, and 2.33% superior to the existing GA, ABC, PSO, FF, and GWO approaches. Moreover, the median value of the AE-GWO approach is 0.013641 and it is 5.22%, 2.99%, 3.77%, 3.92%, and 2.41% better than the existing GA, ABC, PSO, FF, and GWO methods. Therefore, the effectiveness of the proposed speech enhancement model is proved. Fig. 5 Statistical analysis of the proposed and existing approaches
Computational time analysis
In this section, the computational time of the proposed and existing methods is evaluated and it is depicted in Fig. 6. From the graph, the computation time of the proposed AR-GWO method is 227.86 and it is 34.07%, 43.57%, 28.86%, 38.88%, and 16.03% better than the existing GA, ABC, PSO, FF, and GWO approaches respectively. Thus, the effectiveness of the adopted AR-GWO based speech enhancement method is validated. Fig. 6 Computational time analysis of the proposed and existing approaches
Practical implications
The major aim of the proposed speech enhancement is to suppress the noise in a noisy speech signal and improve the quality and intelligibility of speech. The proposed speech enhancement approach utilizes in real-time applications such as speech recognition, mobile phones, VoIP, teleconferencing systems and hearing aids.
Conclusion
In this paper, an optimized fuzzy wavelet neural network based speech enhancement model is proposed. In the training phase, the input noise corrupted signal was initially provided as input to both STFT-based noise estimation and NMF-based spectrum estimation for estimating the noise spectrum and signal spectrum, respectively. The obtained noise spectrum and the signal spectrum are fed as input to the wiener filter and these filtered signals are subjected to EMD.Since, tuning factorη plays a key role in wiener filter, it has to be determined for each signals, and is trained in FW-NN. Then, from the denoised signal the bark frequency is evaluated. The computed bark frequency is fed as input to the learning algorithm referred as FW-NN for detecting the suited tuning factorη for the entire input signal in Weiner filter. The AR-GWO is employed for proper tuning of the tuning factor η referred as tuned tuning factor (ηtuned). In the testing phase, the training is accomplished initially and from which the tuning factor is gathered for each of the relevant input signal. Then, the properly tuned tuning factor (ηtuned) from FW-NN is fed as input to EMD via adaptive wiener filter for decomposing the spectral signal and the output of EMD is denoised enhanced speech signal.Theresultant acquired is compared over the existing models in terms of various measures. In case of street noise, at SNR = 0db, the proposed model exhibits an improvement of 1.7%, 0.5%, 1.3%, 1.72% and 1.7% over the classical models like GA based η tuning, ABC based η tuning, PSO based η tuning, FF based η tuning and GWO based η tuning, respectively in terms of CSED. Thus, the effectiveness of the work is validated via the result analysis. However, in statistical analysis, the standard deviation metric value is not better than the existing ones. Hence, in the future work, we enhanced our proposed work by utilizing the recent optimization algorithms and validate the work in real-time applications.
Acknowledgements
I would like to express my very great appreciation to the co-authors of this manuscript for their valuable and constructive suggestions during the planning and development of this research work.
Author contribution
All authors have made substantial contributions to conception and design, revising the manuscript, and the final approval of the version to be published. Also, all authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Data availability
The data that support the findings of this study is “NOIZEUS” openly available in https://ecs.utdallas.edu/loizou/speech/noizeus/.
Declarations
Ethical approval
This paper does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
Not Applicable.
Conflict of interest
The authors declare no conflict of interest.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Letter to the Editor
Accelerated T-cell exhaustion: its potential role in autoimmune disease and hyperinflammatory disease pathogenesis
http://orcid.org/0000-0002-4843-9835
Roe Kevin [email protected]
San Jose, CA USA
7 12 2022
14
16 11 2022
1 12 2022
© The Author(s) under exclusive licence to Japan Human Cell Society 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
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pmcThere can be significant interactions between intracellular pathogens infecting the same cells [1]. One possibility is that a chronic and/or latent first pathogen infection can cause conventional T-cell exhaustion for T-cells targeting itself, and also accelerate T-cell exhaustion for T-cells targeting a second pathogen [1]. This could involve creating a cytokine environment which facilitates T-cell exhaustion, inducing T-cell expressions of inhibitory receptors, such as PD-1; and inducing infected host cell expressions of inhibitory ligands, such as PD-L1, to bind to the T-cell inhibitory receptors [1]. A second distinct pathogen infection, particularly a virulent pathogen which creates high antigen titers, can benefit from the T-cell exhaustion facilitating cytokine environment, and/or expression of inhibitory ligands by the same infected cells, and accelerate a T-cell exhaustion for the second pathogen [1].
T-cell exhaustion has been repeatedly linked to COVID-19 cases having severe outcomes and/or mortality [2]. T-cell exhaustion can degrade the functions of both CD8+ and CD4+ T-cells. This also includes follicular helper CD4+ T-cells, located primarily in lymph node and spleen germinal centers, where these CD4+ T-cells have critical roles in enabling antibody affinity maturation, isotype switching, generation of memory B-cells and in B-cell differentiation into immunoglobulin (antibody) secreting plasma cells [3]. Accelerated T-cell exhaustion could have significant effects on first-time infections by the second pathogen, if germinal center follicular helper CD4+ T-cell functions are inhibited, and immunoglobulins (antibodies) from B-cells are numerically decreased or qualitatively inadequate in affinity selection/maturation from somatic hypermutation to suppress the second pathogen [1, 4].
Such inadequate B-cell populations have been documented in severe cases of COVID-19, where patients have relatively higher population fractions of the less-developed membrane-bround IgM immunoglobulins on B-cells, in contrast to relatively higher population fractions of the more developed membrane-bound IgG immunoglobulins on B-cells observed in control patients or patients with mild cases [5]. These observations of isotype differences in the immunoglobulin expression by B-cells suggest follicular helper CD4+ T-cell interactions with B-cells in germinal centers did not promote adequate somatic hypermutation and isotype switching and affinity maturation of immunoglobulins targeting the SARS-CoV-2 virus, which can be a result of CD4+ T-cell exhaustion in these severe cases [4].
In summary, accelerated T-cell exhaustion by its inhibition of follicular helper CD4+ T-cells critical for conventional B-cells, can cause impaired B-cells and their production of abnormally high proportions of less-developed antibodies.
One observed result of accelerated T-cell exhaustion may be elevated mortality rates for COVID-19 and other epidemics, in which the second pathogen infection quickly achieves T-cell exhaustion, and fatally overwhelms an individual's adaptive immune system [1].
However, dysfunctionality can have various degrees of expression. There may also be rarer instances of accelerated T-cell exhaustion which result in dyfunctional B-cells which release numerous quasi-dysfunctional immunoglobulins/antibodies sufficiently functional to avoid mortality and severe infections, but having alternative unfortunate consequences. In numerously documented cases, small percentages of mild cases of COVID-19 have resulted in extensive hyperinflammatory diseases, including multisystem inflammatory syndrome (MIS) and autoantibodies [6]. Hyperinflammatory diseases (MIS or other diseases similar to Kawasaki disease) could be consequences of abnormally high levels of antibodies secreted by B-cells and high titers of antigen–antibody immune complexes which could not be promptly phagocytized by a small percentage of individuals [6, 7].
Pathogenesis of hyperinflammatory diseases could be initiated by pathogens that evade/impair T-cell control and thus require antigen neutralization by a very large number of antibodies, creating very large numbers of antigen–antibody immune complexes which cannot be quickly phagocytized by certain individuals having transiently or permanently immuno-deficient immune systems [6]. The steps by which antigen–antibody immune complexes can initiate hyperinflammatory diseases through a Type III hypersensitivity immune reaction in immuno-deficient individuals having impaired phagocytosis have already been outlined [6]. There is also documented support from a 2020 study of intensive care cases of COVID-19, where it was observed that a TH1 (cell-mediated immunity) response evolved into a TH2 humoral immunity (antibody) response that then escalated into a Type III hypersensitivity immune reaction with deposition of antigen–antibody immune complexes in the walls of blood vessels to generate a severely inflammatory systemic vasculitis [8]. Additionally, ten puzzling aspects of hyperinflammatory diseases, including their prevalence in younger patients and mild cases and the tendency of hyperinflammatory diseases to occur only once, can be plausibly explained by the steps previously outlined [6].
Furthermore, hyperinflammatory diseases including MIS typically occur two to four weeks after a SARS-CoV-2 infection [9]. This delay time is shorter than the time needed for conventional complete T-cell exhaustion [1], and this delay time is plausibly more consistent with a multistep process of accelerated T-cell exhaustion, inducing less-developed antibody production, resulting in extensive antigen–antibody immune complex titers in a phagocytosis impaired host, causing a Type III hypersensitivity immune reaction. This would then produce protease secretions and express or expose autoantigens which can result in autoantibodies, and this could ultimately achieve pathogenesis of a hyperinflammatory disease [1, 6–8].
The development of chronic autoimmune diseases is an alternative outcome from a high titer of antigen–antibody immune complexes, which cannot be quickly phagocytized in immuno-deficient individuals, which can cause a Type III hypersensitivity immune reaction with protease secretions which can express or expose autoantigens [7, 8, 10]. Therefore, it is plausible that accelerated T-cell exhaustion in immuno-deficient individuals can be an important factor in the pathogenesis of transient hyperinflammatory diseases, including MIS and the various types of Kawasaki diseases [6], and/or an important factor in the pathogenesis of chronic autoimmune diseases, such as diabetes, lupus or another autoimmune disease [7, 8, 10].
Figure 1 summarizes various outcomes possibly leading to transient hyperinflammatory diseases (e.g., MIS or one of the Kawasaki diseases) or chronic autoimmune diseases (e.g., diabetes, lupus, or another disease).Fig. 1 summarizes accelerated T-cell exhaustion outcomes which can cause one of the transient hyperinflammatory diseases or one of the chronic autoimmune diseases or possibly a fatal outcome
In conclusion, interactions between two intracellular pathogens can have significant consequences, including accelerated T-cell exhaustion for a second pathogen. An immunologically novel second pathogen infection, especially a virulent pathogen that creates large antigen titers, could evade/impair T-cell defenses if there was accelerated exhaustion of T-cells targeting the second pathogen. Accelerated T-cell exhaustion can occur when the second pathogen can reuse the already expressed inhibitory ligands of the infected cells. It is logically plausible that accelerated T-cell exhaustion can be an important factor in causing several hyperinflammatory diseases and/or autoimmune diseases in phagocytosis impaired, immuno-deficient individuals, by inhibiting follicular helper CD4+ T-cell assistance to germinal center B-cell somatic hypermutation, affinity maturation and isotype switching of antibodies, eventually resulting in a Type III hypersensitivity immune reaction that leads to pathogenesis of a transient hyperinflammatory disease or a chronic autoimmune disease.
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3. Yesillik S Gupta S Phenotypically defined subpopulations of circulating follicular helper T cells in common variable immunodeficiency Immun Inflamm Dis 2020 8 3 441 446 10.1002/iid3.326 32618135
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7. Roe K An explanation of the pathogenesis of several autoimmune diseases in immuno-compromised individuals Scand J Immunol 2021 93 3 e12994 10.1111/sji.12994 33151588
8. Roncati L Ligabue G Fabbiani L Malagoli C Gallo G Lusenti B Nasillo V Manenti A Maiorana A Type 3 hypersensitivity in COVID-19 vasculitis Clin Immunol 2020 217 108487 10.1016/j.clim.2020.108487 32479986
9. Ailioaie LM Ailioaie C Litscher G Implications of SARS-CoV-2 infection in systemic juvenile idiopathic arthritis Int J Mol Sci 2022 23 8 4268 10.3390/ijms23084268 35457086
10. Kessenbrock K Fröhlich L Sixt M Lämmermann T Pfister H Bateman A Belaaouaj A Ring J Ollert M Fässler R Jenne DE Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin J Clin Invest 2008 118 7 2438 2447 10.1172/JCI34694 18568075
| 36478089 | PMC9735067 | NO-CC CODE | 2022-12-14 23:28:32 | no | Hum Cell. 2022 Dec 7;:1-4 | utf-8 | Hum Cell | 2,022 | 10.1007/s13577-022-00839-6 | oa_other |
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Rev Endocr Metab Disord
Rev Endocr Metab Disord
Reviews in Endocrine & Metabolic Disorders
1389-9155
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10.1007/s11154-022-09774-1
Article
Phase angle (PhA) in overweight and obesity: evidence of applicability from diagnosis to weight changes in obesity treatment
Cancello Raffaella [email protected]
1
http://orcid.org/0000-0003-3059-544X
Brunani Amelia [email protected]
2
Brenna Ettore [email protected]
3
Soranna Davide 3
Bertoli Simona [email protected]
14
Zambon Antonella [email protected]
35
Lukaski Henry C. [email protected]
6
Capodaglio Paolo [email protected]
[email protected]
27
1 grid.418224.9 0000 0004 1757 9530 Obesity Unit and Laboratory of Nutrition and Obesity Research, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
2 grid.418224.9 0000 0004 1757 9530 Laboratory of Biomechanics, Rehabilitation and Ergonomics, IRCCS, Istituto Auxologico Italiano, Piancavallo Verbania, Italy
3 grid.418224.9 0000 0004 1757 9530 Biostatistic Unit, IRCCS Istituto Auxologico Italiano, Milano, Italy
4 grid.4708.b 0000 0004 1757 2822 Department of Food, Environmental and Nutritional Sciences (DeFENS), International Center for the Assessment of Nutritional Status (ICANS), University of Milan, Via Sandro Botticelli 21, 20133 Milan, Italy
5 grid.7563.7 0000 0001 2174 1754 Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
6 grid.266862.e 0000 0004 1936 8163 Department of Kinesiology and Public Health Education, University of North Dakota, Grand Forks, USA
7 grid.7605.4 0000 0001 2336 6580 Department of Surgical Sciences, Physical Medicine and Rehabilitation, University of Torino, 10126 Torino, Italy
9 12 2022
114
28 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Phase angle (PhA) is a recently proposed marker of nutritional status in many clinical conditions. Its use in patients with obesity presents different critical concerns due to the higher variability of the two measured parameters (resistance, R, and reactance, Xc) that contribute to the determination of PhA. Controversial is the relation between PhA and BMI that might vary with graded levels of obesity due to the variation in fat and free fat mass. Obesity is frequently associated with metabolic, hepatic, cardiovascular and kidney diseases that introduce variations in PhA values, in relation to multimorbidity and severity degree of these diseases. It is reported that the improvement of clinical condition is associated with a positive change in PhA. Also, the treatment of obesity with weight loss might confirm this effect, but with different responses in relation to the type and duration of the intervention applied. In fact, the effect appears not only related to the percentage of weight loss but also the possible loss of free fat mass and the nutritional, metabolic and structural modifications that might follow each therapeutic approach to decrease body weight. We can conclude that the PhA could be used as marker of health status in patients with obesity supporting an appropriate weight loss intervention to monitor efficacy and fat free mass preservation.
Keywords
Obesity
Phase angle
Bioelectrical impedance analysis
BIA
BIVA
Weight loss
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pmcIntroduction
In 2022, the European Regional Office of the World Health Organization (WHO) updated its Report on Obesity in the European region, which highlights overweight and obesity rates that have reached epidemic proportions [1]. The document shows that 59% of European adults and almost 1 in 3 children (29% of males and 27% of females) are overweight or suffer from obesity, now considered a disease [1]. Overweight and obesity are in fact among the main causes of death and disability also in the European Region and recent estimates suggest that they cause more than 1.2 million deaths per year, corresponding to over 13% of total mortality. Obesity increases the risk of many non-communicable diseases, including cancer, cardiovascular disease, type 2 diabetes mellitus, and chronic respiratory disease [2]. Additionally, obesity is associated with an increased risk of complications and mortality in the case of SARS-CoV-2 infection [3, 4]. The prevalence of obesity in adults in the European region is higher than in any other WHO region, except the Americas [5]. Over the last five years to 2022, obesity rate among adults aged 18 and older has increased an annualized 1.8% to 33.0 people per 100 individuals [6]. WHO estimates that by 2025, approximately 167 million people (considering adults and children) will become less healthy because of overweight or obesity [1, 6].
Obesity is characterized not only by an increase (from moderate to severe) of body adipose tissue but also by alterations in the metabolic, structural and functional characteristics of skeletal muscle (i.e. low muscle quality) [7]. Surrogate measures, such as the body mass index (BMI) give no indication of fat free mass, muscle mass or nutritional state. Although obesity treatment can begin with a screening threshold of a BMI ≥ 30 Kg/m2, a proper body composition analysis is important to determine baseline fat mass and fat free mass (lean soft tissue mass). Different methods are used for body composition assessments depending on practicality and feasibility, including bioelectrical impedance analysis (BIA), anthropometry (skinfold thicknesses, body girths) and dual-energy X-ray absorptiometry (DXA) [8–10]. BIA is a simple, inexpensive, quick and non-invasive technique for assessing body composition and its changes over time. BIA is used in various clinical settings due to its safety and cost-effectiveness compared to DXA [11–13]. However, at present, the routinely use of body composition analysis by BIA for obesity treatment is still debated. Concerns include the assumption of constant hydration of the fat free mass and validity of multiple regression prediction models for fat free mass. Importantly, the water content of adipose tissue is appreciable with estimates highly variable (6 to 36%) due to limited samples and diverse anatomical sampling locations [14] with a generally accepted value of 15% [15]. Phase angle is a unique biomarker that discriminates the expanded ECW in adipose tissue [16]. It is a unique bioelectrical impedance variable to overcome these limitations because it accounts for hydration status and cell mass [12]. The PhA has been related to muscle strength, being higher in athletes and lower in sarcopenic obese subjects [17, 18]; low PhA values are associated with impaired quality of life and poor prognosis in various chronic diseases [19]. The European Working Group on Sarcopenia in Older People recently proposed the PhA as a possible indicator of muscle quality [20].
Presently, PhA has limited usefulness in clinical practice because of a lack of reference values for overweight and obese populations. Also, variability exists in responses of PhA to weight loss induced by different diet and physical activity treatments, different types of bariatric surgery and the metabolic impact of reducing inflammatory processes. The aim of this narrative review is to depict the evidence of importance and applicability of PhA in patient with obesity and in the treatment of obesity through weight reduction as well as improvement of metabolic and clinical conditions associated with obesity.
What is the physiological meaning of “phase angle” in patients with obesity?
The use of PhA and its raw BIA components has gained attention as an alternative to conventional error-prone estimation of body composition. BIA measures whole-body impedance, the opposition of the body to alternating current caused by water and electrolytes and consists of two components: resistance (R) and reactance (Xc) [21]. Resistance is the decrease in voltage reflecting conductivity through ionic solutions. Reactance is the delay in the flow of current measured as a phase-shift, reflecting dielectric properties (i.e. capacitance of cell membranes and tissue interfaces). BIA is not a direct method for body composition assessment and its accuracy in estimating body composition relies on the assumption of constant hydration of the fat free mass sample-specific regression equations [22].
The PhA is calculated with R and Xc values: PhA (°) = arctangent (Xc/R) x (180°/π); it is related to the distribution of intracellular and extracellular fluids and integrity of cells membrane [23, 24]. Importantly, from a strictly mathematical point of view, the values of R differ from those of Xc by an order of magnitude, therefore, the variability of Xc will have a significantly greater effect than those of R in the value of PhA. Biological variations in intracellular or extracellular fluids and cell membrane integrity are reflected on R and Xc values, and consequently on PhA. For this reason, some researchers have already highlighted the need to adjust for hydration status when measuring PhA. For instance, the PhA and the extracellular/total body water (ECW/TBW) ratio were important factors in malnutrition and predictors of clinical outcomes. The excess of ECW, unlike the increase in the relative intracellular water (ICW), is almost always a condition to be avoided. In many scientific studies it is often found that the increase in FM is correlated with an altered distribution of body fluids. Overweight and / or obese subjects may have a high percentage of ECW and an ECW/ICW ratio above 0.85, higher than the average for the normal weight population (about 0.70–0.75) [25, 26]. This condition is partly proven by the fact that the adipose tissue itself has a higher ECW / ICW ratio than muscular mass. In fact, while FFM has an average ECW/ICW ratio of about 0.80, adipose tissue can achieve an ECW/ICW ratio of up to about 3.7 [27 Wang J.] Consequently, a high percentage of FM can help increase the percentage of ECW. The ECW/ICW ratio could be particularly altered when the extra adipose tissue is present in the abdominal area or as a result of different mechanisms, such as water retention, total body water (TBW) in excess caused by an altered regulation of the state of hydration, edema (generally present in the lower limbs), hormonal responses related to adipose tissue, insulin resistance, high triglyceride levels, low HDL cholesterol levels, metabolic syndrome, malnutrition [28, 29]. The high ratio of ECW/ICW could also reflect a state of cellular dehydration or any physiological shifts of intracellular towards the extracellular water (such as when an inflammatory state or a stressful condition at the cellular level is present in the body). A high ECW/ICW ratio in overweight and/or obese subjects may also be associated with impaired metabolic regulation, glucose intolerance, reduced lipolysis and increased risk of diabetes. A systemic inflammatory condition, such as that found in obese individuals is responsible for these changes. Research has shown that isotonic and endurance physical activity can promote an increase in ICW, a signal for an increase in cell mass, muscle mass, basal metabolic rate, strength and improvement of the immune system. Conversely, low values of the ECW / ICW ratio (< 0.60) can be used to detect any risk conditions or the presence of dehydration.
The alterations in the PhA associated with disease, malnutrition, and physical inactivity could be justified by modifications in FFM that have been commonly shown in patients with obesity. However, even in situations when FFM loss has not occurred, extracellular fluid expansion can lead to an increase in the ECW/ICW ratio, for example in sepsis and the early phases of malnutrition leading to a decrease in the PhA [30–32]. It is important to note that the resistance measure (R) refers to the compartments of fluid and electrolyte-containing tissues (e.g. soft tissue mass), which offer greater resistance to the passage of this current [33], is higher in obesity and produces a reduction in PhA. On the other side, reactance is decrease for cellular injury, cachectic or inflammatory conditions such as in neoplastic or immunological diseases. Furthermore, it is suggested that BCM in obesity presents modification in selective permeability [34] due to a subclinical inflammation condition by different cytokine production by adipose tissue and also an increased production of reactive oxygen species (ROS) that oxidize lipids and proteins, including those in the cell membrane, which decreases cellularity [35]. All these conditions interfere with phase angle values, as summarized in Fig. 1.
Fig. 1 Phase angle distribution in normal-weight subjects and in patients with overweight/obesity. The PhA ranging from 3.9° to 4.9° and 4.1° to 5.1° in women and men respectively showing a decrease range when compare to normal-weight (6.7°-7.8° in women and 7.2°-8.4° in men)[44]. Multiple reasons might be responsible to this shift including increased adiposity, hyperhydration, body cell mass, FFM, inflammation and malnutrition
The PhA of healthy individuals can vary between 6º and 7º with a possible cut-off value at a value of 6.96º [24, 32]; in athletes it may reach value > 8.5° [36]. Reported high values may exceed 8° whereas values < 6° reflect a poor clinical prognosis [36, 37]. As reported in a systemic review by DiVincenzo et al. [38], the PhA of individuals with obesity presents a large range of values with no range of normal values. This variability may be explained by a combination of factors including diverse underlying clinical conditions and the different technologies in BIA instruments and electrode placement.
Importance of gender and ethnic differences
Gender is a determinant of PhA values. Women tend to have lower PhA values than men [24] largely due to lesser Xc values attributed to reduced fat free mass [39]. Additionally, an increased adipose tissue mass, which includes substantial water content (~ 20%), is associated with larger TBW and reduced R [24]. Ethnic differences reflect the variance in percentage of FM for the same BMI. In a study with 3 ethnic groups, the lower PhA was reported in Japanese compared with Germans in all age groups and it was depended by higher ECW/TBW ratio, with a lower skeletal muscle mass (SMM)/FFM [40]. A higher PhA for Mexicans in comparison with Germans is in accordance with differences in the height, which is highly correlated with fat free mass, in all groups [40].
Age, Height and PhA
A physiological change of PhA occurs with age. Findings indicate a general trend for PhA to decline with aging due to reduction of the parallel reactance with the loss of muscle mass and a concurrent increase in resistance associated with the decline in TBW at the expense of increasing in adipose tissue [19, 41]. The association of a deficit in muscle strength and a reduction in total muscle mass with aging is defined sarcopenia [42]. Phase angle has been associated with functional tests, such as gait speed and hand grip strength, in older women [43], and explained by the decline of Xc and the deleterious changes in electric properties of skeletal muscle with aging [32]. Multiple linear regression analysis revealed that age, skeletal muscle mass index (SMI), and muscle quality (evaluated by handgrip strength, HG) were independently associated with PhA in both sexes [44]. Recently, the cut-off PhA values are reported for predicting sarcopenia: 5.95°, 5.04°, 5.02°, and 4.20° in young male, elderly male, young female, and elderly female participants, respectively [44]. In a recent review, PhA was decreased in sarcopenic subjects [38]. Among different studies, the absolute values of PhA and the frequencies of sarcopenia might depend of gender, age and the clinical condition of the individual (e.g. COPD, cirrhosis, kidney transplant, cancer patients) probably in relation to nutritional state. The cut-off values of PhA varied from 4.05 to 5.05, possible because of the methods used for their identification. A significant association between PhA and functional test performance (e.g. six minutes walking test-6MWT) in older female adults, regardless of the potential confounding effects related to body composition [45]. A direct relation has been found with the muscle mass and strength [17, 18], as physical activity level influences body composition and seems to be positively associated with high PhA values [19]. Nescolarde et al. [46] showed that Xc and PhA decrease after an acute muscle injury.
Excess adiposity is one component of the specific condition termed sarcopenic obesity [42]. These patients present an increased ratio of intramuscular and intermuscular fat infiltration and a decreased ratio of muscle mass to total body mass related with metabolic abnormalities, low strength, and decreased mobility. The frequency of this condition is variable, ranging from 11 to 28%. In women with obesity, PhA was positively correlated with ultrasound-determined muscle area, muscle circumference, muscle echo intensity, serum albumin and total protein concentrations [47]. PhA was shown to be inversely correlated with body fat % (r = − 0.74; p < 0.001), and positively correlated with peak oxygen uptake (r = 0.50; p < 0.001) and lower- and upper-body maximal strength (r = 0.65; r = 0.70; p < 0.001, respectively). Thus, PhA was proposed as a clinically tool to screen the physical fitness and functional status of adults with obesity [39].
Few studies demonstrated, in multivariate regression analysis, that height exerted largest impact on PhA followed by body weight and muscle mass [40]. Since height and weight are representatives of somatic development reflecting skeletal and muscular growth and collectively they increase percentage of FFM and thus influence resistance and PhA.
Influence of BMI on PhA
Conflicting data describe the relationship between PhA and BMI. Reports indicate a positive [41] and a negative correlation [42] and other findings no effects were evident [43]. Bosy-Westphal et al. [32] showed that PhA tended to increase with BMI up to 35 kg/m2 and then decreased when BMI was > 35 kg/m2; in both genders PhA was negatively associated with BMI values > 40 kg/m2. Our group described in a wide cohort of patients with obesity a progressive decrease in PhA, in men and women both [44]. In particular, a reduction starting from a BMI of 40 kg/m2 then becoming highly significant for BMI values higher than 50 kg/m2, demonstrating the effect of adiposity excess and the low cellular integrity in case of extremely increased BMI (high resistance, low reactance). Thus, these data confirm that PhA in obesity is affected by multiple variables: sex, age, FM, FFM, hydration status, and nutritional state that directly influence resistance and reactance and not to BMI alone. It is notable that the increase in % fat, particular visceral FM, was associated with a reduction in PhA [24, 39, 40, 42, 45], probably for the alterations in the cell size, the permeability of the cell membrane, or differences in the distribution of fluids in the tissues, specifically an increase in ECW/ICW [46]. The parameter that most affects the PhA, in normal weight and normally hydrate adults, is FFM [30], in particular the skeletal muscle mass. Skrzypek et al. [45] confirmed, in a normal weight population, that PhA was positively correlated with muscle mass as well as with muscle strength. In fact, not only muscle mass is important, but also muscle quality due to fibre composition, metabolism, aerobic capacity, insulin resistance, and fat infiltration/fibrosis as in patients with obesity [45].
Phase angle in patients with obesity and different associated clinical conditions
Phase angle has been studies as a prognostic marker in several clinical conditions (e.g. cancer, kidney and cardiac diseases, HIV infection, etc.) and in diseases frequently associated with obesity such as metabolic dysfunction, insulin-resistance, inflammation and disability, and in the development of chronic diseases such as diabetes, dyslipidaemia and cardiovascular diseases; moreover, the possibility to monitor the progression of metabolic or cardiovascular risk factors with PhA changes is very promising (see Sect. 4). The metabolic syndrome (MS) includes risk factors associated with heart disease, obesity, and diabetes. In a recent study [46] only the waist circumference was associated with lower PhA values. For the glucose, non-HDL-C, triglycerides, CRP, HOMA-IR and uric acid levels there was no association with PhA in the adjusted models. Furthermore, women with obesity and a low PhA tertile had high fat mass with high levels of glucose, HOMA, IL-6 and leptin, which are risk factors for atherosclerosis and cardiovascular disease in obese patients [47]. Low values of PhA were found in adults with higher prevalence of hyperuricemia, that increases oxidative stress and a proinflammatory state even after adjustment for waist circumference, hyperglycemia and arterial hypertension but not with physical activity [48].
In patients with diabetes, Buscemi et al. [49] observed a negative correlation between fasting plasma glucose level and PhA that was inversely related to the ECW/TBW ratio because hyperglycaemia induces an osmotic effect and higher resistance value. Pillon et al. [50] showed that in diabetes there is reduced ability to exchange potassium due to a decreased active cell mass. Therefore, the smaller PhA could be considered marker for the catabolic state in people with diabetes [51, 52]. An important application is the evaluation of nutritional state in diabetic chronic kidney disease patients. These patients present a hyper-hydration and a significant association with glomerular filtration rate (eGFR) and albumin level with undernutrition (PhA < 4.17◦) [53]. The loss of muscle mass was also significantly related to the eGFR decline [54]. Recently Barrea et al. [55] reported, in a group of patients with PCOs, two significant results: PhA was negatively associated not only with the inflammatory status but also with the hyperandrogenemia in BMI-matched controls than suggest PhA as an endocrine marker of the severity of the PCOs. In the second study [56] the same Authors reported that PhA is significant low in patients with metabolically unhealthy obese (MUO) characterizes by highest percentage of severe obesity, low adherence to the Mediterranean diet, high CRP levels and frequency of MS diagnosis; for this data PhA was considered in the definition of relative prognostic value of MUO-PCOS phenotype [56]. Thus, decreased PhA values apparently are a consequence of metabolic perturbations associated with a pro-inflammatory state and its effects on body composition.
The presence of the metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis (NASH) range from 70 to 80% of patients with obesity and diabetes with a possible progression in fibrosis and cirrhosis. The accumulation of hepatic fatty acid within the liver, cause MAFLD and is associated to hepatic insulin resistance and an increase in pro-inflammatory mediators (IL-6, high sensitivity C-reactive protein and TNF-α) [57]. In patients with MAFLD but without fibrosis and severe steatosis, PhA rises proportionally to the increase in fat mass and BMI and decreases in advanced liver fibrosis [58]. A previous study reported that PhA values were significantly higher in well-nourished patients than in malnourished patients, characterized by both increased ECM and decreased BCM, but no statistically significant correlation was found between PhA, R and Xc values and Child-Pugh score [59]. Positive correlation with albumin levels suggested PhA as an indicator of nutritional status [59, 60].
Obesity is associated with a high risk of heart failure (HF) caused by both fluid retention (excessive fat mass) with cardiac overload and also malnutrition (“cardiac cachexia”, with loss of muscle mass and systemic inflammatory in adipose tissue). The PhA showed lower values in patients in New York Heart Association (NYHA) classes III-IV than in those in classes I-II and is an independent predictor of mortality in HF patients. Relative Plasma Volume Status (“intravascular” congestion) was the major determinant (20% of PhA variability), while peripheral oedema and BNP plasma levels (markers of congestion) explained 12% and 2% of variability, respectively [61]. High values in central venous pressure (i.e. expansion of plasma volume) were associated to downward displacement of the impedance vector, and lower phase angle value on the R/Xc graph [62].
A direct role of obesity in kidney injury has been demonstrated. The Obesity-Related Glomerulopathy should be defined as a special form of focal-segmental glomerulosclerosis with cellular fat load and perivascular fat depot as well as so-called fatty kidney with fat depot in the perirenal and renal sinus. The clinical consequences are the higher prevalence of urinary albumin excretion, sub-nephrotic syndrome, nephrolithiasis, increased risk of developing CKD. Furthermore, obesity is frequently associated with hypertension, MS, insulin resistance, diabetes and atherogenic dyslipidemia that contribute to renal damage through mechanisms that include inflammation, oxidative stress, renin-angiotensin-aldosterone system up-regulation, increased sympathetic activity, and endothelial dysfunction [63]. Fluid overload and protein-energy wasting are common in patients with end-stage renal disease and lead to a poor prognosis. The PhA was found to be positively associated with a geriatric nutritional risk index, lean tissue index and albumin while over-hydration/ECW showed an inverse correlation [64].
Obesity and particularly central adiposity are potent risk factors for obstructive sleep apnoea syndrome (OSAS) [65]. The severity of the diseases (measured with AH Index) was positive related with ECW% while negative correlation was demonstrated with PhA and MM%. A possible explanation is an overnight rostral fluid displacement from the legs independent of body weight with an increase of cardiovascular risk again [66].
The aging process and the progression of obesity-related disease are characterized by increased levels of inflammatory mediators such as IL-6, TNF-α, and acute phase CRP as well as increased production of reactive oxygen species (ROS) and inhibition of antioxidant enzymes. It is reported an inverse relation between PhA and inflammatory biomarkers (IL-6, TNFα, and CRP) and the significant positive relation with antioxidant enzymes and the total radical-trapping antioxidant (TRAP), regardless of age, number of diseases, and body composition in older women [67]. A possible explanation is that an increase in inflammatory biomarkers is the first response to tissue and cellular injury while low levels of oxidative stress participate in the regulation of cellular activities such as cell growth [68]. Barrea et al. [69] demonstrated, in both sexes with large range of BMI, that smaller PhA was associated with higher CRP levels, independently of age, physical activity, anthropometric measurements, and adherence to the Mediterranean diet; this indicated PhA as a marker of meta-inflammation. The PhA was assessed in patients with HIV infection in new diagnosis with unintentional weight loss or low percentage of CD4+ T cell. In patients with controlled viremia but decreased in cellular integrity (nutritional decline, or CD4+% < 15%), PhA is used for monitoring intensive nutrition therapy (body protein stores). The combination antiretroviral therapy (cART) regimens, with less toxicity on metabolic parameters, registered an increase in patients with obesity. They present PhA lower than healthy, HIV-uninfected groups, higher percentage of body fat mass and lower percent lean mass but PhA is not correlated with mortality risk. It is also possible that obese individuals with HIV maintain adequate cellular mass for survival even when general cellular degradation that reflects a systemic reaction to infection, results in a declining PhA [70].
Different epidemiologic studies showed, in patients with COVID-19 infection, an association between increased BMI and the severity of the disease and mortality. On the contrary, low PhA (< 3.95°), independent of age, sex, BMI, and comorbidities, is a significant predictor of mortality risk in COVID-19 [71] and is associated with an increase in disease severity, reflected by the need for intensive care unit admission, morbidity and mortality [72]. Low PhA showing a situation of inflammation and cell injury associated with SARSCoV-2 infection, indicating a deteriorating nutritional status with higher state of hydration (ECW and hydration percentage) and decreased BCMI, associated with proinflammatory and immune response (CRP, lymphocytes, CRP/pre-albumin) [71]. In post-Covid rehabilitation, recovery of malnutrition state might be monitoring with the increasing PhA values [73].
Weight loss and phase angle changes
Weight loss is the main outcome of obesity treatment. It induces an improvement of the clinical condition with a prevention of associated obesity disease appearance and progression, a reduced risk of development of disability and reduction in mortality risk. To induce weight loss, different strategies might be performed, starting from lifestyle modifications to bariatric surgery procedures depending of the obesity grading. In the last years a close attention to the kinetics of weight loss was studied, in order to depict and reduce the risk of sarcopenia (loss of quantity and quality of muscle mass) that could be associated to the loss of body FM. Monitoring PhA change during weight loss appear as a useful marker to evaluate the risk of malnutrition or the recovery of health status (improvement of metabolic parameters and decrease of inflammation).
Nutritional intervention
No data are available on the effects diet-induced (hypocaloric) weight loss alone on PhA in obesity. The PhA has been previously investigated in patients with obesity after three sequential 10-day cycles of ketogenic enteral nutrition (a total of 205–270 calories/daily) with rapid weight loss (-6.4 kg). Results obtained at day 50, after the 3 treatment cycles, evidenced significant decreases in FM. This effect might be due to the reduction in lipogenesis and increased lipolysis typical of ketogenic diets. Lean mass decreased less than expected probably due to the assumption of leucine that stimulate downstream control of protein synthesis. PhA decreased in association with the greater weight loss [74]. On the contrary, Barrea et al. [75] reported that PhA increased during the active stage of VLKCD, very early and independently of weight loss amount (mean weight loss reported as -7.3 kg) and with a significant increase of Xc. We can speculate that ketogenic diet might change different parameters: reduction in ECW, insulin-resistance on cell surface, interlukine production. These data, and the mechanisms involved, need to be better investigated in wider cohorts and in longer temporal follow-up.
Physical activity
Patients with obesity generally have sedentary behaviour and the body composition and the response to physical activity, cannot be comparable with general population nor athletes, since they present reduced muscle mass and/or functional deficit, “obesity sarcopenia”, comparable to elderly patients. The physical activity level influences body composition and seems to be positively associated with PhA values, as found among non-institutionalized physically active elderly subjects with high phase angle values [19]. The application of different weekly resistance training frequencies performed over a 24 weeks exercise program produce a significant reduction in body weight, waist circumference, and FM% in both group but PhA increased only in the group that performed the training program at a higher weekly frequency [76]. The hypothesis suggested is an increase in reactance and a reduction in the ECW/ICW relationship due to weight loss. Ribeiro et al. [77] showed improvements in PhA following resistance training exercises carried out 3 times a week in obese women. In their study, after 8 weeks of training in obese old women, a significant increase in FFM, ICW and PhA were observed [78] as in old normal weight women [79]. This finding is probably reflected in the increase in muscle mass, a tissue that holds a large amount of ICW, resulting in better electrical conductivity and, thus, a concomitant increase in PhA. Others cellular mechanisms might be involved if we considering that exercise results in a greater reduction in CRP, IL-6, and TNF-a when accompanied by a reduction in BMI or FM% in overweight/obese individuals [80]. Furthermore, studies have shown that PhA increases after a training period or is higher in active subjects compared to less active ones, suggesting that many of the exercise-induced systemic adaptations can impact cell integrity and functionality [78, 81, 82].
Lifestyle modification
A comprehensive program of lifestyle modification (diet, exercise, and behaviour therapy) is considered the first option for patients with obesity and overweight. The aim of this program is a 5–10% reduction in initial body weight that is associated with clinically meaningful improvements in several CVD risk factors, including the prevention of type 2 diabetes [83]. No data were available for PhA changes after lifestyle intervention program in patients with obesity. For this reason, we evaluated the PhA changes in a group of patients with obesity (mean age 53yrs) following a lifestyle program for weight management (mean baseline BMI: 29,2 Kg/m2) that reached a mean body weight loss − 6.3% after six months follow up (Table 1), mean PhA was 5.54° at baseline, and 5.94° after 6 months with a significant increase of Xc values (unpublished data).
Table 1 Changes in Body Impedance Analysis before and after 6 months of lifestyle intervention in a cohort (N = 61) of outpatients with overweight and/or obesity
Before (T0) After (6 Months)
Mean SD Mean SD p-value
BMI (Kg/m2) 29.24 5.43 27.08 4.99 0.020
Weight (kg) 80.85 17.51 74.81 15.40 0.040
R (Ω) 482.05 70.73 487.72 71.87 ns
Xc (Ω) 46.33 7.57 50.41 8.54 0.006
PhA (°) 5.54 0.89 5.94 0.90 0.010
FM (%) 30.68 9.25 26.81 8.05 0.015
FFM (%) 69.32 9.25 73.19 8.05 0.012
ECW (%) 48.23 4.50 46.28 4.17 0.011
ICW (%) 51.77 4.50 53.72 4.17 0.010
ECW/ICW (L) 0.48 0.09 0.47 0.09 ns
BMI: body mass index; R(resistance); Xc (reactance); PhA (Phase angle); FM (fat Mass); FFM (free fat mass); ECW (extra cellular water); ICW (intra cellular water). Significant p-value < 0.05 (paired T test)
Intensive Rehabilitation program
The combination of nutritional intervention and physical activity in intensive rehabilitation program on PhA was not previously reported. In line with analysis reported in Sect. 4.3 we checked body impedance changes in a cohort of inpatients with obesity and different comorbidities (diabetes, dyslipidaemia, hypertension, heart failure, COPD, OSAS, hepatic steatosis, osteoarticular diseases). Patients were admitted in Clinical Rehabilitation Unit for hypocaloric diet (15% of energy deficit of resting energy expenditure) + physical activity (about 2 h/day of aerobic activity for five days/week) during a mean 28days period. We selected patients that obtained a weight loss over 5% of initial body weight (mean values 6,50%), we have a data setting of 1,081 subjects, mean age 53 ± 13.9yrs (18-50yrs 38%, 51-70yrs 51% and 70 + yrs 10%). Mean PhA was 4.34° at admission and 4.41° at discharge with a significant increase of Xc values (Table 2) (unpublished data).
Table 2 Changes in Body Impedance Analysis before and after 28 days of intensive multidisciplinary rehabilitation program in a cohort (N = 1081) of inpatients with obesity
Before (T0) After (28 days)
Mean SD Mean SD p-value
BMI (Kg/m2) 44.28 7.25 41.43 6.76 0.0001
Weight (kg) 123.74 24.29 115.79 22.60 0.0001
R (Ω) 453.67 72.85 477.72 72.01 0.0001
Xc (Ω) 34.85 11.57 37.10 11.43 0.0001
PhA (°) 4.34 1.11 4.41 1.07 0.0119
FM (%) 46.23 7.26 46.07 7.49 ns
FFM (%) 53.77 7.26 53.93 7.49 ns
ECW (%) 42.71 3.78 42.68 3.55 ns
ICW (%) 57.29 3.78 57.32 3.55 ns
ECW/ICW (L) 0.76 0.21 0.75 0.14 ns
BMI: body mass index; R(resistance); Xc (reactance); PhA (Phase angle); FM (fat Mass); FFM (free fat mass); ECW (extra cellular water); ICW (intra cellular water). Significant p-value < 0.05 (paired T test)
Bariatric surgery
Some studies were performed to evaluated the shift on PhA after bariatric surgery. In a recent review, DiVincenzo O et al. [38] found 8 eligible papers (4 with LSG, 2 RYGB and 1 LGB) comparing values before and from 6 weeks to 2 years after surgery and recovery [84–91]. The greatest decrease in PhA values was observed in patients with the highest loss of body weight following RYGB or LSG either after 24 months [89] or after 6 months [87, 88]. Teixeira et al. [91] reported that the decline of PhA after RYGB was negatively associated with weight loss and positively with the decrease of BMI, skeletal muscle mass, FM, and visceral fat area. The authors observed that, in six out of the eight selected papers PhA decreased by 1–20%, independently of the type of surgery (RYGB o LSG) [84–91]. To understand the mean of these changes, raw BIA variables (R and Xc) need to be considered. Unluckily, at present these data are not reported. Previous studies with tritiated or bromide water dilution analysed fluid change distribution after bariatric surgery. Mazariegos M et al. [28] reported that total body water, ECW and ICW decreased in LSG and in RYGB group but the ECW/ICW ratio remained unchanged in the LSG group, and significantly increased in the RYGB. They conclude that malassorbitive surgical procedures cause a further increase in ECW/ICW ratio, possibly through mild malnutrition not detectable by conventional serum markers of nutritional state, which implies that the ECW/ICW ratio might be an early marker of nutritional state worsening. Furthermore, Levitt et al. [92] show that ECW/ICW was significantly increased above normal before surgery (RYGB), and it increased slightly after surgery. These changes are consistent with the expected physiological changes in body composition after surgery. More recently, using impedance analysis, during 6 months of follow-up after RYGB surgery [84], a significant decrease in TBW accounting for a decrease in ICW, mismatching with a non-significant decrease of BCM and body cell mass index, was observed. In another study [87], TBW, ECW and ICW significantly decreased in patients with RYGB and LSG after 6 months but no difference was reported between two groups. In the absence of other measurements of muscle quality, there is no obvious explanation for the involving of FFM or MM; explanations suggested a worsening of nutritional status [86] and another two an increased risk of developing malnutrition [87, 88], with no comments in the others. In other groups of RYGB patients, the reduction in body weight and BMI, body fat mass, FFM as well as BCM, PhA and SM Index were significantly different for follow-up periods of 1–2 or 5years after surgery [93–95]. The reduction of BCM results in an increase of the ECM/BCM Index, indicating malnutrition. According to these results, FFM and skeletal muscle mass reduction occurs frequently after bariatric surgery and mainly during the first year after surgery with an increase risk to develop sarcopenia. In a previous study in RYGB and the LSG treated patients, there was a significant reduction of BMI, FM, FFM, PhA and CPR after 6 months in both groups, not significantly different. Only in RYGB group a decreased in advanced oxidation protein products, was registered. In the interpretation of the results it is suggested that BMI reduction in the RYGB group support a concomitant decrease of lipid oxidative damage, whereas in the LSG group, changes in BIA parameters—PhA, resistance, and reactance—suggest inverse changes in protein oxidative damage [90]. In a small study of women who underwent RYGB, PhA reduction was accompanied by a significant decrease in body weight and BMI after 3 months then PhA remained stable after 6 months.
Friedrich et al. [86] compared one-year changes in body composition following sleeve gastrectomy (LSG) and multidisciplinary weight loss program (MIP). They found a more significant reduction in PhA with LSG than with MIP after 6 months with no significant difference in weight and total water loss between the two groups. Fat mass loss at 6 months was not different in the two groups while BCM was significant higher in MIP and result in an increased also in ECM/BCM index. Cell proportion, which is defined as the percentage of cells within the BCM, is thought to indicate the individual nutritional and training status. This parameter deteriorated significantly in the LSG group, but was preserved in the MIP group within 12 months, whereas both treatments resulted in a decrease in basal metabolic rate. It is suggested that LSG is a risk for worsened nutritional status with notable evidence for protein–energy malnutrition.
Pre-operative PhA values also has prognostic value. Vassilev et al. [85] reported that high admission PhA values before bariatric surgery (127 RYGB and 46 LSG) predicted a successful weight loss reduction with surgery; furthermore, preoperative PhA values were correlated with FM reduction and preservation of FFM in early phase, 6 and 18 weeks, or in follow up, 6-9-12 months after surgery. Gerken et al. [89] similarly reported beneficial effects of increased PhA in 198 patients 24 months after LSG or RYGB interventions. Preoperative PhA had a moderate/weak relation with total weight loss after RYGB and with loss of excess weight after both LSG and RYGB.
Discussion
Clinical use of PhA in obesity can be an important marker to describe health status but with some observations. As a screening tool, PhA values vary widely in individual who are overweight and obese but a low PhA value is common compared to healthy gender-matched adults (Fig. 2). Disparities in body composition and hydration status contribute to this variability in PhA values. BMI is a weak moderator of PhA distribution among individuals with excess adiposity with BMI ≥ 35 kg/m2 indicative of excessive fat accumulation and overhydration. Fat free mass, muscle mass and altered ECW/ICW are the major factors affecting PhA in these patients. It is dubious to define PhA cut-off in obesity due to the multiple factors that contribute to obesity pathophysiology that directly impacts Xc and R. Obesity is a complex metabolic disorder with a multifactorial origin. It is associated with hyperglycaemia and hyperinsulinemia, hyperlipidaemia, hyperleptinemia from adipose tissue, endothelial dysfunction also with alteration in renin–angiotensin system, mitochondrial dysfunction from muscle activity, chronic low grade of inflammation with alteration in cytokines production, vitamins and minerals deficiencies derived from unhealthy eating behaviour that contribute to an increase oxidative stress [96]. Any of these mechanisms can contribute to a pro-inflammatory state that might induce fluid disturbances, adversely affect the integrity of cell metabolism and promote loss of cells. Identification of individuals with low PhA is important for the clinical practice physician to identify individuals at increased risk of morbidity and mortality [97], to treat critical clinical condition.
Fig. 2 Cause of change in PhA values in patients with obesity
Monitoring PhA changes during weight loss appear as a useful marker to evaluate the risk of malnutrition (excessive loss of FFM or protein deficit) and recovery of health status (improvement of metabolic parameters, decreased inflammation and oxidative stress). At present inconsistent findings of changes in PhA after surgical interventions for weight loss do not allow any conclusion. We need standardized protocols to well define PhA changes during weight loss and in particular after bariatric surgery.
Conclusion
The integrity of the cell membrane and the abundance of lean mass coincide with health and their recovery and conservation constitute the highest goal in all therapies, especially in obesity. The data here reported demonstrate that the PhA is a good indicator of health, because it measures the integrity of the cells and, therefore, their functionality. In general, high PhA values indicate a good healthy state, while low values should be investigated, in relation to the clinical history of the patient. In pathological subjects, the PhA tends to have low values and is actually used as an indicator of poor nutritional status, prognosis and increased mortality risk. Phase angle values are influenced by age, gender, height, ethnicity and BMI. The data in the literature highlight the possibility of using the PhA as new cellular health markers during weight loss phases. Furthermore, the PhA could be used as a prognostic marker for clinical conditions associated with obesity (such as fluid overload as in HF, worsening of diabetes and its complications, inflammatory state etc.) and to monitor some diagnoses linked to inflammatory, metabolic or endocrine alterations. It is essential to increase research on PhA to develop new therapeutic strategies for obesity and obesity complication treatment in the near future. For instance, when studying body composition it is now crucial to well define the population used (from overweight to obesity and morbid obesity, and taking into account age and sex, inflammation degree and therapies), monitoring and reporting the PhA values and its variations with weight loss, to well define the effects of new pharmacological treatments (such as GLP-1 agonists), lifestyle and physical activity program (aerobic exercise combined with short bouts of resistance training), nutritional intervention and bariatric surgery procedures on body composition. The focus on PhA and body composition is of utmost importance also for the establishment of weight maintenance protocols after weight loss.
Declarations
The authors did not receive support from any organization for the submitted work.
Conflict of interest
All the authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported.
Abbreviations
6MWT Six minutes walking test
BCM Body cell mass
BIA Bioelectrical impedance analysis
BMI Body mass index
BNP B-type natriuretic peptide
cART Combination antiretroviral therapy
COVID-19 Corona Virus Disease-2019
CAT Catalase
CKD Chronic kidney disease
COPD Chronic obstructive pulmonary disease
CRP C-reactive protein
CVD Cardiovascular diseases
DXA Dual energy X-ray absorptiometry
ECW Extracellular water
eGFR Glomerular filtration rate
FM Fat mass
FFM Free fat mass
HF Heart failure
HG Hand grip
HOMA-IR Homeostatic model assessment of insulin resistance
ICW Intracellular water
IL-6 Interleukin-6
LSG Laparoscopic sleeve gastrectomy
LGB Laparoscopic gastric banding
MAFLD Metabolic-associated fatty liver disease
METs Metabolic equivalent of task
MS Metabolic syndrome
MIP Multidisciplinary weight loss program
MHO Metabolic health obesity
MUO Metabolic unhealth obesity
NASH Non-alcoholic steatohepatitis
OSAS Obstructive sleep apnea syndrome
PCOS Polycystic ovary syndrome
PhA Phase angle
R Resistance
RYGB Roux-en-Y gastric bypass
ROS Reactive oxygen species
SMI Skeletal mass index
SMM Skeletal muscle mass
TBW Total body water
TNF α, Tumor necrosis factor-α
TRAP Total radical-trapping antioxidant
TWL Total weight loss
VLKCD Very low caloric diet
VO2 Oxygen consumption
WHO World Health Organization
Xc Reactance
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36484943 | PMC9735068 | NO-CC CODE | 2022-12-14 23:28:32 | no | Rev Endocr Metab Disord. 2022 Dec 9;:1-14 | utf-8 | Rev Endocr Metab Disord | 2,022 | 10.1007/s11154-022-09774-1 | oa_other |
==== Front
Energy Syst
Energy Systems
1868-3967
1868-3975
Springer Berlin Heidelberg Berlin/Heidelberg
554
10.1007/s12667-022-00554-z
Original Paper
Testing the law of one-price in the US gasoline market: a long memory approach
Barassi Marco R. 1
http://orcid.org/0000-0003-2233-3706
Pascale Gianluigi De [email protected]
2
Lagravinese Raffaele 3
1 grid.6572.6 0000 0004 1936 7486 Department of Economics, University of Birmingham, Birmingham, UK
2 grid.10796.39 0000000121049995 Department of Economics, University of Foggia, Foggia, Italy
3 grid.7644.1 0000 0001 0120 3326 Department of Economics and Finance, University of Bari“A.Moro”, Bari, Italy
8 12 2022
125
3 1 2022
28 11 2022
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This paper aims to shed new light on“law of one-price” in the United States’ gasoline market over the period June-2003–December-2019. Specifically, we test for convergence of the retail prices of gasoline in different US PADDs, states and cities using the Local Whittle estimator (LW) and its variants (Robinson 1995, Shimotsu and Phillips 2005). Mean/trend reversion of the relative price of each unit will imply convergence toward the average price in the US thereby offering support for the law of one-price. LW estimators allow us to consider the case where relative gasoline price are fractionally integrated process and may display long memory implying a slow process of convergence. The results obtained generally offer support for the law of one-price albeit with significant differences in the rate of convergence between PADDs, States and Cities. In detail, a slow convergence (long memory process) is observed for PADD3 (Gulf Coast), PADD5 (West Coast) and then confirmed at the level of States (California, Texas and Washington) and at the level of Cities (Los Angeles, San Francisco and Houston). Among the cities, two of four empirical model employed find a slow convergence process is also in the cities of New York, Cleveland and Miami.
Keywords
Gasoline price
Convergence
Fractional integration
Whittle estimator
JEL Classification
Q4
Q41
C01
C22
==== Body
pmcIntroduction
This paper investigates the Law of one Price (LOP hereafter) in United States gasoline market over the period June-2003–December-2019 using a long memory approach which relies on the Local Whittle estimator (LW) and its variants (Robinson 1995, Shimotsu and Phillips 2005). The LOP states that in the absence of arbitrage or trade frictions (such as transport costs and tariffs), and under conditions of perfect competition and price flexibility (where no individual sellers or buyers have the power to manipulate prices and prices can freely adjust), identical goods sold in different locations must sell for the same price when prices are expressed in a common currency [18].
The reason to study the LOP on gasoline market lies in the fact that fuel is a strategic productive factor for the economy of a country in general and, particularly, for the lives of people and businesses. The retail gasoline price substantially affects the costs of production and, at the same time, has a significant impact on the mobility of vehicles and people [5]. For the gasoline market, the LOP would be seen to hold if the difference in prices at-the-pump in different locations either is, or converges to zero.
In this paper we focus on the convergence between the retail prices of gasoline within three sets of US units: Petroleum Administration Defense Districts (PADDs), States and Cities. Studying the convergence of gasoline prices in the US is particularly important, both for evaluating the deregulation process that has involved this market since the 1980s, and because of the significant economic differences that has persisted in recent years between and within the US states and cities. The US states represent a particularly relevant case study thanks to a far greater capital and people mobility compared to that in European states. Indeed, US states share widely interdependent production processes and federal and state public policies that can certainly have effects between neighboring states. Yet, despite a much more pronounced integration process than in Europe, several studies in recent years have shown that there are still significant price differences between US states. It has been seen that these differences are partly generated in the various intermediate steps between the price of crude oil and the price at-the-pump [3, 4], and accentuated as a result of structural breaks [1]. With regard to the gasoline market, within individual countries/regions or in any case in the presence of homogeneous territories that share the same market, it would be desirable to have the same price at the pump in order to avoid tax dumping or alterations in the price of goods due to asymmetries in the price of production factors. For example,Cárdenas et al. (2017) [7] analyzed the diesel convergence process between gas stations in France, finding a significant convergence between the various most homogeneous and close geographic areas. Suvankulov et al. (2012)[22] analyzed the integration process in Canadian provinces between 2000 and 2010 by observing a substantial convergence of prices on average but with six cities in the province of Nova Scotia which had a divergent pattern compared to the rest of the country. Balaguer and Ripollés (2018)[2] observe a significant divergence in the price of gasoline in the Spanish provinces suggesting a lack of market integration at regional level. The different level of prices can be attributed to transportation costs, taxation, and other explicit barriers. Furthermore, the price convergence can shift an energy tax burden onto the producers which leads to a competitive disadvantage for firms in high-tax regions(Holmes et al.(2013), Suvankulov et al. (2012)) [12, 22]). To date, most studies on the US gas price convergence process have focused on integrating the 7 PADDs into which the 50 American states are divided. In particular, Paul et al. (2001)[16] analyze the integration of gasoline price from January 1983 to December of 1998 in the PADDS and find a high degree of market integration in the gasoline markets as evidenced by the Engle and Granger and Johansen cointegration tests. Ye et al. (2005) [24] investigate the pass-through mechanism from wholesale gasoline spot prices to retail gasoline prices on a regional basis. Their results underline the presence of Asymmetric price transmission (called the“rockets and feathers phenomenon”1) in all regions with price increases being passed along faster than price decreases. Holmes et al. (2013)[12] employ a pair-wise approach to examine regional integration using State date in the US gasoline market. Their findings show that a price convergence to the long-run equilibrium depends on distance and station homogeneity between states. More recently, Blair et al. (2017) [3] used an error-correction model in a seemingly unrelated regression framework to examine the differences between PADDs. Their finding suggest that regional differences exist both in the short run and long run adjustment processes.
This paper attempts to enrich this literature on the LOP by introducing two significant novelties. The first is methodological in nature since as far as we are aware, it is the first time that a long memory approach is used in this strand of literature. The reason for our choice of methodology stems from the fact that the studies conducted so far have shown how different methodologies lead to conflicting results with respect to the convergence process between prices in the different geographical areas. We believe that the reason for these contrasting results is mostly due to the fact that previous studies have always confined the analysis within the I(1)-I(0) world, where I(1) non-stationary relative prices would indicate lack of convergence while stationary I(0) relative prices indicate convergence and support for the LOP. The second novelty lies instead in the geographical areas analyzed. Indeed, so far, given the availability of the data, the main studies on the subject have concerned the PADDs (e.g.Holmes et al. (2013), Paul et al. (2001) [12, 16]) or the States [3]. However, in addition to offering an updated historical series for the individual PADDs, the Energy Information Administration (EIA) offers monthly data for 9 states and 10 cities for period from 2003 to 2019.
In brief, we exploit the entire information base made available by the EIA to test the convergence / divergence process through the Local Whittle (LW) estimator [19] of the fractional integration parameter and its variations (Exact Local Whittle (ELW) and Feasible Exact Local Whittle (FELW) in order to test the hypothesis that relative gasoline prices contain a unit root (non convergence) against the alternative that they are long memory processes implying slow convergence. Our analysis shows significant differences in the results as compared to those obtained using Augmented Dickey Fuller (ADF) and the Kwiatkowski Phillips, Schmidt and Shin (KPSS) type of tests. In particular, our findings suggest that all series analysed are convergent but with very different speeds [9, 14, 15]. In detail, a slow convergence (long memory process) is observed for PADD3 (Gulf Coast), PADD5 (West Coast) and then confirmed at the level of States (California, Texas and Washington) and at the level of Cities (Los Angeles, San Francisco and Houston). Among the cities, two of four empirical model employed find a slow convergence process is also in the cities of New York, Cleveland and Miami.
The remainder of the paper is structured as follows: Sect. 2 describes the data for the individual PADDs / States / Cities; Sect. 3 describes the estimation and testing methodology; Sect. 4 reports the results; and Sect. 5 offers some conclusions.
Data
We use the monthly data on the Retail Gasoline Prices (Dollars per Gallon) from the Energy Information Administration (EIA) of the US government at www.eia.gov. The time series are provided at PADD level which aggregates the 50 states from June 1993 until December 2019. Originally, the 50 American states were divided into five PADDs (East Coast, Midwest, Gulf Coast, Rocky Mountain, and West Coast) to capture the five major regions and later the East Coast PADD was further divided into three: 1A (New England), PADD 1B (New York to Maryland), and PADD 1C (Virginia to Florida). This outline derives from the II world war, when U.S. government equipped a chain to supply the war machine with fuel, and has been kept beyond the conflict until today as a geographical framework for data collection being managed by EIA.
The EIA also collects and provides data series for 9 states (Florida, Massachusetts, Minnesota, New York, Ohio, Texas, Washington, Colorado and California) and ten cities (Boston, Chicago, Denver, Houston, Los Angeles, Miami, New York City, San Francisco, Cleveland and Seattle). Unlike previous studies (e.g. [3, 16], it was therefore decided not to analyze only the PADDs but to offer a more detailed analysis at the level of single states and specific cities in order to observe if there was heterogeneity between geographical areas. The time series are available for PADDs, States and Cities from June 2003 until December 2019, so our analysis is carried out in this temporal span. We deliberately analyzed a period before COVID-19 to avoid critical issues in the analysis due to the economic shock. Figure 1 shows in detail the partition in PADDs and identifies the states and cities object of our analysis.Fig. 1 EIA PADDs, States and Cities
Figures 2, 3 and 4, on the other hand, show the trend of the retail gasoline price for the PADDs, States and Cities analyzed (in logarithms).
The PADD level analysis offers a general overview of the gasoline price evolution that does not take into consideration the price dynamics reflecting the specific features of states and cities. Therefore, to deal with these probable differences due to the level of aggregation which can be caused by heterogeneity within each unit, we also look at convergence of gasoline prices using data at State and City levels. In this respect, Fig. 3 shows the price evolution of the 9 states for which EIA collects data, while Fig. 4 reports the prices of the 10 cities available. For the purpose of this study, such a comparison between results for different sets of units, aims at testing the robustness of the results in that, if there is homogeneity of the price trends at all levels of aggregation, our analysis should deliver consistent results. On the other hand, heterogeneity within the different levels of data aggregation (i.e. the case where Houston is very different from the rest of Texas which is very different from the rest of the states in PADD3) is likely to returns different and even contrasting results. This will all be confirmed or otherwise by the long memory approach used here, whose results will shed some light not only on whether the law of one-price (convergence between gasoline prices) holds in the US, but will also allow us to understand the degree of heterogeneity/homogeneity between the units.
At first glance, Fig. 2 seems to reveal similar evolution in the prices across the 7 PADDs for the whole time-span. Although the increasing trends, the gasoline prices are affected by a significant volatility between 2003 and 2008. In 2008, indeed, the world economic and financial crisis caused a structural break so that PADD’gasoline prices collapsed. From then to 2011, prices turned to rise until 2011 when the price evolution became stable for almost three years. In 2014, prices dramatically collapsed again, then turned to slowly increase. Figure 3 reports the gasoline price of the 9 US states collected by EIA. From this perspective, the graphical illustration confirm an homogeneous trend for 8 out of 9 states. These trends, in turn, reflect those of the PADDs they belong to. By contrast, in California the situation appears changing since 2015: the gasoline price evolution takes different pathway compared to the PADD5 (West Coast). The heterogeneity emerges due to data disaggregation. Figure 4 breaks further down the data by considering gasoline price at the 10 city level, as data are provided by EIA. In this case, 4 out of 10 cities lead to heterogeneous pathways compared to the PADDs level. This happens for Los Angeles, San Francisco and Seattle belonging to PADD5, and, with lower differences for Miami, included in PADD1C (Lower Atlantic). The evidence raised by city disaggregation confirms the signal concerning the West Coast conveyed by Fig. 3. Importantly, the two cities located in California register a greater gasoline price increase in the last 5 years than what happens at PADD level, that is the result obtained with the country’level disaggregation. By contrast, Seattle shows a different price evolution, even though no differences were found out between PADD and state level (Washington).
Instead, Miami’prices registered a spike in 2017, before immediately declining and keep on following up this gait. The emerging trend in Miami, is different from the PADD1C and the Florida ones.Fig. 2 Gasoline prices in PADDs
Fig. 3 EIA:States Trend
Fig. 4 EIA:Cities Trend
This first attempt of interpreting the U.S. gasoline price time series shall be compared to the analytic computation presented in the Sect. 4 in order to realize if the series follow a reasonable (stationary) or a random walk path.
Methodology
Testing for convergence
The methodology employed is in line with [21] previously adopted for CO2 emissions. In detail we carried out unit root, stationary and fractional integration tests on the basis that, if retail gasoline prices between a set of geographical areas (in our case we consider three different areas: PADDs, States, Cities) are converging (in a stochastic sense) then the log of the ratio of gasoline prices in the geographic are g and the average of gasoline prices of the set of all geographic area (RPgt) should be a stationary or at least a mean (trend) reverting process. First of all we model the natural logarithm of a geographic area’s gasoline prices (RPgt) as:1 RPgt=RPg∗+ugt,
where RPg∗ is a time invariant equilibrium differential,2 RPg∗=GRPgN-1∑g=1NGRPg,
GRPg is the gasoline price of a specific area g and ugt is a time and area specific deviation from that differential which can be written as:3 ugt=cg0+ϵgt,
where cg0 is the initial deviation from the equilibrium differential and ϵjt are the gth geographic area each with mean zero and finite variance σj2. Combining Eqs. (2) and (4) we get:4 RPgt=RPg∗+cj0+ϵgt,
Testing for non-convergence is then done by testing whether the relative gasoline prices in geographic area g, ygt=(RPgt-RPg∗) contain a unit root (or are indeed trend stationary or mean/trend reverting).
In conducting the test, Eq. (5) is expanded to include a linear time trend (which may be area specific) such that after a re-ordering of terms, Eq. (5) can be re-written as:5 (RPgt-RPg∗)=cg0+γgt+ϵgt,
The term on the left hand side of Eq. (5) is then tested for a unit root (trend stationarity) against the alternative of trend stationarity/mean reversion and long memory (unit root). If a unit root is rejected, for a given initial deviation from equilibrium cg0, stationarity/mean reversion (and long memory) of relative emissions can be taken as evidence of convergence of gasoline prices.
It is well known that standard unit root tests may provide incorrect results in the presence of structural breaks in the deterministic terms [17, 23]. Also, the tests used may have low power near the alternative, and moreover, they cannot provide information about the level of persistence of the series. In our analysis we consider the possibility that relative gasoline prices are actually mean/trend reverting long memory processes and that is the reason why standard unit roots or stationarity tests may fail to offer consistent findings with regard to their order of integration (see Sect. 3.2 for a short introduction on long memory). Fractional integration I(d) with 0<d<1 of relative gasoline prices implies their high persistence (even covariance non-stationarity) but mean/trend reversion in the long run. This translates into the occurrence of perhaps slow convergence of a gasoline price relative to the national average price in the long run.
The use of fractional integration may also be motivated by the presence of occasional breaks in the price series which otherwise would be only weakly autocorrelated. This can be appealing in the case of gasoline prices because cities o country regulations, new technologies or catastrophic events (e.g. storms, earthquakes, epidemics), although infrequent, may still cause shifts in the deterministics of a specific geographical area’s gasoline price series. Moreover, Granger and Hyung (2004) [10] show that fractional integration and infrequent breaks may be virtually impossible to distinguish from each other and adopting fractional integration modelling strategies produce good forecasts.
Long memory models
In this subsection we briefly introduce fractionally integrated/long memory models and their estimation. Granger and Joyeux (1980) [11] suggest that a stationary time series {yt} has long memory if there is a non zero d∈(-0.5,0.5) such that its spectral density obeys a power law f(λ)∼kλ-2d as λ→0+. Clearly, as λ→0, f(λ)→∞, if d>0 or f(λ)→0, if d<0. In the case where d=0, {yt} will have short memory and (0<f(0)<∞) such as in the case of all the stationary and invertible ARMA processes. Moreover,HoskNG (1981) [13] identified the relationship between long memory models and fractional differencing, proposing a class of models denominated fractional ARIMA, where the degree of differencing can be any real number2. The simplest of these is the fractionally integrated noise or ARIMA(0, d, 0) defined for d>-1, that is:6 Δdyt=ϵt;ϵ∼iid(0,σ2),and,Δd=(1-L)d.
To obtain an ARIMA(0, d, 0) for d that lies outside the range (-0.5,0.5), it is sufficient to start with an ARIMA(0,d¯,0), with d¯∈(-.05,0.5), such that d-d¯ is an integer. If d>0.5, we need to integrate d-d¯ times, if d<0.5, we difference d-d¯ times. The result will be an ARIMA(0, d, 0) which however will not be stationary if d≥0.5.
The more general fractional ARIMA (p,d,q)can be written as:7 ϕ(L)Δdyt=θ(L)ϵt,
where ϵt is as before a zero mean white noise process, d∈(-0.5,0.5), and ϕ(L) and θ(L) are polynomial in the lag operator or order p and q respectively. The ARIMA(p,d,q) can also be written as8 ϕ(L)yt=θ(L)(Δ-dϵt),
showing that the ARIMA(p,d,q) can be thought of as an ARMA(p,q) driven by a fractionally integrated ARIMA(0,d,0) noise, Δ-dϵt. The spectral density for the ARIMA(p,d,q) is:9 f(λ)=σϵ22πθ(e-iλ)/ϕ(e-iλ)21-e-iλ-2d
and as λ→0+10 f(λ)=σϵ22πθ(1)/ϕ(1)2λ-2d.
Again, if d≠0, then yt is a long memory process and it can be shown that its autocovariances obey the power law cr∼kr2d-1 as r→∞.
Alternatively we could write the spectral density of the fractional ARIMA(p,d,q) as:11 f(λ)=σ22π1-e-iλ-2dg(λ)
where g(λ) is the spectral density of an ARMA(p,q).3
The ARMA parameters as well as d are unknown and must be estimated. Assuming that p and q are known and that {ϵt} are Gaussian, we can use maximum likelihood estimation (MLE) to estimate the ARMA parameters as well as d. However, the MLE of this type of model requires O(n3) operations to evaluate the likelihood function. To avoid such intense computation, Fox and Taqqu (1986) suggest using the Whittle approximation to the likelihood function, that is:12 -2logl(Θ)≈∑j=1n/2[logfΘ(λj)+Ij/fΘ(λj)],
where Θ is the vector of ARMA parameters plus d, and fΘ(λ) is the spectral density of the ARIMA(p,d,q) process. The Whittle estimator (WE) is obtained by minimisation with respect to Θ. Fox and Taqqu (1986) show that the Whittle estimator of Θ, say Θ^W, is asymptotically equivalent to the exact MLE assuming that d>0, the model is correct, and the order of p and q is known.
However, p and q are unknown, and as a result both the ML and W estimators of d will be asymptotically biased. The same problem will arise if g(λ) is not ARMA but it is assumed that it is.
To overcome the problem, Robinson (1995) proposed a semi-parametric Gaussian estimator for d known as the Local Whittle (LW) estimator, which is developed under the assumption that yt is stationary and its spectral density behaves like Gλ-2d as λ→0+. The frequency domain Gaussian likelihood in the vicinity of the origin is:13 Qm(G,d)=m-1∑j=1mlog(Gλj-2d)+λj2dGI(λj),
where as before m<n is an integer controlling the number of frequencies included in the local likelihood. Estimates of G and d are then obtained through the minimisation of Qm(G,d) such that:14 (G^,d^)=argminG∈(0,∞),d∈[Δ1,Δ2]Qm(G,d),
with Δ1 and Δ2 are numbers such that -∞<Δ1<Δ2<1/2. Concentrating the likelihood with respect to G, it is found that d^ satisfies:15 argmind∈[Δ1,Δ2]logG^(d)-2d1m∑j=1mlogλj,G^(d)=m-1∑j=1mλj2dI(λj).
Under appropriate assumptions and conditions, and for d0∈(-1/2,1/2), Robinson(1995) and Shimotsu and Phillips (2006) show that m(d^-d0)→N(0,1/4).
Phillips and Shimostu (2004), among others, show that when d>1/2 the LW estimator exhibits non standard behaviour. Although it is consistent for d∈(1/2,1] and asymtotically normal for d∈(1/2,3/4), the LW has non normal asymptotic distribution for d∈[3/4,1], and d>1, but also converges to 1 in probability and is inconsistent.
The solution to the problem is provided by Shimotsu and Phillips (2004, 2006) who developed the Exact Local Whittle (ELW) estimator and its variants, whose asymptotics are based on the exact frequency domain (or its estimate which will give rise to FELW estimator) of the data generating process which is obtained from the minimisation of the objective function:16 Qm∗(G,d)=m-1∑j=1m[log(Gλj-2d)+λj2dGI(1-L)dy(λj)].
The ELW is computationally more demanding than LW but is shown to be consistent and asymptotically normally distributed for any value of d and therefore is valid under a wider range of cases.
Shimotsu and Phillips (2006) discuss the importance of the choice of m, explaining that as in the case of LW and ELW estimation, m has to grow fast for d^ to be consistent, but also that a too large value of m may induce a bias to the estimator from the short run dynamics. A rule of thumb suggests that within m=nα, we should choose a value of α around 0.6 (see Shimotsu and Phillips 2006). As we use LW, ELW and FELW to estimate d^ and perform the test H0:d^=1 vs HA:d^<1 for all our series, we derive the exact distribution of the LW, ELW and FELW estimators for n=200 and different values of α in the interval [0.575, 0.65] as displayed in Table 5 in Appendix. Notice that we shall only be concerned with the hypothesis that d^=1 (the series tested has a unit root) against the one sided alternative that d^<1 (the series has long memory but is mean reverting and possibly covariance stationary). That implies that the relevant 90% and 95% critical values are the ones corresponding to the 0.1 and 0.05 quantiles respectively for the different values of α.
Results
The results of our analysis are presented as follows. First, we test the relative gasoline prices of the various units for the null of a unit root/stationarity by means of ADF and KPSS. Then, we consider the possiblity that relative gasoline prices may be long memory processes and using the Local Whittle (LW), Exact Local Whittle (ELW), Feasible Exact Local Whittle estimators (FELW) and Feasible Exact Local Whittle estimators with de-trending (FELW dt) we test for the order of integration d=1 versus a fractional alternative, as discussed above. Our analysis is conducted for different geographical level (PADDs, States, Cities) to take into account any potential differences due to levels of data aggregation.
Table 1 provides the results of ADF unit root test and KPSS stationary test by including the trend and the constant in the auxiliary regressions. The ADF test is carried out under the null hypothesis that the series contains a unit root, which means that if the null hypothesis is not rejected, the series follows a random walk process (d=1) and as such it is not converging toward the cross-sectional mean.
For the ADF test the issue of the choice of the optimal lag was addressed by means of the Modified Akaike’s Information Criterion (MAIC). Table 1 shows that ADF tests cannot reject the null for all series (except for Denver), implying that the series are not converging. The KPSS test mostly confirms the results of ADF tests. However, it provides contrasting evidence in some cases as for example it cannot reject the null of stationary for one PADD (PADD1B), two States (Colorado and Massachussetts) and three cities (Boston, Denver and Miami) thus providing some evidence of convergence.Table 1 Unit Root tests for PADDs, Countries and Cities series - ADF vs. KPSS
Series ADF C &T KPSS C &T Convergence?
(Lag - MAIC) (Bandwith)
PADDs
PADD1A −1.141(10) c 0.272(8) c+t NO
PADD1B −2.042(11) c 0.076(3) c+t YES(KPSS)
PADD1C −1.357(10) c+t 0.311(9) c+t NO
PADD2 −2.211(13) c+t 0.372(7) c+t NO
PADD3 −2.348(10) c+t 0.329(10) c+t NO
PADD4 −1.357(12) c 0.264(4) c+t NO
PADD5 −2.0530(6) c+t 0.308(10) c+t NO
States
California −1.683(7) c+t 0.320(10) c+t NO
Colorado −1.415(14) c 0.137(2) c+t YES(KPSS)
Florida −1.182(10) c+t 0.197(7) c+t NO
Massachusetts −2.159(10) c 0.141(6) c YES(KPSS)
Minnesota −1.321(10) c 0.377(8) c+t NO
New York −0.039(11) c 0.302(6) c+t NO
Ohio −2.438(14) c+t 0.300(7) c+t NO
Texas −2.248(10) c+t 0.324(10) c+t NO
Washington −1.732(12) c+t 0.298(9) c+t NO
Cities
Boston −1.967(10) c+t 0.146(8) c+t YES(KPSS)
Chicago −1.346(13) c 0.391(6) c+t NO
Cleveland −2.589(9) c+t 0.359(9) c+t NO
Denver −5.853(0) c+t 0.076(1) c+t YES(both)
Houston −2.256(8) c+t 0.297(10) c+t NO
Los Angeles −2.240(7) c+t 0.255(10) c+t NO
Miami −0.246(10) c+t 0.159(9) c+t YES(KPSS)
New York City −1.877(10) c+t 0.192(7) c+t NO
San Francisco −1.432(7) c+t 0.352(10) c+t NO
Seattle −1.705(10) c+t 0.302(9) c+t NO
ADF critical values with const.+trend: -4.008 (1%); -3.433 (5%); -3.140 (10%) ADF critical values with const.: -3.465 (1%); -2.876 (5%); -2.574 (10%) KPSS critical values with const.+trend: 0.216 (1%); 0.146 (5%); 0.119 (10%) KPSS critical values with const.: 0.739 (1%); 0.463 (5%); 0.347 (10%)
Tables 2, 3 and 4display the results of the LW-based tests versus the alternative of Long Memory for PADD, States and Cities, respectively. These findings report the estimated order of integration (d^) as well as the test statistic for the null that d=1 obtained by considering different bandwidths between 0.575 and 0.65 following the approach suggested by Shimotsu and Phillips (2006) [20]4. This statement applies to all the four methods used to test for long memory (LW, ELW, FELW, FELW dt).
In interpreting long memory tests it is worth bearing in mind the following implications of the different values of the estimated order of integration d for the relative price series:A series with order of integration I(0≤d<12) is mean/trend reverting and covariance stationary and therefore convergent (albeit slowly if d>0);
A series with order of integration I(12≤d<1) is still mean/trend reverting but not covariance stationary. The implication of this is that although the series still converges, it does that very slowly.
In reading the Tables, it is also recommended to pay particular attention to the values returned by FELW dt when the series contains a trend as it is more precise.
In the Table 2, the fractional integration tests show strong evidence of convergence for all PADDs, and for 4 of them (PADD1A, PADD1B, PADD2, PADD4) with an order of integration of relative gasoline price almost always less the 0.5, and for PADD1C PADD3 and PADD5 with fractional integration order between 0.5 - 0.7. In detail, for the PADD1A (New England) there is evidence that the fractional integration order goes from 0.2305 through 0.4327 (in this case, the de-trending process is not necessary to be considered). For PADD1B (Central Atlantic), results suggest that the integration order revolves around 0. This implies that the series is pretty much I(0) stationary and takes a convergent pathway. For PADD1C (Lower Atlantic), the fractional integration order of FELW dt lies between 0.4365 and 0.6291, and for this range of values, the trend matters. There is, therefore, some good evidence of a long memory process that leads to a relatively slow convergence. For PADD2 (Mid West) the fractional integration order of FELW is stable around 0.3. It means that the long memory dynamism leads to a stationary gait resulting in convergence both when considering trend and no trend procedures. In PADD3 (Gulf Coast), the gasoline price series is always“non covariance-stationary”(both in case of trend and de-trend). The estimation of d^ provides values around 0.7 leading to the interpretation that it is still mean/trend reverting and characterised by a very slow convergence. For the PADD 4 (Rocky Mountain) the order of integration of FELW dt ranges from 0.04 and (that are not distinguishable from 0) to 0.10 implying a strong evidence of convergence. Finally, for PADD5 (West Coast), the fractional integration order is constant around 0.65, as values resulted with de-trending procedure shall be considered. This result suggests that convergence occurs slowly and with a no stationarity in covariance.Table 2 Long memory test for PADD’ gasoline price time series
LW ELW FELW FELW dt
PADD1A − 199 obs.
α= 0.575 d^ 0.2305 0.2751 0.2863 0.2763
H0:d=1 −3.4415 −3.2420 −3.1918 −3.2364
α= 0.6 d^ 0.2902 0.3376 0.3397 0.3282
H0:d=1 −3.4040 −3.1767 −3.1666 −3.2220
α= 0.625 d^ 0.3314 0.3770 0.3736 0.3616
H0:d=1 −3.4739 −3.2371 −3.2549 −3.3172
α= 0.65 d^ 0.3914 0.4408 0.4327 0.4207
H0:d=1 −3.3888 −3.1137 −3.1587 −3.2253
PADD1B − 199 obs.
α= 0.575 d^ −0.0056 0.0433 0.0009 −0.1976
H0:d=1 −4.4971 −4.2787 −4.4683 −4.4683
α= 0.6 d^ 0.0428 0.0714 0.0496 −0.1238
H0:d=1 −4.5668 −4.4534 −4.5577 −5.3894
α= 0.625 d^ 0.1030 0.1033 0.1006 −0.0408
H0:d=1 −4.6608 −4.6595 −4.6736 −5.4081
α= 0.6 d^ 0.1809 0.1556 0.1746 0.0728
H0:d=1 −4.5606 −4.7013 −4.5954 −5.1624
PADD1C − 199 obs.
α= 0.575 d^ 0.4365 0.4506 0.4860 0.3929
H0:d=1 −2.5020 −2.4571 −2.2986 −2.7152
α= 0.6 d^ 0.4648 0.4775 0.5155 0.4316
H0:d=1 −2.5666 −2.5057 −2.3235 −2.7259
α= 0.625 d^ 0.5363 0.5492 0.5943 0.6298
H0:d=1 −2.4094 −2.3423 −2.1080 −1.9239
α= 0.65 d^ 0.5504 0.5784 0.5992 0.6291
H0:d=1 −2.5031 −2.3474 −2.2318 −2.0653
PADD2 − 199 obs.
α= 0.575 d^ 0.3130 0.2482 0.3201 0.2232
H0:d=1 −3.0724 −3.3620 −3.0408 −3.4741
α= 0.6 d^ 0.2428 0.2190 0.2636 0.1738
H0:d=1 −3.6315 −3.7455 −3.5517 −3.9623
α= 0.625 d^ 0.2867 0.2608 0.3086 0.2285
H0:d=1 −3.7062 −3.8412 −3.5926 −4.0089
α= 0.65 d^ 0.2998 0.2801 0.3236 0.2518
H0:d=1 −3.8984 −4.0082 −3.7663 −4.1658
PADD3 − 199 obs.
α= 0.575 d^ 0.7568 0.6251 0.7577 0.7124
H0:d=1 −1.0878 −1.6764 −1.0835 −1.2862
α= 0.6 d^ 0.7030 0.6311 0.7165 0.6832
H0:d=1 −1.4245 −1.7693 −1.3597 −1.5930
α= 0.625 d^ 0.7589 0.6731 0.7524 0.7143
H0:d=11 −1.2549 −1.6986 −1.2865 −1.4844
α= 0.65 d^ 0.7237 0.6881 0.7318 0.6970
H0:d=1 −1.5381 −1.7367 −1.4930 −1.6868
PADD4 − 199 obs.
α= 0.575 d^ −0.0066 −0.0334 −0.0645 0.0579
H0:d=1 −4.5014 −4.6214 −4.7605 −4.7309
α= 0.6 d^ 0.0240 −0.0009 −0.0210 −0.1940
H0:d=1 −4.6809 −4.8000 −4.8963 −4.8890
α= 0.625 d^ 0.0778 0.0579 0.0493 0.0452
H0:d=1 −4.7931 −4.8955 −4.9398 −4.9615
α= 0.65 d^ 0.1274 0.1156 0.1116 0.1042
H0:d=1 −4.8583 −4.9243 −4.9462 −4.9877
PADD5 − 199 obs.
α= 0.575 d^ 0.7293 0.7609 0.7738 0.6637
H0:d=1 −1.2108 −1.0694 −1.0118 −1.5038
α= 0.6 d^ 0.6826 0.7707 0.7243 0.6396
H0:d=1 −1.5223 −1.0995 −1.3224 −1.7284
α= 0.625 d^ 0.7185 0.7354 0.7445 0.6576
H0:d=1 −1.4627 −1.3747 −1.3278 −1.7791
α= 0.65 d^ 0.6836 0.6991 0.6828 0.6457
H0:d=1 −1.7615 −1.6756 −1.7659 −1.9728
From Table 3 we observe strong evidence of convergence with stationarity in covariance for the states of Colorado, Florida, Massachussets, Minnesota, New York and Ohio, with an order of integration is always <0.5 regardless of the value of the bandwidth α and for all the four methods employed. Note that, however, the relative price of gasoline in Colorado is very likely to be an I(0) stationary“short-memory”process. On the other hand, relative prices of California, Texas and Washington report an order of integration always above 0.5 indicating a possibly very slow convergence to“one-price”due to mean(trend) reversion but non-stationarity in covariance.Table 3 Long memory test for State’ gasoline price time series
LW ELW FELW FELW dt
California − 199 obs.
α= 0.575 d^ 0.7516 0.7781 0.7768 0.6562
H0:d=1 −1.1110 −0.9925 −0.9983 −1.5374
α= 0.6 d^ 0.6883 0.7503 0.7073 0.6309
H0:d=1 −1.4950 −1.1976 −1.4039 −1.7701
α= 0.625 d^ 0.7433 0.7596 0.7572 0.6510
H0:d=1 −1.3338 −1.2492 −1.2616 −1.8134
α= 0.65 d^ 0.7162 0.7459 0.7208 0.6408
H0:d=1 −1.5801 −1.4149 −1.5545 −2.0000
Colorado − 199 obs.
α= 0.575 d^ 0.0069 0.0503 −0.0103 −0.1296
H0:d=1 −4.4414 −4.2471 −4.5180 −5.0515
α= 0.6 d^ 0.0032 0.0494 −0.0134 −0.1217
H0:d=1 −4.7807 −4.5588 −4.8601 −5.3797
α= 0.625 d^ 0.0496 0.0698 0.0329 −0.0606
H0:d=1 −4.9384 −4.8333 −5.0251 −5.5110
α= 0.65 d^ 0.0795 0.0838 0.0647 −0.0158
H0:d=11 −5.1254 −5.1013 −5.2077 −5.6558
Florida − 199 obs.
α= 0.575 d^ 0.3196 0.3620 0.3885 0.0651
H0:d=1 −3.0429 −2.8533 −2.7346 −4.1808
α= 0.6 d^ 0.3610 0.3952 0.4224 0.1580
H0:d=1 −3.0645 −2.9004 −2.7700 −4.0382
α= 0.625 d^ 0.4451 0.4613 0.4898 0.2960
H0:d=1 −2.8836 −2.7993 −2.6513 −3.6583
α= 0.65 d^ 0.4986 0.5035 0.5271 0.3833
H0:d=1 −2.7919 −2.7643 −2.6330 −3.4337
Massachussets − 199 obs.
α= 0.575 d^ 0.1092 0.1529 0.1404 0.1415
H0:d=1 −3.9837 −3.7883 −3.8443 −3.8395
α= 0.6 d^ 0.1745 0.2059 0.2040 0.2029
H0:d=1 −3.9590 −3.8084 −3.8177 −3.8228
α= 0.625 d^ 0.1977 0.2181 0.2209 0.2190
H0:d=1 −4.1687 −4.0627 −4.0486 −4.0581
α= 0.65 d^ 0.2596 0.2822 0.2879 0.2846
H0:d=1 −4.1222 −3.9966 −3.9650 −3.9829
Minnesota − 199 obs.
α= 0.575 d^ 0.3668 0.28299 0.3863 0.3369
H0:d=1 −2.8317 −3.2069 −2.7447 −2.9656
α= 0.6 d^ 0.2832 0.2435 0.3142 0.2684
H0:d=1 −3.4379 −3.6280 −3.2890 −3.5086
α= 0.625 d^ 0.3218 0.3027 0.3604 0.3198
H0:d=1 −3.5242 −3.6234 −3.3234 −3.5345
α= 0.65 d^ 0.3691 0.3564 0.4057 0.3693
H0:d=1 −3.5127 −3.5833 −3.3091 −3.5117
New York − 199 obs.
α= 0.575 d^ 0.1693 −0.0410 0.2401 0.0750
H0:d=1 −3.7148 −4.6553 −3.3983 −4.1366
α= 0.6 d^ 0.2180 0.2812 0.2709 0.1120
H0:d=1 −3.7505 −3.4474 −3.4967 −4.2587
α= 0.625 d^ 0.2740 0.3867 0.3147 0.1656
H0:d=1 −3.7723 −3.1870 −3.5608 −4.3357
α= 0.65 d^ 0.3459 0.4796 0.3785 0.2425
H0:d=1 −3.6418 −2.8972 −3.4602 −4.2174
Ohio − 199 obs.
α= 0.575 d^ 0.3829 0.3223 0.3861 0.2742
H0:d=1 −2.7596 −3.0306 −2.7454 −3.2459
α= 0.6 d^ 0.3362 0.2969 0.3448 0.2419
H0:d=1 −3.1833 −3.3721 −3.1421 −3.6359
α= 0.625 d^ 0.3874 0.3385 0.3877 0.2998
H0:d=1 −3.1830 −3.4372 −3.1818 −3.6383
α= 0.65 d^ 0.3232 0.2966 0.3345 0.2507
H0:d=1 −3.7685 −3.9163 −3.7055 −4.1718
Texas − 199 obs.
α= 0.575 d^ 0.6407 0.5143 0.6810 0.6950
H0:d=1 −1.6068 −2.1720 −1.4267 −1.3640
α= 0.6 d^ 0.6223 0.5553 0.6649 0.6820
H0:d=1 −1.8112 −2.1327 −1.6070 −1.5250
α= 0.625 d^ 0.6893 0.6358 0.7205 0.7152
H0:d=1 −1.6144 −1.8922 −1.4525 −1.4799
α= 0.65 d^ 0.6490 0.6511 0.6909 0.6939
H0:d=1 −1.9543 −1.9427 −1.7207 −1.7044
Washington − 199 obs.
α= 0.575 d^ 0.6389 0.5283 0.6279 0.6457
H0:d=1 −1.6149 −2.1097 −1.6642 −2.3884
α= 0.6 d^ 0.6146 0.5386 0.6346 0.4812
H0:d=1 −1.8481 −2.2130 −1.7525 −2.4880
α= 0.625 d^ 0.6593 0.5593 0.6394 0.5480
H0:d=1 −1.7704 −2.2899 −1.8736 −2.3487
α= 0.65 d^ 0.6272 0.5361 0.6171 0.4961
H0:d=1 −2.0757 −2.5826 −2.1319 −2.8058
Table 4 reports the results for the 10 American cities for which data are available. Again, in this case, the null of a unit root for relative prices of gasoline is rejected in almost all cases and very convincingly for some cities like Boston, Chicago and Denver where the estimates for d are always <0.5 implying mean/trend reversion and covariance-stationarity albeit slow convergence. Furthermore, whilst there are no gasoline prices reporting an order of integration close to 0, relative prices in New York City have order of integration (d^) ranging between 0.3113 and 0.5214 (in FELW model) and are mean reverting long memory processes but possibly not covariance-stationary. The same situation occurs for the cities of Cleveland and Seattle where the estimated values of d are found to be greater than 0.5 when using LW, ELW and FELW, but slighly below the covariance non-stationarity threshold when FELW de-trending is used (this ranges between 0.37 and 0.48 for Cleveland and between 0.44 and 0.45 for Seattle). The city of Miami, in contrast with the tendency emerged in its state (Florida), shows an integration order between 0.5944 and 0.6481 with FELW dt, implying a slower convergence process and non-stationarity in covariance. On the contrary, the cities of Los angeles and San Francisco present (d^) values in line with the state of California with a range between 0.62 and 0.65. These results suggest, non-stationarity and very slow convergence. Houston has the highest (d^) values compared to all other cities (also in line with the state of Texas) suggesting a slower convergence process compared to the other cities (the (d^) values are higher in all estimated models ranging between 0.69 and 0.72).Table 4 Long memory test for City’ gasoline price time series
LW ELW FELW FELW dt
Boston − 199 obs.
α= 0.575 d^ 0.3087 0.2997 0.3560 0.2374
H0:d=1 −3.0918 −3.1319 −2.8801 −3.4105
α= 0.6 d^ 0.3764 0.3365 0.4075 0.3002
H0:d=1 −2.9907 −3.1822 −2.8417 −3.3563
α= 0.625 d^ 0.4140 0.3571 0.4320 0.3352
H0:d=1 −3.0450 −3.3409 −2.9513 −3.4545
α= 0.65 d^ 0.4534 0.4064 0.4736 0.3926
H0:d=1 −3.0432 −3.3048 −2.9307 −3.3818
Chicago − 199 obs.
α= 0.575 d^ 0.1502 0.1432 0.1402 0.1209
H0:d=1 −3.8002 −3.8317 −3.8453 −3.9315
α= 0.6 d^ 0.1348 0.1362 0.1368 0.1190
H0:d=1 −4.1496 −4.1429 −4.1396 −4.2250
α= 0.625 d^ 0.1697 0.1766 0.1765 0.1593
H0:d=1 −4.3143 −4.2784 −4.2788 −4.3685
α= 0.65 d^ 0.1985 0.2120 0.2119 0.1959
H0:d=1 −4.4628 −4.3871 −4.3879 −4.4771
Cleveland − 199 obs.
α= 0.575 d^ 0.6361 0.5287 0.5929 0.4886
H0:d=1 −1.6273 −2.1075 −1.8206 −2.2872
α= 0.6 d^ 0.5052 0.4412 0.4946 0.3855
H0:d=1 −2.3728 −2.6797 −2.4236 −2.9473
α= 0.625 d^ 0.5606 0.4811 0.5352 0.4407
H0:d=1 −2.2831 −2.6965 −2.4153 −2.9063
α= 0.65 d^ 0.4779 0.4254 0.4722 0.3771
H0:d=1 −2.9070 −3.1992 −2.9388 −3.4682
Denver − 199 obs.
α= 0.575 d^ 0.1638 0.1425 0.1628 −0.1797
H0:d=1 −3.7397 −3.8351 −3.7440 −5.2757
α= 0.6 d^ 0.1491 0.1409 0.1497 −0.1669
H0:d=1 −4.0808 −4.1202 −4.0779 −5.5964
α= 0.625 d^ 0.1871 0.1553 0.1823 −0.1018
H0:d=1 −4.2241 −4.3892 −4.2489 −5.7250
α= 0.65 d^ 0.2157 0.1666 0.2085 −0.0458
H0:d=1 −4.3668 −4.6401 −4.4068 −5.8229
Houston − 199 obs.
α= 0.575 d^ 0.6823 0.5023 0.7074 0.7067
H0:d=1 −1.4209 −2.2260 −1.3087 −1.3118
α= 0.6 d^ 0.6446 0.5778 0.6855 0.6845
H0:d=1 −1.7047 −2.0248 −1.5084 −1.5133
α= 0.625 d^ 0.7247 0.6953 0.7589 0.7296
H0:d=1 −1.4304 −1.5835 −1.2530 1.4050
α= 0.65 d^ 0.6727 0.7604 0.7337 0.6972
H0:d=1 −1.8221 −1.3338 −1.4825 −1.6861
Los Angeles − 199 obs.
α= 0.575 d^ 0.6423 0.6790 0.6833 0.6404
H0:d=1 −1.5997 −1.4354 −1.4163 −1.6082
α= 0.6 d^ 0.6302 0.7065 0.6794 0.6262
H0:d=1 −1.7736 −1.4078 −1.5374 −1.7927
α= 0.625 d^ 0.6783 0.7144 0.7041 0.6505
H0:d=1 −1.6714 −1.4839 −1.5376 −1.8160
α= 0.65 d^ 0.6535 0.7021 0.6828 0.6344
H0:d=1 −1.9290 −1.6587 −1.7660 −2.0353
Miami − 199 obs.
α= 0.575 d^ 0.4750 0.5961 0.5851 0.5944
H0:d=1 −2.3478 −1.8062 −1.8555 −1.8138
α= 0.6 d^ 0.5369 0.6359 0.6225 0.6238
H0:d=1 −2.2209 −1.7463 −1.8103 −1.8043
α= 0.625 d^ 0.5864 0.6671 0.6535 0.6463
H0:d=1 −2.1492 −1.7296 −1.8006 −1.8381
α= 0.65 d^ 0.5980 0.6481 0.6466 0.6481
H0:d=1 −2.2381 −1.9593 −1.9674 −1.9591
New York City − 199 obs.
α= 0.575 d^ 0.3113 0.3793 0.3969 0.2024
H0:d=1 −3.0798 −2.7760 −2.6971 −3.5672
α= 0.6 d^ 0.3879 0.4323 0.4554 0.2851
H0:d=1 −2.9357 −2.7227 −2.6117 −3.4287
α= 0.625 d^ 0.4458 0.4544 0.4814 0.3305
H0:d=1 −2.8799 −2.8351 −2.6947 −3.4790
α= 0.65 d^ 0.5179 0.4940 0.5214 0.3944
H0:d=1 −2.6840 −2.8170 −2.6650 −3.3717
San Francisco − 199 obs.
α= 0.575 d^ 0.7153 0.6822 0.7523 0.6480
H0:d=1 −1.2734 −1.4213 −1.1076 −1.5743
α= 0.6 d^ 0.6353 0.6705 0.6047 0.6181
H0:d=1 −1.7489 −1.5803 −1.8957 −1.8316
α= 0.625 d^ 0.6855 0.6656 0.6394 0.6401
H0:d=1 −1.6344 −1.7375 −1.8739 −1.8699
α= 0.65 d^ 0.6945 0.6804 0.6458 0.6429
H0:d=1 −1.7011 −1.7792 −1.9721 −1.9884
Seattle − 199 obs.
α= 0.575 d^ 0.6339 0.5603 0.6334 0.4516
H0:d=1 −1.6373 −1.9664 −1.6394 −2.4526
α= 0.6 d^ 0.5659 0.5407 0.6378 0.4401
H0:d=1 −2.0818 −2.2028 −1.7368 −2.6850
α= 0.625 d^ 0.6056 0.5471 0.6302 0.4599
H0:d=1 −2.0496 −2.3533 −1.9216 −2.8066
α= 0.65 d^ 0.6075 0.5309 0.6105 0.4502
H0:d=1 −2.1853 −2.6116 −2.1686 −3.0609
It is apparent that, overall, the estimated orders of (fractional) integration at PADD, State and City levels are in sharp contrast with those obtained by means of the ADF and KPSS type of tests. Our results clearly suggest that the law of one-price in US gasoline price market seems to hold, although the speed of convergence may be different between (and within) PADDs, states and cities.
The change in speed of convergence area by area, may be linked to heterogeneous development of the private and public initiatives at State level, and mainly to the demand dynamics at City level. In this respect, as found by Holmes et al. (2013) [12], the heterogeneous evolution of the price speed convergence is constrained by different taxation policies issued at state level, different capacity of the refineries as well as the number of retailers and the payload of the pipelines connecting the refineries with U.S. regions. Note that, this is in line with Blair et al. (2017) [3] who argued that both in the short and long run there is heterogeneity in the speed of convergence that hinders the accomplishment of the law of one-price.
Conclusion and policy implications
The retail gasoline may appear to be one of the sectors in which there is inevitable convergence in the US market, thanks to the homogeneity of the product, the deregulation policies of recent years and the full availability of price information. In this paper we have used an alternative approach to studying the convergence of gasoline prices between American PADDs, states and cities. Previous studies using different methodologies achieved mixed results on the process of convergence between US PADDs, States and Cities. Using the Local Whittle estimator of the fractional integration parameter and its variations (Exact Local Whittle and Feasible Exact Local Whittle) we have tested the hypothesis that relative retail gasoline prices contain a unit root (implying non-convergence) against the alternative that they are fractionally integrated long memory processes (implying convergence albeit a slow one). This has allowed us to consider a more flexible alternative than the usual stationarity with weak dependence implied by ADF type of tests. In terms of energy policy, the convergence process is not achievable at the same time or speed in different US geographical areas. This may be due to the existence of a variety of institutional actors, geographically dispersed markets due to transport constraints and different taxation. In detail our results suggest that while for 2 of our 7 PADDs, there is evidence to suggest that relative gasoline prices are not fractionally integrated processes and are instead I(0), evidence points at fractional integration of relative prices of gasoline for the remaining PADDs. These findings support the law of one-price in the long run and holds also among American states and cities. The results are fairly consistent for states and their cities like in the case of California, for Los Angeles and San Francisco and Texas with Houston. We found mean reversion also for others cities like New York City, Cleveland and Miami and their relative states (New York, Ohio, Colorado). However, for these states and cities the relative price series showed non stationarity in covariance and thus very slow convergence patterns.
We do not provide evidence of the numerical on time-price-slope to understand whether a slower convergence process is linked to a high price level so that decreasing like a feather toward the convergence point, but it is clear that the issue of being no co-variance stationary can generate spikes in increase such that turning to the convergence point of cross-sectional mean (the one-price) could happen much more slowly.
Given the difference in our results, compared to the other studies, further analyses may be conducted on other markets (e.g. the electricity market) and in other geographical contexts (e.g. European countries, regions).
Appendix
See Table 5.Table 5 Quantiles of: H0:d^=1, n=200, α∈{0.575;0.6;0.625;0.65}
Quantile LW ELW FELW FELW dt
α= 0.575
0.025 −1.3675 −1.4633 −1.3909 −1.6551
0.050 −1.1191 −1.2203 −1.2013 −1.3535
0.100 −0.8713 −0.9189 −0.9233 −0.9553
0.250 −0.4624 −0.4650 −0.4632 −0.5053
0.500 −0.0649 −0.0251 −0.0239 −0.0405
Mean −0.0942 −0.0530 −0.0479 −0.0811
St. Dev. 0.6014 0.6726 0.6520 0.6979
α= 0.6
0.025 −1.3306 −1.3962 −1.3474 −1.6071
0.050 −1.1066 −1.1415 −1.1397 −1.2028
0.100 −0.8452 −0.8676 −0.8633 −0.9085
0.250 −0.4487 −0.4446 −0.4426 −0.4669
0.500 −0.0592 −0.0016 −0.0040 −0.0209
Mean −0.0875 −0.0295 −0.0253 −0.0530
St. Dev. 0.5855 0.6533 0.6385 0.6780
α= 0.625
0.025 −1.3427 −1.3672 −1.3577 −1.5217
0.050 −1.0949 −1.1116 −1.1165 −1.1533
0.100 −0.8346 −0.8380 −0.8409 −0.8917
0.250 −0.4579 −0.4312 −0.4310 −0.4598
0.500 −0.0752 0.0034 0.0054 −0.0084
Mean −0.0989 −0.0166 −0.0143 −0.0376
St. Dev. 0.5815 0.6535 0.6445 0.6753
α= 0.65
0.025 −1.2798 −1.3083 −1.3175 −1.3563
0.050 −1.0617 −1.0792 −1.0726 −1.1109
0.100 −0.8415 −0.8192 −0.8185 −0.8532
0.250 −0.4644 −0.4034 −0.4031 −0.4254
0.500 −0.0987 0.0106 0.0127 0.0048
Mean −0.1188 −0.0094 −0.0078 −0.0250
St. Dev. 0.5564 0.6299 0.6235 0.6441
Funding
No funding was received.
Declarations
Conflict of interest
Marco R. Barassi declares that he has no conflict of interest; Gianluigi De Pascale declares that he has non conflict of interest; Raffaele Lagravinese declares that he has no conflict of interest. Ethical approval: This article does not contain any studies with human participants performed by any of the authors.
1 rockets and feathers”refers to pricing phenomenon occurring when downstream prices react in a different manner to upstream price changes, depending on the characteristics of upstream prices or changes in those prices.
2 Based on Box and Jenkins (1970)[6], ARMA and ARIMA, respectively, stand for Autoregressive-moving-average and Autoregressive-integrated-moving-average models.
3 The fractional ARIMA(p,d,q) is particularly convenient as it can be used to describe both the long and the short term behaviour of the yt. In fact d determines the long term correlations and the behaviour of the spectral density near zero frequency and the AR and MA parameters describe the short term correlations and shape the spectral density for frequencies not near zero, independently from d.
4 The test statistic is then compared to the relevant quantiles reported in Table 5 in Appendix. It is worth noticing that as suggested by Shimotsu and Phillips (2006)[20] using a bandwidth between [0.6, 0.65] provides a distribution of the test statistic under the null hypothesis H0:d^=1 where the 0.5 quantile (median) is closer to the mean value which is closer to 0 as α→6.5. [8]
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3. Blair BF Campbell RC Mixon PA Price pass-through in us gasoline markets Energy Econ. 2017 65 42 49 10.1016/j.eneco.2017.04.011
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8. Dubois E Lardic S Mignon V The exact maximum likelihood-based test for fractional cointegration: critical values, power and size Comput. Econ. 2004 24 3 239 255 10.1007/s10614-004-3544-x
9. Engle, R. F., Granger, C. W. : Co-integration and error correction: representation, estimation, and testing. Econ. J. Econ. Soc. 251–276 (1987)
10. Granger CW Hyung N Occasional structural breaks and long memory with an application to the s &p 500 absolute stock returns J. Empir. Financ. 2004 11 3 399 421 10.1016/j.jempfin.2003.03.001
11. Granger CW Joyeux R An introduction to long-memory time series models and fractional differencing J. Time Ser. Anal. 1980 1 1 15 29 10.1111/j.1467-9892.1980.tb00297.x
12. Holmes MJ Otero J Panagiotidis T On the dynamics of gasoline market integration in the united states: Evidence from a pair-wise approach Energy Econ. 2013 36 503 510 10.1016/j.eneco.2012.10.008
13. HoskNG J Fractional differencing Biometrika 1981 68 165 76 10.1093/biomet/68.1.165
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20. Shimotsu K Phillips PC Local whittle estimation of fractional integration and some of its variants J. Econ. 2006 130 2 209 233 10.1016/j.jeconom.2004.09.014
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Eye (Lond)
Eye (Lond)
Eye
0950-222X
1476-5454
Nature Publishing Group UK London
36460858
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10.1038/s41433-022-02313-x
Review Article
Transforming ophthalmology in the digital century—new care models with added value for patients
Faes Livia 1
Maloca Peter M. 2345
Hatz Katja 67
Wolfensberger Thomas J. 8
Munk Marion R. 910
Sim Dawn A. 11121314
http://orcid.org/0000-0002-9868-154X
Bachmann Lucas M. [email protected]
1516
Schmid Martin K. 17
1 grid.439257.e 0000 0000 8726 5837 Moorfields Eye Hospital, 162 City Rd, London, EC1V 2PD UK
2 grid.436474.6 0000 0000 9168 0080 Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London, EC1V 2PD UK
3 grid.508836.0 Institute of Molecular and Clinical Ophthalmology (IOB), Basel, Switzerland
4 grid.6612.3 0000 0004 1937 0642 OCTlab, University Basel, Mittlere Strasse 91, CH-4056 Basel, Switzerland
5 Hirslanden St. Anna im Bahnhof Luzern, Lucerne, Switzerland
6 Vista Eye Clinic Binningen, Hauptstrasse 55, CH-4102 Binningen, Switzerland
7 grid.6612.3 0000 0004 1937 0642 Faculty of Medicine, University of Basel, Basel, Switzerland
8 grid.9851.5 0000 0001 2165 4204 Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
9 grid.411656.1 0000 0004 0479 0855 Ophthalmology, Inselspital, University Hospital Bern, Bern, Switzerland
10 grid.16753.36 0000 0001 2299 3507 Northwestern University, Feinberg School of Medicine, Chicago, IL USA
11 grid.436474.6 0000 0000 9168 0080 Moorfields Ophthalmic Reading Centre and Artificial Intelligence Lab, Moorfields Eye Hospital NHS Foundation Trust, London, UK
12 grid.436474.6 0000 0000 9168 0080 Medical Retina Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
13 grid.83440.3b 0000000121901201 Institute of Ophthalmology, University College London, London, UK
14 grid.451056.3 0000 0001 2116 3923 NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, England
15 grid.483560.c Medignition AG, Engelstrasse 6, 8004 Zurich, Switzerland
16 grid.7400.3 0000 0004 1937 0650 University of Zurich, CH-8091 Zurich, Switzerland
17 grid.413354.4 0000 0000 8587 8621 Eye Clinic, Lucerne Cantonal Hospital LUKS, 6000 16 Lucerne, Switzerland
3 12 2022
14
9 8 2022
31 10 2022
10 11 2022
© The Author(s), under exclusive licence to The Royal College of Ophthalmologists 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2–3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.
Subject terms
Scientific community
Health care
==== Body
pmcDigitalization accelerates change
Digitalization has radically changed many areas of our lives. Astonished teenagers listen with eyes wide to the stories of cassette recorders, booking air travel on the telephone, looking through library card index for research, or visiting the bank teller to withdraw money for the week. Growing up in a world of Spotify, travel portals, AirBnB, Amazon, Google, Neobanks and multiplayer online games, these tales seem like stories from an old, distant world, even though they were the norm a mere few decades ago.
Conversely, such disruptive and radical changes have not yet occurred in the medical domain [1]. Despite the availability of technology for the purpose of delivering digital first solutions such as electronic medical records, algorithmically supported image analysis and remote diagnosis with telemedicine, change in healthcare has been slower, more cautious, and unequally distributed compared to industries such as retail, commerce, or banking [2, 3].
Digitalization in medicine
Many areas of medical care have remained essentially unchanged for half a century. Medical practice remains to a large extent institution-bound and doctor-centred [4]. The patiens [lat] - the patiently sufferer, goes to the place of medical knowledge - the medical centre - to obtain advice on the existence and the course of (his) disease. While digitalization has led to comprehensive customer-centricity in many areas, such examples are rare in medicine. While doctor-centred institution-bound care will remain important throughout digital innovation in medicine, it will be crucial to determine which aspects of care can be decentralized to the benefit of relieving the pressure of healthcare systems, patients, and medical personnel. Approaches to greater patient-centricity and more decentralized care can be observed in chronic diseases such as bronchial asthma, chronic obstructive pulmonary disease, heart failure and diabetes mellitus (summarized in [5]). For some, rarer diseases, so-called home care approaches have become established, in which patients are visited at home by specialized nurses and treated with infusions, for example [6].
Digitalization in ophthalmology — hurdles and opportunities
In ophthalmology, new approaches making benefit of innovative digital solutions have been developed, particularly in Northern Europe, the UK and Australia, partly in national programmes, in the care of patients with chronic retinal diseases such as diabetic macular oedema (DMO) and age-related macular degeneration (AMD) [7–21]. Both conditions are chronic and lead to severe visual impairment if left untreated. If detected, they can be controlled albeit with complex, variable, frequent and prolonged treatments regimes - the regular application of the active substance directly into the eye several times a year. The strain on the patient and their carers to follow such a therapy for a longer period of time is considerable [22]. Unfortunately, we still observe too many therapy discontinuations and only some of the reasons are known including low vision at baseline and extent of co-morbidity [23]. This occurs despite overwhelming evidence that therapy interruptions lead to a lack of care, which results in vision loss and a large national disease burden and in many regions treatment discontinuation is not detected and acknowledged. However, it may be difficult for ophthalmologists to perceive this problem in their daily practice.
Many initiatives, including telemedicine services or home-monitoring programmes aimed at introducing digital innovations into ophthalmic care to combat treatment disruptions are still in their infancy, despite their medical and economic importance. The obstacles to implementing innovation are complex and country specific. In a survey of global experts in retinal diseases on their views on the introduction of digital health applications, many were rather sceptical. The lack of reimbursement for these kinds of services was the main reason cited for not offering tele-ophthalmology, a barrier that was removed during the SARS-CoV-2 pandemic [1].
A lack of pressure to innovate and a lack of incentive systems, regulatory concerns such as data security and unsuitable tariff structures for mapping innovative care systems in existing remuneration models and financial losses on the part of the physician are other frequently cited factors. Again, the emergence of the SARS-CoV-2 pandemic and the associated lockdown abruptly changed this in many countries [24].
In most countries, outpatient ophthalmology services were largely disrupted if not completely halted within days. Patients feared infection in hospital, medical staff were withdrawn to treat Covid-19 patients and regular services were suspended for safety reasons. In the UK, where the impact of the pandemic on ophthalmic care was analyzed in detail, 80% of outpatient consultation capacity was suddenly stopped for several months. In the USA, but also in Switzerland, the processes of follow-up examinations, for example in patients with diabetic retinal diseases, had to be drastically adapted for social distancing purposes. In some cases, vision tests and imaging diagnostics were abandoned and only treatment was given. Furthermore, many patients with chronic eye diseases, who would have needed treatment chose to remain at home and thus risked - and sometimes experienced - permanent vision loss.
The SARS-CoV-2 pandemic as a catalyst for innovation
In this crisis, the ophthalmologic routine was shaken up and there was suddenly room for new ideas. There was pressure to innovate, and the delivery of care now suddenly had to reach the patient rather than the other way around. Across the globe, initiatives developed to ensure minimal necessary care using home measurements, telemedicine services and telephone consultations [25].
Out of the need to innovate, new types of care structures quickly emerged, which were also able to demonstrate their benefits in scientific studies. New paradigms were created out of pure necessity of the pandemic situation where the patient is at the centre of care. This focus leads to a more decentralized medicine, a stronger networking of different specialists in patient care and - through the inclusion of home measurements - a new quality of data for the monitoring of disease progression. From this interplay, a new vision of ophthalmic care emerges which even today has a great rationale. Table 1 provides a selection of monitoring tests available to assess the visual system at home.Table 1 A selection of monitoring tests available for home evaluation of ophthalmologic parameters.
Clinical parameter Test User
Visual acuity
Eye Test Patient
OptOK Patient
Snellen Patient
HOTV Acuity Patient
Eye Test Free Patient
Check My Eyes Patient
iSnellen Patient
Eye Test Dr Patient
Eye Chart Patient
iExam Patient
Optician Patient
logMAR Tumbling-E VA charts Family screeners
Sightbook Patient
Checkup Vision Assessment (Digisight) Patient
Telephone assisted five-staged evaluation tool Interviewer
Ridgevue Vision application Lay person, Patient
Odysight Patient
Metamorphopsia/Hyperacuity
Alleye Patient
ForeseeHome AMD Monitor Patient
Home Vision Monitor / mVTX Patient
MacuFix Patien
PreView preferential hyperacuity perimetry Patient
M-CHARTS Patient
3D display device Patient
Amsler grid Patient
Retinal morphology
Self-Examination Low-Cost Full-Field Optical Coherence Tomography (SELFF-OCT) Patient
notal home optical coherence tomography Patient
Intraocular pressure Proview eye pressure monitor Patient
iCare® Home Patient
Visual Field Test Melbourne Rapid Field Patient
visualFields Easy Patient
Eyecatcher Patient
The new supply reality
The care of AMD and DMO is facing major challenges due to socio-demographic change. According to the latest figures, the number of patients with AMD will rise from around 200 to 290 million worldwide by 2040, and the number of patients with diabetes from around 400 to 650 million [26, 27]. In Switzerland for example, the number of patients with AMD and DMO treated with intravitreal injections is currently estimated at approximately 30,000. Around 350 ophthalmologists currently administer around 170 thousand injections per year. In recent years, the market for intravitreal injections has grown by about 17 percentage points per year [28]. Due to demographic changes, the AMD market will grow significantly over the next two decades.
If care remains the same, treatment bottlenecks are to be expected only from demographic shifts. Moreover, further pressure on care will soon be caused by drugs targeting at the much larger group of patients with the so-called dry form of AMD. Two pivotal phase 3 trials on the treatment of advanced dry AMD were recently finalized and are currently submitted to the regulatory authorities [29]. This will increase the volume of patients many times over.
Pharmaceutical companies are already advanced in developing innovative therapy options with reduced number of annual treatments. In addition, two novel therapy concepts for AMD and DMO are about to enter the market, which can reduce the therapy intensity to half or even one third [30–32]. Although these innovations will bring initial relief to the care system, care efficiency must also increase and attractive, innovative reimbursement models must be implemented [1].
Individualization of treatment — Personalized Healthcare
Ideally, treatment is directed to the specific treatment needs of a patient. If the condition is stable and no treatment is needed at the medical centre, there should be no in person consultation. The so-called treat and extend strategy is already in use in many patients and combines a clinical follow-up with the treatment visit. But due to possible appointment delays and deterioration in the fellow untreated eye, an additional safety net is necessary, especially for patients with long treatment intervals. If treatment is necessary, it should be possible to provide it flexibly. In principle, this ideal type of care is within reach because all the necessary organizational and technological requirements are already in place. Ironically, one is almost inclined to say, it was the pandemic crisis that opened our eyes to this. It highlights again that social and medical transition cannot be planned; sometimes it progresses slowly, sometimes quickly based on crisis and need [33].
An important piece of the puzzle of this care is the patient’s simple self-measurement of the course of the disease. The data from these measurements are automatically categorized (green, yellow, red) and sent to the attending physician or the clinic via telemedicine platforms and the patient receives instant feedback about his status. If the data show abnormalities in the sense of a worsening of the disease, the clinic contacts the patient and plans further care or vice versa and needs to be agreed with the patient initially. Currently, two mobile applications that test a specific visual function and can be used on smartphones or tablets. Clinical studies have shown that therapy management through self-measurement with home monitoring assessing visual function is able to identify the group of patients who need treatment [11, 12, 15, 17, 20, 24]. Very recently, also a mobile imaging device (Optical Coherence Tomography (OCT)) has become available for home measurement by the patient, providing real-life structural retina data [16]. A few home OCT devices have already been tested for their applicability in clinical studies [18, 34]. Ultimately, a home measurement system creates an additional opportunity of patient doctor interaction and a channel to address fears and uncertainties regarding the therapy.
Relief from physician-centred care structures
Such an innovative and patient-centred care system could be supplemented by the inclusion of other non-medical stakeholders who care for the patient regarding visual function if patient number pressure requires it. It is readily conceivable that regular imaging examinations – which are typically performed in hospitals or by specialists in private practice and provide the indication to treat according to the guidelines – could be performed in a decentralized system at the optician’s or pharmacist’s premises under the supervision of ophthalmologists and in conformity with the legal system.
If patients are severely restricted in their mobility, a team of non-medical specialists can also carry out a basic ophthalmological examination with a telemedical assessment on site within a home care framework. Such a service has been available in Switzerland for about two years and is reimbursed by health insurances [35]. Patients and doctors can derive a lot of benefit from this additional service. For patients, the hurdle to accessing medical care is noticeably reduced and the attending physicians can create the necessary organizational prerequisites before the doctor’s visit to ensure an efficient examination and treatment due to the information they receive from the referring service.
Image analysis can also be performed by specially trained non-medical professionals, supported by automated image analysis outside the hospital in a reading centre. Reading centres and other specialists with the help of retina experts are the ones who currently develop AI based systems which should be able to decide if there is disease activity and make treatment suggestions, e.g., treatment intervals [10, 14, 21, 36–38]. In the UK, a national system organized in this way to detect diabetics with retinal diseases requiring treatment has led to a marked reduction in legal blindness and an improvement in care without the need to increase medical staff [19]. Key of these approaches is the hybrid model, combining advanced imaging technology with an initial automated assessment, followed by a second human virtual re-examination if needed.
Reduction of opportunity costs for patients and their relatives
The organization of treatment for AMD and DMO also has resource-binding consequences for the patient, carer and relatives. However, reliable study data on this subject are hard to find [22]. Going to a medical consultation and treatment often requires accompanying persons who will stay away from work during this time, driving services and planning. In the best case, these efforts are limited to times when the use of medical services is indispensable. The introduction of a telemedicine service at the renowned Moorfields Eye Hospital in London during the lockdown in 2020 reduced the number of patient journeys by 1.4 million kilometres in the emergency department alone. It saved patients and their carers 6.4 years of travel time and avoided the equivalent of 51,000 litres of CO2 emissions from petrol (Dr Dawn Sim, personal communication).
Outlook
Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even the health systems that have so far been able to cope will face similar pressures of a global aging demographic and need for highly qualified professionals. The digital era offers new innovative approaches to decentralized, personalize, and democratize eye care for patients whilst allowing the healthcare workforce to practice at the top of their license. The overwhelming challenges for ophthalmologists in the coming years to cope with the large number of additional patients in the practice require a concerted interaction of new therapeutic approaches, technological innovations but also regulatory support and incentive systems so that the change can be initiated in time. To this end, it is also necessary to provide training for professionals on the new technologies and possibilities so that sufficient competence is built up for the implementation of new care structures.
Author contributions
LF, DAS, and LMB initiated the project and wrote a first draft of the text. All authors made textual additions and provided critical intellectual input. All authors approved the content of the final manuscript.
Data availability
No research data are provided in this manuscript.
Competing interests
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Article
Blockchain acceptance rate prediction in the resilient supply chain with hybrid system dynamics and machine learning approach
Roozkhosh Pardis [email protected]
1
http://orcid.org/0000-0001-6000-3535
Pooya Alireza [email protected]
2
Agarwal Renu [email protected]
3
1 grid.411301.6 0000 0001 0666 1211 Department of Management, Faculty of Economics and Administrative sciences, Ferdowsi University of Mashhad, Mashhad, 9177948951 Iran
2 grid.411301.6 0000 0001 0666 1211 Department of Management, Faculty of Economics and Administrative Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
3 grid.117476.2 0000 0004 1936 7611 Management Department, University of Technology Sydney (UTS), Sydney, Australia
5 12 2022
121
26 7 2022
10 11 2022
24 11 2022
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In today’s era, the importance and implementation of blockchain networks have become feasible as it improves the resilience of the supply chain network at all levels by clarifying information and creating security in the network, improving the speed of response, and gaining the trust of customers. This paper aims to investigate the behavior of the blockchain acceptance rate (BAR) in the home appliances flexible supply chain in Iran using. system dynamics (SD), which is used to better define the relationships between the variables of the model that are non-linearly connected. Through simulating the behavior of the BAR in the long term in the supply chain, whilst conducting sensitivity analysis, policy design, and validation, this model will be implemented for the years 2020 to 2030. Additionally, post-simulation, blockchain acceptance behavior will be assessed by having simulated data considered as input for studied Multi-Layer Perceptron (MLP) and Vector Regression (SVR) (data that have the highest correlation with BAR). The acceptance rate behavior is predicted with the help of machine learning methods to have the best behavior and prediction for the data of 2020-2022 since the prediction function is compared to daily real data obtained these years. The results show that in 2030, the BAR will be around 0.6 if the COVID-19 outbreak impact is medium, and if the considered policy designs are implemented, this rate will reach a maximum of 0.8. So paying attention to the creation and design of policies can achieve positive implications for increasing the resilience of the supply chain in the long run. Findings suggest that the SD-MLP method is better than the SD-SVR method as it has less error and can predict the better behavior of the BAR.
Keywords
Blockchain
Prediction
System dynamics
MLP
SVR
==== Body
pmcIntroduction
With the advent of emerging AI and I4.0 technologies, and In order to mitigate risks, increase efficiency and reduce the costs of procurement and sourcing operations in supply chains, it is necessary to create a secure technological platform for suppliers, manufacturers, distributors, and customers of a supply chain to allow them to efficiently and effectively operate so as to create a dynamic network. For this purpose, supply chain networks (SC) have been created, which include different stages in an SC of meeting the needs of customers from the beginning of the SC cycle (primary raw material) to the end or even to recycling the product. So that their time and expenses are in the most optimal state (Adobor 2020). On the other hand, traditional supply chain networks need to be transformed to increase resilience along the network. So that if the network faces problems such as floods, earthquakes, or as in recent years, the spread of COVID-19, these networks can adapt and respond with agility to the new environmental conditions (Centobelli et al. 2020). For this purpose, resilient supply chain (RSC) networks have been formed which provide a stable structure when operating in difficult and volatile situations, especially when the supplier may not be able to meet their customer demand and/or there is a disruption in the SC transportation network (de Sá et al. 2019).
In this regard, different modeling techniques have been adopted over the past several decades. For example, Markley and Davis (2007) used graph theory to provide a model and interpretive structural modeling to find interrelationships to have more resilience in the supply chain (Markley and Davis 2007). Lockamy (2014) assessed the risk of supplier shortages for an automotive foundry supplier based in the United States and found that Bayesian networks can be effectively used to help managers make decisions about current and potential suppliers (Lockamy 2014). Torabi et al. (2015) developed a two-stage probabilistic hybrid stochastic programming model to create supplier resilience under operational risk and disruption to address the supplier selection and order allocation problem. In order to create a flexible supply base under operational risks and disruption, findings showed a significant effect of considering natural events on the supply chain’s levels (Torabi et al. 2015).
More recent studies included additional dimensions. For example, Saenz et al. (2018) investigated the role of resilient management in the SC where they presented a framework that captured the dynamics of supply chain flexibility and related supply chain portfolio design to supply chain vulnerabilities (Saenz et al. 2018). Parkouhi et al. (2019) considered two dimensions of resilience enhancer and resilience reducer for selecting and segmenting suppliers where they used the Gray DEMATEL technique to determine the degree of importance of the criteria for each of these two dimensions. This helped them determine the score of each supplier based on each dimension; with the backup buffer as the most critical enhancer and the supplier’s capacity restriction being the most important reducer (Parkouhi et al. 2019).
Also, it is important to note that the most critical resilient enhancer and reducer criteria for selecting and segmenting suppliers ie., backup supplier and lack of excess capacity possessed, can only be useful after the critical incident has occurred. Although these two policies are very important in times of crisis, their implementation across an SC can still disrupt due to the lack of coordination and transparency between inter- and intra- organizations. For this purpose, a technological platform that can proactively maintain sufficient security throughout the network; one that creates the necessary transparency for all participants in the network so that they can take the necessary measures in critical situations with agility in the shortest time and with the least risk be created A resilient technological platform, enabled through blockchain, an emerging technology which is a distributed database of records or a shared public/private ledger of all digital events executed and communicated among individuals partaking in the blockchain can help transform SC, especially in critical situations (Eyal 2017).
Moreover, in past studies system dynamics (SD) has been used for the supply chain and examined the risk and some latest technology effects on it. But the blockchain network impacts on the supply chain when natural events occur have not been investigated yet (Rane et al. 2020). So, this paper aims to address the issue of the behavior of the chief variable in an RSC and show how blockchain acceptance rate (BAR) in an RSC with SD and MLP methods can result in a dynamic network. Since many variables are involved in examining the behavior of the BAR in the RSC, a simulation model has been created that can show the interaction across all the variables resulting in demonstrating the behavior of BAR in the long term. This study has prioritized and identified the most effective variables and their relationships in the RSC according to past studies (Adobor 2020; Taleizadeh et al. 2022; Fanning and Centers 2016; Hofmann et al. 2018; Rane and Thakker 2019) for the first time and presented a simulated model of the problem. Also, by presenting the design policies, the theoretical and practical implications that analysts and policymakers can adapt according to the conditions and level of COVID-19 are expressed. In general, the main aim of this paper is to investigate the behavior of BAR in the long term and to examine the behavior of effective variables based on different design policies (i.e., investigating the effects of the exchange rate, inflation, domestic policy, and research and development on the SC variables). Underpinning this, the main contributions of this paper provided for the first time are as follows:Identifying and examining the factors that play a key role in the BAR in an RSC network.
Predicting the blockchain acceptance behavior in the network through model simulation with SD using data for 10 years
Using MLP and SVR methods to predict the blockchain acceptance function over the years 2020 to 2022 (optionally also creating an innovative combined SD-MLP and SD-SVR method)
The paper is structured as follows. The second section describes the theoretical section, research methodology, whilst in the third section, the design and validation of the blockchain acceptance function /model and the design of policies as applied to the theoretical model are presented, in the fourth part, the implementation of the model for a case study, the evaluation of the model behavior, the evaluation of the results and the sensitivity analysis are done. In the next section, the blockchain acceptance function is finally estimated using machine learning methods and the best method is introduced. Finally, implications, future research, limitations of this research study, and the conclusion are presented.
Literature review
The role of blockchain
In the blockchain, an agent makes a new transaction to be added to the chain. This new transaction is broadcasted across the SC network for validation and audit. When the majority of nodes in the chain endorse this transaction due to the predetermined rules, this new transaction is added to the chain as a new block. Once the new record is confirmed and added to the blockchain, multiple copies are created and decentralized to create a chain of trust. Decentralization and verification of any falsification of information are the important features of blockchain technology, thus increasing the credibility of information (Fanning and Centers 2016).
Blockchains are potentially a comprehensive technology for the organization, design, operation, and overall management of supply chains. Blockchain’s ability to ensure the reliability, traceability, and authenticity of the information, along with smart contract relationships for a trust-less environment, all indicate the need for a major rethink in SC and supply chain management. The smart contract, as one of the important features of blockchain technology, provides the possibility of valid transactions without the involvement of third parties (Hofmann et al. 2018). Blockchain-based supply chain networks may need a closed, private, and permissioned blockchain with a restricted number of participants. Four main institutions play a role in blockchain-based supply chains, some of which are not seen in conventional supply chains (Rane et al. 2020). Registrars, provide unique identities to people on the network (Rajabi et al. 2022). Standards organizations, which represent standard schemes, such as Fair Trade for Sustainable Supply Chains or blockchain policies and technology requirements. Certifiers who provide certificates to people to participate in the SC network. Participants, including manufacturers, retailers, and customers, must be certified by a registered auditor or certifier to maintain system trust (Rane et al. 2019; Saberi et al. 2018).
RSC – Dynamic networks
Many simulation studies have been conducted on RSC and the role of blockchain in improving the performance of the supply chain structure. In this section, the most important studies are stated. Focusing on RSCs, Sawik (2022) presented a model to minimize production costs and maximize estimated demand using a multi-portfolio approach and stochastic models with scenario-based mixed integer programming (MIP) to solve the model. The model allowed calculation of the amount of extra inventory required to reduce risk level, which is used as the excess capacity for building more resilience in the SC as trade-off to, the amount of production, and the supply of parts by the factory and suppliers (Sawik 2022).
Similarly, Zahid Piprani et al. (2022) showed that natural events increase SC risks (Zahid Piprani et al. 2022). Taleizadeh et al. (2022) evaluated resilience variables and pricing decisions to optimize an SC where they used two-level planning and the Stackelberg game model to calculate the amount of inventory backup buffer. As part of this modeling, the authors considered preventive and recovery policies at the same time, and found that maintaining a contingency stock strategy is highly recommended, but considering multiple suppliers and additional reserve capability is not almost always preferred to reduce the negative effect of disruptions in the case study (Taleizadeh et al. 2022). Hasani et al. (2021), using a multi-objective nonlinear model, maximized profit, minimized facilities, and carbon dioxide, and considered both green and RSC criteria (Hasani et al. 2021). Also, Hosseini Arian et al. (2021) used the SD simulation for investigating cutting-edge technology like 3D printing in a home appliances SC. They showed the dynamics behavior of 3D printing over the times. Also, they investigated the personnel skills effects on production in the SC (Hosseini et al. 2021). Moreover, some recent papers like: Aloui et al. (2021), Flynn et al. (2021), Ivanov (2022), Sawik (2022), and Shokouhifar and Ranjbarimesan (2022) considered the effects of COVID-19 on different SC. They show that COVID-19 can face the supply chain’s irreparable consequences (Sawik 2022; Aloui et al. 2021; Flynn et al. 2021; Ivanov 2022; Shokouhifar and Ranjbarimesan 2022; Alazab et al. 2021; Kamble et al. 2021).
Although blockchain can help to improve and reform the SC, many governments and organizations are not willing to accept it for their reasons (Alazab 2021; Kamble 2021). A lot of research has been done on blockchain acceptance in the RSC. In general, these studies have not focused on predicting the acceptance rate of blockchain in an RSC. Although there are studies, Casado-Vara (2018) critically reviewed blockchain technology and smart contracts with potential application to SC management. Due to local and global government, community, and consumer pressures to achieve sustainability goals, they investigated how to implement blockchain to help SC sustainability. They have only used a questionnaire to find the effective criteria of blockchain in the RSC. This study uses previous articles and tries to complete them (Casado-Vara 2018). Table 1 shows the previous studies about RSC and blockchain acceptance rate prediction in SC and their comparison with the present study.Table 1 The comparison of proposed method with past studies
Authors Features and model solution method The purpose of the model Case Study
Torabi et al. (2015) Two-stage probabilistic hybrid dual-objective stochastic programming for RSC Minimizing costs, Minimizing risk Numerical examples
Casado-Vara (2018) Integer combinatorial linear programming, Uncertainty in demand, Cost minimization Minimizing costs A European company
Aloui et al. (2021) Two-stage random mixed integer programming, Demand uncertainty Minimizing costs Numerical examples
Taleizadeh et al. (2022) Two-level programming, Stackelberg game model Optimizing a sustainable SC considering resilience factors and pricing decisions Manufacturing cartridges in Iran
Shokouhifar and Ranjbarimesan (2022) Deep learning, Multivariate time series Demand forecasting, COVID-19 disruptions Iranian blood donation organization
Alazab et al. (2021) Investigating the effective BAR factors in SC, Applied structural equation modeling Finding the key factors for BAR in SC Industry factory in Jordan
Kamble et al. (2021) A machine learning approach (Bayesian network), Using the technology acceptance model (TAM) for showing concept of BAR model in SC Predicting blockchain acceptance rate in SC Mumbai-Pune and Bangalore –Chennai companies in India
Proposed study Predicting the BAR function in RSC, Considering the most comprehensive variables of model for simulating, Investigating variables behavior during the time, Analyzing the effective policies during the disruptions, Designing new method based on SD and machine learning Investigating model behavior based on some policies, predicting BAR in RSC Home appliance SC
In these two sections, the previous studies were described more fully and finally, the research gap and our contributions were reported. In the literature studies, although they have tried to show the influential variables of blockchain acceptance in RSC, none of the studies have presented long-term behavior for BAR changes. Also, another important difference between this paper and previous studies is that it presents policies that can not only affect the acceptance rate of blockchain but also change other variables. Also, the method used to estimate the acceptance function of the blockchain (SD-MLP and SD-SVR) is another innovative contribution of this paper.
Theorizing the research model – RSC and BAR
Since global economic policy uncertainty and domestic political stability have significant positive and negative effects on the banks and business of countries’ profitability, so the adjustment of the plans for making the far-reaching positive change can develop trade, reduce inflation, increase exchange rate, and improve supply chain structure (Athari 2021). In this regard, political risk stability was investigated in this study as a policy. This paper shows that the total transactions by smart contracts (since political stability is caused by constructive communications between all levels of the SC), the BAR, the number of blocks, backup buffer, and inventory can be increased based on improving political risk in the RSC. In general, after analyzing the impact of COVID-19 on the subsystems presented in the simulation model, it can be concluded that to face the disruption, there is a need to explain the policies that cause resistance to chain disruptions.
Also, there are lots of studies that identified the effective criteria for an RSC and BAR. Sachin et al. (2021) have investigated the possibility of blockchain acceptance in the SC using the Bayesian method. They defined blockchain technology as a dynamic capability that must be possessed by organizations to remain competitive. They identified the most effective influencing factors in blockchain acceptance behavior and tried to use them to predict the probability of blockchain acceptance in their organization by company managers (Sachin et al. 2021). But since the acceptance of blockchain depends on many factors and the changes of each factor can cause many changes in the blocking process, its prediction requires dynamic tools to include non-linear dependence between variables. SD is one of those tools that consider the non-linear relationships between variables to show variable behavior in the long term. None of the previous studies have used SD to investigate BAR behavior. Table 2 shows the list of variables and their direct relationships that have been established in past research.Table 2 Relationships between variables in previous studies
Variables Relation to other variables Studies
Backup buffer RSC, Response time, Number of supplier, Vehicles (Eyal 2017; Fanning and Centers 2016; Hosseini et al. 2021; Crosby et al. 2016; Tsolakis and Srai 2018)
BAR Security, Information sharing, Transactions, Collaborative integration, The number of blocks, Total costs, R& D (Rane and Thakker 2019; Casado-Vara 2018; Sachin et al. 2021; Sterman 2000)
Confirmed transactions Main inventory, Smart contracts, Investments (Saberi et al. 2018; Meadows 1972)
Personnel skills R& D, Training, Total costs (Saenz et al. 2018; Hofmann et al. 2018)
In general, although previous studies have examined one or two variables in RSC and blockchain influencing variables in the SC, none of them have comprehensively explored all the behaviors of RSC variables in terms of blockchain. Also, this study has another interesting output that can help predict the BAR rate function. According to the purpose of this study, policies have been designed to increase the resilience of the supply chain, especially in the event of a crisis. On the other hand, since the SC is being studied in Iran and this country in the last decade encountering all the policies examined in this paper, the necessity of designing these policies have multiplied. Table 3 shows these policies and how they affect the SC.Table 3 Review of policies in the SC in past studies
Policy Relation with SC Source
Exchange rate Exchange rate risk can show the company’s risk tolerance in transactions and outsourcing. (Liu and Nagurney 2011; Das and Rout 2018; Kondoz et al. 2021)
Inflation The inflation rate can have a significant impact on contracts and transactions. It also affects inventory changes. (Sarker et al. 2000; Wan and Chen 2017; Athari et al. 2021)
R &D R &D increases the innovation of companies and strengthens the speed of acceptance of new technology. (Chan et al. 2014; Forrester 1958)
Domestic political stability Domestic policies can be influential in some domestic decisions such as accepting or rejecting a technology, systematic change or relations with other countries, and sanctions issues. (Athari 2021; Nepstad et al. 2014; Athari et al. 2022)
Research design
This paper addressed the behavior of the BAR in the RSC during the time by using the new method as shown in Fig. 1. There are several stages to this model. In this model, there are many variables in determining the acceptance rate of blockchain in the RSC. As the variables have non-linear relationships with each other, so the best way is to use the SD simulation. Therefore, in the first stage, the boundary of the system is determined, and the most important variables are identified within the boundary, and the relationships between them are determined according to past literature and experts’ opinions. In the second step, a stock-flow diagram is drawn for the relationships between the variables. According to the variables, this chart has three types of stocks (accumulation mode), flow (rate variables), and auxiliary variables (internal and external), which can be used to formulate the model according to the relationships between the variables. In the third stage, after the implementation of the model, the results that show the behavior of each of the variables in the long term (in this model, 2020-2030) are reported. Also, in the fourth step, its results are evaluated to determine the validity of the model. This evaluation consists of two stages, first is the sensitivity analysis, which examines whether the behavior of the other variables is reasonable or not for changing one of the external variables and keeping the rest of the variables constant and another is to compare the results of the model with the variables that behavior is already available (reference modes. In this study, backup buffer, profitability, and main inventory), which can evaluate how similar the past behavior of the model is to the actual behavior. In addition, the simulated model can provide them with the necessary information to examine the conditions in the future by managers and politicians who want to develop policies that take into account the natural factors that may occur. In this paper, during three scenarios for the Covid-19 pandemic (low, medium, and sharp scenarios), several different policies are evaluated according to the case sample.
In the next step, machine learning methods are used to improve the accuracy of predictions and model behavior. So that after receiving the results from the SD model, the correlation of the main variables is calculated with BAR. So, given that machine learning methods, are trained using past historical data to predict future behavior based on this training, this paper uses these methods to improve the BAR function for 2020-2022. The amount of input data for prediction with MLP and SVR is determined in two ways. Firstly, because the past behavior of some variables (such as backup buffer, total transactions, and main inventory) is available, real data is used for these features, and secondly, for features that real data are not available, their simulation data is used. After checking the errors of each method, the most effective function is specified. The detail of these stage has been expressed below. Fig. 1 shows the flowchart of all the steps of the paper. All of the steps are explained below.Fig. 1 The methodology flowchart of the study
Stage one: system dynamics model design
The SD model is an interdisciplinary subject based on system science and management science that can reveal the intrinsic motivation of a complex system and perform optimization methods (Pham et al. 2021). SD is an approach to understanding the nonlinear behavior of complex systems over time using feedback loops. This method was introduced by (Forrester 1958) in the book industrial dynamics and spread rapidly. The main roots of this method come from systems theory, which is a modern approach to management theories. This method has two main differences from statistical methods in solving problems. First, unlike statistical methods, it does not intend to limit variables. Dynamic analysis of systems tries to analyze all the elements involved in the phenomenon’s behavior in a closed boundary. Second, all relationships are considered, including the feedback loop. Although the causal loop diagram is an effective tool for showing feedback relations, it cannot quantify for simulating models. So the best way to formulate simulation models is using the “stock-flow” diagrams. Also, the other limitations of causal loop diagrams is their inability to show the variable structure of the state and flow of systems. Stocks and flows, along with feedback, are two main concepts in the theory of dynamic systems.
For example, Meadows (1972) designated a global model for investigating industries, pollution, population, and other significant factors using the SD model. From its birth in the 1950s, the SD model became widely used globally and acquired more comprehensive development as an outcome in the fields of policy development, project management, learning organization, logistics and supply chains, and a company’s strategic areas. The standard SD approach is as follows: first, determine the problems and define the boundaries of the system; second, make a dynamic hypothesis, find the formulation, and carry out the simulation test; and eventually, complete the policy design and evaluation. Each causal loop in SD models must have at least one stock; otherwise, no cumulative will occur. Also, just the flow can change the stock value since all variables change. As SD theory has grown, the application scope has widened to include industry, finance, medical science, education, resources, the environment, real estate, and other fields. Stock variables are the accumulations that determine the state of the system. Also, they provide data that can decide based on them. Stock variables also create delays by accumulating the difference between the input flow to a process and the output flow from them. For example, the factory inventories, or the number of staff are the sample of stock variables (Li et al. 2020).
Indeed, investigators can develop possible policies according to the analysis and simulation outcomes provided by the SD model. Moreover, SD can reflect the complex relationship between enormous numbers of variables in immense systems. Thus, it is broadly used in complex nonlinear systems, and it can make better mid- or long-term predictions (Li et al. 2020). Fundamentally, there are five different types of variables for an SD model: stock variables, flow variables, rate variables, auxiliary variables, and constant variables. The stock variable is defined by Eq. 1.1 Stock(t)=S(t0)+∫(inflow(t)-outflow(t))dt
where Stock(t) is the accumulation value of stock variables at t moment, which is illustrated by stocks in feedback diagrams. Inflow(t) or outflow(t) are the types of flow variables (they can change the rate of stock variable). Also, S(t0)is the initial value of the stock variable. As it turns out, flow variables are derived from the instantaneous changes of the stock variable (Sun et al. 2017).
Stage two: Multi-Layer Perceptrons (MLP) for estimation BAR
MLP is a class of artificial neural networks. An MLP includes at least three layers of nodes: an input layer, a hidden layer, and an output layer. Excluding the input nodes, per node is a neuron that employs a non-linear activation function (Box and Jenkins 1976). MLP utilizes a supervised learning method named feedback for training. Its multiple layers and nonlinear activation differentiate MLP from a linear perceptron. Indeed, it can determine data that are not linearly detachable. Basically, the output activations(l+1)layer l+1 is derived by the input activation s(l), as it is indicated in Eq. 2.2 s(l+l)=σ(w(l)sl+b(l))
where l corresponds to s specific layer, w(l) and b(l) designate the weight and bias at layer l, and σ denotes the nonlinear activation operation (e.g. sigmoid, hyperbolic tangent, rectified linear units) function. For an m layer multi-layer perceptron, the first input layer is sl=x while the last output layer is (Eq. 3).3 hw,bx=s(m)
The b bias and w weights in Eq. 3are recognized by supervised training using a back-propagation algorithm to approximate an anonymous input-output relation (Del Frate et al. 2007) (Berat et al. 2020). The objective function is to minimize the distinction between the predicted outputs and the expected outputs (Eq. 4).4 J(w,b,x,y)=12||hw,b(x)-y|2
Stage three: Support Vector Regression (SVR) for estimate BAR
SVR is a robust approach for creating a classifier for regression and classification first presented by Vladimir Vapnik and his research team in 1992 (Guyon et al. 1992). The SVR algorithm makes a decision limit, known as the hyperplane, between two classes that allow anticipating labels from one or more feature vectors. This decision limit is oriented such that it is as far as possible from the closest data points from each of the classes. These closest points are named support vectors. Due to a labeled training dataset,Z≡x1,y1,x2,y2,…,xB,yn, x1∈Rd and yi∈(-1,+1). The optimal hyperplane can then be described as Eq. (5):5 wxT+b=0
where w is the weight vector, x is the input feature vector, and b is the bias. The hyperplanes would be defined by Eqs. (6) and (7) respectively:6 wxiT+b≥+1ifyi=1
7 wxiT+b≤-1ifyi=-1
The purpose of training an SVR algorithm is to obtain w and b so that the hyperplanes separate the data and maximize the margin 1/‖w‖2. Initially suggested to build a linear classifier, the SVR algorithm would be applied to model higher dimensional or nonlinear models utilizing the kernel function (Hastie et al. 2009; Haykin 1999). For example, in a non-linear problem, the kernel function would be used to present extra dimensions to the raw data and turn it into a linear problem in finding higher dimensional space. The kernel function would present faster computations that require calculations in high dimensional space. The kernel is an internal product, which would be linear or nonlinear (Polynomials), Radial-Basis Function (RBF), and the Sigmoid. It is described as Eq. (8):8 K(x,y)=<f(x),f(y)>
Step four: Proposed method: SD-MLP and SD-SVR
After SD simulation, the BAR is calculated. This paper for improving the behavior uses the MLP and SVR methods to estimate the best function for BAR in the RSC. In this regard, data that they have obtained from SD simulation during the time (2020-2030), are the input for MLP and SVR. For improving the relationships between BAR and other variables, correlation is used. Some variables that have a low correlation (lower than 0.3), are omitted. So the function is estimated based on the effective variables. Table 5 shows the correlation between BAR and other decision variables.
Research Methodology
In this paper, Stella Architect software for drawing and Vensim PLE x32 for formulating are used. The model structure includes three subsystems; the BAR, RSC, and personnel skills. Table 4 shows the value of simulations variables. The primary values of data have been collected based on the average of experts’ opinions for 50 home appliances companies in Iran and data on companies’ figures. The initial value for the stock variables and parameters are assumed at the beginning of 2020, and the simulation is performed over 4000 days (10 years).
Data resources
The data used in this paper is taken from asstra.com/industries/household-appliances-and-electronics/, clicktrans.com/transport/household-appliances/, www.amar.org.ir/english/Statistics-by-Topic/Household-Expenditure-and-Income, islamicmarkets.com/publications/blockchain-technology-and-islamic-capital-markets-in-iran, and www.blockchain.com/charts/ sites.Table 4 Values used for variables and parameters in the simulation
Variable Initial value Unit
Maximum of supplier in network 856 Number
Maximum inventory per day 23000 Number
Average of each vehicle’s capacity 3.5 Ton
Main inventory 1007 Number
Backup buffer 108 Number
The number of blocks 100301 Number
Total costs 801000 Dollar
National event rate 0.3
Cost of storage 250000 Dollar
Production costs 12985 Dollar
Average salary per staff 2600 Dollar
Work time 9 Hour
Total transactions 100874 Number
Average block creation time 0.42 Hour
Personnel 415 Number
Increasing inventory rate 0.6
Using probability of inventory per day 0.4
Model assumptions
Model time period: The developed model was run from 2020 to 2030 daily. The developed model was simulated in three-month time steps in 2020-2030 by calculating reserves, flows, and converters in each time step adopted for the entire simulation phase. The model was then tested for 2 years from 2020 to 2022 to compare the model’s simulated results with historical data of key variables obtained from the home appliance factory. Main inventory, backup buffer, personnel skill, number of blocks, the total number of transactions, and confirmed and unconfirmed transactions. The duration of this simulation was more than 10 years so that the long-term dynamics of the system under the influence of alternative intervention scenarios could be recorded.Scope of the model: The boundary of the model was determined according to the policies of the intelligent RSC. Factors such as mining costs, energy consumption, and other factors specific to blockchain are considered outside the system boundary. Because the goal is to check the acceptance rate of blockchain in the SC. Therefore, they are not considered in the model.
Model development parameters and input data: To enable the simulation, the model includes the identification of all relevant parameters, including initial stock values at the start of the simulation, and almost all initial stock values are 2020 data (Table 4), except the investment that is the observed data for 100 days from the beginning of 2020. Inventory, buffer, numbers of suppliers, vehicles, and related to the SC figures are obtained or calculated based on appliance factory data. Where data were not available, assumptions were made based on current literature and expert suggestions from stakeholders in the study reported in Sachin et al. (2021). There are relationships between these subsystems. In past studies, this relation is investigated. After simulating the behavior of the BAR in the SC, machine learning is used to improve the behavior of its function so that it can estimate the best function according to the data obtained from the SD. In this paper, SD-MLP and SD-SVR are proposed.
Dataset Normalization
The dataset should be normalized since the features intended for BAR prediction do not have the same unit and range. The method which is applied for normalization in this paper is mean-normalization. Eq. (9) represents the mean-normalization formula.9 fi=fi-μimax(f)-min(f).
where fi is the ith feature, μi is the average of ith feature in the corresponding period and fi is a normalized feature of fi(Das and Rout 2018).Table 5 The correlation between BAR and decision variables
Variable Correlation
Confirmed transactions 0.991525
Total transactions 0.979279
Number of unconfirmed transactions 0.991525
The number of blocks 0.942144
Total costs 0.962897
Main inventory 0.121484
Backup buffer 0.997216
SC resilience 0.997216
Customer response speed 0.996946
Personnel skills 0.056297
Profitability 0.962897
In Table 5 personnel skills and main inventory have a low correlation with BAR (they are lower 0.3), so they are removed from the regression estimation equation. The MLP and SVR can help SD to be modified the behavior function.
Model description
The BAR SD model is an integrated model containing three joint subsystems that interact to build the behavior over time of the system. Variables in one subsystem impact variables in other subsystems. The part below focuses on separate subsystems to enable a thorough analysis of the interrelationships between variables and the structural and behavioral assumptions of the model.
Subsystem 1: Blockchain acceptance rate concept in RSC
As mentioned in previous studies (Saberi et al. 2018; Hosseini et al. 2021; Forrester 1958; Li et al. 2010; Ruskey and Rosenberg 2022), many effective variables are effective in improving SCR, and these variables in turn affect other variables. Also, due to the introduction of blockchain as a new technology in the SC, knowledge and training of personnel are prioritized because skilled personnel is needed for the implementation of this technology. So another subsystem that can help improve the structure of the RSC is employee training (Rajabi et al. 2022). On the other hand, one of the modulating factors of blockchain technology is the costs that are spent on providing infrastructure, equipment, and training. So the effects of these costs are discussed in the model. In general, the implementation of this subsystem in the SC helps to reduce risk, the speed of responding to customers, quality, and resilience, thus amplifying the RSC subsystem (Casado-Vara 2018; Tian 2016). The BAR subsystem illustrates the interrelationships between the area and output of blockchain and the variables influencing these (Fig. 2). Total transactions, confirmed transactions, unconfirmed transactions, the number of blocks, and total costs are proposed as stocks for this subsystem and interconnected through various variables. In our model, the BAR is supposed to depend on the total transactions and confirmed transactions. The total transactions are determined by the number of smart contracts per day, company trust rate, and investments.
The total costs are supposed to be approximately 8 billion dollars in the first year of simulation. This figure allows close-to-reality simulation of BAR growth dynamics, given historical data on the total production, storage, blockchain cost, and transportation over 2020–2022 in the case study area. Smart contracts are affected by the performance of investments. The confirmed transactions increase the number of blocks. Also, in the model, the confirmation probability of transactions plus the rejection probability of transactions is considered equal to one. Besides, the average transaction confirmation time is 30 minutes.
As shown in Eq. 10, the BAR is obtained from the number of approved transactions per total transaction. Approved transactions at each stage of the RSC depend on a number of factors, and one transaction is approved when all participants in the network approve it.10 Blockchainacceptancerate=ConfirmedtransactionAlltransactions
On the other hand, if a new transaction in the network is indicated by x, it can be said that the probability of its acceptance depends on all participants in the network. If a new transaction with a1 is considered at the supplier stage, with a probability a2 at the manufacturer stage, with a3 probability at the distributor stage, and with a4 probability at the customer stage, the probability of accepting a new transaction is as Eq. 11.11 Pconfirmedtransaction∣a1,a2,a3,a4=Pa1,a2,a3,a4∣confirmedtransaction×Pa1,a2,a3,a4P(confirmedtransaction)
If all four transactions are members of approved transactions at each stage, then x is approved. Also, since the SC is resilient, each of a1. a2, a3, a4 depends on other factors that must first be identified (such as unforeseen natural events) that cause inventory shortages, increase service time, and incompatibility of partners, etc. For example, if b1 is the first effective factor (e.g. interoperability) in the supplier stage (a1), then the probability that the effective factors will continue to affect a1 is Eq. 3. Similar to this probability will be obtained for a2, a3, and a4 (Eqs. 11 and 12).12 Pa1∣b1,…=Pb1,…∣a1×Pb1,…Pa1
All in all, in this paper, to predict the BAR and examine the variables affecting it, information about several companies (home appliances) with their characteristics will be collected in a specific time period. This section is said for understanding the concept of BAR in the RSC.Fig. 2 Blockchain acceptance rate subsystem
Subsystem 2: RSC
Figure 3 depicts the RSC subsystem and how this can influence the BAR. In the factory, the parts are supplied by the supplier, which forms the main initial stock of the factory, but a support buffer is also considered to deal with the risk and possible natural accidents. For all participants in the network to know about the incident earlier when natural events occur, and if, for example, one supplier fails to provide service, another one is available in the network and covers the demand, the blockchain network is used. In addition to helping to increase the security of the SC network, this network can increase the speed of decision-making and risk management when problems occur. Increasing blockchain acceptance reduces risk and improves crisis management, which ultimately contributes to the stability and resilience of the SC.
The rate of natural disasters was investigated for two years 2020-2022. The average number of days that factories were involved in natural events such as Corona, breakdowns of transport machines, political risks and excessive inflation, which caused the bankruptcy of home appliance suppliers or the import of parts, was divided by the total days of the year. So, the rate of natural disasters for the SC of household appliances in Iran was calculated, and this rate was estimated to be 0.32 (Eq. 12). On the other hand, if the withdrawal of the main stock increases or more natural disasters occur, the probability of using the buffer stock increases. Finally, in this subsystem, it can be said that the more resilient the SC is, the greater the trust of the blockchain company. Increasing trust in blockchain, as discussed in the previous subsystem, will increase smart contracts and, as a result, increase the acceptance rate of blockchain in the network.Fig. 3 RSC subsystem
Subsystem 3: personnel skills
Since the BAR increases with the increase of staff skills and their familiarity with blockchain, this part is very important. In this part, it was shown in the model that the skill of personnel depends on two factors: repetition of daily tasks and training (Zahid et al. 2022). Also, negligence and incompetence of employees reduce this amount. The three factors learning rate, learning time, and working hours are important in this department. The average working hours in Iran’s home appliances factory is 8 hours. The average learning time is two hours. The skill level of the employees was considered as a maximum of 5000 units with the advice of experts. In fact, by increasing the skills of employees, on the one hand, risk and crisis management improves, and on the other hand, human resources cost increase. Therefore, in the model, a maximum rating of 5,000 units is considered for the skills of employees. Figure 4 shows the stock flow chart for this subsystem.Fig. 4 Personnel skills subsystem
Sensitivity analysis
The dynamic systems approach can test different design policies and evaluate their results over time, so it is a good tool for adapting the model to the real environment. This method, unlike other approaches for system analysis, in addition to breaking down the system into its subsystems, combines subsystems and considers their connections (Tsolakis and Srai 2018). This capability allows the decision-maker to test his proposed policies in the simulated model before applying them in the real world and to observe its effects and results over long-term periods. In this step, different policies are simulated and the final goal is to investigate the effect of different policies on the behavior of the system. In this method, all variables are kept constant and only the tested variable is changed±10% to determine the effect it has on other variables. In the following section, BAR and RSC have been analyzed, and the effects that other variables receive if they increase or decrease are reported. In general, the learning staff rate about blockchain is changed by ±10% in the model and its impact on the BAR and the total costs due to more/less staff training and more/less usage compared to the base case have been investigated. As shown in Fig. 5, a -10% reduction in the personnel training rate will decrease the BAR exponentially, the backup buffer, and total costs. Although blockchain helps the resilience of the SC, it creates costs for the network. Moreover, with a +10% increase in the training rate of personnel, due to the increase in personnel information and the increase in their skills in learning and working with the blockchain network, its acceptance rate in the SC increases, which increases the backup buffer to face the possibility of disruptions in the SC. But the total costs would increase slightly with the BAR in the network, which is justified because the resilience of the SC is much higher than normal. Also, in the continuation of Table 6, there is a kind of sensitivity analysis test based on scenario.Fig. 5 The sensitivity analysis on profitability with the changes in rate of learning staff about blockchain
Policy scenario design and evaluation
The scenario refers to the environmental conditions that occur randomly, and the policy refers to the actions of humans on the model that is under control. Policy design plays a vital role in model evaluation. This usually contains a model simulation with a spectrum of policy parameters utilizing the existing model form, then setting the model structure to investigate the impact of diverse policies on decision-making (Tian 2016; Sai et al. 2021). According to the sensitivity analysis which led to a set of parameters that have most affected the behavior of the model during the time, a set of policy scenarios was designed and simulated between 2020 and 2030 to know how the blockchain rate might alter under distinct circumstances. This step includes several trials with diverse combinations of model parameters, which were synced to investigate the behavior of the model under these changes. Also, Three state of COVID-19 pandemic consider as the scenarios (low, medium, and sharp).
Particularly, Policies with changes in individual parameters chosen in line with current provincial development plans and past studies (e.g. a 10% decrease in the probability of transaction approval for blockchain indicate the lack of cooperation between participants of the smart SC, who have delayed the registration of contracts and their approval in the network.)
In the base-case or business-as-usual Policies (S1), policy interventions were supposed to be absent over the simulation period. Five policy scenarios were then simulated (Table 6). Inflation control increased research and development, political risks, and exchange rate control.
Inflation control (S2): One of the most important factors that cause problems in the SC is the excessive increase in the number of raw materials and prices that happen due to inflation. Considering that Iran has recently been sanctioned, the inflation rate in this country is very high, which has reduced the resilience of the chain. For this reason, companies can greatly contribute to the resilience of the chain by using policies to control internal inflation. If the inflation is 15% more controlled, the smart contracts can be more, so the number of blocks can be more.
Increasing research and development (R &D) (S3): Increasing the skills of employees and their familiarity with modern methods will provide the infrastructure for the implementation of blockchain and also help the resilience of the chain as presented in Table 6. Therefore, policy and research, and development allow companies to increase the speed of implementation of new technologies (Zahid et al. 2022). So the number of confirmed transactions can increase.
Exchange rate control (S4): Considering that COVID-19 has caused many changes in the exchange rate, especially in developing countries like Iran, it is important to examine the changes in the exchange rate on the variables of the RSC (Athari et al. 2021). A 10% increase in the exchange rate affects the purchase, and the sale price of products, and back-up buffer, as well as can disrupt the SC.
Domestic political stability (S5): Since political issues and sanctions, especially for the country of Iran, have provided many problems, including preventing the import of parts and raw materials, this issue is investigated in the simulation model. If policymakers try to decline this risk, they can improve inflation, political risks, exchange rates, and the development of new technologies such as blockchain in the SC (Kondoz et al. 2021). Therefore, the political risk control policy has been considered by 15% change. Moreover, it is examined how this risk can change the behavior of the number of confirmed transactions and, as a result, the BAR in the SC.
Best case (S6): When all three of the above policies are implemented where exchange rate, inflation control, and development research are maximized.
Worst case (S7): The worst case is the Policy in which inflation increases and R &D and inspection rates decrease by 10%-15%, which is likely to happen under the current events, is also stimulated to illustrate the worst case among all simulation scenarios of the model.
Evaluation Metrics
Due to the assessment model, the error is assessed through Mean Absolute Percentage Error (MAPE), and Root Mean Squared Error (RMSE) which are proposed as Eq. (13):13 MAPE=1n∑t=1nyt-y^tyt×100
RMSE=1n∑t=1nyt-y^tyt2
where yt is the actual values and y^t are the forecasted values. In this section, the findings calculated by the deterministic models are demonstrated. The architecture of the model for the primary MLP structure. After SD simulation implementation, the BAR function from 2020 to 2022 is predicted by MLP. It helps the model to have the best behavior in comparison with SD.
The trained MLP model includes 4 layers, each with the same activation function ReLU, and is trained to utilize the Adam algorithm for 300 epochs. The input includes the daily variation of BAR and 9 other dependent variables. The layers contain 1, 2, 5, and 10 neurons hierarchically in the input to the output direction.
For the secondary MLP neural network, the trained MLP model includes 4 layers, each with the same activation function ReLU, and trained employing the Adam algorithm for 700 epochs. The input includes 18 features over the specific period from the previous step. The layers contain 200, 90, 50, and 1 neurons hierarchically in the input to the output direction.
The suggested method is accomplished on a system with the specifications (CPU:2.3GHz core i5, RAM:4GB) which represents does not require a highly trained configuration. Each epoch of primary and secondary neural network learning took 0.05 and 0.2 seconds respectively. Besides, this system has been simulated on the Jupyter notebook which is a strong compiler in Python language.
Model testing
The simulation model was tested using structural and behavioral validity analyses to see if it could adequately depict the structure of the real system and if it could produce behavior that was acceptable in comparison to the patterns seen in reality (Li et al. 2010; Abeyratne and Monfared 2016). For model behavior verification, severe condition and behavior reproduction tests were carried out, whereas conservation of matter, dimensional consistency, and structural verification tests were utilized for model structure evaluation (Ruskey and Rosenberg 2022; Tukamuhabwa et al. 2015). This means that a stock must never go negative and the difference in stock at any point must equal the net flow, which is the sum of inflows minus outflows. The conservation of matter test is used to determine whether the model violates these fundamental physical laws.
A difference in a stock like the number of blocks, for instance, should equal the sum of creation block inflows minus the sum of the reduction rate utilizing blockchain outflows. For example, a stock like the number of blocks will never dip below zero. The purpose of the dimensional consistency test is to examine the model equations for ambiguous parameters and relationships assigned to them as well as to check the measurement units for all variables to diagnose any faults resulting from unit mistakes. Specifically, reinforcing and balancing feedback loops should show the proper polarities and behaviors (Suryawanshi and Dutta 2022; Javed et al. 2020). Structural verification means that all structural components of the model should produce acceptable behavior as predicted.
Figure 6 illustrated the outcomes of behavior replication tests performed by a comparison between model simulation outputs and historical data. The extreme condition test is to examine if the model makes adaptable behavior when extreme values such as zero or infinity are used in model inputs (Sterman 2000). For instance, if there is no transaction or smart contract inflow, the overall number of transactions, confirmed transactions, unconfirmed transactions, and blocks should all decrease after any possible delays, indicating that the model structure is accurate to the system it represents. Two extreme circumstances, including extreme values for resilience and blockchain-related variables, were employed to assess the model’s robustness in this study. For behavior design appraisal, an inconsistency coefficient (Q) was utilized at the ultimate step, after the show passed all past approval examinations, to degree the disparity between the simulated behavior and checked the information of primary factors. The values of Q run from (culminate expectations) to 1 (most noticeably awful forecasts); a demonstration may be respected as great to normal where Q ranges between 0.4 and 0.7 (Remington et al. 2018). In this study, three key parameters were chosen for the model behavior pattern validation: main inventory, backup buffer, and profitability. The simulated trends of these variables were compared to their historical data over two years from 2020 to 2022 and reflected in the values of Q.Fig. 6 A comparison of the behavior of simulation outputs with historical data
A sensitivity analysis was performed to identify the parameters most likely to influence model behavior. Since the purpose of this model is to analyze how the blockchain behaves under her RSC conditions, the rate of block and inventory change in response to changes in the selected model parameters was evaluated. The results show that the number of confirmed transactions and blocks is the most sensitive to changes in investments per day. Variations in the values of other auxiliary variables which are considered constant, are insignificant to the behavior of the model. Changes in model dynamics corresponding to variations in model parameters of up to 15% indicate that the model has low to moderate sensitivity (Tapscott and Tapscott 2017; Min 2019). This means that a single model parameter alone cannot significantly change the SD represented by the model, which has important implications for the design of policy scenarios in the next step.
Results
The simulation results of the base-case or business-as-usual (BAU) and policy intervention scenarios are presented in Fig. 7 for the BAU scenario, the BAR, and the number of blocks in years when natural events (COVID-19) occurred such as in 2021 and 2022. Under this scenario, the BAR and the number of blocks are predicted to plateau around 2030 at approximately 0.61 and 30934700 number, respectively, resulting in a peak in BAR at the same time. This is associated with a peak in transactions and main and buffer inventory availability. Key variables of the model exhibit the “reinforcing to growth” behavior in all scenarios over the simulation period, except for the carrying capacity of production will most likely continue to grow to balance. This upward tendency of blockchain rate will likely contribute to increasing smart contracts in the investments in the future, affecting an RSC, with backup buffer and company trust rate quickly reaching their peaks within the simulation time. Under ‘medium COVID-19 outbreak’ conditions, the maximum growth in confirmed transactions and the number of blocks is expected to happen under the S6 scenario – reaching approximately 16569100 and 28201731, respectively, by 2030 – when a combination of policies including inflation control, domestic political stability, increasing research and development, and exchange rate is enforced (Table 6).
In scenario S1, the basic state is when the COVID-19 outbreak is medium, the BAR, the number of blocks, and the number of transactions in the RSC are higher than when the COVID-19 outbreak is sharp. According to Fig. 7, the effect of applying policies in the model can be seen and the BAR first declines and then grows. This makes perfect sense as blockchain acceptance in the SC is not yet widespread and is growing. As it is clear from the policies when the worst case is applied because all the policies are in their worst state, the BAR is also in the lowest state, i.e. scenario S7, and when the best policy is applied, it can be seen that the block acceptance rate China will grow to about 80% in 2020. But on the other hand, it can be seen that with the acceptance of blockchain, because the fixed and variable costs of creating blocks are applied to the chain, the total costs will increase in the S6 scenario (the best case). The higher the BAR, the higher the total costs. Also, the total transactions will have an almost balancing behavior (limits to growth) over time. This means that over time the participants that trade in the chain via blockchain and smart contracts are increasing at a lower rate. Also, in Fig. 7 the importance of the backup buffer when the best policy (S6) is applied is clear because the existence of the backup buffer will make the SC more resilient.
Overall, the best scenario with a combination of inflation, domestic political stability, research and development measures, and exchange rate control appears to produce the greatest benefit in the region. This result plays an essential part in confirming the significance of the BAR in the RSC, contributing to encouraging traditional supplier contract change to the smart contract and blockchain technology acceptance in the SC.Table 6 Policy scenarios for BAR in the SC of household appliances in Iran
Base-case and intervention scenarios with the percentage of change compared to the base-case
Policy S1 S2 S3 S4 S5 S6 S7
Parameters Base-case (No intervention) Inflation control R & D Exchange rate control Domestic political stability Best-case Worst-case
Confirmed transactions 99000 0% 10% 0% 15% 15% -15%
Backup buffer 10800 0% 0% 10% 0% 10% -10%
Number of blocks 10000 15% 0% 0% 0% 15% -15%
Main inventory 1007 10% 0% 10% 0% 10% -10%
Total costs 801000 10% 0% 10% 0% 10% -10%
Table 7 The simulated value of the main variables by 2030 under base-case and policy scenarios
Policy S1 S2 S3 S4 S5 S6 S7
Parameters Base-case (No intervention) Inflation control R & D Exchange rate control Domestic political stability Best-case Worst-case
BAR
Medium COVID-19 outbreak 0.61 0.68 0.63 0.62 0.66 0.69 0.42
Sharp COVID-19 outbreak 0.32 0.45 0.49 0.39 0.42 0.58 0.233
Low COVID-19 outbreak 0.63 0.7 0.67 0.68 0.75 0.79 0.48
Number of blocks
Medium COVID-19 outbreak 28201731 32801031 38901511 34701787 39401250 51320092 10440911
Sharp COVID-19 outbreak 18532092 23532659 25536100 29913189 29076126 33023108 6505673
Low COVID-19 outbreak 31007519 357501865 39100412 53300075 57012601 60000800 16050105
Total transactions
Medium COVID-19 outbreak 30934700 31000574 31000532 31000861 30912460 31002109 31000001
Sharp COVID-19 outbreak 29900420 29983160 30002000 30005100 30101236 30508180 29830100
Low COVID-19 outbreak 31678900 31998600 31998600 31751500 31094319 32007514 31321085
Fig. 7 A comparison of the behavior of simulation outputs with historical data
Figure 8 shows a comparison of MLP, SVM and SD-behavior (real) of BAR since 2020 to 2022 which is included 160 backtesting data. It is worth to mention that the backtesting data is not used on training procedure.Fig. 8 Trend line in BAR Prediction in MLP and SVR (2020-2022)
Table 8 shows the comparison between SVR and MLP since 2020 to 2022 including 160 backtesting data.Table 8 MAPE and RMSE for BAR with SD-MLE and SD-SVR methods
Model MAPE RMSE
MLP 0.097195996 0.122225952
SVM 0.171057854 0.306167098
By paying attention to Table 8, MAPE and RMSE as proper measurements to compare methods is significantly lower in MLP compared to SVR under similar situation. In general, the behavior of the BAR in the SC of home appliances in Iran was first simulated using the dynamics of the systems. Then, for the years 2020 to 2022, this function was estimated using simulation data for the acceptance rate and other data that had a high correlation with the acceptance rate using MLP and SVR to obtain a more accurate behavior of the acceptance rate.
The theoretical and practical policy implications
Reviewing and creating policies can help improve the structure of the SC in the long term and pose positive implications. As shown in Tables 6 and 7, by controlling the exchange rate and the inflation of the purchase and sale prices of products, the costs of buying raw materials, the costs of creating backup buffers, and the cost of keeping goods and transporting them are reduced. Explanation and careful monitoring to prevent the increase of these rates, especially in a situation where a disorder like COVID-19 automatically increases inflation and exchange rates, can help the resilience of the SC. In this study, it was shown that with a 15% increase in inflation control, the backup buffer can be improved by about 20%, and on the other hand, the BAR increases due to the reduction of total costs. This condition is the same for the exchange rate. On the other hand, the policy of increasing research and development leads to more familiarity of the employees with the blockchain, and since the implementation of the blockchain requires familiarity with its mechanism, the exponential growth of these variables was seen in the long-term behavior of the BAR and the variable of the number of blocks (Fig. 7).
In addition, as shown in Fig. 7, the total number of transactions that take place through the blockchain network increases sharply at first according to the policy, but after a while, it is almost stable. This shows that in the long term, all people in the network do their transactions using smart contracts and in the blockchain network, the amount of transactions reaches its optimal and almost maximum per day. This is confirmed by the BAR after 4000 days, which is close to one. Although at the beginning of blockchain acceptance, there is a decrease in BAR for about 100 days, this rate grows after this period. The reason for this is that it is difficult to provide a suitable platform for the use of blockchain in the SC after the disruption, but after the training of the employees and the learning of all the participants in the chain, this rate will increase.
The managerial insights
Nowadays due to the COVID-19 outbreak, SC management has undergone many disruptions (Athari et al. 2022). Therefore, managers and policymakers are looking to improve the resilience of their SC. This study provided a comprehensive analysis considering the severity of Corona and various policies that can strengthen the SC in the face of this disease. Also, the current research has strong results that can be a panacea to guide managers in improving the resilience of the supply chain. In this section, management insights are expressed based on the results.This paper shows that for the resilience of the SC, the most important priorities should be paying attention to the skills of the personnel, their timely and correct training to communicate with new technologies, recognizing and using blockchain to increase the speed of action, transparency, and security in the network. Although using these factors can increase the costs of the entire network, in the long run, it increases the profitability and resilience of the SC.
Managers can strengthen their supply chain structure by adopting blockchain. As shown in this study, the more blockchain acceptance increases, the more backup buffer, response speed, and inventory in critical situations will increase.
Also, another policy that makes the system resilient is the policy makers’ attention to exchange rates, political risk and inflation (especially in developing countries). As shown in Table 7, controlling these factors helps to minimize the impact of COVID-19 on the SC.
In a smart RSC, profitability, customer satisfaction, and minimizing the effects of disruptions in responding to customer needs have a more prominent priority. In this research, the SC of household appliances in Iran was chosen because political risk, inflation, exchange rate changes, and the effects of COVID-19 on the SC are strongly felt in this country. Therefore, for better management of the chain in this country, the need for full acceptance of blockchain, proper training of employees, and other arrangements that make the RSC is well felt.
Conclusion
This study presents an approach based on a whole-of-system view to understand the dynamics of natural events’ impacts on SC development using a case study in a home appliance SC in Iran and finding the BAR in that network. Also, this paper uses simulation data for improving the acceptance function estimation. Indeed, it is a new method based on SD-MLP and SD-SVR. In general, this paper is the first research that simulates the BAR in an RSC and provides a new method for predicting the function behavior.
In a nutshell, a detailed study of the feedback interactions between system components will make it possible to identify the key dynamics that affect blockchains and identify the impact of transformations on system behavior. Test results of the SD model output confirmed its ability to reproduce well the historical behavior of the system it represents. It is worth noting to recognize that while natural phenomena are one of the factors influencing SC, they are not the determinant of SC sustainability. Our model results show that the control of inflation, R &D, exchange rate, and political risks play important roles, and it is these dynamics that drive the RSC. In the current situation, conditions related to smart contract trading may be exacerbated by the conditions of natural events, but applying a range of policy interventions, such as managing inflation, political risks, and exchange rates, can reduce the impact can be greatly minimized. The best-case scenario that allows BAR spending to reach potentially maximum acceptance in SC is a strategy that combines all these guidelines.
For future research, in addition to the approach presented in this study, other methods can be used to make the RSC, such as the optimization approach, robust planning to consider the uncertainty of parameters, and the use of mathematical models considering two dimensions, i.e. profitability and resilience (blockchain costs and smart contracts to increase profitability and reducing unfulfilled demand to increase resilience). It is also possible to use other implementation policies, such as the use of fast production methods such as 3D printing (additive manufacturing) in the blockchain platform to increase the speed of responding to customers. Because 3D printing can reduce SC levels, bring production closer to customers, and thus neutralize the effects of disruption to a large extent. Also, Bayesian Monte-Carlo or robust Bayesian can be suitable methods for future research to find the BAR.
Funding
The authors did not receive support from any organization for the submitted work.
Availability of data and materials
All data and material is available upon request.
Code availability
Software application is available upon request.
Declarations
Consent for publication
The manuscript is not currently being considered for publication in another journal.
Competing interest
The authors have no competing interests to declare that are relevant to the content of this article. The authors have no relevant financial or non-financial interests to disclose.
Publisher’s Note
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NeuroTransmitter
NeuroTransmitter
1436-123X
2196-6397
Springer Medizin Heidelberg
2994
10.1007/s15016-022-2994-5
Aus den Verbänden
Stabilität im und durch Wandel
Kumpe Heike 15016107865001
Meißner Ramon 15016107865002
15016107865001 Fachärztin für Neurologie und Fachärztin für Psychiatrie, Mühlenstraße 32, 23966 Wismar, Germany
15016107865002 Facharzt für Neurologie und Psychiatrie, Hinter der Kirche 1b, 19406 Sternberg, Germany
9 12 2022
2022
33 12 1819
© Berufsverband Deutscher Nervenärzte e.V. (BVDN) 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
issue-copyright-statement© Berufsverband Deutscher Nervenärzte e.V. (BVDN) 2022
==== Body
pmcDer Landesverband Mecklenburg-Vorpommern berichtet über Veränderungen durch die Digitalisierung, neue Richtlinien und Wahlen der Vorstandsmitglieder.
In den beiden vergangenen Jahren gab es bei aller Dynamik der Ereignisse in der Welt und im Land keine schwerwiegenden Veränderungen. Natürlich kam es durch die COVID-19-Pandemie zu Einschränkungen im Praxisalltag sowie bei Haus- und Heimbesuchen. Einige Kolleginnen und Kollegen oder ihre Mitarbeitenden erkrankten an der Infektion, zum Glück meist ohne gravierende Folgen. Große Verwerfungen oder Einbußen beim Honorar gab es in unseren Fachgruppen in dieser Zeit nicht. Einige von uns beteiligten sich auch aktiv an der Impfkampagne.
Holpriger läuft es dagegen bei der von der Politik initiierten und unzureichend vorbereiteten Digitalisierung. Bis heute gibt die Umsetzung kein gutes Bild ab und den meisten Beteiligten bringt sie noch wenig Nutzen. Es ist unserem BÄK-Präsidenten, Dr. Klaus Reinhardt, zuzustimmen, der im Deutschen Ärzteblatt kritisierte: "Es fehlen für eine erfolgreiche Digitalisierung im Gesundheitswesen ein politischer Ordnungsrahmen und eine versorgungsorientierte Strategie" [Dtsch Arztebl 2021;118(35-6):A-1562]. Trotzdem bemühten sich die Kolleginnen und Kollegen alle bisher zur Verfügung stehenden Module zu installieren, auch wenn es immer wieder Stolpersteine gab (z. B. Fehler beim Einlesen der neuen Krankenkassenkarten [G 2.1]).
MSnetWork läuft gut an
Bei der Durchführung der berufspolitischen Aktivitäten wich der Vorstand auf regelmäßige Telefonkonferenzen aus, jedoch konnten ab Sommer 2021 vereinzelt auch wieder Fortbildungsveranstaltungen in Präsenz organisiert werden. Diese waren alle gut besucht und wir konnten neue Mitglieder gewinnen. Nach der schwierigen Startphase läuft das Projekt MSnetWork auch in Mecklenburg-Vorpommern, wie in den anderen beteiligten Regionen, nun erfolgreich an, nicht zuletzt aufgrund des Einsatzes von BDN-Landessprecherin Dr. Katrin Hinkfoth. Die neuen Möglichkeiten, die sich durch die KSV-Psych-Richtlinie ergeben, sind angesichts der Anforderungen und Voraussetzungen in unserem dünn besiedelten Land mit großen Entfernungen nur schwer zu nutzen. So gibt es nach wie vor nur eine punktuelle ambulante psychiatrische Pflege und keine Soziotherapie. Wie sich die Zusammenarbeit mit den Kliniken sowie Psychotherapeutinnen und -therapeuten gestalten wird, müssen wir abwarten. Unsererseits werden wir weiterhin entsprechende Kontakte suchen.
Frühjahrstagung mit Mitgliederversammlung
Auf der zwangsweise zweimal verschobenen Frühjahrstagung in Waren (Müritz) am 9. April 2022 konnten wir unsere Neumitglieder begrüßen. Zusätzlich zu den wissenschaftlichen Vorträgen fand ein reger Austausch untereinander statt und am Abend gab es in gewohnter Weise ein fröhliches Beisammensein. Alle Teilnehmenden einschließlich der Referierenden sowie Sponsoren waren über die Fortsetzung unserer Tradition erfreut.
Bei der Abstimmung über einen angepassten Seniorbeitrag für alle Neusenioren ab dem Jahr 2023 (120 €), die einem Beschluss auf der letzten Länderdelegiertenversammlung (LDV) in Köln folgte, wurde eine Erhöhung knapp abgelehnt. Es bleibt also bei den derzeitigen 60 €. Wir werden hierzu sicherlich neue Überlegungen und Diskussionen führen müssen. Ziel sollte eine bundeseinheitliche Beitragsregelung sein, um unsere Berufsverbände gemeinsam stark aufzustellen. Wesentliche Regelungen im EBM erfolgen auf Bundesebene zwischen der KBV und dem GKV-Spitzenverband, nicht auf Landesebene. Unser Bundesvorstand ist jedoch über den Spitzenverband ZNS gut mit den Entscheidungsträgern vernetzt, sodass bei grundsätzlichen Veränderungen eine Beteiligung unserer Vertreterinnen und Vertreter möglich ist.
In diesem Jahr fand turnusgemäß die Wahl des Vorstandes statt. Der scheidende Vorsitzende Ramon Meißner bedankte sich bei den Mitgliedern des alten Vorstandes für die gute Zusammenarbeit. Der Vorstand eines Vereins braucht aber auch Veränderungen durch Verjüngung und neue Impulse, um nicht in Monotonie und Routine zu verfallen. Einige weitere Vorstandsmitglieder schieden nach langjähriger aktiver Mitarbeit ebenfalls aus oder übernahmen eine andere Funktion, neue Mitglieder konnten gewonnen werden. Mit dem jetzigen Vorstand ist der Mitgliederversammlung wohl die Wahl einer hoffungsvollen Mischung aus Erfahrung und Erneuerung gelungen. Auch blieb eine regional und neurologisch-psychiatrisch breite Aufstellung erhalten, neue Vorsitzende ist Dr. Heike Kumpe aus Wismar.
Auf unserer Landesseite der BVDN-Homepage finden Sie zukünftig alle relevanten Informationen, unter anderem Termine für die regionalen Fortbildungszirkel in Crivitz (seit November in Schwerin), Neetzow und Rostock, die Frühjahrstagungen und Herbstversammlungen sowie die Ansprechpartnerinnen und -partner im Land, nebst der Beitragsordnung und Satzung.
Wahlen für die KV-MV und ÄK-MV
Bei den Wahlen zur Vertreterversammlung (VV) im Juni kandidierten drei Mitglieder unserer Berufsverbände auf einer gemeinsamen landesweiten Facharztliste. Auch wenn niemand von uns in die VV gewählt wurde, so schafften es die Fachärztinnen und -ärzte erstmalig, die Mehrheit in der VV zu gewinnen. Außerdem wurde Dr. Katrin Hinkfoth in den Beratenden Ausschuss des Vorstandes für die fachärztliche Versorgung berufen.
Bei der Wahl zur Kammerversammlung im November (nach Redaktionsschluss) kandidierten sieben Kolleginnen und Kollegen aus unseren Fachbereichen, wovon zwei Weiterbildungsassistenten und drei Mitglieder in unserem Berufsverband sind.
Mit der Wahl dieser Selbstverwaltungsorgane haben wir die Chance, trotz diverser externer Regelungen durch den Gesetzgeber, unsere Arbeitsbedingungen in großen Bereichen selbst zu gestalten. Das betrifft zum Beispiel Arbeitszeit und -ort, Interessenschwerpunkte, Qualitätsansprüche, Weiter- und Fortbildung, Zusammenarbeit, Schaffung eines Versorgungswerkes und andere. Wir sollten uns die Freiberuflichkeit durch eine rege Teilnahme an den Wahlen erhalten. Die Begehrlichkeiten in der Politik zur Regulierung unserer ureigenen Interessen sowie das geringe Verständnis in der EU dafür sind oft zu spüren. Auch wenn Begriff und Inhalt der Freiberuflichkeit nicht scharf definiert sind, so steht dennoch in unserer Berufsordnung (§ 1): "Der ärztliche Beruf ist kein Gewerbe. Er ist seiner Natur nach ein freier Beruf." Damit sind alle, gleich ob selbstständige, angestellte oder verbeamtete Ärztinnen und Ärzte gemeint, so wie es unser BÄK-Präsident anlässlich der Festveranstaltung zum 75. Jubiläum der BÄK in Berlin am 6. Oktober 2022 formulierte: "Die medizinisch-fachliche Weisungsfreiheit aller Ärztinnen und Ärzte und ihre im ärztlichen Berufsrecht verankerte Verpflichtung zur Übernahme persönlicher Verantwortung für das Wohl der Patientinnen und Patienten ist (…) Grundvoraussetzung für eine gute Patientenversorgung. (…) Trotz zunehmender staatlicher Einflussnahmeversuche können wir immer noch wichtige Rahmenbedingungen unserer Berufsausübung selbst gestalten." [Dtsch Arztebl 2022;119(41):A-1732]) Das sei in hohem Maße sinnstiftend und befriedigend. Mögen wir es uns erhalten!
Termine
Zum Schluss möchten wir auf unsere Frühjahrstagung im neuen Jahr in Hasenwinkel bei Warin in der Nähe von Wismar vom 21. bis 23. April 2023 hinweisen und bereits heute alle einladen. Gäste sind uns stets willkommen - lernen Sie unsere schöne Heimat kennen!
Wir wünschen allen ein friedliches Jahresende und einen guten Start ins neue Jahr.
Dr. Heike Kumpe Fachärztin für Neurologie und Fachärztin für Psychiatrie
Mühlenstraße 32
23966 Wismar
[email protected]
Dipl.-Med. Ramon Meißner Facharzt für Neurologie und Psychiatrie
Hinter der Kirche 1a
19406 Sternberg
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J Ambient Intell Humaniz Comput
J Ambient Intell Humaniz Comput
Journal of Ambient Intelligence and Humanized Computing
1868-5137
1868-5145
Springer Berlin Heidelberg Berlin/Heidelberg
4483
10.1007/s12652-022-04483-8
Correction
Correction to: A study of plithogenic graphs: applications in spreading coronavirus disease (COVID-19) globally
Sultana Fazeelat [email protected]
1
http://orcid.org/0000-0002-6438-1047
Gulistan Muhammad [email protected]
1
Ali Mumtaz [email protected]
2
Yaqoob Naveed [email protected]
3
Khan Muhammad [email protected]
4
Rashid Tabasam [email protected]
5
Ahmad Tauseef [email protected]
6
1 grid.440530.6 0000 0004 0609 1900 Department of Mathematics and Statistics, Hazara University Mansehra, 21120 Mansehra, Khyber Pakhtunkhwa Pakistan
2 grid.1021.2 0000 0001 0526 7079 Deakin-SWU Joint Research Centre on Big Data, School of Information Technology, Deakin University, Burwood, VIC 3125 Australia
3 grid.414839.3 0000 0001 1703 6673 Department of Mathematics and Statistics, Riphah International University, I-14 Islamabad, Pakistan
4 grid.440530.6 0000 0004 0609 1900 Department of Genetics, Centre for Human Genetics, Hazara University Mansehra, 21120 Mansehra, Khyber Pakhtunkhwa Pakistan
5 grid.444940.9 Department of Mathematics, University of Management and Technology, Lahore, Pakistan
6 grid.263826.b 0000 0004 1761 0489 Department of Epidemiology and Health Statistic, School of Public Health Southeast University, Nanjing, 210009 China
6 12 2022
11
© Springer-Verlag GmbH Germany, part of Springer Nature 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
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pmcCorrection to: Journal of Ambient Intelligence and Humanized Computing 10.1007/s12652-022-03772-6
In this article the author name 'Tauseef Ahmad' was incorrectly written as 'Tauseef Ahmed’.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Educ Inf Technol (Dordr)
Educ Inf Technol (Dordr)
Education and Information Technologies
1360-2357
1573-7608
Springer US New York
11490
10.1007/s10639-022-11490-x
Article
Enhancing teacher collaboration in higher education: the potential of activity-oriented design for professional development
http://orcid.org/0000-0001-6697-2118
Pischetola Magda [email protected]
1
Møller Jeppe Kilberg [email protected]
2
Malmborg Lone [email protected]
3
1 grid.5254.6 0000 0001 0674 042X Department of Communication, University of Copenhagen, Copenhagen, Denmark
2 grid.32190.39 0000 0004 0620 5453 Center for Computing Education Research, IT University of Copenhagen, Copenhagen, Denmark
3 grid.32190.39 0000 0004 0620 5453 Department of Digital Design, IT University of Copenhagen, Copenhagen, Denmark
5 12 2022
130
31 5 2022
28 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Professional development programs for teachers in higher education are often characterized by top-down approaches, which fail to make appreciable differences in teaching practices. This study uses a qualitative approach to explore activity-oriented design (AOD) as an instrument for collaborative learning in higher education teacher professional development. We examine Teknosofikum, an ongoing project developed in Denmark along three iterations, involving a total of 64 course participants (42 in the hybrid format; 22 online). The study applies the methodology of design-based research: data was collected via 15 semi-structured group interviews, online forums, and field notes/recordings from online meetings and onsite workshops. Data analysis follows the methodology of grounded theory and evidence is given significance inductively, based on contextual data. Four activities were selected to assess the potential of AOD methods in enhancing teacher collaboration, with different aims reflection, discussion, theory-practice alignment, and participation. Our analysis revolved around three main categories: trust, deep interaction, and shared beliefs/values. The results show how collaborative group work activities have improved trust and knowledge-sharing among participants and have contributed to creating a safe learning environment. The paper concludes that AOD methods could better assist educational designers in promoting professional development courses that aim at enhancing teacher collaboration in higher education.
Keywords
Activity-oriented design
Higher education
Teacher professional development
Collaborative learning
Styrelsen for Forskning og Uddannelse (DK)9156-00008B
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pmcIntroduction
Teacher professional development1 involves “activities that develop teachers’ skills, knowledge, expertise and other characteristics as a teacher” (OECD, 2009: 49). It is intended to improve the quality of education and extend teachers’ commitments as “change agents” (Day, 1999). Nevertheless, initiatives aiming at developing in-service teachers’ professional skills are often characterized by top-down approaches (Riedner & Pischetola, 2021), which fail to address the real needs of participants (Dilshad et al., 2019; Roseler & Dentzau, 2013) and to make appreciable differences (Dysart & Weckerle, 2015). Research has shown that professional development programs also fail to actively acknowledge teachers’ self-efficacy (Pischetola, 2020) and self-concepts (Wang et al., 2004), both of which are crucial for producing significant change in teaching practices.
A growing body of research is pointing to the need for collaborative approaches in education (Cumbo & Selwyn, 2022; van der Rijst et al., 2022) and the importance of giving value to socially constructed learning processes in the classroom ecosystem (Pischetola & Miranda, 2020). Recent studies have shown that collaborative knowledge-building practices can have meaningful, lasting impacts (Bødker & Kyng, 2018; Stahl, 2006a) and can elicit collectively generated shifts in practices (Brodie, 2021; Hairon et al., 2017). Most of these studies, however, focus on primary and secondary education (Tuhkala, 2021); considerably less research has examined the professional development of higher education teachers (Avalos, 2011; Svendsen, 2020).
As White et al. (2016) argue, a transition in teaching formats in higher education requires teachers’ involvement and reasoning about each component of their practice. Thus, a professional development program should seek to promote teachers’ agency in making professional decisions about what they need to learn and how they might challenge themselves to acquire new skills (Brodie, 2021). More qualitative approaches are needed in the assessment of academic professional development, to better explore how programs focusing on forging relationships and building trust can have lasting impacts (Pleschová et al., 2021; van der Rijst et al., 2022).
In this paper, we aim to address this research gap by presenting a case of collaborative knowledge-building practices in a professional development program for higher education teachers in Denmark. The program adopts a framework of activity-oriented design (AOD; Durand & Poizat, 2015; Li et al., 2015), which has its roots in activity theory (Engeström et al., 1999; Leont’ev, 1981; Vygotsky, 1978) and computer-supported collaborative work (Nardi, 1996). AOD methods allow for the involvement of participants in creating productive learning spaces, artifacts, and collaborative learning environments (Carvalho & Yeoman, 2017; Yeoman & Wilson, 2019), by engaging simultaneously with theory and practice in learning situations (Durand & Poizat, 2015; Goodyear et al., 2021). AOD is also a key instrument in supporting higher education curriculum reform (Li et al., 2015), as it enables participants to connect learning theories and teaching practices (Anderson & Shattuck, 2012; Christiansson et al., 2018).
The program presented in this paper is the outcome of Teknosofikum, an ongoing (2020–2023) project funded by the Danish Ministry of Higher Education and Science and developed collaboratively by four institutions. The aim of the project is to expand professional skills related to technology education, based on an understanding of technology as an agent in teaching and learning practices (Dakers, 2006; Pischetola, 2021).
The project is conceived as design-based research, which in turn is characterized as an interdisciplinary approach conducted in real-world settings (Reimann, 2011; Wang & Hannafin, 2005) through iterative analyses that support educational designers in implementing innovative proposals (Cobb & Gravemeijer, 2008). In the case of Teknosofikum, the innovative proposal concerns the use of AOD both in the organization of the online learning environment and in onsite workshop activities, with the aim of empowering higher education teachers in the pedagogical use of technologies, thus mitigating many of the difficulties they might encounter in planning meaningful activities. In the first three iterations of the project, 64 participants completed the course, 42 of which attending it in the hybrid format and 22 in the online format.
The following research questions guided our study:
How can the professional development of higher education teachers be conceived as collaborative knowledge-building?
How can activity-oriented design methods contribute to collaborative knowledge building in a professional development program for higher education teachers?
Activity-oriented design
Activity theory has contributed greatly to the field of computer-supported collaborative learning since the 1990s (Gifford-Enyedy, 1999; Nardi, 1996). At the core of this theory is the idea that culturally defined activities are internalized through social interaction, in the process of learning. That idea inspired the creation of a model of design for computer-supported learning environments, called activity-centered design (Gay & Hembrooke, 2004). In this model, social interaction is conceived as generating both cultural tools and cognitive processes, and learning is understood as a culturally mediated practice. Activities through which an individual learns can be defined by a hierarchical order, from organizations, to actions, to specific operations (Nardi, 1996).
In accordance with this idea, computational activities can also be organized and classified in the same way that human activities are (Christensen & Bardram, 2002). For example, a computer-mediated environment organized through an activity-centered design approach will feature a focus on interactions and interdependencies among teachers, students, tasks, and mediating materials (Gifford-Enyedy, 1999). It will also be structured around human activity (Baldwin et al., 2020).
More recently, the literature has introduced a new framing of this model, namely AOD, which uses activity theory as a paradigm for computer-supported collaborative learning. Here, activity is understood not only as an internalization process of learning, but also as a mechanism for making knowledge actionable (Markauskaite & Goodyear, 2017) by translating learning to practice. In fact, engaging with AOD mechanisms supports the translation of conceptual frameworks into concrete actions (White et el., 2016).
AOD is based on the idea that learning is not only culturally and historically situated (Engeström et al., 1999; Vygotsky, 1978), but also driven by different epistemologies (Goodyear et al., 2021). Therefore, it acknowledges that working collaboratively might be challenging, especially in community-based participatory designs (Grönvall et al., 2016) and in interdisciplinary projects (Santaolalla et al., 2020), where conflicting values and points of view may arise. This is precisely why this model is relevant for teachers’ professional development, where different theories and beliefs need to be articulated in order to seek convergence and shared epistemic grounds (Fischer et al., 2021).
With regard to approaches grounded on activity theory, several scholars have underlined the importance of producing design principles that can adjust interventions to their situated contexts, thus optimizing outcomes. For the purposes of this paper, we refer to the formulation of Yeoman and Carvalho (2019) on the need to use principles and theories as tools. According to the authors, the theoretical framework of the activity supports “designable components” (Carvalho & Yeoman, 2017: 193) that will be used to define the material structure of learning activities.
Teacher collaboration
The educational sector is increasingly confronted with the need to develop collaborative skills and collaborative work environments (Riedner & Pischetola, 2021). As Vangrieken et al. (2015, p. 18) point out, “proficient collaboration” among teachers is required, not only to achieve high performance in teaching, but also to enhance collaboration among students.
In higher education, AOD allows learning to be shaped as a collaborative process among teachers. In fact, in educational settings following this model, constant dialogue is maintained between the course design teams and the participants (Greenhow & Belbas, 2007), who themselves undertake the role of designers (Konnerup et al., 2018).
Research suggests that the quality of collaborative processes in professional communities depends on several aspects. First, trust among the participants is crucial (Brodie, 2021; Schechter, 2012), all the more so within computer-supported learning environments, as online settings happen to limit trustful collaboration and knowledge-sharing (Booth, 2012; Gerdes, 2010).
Second, the frequency and depth of interactions are key factors for improving collaborative knowledge-building practices (Dollinger et al., 2018). Collaborative learning among teachers can be induced, for example, by sharing experiences, observing each other’s practices, or by discussing and reflecting together (Plauborg, 2009).
Third, teacher collaboration is not simply exchanging information to achieve a better result. Working in a collaborative way implies interdependence and shared responsibility towards a common goal (Romeu et al., 2016). Deep-level collaboration inevitably requires touching upon beliefs and values, which in some cases can be perceived as threatening, as disagreement often generates conflict. However, striving for dialogue and towards cohesion has proven a key factor for the growth of teacher collaboration practices (Vangrieken et al., 2015). In this sense, AOD methods are useful when moving from specific tasks toward exchanges about differing values (Goodyear et al., 2021) and contributing to the collective knowledge of a group (Romeu et al., 2016).
This paper explores the potential of AOD in higher education teachers’ professional development, where the emergence of collaborative practices and trustful relationships can have a positive and lasting impact (van der Rijst et al., 2022). We anticipate that the findings of our research could better assist educational designers in promoting professional development courses that aim at enhancing teacher collaboration in higher education.
The Teknosofikum project
Teknosofikum is a three-year project (2020–2023) funded by the Danish Ministry of Higher Education and Science. Its goal is to prepare higher education teachers for the professional opportunities and challenges entailed by digital technologies. The expected outcome is a 20–37-hour modular hybrid learning course. Four partner institutions—the IT University of Copenhagen, the Royal Danish Academy - Architecture, Design, Conservation, the University of Copenhagen’s Faculty of Law, and Design School Kolding—are collaborating on the learning design, content development, and implementation of Teknosofikum, in five iterations. A total of 500 in-service teachers from all over Denmark are expected to attend the course over the duration of the project.
The overarching goal of Teknosofikum is to motivate and inspire higher education teachers to incorporate technology into their teaching practices in meaningful ways, through different digital tools/platforms, and with an understanding of the mutual influence between technologies and society (Hasse, 2017). This includes an interdisciplinary perspective at the crossroads between Law, Computer Science, and Design, with activities geared toward the acquisition of new information, reflection upon critical issues, and implementation of new ideas and concepts in teaching.
Teknosofikum is also intended to actively treat teachers as agents of their own professional development (Brodie, 2021). Thus, course participants are free to choose among two formats: an online course in the virtual learning environment (20 h) or a hybrid course with two additional onsite workshops (37 h). Figure 1 below shows the two learning paths for the respective courses.
Fig. 1 Visual representation of the two learning paths of Teknosofikum
In the virtual learning environment, the course participants are offered roughly 30 topics, divided between two categories of content: technology and education. Participants define their own professional needs and choose a suggested amount of five topics for each category. Each topic is accompanied by an activity that explores collaborative knowledge-building.
Furthermore, at the final workshop/online meeting, participants prepare teaching plans based on the ideas they were inspired with in collaborative activities during the process.
Drawing on the aforementioned concept of teacher collaboration, Teknosofikum’s educational design team has identified three key goals to be achieved through the activity-oriented design of the course: trust, deep interaction, and discussion of beliefs/values. In light of these core goals, activities have been designed to be ca-rried out in small groups of four or five participants from different institutions. In fact, the literature on technology, interaction, and cognition has given particular emphasis to the role of small working groups, reading circles, and informal professional discussions for the genesis of insights and new ideas (Greenhow & Belbas, 2007; Stahl, 2006b). The participants form groups at the first onsite workshop/online meeting.
Research methods
The study presented in this paper examines the use of AOD methods in collaborative knowledge-building within a professional development program for higher education teachers in Denmark. The methodology used for the study is design-based research, an approach that is considered systematic but flexible (Sandanayake et al., 2021), as well as effective in bridging the gap between research and practice (Barab & Squire, 2004). As Reimann (2011) explains, design-based research is an investigation of educational interactions, provoked by a set of tasks, materials, and tools that characterize a whole learning environment. Common characteristics of design-based studies are their relatively extended duration (weeks or months – in our case years) and the close involvement of a team of educational designers in the research design.
Anderson and Shattuck (2012) summarize the aspects that make design-based research interesting for educational settings as follows: being situated in a real context; focusing on design/testing of a meaningful intervention; using mixed research methods; involving multiple iterations; promoting collaborative partnerships between researchers and practitioners.
Cobb & Gravemeijer (2008) define three phases in the design-based research process:
Phase 1: Preparation.
Phase 2: Experimentation.
Phase 3: Retrospective analysis.
The first phase is the most delicate, as it calls for epistemological alignment and a shared understanding of purposes. Once these are clarified and a common vocabulary is created among the designers, it is necessary to envision a theory of learning and an expected learning trajectory. The phase of experimentation will inform the researchers about the need to adjust future learning designs. Finally, in the retrospective analysis, tools and methods are assessed in terms of their suitability, given the initial theories, so as to inform redesign (preparation) in the next iteration (see Fig. 2 below).
Fig. 2 Visual representation of the design-based research methodology
Participants
The three first iterations of Teknosofikum involved a total of 64 teachers from the four different partner institutions. Of those teachers, 42 attended the course in the two different formats, as follows:
May 2021 (first iteration): 7 online participants.
October 2021 (second iteration): 22 hybrid participants.
March 2022 (third iteration): 20 hybrid participants; 15 online.
The participants were recruited by each institution in different ways, through newsletters, public calls at faculty meetings, top-down requirements from heads of departments, and in some cases through local in-service teacher development programs for junior teachers. Participants were evenly divided among teachers occupying junior positions (one PhD fellow, nine postdoctoral fellows, four teaching assistants, and 14 assistant professors) and senior positions (15 associate professors and three professors with special responsibilities). In addition, 18 part-time lecturers were recruited for the third iteration.
Data collection and analysis
The instruments used for data collection were 15 semi-structured group interviews, online forums in the virtual learning platform, and notes/posters resulting from four selected collaborative activities conducted during synchronous online meetings and onsite workshops. The details of each activity are presented in the Experimentation phase subsection below.
In one activity (#3), the participants were required to fill an online survey about their teaching perspectives (Pratt et al., 2001). The instrument was considered a conversational tool, to spark discussion among the participants, and not used for data collection itself. Other online surveys were used also during online meetings and onsite workshops, to give feedback to researchers and educational designers about the most valued aspects of the proposed AOD activities.
Five semi-structured group interviews were undertaken online at the end of each iteration with the aim to collect the participants’ feedback on all the aspects of the course (learning path, topics available on the virtual learning platform, overall assessment of the learning process, activities, and most valuable outcomes). The interviews were recorded, transcribed, and analyzed with the use of the software NVivo 12. The online forums were downloaded in PDF format and imported into NVivo 12 as well. Three researchers were involved in the process of reading the collected material multiple times, to gain familiarity with its content. A descriptive open coding method was employed to categorize the findings with a keyword or a short sentence. Finally, the field notes from online and onsite meetings were used to support the process of recoding around the key features of teacher collaboration. This triangulation strategy is common in qualitative data collection and analysis, to improve the trustworthiness of the research (Oliver-Hoyo & Allen, 2006). Based on the literature on AOD methods, we organized data into three categories: trust, deep interaction, and discussion of teachers’ beliefs/values.
It is important to emphasize that, in design-based research, there is no strict separation between theory development and theory application, as “data acquisition and analysis have to be (close to) continuous in order to drive forward multiple cycles of testing and design optimization” (Reimann, 2011, p. 39). This is why the data analysis of design studies resembles the methodology of the grounded theory (Glaser & Strauss, 1967), where evidence is given significance inductively, based on the analysis of contextual data (De Villiers, 2005). Similarly, the design-based research process allows for a constant dialogue between theoretical frameworks and their tested applications. Following the design-based research process, we used the results to redesign the course and the virtual learning environment at each iteration. In this way, theory and practice advanced concurrently, so as to solve real problems in real contexts.
Results
In what follows, we briefly describe our uses of AOD methods during the preparation and experimentation phases of each iteration. Then, in the retrospective analysis, we analyze qualitatively the collaborative processes generated by these activities, drawing on the collected data.
Preparation phase
In the preparation phase, AOD methods served different purposes at each iteration of the project. The first two iterations of Teknosofikum (May 2021 and October 2021) focused on the conceptualization of technology education for higher education teachers, in order to organize the virtual learning platform’s contents by relevance. The third iteration (March 2022) focused on interdisciplinary dialogue among the participants, for increasingly in-depth explorations of the collaborative processes of knowledge-building in professional communities.
At each iteration, the preparation phase had the purpose of (re-)designing the course, based both on the proposals from the design team and on the feedback from the course participants. As a result, the virtual learning environment changed significantly over the three iterations, from a content organization concerned with topics (iteration #1), to a content organization focusing on disciplines, based on the expertise of the participating partner institutions (iteration #2), to an organization addressing knowledge areas (iteration #3). Figures 3 and 4, and 5 below present the respective entrance page for course participants at each iteration.
Fig. 3 Learning environment iteration #1. Content organized on topics
Fig. 4 Learning environment iteration #2. Content organized on disciplines (IT, Law, Design)
Fig. 5 Learning environment iteration #3. Content organized on knowledge areas (Technology & Education)
Experimentation phase
At each iteration, the experimentation phase allowed us to test the concepts defined during the preparation phase. The first iteration took place in May 2021, with seven participants in the online format only, due to Covid-19 restrictions. The second iteration took place in October 2021, with 22 participants in the hybrid format only, in order to test the design of the onsite workshops. In the third iteration in March 2022, both formats were implemented, with 15 and 20 participants, respectively. AOD methods were constantly applied in both the virtual learning environment and the onsite workshops. A summary of the activities is presented in Table 1 below, and a detailed explanation of each activity follows.
Table 1 Activities of experimentation phase at each iteration
Activity-oriented design
Iteration #1
online only;
7 participants
Iteration #2
hybrid only;
22 participants
Iteration #3
15 online participants;
20 hybrid participants
Virtual learning environment
(asynchronous/ individual study)
Debates in forums Debates in forums
Media content production
Debates in forums
Media content production
“How might I…”
sheet completion
Midway online meeting
(synchronous/ group work)
Activity not held at this iteration Discussion
of content
Feedback
on format
Discussion
of content
Knowledge-sharing
Planning for next phase (“How might I…”)
Online kick-off and round-up meetings
(group work)
Two one-hour online meetings
Online 1:
Brief presentation of the virtual learning platform
Activity not held at this iteration Online 1:
Teaching perspectives
Technology implosion
Online 2:
Discussion
about content
Feedback
about format
Online 2:
Mapping teaching ideas
Design your teaching experiment
Share your experiments
Onsite workshops
(group work)
Two days from 10:00 until 3:30pm
Activity not held at this iteration Workshop 1:
Teaching perspectives
Technology implosion
Workshop 1:
Teaching perspectives
Technology implosion
Workshop 2:
Personas
Cards-game
Sketch prototyping
Workshop 2:
Mapping teaching ideas
Group reformulation
Design your teaching experiment
Share your experiments
For the sake of clarity, we will divide descriptions of the activities into online and onsite.
Online activities
In the virtual learning environment, the course participants worked individually in asynchronous mode. Along the three iterations, the activities grew in intensity and complexity. In the first iteration, they included only debates in forums, which occurred after watching a video, reading a paper, or listening to a podcast about a specific topic. In the second iteration, aside from debates in forums, the activities also included media content production. The course participants were asked to produce a small video, a podcast, or a mind-map about a subject they were teaching or had taught in the past. In the last iteration, in addition to these activities, the course participants were also asked to reflect in a more in-depth manner on their teaching practices and to fill out a “How might I…” sheet with new teaching ideas to be discussed in groups during the workshop 2 or online round-up meeting.
The synchronous activities included a midway online meeting for all course participants, divided into small working groups, and online kick-off/round-up meetings for the online format (implemented in the third iteration).
The midway online meeting was introduced in the second iteration of the course, in order to gather feedback from the course participants about the content and the format of the virtual learning environment. Based on positive evaluations by the design team, in the third iteration, this meeting was introduced as part of the learning path for both formats and was used to support course participants in their self-study. The main purpose of this meeting is to motivate the groups to work collaboratively, despite the fact that course participants belong to different higher education institutions in Denmark.
The online kick-off and round-up meetings have radically changed their formats from merely informative encounters between the design team and the course participants (iteration #1) to sessions involving more substantial collaborative work and group discussions (iteration #3). The activities of both meetings were designed based on the onsite workshops’ activities and were adapted for a one-hour online meeting.
Onsite activities
The two onsite workshops were where the collaborative potential of AOD was most prominently tested. Teknosofikum’s first workshop ever was held in October 2021 (iteration #2) and was organized around two group activities: teaching perspectives and technology implosion. In the first of these, course participants shared their thoughts, beliefs, and experiences relating to teaching. In the second activity, each participant picked a technology (e.g., wi-fi router, self-driving car) and shared their knowledge/ignorance about it. Both activities concluded with plenary sessions in which each participant would present their reflections. This workshop’s format was maintained in iteration #3, as it proved to be very productive. The format of the second workshop, in contrast, changed radically from iteration #2 to iteration #3, from a design-centered format aiming at refining the content organization in the platform to a more teacher-centered format focused on transforming teaching practices. This was due to the differing purposes of the iterations, given that the third iteration was closest to the final Teknosofikum course.
Selected collaborative activities
We now present the four online/onsite activities designed to trigger collaborative knowledge-building practices among course participants (see Table 2 below).
Table 2 Description of the four selected activities examined in this study
Activity #1 Reflections in forum (online asynchronous)
After each topic accessed in the learning environment, course participants are asked to post their reflections in the forum and to share their professional knowledge about a specific technology trend and/or teaching practice.
Activity #2 Discussion about content (online synchronous)
At the online midway and round-up meetings, course participants share their opinions about the most relevant topics encountered and the most interesting activities that produced knowledge-building.
Activity #3 Teaching perspectives (onsite—workshop 1)
The course participants are introduced to learning theories and their relation to practice. They complete a survey about their own teaching perspective(s) and then, in groups, discuss some of their teaching beliefs/values/actions.
Activity #4 Redesign of virtual learning platform (onsite—workshop 2)
The participants are asked to give suggestions for the future shape of the course, by discussing the topics presented throughout the course and diving into the specific components (what should be kept, eliminated, reformulated?).
Retrospective analysis
Data from the online forums, online meetings, and onsite workshop materials are examined in relation to each activity. Data is organized around three key features of teacher collaboration in professional communities, as highlighted by the literature:
Trust.
Deep interaction.
Shared beliefs/values.
Results
Activity #1—Reflections in forums
As it would be too extensive to present all the topics discussed in the forums, we have selected a few participants’ exchanges as examples of asynchronous debates centered on proposed topics. The interesting aspect of the forums is that course participants can build on discussions from previous iterations of the course, as all posts continue to be preserved by the design team (Fig. 6).
Fig. 6 Activity in forum on the topic “Technological attentionality.”
Activity #2—Discussions about content
In what follows, we provide a few excerpts from the online meetings with small groups (3–6) of course participants. Given the space limitations, we have selected the most representative quotations from each iteration, which express opinions that were also conveyed by other participants. (Codes and numbers are used to preserve anonymity.)
Iteration #1I really liked this kind of an evaluation of your teaching. There was this discussion on what your roles are as a university professor. Are you a teacher, a facilitator, an instructor, or all of these? Are you some? Are you none? Reflecting back to your question, I think that what we need [in Teknosofikum] is to think: how can we make the teachers better? I think it´s to offer different kinds of scenarios. (L1, round-up meeting)
What I would really, really like would be sharing examples of how other teachers did what was inventive, with diverse methods, how they were thinking outside the box, and how they did it, because I get really inspired from other people’s examples of teaching. […] So, facilitating group discussions that start with an example or good ideas or something would really help me, instead of another webinar and sitting on planning webinars on my own. I would like more interaction with people to discuss things further. I’ve been on my own for a year now […] I’m screen tired. (D3, round-up meeting)
Iteration #2I’m still kind of confused by the content. I don’t know if I understand what I should get out of this. […] Is this for students or for educators? Is this for technology being used by students as part of education? Is this for educators using technology in support of their educational practices? (CS8, midway meeting)
You know, what is technology? It’s very different when you’re talking about design technology, than it is when discussing the software platform. Is it actually learning how to code? How do you do that? How do we teach students how to code interactively online or whatever? (D5, midway meeting)
I really liked those active learning tools, especially. I think that helped me a lot in moving forward with my education. And I also liked the podcast/video exercise. […] It wasn’t many students that gave me feedback. But some of them said that it really worked well. […] I would have not considered making a video if it hadn’t been a task in the exercise, but I think I would consider doing it in my next courses as well. (D11, midway meeting)
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Iteration #3The topic of critical literacy in computing was by far the most interesting. I was eager to know more. Is there going to be a part 2? (CS15, midway meeting)
I only took Tech topics so far, and they all confirmed what I know already. Especially regarding conspiracy theories, my concerns were confirmed. However, as for the Blockchain topic, I was surprised about how non-critical that part is! It did not mention the environmental challenges at all, bitcoin, and stuff. I think in Teknosofikum there’s the idea that we need to be critical towards technology, right? (SS1, midway meeting)
We had great group communication when we met, but it has been more difficult since then. Life is very busy, but this meeting helps me get back to it. (D12, midway meeting)
It’s always nice to meet colleagues who are teaching, we always have interesting and engaging exchanges from it! (L14, workshop 1)
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Activity #3—Teaching perspectives
In the first iteration, teaching perspectives were not discussed in group work. Reflecting on them was proposed as an individual activity in the asynchronous mode, through the forums. This changed in subsequent iterations of Teknosofikum, and a stronger focus has been put on this activity, first in onsite workshops (iteration #2) and later also in the online kick-off (iteration #3). Each course participant was asked to complete an online survey, which would generate an individualized profile related to their own teaching perspective(s). A topic was also created by the design team in the virtual learning platform, with a video explaining five teaching perspectives and the corresponding learning theories.
Iteration #1These teaching perspectives are totally new to me […] I could have answered the test based on a different course and gotten different results; therefore, I don’t find it conclusive. My teaching is generally based on both teaching and supervision, which demand different approaches. As a teacher, I am keener to share my knowledge, and as a supervisor, I mostly enable the student to find his/her way and solutions. (L2, forum)
While there is the issue of big classrooms making it hard to nurture learning and self confidence in analysis, it is very much the idea guiding teaching at my university, I think. Social reform [one of the teaching perspectives], however, is much less clearly institutionalized. I think that my kinds of social reform—critique and justice around gender and sexuality—are not on the map. Hence, every engagement I do to push students towards these critiques feels like they are on my own account…meaning that if I fail in any way, like if students are unhappy with it, it is unclear to me what sort of [institutional] backup I will get. (CS1, forum)
We all come from various kinds of education, so I think it’d be useful to also hear the students. It could be a way of seeing yourself from the perspective of the student. This feedback would help you a lot. […] And if the theme is, e.g., assessment, it doesn’t matter if it’s Medicine students or Design students, then you have a theme that is the same for all of us, where we could sit down and have a discussion and check examples. (L4, round-up meeting)
.
Iteration #2In the group discussion, we realized that we have perspectives that are very alike! I would expect that we’d be more different from each other. This discussion was like a mirror. It helped us look both at the individual actions and at what we aim for, in our teaching. It was really interesting to learn about the others, a mirror for all of us. Thank you for choosing this way; it’s very concrete. It gives us personal agency and interdisciplinary dialogue. (CS7, onsite workshop 1)
It was quite difficult to understand the categories. They are too open-ended and miss out on a more direct discussion of what is our role as teachers. Aside from this, we had a similar experience to the other groups’. It was surprising to recognise our similarities. […] We also talked about the need to reflect more on teaching from the point of view of our corporate identity [our field and institution]. (D8, onsite workshop 1)
We had several doubts: Are we discussing learning in general or learning in higher education? Is this about theory or are we to think about concrete actions? Some questions were ambiguous, and we thought that the teaching perspectives should not be framed as a “checklist.” It should be considered, for example, that the course manager also has expectations about our teaching. So, how much can we really act upon our beliefs? (L8, onsite workshop 1)
.
Iteration #3
For the onsite workshop, the design team had planned an exercise for gathering feedback on the teaching perspectives exercise. After a 45-minute group discussion following the results of the initial online survey, course participants were asked to prepare some questions to submit to other participants in a plenary discussion. They did so through a new online survey, which yielded the following results (see Table 3):
Table 3 Participants’ questions on teaching perspectives, workshop 1, anonymously posted on Mentimeter. At the end of the workshop, each participant was also asked to fill out a survey regarding their takeaways. A total of 13 participants gave their feedback on the teaching perspectives activities (see Table 4 below)
Questions emerging from group discussions on teaching perspectives
How much are these five perspectives dependent on discipline (i.e., teaching domain)? For example, is the experience perspective more important in art teaching than the transmission perspective? How about teaching technology?
I want to have the students reflect, but the students are scared, do not have the basic knowledge, or do not dare to not have the right answer.
What is to be done when teachers are happy with the creative and empowering learning process and outcome—and the student, after the course, says they did not understand what the purpose was?
It’s problematic when you have 100 students and want to give feedback…but don’t have enough time.
What is effective teaching?
What is good teaching?
When do we do “transmission” teaching?
How can one bridge the space between theory and practice?
What is the distinction between course learning objectives vs. teaching perspectives?
How do the different teaching perspectives or teaching styles influence teaching activities—for example, can you do peer-to-peer teaching for all five?
Doesn’t good/effective/useful teaching involve all five perspectives?
It was very interesting to learn that—across very different institutions—we face quite similar issues of how to deal with designing and executing education/courses aiming for empowerment, when students are so focused on getting things “right.”
How does one use technology to facilitate constructive peer feedback/learning?
How does the context influence the teaching perspectives—for instance, the difference between classroom teaching and lectures with 300 students?
Do you think that that technology has changed the way students see themselves and, by extension, their view of their education?
I would like to see more emphasis given to the importance of paying attention to responsive processes learning.
Table 4 Participants’ takeaways activity on teaching perspectives, workshop 1, anonymous survey. The same feedback was requested from online participants at the kick-off meeting, with the following results (Table 5)
Takeaways from teaching perspectives activity (workshop)
I have become aware of new teaching perspectives.
This was interesting. I look forward to digging into it more. We had some very good discussions.
This was a good overview.
Networking with people was useful.
I appreciated getting new ideas to implement digitization with a critical perspective in teaching.
I became more clear about my own preferences.
The activity confirmed my approach.
It was helpful to learn of the experiences and teaching perspectives from other disciplines.
I am now more aware of when I apply certain ways of teaching, and I could perhaps even inform the students about why they are taught in specific ways in specific contexts.
The activity showed the complexity in diverse perceptions of what teaching is and how we teach as individuals.
I learned that I both value and enact a lot of empowerment in my teaching, which I think is very much suited for the course in mind.
It is general and broad. Some new perspectives were provided in the teaching and group works.
The activity provided a nice overview but was far from reality (in practice, it is more mixed).
Table 5 Participants’ takeaways from the teaching perspectives activity, kick-off meeting, anonymously posted on Mentimeter
Takeaways from teaching perspectives activity (online)
This was interesting. I would have loved having more time to discuss the content.
This was very interesting—great to know.
Food for thought on how we adapt the different teaching styles to context and students’ personalities.
OK, I am looking forward to getting new inspiration.
I appreciated the content on the relationship between intentions, actions, etc.
There might be discrepancies between intention and action; the reality of the classroom can be a factor.
There was an interesting debate on individual profiles and takes on professional identity.
It was nice to hear how others interpreted their results.
I found it noteworthy that my beliefs and my intentions scored higher than my actions!
The online participants also commented spontaneously on the teaching perspectives exercise a few times during the midway meetings and in the forum. They referred both to the exercise (survey and discussion) they had participated in during the kick-off meeting, to breakout rooms, and to a summarizing video they could watch in the virtual learning environment (Fig. 7).
Fig. 7 Participants’ posts about teaching perspectives in the forum
The five teaching perspectives are very cool—eye-openers. I understood also why I do what I do, and it’s very empowering. I am sending students to the industry and to learn from each other, and there’s a lot of complexity. Part of my course is lecture. (CS16, midway meeting)
I think that the very best educators [for teacher professional development] are those who really know what they are talking about. Smart methods cannot replace expertise but can help the learning process. (CS19, midway meeting)
Activity #4—Redesign of the virtual learning platform
In the process of Teknosofikum’s reconceptualization and redesign, some common critiques emerged from contrasts between participants’ expectations and their experiences during the course, both in iteration #1 and in iteration #2. All groups stressed the need for more communication and clearer information about the learning path and the required time investment—in short, the user journey. Bearing these issues in mind, participants reflected upon the course’s topics and proposed new design elements for the subsequent iteration (see Fig. 8).
Fig. 8 Posters constructed by participants in Re-design activity, during onsite workshop 2, iteration #2
Groups A and B focused particularly on the format of contents, suggesting that some of the videos should be replaced by podcasts or papers. In these redesign proposals, attention was drawn to micro elements of the course, rather than the overall structure and purposes. On the other hand, groups D and C were more innovative in their proposed overviews of the course, advocating a spiral model and a flipped model, respectively. In the following, a few excerpts from their video-recorded feedback convey the arguments for these choices.
Group D—spiral modelThis [points at the center of the image] should be a circular thing, not a linear thing, so that you could actually come back again and keep on improving. That’s why we have this spiral model in the middle. […] We really liked the overall framework; it is like a gift to us. Of course, in the beginning you don’t get it in depth, so there’s something about revisiting the topics in this…well, we called it a journey. (D6, workshop 2)
We had some very practical new ideas about visiting each other at different institutions, having a look at the “operation room,” and getting feedback about teaching. We talked about the fact that most people are too polite to be honest, and it could be really interesting to have someone by your side to tell you, “This is really boring,” or, “This is really powerful”—honest opinions. That would also allow us to build some deeper relationships. […] Or we could have a common case, that we implement at different institutions and then compare with each other. We included in our model a case bank, which would be extremely relevant for all the colleagues here. With it, we could do something at the student level, or better, at the teacher-student level. (CS7, workshop 2)
It is so much easier now to call any of you, because we have been in the same room and have shared this experience before going online, so you are not total strangers. This aspect is very important, as networking is also relevant for us academics. It’s so seldom that people are actually really honest and say what they think works and what they think does not work. So, being able to facilitate this safe space of shared practice—I don’t know what to call it—where it feels “all right,” that would really be teaching me something. (D6, workshop 2)
You see that there is a “back” line that indicates iterations. As we were saying, it could be stretched out to “lifelong.” When the idea is to develop critical reflections about teaching, this is nothing that we do like this [snaps fingers]. Instead, we could all relax if we visited a different colleague at different institutions every term and give feedback to each other about teaching, so that we really improve all the time. That makes it really concrete to us, close to our practice. (CS7, workshop 2)
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Group C—flipped modelI think it is essential to have some time to work with each other in an unstructured way. […] Fundamentally, what we propose is a kind of flipped procedure, which starts by creating personas and discussing how our field engages with technology, sharing with each other how we construct technology, not as teachers, but from the point of view of our disciplines, the fields that we’re acting in. To give each other this vocabulary about what technology is, how we understand technology to be […], providing some examples, and having some collaborative discussions about how tech affects the field. And then, we would meet online and take a more pedagogical approach of how to teach using technology, maybe taking the approach of how things are changing … this might be one way to move forward. Then, when we meet again, we could refine our personas, update our teaching styles, and reflect on technology education and how we could incorporate technology in multiple dimensions. (D7, workshop 2)
Once you presented the circular idea [looks at the members of group D], that would also benefit our model, where we thought that teachers from Law, Design, and Computer Science could collaborate on designing a case for the three areas. That could be done by revisiting the contents at different moments. Or this could be done by having all the participants from the same field, e.g., Design, working together on a case. (L8, workshop 2)
We also pointed out some takeaways. I feel that my attention has really been raised during the course. I am much more aware of the issues that concern technology in education, and I will live with that. (D7, workshop 2)
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To sum up, three core principles appear to be relevant to the reframing of Teknosofikum: the modularity of contents, peer collaboration, and the variety of formats. For the purposes of this study, we will analyze how teacher collaboration appears as a transversal aspect in these results.
Discussion
We begin this section by addressing the second and more specific research question that guided this study:
How can activity-oriented design methods contribute to collaborative knowledge building in a professional development program for higher education teachers?
Our results reflect the increasing complexity of the Teknosofikum course and concept over their development in the three iterations, with a total of 64 participants completing the course.
Overall, a first result that emerges from our data analysis is that AOD has contributed to differentiating the tasks that course participants were asked to perform, with the purpose of achieving different aims: reflection (activity #1), discussion (activity #2), theory-practice alignment (activity #3), and participation (activity #4). Among these goals, the latter was mostly directed at the improvement of the course for subsequent iterations of the project, while the other three defined achievements of both individual participants and groups.
Individual achievements.
Among the individual achievements, the participants mentioned that reflections on topics in the learning platform are useful (activity #1), but practice-based reflections (activity #3) are even more meaningful, as they can be “very concrete” and may promote “personal agency.” Based on a similar line of reasoning, the contents that participants found most relevant to their own development as higher education teachers were those that provided them with examples of activities, tools, and strategies they could use in their teaching. As one participant put it, what she found in Teknosofikum was inspiring ideas “for new ways to do stuff.”
Some common critiques have also emerged from the participants’ experiences during the course. They have stressed the need for more communication and clearer information about the required time investment—that is, the user journey—and they have expressed some doubts about the design of some activities. Regarding activity #3, for example, one participant said, “It is general and broad,” while another described it as a “nice overview … but was far from reality.” Doubts were also expressed about the core concept discussed in the activity on teaching perspectives: “What is effective teaching?”, “Are we discussing learning in general or learning in higher education?”, “Is this about theory or are we to think about concrete actions?”
It is worth emphasizing that, even in these critiques, it is possible to discern a high degree of reflection that benefits teachers in terms of professional development. However, the findings that mostly relate to our focus of analysis are the ones that concern collective achievements during the Teknosofikum course.
2) Group achievements.
Group work and collaborative practices have proven to be the most meaningful, as regards teachers’ professional development. Data analysis shows that all three key features found in the literature on collaborative knowledge-building practices are present in the reports on the four selected activities, both online and onsite. We examine these features in detail below.
Trust.
When asked to share their opinions on the Teknosofikum format (activities #2 and #4), the participants did not express any special interest in specific educational tools or platforms, or in guidelines for using technologies in teaching. Rather, they stressed the power of peer exchange, unstructured discussions, and mutual feedback regarding teaching formats and strategies.
What they mentioned as “really powerful” in the project is the “shared experience” and “shared practice” of “being in the same room,” thus moving from being “total strangers” to creating networks of peers. In the words of one participant, Teknosofikum has created a “safe space” where “it feels all right” to give each other honest feedback. This result corroborates the importance of collaboration and teamwork in multidisciplinary fields (Romeu et al., 2016) and shows the potential of working actively around a common task. This result also supports the idea that, in a course for higher education teacher development, what is most effective and meaningful is an approach that emphasizes integrated knowledge, where disciplinary perspectives come into play and where networking is part of growing as a professional.
Deep interaction.
The focus on group activities allowed participants to address complex questions (e.g., “What should technology education address?”) using a practice-based approach. This fostered intensive and deep interactions among the course participants, who particularly appreciated the collaborative activities centered on specific tasks. In the onsite workshop, for example, activity #4 required the use of posters, where different opinions and debates had to be summarized using keywords. From a bottom-up perspective, the participants needed to redesign the course for the next iteration, and they had the chance to explore what they knew about technology education and what they thought about it. Two groups out of four concluded that, for higher education teachers’ professional development, technology education is a “lifelong process,” which cannot be completed in a 37-hour course but can at most be initiated by it. They designed a model of exchange that enabled their newfound networks to survive after Teknosofikum, in order to “build some deeper relationships.” In addition, many participants asked the design team to provide them with access to the virtual learning environment after the course, so they would be able to check the materials again, for further ideas for teaching.
Discussing beliefs/values.
Participants described sharing their teaching beliefs and values with peers (activity #3) as “an eye-opener,” a “bridge between theory and practice,” and a “mirror,” as they discovered similarities in terms of practices and challenges with colleagues from other institutions. Most participants did not know that their teaching practices were driven by distinctive epistemic beliefs, and they had fun discovering the discrepancies between what they think is important and what they do to achieve their purposes as teachers. Working in a collaborative and cross-disciplinary way therefore provided opportunities for articulating their thoughts and learning about themselves. These results show how the involvement of participants in creating a productive collaborative environment can engage them both with theory and practice (Goodyear et al., 2021). In this sense, AOD methods have proven effective in achieving a reflection about epistemic and pedagogical grounds of participants’ teaching practices (Pischetola, 2020).
Conclusion
The purpose of this design-based research study was to qualitatively assess the potential of AOD methods for higher education teacher collaboration in the context of a program for professional development. Our results demonstrated that AOD can be very useful for creating an environment of active learning, participation, and collaboration centered on specific activities that higher education teachers might consider relevant for their own teaching. Moreover, the research sheds light on how teacher professional development itself can be conceived as a space for collaborative learning, per the first research question guiding this study.
Based on the data analysis and the results presented in the previous section, we can identify at least two elements that characterize a program of teacher education as one that might enhance collaborative knowledge-building. First, collaborative activities are much more likely to be productive when a safe learning space for participating teachers is generated, whether online or onsite. In our study, the four selected activities allowed for an exploration of situated and self-aware learning (Goodyear et al., 2021), as each teacher applied their ability to think consciously about educational design (Scott & Lock, 2021) and technology adoption (Pischetola, 2021). The safe space—as mentioned by one interviewee—consisted of an environment of informal discussion and feedback, where participants felt free to share their experiences. This result confirms that “academic development impact cannot, and should not, be solely restricted to quantifiable data” (van der Rijst et al., 2022, p. 2), but it should include social relations and sharing practices as important outcomes. Following design-based research, “safe learning space” can become a powerful design concept in the implementation of teacher professional development programs.
Second, in line with previous research (Cumbo & Selwyn, 2022; Santaolalla et al., 2020), this study has demonstrated the potential of collaborative practices in creating cross-disciplinary networks of academics who will continue to share ideas, practices, and teaching experiments. In fact, participants expressed the wish to continue to communicate and give each other feedback after the course, in order to further develop their teaching practices and experiment with new tools and strategies. In this result, we recognize the potential of collaborative practices for transforming learning into action (Markauskaite & Goodyear, 2017), which is especially important for the effective use of technologies in teaching (Riedner & Pischetola, 2021). Due to the qualitative nature of our study and the small sample size, this result cannot be generalized. Nevertheless, this finding offers an insight of aspects that higher education teachers value in a professional development program. It also offers valuable lessons regarding the format of the activities that could be implemented to improve teachers’ awareness about their own beliefs and ideals guiding their actions.
As our results illustrate, one crucial step toward increasing teachers’ levels of motivation consisted in investing in the quality of interactions that characterized the group work in Teknosofikum. In all the proposed activities, course participants shared personal experiences, discussed personal values and beliefs, and reflected together on the direction of in-depth exchanges. In this process, they also recognized many of their similarities, despite belonging to distinct disciplinary fields and institutions and coming from different backgrounds. They sometimes mentioned their surprise at finding such a fertile base of shared feelings and experiences, given the fact that they had not met before. Therefore, “network” is the second element emerging from our study that has both theoretical and practical implications. In fact, this aspect confirms the concept of learning as being culturally and historically situated (Engeström et al., 1999), but it also gives value to encountering different values and epistemologies (Goodyear et al., 2021). In practical terms, creating and engaging with a network of shared and collaborative practices is fundamental to innovation in the professional development of higher education teachers. As Dollinger et al. (2018) have pointed out, the quality and depth of interactions are key elements for meaningful collaborative knowledge-building.
A final point emerging from this study concerns the importance of designing professional development courses that consider teachers themselves as designers (Hjalmarson & Diefes-Dux, 2008; Yoon et al., 2006). At this respect, it is worth emphasizing that the Teknosofikum course design changed radically over the three iterations (Pischetola et al., 2022), in response to critiques, requests, and suggestions offered by the course participants. The iterative virtual learning platform redesign facilitated refinements of the AOD methods, inclining participants to become more interactive as the course progressed, which in turn resulted in increased benefits from mutual feedback.
Involving teachers in the redesign of the course is also a way to foster their self-efficacy (Wang et al., 2004) and agency in making decisions (Brodie, 2021) on what a professional development program should offer. This supports the conceptualization of teacher professional development as a process that aims at extending teachers’ commitments as “change agents” (Day, 1999), where agency is not merely an individual achievement, but rather a dialogic process between the individual and the educational ecosystem (Miranda & Pischetola, 2020). In this sense, AOD and collaborative knowledge-building practices can be useful to frame meaningful proposals for professional development in higher education.
Limitations and recommendations
Several limitations underlie our study. Firstly, the sample studied is small (N = 64), which constitutes a limitation on the generalizability of our results. Due to this small sample size, it is reasonable to estimate that the participants’ responses might not reflect proportionally the whole teacher body at the four participant institutions. Two further iterations of Teknosofikum will be conducted in 2023 and will include increasingly larger participant groups, as well as extend the project to other higher education institutions in Denmark. Therefore, it will be instructive to observe the AOD methods in those iterations and to compare their results with the previous data analysis. In the long-term, if Teknosofikum will be establish as a course that all Danish higher education institutions offer to their teachers, it will also be possible to undergo quantitative and more generalizable analysis.
Another limitation affecting the generalizability of our findings is the relatively narrow disciplinary origins of course participants, being recruited exclusively from the fields of Design, Computer Science, and Law. Moreover, three out of four partner institutions are relatively small, in terms of the number of faculty members, while the fourth (the University of Copenhagen’s Faculty of Law) is approximately four times the size of any of the other three. The number of course participants was calibrated proportionally in the project design. Nevertheless, this element could have a relation to the culture of origin at each institution, in the sense of being more or less focused on collaborative knowledge-building practices. In the next two iterations, the course will be open to participants from Social Sciences and the Humanities. With teachers from other fields, the results might be significantly different.
Thirdly, our analysis did not take into account the seniority of the course participants and its relation to collaborative practices. Further research should investigate the relationship(s) between these aspects—disciplinary fields, institutional culture and size, and seniority of the participants—and the motivations of higher education teachers pertaining to participation in collaborative group work.
Finally, a limitation that our study shares with all design-based research is the fact that learning is studied in a designed environment and considered as an experiment guided by theoretical constructs – namely AOD in our study. Despite design-based research having internal coherence in terms of methodology, there is no general agreement among researchers about how to ensure validity in a designed context (Jan et al., 2010). We reckon that to strengthen the validity of our study, it would be needed to unpack the design process of the project in its different iterations. This was not examined here for space limitations. However, the design principles of Teknosofikum have been partially covered in the work by Pischetola et al. (2022) and will be the core topic of another forthcoming article.
Future studies applying the methodology of design-based research in educational settings might consider focusing on the relationship between the design principles of a course and its outcomes in terms of teacher collaboration. Promising lines for research include both quantitative and qualitative approaches examining the impacts of activity-oriented design within professional development in higher education, with emphasis on social relations, shared practices, and network formation among teachers. Another important aspect to be deepened is the potential of activities that aim at teachers’ reflections on their own beliefs, as well as the theoretical and epistemic grounding of each component of their practice.
Acknowledgements
The authors sincerely appreciate the contributions of the participants in the first three iterations of the project.
Funding
This research was supported by the Danish Ministry of Higher Education and Science – Styrelsen for Forskning og Uddannelse, grant 9156-00008B, project Teknosofikum.
Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Conflict of interest
The authors declare no conflicts of interest.
1 In the relevant literature, it is also known as continuing education, continuous professional development, in-service teacher education, or lifelong professional learning.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735077 | NO-CC CODE | 2022-12-14 23:28:32 | no | Educ Inf Technol (Dordr). 2022 Dec 5;:1-30 | utf-8 | Educ Inf Technol (Dordr) | 2,022 | 10.1007/s10639-022-11490-x | oa_other |
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Evid Based Dent
Evid Based Dent
Evidence-Based Dentistry
1462-0049
1476-5446
Palgrave Macmillan UK London
36477677
831
10.1038/s41432-022-0831-0
Review
Mental health and wellbeing interventions in the dental sector: a systematic review
Plessas Anastasios [email protected]
4143210270001
Paisi Martha 4143210270001
Bryce Marie 4143210270002
Burns Lorna 4143210270001
O’Brien Timothy 4143210270001
Hanoch Yaniv 4143210270003
Witton Robert 4143210270001
4143210270001 grid.11201.33 0000 0001 2219 0747 University of Plymouth, Peninsula Dental School, Faculty of Health, Plymouth, UK
4143210270002 grid.467855.d 0000 0004 0367 1942 University of Plymouth, Peninsula Medical School, Faculty of Health, Plymouth, UK
4143210270003 grid.5491.9 0000 0004 1936 9297 University of Southampton, Business School, Southampton, UK
7 12 2022
18
3 2 2022
30 3 2022
© The Author(s), under exclusive licence to the British Dental Association 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Introduction UK dentists experience high levels of stress, anxiety and burnout. Poor mental health can lead practitioners to exit the profession, contributing to workforce and service loss. Therefore, there is a need to focus on interventions to protect the mental health and wellbeing of dental teams. Three levels of intervention can be deployed in the workplace to support mental health and wellbeing: primary prevention, secondary prevention, and tertiary prevention.
Aim The aim of this systematic review was to identify evidence on interventions used to prevent, improve or tackle mental health issues among dental team members and dental profession students in countries of very high development.
Methods This systematic review was conducted according to a predefined protocol and reported according to PRISMA guidelines. The MEDLINE, Embase CINAHL, DOSS, Scopus, and PsycINFO databases were searched. Prospective empirical studies were considered for inclusion. The Effective Public Health Practice Project Quality Assessment Tool (EPHPP) was used to assess the methodological quality of the included studies. The identified interventions were categorised according to level of prevention.
Results The search yielded 12,919 results. Eight studies met the inclusion criteria. All of the studies concerned dentists or dental students. There were no studies for other groups of dental professionals. No primary prevention-level studies were identified. Secondary prevention-level studies (n = 4) included various psychoeducational interventions aiming to raise awareness and improve coping skills and led to significant improvements in stress levels and burnout of dentists and dental students. Tertiary prevention-level studies (n = 4) mainly employed counselling which was shown to be beneficial for dentists and students experiencing psychological ill-health.
Conclusions Mental wellbeing awareness should be put at the centre of dental education and the workplace. Leadership and innovation are required to design primary-level interventions which can be implemented in the UK dental sector, with its distinct organisational and service characteristics.
Supplementary Information
Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1038/s41432-022-0831-0 für autorisierte Leser zusätzliche Dateien abrufbar.
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pmcKey points There is a paucity of research and evaluation on interventions to improve mental health and wellbeing within the dental sector, especially at primary prevention level.
There is a need for robust studies to evaluate the effectiveness of psychoeducational and/or organisation/systems-level interventions. Examples of such interventions can be adapted from other healthcare professions to fit in with the distinct nature and characteristics of dental education and dental practice.
Raising awareness and facilitating early recognition of poor mental health as well as effectively responding to these early signs should take place as early as a dental professional's training and continue throughout their professional lives.
Introduction
UK dentists report high levels of stress, anxiety, and burnout, with general dental practitioners (GDPs) and community dentists as well as dentists working in England being more severely affected than dentists in other fields of practice.1,2 Signs of burnout may appear as early as the undergraduate years and the first years of clinical practice.3,4 Despite these indications, data on dental care professionals' mental wellness are currently scarce.5
Dental care teams face numerous stressors in their daily practice; namely: business-led stressors, clinical situations-led stressors, society and person-led stressors, regulation-led stressors and working environment-led stressors.5 Additional stressors due to the COVID-19 pandemic have also been reported among dental professionals, such as fears for the health of friends and family, financial viability, and personal protection.6,7A model developed by Salazar et al. (2019) depicts the complex interplay between different determinants of dentists' mental health and wellbeing including personal factors, career stage, professional and social relationships, job specification, workplace characteristics, dental healthcare systems and regulation.8 A study by the British Dental Association (BDA) suggested that working conditions, working environment, regulatory bodies, and the NHS were the most significant factors impacting dentists' mental health and wellbeing.9 Regulation and fear of litigation have been identified as the most stressful aspects of practising dentistry in the UK.2,10
Poor mental health and wellbeing can affect dentists' decision-making and performance which could impact on patient care and safety.11,12,13,14 Poor mental health and wellbeing can also have a negative impact on workforce sustainability. Dentists facing mental health and wellbeing difficulties may consider exiting the profession/UK practice; for example, through retirement, migration, or changing career.13,14,15 The profession is currently facing a sustainability crisis and thus interventions to safeguard the mental health and wellbeing of dental teams are urgently needed.16,17,18 When it comes to preventing mental health and wellbeing issues in the workplace, three levels of intervention can be employed: primary prevention, secondary prevention and tertiary prevention.19 A definition for each intervention/prevention level is provided in Figure 1. Each level in turn places separate but related responsibilities on both the individual and the system or environment they operate in (that is, practice, service, organisation, healthcare system).19 The available evidence identified in the literature will be discussed in turn as regards to these levels.Fig. 1 Levels of intervention for prevention of mental health and wellbeing issues in the workplace19
The aim of the present review is to answer the following research question: 'What interventions have been used and evaluated to prevent, improve, or tackle mental health issues among dental team members and dental profession students in countries of very high development?'
Materials and methods
Protocol
This systematic review was conducted according to a predefined protocol and reported according to PRISMA guidelines. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42021261854. This review is an update of a rapid evidence assessment commissioned by the General Dental Council.5
Selection criteria
Studies evaluating the effectiveness of interventions implemented in a dental setting (education, primary or secondary care) in countries of very high development as indicated by the Human Development Index (HDI),20 to improve mental health and wellbeing were considered for inclusion. Studies presenting self-reported coping strategies or interventions whose effect had not been evaluated were not considered for inclusion. Only studies reported in English were included.
Search strategy
A sensitive and comprehensive search strategy was developed by an information specialist. The strategy was comprised of terms for mental health or wellbeing, and dentistry. The following bibliographic databases were searched on 28 June 2021: MEDLINE, Embase, CINAHL, DOSS, Scopus and PsycINFO. The search strategy used for MEDLINE is provided in online Supplementary File 1. Supplemental searching including backward and forward citation searching against the included studies was also performed.
Screening and selection of studies
The citations retrieved from the above search were inserted into the reference management software Endnote X9. The first author screened all the titles and abstracts of the retrieved citations using the Rayyan systematic review web app,21 while the second reviewer independently assessed 20% of the results set. Inter-rater agreement was very high (97%) for this random sample of citations. Full-text screening was completed independently by the two reviewers. Any differences concerning eligibility after full-text screening were resolved through consensus. A record of reasons for excluding studies was kept during the review process and presented in online Supplementary File 2.
Critical appraisal
The quality of the included studies was assessed independently by both authors using the Effective Public Health Practice Project Quality Assessment Tool (EPHPP). Any disagreement in the ratings was resolved with discussion.
Data extraction
The data of included studies were extracted by a single reviewer and verified by the second reviewer, using a piloted data extraction form. Any disagreement was resolved with discussion.
Results
The electronic searches yielded 12,919 citations. After the duplicates were removed, 7,772 titles and abstracts were screened for relevance. Of those, 22 were considered eligible for full-text screening and nine articles met the inclusion criteria. Two articles presented results of the same study in different time points, and hence are treated as the same study.22,23 Therefore, eight studies were included in this systematic review. The selection process for relevant studies and the numbers at each stage are shown in Figure 2. No new studies were found after performing forward and backward citation searching against the included studies.Fig. 2 PRISMA 2020 flowchart: study selection process
Study characteristics
The study characteristics are presented in online Supplementary File 3. Overall, the study samples were low, ranging from 5-103 participants. Three studies were conducted in the US,24,25,26 two in England,27,28 one in the Netherlands,22,23 one in Saudi Arabia,29 and one in Chile.30 The majority of studies recruited dental students,24,25,26,29,30 while only three studies recruited dental practitioners.22,23,27,28 There were no studies recruiting other dental professional groups.
Methodological quality
All studies used quasi-experimental designs. Two were judged as of moderate quality24,29 and the rest of weak quality.22,23,25,26,27,28,30 The critical appraisal ratings are presented in Table 1.Table 1 Critical appraisal results
Study Selection bias Study design Confounders Blinding Data collection method Withdrawals and dropouts Global rating
Aboalshamat et al. (2020) Moderate Moderate Strong Weak Strong Strong Moderate
Adams (2017) Weak Weak Weak Weak Strong Weak Weak
Brake et al. (2001)
Gorter et al. (2001)
Weak Moderate Weak Weak Strong Strong Weak
Chapman et al. (2017) Weak Moderate Strong Weak Strong Moderate Weak
Gonzalez & Quezada (2016) Weak Weak Weak Weak Strong Strong Weak
Metz et al. (2020) Strong Moderate Strong Weak Strong Strong Moderate
Newton et al. (2006) Weak Moderate Weak Weak Strong Weak Weak
Piazza-Waggoner et al. (2003) Strong Moderate Weak Weak Strong Weak Weak
Outcome measures
A summary of the outcome measures used in the identified studies alongside a short description of the tools used is given in Table 2.Table 2 Outcome measures
Outcome measure/tool Description of tool Citations
Anxiety
Dentists Anxieties in Clinical Situation Scale (DACSS) It consists of 20 frequently experienced stressful situations. Dentists are asked to rate their anxiety for each situation on an 11-point Likert scale anchored 0 (not at all) & 10 (the most intense emotion you can experience). For each item they are asked, 'Does the anxiety ever change something about the way you work?' and are asked to indicate yes or no (Y/N). The scale has 2 subscales; the DACSS-R which rated anxiety and the DACSS-C which reported change in decision-making. Chapman et al. (2017)27
Depression, Anxiety and Stress Scale (DASS-21) It is used to measure the levels of depression, anxiety, and stress. It contains 21 questions with subscales for each of the three domains. Each question has four answers, ranging from 0 'Did not apply to me at all' to 3 'Applied to me very much, or most of the time.' The score in each subscale ranges from 0 to 21, and the lower the score, the lower the level of psychological distress. Aboalshamat et al. (2020)29
Spielberger State-Trait Anxiety Inventory (STAI) There are 2 subscales within this measure. First, the State Anxiety Scale (S-Anxiety) evaluates the current state of anxiety, asking how respondents feel 'right now' using items that measure subjective feelings of apprehension, tension, nervousness, worry, and activation/arousal of the autonomic nervous system. The Trait Anxiety Scale (T-Anxiety) evaluates relatively stable aspects of 'anxiety proneness' including general states of calmness, confidence, and security. The STAI has 40 items, 20 items allocated to each of the S-Anxiety and T-Anxiety subscales. Piazza-Waggoner et al. (2003)26
Burnout
Malshach Burnout Inventory (BMI) It contains 22 statements which relate to each of the three burnout domains, emotional exhaustion (EE), depersonalisation (DP) and personal accomplishment (PA). Respondents are asked to use a seven-point Likert scale to indicate the frequency with which they experience the feeling described by the statement, ranging from 0 (never) to 6 (every day). Summing the appropriate items derives scores for each of the three domains. Indicative of burnout are high scores on EE and DP and low scores on PA. No summative burnout score is made. Brake (2001)22
Chapman et al. (2017)27
Gorter (2001)23
Depression
Depression, Anxiety and Stress Scale (DASS-21) It is used to measure the levels of depression, anxiety, and stress. It contains 21 questions with subscales for each of the three domains. Each question has four answers, ranging from 0 'Did not apply to me at all' to 3 'Applied to me very much, or most of the time.' The score in each subscale ranges from 0 to 21, and the lower the score, the lower the level of psychological distress. Aboalshamat et al. (2020)29
Impostor syndrome
Clance Impostor Phenomenon Scale (CIPS) It consists of 20 Likert-scale questions, with responses ranging from (1) not at all true to (5) very true. A total score ranges from 20 to 100. The higher the score, the more frequently and seriously the Impostor Phenomenon interferes in a person's life. Metz et al. (2020)24
Resilience
Resilience scale RS-14 It is a seven-point Likert scale. Total scores range from 14 to 98, and the higher the score, the greater the resilience. Aboalshamat et al. (2020)29
Psychological health and wellbeing
Clinical Outcomes in Routine Evaluation (CORE) It is a self-report measure of psychological distress designed to be administered before and after counselling or psychotherapy. The client is asked to respond to questions about how they have been feeling over the last week, using a 5-point scale ranging from 'not at all' to 'most or all of the time'. It covers four dimensions: subjective wellbeing, problems/symptoms, life functioning and risk/harm. Newton et al. (2006)28
Counselling Centre Assessment of Psychological Symptoms - 34 (CCAPS-34) It is a 34-item, standardised, multidimensional assessment tool designed to be administered before and after counselling or psychotherapy. It provides a brief measurement tool targeting symptoms and presenting problems that most commonly affect students in university settings. Items on the CCAPS-34 are scored along a 5-point, Likert-type rating scale. Adams (2017)25
General Health Questionnaire (GHQ-12) It consists of 12 items, each assessing the severity of a mental problem over the past few weeks using a 4-point scale (from 0 to 3). It is comprised of 6 positive and 6 negative items to assess positive and negative mental health. The score can range from 0 to 36, with higher scores indicating worse conditions. A bimodal scoring can also be used, ranging from 0 to 12, in which case a cut-off point of >3 is a determinant for psychological ill health. Newton et al. (2006)28
Outcome Questionnaire - 45.2 (OQ 45.2) It comprises of 45 items associated with a person's quality of life, designed to measure repeatedly changes during and after counselling or psychotherapy. It yields a total score in which higher scores indicate lower levels of general wellbeing. Its cut-off point is 73, therefore scores under 73 belong to the normal population and those above 73 belong to the dysfunctional population. It also provides information on three sub-scales: anxiety-depressive symptomatology (DS), interpersonal relations (IR), and social relations (SR), whose cut-off points are 43, 16 and 14, respectively. Scores above these values imply significant interference in the life of the individual. Gonzalez & Quezada (2016)30
Outcome Rating Scale (ORS) It is a four-item measure designed to assess overall counselling or psychotherapy outcomes. The items assess individual, interpersonal, social, and overall wellbeing. Adams (2017)25
Psychological Well-Being Scale - Short (PWB-S) It is an 18-item seven-point Likert-type scale with responses ranging from 1 'strongly disagree' to 7 'strongly agree.' It measures six psychological fields of wellbeing: autonomy, environmental mastery, self-acceptance, positive relations with others, purpose in life, and personal growth. Each one of the domains is calculated by sum field's questions. PWB-S is not represented as one total score. Lower scores reflect low levels of psychological wellbeing. Aboalshamat et al. (2020)29
Stress
Dental Environment Stress questionnaire (DES) The DES questionnaire assesses sources of stress associated with undergraduate course work and training in dental students. The DES can be used in two versions, the 38-item full version or the 16-item short version. Each item is scored in a four-point Likert scale, with scores ranging from one (not stressful) to four (very stressful). Higher scores on this scale indicate greater levels of stress. It includes six areas: academic load; pre-clinical and clinical practice; treatment of patients; faculty and administration; interpersonal relations and others. However, these domains may be adapted to each dental school's needs and characteristics. Gonzalez & Quezada (2016)30
Depression, Anxiety and Stress Scale (DASS-21) It is used to measure the levels of depression, anxiety, and stress. It contains 21 questions with subscales for each of the three domains. Each question has four answers, ranging from 0 'Did not apply to me at all' to 3 'Applied to me very much, or most of the time.' The score in each subscale ranges from 0 to 21, and the lower the score, the lower the level of psychological distress. Aboalshamat et al. (2020)29
Work Stress Inventory (WSI) This scale comprises a number of sources of stress and respondents are asked to indicate which source of stress they have experienced in their work life recently. Higher scores on this scale indicate higher amounts of stress. Newton et al. (2006)28
Primary prevention
No primary prevention studies were identified in the dental literature.
Secondary prevention
Studies on dentists
Only one study, employing a psychoeducational intervention, recruited GDPs. Chapman et al. (2017) examined the effect of a cognitive behavioural therapy (CBT)-based bibliotherapy continuing professional development (CPD) psychoeducational programme on GDPs' mental health, wellbeing and decision-making.27 The study had two arms. Both arms received a self-help CBT package specially designed for dentists, which was written to tackle stress by building resilience. The second arm received an additional three-hour face-to-face workshop.27 Twenty dentists were allocated to each arm of the study based on their willingness to participate in the workshop. The results of the study revealed that depression (DASS-21) and stress (DASS-21) were significantly reduced at six weeks compared to the baseline, with the reductions maintained at six months (DASS-21). Anxiety was significantly reduced at six weeks (DASS-21), but it relapsed back to baseline levels in six months. Significant improvements in the participants' burnout scores were also observed. In particular, emotional exhaustion was significantly reduced at six weeks (MBI) with the reduction maintained at six months (MBI), while personal achievement was significantly improved at six weeks (MBI); however, this was not maintained at six months. The authors also observed an improvement in dentists' decision-making with a significant reduction in hypervigilance at six weeks compared to baseline values (MDMQ), which was maintained at six months (MDMQ). Notably, there was no significant difference in any of the outcome measures across mode of delivery (self-help vs guided self-help). The participating dentists were overwhelmingly positive in their evaluation of the project and reported that they used most of its contents.27
Studies on students
Aboalshamat et al. (2020) introduced a life coaching programme delivered by five senior dental students who had received intensive coaching training by an expert coach.29 Students in the life coaching intervention group (44 female students) attended five one-on-one standardised 15-minute phone coaching sessions at the beginning of each week, while the control group (44 female students) received no coaching or other intervention during that time. All participants in both groups were asked to select a goal they wanted to achieve by the end of the intervention period (five weeks). The results showed that there were significant differences between the groups in depression (DASS-21), stress (DASS-21), and self-acceptance (PWB-S). However, there was no statistically significant difference observed for anxiety (DASS-21), resilience (RS-14) and the other components of the psychological wellbeing scale (PWB-S: autonomy, environmental mastery, positive relations with others, purpose in life, and personal growth).29
Piazza-Waggoner et al. (2002) compared two psychoeducational interventions. In this study, one group received training on relaxation strategies (that is, deep breathing, progressive muscle relaxation) and the control group attended a lecture on the relation among stress, anxiety, and health.26 Although both groups showed a reduction in their anxiety levels, both state and trait anxiety (STAI), the differences between groups did not reach statistical significance.26
Finally, Metz et al. (2020) assessed the impact of a psychoeducational intervention on dental students' feeling of impostorism.24 One hundred and three first-year dental students were recruited and were shown an 'Impostor Video'. The video's content included taped confessions from former dental students regarding their impostor thoughts and an explanation of the basic traits of the condition. The video elaborated on the impostor cycle and identified six specific coping mechanisms for impostor thoughts. The coping mechanisms presented in the video focused on preventing procrastination through study schedules and reducing the time spent on non-essential tasks. After the video, students were provided with small, double-sided reminder cards, containing a graphic of the impostor cycle and a summary of the six coping mechanisms. There was a statistically significant decrease in impostor thoughts following the intervention (CISP). The percentage of students exhibiting intense impostor experiences decreased from 13.6% to 4.9%. The majority of students indicated that the video was successful in raising awareness of the impostor phenomenon, and they recommended repeated exposures to the video throughout their course.24
Tertiary prevention
Studies on dentists
One UK-based study by Newton et al. (2006) evaluated the Dental Practitioner Support Service (DPSS) in Kent, available to dentists facing high levels of stress.28 This service included an initial assessment by a counsellor, followed by a maximum of six one-hour counselling sessions in a personalised, problem-focused programme. The programme sessions covered areas including personal issues such as high expectations of self; low self-esteem; unresolved traumatic experiences; home/work balance; practice issues such as paperwork and patient complaints; interpersonal stress within the practice; and concern regarding the ubiquity of stress among NHS dentists. The counsellors adopted various techniques included counselling and therapeutic approaches, teaching and role play, and the identification of information and resources. Of the 20 GDPs initially recruited, 16 participated in the study, and 9 completed a one-month follow-up. A statistically and clinically meaningful decrease in psychological health and distress (GHQ) was observed. Participants found the service acceptable and rated their progress in dealing and coping with their stress as good.28
In a study by Gorter et al. (2001), 19 Dutch dentists experiencing burnout received intensive counselling and three group sessions over six months. The control group was composed of 103 dentists similarly at risk of burnout, but who did not want to participate in the intervention. The dentists in the control group were subsequently divided into those who spontaneously took some action to alleviate their burnout, and those who did not take any further actions. Participants in the psychological intervention showed decreased burnout scores (MBI) at the end of the intervention.23 Dentists in the self-initiative group showed improvements in emotional exhaustion and personal accomplishment, while those who did nothing showed no improvement in MBI scores.23 However, Brake et al. (2001), presenting one-year follow-up results, demonstrated that participants in the intervention group demonstrated relapse in their burnout scores; however, those who had spontaneously acted to reduce their stress showed sustained improvements.22
Studies on students
In a very small-scale study (five participants) in Chile, dental students were offered eight 45-minute weekly psychotherapy sessions.30 These sessions aimed to educate the participants about symptomatology and help them cope with dental environment-related problems. After attending the eight sessions, all five participants reduced their perceived stress (DES).30 Two of the participants initially had dysfunctional psychological health scores (OQ-45.2) and their scores were deemed normal by the end of the therapy. The rest of the participants retained their scores within the normal range. Additionally, all participants reported that the intervention helped them improve their coping skills.30
Similarly, a US Dental School in Iowa offered counselling by a full-time psychologist in an in-house counselling office embedded within the school.25 Fifty-five students attended 251 counselling appointments, with an average of 4.5 appointments per student. A positive relationship was found between the number of counselling appointments and overall functioning and psychological wellbeing (CCAPS-34).25 Within the same dental school, lunchbreak outreach educational group sessions were offered, which students could voluntarily attend. These sessions were designed to increase student knowledge, awareness, and self-efficacy regarding psychological stress management practices and led to a moderate improvement in awareness, knowledge, and coping skills, but not an increase in willingness to engage in counselling.25 Interestingly, some of the students reported an increased willingness to seek counselling when the office was relocated to a more confidential setting in the building.25
Discussion
Although there is some research activity at the secondary and tertiary level within the dental sector, this review identified a lack of primary or organisation and systems-level strategies. Similarly, no studies have yet recruited dental professionals, other than dentists and dental students. Individualised counselling was found to be useful for dentists and students who have suffered or are suffering from psychological ill-health.28 These services are more likely to be accessed and used if they are confidential and they take into account the nuances of the dental environment.9,25
Psychoeducational interventions sit at the secondary prevention level and aim to facilitate early recognition of symptoms of poor mental health and wellbeing, while tackling the stigma around mental wellness. These interventions address the consequences rather than the sources of stress by improving the adaptability of the individual to the workplace environment, and the organisation or system's structure and culture.19 Evidence from the wider health sector suggests that psychoeducational interventions have a small albeit statistically significant and meaningful effect in reducing healthcare professionals' burnout and stress levels.31,32,33 These results are in line with findings in the dental literature with a bibliotherapy CBT CPD programme designed for GDPs being deemed successful in reducing practitioners' burnout and improving their decision-making.27 Well-powered and methodologically robust studies employing psychoeducational activities such as communication and coping skills training, emotional intelligence training, stress management training, resilience training, mindfulness-based practice, or combination are urgently needed.
Although secondary- and tertiary-level interventions have a useful role to play in the prevention and rehabilitation of mental health and wellbeing issues, their long-term effectiveness as stand-alone interventions may be questionable, unless attempts are also made to address the sources of stress alongside the organisational and systems structures and culture through primary-level prevention. The evidence from the broader healthcare literature advocates organisation-directed interventions as being more effective in improving healthcare workers' mental health and wellbeing.32 Most of these interventions aim to lessen workload pressures by reducing or changing shift patterns, while multifaceted approaches including structural changes, quality improvement and psychoeducational training have also been utilised in a minority of studies.32 Such interventions are currently not widely in use within dentistry.
While some stressors faced by dental professionals can be controlled by the individual, a systems-level approach would allow for modification or elimination of the stressor in the first place. For example, workload pressures imposed by the need to catch up with UDA targets in England is a frequently occurring stressor among GDPs.2,9,12 At a practice or service level, incorporating short breaks or time away from clinics within the work schedule or staff rotas may decrease the stress related to the heavy workload. On the other hand, at policy level, moving away from a target-based dentist remuneration system may be needed in order to positively impact GDPs' mental health and wellbeing through dental contract reform.
Such system-level change would be complex, and necessitate consideration of a wide range of factors beyond professionals' mental wellbeing, but may be even more pressing in the post-pandemic era. COVID-19 restrictions have adversely affected the capacity of NHS primary dental care services, causing a backlog in patient appointments and a widening gap in dental access across different population groups.17
Primary prevention strategies are often a vehicle for cultural change.19 In light of the impact of regulation and litigation on dentists' mental health and wellbeing, shifting the culture in dentistry from a blame culture to a safety culture is timely.34,35 'Safety culture' relates to the extent to which organisations or systems prioritise and support improvements in safety.36 A punitive approach to error, for example, encourages a blame culture and an increase in malpractice litigation, which can have a detrimental effect on practitioners' mental health and wellbeing. In addition, it can also lead to defensive behaviours and in turn, potentially jeopardise patient safety.37
It therefore becomes apparent that the collective attention and collaboration of UK policymakers, regulators and relevant stakeholders is urgently warranted. It is imperative we use the COVID-19 pandemic as an opportunity to put mental wellbeing awareness at the centre of the dental workplace and education, so that dental professionals and dental teams feel empowered to thrive and patient safety is optimised.38 The recently published Mental Health Wellness in Dentistry Framework provides a unique opportunity to make mental health a key priority and to encourage early recognition, intervention and safe signposting among all dental professionals and drive change through a systems-level approach.38
Conclusion
Mental wellbeing awareness should be put at the centre of the dental workplace and education. Early recognition of poor mental health as well as timely and effective response to these early signs should take place as early as a dental professional's training and continue throughout their professional lives. The findings of this review highlight the need to address 'latent' or 'system-related' factors in order to safeguard the mental wellbeing of dental team members and secure a sustainable workforce. Leadership and innovation are required to design and implement primary-level interventions in the UK dental sector, within its distinct organisational and service characteristics.
Supplementary Information
Supplementary Tables 1-3 (PDF 165KB)
Author contributions
AP: First reviewer: review protocol, study selection, critical appraisal, data extraction, data synthesis, production of draft manuscript. MP: Second reviewer: study selection, critical appraisal, data extraction, data synthesis, and critical review of manuscript. MB: Third reviewer: available to resolve disagreement if consensus could not be reached, methodology advice, critical review of manuscript. LB: Information specialist: search strategy and electronic searches, management of citations, critical review of manuscript. ToB: Input in discussion (implications for education, practice and policy), critical review of manuscript. YH: psychology-related expertise, critical review of manuscript. RW: Input in discussion (implications for education, practice and policy); critical review of manuscript.
Ethics declaration
The authors declare no conflicts of interest. This research is an update of a bigger project commissioned by the General Dental Council (GDC): 'Mental Health and Wellbeing in Dentistry: A Rapid Evidence Assessment'. The views and opinions expressed in this publication are those of the authors and do not necessarily reflect those of the GDC.
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| 36477677 | PMC9735078 | NO-CC CODE | 2022-12-14 23:28:32 | no | Evid Based Dent. 2022 Dec 7;:1-8 | utf-8 | Evid Based Dent | 2,022 | 10.1038/s41432-022-0831-0 | oa_other |
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Oper Manag Res
Operations Management Research
1936-9735
1936-9743
Springer US New York
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10.1007/s12063-022-00332-1
Article
Do quality and business excellence models improve quality and operational results in educational organizations? A repeated cross-sectional analysis
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Parast Mahour Mellat [email protected]
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Improving quality and operational practices in education organizations and developing a culture of continuous improvement are crucial yet challenging endeavors because of the complex nature of education organizations. While quality management practices can clearly improve the quality of these organizations in several aspects, empirical research for quality management in educational organizations is sparse because of the lack of suitable frameworks for assessing quality. In this paper, we present the first large-scale empirical study of implementing quality management practices in educational organizations in the United States. It is based on seven years of objective data for quality assessments by external professional reviewers as part of the U.S. government’s Malcolm Baldrige National Quality Award (MBNQA) program. Our findings provide empirical evidence for the reliability and robustness of the Baldrige model as an effective quality assessment for educational organizations. Controlling for the applicant’s year, our findings show that Information and knowledge management is a key influencer and predictor of Customer satisfaction and focus, and Management of process quality is a key influencer and predictor of Quality and operations results. This study also provides effective insight and recommendations for how to improve quality systems and achieve business excellence in educational organizations using the Baldrige model. The findings will therefore help managers and administrators to make informed decisions about key factors that impact quality in educational organizations.
Keywords
Quality management
Malcolm Baldrige National Quality Award (MBNQA)
Educational organizations
Quality results
==== Body
pmcIntroduction
Over the last several decades, quality management principles have shaped organizational thinking and business practices to improve organizational processes and achieve better customer satisfaction (Kok et al. 2001; Gonza´lez-Cruz et al. 2018; Parast and Golmohamamdi 2019). Although quality management research has helped both manufacturing organizations and service organizations to improve their quality and organizational processes, one important segment of the economy has had limited discussion in scholarly research: educational organizations.
The main challenge to understanding and implementing quality management in education is a lack of clarity about what quality means in the education context (Brockerhoff et al. 2015; Dicker et al. 2019). Quality in education is considered a multi-dimensional term: a term that is simultaneously dynamic and contextual (Krause 2012). There are multiple stakeholders involved in education, adding to the complex nature of managing quality in such a dynamic system (Latif et al. 2019). In addition, the meaning of customers and customer satisfaction is also not clear in education settings. While education can be viewed as a service, it simultaneously deals with both tangible dimensions (e.g., course materials) and intangible dimensions (e.g., advising and serving students) of quality. The ethical and social responsibility dimensions are also important in education settings (Harris et al. 2011), further adding to the complex nature of quality assessment in education.
The first step in understanding quality management in education settings is to develop a quality framework that will provide a holistic approach to understanding quality, using an established quality framework such as the EFQM or Baldrige model (Osseo-Asare and Longbottom 2002; Lomas 2004; Araújo and Sampaio 2014; Martín-Gaitero and Escrig-Tena 2018; Castka 2018). Despite the clear importance of quality in education, very limited scholarly studies have sought to understand quality management practices in education. We therefore aim to address this gap in the literature on quality management and business excellence by applying the model of the Baldridge Performance Excellence Program.
The Malcolm Baldrige National Quality Award (MBNQA) is an annual assessment program for quality and business excellence led by the National Institute of Standards and Technology (NIST), which is a part of the U.S. Department of Commerce. The MBNQA is an effective framework for assessing and improving an organization’s quality and operations, and it is said to be useful and applicable to any type of organization, regardless of size or industrial sector (Bandyopadhyay and Leonard 2016). For a long time, it was not possible to assess the impact of the MBNQA on enhancing organizational quality and operational results because the data for the MBNQA assessments were confidential and not publicly available.1 Therefore, understanding the long-term effect of quality management practices in educational organizations remains an unexplored area that warrants further research.
In this study, we seek to address these gaps by understanding quality practices in educational organizations (public schools, universities, and other non-profit educational organizations). To achieve this, we first examine how quality management practices can improve quality outcomes using the MBNQA criteria. The MBNQA is a robust framework, so it provides an excellent foundation to better understand quality issues in education in terms of theoretical rigor as well as managerial relevance (Parast 2015; Parast and Golmohammadi 2019; Parast and Safari 2021, 2022). In addition, by using scores from independent reviewers (which is embedded in the quality assessment process of the Baldrige program), we ensure that the data is objective. This approach to quality assessment avoids the shortcomings of collecting data through self-administered surveys (Sofaer and Firminger 2005). In addition, the Baldrige data for education organizations spans seven years, thus providing a suitable basis for examining the relationships between quality practices over time. This provides important evidence for moving beyond correlations analysis and establishing causality. This approach will therefore improve both the theory and practice of quality management in the education domain.
Quality management in education
Defining quality and its management in education settings is a debatable issue. Some argue that the concept of quality and the interplay between different entities in educational settings is similar to that of manufacturing and other service enterprises, but the concept of quality and how it is defined clearly needs to be refined to fit the nature of education (Owlia and Aspinwall 1997). Some argue that there is no clear definition of what quality means in education (Brockerhoff et al. 2015). Educational organizations deal with multiple stakeholders, each with its own idea of quality (Schindler et al. 2015). Thus, what students perceive as high-quality education may differ from that of an employer or a funding agency (Dicker et al. 2019). In addition, concepts such as ethics and social responsibility should be emphasized in education settings to prepare students for their future roles in society (Harris et al. 2011). Quality assessment in education should therefore develop a holistic and systematic approach that incorporates all the complementary perspectives of quality (Goldberg and Cole 2002).
Quality, ethics, and social responsibility
From a solely economic perspective, organizations’ primary objective is to maximize their profits and shareholder value; thus, in a competitive business environment, business and ethics are not necessarily compatible (Ahmed and Machold 2004). While the relationship between quality, ethics, and social responsibility has been widely debated for the business environment, the relationship and its internal compatibility in the context of educational organizations needs further attention to address the needs and interests of the various stakeholders.
Quality management studies have long acknowledged the link between quality and ethics. Ishikawa (1985) alluded to this by articulating how quality control principles relate to believing in the goodness of people. This is reflected in the Kaizen quality management concept of a continuous improvement in the quality of life for individuals (Evans and Lindsay 1993). The literature suggests that adhering to quality management principles shapes corporate culture and encourages ethical leadership principles; this is reflected in the MBNQA (Steeples 1994). While there is a relationship between quality and ethics from a theoretical perspective (Chen et al. 1997; Raiborn and Payne 1996), numerous unethical practices are prevalent in the business world. Boisjoly (1993) argues that such unethical practices mostly result from cultural failures and shortcomings in management systems, so implementing a quality management system like the MBNQA may address this issue.
Several authors argue that a quality management system can address the ethical dimensions of management systems and the institutionalized ethical principles within organizations. Wicks and Freeman (1998) note that TQM principles address management practices while promoting moral values. What is needed is to broaden the concept of quality, which has happened in the quality management domain. Indeed, the concept of quality has evolved from statistical values for quality control and process improvement to considering more nuanced factors like customer satisfaction, employee engagement, and learning and innovation (Kok et al. 2001; Perdomo-Ortiz et al. 2009; Maletič et al. 2014; Psomas and Antony 2015). The recent trends toward sustainability and social responsibility have led to the quality management literature focusing more on the role of quality in improving an organization’s relationship with its stakeholders (Parast 2013, 2014; Wagner 2015). Organizations that implement quality management practices are more inclined to adhere to the principles and premises of social responsibility and ethical conduct, suggesting the existence of direct links between quality, ethics, and social responsibility (Erwin 2011; Attig and Cleary 2015). Thus, implementing quality management in educational organizations could not only lead to improvements in business processes and outcomes, it could also provide a suitable platform for addressing codes of conduct, ethical principles, and corporate social responsibility for the various stakeholders.
Studies of quality in educational organizations
Research into quality in education has been conducted from three perspectives. The first perspective, which is by far the most dominant, is concerned with theorizing and conceptualizing quality in education. This stream of research provides different directions and conceptualizations for quality in education and discusses the challenges associated with measuring it (Crawford and Shulter 1999; De Jager and Nieuwenhuis 2005; Becket and Brookes 2006; Sharabi 2013). The second perspective on quality in education is concerned with assessing customer satisfaction, which involves primarily looking at students’ perceptions of quality for an educational organization and its instruction. This is largely influenced by the literature on service quality, which generally measures quality on a multidimensional scale that evaluates a service from the customer’s (i.e., the student’s) viewpoint (Parasuraman et al. 1985, 1988). Although this branch of research provides important insight into the quality of service delivery and student satisfaction, it is primarily concerned with customer interaction and the delivery of services, so it does not capture the inherent nuances of quality in an education setting (Verma and Parasad 2017). This stream of research examines the dimensions of quality in education and the service sector from a student’s point of view, and it has found that students regard as valuable components of a quality education features such as courses offered and delivered, information management and responsiveness, collaboration and comparisons, internal audit assessment, IT equipment and infrastructure, and library resources (Lagrosen et al. 2004). Finally, the third perspective on quality in education deals with measuring quality in education and identifying important quality practices to enhance quality outcomes and business results in education settings (Asif et al. 2013). While these studies provide insights into quality issues by conducting surveys, they usually suffer from weak research design, a poor methodological approach, and a limited view of quality, all of which raise concerns about the validity and reliability of their findings. Our study is concerned with this third perspective on quality in education. We use the Baldrige model for quality to examine the relationship between quality management practices and an organization’s operational and business results. We assess the impact of quality management practices (leadership, management of process quality, information and analysis, human resources development and management, and strategic planning for quality) on customer focus and satisfaction and operational and business results, as shown in Fig. 1.Fig. 1 Structural Model/Framework for Quality Management in Educational Organizations (Adapted from Parast 2015)
Table 1 presents a review of studies concerned with quality management in educational organizations. Most of these studies are concerned with conceptual development and the articulation of definitions for quality in education (Crawford and Shulter 1999; De Jager and Nieuwenhuis 2005; Becket and Brookes 2006; Sharabi 2013), as well as some case studies (Michael et al. 1997; Mergen et al. 2000; Goldberg and Cole 2002). While some studies survey students (Aly and Akpovi 2001; Csizmadia et al. 2008), most of them sought to solicit information from different stakeholders (e.g., students, faculty, and staff) about quality, and the analyses are limited to providing descriptive statistics about key variables. These studies mainly do not follow a rigorous process of survey design, sampling strategy, and survey implementation. A similar criticism can be directed against the qualitative studies, which provide some limited knowledge about the cases being discussed (Michael et al. 1997; Newton 2002; Sadiq Sohail et al. 2003). Therefore, these studies are limited to the specific sample and context being examined.Table 1 Studies of Quality Management in Educational Organizations (in alphabetical order)
Study Research Country Baldrige Major Findings
Ah-Teck and Starr (2013) Survey Mauritius Yes This study used the MBNQA principles/model to evaluate the performance of primary and secondary schools in Mauritius. They found that school leadership in Mauritius has direct and indirect impacts on outcomes through inner factors of the schools
Aly and Akpovi (2001) Survey U.S No Over half of California’s public universities apply quality management, but the scope of its implementation is limited to business finance and administrative services
Ardi et al. (2012) Survey Indonesia No Based on this study, faculty commitment, delivery quality, and effective processes for obtaining and improving quality significantly influence students’ satisfaction
Asif et al. (2013) Survey Pakistan No Based on their study, key elements of successful quality management in a higher-education environment are organizational vision, effective leadership, performance measurement and analysis, process management and control, resource allocation and program design, and effective stakeholder relationships
Badri et al. (2006) Survey UAE Yes They confirmed that leadership is a significant driver for all MBNQA elements, and all these elements are associated with organizational outcomes as well as the organization’s stakeholder focus, student focus, and market focus
Basari and Altinay (2018) Interview Cyprus No Their suggestions include prioritizing quality policies and concepts at a high level and in all units of an educational institution, while considering that equality in education and developing a quality consciousness and a strategic plan are important for higher education institutions
Becket and Brookes (2006) Conceptual U.K No Effective evolution and subsequent change management are crucial for executing quality enhancement
Brennan and Shah (2000) Conceptual Global No Questions about power and values are central points when establishing quality management. Quality management systems can therefore challenge the intrinsic value systems of an educational institution. Quality management is also an effective mechanism for considering and applying extrinsic values from society and the economy and incorporating them into education life with greater importance
Buranakul et al. (2017) Survey Thailand Yes Their study suggests that universities apply TQM to improve organizational capacity for innovation and to develop strategies for building a knowledge sharing environment as a positive driver of tacit knowledge and innovation capacity
Chin et al. (2003) Survey Hong Kong Yes They developed a self-assessment training toolkit to measure and evaluate organizational performance. The kit was designed based on MBNQA criteria for an engineering management curriculum
Crawford and Shulter (1999) Conceptual Global No There is a different understanding of TQM in education compared to TQM in industry. We may experience contradictory outcomes when we apply quality management in educational institutions because it may lead to the learning process focusing on good examination grades. This differs from the main concept of TQM because efforts at continuous improvement are relevant even to educational institutions, such as by improving the quality of instruction and developing students into more creative and critical thinkers
Csizmadia et al. (2008) Survey Hungary No The study states that in the Hungarian higher education system, these organizational characteristics are important in implementing quality management practices: leadership commitment and support, external consultants’ involvement, organizational reputation, and political and bureaucratic decision-making processes
De Jager and Nieuwenhuis (2005) Conceptual South Africa No The challenge is to successfully align the quality management concept with outcome-based education principles, to benefit from applying quality management solutions in higher education systems
Dicker et al. (2019) Survey U.K No The study confirms that employers look for high-quality personal traits in graduates. However, academic staff and students mostly focus on learning and teaching, feedback, and relationships. Students expressed uncertainty about the quality of the education they receive. The high-level administration teams of higher education organizations should highlight the value they deliver to their students/clients
Elmuti et al. (1996) Survey
and Interview
U.S No Continuous improvement can come from the main fundamentals of an effective quality management system: leadership commitment, customer orientation, employee engagement, quality-oriented vision, and effective benchmarking. In an education system, however, the university leadership and administration present the main challenge. While a great deal of time, effort, training, and resources should be allocated to implementing quality management, the top management teams in many higher education institutions are unable or unwilling to support such programs
Goldberg and Cole (2002) Case study U.S No Based on this study, by applying a cycle of planning, analyzing, and continuously improving, as well as using data from the education process, institutions can make informed decisions and determine areas of success and areas for improvement
Hoecht (2006) Conceptual/interview U.K No While accountability and transparency are well developed in academia, quality practices are very bureaucratic, with a high opportunity cost and usually only addressed on a superficial level
Jaraiedi and Ritz (1994) Conceptual U.S No While teaching is a crucial factor in the quality puzzle, a higher education institution should review its policies and practices to assess whether they really satisfy the needs of the institution's primary customers: the students
Johnson and Golomski (1999) Conceptual U.S No The study recommends applying quality management principles in an education curriculum, improving administration processes and business operations, reducing cycle times, enhancing learning and leadership, understanding and engaging stakeholders and other parties, and identifying opportunities for improvement
Kanji et al. (1999b) Survey Malaysia and U.S No Higher education needs to be guided through quality management and supported by the top management of the organization to enhance business performance. Leadership is therefore the most important factor. Higher education institutions that implement quality management outperform those that do not
Kanji et al. (1999a) Survey U.S No Measuring quality management and core concepts are considered critical success factors for higher education institutions to achieve business excellence
Koch and Fisher (1998) Conceptual U.S No There are limited empirical studies about quality management in educational organizations. Major quality issues at universities include the nature of the curriculum, effective collaboration with industry, and management and leadership arrangements
Lagrosen et al. (2004) Survey Austria
Sweden
U.K
No This study examined the dimensions of higher education’s quality and service quality from the students’ perspective, highlighting information and responsiveness, courses offered, internal audits, computing and IT facilities, collaborations and comparisons, and library resources
Latif et al. (2019) Survey Pakistan No Six quality drivers in higher education services were identified: leadership, teaching, administration services, knowledge services, other activities, and continuous improvement
Lomas (2004) Conceptual U.K No Organizations should identify, train, and nurture transformational leaders and other human actors who are adept in leadership skills and HR management. Organizations may apply specific quality management practices, such as EFQM or TQM, to achieve business excellence
Mahajan et al. (2014) Survey India No Leadership is the most crucial factor, followed by organizational structure and practices. Most factors are interdependent, and they should be seen coherently when assessing their effects on students’ education
Mergen et al. (2000) Case study U.S No This study assessed and showed the impacts of quality on design, conformance, and performance as an effective quality management model in higher education
Michael et al. (1997) Case study U.S No Quality management and improvement in higher education begins at the higher levels of administration. Providing enough training for management and staff is crucial. There may be resistance from top management teams about relinquishing authority to empower staff. These organizations need to change their management behavior, too
Motwani and Kumar (1997) Conceptual U.S No Top management should be involved in understanding and developing an effective plan to successfully achieve quality management. The organizational administration should conduct an internal quality assessment to determine strengths and weaknesses, obtain opinions and feedback from internal and external customers to assess its current state and identify improvement opportunities, and recognize and reward any quality improvements
Newton (2002) Case study U.K No By stressing autonomy, ownership, and self-assessment, an assurance system for quality management helps organization leadership in higher education to understand problems and the risk of exacerbating or exposing them. To conduct change in quality management, top leadership and management teams should assess the status of operations and their emerging trends
O’Mahony
and Garavan (2012)
Case study Ireland No Four key parameters are involved in implementing effective quality management in higher education institutions: senior leadership sponsorship and support, stakeholder involvement, execution of quality practices, and management of cultural change
Osseo-Asare and Longbottom (2002) Case study U.K No This study highlights the importance of staff development strategies for deans, assistant deans, and other staff involved in quality and operational improvement. The strategies should be based on integrating the EFQM model and the U.K. Quality Assurance Agency model. This study suggests comparing the EFQM and MBNQA models for education criteria
Owlia and Aspinwall (1997) Case study Global No From a theoretical perspective, the most critical principle of quality management in universities is customer orientation, because the motivation for academia does not usually depend on market issues. Based on this study’s analysis, the type of activities in educational institutions do not differ from those of manufacturing or other service enterprises. This study demonstrates the importance of several factors: morality among students and stuff, a high level of productivity, and customer focus and satisfaction
Psomas and Antony (2017) Survey Greece No Quality management practices in the Greek higher education system reveal the following concerns: leadership support and commitment, strategic plan for quality, student focus, process management, teaching team, employee engagement, and positive impacts on society
Sahney et al. (2004) Conceptual Global No This study viewed the input quality of educational institutions through the students, teachers, supporting staff, infrastructure, and the process quality of institutions in the form of its teaching and learning activities. Output quality was viewed in terms of the graduating students leaving the institution. This study also treats an educational institution or system as a transformational process that converts unskilled students into competent ones. In this system, the outputs include examination outcomes, employment, earnings, and satisfaction
Sahney et al. (2008) Survey India No Employee satisfaction is the main determinant for adopting an effective “customer-centric philosophy.”
Sarrico and Rosa (2016) Case study Portugal No The main challenges in supply chain quality management in the education sector relate to trust, sharing information, leadership, and integration. There is also a problem in supply chain integration. Developing SCQM models for this sector may aid this integration and lead to performance improvements
Sharabi (2013) Conceptual –- No In education institutions, the service quality delivered to students by the employees in contact with them is highly related to the top management and various departments of the educational institution
Sadiq Sohail et al. (2003) Case study Malaysia No Quality management practices encourage educational institutions to collect data, measure their performance, establish standards, benchmark, and make effective decisions
Srikanthan and
Dalrymple (2004)
Conceptual –- No Developing an effective quality system in education requires transforming it into a learning organization with quality monitoring for learning. Higher education institutions need to develop a vison to guide their actions. Student learning should be the main measure of academic quality, and customer responsiveness needs to be practiced and emphasized
Stahl (2004) Conceptual –- No Both e-teaching and information technology application in teaching may morally threaten the legitimacy of the education process. Strong association between teaching and business interests is one of the main reasons for this issue
Thakkar et al. (2006) Case study India No This study highlights the importance of continuous improvement, cultural improvement, and the optimal use of financial resources to improve service value at all levels
Tsinidou et al. (2010) Survey Greece No Quality of education is studied from the perspective of students. Based on the students’ outcomes, students’ success in the market can be improved by higher quality of teaching, effective library services, skilled employees, and the development of more specialized subjects. Such results also increase the interaction between a university and society
Venkatraman (2007) Conceptual New Zeeland No This study developed a quality management model for higher education that covers leadership, HR management, education management, information management, customer orientation and satisfaction, and partnership
Verma and Parasad (2017) Survey India No This study discusses service quality from a multi-dimensional construct with variables for six aspects: professional, academic, behavioral, industry interaction, physical, and non-academic. The results show internal consistency across the samples
Vesper and Gartner (1997) Survey U.S., Canada, and others Yes They ranked entrepreneurship programs based on seven criteria: courses offered, faculty publications, impact on the community, alumni accomplishments, innovations, alumni startups, and outreach to scholars. They also applied the seven MBNQA criteria to the quality of their programs
Voss et al. (2005) Survey U.S No In both private and public enterprises, progressive HR management leads to greater employee satisfaction, which consequently improves service quality and customer satisfaction. Research shows that HR practices have more impact on these elements than quality practices
Williams (1993) Conceptual –- No To have effective and efficient educational institutions, we need to focus on consistent quality services, continuous improvement, customer satisfaction, and a system for recognizing poor quality and correcting it
Willis and Taylor (1999) Survey U.S No From the employers’ perspective of business school graduates, communication skills and work ethics are the main weaknesses, while IT skills are the main strength. The lack of patience and commitment is another issue that business schools should consider to improve quality outcomes, although some employers asserted that certain schools produce superior graduates
There have been several calls to use well-established quality models like the Baldrige or EFQM models in education settings (Osseo-Asare and Longbottom 2002; Lomas 2004). The studies that used the Baldrige model have collected data using surveys, which solicit the opinions of managers or key stakeholders. These studies targeted primary/secondary schools (Ah-Teck and Starr 2013) or universities/colleges (Vesper and Gartner 1997; Badri et al. 2006; Chin; Buranakul et al. 2017). Ah-Teck and Starr (2013) used MBNQA criteria to conduct a survey and assess the performance of primary and secondary schools in Mauritius. Vesper and Gartner (1997) used MBNQA criteria to assess entrepreneurship programs in the U.S., Canada, and overseas. Badri et al. (2006) used MBNQA criteria to conduct a survey among universities and colleges in UAE. Buranakul et al. (2017) used TQM methods, MBNQA criteria, and survey data to assess TQM impacts on the innovation capabilities of private universities in Thailand. In Hong Kong, Chin et al. (2003) used MBNQA principles to develop a performance toolkit for teaching courses and evaluating performance; they used a survey for their validation phase.
While these studies provide insights into quality management in the education domain, they do not provide a comprehensive assessment of quality management that is grounded in the theory and practice of quality management. Thus, we see a gap in using quality management frameworks such as the Baldrige model in the context of educational organizations. In addition, we could not find any comprehensive study that examined the relationship between quality management practices and operational and business outcomes in educational organizations from a longitudinal aspect. A longitudinal aspect is important, since it provides insight into ways that quality management practices can improve organizational quality outcomes over time and the potential invariance of these relationships over time. Thus, we provide a more nuanced assessment of quality management in educational organizations that examines quality using the Baldrige criteria. Using such a well-rounded framework for quality management provides more insight into the management of quality in educational organizations.
Theory development and research hypotheses
To examine the impact of quality management on quality and operational outcomes in educational organizations, we applied the MBNQA criteria. Previous studies about these criteria have confirmed the relation between leadership and other MBNQA model components (Pannirselvam et al. 1998; Wilson and Collier 2000; Pannirselvam and Ferguson 2001; Parast 2015). Empirical analyses of the MBNQA data show that leadership is a key quality driver because it impacts strategic quality management, information and knowledge management, process quality management, and HR development and management. In the MBQNA program, leadership is the key construct reflecting senior management’s responsibilities and efforts to apply effective leadership practices to cultivate motivation and teamwork, thus building a culture with a high level of trust and creating a successful organization for the near term and the long term. These practices collectively bring about quality and operational outcomes as well as customer orientation and satisfaction. This study examines the relationships among the elements in the MBNQA framework (see Fig. 1 below) and tests the hypotheses using objective data for educational organizations. Table 2 shows our research hypotheses developed in this study and provides a summary of the literature that supports the hypotheses developed in this study.Table 2 Hypotheses for MBNQA in Educational Organizations
Hypothesis Justification
H1a: In education organizations, leadership positively influences the management of process quality Based on the Baldrige model, leadership directly affects process quality. Wilson and Collier (2000), Meyer and Collier (2001), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that quality leadership is significantly related to management of process quality. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) found that leadership support and commitment is the key factor in effective implementation of quality management
H1b: In education organizations, leadership positively influences information and knowledge management Based on the Baldrige model, leadership directly affects information and analysis. Wilson and Collier (2000), Meyer and Collier (2001), and Parast and Golmohammadi (2019) showed that quality leadership is significantly related to information and knowledge management. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) found that leadership support and commitment is the key factor in effective implementation of quality management
H1c: In education organizations, leadership positively influences HR development and management Based on the Baldrige model, leadership directly affects human resource development and management. Wilson and Collier (2000), Meyer and Collier (2001), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that quality leadership is significantly related to human resource development and management. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) argued that leadership support and commitment is the key factor in effective implementation of quality management
H1d: In education organizations, leadership positively influences strategic planning for quality Based on the Baldrige model, leadership directly affects strategic quality planning. Wilson and Collier (2000) and Parast and Golmohammadi (2019) confirmed that quality leadership is significantly related to strategic planning for quality. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) found that leadership support and commitment is the key factor in effective implementation of quality management
H2a: In education organizations, management of process quality positively influences customer focus and satisfaction Wilson and Collier (2000), Meyer and Collier (2001), and Pannirselvam and Ferguson (2001) confirmed that management of process quality is significantly related to customer focus and satisfaction. Research shows that process factors are closely related to service quality and customer satisfaction (Dabholkar and Overby 2005). Asif et al. (2013) discussed that process management is a key element of a successful quality system. Improving process quality was shown to have a positive impact on customers (students) in educational organizations (Ardi et al. 2012)
H2b: In education organizations, management of process quality positively influences quality and operational outcomes Wilson and Collier (2000) and Pannirselvam and Ferguson (2001) confirmed that management of process quality is significantly associated with quality and operational outcomes. Asif et al. (2013) found that process management is a key element of successful quality systems. Thakkar et al. (2006) highlight the importance of continuous improvement, cultural improvement, and the optimal use of financial resources to improve service value at all levels
H3a: In education organizations, information and knowledge management positively influences customer focus and satisfaction Wilson and Collier (2000) and Pannirselvam and Ferguson (2001) confirmed that information and knowledge management is significantly associated with customer focus and satisfaction. Asif et al. (2013) found that information and knowledge management is a key element of a successful quality system. Seeman and O’Hara (2006) discussed the important role of information systems in promoting the student-school relationship
H3b: In education organizations, information and knowledge management positively influences quality and operational outcomes Meyer and Collier (2001) and Parast and Golmohammadi (2019) confirmed that information and knowledge management is significantly associated with quality and operational outcomes. Chavez et al. (2015) showed that information quality mediates the relationship between customer integration and operational performance. Asif et al. (2013) discussed that information and knowledge management is a key element of successful quality systems
H4a: In education organizations, HR development and management positively influences customer focus and satisfaction Wilson and Collier (2000), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that human resource management is significantly associated with customer focus and satisfaction. According to Tsinidou et al. (2010), skilled employees have a positive impact on quality outcomes. Employee satisfaction is the main determinant for adopting an effective “customer-centric philosophy” (Sahney et al. 2008). Voss et al. (2005) argue that HR practices have a significant impact on quality outcomes
H4b: In education organizations, HR development and management positively influences quality and operational outcomes Wilson and Collier (2000), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that human resource management is significantly associated with quality and operational outcomes. According to Tsinidou et al. (2010), skilled employees have a positive impact on quality outcomes in educational organizations. Voss et al. (2005) found that HR practices have a significant impact on quality outcomes
H5a: In education organizations, strategic planning for quality positively influences customer focus and satisfaction Wilson and Collier (2000), Meyer and Collier (2001), and Parast and Golmohammadi (2019) confirmed that strategic planning for quality is significantly associated with customer focus and satisfaction. Fooladvand et al. (2015) discuss the important role of strategic planning in improving quality outcomes in educational organizations. According to Tsiakkiros and Pashiardis (2002), strategic planning is critical to achieving organizational goals and long-term survival
H5b: In education organizations, strategic planning for quality positively influences quality and operational outcomes Wilson and Collier (2000) confirmed that strategic planning for quality is significantly associated with quality and operational outcomes. Fooladvand et al. (2015) discuss the important role of strategic planning for quality in improving quality outcomes in educational organizations. Tsiakkiros and Pashiardis (2002) found that strategic planning in educational organizations is critical to achieving organizational goals and long-term survival
Methodology
This study uses the MBNQA (Baldrige) model and its criteria for quality management, which are the same criteria that were used when collecting the data. These are the criteria: 1) Leadership; 2) Strategic Planning for Quality; 3) Customer Focus and Satisfaction; 4) Information and Knowledge Management; 5) HR Development and Management; 6) Management of Process Quality; and 7) Quality and Operational Outcomes (NIST 2020). An overview of each criterion follows.
Leadership
This key aspect reflects senior management’s responsibilities and efforts to apply effective leadership practices to cultivate motivation and teamwork, thus building a culture with a high level of trust and creating a successful organization for the near term and the long term.
Strategic planning for quality
This reflects an organization’s strategic goals and objectives, its long-term and short-term plans, its action plan, how it measures progress, and how it changes plans when necessary.
Customer focus and satisfaction
This component of quality management relates to how an educational organization engages with its students and other customers. This involves ensuring students’ success but also listening to their voices, so their expectations are addressed and an effective relationship with them is built. This component therefore emphasizes customer engagement and satisfaction as a critical element of effective learning and education performance. In addition to students, there are other important customers such as parents, local businesses, other educational organizations that may receive the students later, and potential employers of the students. A major challenge for educational organizations is finding a balance between the different expectations of students (as the primary customer) and these other stakeholders.
Information and knowledge management
This is considered the core component for aligning operations with strategic goals and objectives. The criteria for education cover the main information for understanding, measuring, evaluating, and improving an educational organization’s performance and knowledge management in order to enhance innovation and competitiveness.
HR development and management
This addresses workforce practices in educational organizations, including the persons who create value and those who support them in doing so, such as teachers, trainers, administrators, and the management team.
Management of process quality
This focuses on educational organizations’ processes and activities, program types, service design and delivery methods, innovation, and operational effectiveness plans and practices for the near term present and long term.
Quality and operational outcomes
This focuses on the results and outcomes that are necessary for sustaining or growing an educational organization, including the results of educational processes, student learning, leadership and governance, workforce outcomes, satisfaction, financial outcomes, and marketing performance.
Data
The required data for each educational organization were collected as part of the MBNQA program. These data consist of 115 organizational scores for educational organizations in the U.S. over a seven-year period from 1999 to 2006, but any given educational organization may not appear in all seven years. Due to the robustness, soundness, and objectivity of the evaluation process, the data are highly reliable (Parast 2015; Parast and Golmohammadi 2019; Parast and Safari 2021, 2022).
Sample
This study’s sample is the data from U.S. educational organizations that applied for the MBNQA award between 1999 and 2006. The data for 1999 were excluded from our analysis, since 1999 was the first year of such data collection. In total, there are 115 observations for the 1999–2006 period.
Table 3 presents a summary of the data for each criterion for each year (mean and standard deviation). The first column gives the year and (in parentheses) the sample size for that year. To examine the normality of our dataset, we needed to estimate the skewness (asymmetry) as well as kurtosis (peakedness) of the dataset. Our estimates for both asymmetry and kurtosis fell between -0.851 and 0.302, which are both within the acceptable range of -1.5 to + 1.5. This demonstrates that our dataset has normal univariate behavior (Tabachnick and Fidell 2013) and meets the requirement of normality. Table 3 Descriptive Statistics
Year Leadership Strategic Planning for Quality Customer Focus and Satisfaction Information and Knowledge Management HR Development
and Management Management of Process Quality Quality and Operational Outcomes
1999 (16) (.43, .16) (.38, .15) (.40, .12) (.36, .15) (.39, .14) (.42, .12) (.35, .16)
2000 (11) (.48, .09) (.42, .13) (.41, .09) (.41, .14) (.42, .09) (.43, .14) (.36, .15)
2001 (10) (.48, .12) (.44, .15) (.43, .12) (.48, .14) (.43, .11) (.43, .11) (.37, .18)
2002 (10) (.35, .10) (.32, .10) (.35, .10) (.35, .13) (.35, .07) (.36, .07) (.29, .08)
2003 (19) (.40, .13) (.33, .12) (.38, .12) (.40, .12) (.38, .08) (.37, .11) (.29, .14)
2004 (17) (.54, .10) (.42, .13) (.44, .11) (.46, .13) (.45, .06) (.45, .12) (.36, .10)
2005 (16) (.49, .12) (.43, .13) (.46, 11) (.48, .11) (.47, .12) (.47, .13) (.39, .13)
2006 (16) (.53, .09) (.51, .11) (.53, .09) (.51, .11) (.52, .11) (.53, .12) (.42, .13)
Table 3 shows that there were significant improvements in the mean value for most criteria (constructs) over the seven years from 1999 to 2006, which could be a result of the widespread application of quality practices. For instance, the Leadership score improved from 0.43 to 0.53 (+ 23%) during this seven-year period. The improvement in the Leadership score can be attributed to the fact that different educational organizations, more advanced in quality management, applied in the later years. We can see similar improvement patterns for other MBNQA constructs: Strategic Planning for Quality increased from 0.38 to 0.51 (34.2%), Customer Focus and Satisfaction increased from 0.40 to 0.53 (32.5%), Information and Knowledge Management increased from 0.36 to 0.5 (41.7%), HR Development and Management increased from 0.39 to 0.52 (33.3%), and Management of Process Quality increased from 0.42 to 0.53 (26.2%), and most importantly, Quality and Operational Outcomes increased from 0.35 to 0.42 (20%) as our main output. While we have seen declines in quality and operational results in other segments such as healthcare (Parast and Golmohammadi 2019), the overall improvement in the education sector is quite significant.
Table 4 presents the overall mean, standard deviation (SD), and pairwise correlation of the MBNQA criteria. It shows that the scores for quality management constructs in these educational organizations range from 0.36 to 0.45 (out of 1), implying that there is a significant shortfall in effectively applying quality management practices in these organizations. Furthermore, these constructs are highly correlated, which reflects the considerable interrelationships among the MBNQA model elements that were supported and envisioned in the literature.Table 4 Overall Attributes and Pairwise Correlation of Criteria (Constructs)
Mean S.D 1 2 3 4 5 6 7
1. Leadership .45 .13 1.00
2. Strategic planning for quality .41 .14 .842*** 1.00
3. Customer focus and satisfaction .43 .12 .863*** .840*** 1.00
4. Information and analysis .43 .14 .822*** .853*** .851*** 1.00
5. HR development and management .43 .11 .842*** .808*** .832*** .802*** 1.00
6. Process management for quality .44 .13 .824*** .820*** .817*** .837*** .812*** 1.00
7. Quality and operational outcomes .36 .14 .777*** .809*** .767*** .779*** .749*** .800*** 1.00
***p < .01
Data analysis and estimation procedure
In this study, we applied the structural equation modeling (SEM) approach for our analysis. SEM allows the analysis and testing of complex associations among various independent and dependent variables simultaneously, so there can be more than one output variable. Additionally, SEM can be regarded as effectively combining both factor analysis and regression analysis to analyze the structural associations among observed and latent variables (Bagozzi and Yi 2012).
Measurement model—validation and analysis
To verify our SEM analysis and examine the overall fitness of our MBNQA model for educational organizations, we used confirmatory factor analysis (CFA), because, as stressed by Hair et al. (2009), CFA is an important method for full model measurement. Our CFA goodness-of-fit statistic showed the overall fitness of the model to be (χ2/df = 1.17, RMSEA = 0.038 (0.01, 0.065); RMR = 0.001). Based on this result, all the key parameters of Chi-Square, RMSEA, and RMR fall within the respective acceptable and recommended ranges (Hu and Bentler 1999). In addition, we applied the Kaiser–Meyer–Olkin method of sampling adequacy to evaluate the validity of the factor model (Kärnä et al. 2003). We received a result of KMO = 0.96 and χ2 = 2201.24 with p < 0.01, which suggests there are no concerns regarding the factor model.
Next, we estimated the reliability for our main constructs using Cronbach’s alpha. These values were also found to be within the recommended range (between 0.84 and 0.93). A reliability value greater than or equal to 0.7 is acceptable for survey study (Hair et al. 2009). As Table 5 shows, our estimation of the standardized loadings for the model are all significant, thus proving the convergent validity of the model. Additionally, we tested composite reliabilities and average variance extracted (AVE) to ensure convergent validity and discriminant validity (Fornell and Larcker 1981; Agarwal 2013; Henseler et al. 2015). The “Item” column lists each sub-construct used in our analysis. Descriptions of the entries in this column are provided in Appendix A. Table 5 Properties of the Constructs and Model
Scale Measurements
Reliability Composite reliability Item
(Sub-construct) Loading Average Variance Extracted
Leadership .87 .95 L11 .94 .92
L12 .89
Strategic Planning for Quality .93 .93 S21 .96 .89
S22 .95
Customer Focus and Satisfaction .90 .93 C31 .90 .89
C32 .87
Information and Analysis .89 .96 I41 .95 .93
I42 .91
HR Development
and Management
.89 .97 H51 .87 .88
H52 .93
H53 .85
Process Management .87 .97 P61 .92 .92
P62 .91
Quality and Operational Results .93 .98 Q71 .87 .68
Q72 .95
Q73 .90
Q74 .88
Structural Model and the Testing of Hypotheses
Control variables
There are two control variables, namely for industry (i.e., educational organizations) and application year. We assigned a vector of dummy variables for each year (Y1999 through Y2006), applying 1999 as the reference year.
Statistical procedure
As indicated earlier, to assess the validity of the conceptual framework as shown in Fig. 1, we applied the SEM approach using AMOS 25.0 software. Table 6 shows the outcome of this analysis: the regression coefficients and corresponding p-value for each path. These results are consistent with the main hypotheses H1a through H1d. They show that Leadership significantly and positively influences the following variables: Management of Process Quality (ß = 0.975, p < 0.05), Information and analysis (ß = 0.991, p < 0.05), HR development and managementt (ß = 0.917, p < 0.05), and Strategic quality planning (ß = 0.957, p < 0.05). Information and analysis significantly and positively influences Customer focus and satisfaction (ß = 1.861, p < 0.05) (H3a). Management of process quality is a significant predictor for Quality and operational results (ß = 0.615, p < 0.10) (H2b). The details of all these relations are presented in Table 6. We were not able to find support for hypotheses H2a, H3b, H4a, H4b, H5a and H5b. Table 6 Coefficients
Controls Dependent Variables Independent Variables
Customer focus and satisfaction Quality and operations results Strategic quality planning Information and
analysis HR development and management Management of process quality
Y2000 -.178* .053 .015 .036 .042 -.111*
Y2001 -.392** .053 .043 .199** .068 -.086
Y2002 -220* .046 .075 .210** .096 .063
Y2003 -.423** .024 -.034 .237** .083 -.051
Y2004 -.319** -.019 .090* .292** .225* .085
Y2005 -.331** .011 .001 .208** .141* .006
Y2006 -.113 -.078 .109** .192** .225* .058
Predictors Customer focus and satisfaction Quality and operations results Strategic quality planning Information and
analysis
HR Development Management of process quality
Leadership n.s n.s .957** .991** .917** .975**
Strategic quality planning -.261 .338
Information and analysis 1.861** .013
HR Development -.023 -.034
Management of process quality -.578 .615*
n.s. hypothesis is not stated
*p ≤ .10; * p ≤ .05 **
Robustness and validation tests
Normality test
Even though the normality assumption in data is necessary for regression analysis, it is not required for the SEM approach (Sharma et al. 1989; Lei and Lomax 2005). We applied the skewness and kurtosis measures to examine data symmetry and peakedness, which were found to be in the range of -0.702 to 0.238. Thus, we concluded that normality assumptions for the data were met.
Heteroscedasticity test
To ensure that we obtained unbiased estimates, a heteroscedasticity test was needed. Heteroscedasticity reflects the situation that the regression variance disturbances (or the variance of error terms) is not constant across observations (Greene 2012). We plotted predicted values vs. residuals and found no evidence of heteroscedasticity in the dataset.
Multicollinearity test
The multicollinearity test concerns the insensitivity of the results to interrelationships or correlations among variables. Based on our analysis, all the variable inflation factor (VIF) values estimated by our multiple regression analysis were below the recommended value (10), since the highest VIF value was 4.6. This means that there was no major concern about multicollinearity in the dataset (Belsley et al. 1980; Hair et al. 2009).
Alternative structural models
We evaluated whether the alternative structural models proposed in the literature would significantly improve the model’s fit. An alternative structural model proposed for the MBNQA suggests a mediating relationship between Information and Analysis and other quality management practices (Wilson and Collier 2000). This alternative model shows model fit statistics of χ2/df = 1.983, RMSEA = 0.093; RMR = 0.004; CFI = 0.922. This is not significantly different from the structural model proposed in this study (χ2/df = 1.94, RMSEA = 0.091; RMR = 0.004; CFI = 0.924). The second alternative model, which was proposed by Flynn and Saladin (2001), introduces three more paths in addition to the model proposed by Wilson and Collier (2000): a path from Customer orientation and focus to Process management, a path from HR development to Process management, and a path from Strategic planning to HR development. This structural model gives fit statistics of χ2/df = 1.983, RMSEA = 0.093; RMR = 0.004; CFI = 0.922. Again, this was not significantly different from the structural model proposed in this study. We also realized that these two alterative models were primarily developed and verified in manufacturing settings, where only Quality and operational results is considered for the outcome. Our empirical results, along with the nature of the educational organizations, suggest that the model proposed in this study considers both customer focus and quality results as outcomes for a quality system, so it is a suitable model for quality management and business excellence in educational settings.
Discussion
This study provides the first comprehensive, data-driven, and empirically sound assessment of quality management practices for educational organizations. In addition to providing a suitable theoretical and conceptual framework for assessing quality management in education settings, this study uses assessments from independent reviewers for quality practices to yield a high level of reliability and validity for the data, thus ensuring the robustness of the results and findings. Furthermore, the longitudinal nature of the data, which covers quality practices over a seven-year period, captures the nuances related to the association between quality management practices and quality results over time, thereby increasing the robustness of the results when compared to cross-sectional surveys that are administered at just a given point in time. This means that the relationships go beyond simple correlations and there is a stronger case for causality.
Theoretical contributions
This research makes several contributions to the literature in the field of operations management, quality management, informing public policy, and governance practices at educational organizations. First, to the best of our knowledge, this study is the first empirical assessment of the use of a well-established quality management model in educational organizations. Our findings suggest that quality management models like the MBNQA framework are compatible with educational organizations and can be used to enhance quality outcomes and achieve business excellence.
Second, this study builds upon the relatively dispersed previous research into quality management in educational settings, and it further advances our understanding of how quality management practices, which were developed primarily for production and manufacturing systems, can improve quality results in education settings (Elmuti et al. 1996; Kanji et al. 1999b; De Jager and Nieuwenhuis 2005). Using high-quality data from educational organizations, we have provided an early but comprehensive assessment of quality management in educational settings. This effort addresses two main gaps in the current literature by 1) using independent professional reviewers’ scores, which are objective and reliable, and 2) using seven years of data for educational organizations, thus enabling a more rigorous evaluation of the associations between quality management practices and quality and operational outcomes. The robustness of the MBNQA model and the quality of the data ensure the validity of the results.
Third, our research improves our understanding of how educational organizations can enhance their business operations and quality by applying the MBNQA model. Consistent with prior anecdotal evidence for quality management practices in educational organizations (Elmuti et al. 1996; Csizmadia et al. 2008; Asif et al. 2013), our findings show that Leadership is the key driver of quality management practices in educational organizations, which in turn significantly influence all other quality management elements. This supports prior studies that have suggested an interdependence among quality practices in educational organizations (Mahajan et al. 2014). We examined the Leadership effects from two perspectives. First, Leadership directly and positively impacts other constructs of the model, including Information and analysis, Strategic planning for quality, HR development and management, and Quality process management. This outcome affirms the Baldrige theory that Leadership drives systems, and this outcome also supports previous studies that have articulated how the strong commitment and sponsorship of the senior leadership team is a key driver of quality improvement (Psomas and Antony 2017). It also supports the anecdotal evidence that a university’s top administration presents the main obstacle to implementing a quality management system (Elmuti et al. 1996). Leadership also significantly influences Strategic planning (ß = 0.957, p < 0.05), and this is one of the greatest impacts among the MBNQA criteria. This suggests that in educational organizations, leaders must recognize the importance of long-term strategies for quality; this also supports former studies that have emphasized the crucial role of strategic planning and development as an important factor in the successful implementation of quality management in educational organizations (Osseo-Asare and Longbottom 2002; Basari and Altinay 2018).
Our fourth contribution concerns the significant impact of Process quality management on Quality and operational results (ß = 0.615, p < 0.1). Studies have well discussed the challenges related to process management and process improvement in service organizations (Ettlie and Rosenthal 2011); however, this study found that Management of process quality significantly affects quality and operational results in educational organizations. Studies confirm that applying a process approach to quality improvement (e.g., Lean and Six Sigma) leads to significant improvement in business processes and their outcomes (Assarlind and Gremyr 2016). Our findings support the recommendation put forward in the literature about the important role of process management and process improvement, as well as decision-making processes, in educational organizations (Asif et al. 2013; Goldberg and Cole 2002; Csizmadia et al. 2008). Our results also support the efforts of Zhao et al. (2008) as well as Harris et al. (2011), who showed the importance of process management in a successful implementation of quality management. Our findings extend that effect of process management to educational organizations.
The sixth contribution of this study is about the significant association between Information and knowledge management and Customer focus and satisfaction in educational organizations (ß = 1.861, p < 0.05). This has by far the largest coefficient among quality management and quality outcomes in educational organizations. The important role of information, analysis and knowledge management has been extensively discussed in the literature (Lagrosen et al. 2004; Venkatraman 2007; Sarrico and Rosa 2016), but empirical evidence for the effect of information and knowledge management on improving quality results in educational organizations had thus far been overlooked. Studies of the relationship between investment in information systems and customer satisfaction have also yielded mixed findings in business settings (Mithas et al. 2016). Our empirical results support the previous studies that have highlighted the importance of information systems and knowledge sharing for enhancing organizational performance in a business (i.e., profit-driven) setting (Lloyd-Walker and Cheung 1998; Demirbag et al. 2012). Information analysis, and knowledge management is an engine for quality improvement in educational organizations, and it is a key driver for continuous improvement and the transition to a learning organization in educational organizations (Goldberg and Cole 2002; Srikanthan and Dalrymple 2003).
Finally, our findings provide further important knowledge about the long-term effects of quality management solutions on educational organizations. While the literature expresses mixed opinions concerning the effectiveness of quality management programs (e.g., Asif et al. 2009; Bourke and Raper 2017), we tried to shed more light on the long-term impact of quality management programs on educational organizations. By reviewing the effects for each year and comparing them with our reference year (1999), we could provide valuable insight into this effect for service organizations. Reviewing the coefficients for Customer focus and satisfaction for the year-effect (see Table 6), we found a negative trend from 2000 (ß = -0.178, p < 0.1) to 2005 (ß = -0.331, p < 0.05). This suggests that compared with 1999, there was a decline in customer focus and satisfaction over time. This implies that, on average, the educational organizations were not able to address the needs and interests of their customers over time, hence the declining trend. In contrast, we can see significant improvements in Information and Analysis, where the year-effect shows a positive trend from 2001 (ß = 0.199, p < 0.05) to 2006 (ß = 0.192, p < 0.05). This demonstrates that while implementing quality management in educational organizations improves Information and analysis, it does not necessarily lead to a sustained improvement in Customer focus and satisfaction. The theoretical contribution of these observations is that it suggests diminishing returns on investment, in terms of customer focus practices, from information and knowledge management over time. This accords with the diminishing public trust in educational organizations (Salisbury and Horn 2019). It also provides an interesting observation for explaining the mixed results for the effectiveness of quality management programs, because this temporal effect cannot be captured with cross-sectional surveys. In addition, solely relying on the use of information technologies and information systems does not necessarily lead to better customer satisfaction. The information and analysis need to be incorporated into the development of new processes and reflected in organizational practices in order to address customers’ needs and interests and achieve a sustainable level of customer service quality. If they are not, the effect will be limited, and the information and analysis will not lead to process improvements or changes in organizational practices. Thus, educational organizations need to be aware that simply investing in information systems, library resources, and other informative and educational resources do not necessarily lead to better quality results, especially if input from multiple stakeholders is not incorporated into the design of information systems and improvements for organizational processes.
Implications for education administrators
This empirical study offers suggestions and insights for the administrators of educational organizations. First, as higher education organizations begin to refine their quality initiatives, they can consider using the MBNQA framework and criteria to diagnose their defects and issues and to analyze, restructure, and streamline their business processes, systems, and quality-improvement efforts. When service organizations are committed to enhancing their businesses and operational results, the Baldrige model is an effective and comprehensive approach for assessment. In addition, educational organizations should recognize the crucial role of investment in Information and knowledge management to fulfil their customers’ needs and consider their customers’ opinions in services. Education organizations interact with multiple stakeholders and engage with a variety of customers, so attention must be paid to developing information systems and investing in enterprise information systems that can capture data from multiple stakeholders and incorporate them into organizational processes, because this will be critical for an educational organization’s success. During the COVID-19 pandemic, educational organizations that had invested in information technology, support systems, and other related infrastructure were able to mitigate the impact of the pandemic and transition more smoothly to a virtual learning environment, thus minimizing the impact on student learning.
Education administrators should also consider the crucial role of process management in their business operation. Most business improvement approaches (e.g., TQM, ISO 9000, Kaizen, Lean, and Six Sigma) focus on business processes and continuous improvement to enhance organizational outcomes such as customer satisfaction and quality and operational results. Administrators also need to pay more attention to investing in information systems, analytics, and organizational learning to improve their informed decision making, to enhance their service operations and customer satisfaction using data-driven approaches. Finally, to improve service quality and customer satisfaction, educational administrators should be mindful of the importance of soliciting input from multiple stakeholders and incorporating this into their decisions for improving organizational processes.
Limitations and future research
The MBNQA data for educational organizations is only available for the 1999–2006 period. This study could have been more effective if it had used more recent data for this model. Another limitation of the study is related to the sample size. While we were able to assess the validity of the results using a variety of fit indices, it is recommended that future studies examine the validity of the Baldrige model in educational institutions using a larger sample.
Furthermore, the availability and inclusion of other related parameters—such as age, size, and organizational type (i.e., private vs. public)—could have yielded valuable insights about the effects of these contextual and organizational parameters on quality outcomes in educational organizations. Some argue that the success of an organization such as Arizona State University in revolutionizing its educational system is related to its size (Salisbury and Horn 2019). Thus, the inclusion of other variables would have supported a more nuanced assessment of quality management in educational organizations. We are mindful that access to more detailed information about educational organizations such as type of the organization (e.g., university, non-profit) along with other organizational factors would provide a more robust assessment of quality management in educational organizations.
We should also be careful about generalizing this study’s outcomes. Since we used data from the United States, we may reasonably expect that we could extend the findings to other economies that experience similar management, social, and legal platforms. It would also be interesting to compare, analyze, and generalize the impact of similar quality excellence frameworks—such as the Deming Prize, EFQM, and other national quality award models—on the quality and operational outcomes of educational organizations.
Appendix A Description of each sub-construct listed in
Construct Items (sub-constructs)
1. Leadership (LEA) L11) Senior Leadership: How do your senior leaders lead the organization?
L12) Governance and Societal Contributions: How do you govern your organization and make societal contributions?
2. Strategic Quality Planning (STR) S21) Strategy Development: How do you develop your strategy?
S22) Strategy Implementation: How do you implement your strategy?
3. Customer Focus and Satisfaction (CFS) C31) Customer Expectations: How do you listen to your customers and determine products and services to meet their needs?
C32) Customer Engagement: How do you build relationships with customers and determine satisfaction and engagement?
4. Information and Analysis (INF) I41) Measurement, Analysis, and Improvement of Organizational Performance: How do you measure, analyze, and then improve organizational performance?
I42) Information and Knowledge Management: How do you manage your information and your organizational knowledge assets?
5. Human Resource Development and Management (HRD) H51) Workforce Environment: How do you build an effective and supportive workforce environment?
H52) Workforce Engagement: How do you engage your workforce for retention and high performance?
6. Management of Process Quality (PRO) P61) Work Processes: How do you design, manage, and improve your key products and work processes?
P62) Operational Effectiveness: How do you ensure effective management of your operations?
7. Quality and Operational Results (RES) Q71) Product and Process Results: What are your product performance and process effectiveness results?
Q72) Customer Results: What are your customer-focused performance results?
Q73) Workforce Results: What are your workforce-focused performance results?
Q74) Leadership and Governance Results: What are your senior leadership and governance results?
Q75) Financial, Market, and Strategy Results: What are your results for financial viability and strategy implementation?
1 The data for Baldrige assessments became available in 2011.
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Oper Manag Res
Operations Management Research
1936-9735
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Springer US New York
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10.1007/s12063-022-00332-1
Article
Do quality and business excellence models improve quality and operational results in educational organizations? A repeated cross-sectional analysis
http://orcid.org/0000-0001-6589-1076
Parast Mahour Mellat [email protected]
1
Safari Arsalan [email protected]
2
1 grid.215654.1 0000 0001 2151 2636 Ira A. Fulton Schools of Engineering, Arizona State University, Tempe, AZ 85281 USA
2 grid.412603.2 0000 0004 0634 1084 College of Business and Economics, Qatar University, P.O. Box 2713, Doha, Qatar
6 12 2022
119
15 9 2020
22 9 2022
26 10 2022
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Improving quality and operational practices in education organizations and developing a culture of continuous improvement are crucial yet challenging endeavors because of the complex nature of education organizations. While quality management practices can clearly improve the quality of these organizations in several aspects, empirical research for quality management in educational organizations is sparse because of the lack of suitable frameworks for assessing quality. In this paper, we present the first large-scale empirical study of implementing quality management practices in educational organizations in the United States. It is based on seven years of objective data for quality assessments by external professional reviewers as part of the U.S. government’s Malcolm Baldrige National Quality Award (MBNQA) program. Our findings provide empirical evidence for the reliability and robustness of the Baldrige model as an effective quality assessment for educational organizations. Controlling for the applicant’s year, our findings show that Information and knowledge management is a key influencer and predictor of Customer satisfaction and focus, and Management of process quality is a key influencer and predictor of Quality and operations results. This study also provides effective insight and recommendations for how to improve quality systems and achieve business excellence in educational organizations using the Baldrige model. The findings will therefore help managers and administrators to make informed decisions about key factors that impact quality in educational organizations.
Keywords
Quality management
Malcolm Baldrige National Quality Award (MBNQA)
Educational organizations
Quality results
==== Body
pmcIntroduction
Over the last several decades, quality management principles have shaped organizational thinking and business practices to improve organizational processes and achieve better customer satisfaction (Kok et al. 2001; Gonza´lez-Cruz et al. 2018; Parast and Golmohamamdi 2019). Although quality management research has helped both manufacturing organizations and service organizations to improve their quality and organizational processes, one important segment of the economy has had limited discussion in scholarly research: educational organizations.
The main challenge to understanding and implementing quality management in education is a lack of clarity about what quality means in the education context (Brockerhoff et al. 2015; Dicker et al. 2019). Quality in education is considered a multi-dimensional term: a term that is simultaneously dynamic and contextual (Krause 2012). There are multiple stakeholders involved in education, adding to the complex nature of managing quality in such a dynamic system (Latif et al. 2019). In addition, the meaning of customers and customer satisfaction is also not clear in education settings. While education can be viewed as a service, it simultaneously deals with both tangible dimensions (e.g., course materials) and intangible dimensions (e.g., advising and serving students) of quality. The ethical and social responsibility dimensions are also important in education settings (Harris et al. 2011), further adding to the complex nature of quality assessment in education.
The first step in understanding quality management in education settings is to develop a quality framework that will provide a holistic approach to understanding quality, using an established quality framework such as the EFQM or Baldrige model (Osseo-Asare and Longbottom 2002; Lomas 2004; Araújo and Sampaio 2014; Martín-Gaitero and Escrig-Tena 2018; Castka 2018). Despite the clear importance of quality in education, very limited scholarly studies have sought to understand quality management practices in education. We therefore aim to address this gap in the literature on quality management and business excellence by applying the model of the Baldridge Performance Excellence Program.
The Malcolm Baldrige National Quality Award (MBNQA) is an annual assessment program for quality and business excellence led by the National Institute of Standards and Technology (NIST), which is a part of the U.S. Department of Commerce. The MBNQA is an effective framework for assessing and improving an organization’s quality and operations, and it is said to be useful and applicable to any type of organization, regardless of size or industrial sector (Bandyopadhyay and Leonard 2016). For a long time, it was not possible to assess the impact of the MBNQA on enhancing organizational quality and operational results because the data for the MBNQA assessments were confidential and not publicly available.1 Therefore, understanding the long-term effect of quality management practices in educational organizations remains an unexplored area that warrants further research.
In this study, we seek to address these gaps by understanding quality practices in educational organizations (public schools, universities, and other non-profit educational organizations). To achieve this, we first examine how quality management practices can improve quality outcomes using the MBNQA criteria. The MBNQA is a robust framework, so it provides an excellent foundation to better understand quality issues in education in terms of theoretical rigor as well as managerial relevance (Parast 2015; Parast and Golmohammadi 2019; Parast and Safari 2021, 2022). In addition, by using scores from independent reviewers (which is embedded in the quality assessment process of the Baldrige program), we ensure that the data is objective. This approach to quality assessment avoids the shortcomings of collecting data through self-administered surveys (Sofaer and Firminger 2005). In addition, the Baldrige data for education organizations spans seven years, thus providing a suitable basis for examining the relationships between quality practices over time. This provides important evidence for moving beyond correlations analysis and establishing causality. This approach will therefore improve both the theory and practice of quality management in the education domain.
Quality management in education
Defining quality and its management in education settings is a debatable issue. Some argue that the concept of quality and the interplay between different entities in educational settings is similar to that of manufacturing and other service enterprises, but the concept of quality and how it is defined clearly needs to be refined to fit the nature of education (Owlia and Aspinwall 1997). Some argue that there is no clear definition of what quality means in education (Brockerhoff et al. 2015). Educational organizations deal with multiple stakeholders, each with its own idea of quality (Schindler et al. 2015). Thus, what students perceive as high-quality education may differ from that of an employer or a funding agency (Dicker et al. 2019). In addition, concepts such as ethics and social responsibility should be emphasized in education settings to prepare students for their future roles in society (Harris et al. 2011). Quality assessment in education should therefore develop a holistic and systematic approach that incorporates all the complementary perspectives of quality (Goldberg and Cole 2002).
Quality, ethics, and social responsibility
From a solely economic perspective, organizations’ primary objective is to maximize their profits and shareholder value; thus, in a competitive business environment, business and ethics are not necessarily compatible (Ahmed and Machold 2004). While the relationship between quality, ethics, and social responsibility has been widely debated for the business environment, the relationship and its internal compatibility in the context of educational organizations needs further attention to address the needs and interests of the various stakeholders.
Quality management studies have long acknowledged the link between quality and ethics. Ishikawa (1985) alluded to this by articulating how quality control principles relate to believing in the goodness of people. This is reflected in the Kaizen quality management concept of a continuous improvement in the quality of life for individuals (Evans and Lindsay 1993). The literature suggests that adhering to quality management principles shapes corporate culture and encourages ethical leadership principles; this is reflected in the MBNQA (Steeples 1994). While there is a relationship between quality and ethics from a theoretical perspective (Chen et al. 1997; Raiborn and Payne 1996), numerous unethical practices are prevalent in the business world. Boisjoly (1993) argues that such unethical practices mostly result from cultural failures and shortcomings in management systems, so implementing a quality management system like the MBNQA may address this issue.
Several authors argue that a quality management system can address the ethical dimensions of management systems and the institutionalized ethical principles within organizations. Wicks and Freeman (1998) note that TQM principles address management practices while promoting moral values. What is needed is to broaden the concept of quality, which has happened in the quality management domain. Indeed, the concept of quality has evolved from statistical values for quality control and process improvement to considering more nuanced factors like customer satisfaction, employee engagement, and learning and innovation (Kok et al. 2001; Perdomo-Ortiz et al. 2009; Maletič et al. 2014; Psomas and Antony 2015). The recent trends toward sustainability and social responsibility have led to the quality management literature focusing more on the role of quality in improving an organization’s relationship with its stakeholders (Parast 2013, 2014; Wagner 2015). Organizations that implement quality management practices are more inclined to adhere to the principles and premises of social responsibility and ethical conduct, suggesting the existence of direct links between quality, ethics, and social responsibility (Erwin 2011; Attig and Cleary 2015). Thus, implementing quality management in educational organizations could not only lead to improvements in business processes and outcomes, it could also provide a suitable platform for addressing codes of conduct, ethical principles, and corporate social responsibility for the various stakeholders.
Studies of quality in educational organizations
Research into quality in education has been conducted from three perspectives. The first perspective, which is by far the most dominant, is concerned with theorizing and conceptualizing quality in education. This stream of research provides different directions and conceptualizations for quality in education and discusses the challenges associated with measuring it (Crawford and Shulter 1999; De Jager and Nieuwenhuis 2005; Becket and Brookes 2006; Sharabi 2013). The second perspective on quality in education is concerned with assessing customer satisfaction, which involves primarily looking at students’ perceptions of quality for an educational organization and its instruction. This is largely influenced by the literature on service quality, which generally measures quality on a multidimensional scale that evaluates a service from the customer’s (i.e., the student’s) viewpoint (Parasuraman et al. 1985, 1988). Although this branch of research provides important insight into the quality of service delivery and student satisfaction, it is primarily concerned with customer interaction and the delivery of services, so it does not capture the inherent nuances of quality in an education setting (Verma and Parasad 2017). This stream of research examines the dimensions of quality in education and the service sector from a student’s point of view, and it has found that students regard as valuable components of a quality education features such as courses offered and delivered, information management and responsiveness, collaboration and comparisons, internal audit assessment, IT equipment and infrastructure, and library resources (Lagrosen et al. 2004). Finally, the third perspective on quality in education deals with measuring quality in education and identifying important quality practices to enhance quality outcomes and business results in education settings (Asif et al. 2013). While these studies provide insights into quality issues by conducting surveys, they usually suffer from weak research design, a poor methodological approach, and a limited view of quality, all of which raise concerns about the validity and reliability of their findings. Our study is concerned with this third perspective on quality in education. We use the Baldrige model for quality to examine the relationship between quality management practices and an organization’s operational and business results. We assess the impact of quality management practices (leadership, management of process quality, information and analysis, human resources development and management, and strategic planning for quality) on customer focus and satisfaction and operational and business results, as shown in Fig. 1.Fig. 1 Structural Model/Framework for Quality Management in Educational Organizations (Adapted from Parast 2015)
Table 1 presents a review of studies concerned with quality management in educational organizations. Most of these studies are concerned with conceptual development and the articulation of definitions for quality in education (Crawford and Shulter 1999; De Jager and Nieuwenhuis 2005; Becket and Brookes 2006; Sharabi 2013), as well as some case studies (Michael et al. 1997; Mergen et al. 2000; Goldberg and Cole 2002). While some studies survey students (Aly and Akpovi 2001; Csizmadia et al. 2008), most of them sought to solicit information from different stakeholders (e.g., students, faculty, and staff) about quality, and the analyses are limited to providing descriptive statistics about key variables. These studies mainly do not follow a rigorous process of survey design, sampling strategy, and survey implementation. A similar criticism can be directed against the qualitative studies, which provide some limited knowledge about the cases being discussed (Michael et al. 1997; Newton 2002; Sadiq Sohail et al. 2003). Therefore, these studies are limited to the specific sample and context being examined.Table 1 Studies of Quality Management in Educational Organizations (in alphabetical order)
Study Research Country Baldrige Major Findings
Ah-Teck and Starr (2013) Survey Mauritius Yes This study used the MBNQA principles/model to evaluate the performance of primary and secondary schools in Mauritius. They found that school leadership in Mauritius has direct and indirect impacts on outcomes through inner factors of the schools
Aly and Akpovi (2001) Survey U.S No Over half of California’s public universities apply quality management, but the scope of its implementation is limited to business finance and administrative services
Ardi et al. (2012) Survey Indonesia No Based on this study, faculty commitment, delivery quality, and effective processes for obtaining and improving quality significantly influence students’ satisfaction
Asif et al. (2013) Survey Pakistan No Based on their study, key elements of successful quality management in a higher-education environment are organizational vision, effective leadership, performance measurement and analysis, process management and control, resource allocation and program design, and effective stakeholder relationships
Badri et al. (2006) Survey UAE Yes They confirmed that leadership is a significant driver for all MBNQA elements, and all these elements are associated with organizational outcomes as well as the organization’s stakeholder focus, student focus, and market focus
Basari and Altinay (2018) Interview Cyprus No Their suggestions include prioritizing quality policies and concepts at a high level and in all units of an educational institution, while considering that equality in education and developing a quality consciousness and a strategic plan are important for higher education institutions
Becket and Brookes (2006) Conceptual U.K No Effective evolution and subsequent change management are crucial for executing quality enhancement
Brennan and Shah (2000) Conceptual Global No Questions about power and values are central points when establishing quality management. Quality management systems can therefore challenge the intrinsic value systems of an educational institution. Quality management is also an effective mechanism for considering and applying extrinsic values from society and the economy and incorporating them into education life with greater importance
Buranakul et al. (2017) Survey Thailand Yes Their study suggests that universities apply TQM to improve organizational capacity for innovation and to develop strategies for building a knowledge sharing environment as a positive driver of tacit knowledge and innovation capacity
Chin et al. (2003) Survey Hong Kong Yes They developed a self-assessment training toolkit to measure and evaluate organizational performance. The kit was designed based on MBNQA criteria for an engineering management curriculum
Crawford and Shulter (1999) Conceptual Global No There is a different understanding of TQM in education compared to TQM in industry. We may experience contradictory outcomes when we apply quality management in educational institutions because it may lead to the learning process focusing on good examination grades. This differs from the main concept of TQM because efforts at continuous improvement are relevant even to educational institutions, such as by improving the quality of instruction and developing students into more creative and critical thinkers
Csizmadia et al. (2008) Survey Hungary No The study states that in the Hungarian higher education system, these organizational characteristics are important in implementing quality management practices: leadership commitment and support, external consultants’ involvement, organizational reputation, and political and bureaucratic decision-making processes
De Jager and Nieuwenhuis (2005) Conceptual South Africa No The challenge is to successfully align the quality management concept with outcome-based education principles, to benefit from applying quality management solutions in higher education systems
Dicker et al. (2019) Survey U.K No The study confirms that employers look for high-quality personal traits in graduates. However, academic staff and students mostly focus on learning and teaching, feedback, and relationships. Students expressed uncertainty about the quality of the education they receive. The high-level administration teams of higher education organizations should highlight the value they deliver to their students/clients
Elmuti et al. (1996) Survey
and Interview
U.S No Continuous improvement can come from the main fundamentals of an effective quality management system: leadership commitment, customer orientation, employee engagement, quality-oriented vision, and effective benchmarking. In an education system, however, the university leadership and administration present the main challenge. While a great deal of time, effort, training, and resources should be allocated to implementing quality management, the top management teams in many higher education institutions are unable or unwilling to support such programs
Goldberg and Cole (2002) Case study U.S No Based on this study, by applying a cycle of planning, analyzing, and continuously improving, as well as using data from the education process, institutions can make informed decisions and determine areas of success and areas for improvement
Hoecht (2006) Conceptual/interview U.K No While accountability and transparency are well developed in academia, quality practices are very bureaucratic, with a high opportunity cost and usually only addressed on a superficial level
Jaraiedi and Ritz (1994) Conceptual U.S No While teaching is a crucial factor in the quality puzzle, a higher education institution should review its policies and practices to assess whether they really satisfy the needs of the institution's primary customers: the students
Johnson and Golomski (1999) Conceptual U.S No The study recommends applying quality management principles in an education curriculum, improving administration processes and business operations, reducing cycle times, enhancing learning and leadership, understanding and engaging stakeholders and other parties, and identifying opportunities for improvement
Kanji et al. (1999b) Survey Malaysia and U.S No Higher education needs to be guided through quality management and supported by the top management of the organization to enhance business performance. Leadership is therefore the most important factor. Higher education institutions that implement quality management outperform those that do not
Kanji et al. (1999a) Survey U.S No Measuring quality management and core concepts are considered critical success factors for higher education institutions to achieve business excellence
Koch and Fisher (1998) Conceptual U.S No There are limited empirical studies about quality management in educational organizations. Major quality issues at universities include the nature of the curriculum, effective collaboration with industry, and management and leadership arrangements
Lagrosen et al. (2004) Survey Austria
Sweden
U.K
No This study examined the dimensions of higher education’s quality and service quality from the students’ perspective, highlighting information and responsiveness, courses offered, internal audits, computing and IT facilities, collaborations and comparisons, and library resources
Latif et al. (2019) Survey Pakistan No Six quality drivers in higher education services were identified: leadership, teaching, administration services, knowledge services, other activities, and continuous improvement
Lomas (2004) Conceptual U.K No Organizations should identify, train, and nurture transformational leaders and other human actors who are adept in leadership skills and HR management. Organizations may apply specific quality management practices, such as EFQM or TQM, to achieve business excellence
Mahajan et al. (2014) Survey India No Leadership is the most crucial factor, followed by organizational structure and practices. Most factors are interdependent, and they should be seen coherently when assessing their effects on students’ education
Mergen et al. (2000) Case study U.S No This study assessed and showed the impacts of quality on design, conformance, and performance as an effective quality management model in higher education
Michael et al. (1997) Case study U.S No Quality management and improvement in higher education begins at the higher levels of administration. Providing enough training for management and staff is crucial. There may be resistance from top management teams about relinquishing authority to empower staff. These organizations need to change their management behavior, too
Motwani and Kumar (1997) Conceptual U.S No Top management should be involved in understanding and developing an effective plan to successfully achieve quality management. The organizational administration should conduct an internal quality assessment to determine strengths and weaknesses, obtain opinions and feedback from internal and external customers to assess its current state and identify improvement opportunities, and recognize and reward any quality improvements
Newton (2002) Case study U.K No By stressing autonomy, ownership, and self-assessment, an assurance system for quality management helps organization leadership in higher education to understand problems and the risk of exacerbating or exposing them. To conduct change in quality management, top leadership and management teams should assess the status of operations and their emerging trends
O’Mahony
and Garavan (2012)
Case study Ireland No Four key parameters are involved in implementing effective quality management in higher education institutions: senior leadership sponsorship and support, stakeholder involvement, execution of quality practices, and management of cultural change
Osseo-Asare and Longbottom (2002) Case study U.K No This study highlights the importance of staff development strategies for deans, assistant deans, and other staff involved in quality and operational improvement. The strategies should be based on integrating the EFQM model and the U.K. Quality Assurance Agency model. This study suggests comparing the EFQM and MBNQA models for education criteria
Owlia and Aspinwall (1997) Case study Global No From a theoretical perspective, the most critical principle of quality management in universities is customer orientation, because the motivation for academia does not usually depend on market issues. Based on this study’s analysis, the type of activities in educational institutions do not differ from those of manufacturing or other service enterprises. This study demonstrates the importance of several factors: morality among students and stuff, a high level of productivity, and customer focus and satisfaction
Psomas and Antony (2017) Survey Greece No Quality management practices in the Greek higher education system reveal the following concerns: leadership support and commitment, strategic plan for quality, student focus, process management, teaching team, employee engagement, and positive impacts on society
Sahney et al. (2004) Conceptual Global No This study viewed the input quality of educational institutions through the students, teachers, supporting staff, infrastructure, and the process quality of institutions in the form of its teaching and learning activities. Output quality was viewed in terms of the graduating students leaving the institution. This study also treats an educational institution or system as a transformational process that converts unskilled students into competent ones. In this system, the outputs include examination outcomes, employment, earnings, and satisfaction
Sahney et al. (2008) Survey India No Employee satisfaction is the main determinant for adopting an effective “customer-centric philosophy.”
Sarrico and Rosa (2016) Case study Portugal No The main challenges in supply chain quality management in the education sector relate to trust, sharing information, leadership, and integration. There is also a problem in supply chain integration. Developing SCQM models for this sector may aid this integration and lead to performance improvements
Sharabi (2013) Conceptual –- No In education institutions, the service quality delivered to students by the employees in contact with them is highly related to the top management and various departments of the educational institution
Sadiq Sohail et al. (2003) Case study Malaysia No Quality management practices encourage educational institutions to collect data, measure their performance, establish standards, benchmark, and make effective decisions
Srikanthan and
Dalrymple (2004)
Conceptual –- No Developing an effective quality system in education requires transforming it into a learning organization with quality monitoring for learning. Higher education institutions need to develop a vison to guide their actions. Student learning should be the main measure of academic quality, and customer responsiveness needs to be practiced and emphasized
Stahl (2004) Conceptual –- No Both e-teaching and information technology application in teaching may morally threaten the legitimacy of the education process. Strong association between teaching and business interests is one of the main reasons for this issue
Thakkar et al. (2006) Case study India No This study highlights the importance of continuous improvement, cultural improvement, and the optimal use of financial resources to improve service value at all levels
Tsinidou et al. (2010) Survey Greece No Quality of education is studied from the perspective of students. Based on the students’ outcomes, students’ success in the market can be improved by higher quality of teaching, effective library services, skilled employees, and the development of more specialized subjects. Such results also increase the interaction between a university and society
Venkatraman (2007) Conceptual New Zeeland No This study developed a quality management model for higher education that covers leadership, HR management, education management, information management, customer orientation and satisfaction, and partnership
Verma and Parasad (2017) Survey India No This study discusses service quality from a multi-dimensional construct with variables for six aspects: professional, academic, behavioral, industry interaction, physical, and non-academic. The results show internal consistency across the samples
Vesper and Gartner (1997) Survey U.S., Canada, and others Yes They ranked entrepreneurship programs based on seven criteria: courses offered, faculty publications, impact on the community, alumni accomplishments, innovations, alumni startups, and outreach to scholars. They also applied the seven MBNQA criteria to the quality of their programs
Voss et al. (2005) Survey U.S No In both private and public enterprises, progressive HR management leads to greater employee satisfaction, which consequently improves service quality and customer satisfaction. Research shows that HR practices have more impact on these elements than quality practices
Williams (1993) Conceptual –- No To have effective and efficient educational institutions, we need to focus on consistent quality services, continuous improvement, customer satisfaction, and a system for recognizing poor quality and correcting it
Willis and Taylor (1999) Survey U.S No From the employers’ perspective of business school graduates, communication skills and work ethics are the main weaknesses, while IT skills are the main strength. The lack of patience and commitment is another issue that business schools should consider to improve quality outcomes, although some employers asserted that certain schools produce superior graduates
There have been several calls to use well-established quality models like the Baldrige or EFQM models in education settings (Osseo-Asare and Longbottom 2002; Lomas 2004). The studies that used the Baldrige model have collected data using surveys, which solicit the opinions of managers or key stakeholders. These studies targeted primary/secondary schools (Ah-Teck and Starr 2013) or universities/colleges (Vesper and Gartner 1997; Badri et al. 2006; Chin; Buranakul et al. 2017). Ah-Teck and Starr (2013) used MBNQA criteria to conduct a survey and assess the performance of primary and secondary schools in Mauritius. Vesper and Gartner (1997) used MBNQA criteria to assess entrepreneurship programs in the U.S., Canada, and overseas. Badri et al. (2006) used MBNQA criteria to conduct a survey among universities and colleges in UAE. Buranakul et al. (2017) used TQM methods, MBNQA criteria, and survey data to assess TQM impacts on the innovation capabilities of private universities in Thailand. In Hong Kong, Chin et al. (2003) used MBNQA principles to develop a performance toolkit for teaching courses and evaluating performance; they used a survey for their validation phase.
While these studies provide insights into quality management in the education domain, they do not provide a comprehensive assessment of quality management that is grounded in the theory and practice of quality management. Thus, we see a gap in using quality management frameworks such as the Baldrige model in the context of educational organizations. In addition, we could not find any comprehensive study that examined the relationship between quality management practices and operational and business outcomes in educational organizations from a longitudinal aspect. A longitudinal aspect is important, since it provides insight into ways that quality management practices can improve organizational quality outcomes over time and the potential invariance of these relationships over time. Thus, we provide a more nuanced assessment of quality management in educational organizations that examines quality using the Baldrige criteria. Using such a well-rounded framework for quality management provides more insight into the management of quality in educational organizations.
Theory development and research hypotheses
To examine the impact of quality management on quality and operational outcomes in educational organizations, we applied the MBNQA criteria. Previous studies about these criteria have confirmed the relation between leadership and other MBNQA model components (Pannirselvam et al. 1998; Wilson and Collier 2000; Pannirselvam and Ferguson 2001; Parast 2015). Empirical analyses of the MBNQA data show that leadership is a key quality driver because it impacts strategic quality management, information and knowledge management, process quality management, and HR development and management. In the MBQNA program, leadership is the key construct reflecting senior management’s responsibilities and efforts to apply effective leadership practices to cultivate motivation and teamwork, thus building a culture with a high level of trust and creating a successful organization for the near term and the long term. These practices collectively bring about quality and operational outcomes as well as customer orientation and satisfaction. This study examines the relationships among the elements in the MBNQA framework (see Fig. 1 below) and tests the hypotheses using objective data for educational organizations. Table 2 shows our research hypotheses developed in this study and provides a summary of the literature that supports the hypotheses developed in this study.Table 2 Hypotheses for MBNQA in Educational Organizations
Hypothesis Justification
H1a: In education organizations, leadership positively influences the management of process quality Based on the Baldrige model, leadership directly affects process quality. Wilson and Collier (2000), Meyer and Collier (2001), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that quality leadership is significantly related to management of process quality. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) found that leadership support and commitment is the key factor in effective implementation of quality management
H1b: In education organizations, leadership positively influences information and knowledge management Based on the Baldrige model, leadership directly affects information and analysis. Wilson and Collier (2000), Meyer and Collier (2001), and Parast and Golmohammadi (2019) showed that quality leadership is significantly related to information and knowledge management. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) found that leadership support and commitment is the key factor in effective implementation of quality management
H1c: In education organizations, leadership positively influences HR development and management Based on the Baldrige model, leadership directly affects human resource development and management. Wilson and Collier (2000), Meyer and Collier (2001), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that quality leadership is significantly related to human resource development and management. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) argued that leadership support and commitment is the key factor in effective implementation of quality management
H1d: In education organizations, leadership positively influences strategic planning for quality Based on the Baldrige model, leadership directly affects strategic quality planning. Wilson and Collier (2000) and Parast and Golmohammadi (2019) confirmed that quality leadership is significantly related to strategic planning for quality. Elmuti et al. (1996), Kanji et al. (1999b), Csizmadia et al. (2008), and Mahajan et al. (2014) found that leadership support and commitment is the key factor in effective implementation of quality management
H2a: In education organizations, management of process quality positively influences customer focus and satisfaction Wilson and Collier (2000), Meyer and Collier (2001), and Pannirselvam and Ferguson (2001) confirmed that management of process quality is significantly related to customer focus and satisfaction. Research shows that process factors are closely related to service quality and customer satisfaction (Dabholkar and Overby 2005). Asif et al. (2013) discussed that process management is a key element of a successful quality system. Improving process quality was shown to have a positive impact on customers (students) in educational organizations (Ardi et al. 2012)
H2b: In education organizations, management of process quality positively influences quality and operational outcomes Wilson and Collier (2000) and Pannirselvam and Ferguson (2001) confirmed that management of process quality is significantly associated with quality and operational outcomes. Asif et al. (2013) found that process management is a key element of successful quality systems. Thakkar et al. (2006) highlight the importance of continuous improvement, cultural improvement, and the optimal use of financial resources to improve service value at all levels
H3a: In education organizations, information and knowledge management positively influences customer focus and satisfaction Wilson and Collier (2000) and Pannirselvam and Ferguson (2001) confirmed that information and knowledge management is significantly associated with customer focus and satisfaction. Asif et al. (2013) found that information and knowledge management is a key element of a successful quality system. Seeman and O’Hara (2006) discussed the important role of information systems in promoting the student-school relationship
H3b: In education organizations, information and knowledge management positively influences quality and operational outcomes Meyer and Collier (2001) and Parast and Golmohammadi (2019) confirmed that information and knowledge management is significantly associated with quality and operational outcomes. Chavez et al. (2015) showed that information quality mediates the relationship between customer integration and operational performance. Asif et al. (2013) discussed that information and knowledge management is a key element of successful quality systems
H4a: In education organizations, HR development and management positively influences customer focus and satisfaction Wilson and Collier (2000), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that human resource management is significantly associated with customer focus and satisfaction. According to Tsinidou et al. (2010), skilled employees have a positive impact on quality outcomes. Employee satisfaction is the main determinant for adopting an effective “customer-centric philosophy” (Sahney et al. 2008). Voss et al. (2005) argue that HR practices have a significant impact on quality outcomes
H4b: In education organizations, HR development and management positively influences quality and operational outcomes Wilson and Collier (2000), Pannirselvam and Ferguson (2001), and Parast and Golmohammadi (2019) confirmed that human resource management is significantly associated with quality and operational outcomes. According to Tsinidou et al. (2010), skilled employees have a positive impact on quality outcomes in educational organizations. Voss et al. (2005) found that HR practices have a significant impact on quality outcomes
H5a: In education organizations, strategic planning for quality positively influences customer focus and satisfaction Wilson and Collier (2000), Meyer and Collier (2001), and Parast and Golmohammadi (2019) confirmed that strategic planning for quality is significantly associated with customer focus and satisfaction. Fooladvand et al. (2015) discuss the important role of strategic planning in improving quality outcomes in educational organizations. According to Tsiakkiros and Pashiardis (2002), strategic planning is critical to achieving organizational goals and long-term survival
H5b: In education organizations, strategic planning for quality positively influences quality and operational outcomes Wilson and Collier (2000) confirmed that strategic planning for quality is significantly associated with quality and operational outcomes. Fooladvand et al. (2015) discuss the important role of strategic planning for quality in improving quality outcomes in educational organizations. Tsiakkiros and Pashiardis (2002) found that strategic planning in educational organizations is critical to achieving organizational goals and long-term survival
Methodology
This study uses the MBNQA (Baldrige) model and its criteria for quality management, which are the same criteria that were used when collecting the data. These are the criteria: 1) Leadership; 2) Strategic Planning for Quality; 3) Customer Focus and Satisfaction; 4) Information and Knowledge Management; 5) HR Development and Management; 6) Management of Process Quality; and 7) Quality and Operational Outcomes (NIST 2020). An overview of each criterion follows.
Leadership
This key aspect reflects senior management’s responsibilities and efforts to apply effective leadership practices to cultivate motivation and teamwork, thus building a culture with a high level of trust and creating a successful organization for the near term and the long term.
Strategic planning for quality
This reflects an organization’s strategic goals and objectives, its long-term and short-term plans, its action plan, how it measures progress, and how it changes plans when necessary.
Customer focus and satisfaction
This component of quality management relates to how an educational organization engages with its students and other customers. This involves ensuring students’ success but also listening to their voices, so their expectations are addressed and an effective relationship with them is built. This component therefore emphasizes customer engagement and satisfaction as a critical element of effective learning and education performance. In addition to students, there are other important customers such as parents, local businesses, other educational organizations that may receive the students later, and potential employers of the students. A major challenge for educational organizations is finding a balance between the different expectations of students (as the primary customer) and these other stakeholders.
Information and knowledge management
This is considered the core component for aligning operations with strategic goals and objectives. The criteria for education cover the main information for understanding, measuring, evaluating, and improving an educational organization’s performance and knowledge management in order to enhance innovation and competitiveness.
HR development and management
This addresses workforce practices in educational organizations, including the persons who create value and those who support them in doing so, such as teachers, trainers, administrators, and the management team.
Management of process quality
This focuses on educational organizations’ processes and activities, program types, service design and delivery methods, innovation, and operational effectiveness plans and practices for the near term present and long term.
Quality and operational outcomes
This focuses on the results and outcomes that are necessary for sustaining or growing an educational organization, including the results of educational processes, student learning, leadership and governance, workforce outcomes, satisfaction, financial outcomes, and marketing performance.
Data
The required data for each educational organization were collected as part of the MBNQA program. These data consist of 115 organizational scores for educational organizations in the U.S. over a seven-year period from 1999 to 2006, but any given educational organization may not appear in all seven years. Due to the robustness, soundness, and objectivity of the evaluation process, the data are highly reliable (Parast 2015; Parast and Golmohammadi 2019; Parast and Safari 2021, 2022).
Sample
This study’s sample is the data from U.S. educational organizations that applied for the MBNQA award between 1999 and 2006. The data for 1999 were excluded from our analysis, since 1999 was the first year of such data collection. In total, there are 115 observations for the 1999–2006 period.
Table 3 presents a summary of the data for each criterion for each year (mean and standard deviation). The first column gives the year and (in parentheses) the sample size for that year. To examine the normality of our dataset, we needed to estimate the skewness (asymmetry) as well as kurtosis (peakedness) of the dataset. Our estimates for both asymmetry and kurtosis fell between -0.851 and 0.302, which are both within the acceptable range of -1.5 to + 1.5. This demonstrates that our dataset has normal univariate behavior (Tabachnick and Fidell 2013) and meets the requirement of normality. Table 3 Descriptive Statistics
Year Leadership Strategic Planning for Quality Customer Focus and Satisfaction Information and Knowledge Management HR Development
and Management Management of Process Quality Quality and Operational Outcomes
1999 (16) (.43, .16) (.38, .15) (.40, .12) (.36, .15) (.39, .14) (.42, .12) (.35, .16)
2000 (11) (.48, .09) (.42, .13) (.41, .09) (.41, .14) (.42, .09) (.43, .14) (.36, .15)
2001 (10) (.48, .12) (.44, .15) (.43, .12) (.48, .14) (.43, .11) (.43, .11) (.37, .18)
2002 (10) (.35, .10) (.32, .10) (.35, .10) (.35, .13) (.35, .07) (.36, .07) (.29, .08)
2003 (19) (.40, .13) (.33, .12) (.38, .12) (.40, .12) (.38, .08) (.37, .11) (.29, .14)
2004 (17) (.54, .10) (.42, .13) (.44, .11) (.46, .13) (.45, .06) (.45, .12) (.36, .10)
2005 (16) (.49, .12) (.43, .13) (.46, 11) (.48, .11) (.47, .12) (.47, .13) (.39, .13)
2006 (16) (.53, .09) (.51, .11) (.53, .09) (.51, .11) (.52, .11) (.53, .12) (.42, .13)
Table 3 shows that there were significant improvements in the mean value for most criteria (constructs) over the seven years from 1999 to 2006, which could be a result of the widespread application of quality practices. For instance, the Leadership score improved from 0.43 to 0.53 (+ 23%) during this seven-year period. The improvement in the Leadership score can be attributed to the fact that different educational organizations, more advanced in quality management, applied in the later years. We can see similar improvement patterns for other MBNQA constructs: Strategic Planning for Quality increased from 0.38 to 0.51 (34.2%), Customer Focus and Satisfaction increased from 0.40 to 0.53 (32.5%), Information and Knowledge Management increased from 0.36 to 0.5 (41.7%), HR Development and Management increased from 0.39 to 0.52 (33.3%), and Management of Process Quality increased from 0.42 to 0.53 (26.2%), and most importantly, Quality and Operational Outcomes increased from 0.35 to 0.42 (20%) as our main output. While we have seen declines in quality and operational results in other segments such as healthcare (Parast and Golmohammadi 2019), the overall improvement in the education sector is quite significant.
Table 4 presents the overall mean, standard deviation (SD), and pairwise correlation of the MBNQA criteria. It shows that the scores for quality management constructs in these educational organizations range from 0.36 to 0.45 (out of 1), implying that there is a significant shortfall in effectively applying quality management practices in these organizations. Furthermore, these constructs are highly correlated, which reflects the considerable interrelationships among the MBNQA model elements that were supported and envisioned in the literature.Table 4 Overall Attributes and Pairwise Correlation of Criteria (Constructs)
Mean S.D 1 2 3 4 5 6 7
1. Leadership .45 .13 1.00
2. Strategic planning for quality .41 .14 .842*** 1.00
3. Customer focus and satisfaction .43 .12 .863*** .840*** 1.00
4. Information and analysis .43 .14 .822*** .853*** .851*** 1.00
5. HR development and management .43 .11 .842*** .808*** .832*** .802*** 1.00
6. Process management for quality .44 .13 .824*** .820*** .817*** .837*** .812*** 1.00
7. Quality and operational outcomes .36 .14 .777*** .809*** .767*** .779*** .749*** .800*** 1.00
***p < .01
Data analysis and estimation procedure
In this study, we applied the structural equation modeling (SEM) approach for our analysis. SEM allows the analysis and testing of complex associations among various independent and dependent variables simultaneously, so there can be more than one output variable. Additionally, SEM can be regarded as effectively combining both factor analysis and regression analysis to analyze the structural associations among observed and latent variables (Bagozzi and Yi 2012).
Measurement model—validation and analysis
To verify our SEM analysis and examine the overall fitness of our MBNQA model for educational organizations, we used confirmatory factor analysis (CFA), because, as stressed by Hair et al. (2009), CFA is an important method for full model measurement. Our CFA goodness-of-fit statistic showed the overall fitness of the model to be (χ2/df = 1.17, RMSEA = 0.038 (0.01, 0.065); RMR = 0.001). Based on this result, all the key parameters of Chi-Square, RMSEA, and RMR fall within the respective acceptable and recommended ranges (Hu and Bentler 1999). In addition, we applied the Kaiser–Meyer–Olkin method of sampling adequacy to evaluate the validity of the factor model (Kärnä et al. 2003). We received a result of KMO = 0.96 and χ2 = 2201.24 with p < 0.01, which suggests there are no concerns regarding the factor model.
Next, we estimated the reliability for our main constructs using Cronbach’s alpha. These values were also found to be within the recommended range (between 0.84 and 0.93). A reliability value greater than or equal to 0.7 is acceptable for survey study (Hair et al. 2009). As Table 5 shows, our estimation of the standardized loadings for the model are all significant, thus proving the convergent validity of the model. Additionally, we tested composite reliabilities and average variance extracted (AVE) to ensure convergent validity and discriminant validity (Fornell and Larcker 1981; Agarwal 2013; Henseler et al. 2015). The “Item” column lists each sub-construct used in our analysis. Descriptions of the entries in this column are provided in Appendix A. Table 5 Properties of the Constructs and Model
Scale Measurements
Reliability Composite reliability Item
(Sub-construct) Loading Average Variance Extracted
Leadership .87 .95 L11 .94 .92
L12 .89
Strategic Planning for Quality .93 .93 S21 .96 .89
S22 .95
Customer Focus and Satisfaction .90 .93 C31 .90 .89
C32 .87
Information and Analysis .89 .96 I41 .95 .93
I42 .91
HR Development
and Management
.89 .97 H51 .87 .88
H52 .93
H53 .85
Process Management .87 .97 P61 .92 .92
P62 .91
Quality and Operational Results .93 .98 Q71 .87 .68
Q72 .95
Q73 .90
Q74 .88
Structural Model and the Testing of Hypotheses
Control variables
There are two control variables, namely for industry (i.e., educational organizations) and application year. We assigned a vector of dummy variables for each year (Y1999 through Y2006), applying 1999 as the reference year.
Statistical procedure
As indicated earlier, to assess the validity of the conceptual framework as shown in Fig. 1, we applied the SEM approach using AMOS 25.0 software. Table 6 shows the outcome of this analysis: the regression coefficients and corresponding p-value for each path. These results are consistent with the main hypotheses H1a through H1d. They show that Leadership significantly and positively influences the following variables: Management of Process Quality (ß = 0.975, p < 0.05), Information and analysis (ß = 0.991, p < 0.05), HR development and managementt (ß = 0.917, p < 0.05), and Strategic quality planning (ß = 0.957, p < 0.05). Information and analysis significantly and positively influences Customer focus and satisfaction (ß = 1.861, p < 0.05) (H3a). Management of process quality is a significant predictor for Quality and operational results (ß = 0.615, p < 0.10) (H2b). The details of all these relations are presented in Table 6. We were not able to find support for hypotheses H2a, H3b, H4a, H4b, H5a and H5b. Table 6 Coefficients
Controls Dependent Variables Independent Variables
Customer focus and satisfaction Quality and operations results Strategic quality planning Information and
analysis HR development and management Management of process quality
Y2000 -.178* .053 .015 .036 .042 -.111*
Y2001 -.392** .053 .043 .199** .068 -.086
Y2002 -220* .046 .075 .210** .096 .063
Y2003 -.423** .024 -.034 .237** .083 -.051
Y2004 -.319** -.019 .090* .292** .225* .085
Y2005 -.331** .011 .001 .208** .141* .006
Y2006 -.113 -.078 .109** .192** .225* .058
Predictors Customer focus and satisfaction Quality and operations results Strategic quality planning Information and
analysis
HR Development Management of process quality
Leadership n.s n.s .957** .991** .917** .975**
Strategic quality planning -.261 .338
Information and analysis 1.861** .013
HR Development -.023 -.034
Management of process quality -.578 .615*
n.s. hypothesis is not stated
*p ≤ .10; * p ≤ .05 **
Robustness and validation tests
Normality test
Even though the normality assumption in data is necessary for regression analysis, it is not required for the SEM approach (Sharma et al. 1989; Lei and Lomax 2005). We applied the skewness and kurtosis measures to examine data symmetry and peakedness, which were found to be in the range of -0.702 to 0.238. Thus, we concluded that normality assumptions for the data were met.
Heteroscedasticity test
To ensure that we obtained unbiased estimates, a heteroscedasticity test was needed. Heteroscedasticity reflects the situation that the regression variance disturbances (or the variance of error terms) is not constant across observations (Greene 2012). We plotted predicted values vs. residuals and found no evidence of heteroscedasticity in the dataset.
Multicollinearity test
The multicollinearity test concerns the insensitivity of the results to interrelationships or correlations among variables. Based on our analysis, all the variable inflation factor (VIF) values estimated by our multiple regression analysis were below the recommended value (10), since the highest VIF value was 4.6. This means that there was no major concern about multicollinearity in the dataset (Belsley et al. 1980; Hair et al. 2009).
Alternative structural models
We evaluated whether the alternative structural models proposed in the literature would significantly improve the model’s fit. An alternative structural model proposed for the MBNQA suggests a mediating relationship between Information and Analysis and other quality management practices (Wilson and Collier 2000). This alternative model shows model fit statistics of χ2/df = 1.983, RMSEA = 0.093; RMR = 0.004; CFI = 0.922. This is not significantly different from the structural model proposed in this study (χ2/df = 1.94, RMSEA = 0.091; RMR = 0.004; CFI = 0.924). The second alternative model, which was proposed by Flynn and Saladin (2001), introduces three more paths in addition to the model proposed by Wilson and Collier (2000): a path from Customer orientation and focus to Process management, a path from HR development to Process management, and a path from Strategic planning to HR development. This structural model gives fit statistics of χ2/df = 1.983, RMSEA = 0.093; RMR = 0.004; CFI = 0.922. Again, this was not significantly different from the structural model proposed in this study. We also realized that these two alterative models were primarily developed and verified in manufacturing settings, where only Quality and operational results is considered for the outcome. Our empirical results, along with the nature of the educational organizations, suggest that the model proposed in this study considers both customer focus and quality results as outcomes for a quality system, so it is a suitable model for quality management and business excellence in educational settings.
Discussion
This study provides the first comprehensive, data-driven, and empirically sound assessment of quality management practices for educational organizations. In addition to providing a suitable theoretical and conceptual framework for assessing quality management in education settings, this study uses assessments from independent reviewers for quality practices to yield a high level of reliability and validity for the data, thus ensuring the robustness of the results and findings. Furthermore, the longitudinal nature of the data, which covers quality practices over a seven-year period, captures the nuances related to the association between quality management practices and quality results over time, thereby increasing the robustness of the results when compared to cross-sectional surveys that are administered at just a given point in time. This means that the relationships go beyond simple correlations and there is a stronger case for causality.
Theoretical contributions
This research makes several contributions to the literature in the field of operations management, quality management, informing public policy, and governance practices at educational organizations. First, to the best of our knowledge, this study is the first empirical assessment of the use of a well-established quality management model in educational organizations. Our findings suggest that quality management models like the MBNQA framework are compatible with educational organizations and can be used to enhance quality outcomes and achieve business excellence.
Second, this study builds upon the relatively dispersed previous research into quality management in educational settings, and it further advances our understanding of how quality management practices, which were developed primarily for production and manufacturing systems, can improve quality results in education settings (Elmuti et al. 1996; Kanji et al. 1999b; De Jager and Nieuwenhuis 2005). Using high-quality data from educational organizations, we have provided an early but comprehensive assessment of quality management in educational settings. This effort addresses two main gaps in the current literature by 1) using independent professional reviewers’ scores, which are objective and reliable, and 2) using seven years of data for educational organizations, thus enabling a more rigorous evaluation of the associations between quality management practices and quality and operational outcomes. The robustness of the MBNQA model and the quality of the data ensure the validity of the results.
Third, our research improves our understanding of how educational organizations can enhance their business operations and quality by applying the MBNQA model. Consistent with prior anecdotal evidence for quality management practices in educational organizations (Elmuti et al. 1996; Csizmadia et al. 2008; Asif et al. 2013), our findings show that Leadership is the key driver of quality management practices in educational organizations, which in turn significantly influence all other quality management elements. This supports prior studies that have suggested an interdependence among quality practices in educational organizations (Mahajan et al. 2014). We examined the Leadership effects from two perspectives. First, Leadership directly and positively impacts other constructs of the model, including Information and analysis, Strategic planning for quality, HR development and management, and Quality process management. This outcome affirms the Baldrige theory that Leadership drives systems, and this outcome also supports previous studies that have articulated how the strong commitment and sponsorship of the senior leadership team is a key driver of quality improvement (Psomas and Antony 2017). It also supports the anecdotal evidence that a university’s top administration presents the main obstacle to implementing a quality management system (Elmuti et al. 1996). Leadership also significantly influences Strategic planning (ß = 0.957, p < 0.05), and this is one of the greatest impacts among the MBNQA criteria. This suggests that in educational organizations, leaders must recognize the importance of long-term strategies for quality; this also supports former studies that have emphasized the crucial role of strategic planning and development as an important factor in the successful implementation of quality management in educational organizations (Osseo-Asare and Longbottom 2002; Basari and Altinay 2018).
Our fourth contribution concerns the significant impact of Process quality management on Quality and operational results (ß = 0.615, p < 0.1). Studies have well discussed the challenges related to process management and process improvement in service organizations (Ettlie and Rosenthal 2011); however, this study found that Management of process quality significantly affects quality and operational results in educational organizations. Studies confirm that applying a process approach to quality improvement (e.g., Lean and Six Sigma) leads to significant improvement in business processes and their outcomes (Assarlind and Gremyr 2016). Our findings support the recommendation put forward in the literature about the important role of process management and process improvement, as well as decision-making processes, in educational organizations (Asif et al. 2013; Goldberg and Cole 2002; Csizmadia et al. 2008). Our results also support the efforts of Zhao et al. (2008) as well as Harris et al. (2011), who showed the importance of process management in a successful implementation of quality management. Our findings extend that effect of process management to educational organizations.
The sixth contribution of this study is about the significant association between Information and knowledge management and Customer focus and satisfaction in educational organizations (ß = 1.861, p < 0.05). This has by far the largest coefficient among quality management and quality outcomes in educational organizations. The important role of information, analysis and knowledge management has been extensively discussed in the literature (Lagrosen et al. 2004; Venkatraman 2007; Sarrico and Rosa 2016), but empirical evidence for the effect of information and knowledge management on improving quality results in educational organizations had thus far been overlooked. Studies of the relationship between investment in information systems and customer satisfaction have also yielded mixed findings in business settings (Mithas et al. 2016). Our empirical results support the previous studies that have highlighted the importance of information systems and knowledge sharing for enhancing organizational performance in a business (i.e., profit-driven) setting (Lloyd-Walker and Cheung 1998; Demirbag et al. 2012). Information analysis, and knowledge management is an engine for quality improvement in educational organizations, and it is a key driver for continuous improvement and the transition to a learning organization in educational organizations (Goldberg and Cole 2002; Srikanthan and Dalrymple 2003).
Finally, our findings provide further important knowledge about the long-term effects of quality management solutions on educational organizations. While the literature expresses mixed opinions concerning the effectiveness of quality management programs (e.g., Asif et al. 2009; Bourke and Raper 2017), we tried to shed more light on the long-term impact of quality management programs on educational organizations. By reviewing the effects for each year and comparing them with our reference year (1999), we could provide valuable insight into this effect for service organizations. Reviewing the coefficients for Customer focus and satisfaction for the year-effect (see Table 6), we found a negative trend from 2000 (ß = -0.178, p < 0.1) to 2005 (ß = -0.331, p < 0.05). This suggests that compared with 1999, there was a decline in customer focus and satisfaction over time. This implies that, on average, the educational organizations were not able to address the needs and interests of their customers over time, hence the declining trend. In contrast, we can see significant improvements in Information and Analysis, where the year-effect shows a positive trend from 2001 (ß = 0.199, p < 0.05) to 2006 (ß = 0.192, p < 0.05). This demonstrates that while implementing quality management in educational organizations improves Information and analysis, it does not necessarily lead to a sustained improvement in Customer focus and satisfaction. The theoretical contribution of these observations is that it suggests diminishing returns on investment, in terms of customer focus practices, from information and knowledge management over time. This accords with the diminishing public trust in educational organizations (Salisbury and Horn 2019). It also provides an interesting observation for explaining the mixed results for the effectiveness of quality management programs, because this temporal effect cannot be captured with cross-sectional surveys. In addition, solely relying on the use of information technologies and information systems does not necessarily lead to better customer satisfaction. The information and analysis need to be incorporated into the development of new processes and reflected in organizational practices in order to address customers’ needs and interests and achieve a sustainable level of customer service quality. If they are not, the effect will be limited, and the information and analysis will not lead to process improvements or changes in organizational practices. Thus, educational organizations need to be aware that simply investing in information systems, library resources, and other informative and educational resources do not necessarily lead to better quality results, especially if input from multiple stakeholders is not incorporated into the design of information systems and improvements for organizational processes.
Implications for education administrators
This empirical study offers suggestions and insights for the administrators of educational organizations. First, as higher education organizations begin to refine their quality initiatives, they can consider using the MBNQA framework and criteria to diagnose their defects and issues and to analyze, restructure, and streamline their business processes, systems, and quality-improvement efforts. When service organizations are committed to enhancing their businesses and operational results, the Baldrige model is an effective and comprehensive approach for assessment. In addition, educational organizations should recognize the crucial role of investment in Information and knowledge management to fulfil their customers’ needs and consider their customers’ opinions in services. Education organizations interact with multiple stakeholders and engage with a variety of customers, so attention must be paid to developing information systems and investing in enterprise information systems that can capture data from multiple stakeholders and incorporate them into organizational processes, because this will be critical for an educational organization’s success. During the COVID-19 pandemic, educational organizations that had invested in information technology, support systems, and other related infrastructure were able to mitigate the impact of the pandemic and transition more smoothly to a virtual learning environment, thus minimizing the impact on student learning.
Education administrators should also consider the crucial role of process management in their business operation. Most business improvement approaches (e.g., TQM, ISO 9000, Kaizen, Lean, and Six Sigma) focus on business processes and continuous improvement to enhance organizational outcomes such as customer satisfaction and quality and operational results. Administrators also need to pay more attention to investing in information systems, analytics, and organizational learning to improve their informed decision making, to enhance their service operations and customer satisfaction using data-driven approaches. Finally, to improve service quality and customer satisfaction, educational administrators should be mindful of the importance of soliciting input from multiple stakeholders and incorporating this into their decisions for improving organizational processes.
Limitations and future research
The MBNQA data for educational organizations is only available for the 1999–2006 period. This study could have been more effective if it had used more recent data for this model. Another limitation of the study is related to the sample size. While we were able to assess the validity of the results using a variety of fit indices, it is recommended that future studies examine the validity of the Baldrige model in educational institutions using a larger sample.
Furthermore, the availability and inclusion of other related parameters—such as age, size, and organizational type (i.e., private vs. public)—could have yielded valuable insights about the effects of these contextual and organizational parameters on quality outcomes in educational organizations. Some argue that the success of an organization such as Arizona State University in revolutionizing its educational system is related to its size (Salisbury and Horn 2019). Thus, the inclusion of other variables would have supported a more nuanced assessment of quality management in educational organizations. We are mindful that access to more detailed information about educational organizations such as type of the organization (e.g., university, non-profit) along with other organizational factors would provide a more robust assessment of quality management in educational organizations.
We should also be careful about generalizing this study’s outcomes. Since we used data from the United States, we may reasonably expect that we could extend the findings to other economies that experience similar management, social, and legal platforms. It would also be interesting to compare, analyze, and generalize the impact of similar quality excellence frameworks—such as the Deming Prize, EFQM, and other national quality award models—on the quality and operational outcomes of educational organizations.
Appendix A Description of each sub-construct listed in
Construct Items (sub-constructs)
1. Leadership (LEA) L11) Senior Leadership: How do your senior leaders lead the organization?
L12) Governance and Societal Contributions: How do you govern your organization and make societal contributions?
2. Strategic Quality Planning (STR) S21) Strategy Development: How do you develop your strategy?
S22) Strategy Implementation: How do you implement your strategy?
3. Customer Focus and Satisfaction (CFS) C31) Customer Expectations: How do you listen to your customers and determine products and services to meet their needs?
C32) Customer Engagement: How do you build relationships with customers and determine satisfaction and engagement?
4. Information and Analysis (INF) I41) Measurement, Analysis, and Improvement of Organizational Performance: How do you measure, analyze, and then improve organizational performance?
I42) Information and Knowledge Management: How do you manage your information and your organizational knowledge assets?
5. Human Resource Development and Management (HRD) H51) Workforce Environment: How do you build an effective and supportive workforce environment?
H52) Workforce Engagement: How do you engage your workforce for retention and high performance?
6. Management of Process Quality (PRO) P61) Work Processes: How do you design, manage, and improve your key products and work processes?
P62) Operational Effectiveness: How do you ensure effective management of your operations?
7. Quality and Operational Results (RES) Q71) Product and Process Results: What are your product performance and process effectiveness results?
Q72) Customer Results: What are your customer-focused performance results?
Q73) Workforce Results: What are your workforce-focused performance results?
Q74) Leadership and Governance Results: What are your senior leadership and governance results?
Q75) Financial, Market, and Strategy Results: What are your results for financial viability and strategy implementation?
1 The data for Baldrige assessments became available in 2011.
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Soc Psychol Educ
Soc Psychol Educ
Social Psychology of Education
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Article
Resilience and grit predict fewer academic and career concerns among first-year undergraduate students during COVID-19
http://orcid.org/0000-0003-0880-5930
Lytle Ashley [email protected]
1Ashley Lytle
is an Assistant Professor of Psychology at Stevens Institute of Technology in Hoboken, New Jersey, USA. Lytle earned her PhD at Stony Brook University, New York, USA. Her research explores how intergroup dynamics, belief systems, and other psychosocial factors impact academic, social, and health outcomes. Much of Lytle’s research has focused on better understanding prejudice toward older adults, sexual minorities, and women, with the goal of creating simple, yet effective, interventions to reduce bias.
Jiyun Shin Elizabeth L. [email protected]
2Jiyun Elizabeth Shin
is a Lecturer in the Department of Psychology at Binghamton University and earned her Ph.D. in Social Psychology from Stony Brook University. Shin’s research examines various individual beliefs and psychosocial factors that affect students’ academic engagement and outcomes. One of her primary aims is to develop psychosocial interventions to promote positive academic outcomes for students from underrepresented groups and disadvantaged backgrounds.
1 grid.217309.e 0000 0001 2180 0654 College of Arts and Letters, Stevens Institute of Technology, 1 Castle Point on Hudson, 07030 Hoboken, NJ United States
2 grid.264260.4 0000 0001 2164 4508 Binghamton University, Binghamton, United States
5 12 2022
114
30 7 2022
15 11 2022
16 11 2022
© The Author(s), under exclusive licence to Springer Nature B.V. 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Since March 2020, the COVID-19 pandemic has profoundly disrupted higher education in the United States (U.S.). During the first wave of infection and hospitalization, many universities and colleges transitioned classroom instruction to online or a hybrid format. In September 2021, classes largely returned to in-person after the COVID-19 vaccine was widely available and, in some cases, mandated on university and college campuses across the U.S. In the current research, first-year undergraduate students answered a series of questions about their resilience, grit, and perceived academic and career impacts from the ongoing COVID-19 pandemic in Spring (February/March - May) 2021 and 2022. Findings from a series of regression analyses showed that grit and resilience seemed to protect students and help them stay on track, even in the face of the global pandemic. Undergraduate students who reported higher levels of grit and resilience were less likely to worry about job opportunities shrinking as well as less likely to report changing their academic goals, career goals, and proposed major. Future directions and implications are discussed.
Keywords
Academic concerns
COVID-19 pandemic
Grit
Psychosocial factors
Resilience
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pmcSince March 2020, the COVID-19 pandemic has profoundly disrupted higher education in the United States (U.S.). As the COVID-19 pandemic spread, by late March 2020, approximately 1,102 universities and colleges in the U.S. had moved their classes online (Johnson Hess, 2020). Initially the shift to online education was purported to be temporary, as universities and colleges moved operations online for an initial two-week period. However, as the COVID-19 pandemic rapidly evolved, by early April 2020, many institutions of higher education realized the shift to online education would likely be longer, at least through the rest of the semester or term. In reality, hundreds of universities and colleges did not transition back to majority in-person classes until Fall 2021, when vaccinations were more readily available and in some cases had been mandated on campus.
In addition to the shift to online education, COVID-19 caused a profound reckoning among undergraduate students in terms of their career goals and perceptions of career opportunities. In the midst of the first wave of COVID-19 infections in the U.S., during April 2020, 1,500 undergraduate students were asked about their experiences and expectations as a result of the pandemic. 40% of students reported having lost a job, an internship, or an offer of a job or internship as a result of the COVID-19 pandemic. Roughly one third (29%) of undergraduate students reported expecting to earn less at age 35 as a result of the pandemic (Aucejo et al., 2020). In another survey about the COVID-19 pandemic, conducted in Spring 2020, more than one third of undergraduate students reported feeling less certain about their future educational plans (Usher et al., 2021).
Challenges and stressors are a normal part of the college experience, however, the existence of a global pandemic has likely exacerbated an already challenging and stressful time for many. For example, a growing body of research suggests that depression and anxiety symptoms increased among adolescents and young adults in the midst of the COVID-19 pandemic (Hawes et al., 2021). Although this global pandemic likely impacted all students in the U.S. in some way, there may be individual differences in students’ perceptions and responses to the pandemic. For instance, psychosocial factors, such as resilience and grit may serve as protective factors for students during times of heightened stress and uncertainty. Grit and resilience have been associated with academic outcomes such as engagement and retention, and identified as important psychosocial variables during times of transition (Lytle & Shin, 2020; 2022; Galatzer-Levy et al., 2012; Good et al., 2012; Leslie et al., 2015). Given the ongoing global disruptions to academic and career outcomes as result of the COVID-19 pandemic, a better understanding of potentially protective psychosocial factors is essential.
Grit
Grit is perseverance and passion for long-term goals (Duckworth et al., 2007). The concept of grit taps into something not captured by other traditional predictors of success, representing a unique construct as demonstrated by a burgeoning body of research (Duckworth & Quinn, 2009). For example, in Duckworth and colleagues’ (2007) seminal paper on the concept, grit predicted several academic outcomes such as educational outcomes among undergraduate students at elite universities and the rankings of National Spelling Bee contestants. Grit was also associated with a number of career changes among adults, such that high levels of grit predicted fewer career changes (Duckworth & Quinn, 2009).
Past research illustrates that grit was predictive of academic and career outcomes above and beyond IQ, self-control, and personality traits such as conscientiousness (Duckworth et al., 2007; Duckworth & Quinn, 2009; Duckworth & Gross, 2014). Whereas, more recent research has explored grit as a non-cognitive variable predictive of performance in academic domains (Fosnacht et al., 2019). Other findings from the literature include a positive relationship between grit, engagement, and academic productivity (Filmore, 2015; Hodge et al., 2018) and grit as a predictor of academic engagement among college students (Lytle & Shin; 2022; Fosnacht et al., 2019; Hunter, 2020).
In the wake of the COVID-19 pandemic, a slew of new research exploring the psychological effects as a result of lockdowns and social isolation, daily changes to routine, health concerns related to COVID-19, and more emerged (Killgore et al., 2020). For example, in one study conducted among Japanese adults during July 2020, grit had a buffering effect on the relationship between psychological distress and fear of COVID-19 (Masuyama et al., 2022). In another study, grit had indirect effects on social and well-being outcomes among individuals in the U.S. and the Philippines (Datu & Fincham, 2022). Similarly, high pandemic-related stress was associated with lower grit among undergraduate students from different colleges and universities across the U.S. (Schmahl & Nguyen, 2022).
The potential relationship between grit and academic outcomes as a result of the ongoing COVID-19 pandemic are less well understood. A recent study, which examined grit in the context of the pandemic during Spring 2020, found that grit predicted significantly greater pandemic resilience and marginally lower psychological impact among undergraduate students (Bono et al., 2020). In a study of nursing students, which explored challenges and difficulties during COVID-19, grit and resilience were factors that emerged as important to success in nursing programs (Munn et al., 2022).
Resilience
Resilience is the ability to bounce back after a difficult situation or experience. Resilient individuals adapt easily and quickly adjust to stressful situations as well as major life events (Beasley et al., 2003; Loh et al., 2014). Much of the work on resilience has examined this psychosocial variable in the context of real-world events. For example, after natural disasters, resilience is a significant protective factor against mental health disorders such as depression and PTSD and is associated with general health (Kukihara et al., 2014). Past research has explored the onset and offset of psychological issues in the wake of disasters, demonstrating that resilience is a common post-disaster outcome (Goldmann & Galea, 2014). Resilience does not indicate the lack of psychological symptoms after exposure to or experiencing a traumatic event, however, it does involve the ability to rebound to traumatic or challenging events (Klein et al., 2003).
The study of resilience has also been applied to academic contexts, such that resilience has been identified as an important factor in engagement and retention. The ability to adapt and demonstrate flexibility in new environments may be especially important among undergraduate students during the transition to university (Galatzer-Levy et al., 2012). For example, resilience was a significant positive predictor of college adjustment for first-year students in the U.S. (Haktanir et al., 2021). During the transition to college, students encounter various challenges such as increased academic pressures, changes in one’s social support system including the need to develop new relationships, increased personal responsibility, and changes to one’s environment (Galatzer-Levy et al., 2012; Vaez & LaFlamme, 2008).
In the early days of the COVID-19 outbreak in the U.S., resilience was identified as a key factor for coping with the ensuing change, uncertainty, and hardship brought on by the pandemic (Liu et al., 2020; Killgore et al., 2020). In a cross-sectional study which examined protective and risk factors for mental health among young adults in the U.S. between April and May 2020, resilience emerged as a protective factor for mental health (Liu et al., 2020). Simlarly, higher rates of resilience were associated with lower worry about the impacts of COVID-19 (Killgore et al., 2020). In another study, conducted in Colombia during June 2020, undergraduate and post-graduate students with higher levels of resilience were less susceptible to COVID-19’s impact on mental health (Paredes et al., 2021).
Current research
The current study extends existing research on grit and resilience, examining how these concepts may serve as protective factors for undergraduate students during the heightened stress and uncertainty due to the COVID-19 pandemic. More specifically, this novel study examines whether grit and resilience predict perceived COVID-19 impacts on academic and career outcomes. Building on the existing literature on grit and resilience, we hypothesize that undergraduate students’ self-reported grit and resilience will predict fewer perceived impacts due to the COVID-19 pandemic. More precisely, greater levels of grit will predict fewer academic goal changes (H1a), career goal changes (H1b), major changes (H1c), and less career opportunities concerns (H1d). Similarly, greater levels of resilience will predict fewer academic goal changes (H2a), career goal changes (H2b), major changes (H2c), and less career opportunities concerns (H2d).
Method
Participants
Spring 2021: A total of 667 first-year undergraduate students (women = 235, men = 426, gender identity not listed = 6; Mage=18.57, SDage = 0.73) from a private university in the U.S. completed the survey between March - May, 2021. Stevens Institute of Technology is located in the Northeastern U.S. with approximately 4,000 undergraduate students in total. The current research was conducted among first-year students of which there are approximately 1,000 each year. The majority of students major in STEM and the gender split is approximately 70% men and 30% women. Participants were racially and ethnically diverse with 55.6% of participants being European American/White, 16.0% East Asian, 10.3% South Asian, 12.6% Latino/Hispanic, 0.7% African American/Black, 0.7% Native American/American Indian/Alaskan Native, 3.6% other or mixed race, and 0.7% missing response. Consistent with exclusion criteria used in previous research (Lytle & Shin, 2020; 2022), a total of 34 participants were removed for completing the survey in fewer than 3 min or longer than 90 min, resulting in a final sample of 633 participants. The average completion time for the survey was 10.27 min.
Spring 2022: A total of 797 first-year undergraduate students (women = 274, men = 514, gender identity not listed = 9; Mage=18.58, SDage = 1.11) completed the survey between February - May, 2022. Participants were racially and ethnically diverse with 52.2% of participants being European American/White, 12.5% East Asian, 9.5% South Asian, 15.3% Latino/Hispanic, 2.5% African American/Black, 0.4% Native American/American Indian/Alaskan Native, 5.9% other or mixed race, and 1.6% missing response. Consistent with exclusion criteria used in previous research (Lytle & Shin, 2020; 2022), a total of 58 participants were removed for completing the survey in fewer than 3 min or longer than 90 min, resulting in a final sample of 739 participants. The average completion time for the survey was 10.97 min.
Procedure
Participants were recruited via a university subject pool. All first-year students participate in the subject pool and thus the participants are not restricted to social science students or social science majors (e.g., psychology; as is common in many subject pools). Students who do not want to participate in research have the option of completing alternative assignments, although less than 2% opt to complete the alternative assignments.
Approximately 1,000 eligible participants are part of the subject pool each academic year. Students are able to choose different studies to complete. In both Spring (February/March - May) 2021 and 2022, interested participants were directed to a secure website, Qualtrics, to complete a survey about “Careers.” Participants were told that we were interested in their “attitudes and beliefs about their careers.” If participants consented, they were given access to the survey and completed the measures during a single time point. In addition to the psychosocial variables of interest (grit and resilience) and questions about perceived academic and career impacts given the ongoing pandemic, participants also reported their age, gender, and race/ethnicity. The university’s institutional review board approved this research prior to data collection.
COVID-19 context in Spring 2021 and 2022
The context of the COVID-19 pandemic was different in Spring 2021 and Spring 2022. In Spring 2021, the majority of classes at Stevens Institute of Technology were still being conducted online or in a hybrid format. Partway through Spring 2021, vaccines became widely available in the U.S. For example, by April 15, 2021, almost all U.S. states had made COVID-19 vaccines eligible to adults 16+. In Spring 2022, nearly all classes had returned to in-person instruction and a vaccine mandate was in place on campus.
Measures
Grit
An 8-item measure of grit (Duckworth & Quinn, 2009) was used to assess participants’ passion for long-term goals and ability to persevere. The response options ranged from 1 (Very much like me) to 5 (Not much like me at all; α = 0.75) on a 5-point scale. Sample items included: “I often set a goal but later choose to pursue a different one” and “I have difficulty maintaining my focus on projects that take more than a few months to complete.” Four of the items were reverse coded (e.g., “Setbacks don’t discourage me” and “I am a hard worker” ) such that higher scores indicated more grit.
Resilience
A 10-item measure of resilience (Connor & Davidson, 2003) was used to assess participants’ resiliency. Using a 5-point scale, the response options ranged 0 (Not true at all) to 4 (True nearly all the time; α = 0.90). Sample items included: “I can deal with whatever comes my way,” “Under pressure, I stay focused and think clearly,” and “I tend to bounce back after illness, injury or other hardships.” Higher scores indicated greater resilience.
COVID-19 Academic and Career Impacts
Participants’ were asked four questions about their perceived academic and career impacts due to the ongoing COVID-19 pandemic. Participants were asked, “Are you concerned about job opportunities shrinking as a result of the ongoing COVID-19 pandemic?” on a 5-point scale (‘not at all’ to ‘extremely’). In addition, participants were asked, “As a result of the ongoing COVID-19 pandemic, have any of the following changed?” with three categories: “My academic goals,” “My career goals,” and “My proposed major” on a 5-point scale (‘did not change at all to ‘completely changed’).
Analysis overview
All the analyses were performed using SPSS (version 28). Given the significant changes from Spring 2021 to Spring 2022 in COVID-19 vaccine availability, public health guidelines, and the return to in-person learning, prior to the main hypothesis testing, differences in the major study variables (i.e., four perceived academic and career impacts variables) between Spring 2021 and Spring 2022 cohorts were examined. A multivariate analysis of variance (MANOVA) was used for this analysis as it allows simultaneous examination of group differences on multiple dependent variables. The MANOVA was followed up with a series of univariate analysis of variance (ANOVA) to determine which of the four perceived academic and career impacts variables the Spring 2021 and Spring 2022 participants differed on. Furthermore, to examine potential demographic (gender, race, and age) differences between Spring 2021 and Spring 2022 participants, chi-square tests and a t-test were conducted.
To test the main hypotheses that grit and resilience would predict fewer perceived academic and career impacts due to the ongoing COVID-19 pandemic, a series of regression analyses were performed with grit and resilience separately as predictors and the four perceived academic and career impacts variables as the outcome variables.
Results
Table 1 presents the means, standard deviations, and correlations among the study variables separately for Spring 2021 and Spring 2022 participants. A MANOVA was conducted to examine the differences in perceived academic and career impacts of the pandemic between Spring 2021 and Spring 2022 participants while controlling for race as a chi-square test revealed a significant difference in race between these cohorts, X2 (6, N = 1357) = 14.38, p = .026. No other demographic differences were found (gender: X2 (2, N = 1372) = 0.13, p = .94; age: t(1370) = -0.46, p = .65, d = 0.03).
Table 1 Correlations, Means, and Standard Deviations for All Study Variables
Variables 1
Grit 2
Resilience 3
Career Concerns 4
Academic Goals Change 5
Career
Goals Change 6
Proposed Major Change
Scale Range 1–5 1–5 1–5 1–5 1–5 1–5
Spring 2021 (n = 633)
1 - - - - - -
2 .46*** - - - - -
3 -.08 -.04 - - - -
4 -.13** -.17*** .15*** - - -
5 -.12** -.10* .16*** .66*** - -
6 -.07 -.08 .07 .42*** .58*** -
M 3.17 3.74 2.85 1.71 1.53 1.28
SD 0.65 0.63 1.18 1.07 0.99 0.76
Spring 2022 (n = 739)
1 - - - - - -
2 .38*** - - - - -
3 -.09* -.19*** - - - -
4 -.19*** -.14*** .22*** - - -
5 -.15*** -.14*** .28*** .65*** - -
6 -.13*** -.19*** .21*** .54*** .75*** -
M 3.19 3.72 2.20 1.73 1.68 1.54
SD 0.60 0.70 1.00 1.07 1.04 1.04
* p < .05; ** p < .01;*** p < .001
The overall MANOVA was significant, Pillais’ Trace = 0.12, F(4, 1345) = 44.65, p < .001, η2 = 0.12. A series of follow-up univariate analysis of variance (ANOVA) revealed that Spring 2022 participants were less concerned about job opportunities shrinking as a result of the ongoing pandemic (M = 4.20, SD = 1.00) than Spring 2021 participants (M = 4.85, SD = 1.19), F(1, 1348) = 125.61, p < .001, η2 = 0.09 (see Fig. 1). However, Spring 2022 participants were more likely to report changing their career goals (M = 1.68, SD = 1.04) (see Fig. 2) and proposed major (M = 1.55, SD = 1.04) (see Fig. 3) due to the pandemic compared to Spring 2021 participants (career goals: M = 1.53, SD = 0.99, F(1, 1348) = 7.33, p < .01, η2 = 0.01; proposed major: M = 1.28, SD = 0.76, F(1, 1348) = 28.67, p < .001, η2 = 0.02). There was no significant difference in the self-reported changes in the academic goals between Spring 2021 (M = 1.71, SD = 1.07) and Spring 2022 (M = 1.74, SD = 1.07) participants, F(1, 1348) = 0.22, p = .64, η2 = 0.00 (see Fig. 4).
Fig. 1 Career Concerns for Different Cohorts (Spring 2021 vs. Spring 2022). (Note: Participants’ response to the survey item: “Are you concerned about job opportunities shrinking as a result of the ongoing COVID-19 pandemic?”)
Fig. 2 Career Goals Change for Different Cohorts (Spring 2021 vs. Spring 2022). (Note: Participants’ response to the survey item: As a result of the ongoing COVID-19 pandemic, have your career goals changed?)
Fig. 3 Proposed Major Goals Change for Different Cohorts (Spring 2021 vs. Spring 2022). Note: Participants’ response to the survey item: As a result of the ongoing COVID-19 pandemic, has your proposed major changed?
Fig. 4 Academic Goals Change for Different Cohorts (Spring 2021 vs. Spring 2022). (Note: Participants’ response to the survey item: As a result of the ongoing COVID-19 pandemic, have your academic goals changed?)
To test the main hypothesis that grit and resilience would serve as protective factors against perceived academic and career impacts from the pandemic, a series of regression analyses were conducted. Findings showed that higher levels of grit was correlated with lower career opportunity concerns (supporting H1d), R2 = 0.01, F(1, 1362) = 10.15, b = -0.16, t(1362) = -3.19, p < .01 as well as lower self-reported changes in the academic goals (supporting H1a), R2 = 0.03, F(1, 1362) = 34.86, b = -0.27, t(1362) = -5.90, p < .001, career goals (supporting H1b), R2 = 0.02, F(1, 1362) = 24.78, b = -0.22, t(1363) = -4.98, p < .001, and proposed major (supporting H1c), R2 = 0.01, F(1, 1362) = 13.64, b = -0.15, t(1362) = -3.69, p < .001 as a result of the pandemic.
Similarly, resilience was associated with lower career opportunity concerns (supporting H2d), R2 = 0.01, F(1, 1362) = 15.74, b = -0.18, t(1362) = -3.97, p < .001 as well as less self-reported changes in the academic goals (supporting H2a), R2 = 0.02, F(1, 1362) = 30.95, b = − 0.24, t(1362) = -5.56, p < .001, career goals (supporting H2b), R2 = 0.02, F(1, 1362) = 21.38, b = -0.19, t(1362) = -4.62, p < .001, and proposed major (supporting H2c), R2 = 0.02, F(1, 1362) = 31.48, b = -0.21, t(1362) = -5.61, p < .001. Findings from both regression analyses remained consistent even when the cohort (Spring 2021 vs. Spring 2022) was controlled for.
Discussion
The COVID-19 pandemic has upended many aspects of daily life, including higher education. Among the many impacts of the COVID-19 pandemic is the negative and uncertain career prospects that college students anticipate (Aucejo et al., 2020; Usher et al., 2021). Findings from our study add to the emerging body of literature on the perceived impacts that the ongoing COVID-19 pandemic has on college students’ academic and career plans.
Findings from the current study revealed that participants with higher levels of self-reported grit were less concerned about a decrease in career opportunities as a result of the ongoing COVID-19 pandemic and reported fewer changes to their academic and career goals as well as proposed major. In a similar vein, resilience was associated with lower career opportunities concerns and fewer academic and career changes. Our findings demonstrate that even in the midst of the global pandemic, psychosocial factors, such as grit and resilience, can serve as protective factors (Liu et al., 2020). Although the benefits of grit and resilience in academic and professional contexts have been well-established (Duckworth et al., 2007; Galatzer-Levy et al., 2012), to our knowledge, the current study is the first to examine their academic and career impacts among undergraduate students in the midst of the ongoing COVID-19 pandemic.
Importantly, findings remained unchanged even when controlling for the cohort. This is noteworthy as significant differences were found between Spring 2021 and Spring 2022 participants’ perceived academic and career impacts from the pandemic. Findings revealed that Spring 2022 participants reported lower career opportunities concerns than Spring 2021 participants. This result is as expected given that significant changes were observed between Spring 2021 and Spring 2022 in public health situations as well as in school and work environments (i.e., return to in-person classes and work, widespread availability of vaccines). Interestingly, Spring 2022 participants were more likely to report changing their career plans and proposed majors due to the pandemic. This aligns with some other survey research on first-year students entering college in September (Fall) 2021 indicating that the pandemic had influenced their choice of major (Intelligent, 2021).
However, no significant difference was found between Spring 2021 and Spring 2022 cohorts’ changes in their academic goals, which may be independent of their career goals or proposed majors. For example, an individual’s academic goal of earning high grades is not likely influenced by changes in their career goals or majors. Although these findings offer interesting insights into understanding the effects of the changing circumstances of the ongoing pandemic on undergraduate students’ perceived academic and career impacts, it is important to note that potential cohort effects may have influenced the results.
Limitations and future directions
Unlike other studies that rely on subject pools, participants in the current research were not from one major or from a specific course (e.g., introduction to psychology), however, students were from a single U.S. institution, which limits the generalizability of the current findings. As the COVID-19 pandemic is a global event, psychosocial variables such as grit and resilience as well as perceived academic and career outcomes among first-year undergraduates in the U.S. may be different from undergraduates in other parts of the world. Examining grit and resilience among young persons in other countries and cultures as well as individuals outside of institutions of higher education are important areas of future research.
Somewhat unique to this research, we have data across two years (2021 and 2022) among two distinct cohorts of first-year students at a university in the U.S., which enabled us to compare these two groups’ perceived impacts of the COVID-19 pandemic on their academic and career outcomes. The differences in the perceived academic and career impacts we observed between these two cohorts allude to the potential long-term impacts the pandemic had on undergraduate students. However, these were two distinct samples of first-year students, thus longitudinal data could be especially insightful to better understand how COVID-19 may impact students over the years. In addition, given that our two cohorts were first-year undergraduate students, future research should investigate whether grit and resilience serve as protective factors in the context of a globally disruptive and stressful event among second, third, and fourth-year undergraduates as well as graduate students.
An important next step would be to continue to assess whether undergraduate students’ academic and career plans are influenced by the ongoing pandemic. Given that certain psychosocial factors such as grit and resilience serve as protective factors during a time of uncertainty and change, universities could develop and test interventions designed to foster grit and resilience during first-year orientation. In addition, the university’s career services and alumni networks may be able to use their resources to help existing or recently graduated students weather the widespread uncertainty during these times. Alumni services could continue to provide support in the form of continuing education on the benefits of fostering grit and resilience.
As the COVID-19 pandemic continues to impact our lives, it is important for future research to continue to examine its impact on students’ academic and career outcomes, and develop empirically-based interventions to promote grit and resilience among students to protect against the negative impacts of the ongoing COVID-19 pandemic as well as other challenges in life.
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| 0 | PMC9735092 | NO-CC CODE | 2022-12-14 23:28:32 | no | Soc Psychol Educ. 2022 Dec 5;:1-14 | utf-8 | Soc Psychol Educ | 2,022 | 10.1007/s11218-022-09741-3 | oa_other |
==== Front
Neural Comput Appl
Neural Comput Appl
Neural Computing & Applications
0941-0643
1433-3058
Springer London London
8058
10.1007/s00521-022-08058-8
Original Article
A penalty-based algorithm proposal for engineering optimization problems
http://orcid.org/0000-0002-6901-6559
Oztas Gulin Zeynep [email protected]
1
http://orcid.org/0000-0001-6766-3202
Erdem Sabri [email protected]
2
1 grid.411742.5 0000 0001 1498 3798 Department of Business Administration, Pamukkale University, 20160 Denizli, Turkey
2 grid.21200.31 0000 0001 2183 9022 Department of Business, Dokuz Eylul University, 35390 İzmir, Turkey
9 12 2022
124
23 2 2022
15 11 2022
© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
This paper presents a population-based evolutionary computation model for solving continuous constrained nonlinear optimization problems. The primary goal is achieving better solutions in a specific problem type, regardless of metaphors and similarities. The proposed algorithm assumes that candidate solutions interact with each other to have better fitness values. The interaction between candidate solutions is limited with the closest neighbors by considering the Euclidean distance. Furthermore, Tabu Search Algorithm and Elitism selection approach inspire the memory usage of the proposed algorithm. Besides, this algorithm is structured on the principle of the multiplicative penalty approach that considers satisfaction rates, the total deviations of constraints, and the objective function value to handle continuous constrained problems very well. The performance of the algorithm is evaluated with real-world engineering design optimization benchmark problems that belong to the most used cases by evolutionary optimization researchers. Experimental results show that the proposed algorithm produces satisfactory results compared to the other algorithms published in the literature. The primary purpose of this study is to provide an algorithm that reaches the best-known solution values rather than duplicating existing algorithms through a new metaphor. We constructed the proposed algorithm with the best combination of features to achieve better solutions. Different from similar algorithms, constrained engineering problems are handled in this study. Thus, it aims to prove that the proposed algorithm gives better results than similar algorithms and other algorithms developed in the literature.
Keywords
Natural facts
Evolutionary computation
Constrained nonlinear optimization
Engineering benchmark problems
Metaheuristics
Nature-inspired optimization algorithms
==== Body
pmcIntroduction
Most of the research has focused on nature-based algorithms inspired by interactions of living and non-living objects in evolutionary optimization. The main idea is that nature solves problems instinctively, like finding the shortest path between foods and nests for ants and bees. In the state of the art, many algorithms imitate these behaviors and interactions for solving optimization problems. Especially in the last decade, the number of new metaheuristic algorithms based on metaphors has exploded. Therefore, many researchers [1–6] criticized that plenty of metaheuristics have similarities although they introduce different metaphors. According to them, these algorithms should not be regarded as novel algorithms in the literature. However, as Wolpert and Macready [7] mentioned, there cannot be an appropriate algorithm for all problems. The possibility that there may always be a better algorithm motivates researchers to develop new algorithms regardless of metaphors. For this reason, new metaheuristics will continue to be introduced soon [8]. It is worth mentioning that the literature expects algorithms that provide more “optimal-like” solutions without trapping the “novelty” concept.
The term “metaheuristics” incorporates a wide range of techniques. Therefore, it would be better to classify them by considering their solution time, complexity, optimality, and the trade-off between diversification and intensification ability. Fister et al. [9] mentioned that classification of algorithms might depend on various criteria such as main principles, sources of inspiration, perspectives, and motivations. They classified nature-inspired algorithms as the origin of inspirations (Swarm-intelligence-based, bio-inspired, physics-based, chemistry-based).
On the other hand, Blum and Roli [10] summarized the most critical classifications as Nature-inspired vs. non-nature, population-based vs. single point search, dynamic vs. static objective function, one vs. various neighborhood structures, and memory usage vs. memory-less methods. Echevarría et al. [11] classified metaheuristics in terms of the number of solutions and inspiration sources. Beheshti and Shamsuddin [12] handled metaheuristic algorithms regarding inspirations, number of solutions, objective function, neighborhood structure, and memory usage. Sotoudeh-Anvari and Hafezalkotob [13] also classified the origins of inspiration as animals, physics, humans, plants, nature, and biology. They also demonstrated that the most popular foundations of inspiration are animals and physics. In addition, Hussain et al. [14] classified all metaheuristics in terms of their metaphor disciplines biology and physics took the first two places, respectively. Molina et al. [15] proposed two taxonomies as the source of inspiration and the behavior of each algorithm.
This paper proposes an optimization algorithm called Penalty-based Algorithm (PbA) for continuous optimization problems that cannot be solved in polynomial time (i.e., NP-Hard). PbA considers some natural facts and integrates them into an algorithm. Moreover, as a constraint-handling ability of the PbA, we also present a novel multiplicative penalty approach that combines the satisfaction rate and the deviations of constraints besides objective function. Furthermore, the PbA is also inspired by Tabu Search, Elitism selection approaches in terms of memory-based operations. However, memory is used not as a banned list but to eliminate unnecessary repetitive function evaluations in the PbA. Besides, best-so-far solutions which are the best solutions found in the related run are stored to avoid losing them in case of offsets.
It should be noted that the primary purpose of this study is not to duplicate existing algorithms through a new metaphor but to provide an algorithm that reaches the best-known solution values. To obtain better solutions, we constructed the PbA with the best combination of features. Therefore, the primary goal is achieving better results in a specific problem type, regardless of metaphors and similarities.
Moreover, it is seen in the literature that similar algorithms are generally applied in unconstrained problems. Differently, constrained engineering problems are handled within the scope of this study. Thus, it aims to prove that the PbA gives better results than similar algorithms and other algorithms developed in the literature. For this reason, the study will contribute to the literature.
In the following sections, a literature review, and the theoretical background of the PbA are presented, respectively. In the fourth section, the main steps of the PbA are illustrated through an example. After that, the experimental results for specific constrained benchmark problems are given in the fifth section. Finally, the last section concludes and discuss the findings.
Literature review
“Metaheuristics,” firstly used by Glover in 1986, is a search framework that uses heuristic strategies [16]. They all present randomness and thus provide different solutions in different runs. The outstanding characterization of metaheuristics is that they explore several regions in search space and escape from local optima [17].
By the 1960s, the literature on optimization broadened and turned into a different format called “evolution” [18]. Genetic Algorithm, Evolutionary Programming, Evolutionary Strategies, and Genetic Programming belong to the field of Evolutionary Computation that depends on computational methods inspired by evolutionary processes [19]. Since 2000, researchers have focused on developing new algorithms based on various metaphors [18]. The behavior of animals, laws in science, facts of nature, and social behaviors are some of the inspirations used in the literature. Even the hijacking human cell behavior of coronavirus inspired a newly introduced algorithm called COVIDOA [20]. Figure 1 shows various kinds of metaheuristic algorithms published between 2000 and 2021.Fig. 1 Various Metaheuristic Algorithms Developed in the Recent Past
The algorithms given in Fig. 1 can be classified in terms of inspiration. Some algorithms are mentioned as an example of each classification. Cat Swarm Optimization [21], Artificial Bee Colony [22], Wolf Search Algorithm [23], Dolphin Echolocation [24], Ant Lion Optimizer [25], and Hunger Games Search [26] are some of the animal-inspired algorithms; Central Force Optimization [27], Gravitational Search Algorithm [28], Charged System Search [29], Chemical Reaction Optimization [30], Curved Space optimization [31], Henry Gas Solubility Optimization [32], Weighted Vertices Optimizer [33], and Simulated Kalman Filter [34] are science (physics, chemistry, mathematics)-inspired algorithms; Harmony Search [35] and Melody Search [36] are music-inspired algorithms; Anarchic Society Optimization [37], Brain storm optimization [38, 39], Election algorithm [40], Ideology Algorithm [41], and Human Urbanization Algorithm [42] are social-inspired algorithms.
Similar algorithms in the literature have also been examined in this study. Hysteretic Optimization [43] and Electromagnetism-like Optimization [44] algorithms are the first algorithms that have common concepts with the proposed algorithm. Biswas et al. [45], Siddique and Adeli [17] and Salcedo-Sanz [46] published articles focusing specifically on natural facts algorithms and provided comprehensive literature surveys. Similar algorithms to the PbA are given in Table 1 chronologically.Table 1 Similar algorithms in the literature
Algorithm Main subjects Author(s)
Hysteretic optimization (HO) Material–Energy–Magnetic–Glass demagnetization Zarand et al. [43]
Electromagnetism-like mechanism (EM) Particle–Charge–Distance–Attraction Birbil and Fang [44]
Central Force Optimization (CFO) Particle–Mass–Attraction Formato [27]
Magnetic Optimization Algorithm (MOA) Magnetic field–Particles–Distance Tayarani and Akbarzadeh [47]
Artificial Physics Optimization (APO) Particle–Mass–Hypothetical–Attraction–Repulsion Xie et al. [48]
Gravitational Search Algorithm (GSA) Particle–Mass–Attraction–Variable Hypothetical Gravity Rashedi et al. [28]
Charged System Search (CSS) Particle–Charge–Electrostatics–Attraction–Velocity–Force Kaveh and Talatahari [29]
Gravitational Interaction Optimization (GIO) Particle–Mass –Constant Gravity–Interaction Flores et al. [49]
Magnetic Charged System Search (MCSS) Magnetic forces–Particles–Attraction–Repulsion–Absorbing Kaveh et al. [50]
Electromagnetic field optimization (EFO) Attraction–Repulsion–Electromagnets Abedinpourshotorban et al. [51]
As mentioned above, algorithms can be classified in many ways. However, the main point is the ability to converge optimal-like solutions when the performances of the algorithms are considered. Although the algorithms mentioned above have both common and distinctive features with the PbA, the primary purpose of this study is that the algorithm created with the best combination of features provides better results.
Proposed algorithm
The foundation of the PbA was first laid by Erdem [52]. It considers the offset factors that cause changes in fitness values with the minimum objective function value. PbA is a population-based algorithm, and it is structured for solving continuous constrained optimization problems. Various approaches in the literature have inspired the PbA. It is assumed that the global optimum solution is aimed to be reached by considering the interactions of solutions in terms of their fitness values and distances between the potential solutions.
The assumptions considered in the PbA are summarized below:The changes in fitness values are computed by considering both the fitness values of the solutions and distances.
Fitness values are calculated according to the solution point and its selected neighbors.
No negative improvements are allowed.
The multiplicative penalty-based method is used for constraint handling.
No solution can have the same fitness value up to a certain degree of precision.
The best solution in the population is maintained, and with each offsetting, an attempt is made to reach a better than "best-so-far" solution.
Each solution produced in the related run, whether it is a better solution or not; is saved in a database. Thus, extra function evaluation is not required for a previously evaluated solution.
Before explaining each step of the PbA, the pseudocode of the algorithm is given below:
PbA will be discussed under Determine Intervals, Initialization, Multiplicative Penalty-based Method, Repulsive Forces, Neighborhood, Offsetting, Duplication, and Stopping Condition sub-sections, respectively.
Determine intervals
The general pseudo-code starts with determining intervals. This stage aims to determine the search space by considering boundaries and constraints. In this stage, boundaries are initially taken as default lower and upper limits. Then, the lower and upper limits are updated by checking all constraints concurrently in an iterative manner. The pseudocode is given below:
In essence, this approach adopts a principle of searching for the roots of each constraint in light of existing boundaries. This process continues until all constraints are evaluated. Through the process, many potential boundaries are calculated. However, at the end, the minimum values of upper limits and the maximum values of lower limits that satisfy all constraints are determined as final interval values for each variable.
Initialization
In this step, an initial solution set is generated concerning equal chances according to the determined intervals of variables in the hyperspace with multi-dimensions as much as the number of variables in the optimization model. To some extent, this method has been inspired by the “Scatter Search Algorithm” by Glover [53]. The approach for generating random numbers is proposed by Erdem [52], and then applied recently in [54]. The pseudocode is given below:
where δi-, δi+ are lower and upper limits, respectively; xi is a generated random number for ith variable, and random () is defined as a function that generates a random number between [0,1].
The initialization step also includes the evaluations of constraints for each candidate solution vector. The solutions generated randomly are tested to whether they satisfy each constraint or not. The evaluation is conducted to calculate the constraint satisfaction rates and the total deviations. Therefore, a low satisfaction rate and significant deviations have resulted in big penalties in fitness values. This part will be handled in detail under the title of Multiplicative Penalty-based Method (MUPE).
PbA is structured as a memory-based algorithm. Although there are different approaches in the literature to use memory, “Tabu Search” and “Elitism Principle” are the pioneers of these approaches. For this reason, these approaches inspired the memory feature of the PbA. The PbA utilizes memory for two purposes. The first one is creating a database where each solution is recorded in a memory along with the evaluation scores (constraint satisfaction rates, total deviations). This procedure is inspired by the principle that each step in the “Tabu Search” algorithm is kept in a "history" mechanism, and the repetition of previous solutions is prohibited by looking at this memory [55]. However, in the PbA, memory is used not as a banned list but to eliminate unnecessary repetitive function evaluations. The second one is about recording the best-so-far positions of the solutions. This approach is inspired by the “Elitism Principle” in the literature. The elitism principle is the selection technique that saves the best solution in the population to eliminate the risk of losing the best solution between iterations [56]. In the PbA, best-so-far solutions are stored to avoid losing them in case of offsets. However, there are no limitations for the number of elitist solutions differently from the original elitism principle. Namely, the best-so-far solutions are kept separately from the relocated solution set.
Multiplicative penalty-based method (MUPE)
Penalty functions are the most common approaches in the constrained optimization literature for decades [57]. Penalty approaches are utilized to keep violations and feasibility under control by penalizing [58]. The penalty approach developed for the PbA is motivated by the studies [59–63]. The multiplicative penalty-based constraint handling (MUPE) method, firstly proposed by Erdem [52], calculates fitness function by considering satisfied constraints rate and deviations from constraints besides objective function in a multiplicative manner. In the case of unconstrained/bounded problems, the goal function would be the objective function itself. The pseudocode for the calculation of the heuristic fitness function is given below:
Herein goal function combines both the objective function and all constraints. The goal function acts as a heuristic function as shown below:1 Hx→=H(fx→,dx→,tx→)
where, fx→ represents Goal 1 which includes an objective function to be minimized/maximized, dx→ shows the total amount of violations of the constraints, and this function is controlled by Goal 2, tx→ is the ratio of the satisfied constraints which is represented by Goal 3, and finally Hx→ corresponds to the fitness value of a candidate solution. Here Goal 2 and Goal 3 provide a benchmarking because two infeasible solution points have different constraint violation levels. Goal 2 deals with the total amount of violations measure for solutions. On the other hand, Goal 3 incorporates the ratio of satisfied constraints among overall ones. It can be concluded that selecting the “a solution point that has great violation on a single constraint, but the others satisfied” against “a solution point that has little violations for all the constraints” is a benchmarking interest of this method. If all of the constraints were satisfied for the two solution points, Goal 1 would be the only criteria for comparing these solution points.
This multi-objective function structure could have an acceptable convergence by violating constraints within defined precision. It is worth emphasizing that each goal is considered according to different importance scores, namely scores (c1, c2, c3). The sign of the objective function is also added multiplicatively depending on whether the objective function is more significant than zero or not.
Offset factor
In the initialization part, the solutions are randomly assigned values, and then they start to reach better solutions. In PbA, an offset factor represents the relationship between a candidate solution vector and its neighbors. The offset factor exerted on each solution employs Eq. (2) where H(xi→) correspond to the fitness values of candidate solutions and are calculated as below:2 F=CH(xi→)H(xl→)dil2
where F is an offset factor between i and l solution vectors; C is a constant; Hxi→,H(xl→) are the fitness values of solutions i and l, respectively; dil is the Euclidean distance between the solution vectors and the calculation is demonstrated below:3 dil=∑1n(xin-xln)2=(xi1-xl1)2+(xi2-xl2)2+⋯+(xin-xln)2
After calculating the fitness values of each solution vector, the offset factor caused by the neighbors exerted on that solution is considered to find the new solution point. In the PbA, each solution is exposed to that factor from the closest solution vectors in the population by considering the neighborhood principle.
Neighborhood
The determination of the number of neighbors is also another critical issue to be addressed. According to Pareto’s Principle, roughly 80% of the effects come from 20% of the causes [63]. This principle corresponds that when neighborhood vectors are sorted in descending order, the magnitudes of the offset factors decrease sharply after the 2nd–5th vectors. For that reason, the rest of the solutions can be ignored in terms of fitness values. In the PbA, it is thought that the two closest neighbors may have the potential power for each solution to change its fitness value. Thus, these neighbors are utilized for the displacement procedure of the potential solution.
Offsetting
After identifying neighbors, the change in each solution must be calculated as a result of the offset factor. After all the factors exerted on the selected solution xi→, the unified (or compound) net change is calculated, and the new solution is determined. The first iteration is completed after all the factors from neighbors are considered for each solution vector. Algorithm 5 shows the procedure of neighbors affects the solution until a net force is balanced.
After the offset factors exerting on a solution, the unit offsetting can be found by Eq. (4). The amount of change for a related solution would be proportional to the related dimensional factor and its fitness function value as shown below:4 Δxi′=FΔxi2d2H(xi)=FH(xi)Δxi2d2
After considering all offset factors, each solution has a new fitness value in both magnitude and direction. In addition to the neighbors' effects on the related solution, the best-so-far solution also affects the corresponding solution. The new value is determined by the weighted impact of the neighbors and the best-so-far solution. The determination of the new solution is given in Eq. (5).5 xik=xik-1+[Δxik-1α+xbk-11-α],i=1,2,..,n
where n is the number of dimensions, k is the iteration number, αϵ0,1, and it is a dynamic parameter based on the improvement within loops, and xbk-1 is the best-so-far solution. Here α provides an opportunity to control the balance between the neighbors and the best-so-far solution.
In line with the net offset factor, the solutions are exposed; they can change their fitness values if it has a better value, as shown in Eq. (6) for minimization problems. In case of having worse fitness value, the solution retains its current value by preserving the best-so-far solution in the population as in Elitism selection. It would be better to clarify that solution can be changed within the allowed space, determined by the intervals of variables.6 Hxik<Hxik-1
Furthermore, it is essential to clarify that if the new fitness value is out of boundaries, the new solution vector is updated as the boundary. When all offset factors are determined for each solution in the population, the first iteration is completed. These process chains are repeated until no remarkable factor from neighbors occurs. However, if a candidate solution is still under the effect of the offset factor, it changes its current value as a small increased amount of offsetting, as shown in Eq. (7).7 Δxik=ΨΔxik-1
where Ψ∈[1.01,1.1] and a subjective parameter. In case of improvements Δxik-1 continues to be multiplied by Ψ. After considering all the factors caused by the neighbors, the unified net change is checked lastly and in case of remarkable change, new solution vectors are determined.
Duplication
As a diversification procedure, the PbA applies a procedure that two solution vectors cannot occupy the same fitness value in a closed system. Thus, solutions can diversify without trapping into a single point. Our experiments assume that fitness values are the same in the case that the first six decimal places are equal. In this step, the solution set is checked whether there is a duplicated solution or not. Thus, it is aimed that the algorithm does not trap into a local optimum by increasing the solution possibilities in the population.
While duplication check provides diversification, offsetting in a wide range can create too much diversity disrupting the balance. For this reason, the purpose of offsetting around the best-known solution is to balance the exploration–exploitation ability of the PbA.
Stopping condition
The stopping condition is related to the number of function evaluations (FES). The pseudocode for the stopping condition is given below. However, the algorithm will stop in most cases where the main stopping condition is met. The minimum, the maximum, and the average FES values are also reported for each problem.
An illustrative example
In this section, an example is generated to explain the procedure of the proposed algorithm step by step including the most critical issues. The visualization is exemplified through fitness values and the minimization problem as shown in Fig. 2. The demonstration includes 4 crucial issues A. Initial Solution, B. Neighborhood, C. Offsetting, D. Best-so-far effect in the run, respectively. Each step is explained in the following.Fig. 2 An illustration of the PbA
The determination of the search space is the first step of PbA. At this stage, firstly the boundaries of the variables are considered as default, and then the boundaries are updated according to the root value of each constraint in case of having constraints, and the final search space is revealed. After the preliminary preparation is completed, a random initial solution is generated as shown in Algorithm 3 and A section in Fig. 2. The next steps include the efforts to reach a better point in line with the neighborhood relations of the population elements in the initial solution and the relationship between the best-so-far solution (denoted as black) in that solution. In Fig. 2, all steps are visualized over a single solution value denoted red. The neighborhood step identifies the two closest neighbors (denoted as yellow) that may have the potential power for the red solution to change its fitness value. The closeness of the neighbors is considered as the Euclidean distances. Through the offset factors of the neighbors, the red solution will try to reach a better point as shown in section C. The amount of change in its place is calculated with the help of Algorithm 5. Improvement efforts for better solutions are not limited to offset factors of neighbors. Besides, the best-so-far solution in that run also has a certain effect (1 − α) as mentioned in Eq. (5) including the neighbors’ effect (α). Consequently, the red solution takes its new position as shown in section D. It would be better to clarify that these procedures have been applied in case of having better fitness values; otherwise, the solution retains its current position. The first iteration is completed when new solution values are calculated for each solution in the population. These chains of processes are repeated until there is no appreciable offsetting from the neighbors and the best-so-far solution effect.
Constrained engineering optimization problems
According to Ezugwu et al. [65], the strength of the metaheuristics can be shown by the application in engineering design, management, industries, finance, and scheduling. This situation attracts the scientific community and industry practitioners. In general, before proposing a new algorithm, it is required to test its performance with appropriate test benchmarks [66].
The highlight of the PbA is the ability to deal with constraints very well because of the multiplicative penalty method. For this reason, the performance of the algorithm is evaluated with the most frequently used engineering benchmark problems (Pressure Vessel, Welded Beam, Tension/Compression Spring Design, Himmelblau’s Function), which may have complex constraints. In addition, although these benchmarks are referred to as engineering design problems in the literature, problems that are essentially aimed at "cost minimization.” The parameters used in the PbA are determined as a result of a trial-and-error test and presented in Table 2.Table 2 Parameter Settings
The number of trials 30
The importance scores (c1, c2, c3) (MUPE) (0.25, 0.2, 1.8)
The number of the particles (population size) (n) 20
The incremental parameter (Ψ) 1.02
The stopping parameter (β) 0.5*
The neighborhood size (κ) 2
The precision number (ρ) 6
Maximum number of Function Evaluations (Max FES) 30,000**
*1.5
**100,000 for Welded Beam
In general, the algorithms to which the developed algorithm will be compared are randomly selected and re-run and reported independently from the scholars who developed the algorithm. However, this situation may cause manipulation by using different parameters, different software hardware, or even different programming languages, giving biased results. For this reason, it will be better to compare the developed algorithm with the results of other algorithms as reported in the literature. At this point (if specified), the population size, the number of iterations, or the function evaluation value will be good indicators for comparison. Since the main purpose is to reach the best-known solutions so far or a better solution than the best-known, the algorithms developed, especially in recent years presented in Table 3, have been preferred for comparison.Table 3 Parameters used for algorithms published in the literature
Algorithm Population Max iteration Trial FES
Charged System Search (CSS) [29] NA NA 30 NA
Firefly Algorithm (FA) [67] 25 1000 NA 50,000e
Ray Optimization (RO) [68] 40 NA 50 NA
Magnetic Charged System Search (MCSS) [50] NA NA 30 NA
Cuckoo search algorithm (CSA) [69] 25 NA NA 5000
Advanced particle swarm-assisted genetic algorithm (PSO-GA) [70] NA NA 30 5000
Artificial Bee Colony Algorithm (ABC) [71] 20*D 500 30 NA
Plant Propagation Algorithm (PPA) [72] 40 25 100 30,000
Hybrid Flower Pollination Algorithm (H-FPA) [73] 50 1000 30 NA
Modified Oracle Penalty Method (MOPM) [74] 30 NA 100 90,000
Interior Search Algorithm (ISA) [75] NA NA 30 30,000*
Grey Wolf Optimizer (GWO) [76] NA NA NA NA
Optics Inspired Optimization (OIO) [77] 19 NA 30 5000
Hybrid PSO-GA Algorithm (H-PSO-GA) [78] 20*D NA 30 NA
Thermal Exchange Optimization (TEO) [79] 30 10,000 30 NA
Seagull Optimization Algorithm (SOA) [80] 100 1000 30 NA
Pathfinder algorithm (PA) [81] 60 100 NA NA
Hybrid GSA-GA Algorithm (H-GSA-GA) [82] 20*D 200 30 NA
Nuclear Fission-Nuclear Fusion Algorithm (N2F) [83] 40 NA 30 30,000
Marine Predators Algorithm (MPA) [84] NA 500 30 25,000
Equilibrium Optimizer (EO) [85] 30 500 NA 15,000
Search and Rescue Optimization Algorithm (SRO) [86] 20 NA 50 30,000a
Chaotic Grey Wolf Optimizer (CGWO) [87] 100 NA 30 40,000
Slime Mould Algorithm (SMA) [88] NA NA NA NA
Chaos Game Optimization (CGO) [89] NA NA 25 NA
Group Teaching Optimization Algorithm (GTO) [90] 50 NA 30 10,000
Teaching–Learning-based Marine Predator Algorithm (TLMPA) [91] NA NA 30 NA
Smell Bees Optimization Algorithm (SBO) [92] NA NA 50c 14,000b
Improved Grey Wolf Optimizer (IGWO) [93] 20 (D*104)/20d 10 NA
Cooperation Search Algorithm (CoSA) [94] 50 1000 20 NA
Hybrid Social Whale Optimization Algorithm (HS-WOA) [95] 50 NA 30 NA
Hybrid Social Whale Optimization Algorithm (HS-WOA +) [95] 25 NA 30 NA
Atomic Orbital Search (AOS) [96] NA NA 25 200,000
Lichtenberg Algorithm (LA) [97] 100 200 30 NA
Dingo Optimization Algorithm (DOA) [98] 100 500 30 NA
Material Generation Algorithm (MGA) [99] NA NA 25 20,000*D
Rat Swarm Optimizer (RSO) [100] 30 1000 NA NA
Colony Predation Algorithm (CPA) [101] 30 NA 30 1000
Sand Cat Swarm Optimization (SCSO) [102] 30 500 30 NA
Archerfish Hunting Optimizer (AHO) [103] 30*s1.5 200,000/(30*s1.5) 25 NA
*5000 for pressure/8900 for Tension Compression Spring Design
**s is the search space
a15,000 for Welded Beam/25000 for Tension/Compression Spring Design
b13,000 for Tension/Compression Spring Design and Welded Beam
c30 for Welded Beam
dD is the number of variables
e25,000 for Pressure Vessel
In the comparison tables for each problem, six decimal places are documented if reported. The results obtained by the PbA are also presented with the same sensitivity. Moreover, we preferred to code the PbA in Python language by utilizing Python libraries and PyCharm [104]. The experiments are executed on an Intel Core i7 computer with a 2.60 GHz CPU and 12 GB RAM under the windows operating system.
In the following sections, the experimental results for Pressure Vessel, Welded Beam, Tension/Compression Spring Design, and Himmelblau’s Function are presented in detail.
Pressure Vessel
The design of a Pressure Vessel is one of the most used cost optimization problems. The design image of the vessel is given in Fig. 3. This problem has four variables where x3 and x4 are continuous, while x1 and x2 are integers (products of 0.0625 inches) which are the available thickness of the material.Fig. 3 Pressure Vessel [105]
The model of the Pressure Vessel is given below:8 Minimizefx→=0.6224x1x3x4+1.7781x2x32+3.1661x12x4+19.84x12x3Subjecttog1x→=-x1+0.0193x3≤0g2x→=-x2+0.00954x3≤0g3x→=-πx32x4-43πx33+1296000≤0x1,x2∈0.0625,10;x3∈0,100;x4∈0,240
It would be useful to show how the proposed algorithm handles a problem step by step and arrives at a near-optimal result before reporting the final solutions for each problem. The convergence process of the PbA is exemplified for Pressure Vessel in Table 4. The other engineering design problems converge similarly. Table 4 Convergence of the proposed algorithm
Best-so-far solution
x1 x2 x3 x4 Objective value
1st Iteration 0.75 3.6875 38.3180537 233.2875928 14,642.97428
2nd Iteration 0.75 0.5 38.8336281 222.377235 6201.305994
50th Iteration 0.75 0.375 38.85927662 221.3822673 5850.58009901902
150th Iteration 0.75 0.375 38.85987911 221.369303 5850.4220474207
. . . . . .
246th Iteration 0.75 0.375 38.8601 221.3655 5850.38306
The experimental results for Pressure Vessel are summarized in Table 5 as descriptive statistics. Although maximum FES is limited to 30,000, actual FES values are also reported as well.Table 5 Experimental results of Pressure Vessel
Best 5850.38306 Average iteration 163.63
Mean 6659.547045 Minimum FES 2527
Worst 7903.694033 Average FES 20,002.3
Standard deviation 713.15 Maximum FES 30,091
Standard error 130.2
The best-so-far solution for the Pressure Vessel obtained by the PbA is given in Table 6. Moreover, the left-hand side values of each constraint are also provided in Table 6 to show the feasibility of the solution.Table 6 Best-so-far solution for Pressure Vessel
Objective x1 x2 x3 x4
5850.38306 0.75 0.375 38.860104 221.365471
Constraints g1(x) g2(x) g3(x)
− 3.24056E-11 − 0.004275 − 2.41133E-05
In Fig. 4 a graphic is given in order to show the convergence to the global minimum of the algorithm visually. It shows the objective function values obtained according to the FES value in the related run reaching the global minimum within 30 trials. As it is seen, the best-so-far solution has been reached approximately after 5000 function evaluations.Fig. 4 The convergence to the best-so-far solution (pressure vessel)
The Pressure Vessel problem has been handled with many other metaheuristic algorithms previously. Since there are too many algorithms in the literature, only those developed after 2010 are presented chronologically in Table 7. Most of the solutions could not be able to satisfy “having x1 and x2 as integer products of 0.0625.” The feasible best-known solution for Pressure Vessel has been obtained firstly by FA. However, there are no other algorithms that reach this solution. PbA has provided the same best-known solution with a smaller set size compared to FA.Table 7 Comparisons for pressure vessel (Best-so-far solution)
Algorithm × 1 × 2 × 3 × 4 Objective
CSS [28] 0.8125 0.4375 42.103624 176.572656 6059.09
FA [63] 0.75 0.375 38.8601 221.36547 5850.38306
MCSS [49] 0.8125 0.4375 42.10455 176.560967 6058.97
MOPM [70] 0.8125 0.4375 42.098446 176.636596 6059.7143
ISA [71] 0.8125 0.4375 42.09845 176.6366 6059.7143
GWO [72] 0.8125 0.4345 42.089181 176.758731 6051.5639
TEO [75] 0.779151 0.385296 40.369858 199.301899 5887.511073
SOA [76] 0.77808 0.383247 40.31512 200 5879.5241
PA [77] 0.778168 0.384649 40.31964 199.9999 5885.3351
N2F [79] 1.125 0.625 58.290155 43.6926562 7197.72893
MPA [80] 0.8125 0.4375 42.098445 176.636607 6059.7144
EO [81] 0.8125 0.4375 42.098446 176.636596 6059.7143
SRO [82] 0.8125 0.4375 42.098446 176.636596 6059.714335
SMA [84] 0.7931 0.3932 40.6711 196.2178 5994.1857
CGO [85] 0.778169 0.51 40.319619 200 6247.672819
GTO [86] 0.778169 0.38465 40.3196 200 5885.333
TLMPA [87] 0.778169 0.384649 40.319618 200 5885.332774
SBO [88] 0.778169 0.384649 40.319619 199.999999 5885.33262
IGWO [89] 0.779031 0.385501 40.36313 199.4017 5888.34
HS-WOA + [95] 0.778168 0.384649 40.319622 199.999953 5885.331515
HS-WOA [95] 0.778486 0.385076 40.326495 199.998992 5889.976089
AOS [96] 0.778674 0.385322 40.340891 199.721518 5888.457948
DOA [98] 0.8125 0.4375 42.09845 176.6366 6059.7143
MGA [99] NA NA NA NA 6059.714350
RSO [100] 0.775967 0.383127 40.313297 200 5878.5395
CPA [101] 0.81250 0.437500 42.088230 176.763300 6060.9590
SCSO [102] 0.7798 0.9390 40.3864 199.2918 5917.46
AHO [103] NA NA NA NA 6060
Proposed algorithm (PbA) 0.75 0.375 38.860104 221.365471 5850.38306
The descriptive statistics of the experiments are shown in Table 8. As it is seen, the performance of the PbA is better than the solutions reached by other algorithms. Although the worst and the standard deviation are relatively higher than the others, the feasible best-known solution is obtained by the PbA.Table 8 Comparisons for pressure vessel (descriptive statistics)
Algorithm Best Mean Worst Std Dev
CSS [28] 6059.09 6067.91 6085.48 10.2564
FA [63] 5850.38306 NA NA NA
MCSS [49] 6058.97 6063.18 6074.74 9.73494
MOPM [70] 6059.7143 6059.7143 6059.7143 1.94E-08
ISA [71] 6059.714 6410.087 7332.846 384.6
GWO [72] 6051.5639 NA NA NA
TEO [75] 5887.511073 5942.565917 6134.187981 62.2212
SOA [76] 5879.5241 5883.0052 5893.4521 256.415
PA [77] 5885.3351 NA NA NA
N2F [79] 7197.72893 7197.72905 7197.72924 7.90E-05
MPA [80] 6059.7144 6102.8271 6410.0929 106.61
EO [81] 6059.7143 6668.114 7544.4925 566.24
SRO [82] 6059.714335 6091.32594 6410.0868 8.03E + 01
SMA [84] 5994.1857 NA NA NA
CGO [85] 6247.672819 6250.957354 6330.958685 10.75915635
GTO [86] 5885.333 NA NA NA
TLMPA [87] 5885.332774 NA NA NA
SBO [88] 5885.33262 6156.4028 6384.8583 74.9635
IGWO [89] 5888.34 NA NA NA
HS-WOA + [95] 5885.332 5906.331 5998.331 72.1541
HS-WOA [95] 5889.976 5946.629 6231.362 121.0098
AOS [96] 5888.457948 5888.480501 5894.840682 2.199072
DOA [98] 6059.7143 NA NA NA
MGA [99] 6059.714350 6059.694923 6273.765974 0.028912
RSO [100] 5878.5395 5881.5355 5887.3933 167.041
CPA [101] 6060.9590 NA NA NA
SCSO [102] 5917.46 NA NA NA
AHO [103] 6060 7330 6150 6.25
Proposed Algorithm (PbA) 5850.383 6659.547045 7903.694 713.15
Welded Beam
The Welded Beam is a structural optimization problem generally preferred as a benchmark [106]. This structure is about the beam and the weld for mass production, as shown in Fig. 5. This cost optimization problem consists of four design variables and six constraints. The model is given in Eq. 9.9 Minimizefx→=1+c1x12x2+c2x3x4L+x2Subjecttog1x→=τx→-τmax≤0g2x→=σx→-σmax≤0g3x→=x1-x4≤0g4x→=c1x12+c2x3x4L+x2-5≤0g5x→=δx→-δmax≤0g6x→=P-Pcx→≤0τx→=τ′2+2τ′τ″x22R+(τ″)2τ′=P2x1x2;τ″=MRJ;M=PL+X22;R=x224+x1+x322J=22x1x2x2212+x1+x322σx→=6PLx4x32;δx→=4PL3Ex33x4Pcx→=4.013Ex32x4636L21-x32LE4Gx1∈0.125,5;x2,x3∈0.1,10;x4∈0.1,5c1=0.10471;c2=0.04811;P=6000;L=14;E=30000000;G=12000000δmax=0.25;τmax=13600;σmax=30000
Fig. 5 Welded beam [105]
The experimental results for Welded Beam are given in Table 9 as descriptive statistics. Only for Welded Beam problem, maximum FES is limited to 100,000, and actual FES values are also reported as well.Table 9 Experimental results of Welded Beam
Best 1.724872 Average iteration 741.53
Mean 1.799315 Minimum FES 47,257
Worst 2.278059 Average FES 89,236.7
Standard deviation 0.12 Maximum FES 100,126
Standard error 0.02
The best-so-far solution for Welded Beam obtained by the PbA is given in Table 10. Furthermore, to show the feasibility of the solution, each constraint's left-hand side values are also provided. As seen from the constraint values, only one constraint has a 2.96612E-07 violation which is negligible. Therefore, it can be concluded that the solution is feasible as well.Table 10 Best-so-far solution for welded beam
Objective x1 x2 x3 x4
1.724872 0.205715 3.470808 9.036624 0.20573
Constraints g1(x) g2(x) g3(x)
− 3.1307E-06 2.96612E-07 − 1.48238E-05
g4(x) g5(x) g6(x)
− 3.390637 − 0.23554 − 0.001607
In Fig. 6, a graphic is given to show the convergence to the global minimum of the algorithm visually. Figure 6 shows the objective function values obtained according to the FES value in the run reaching the global minimum within 30 trials. The algorithm has converged the best-so-far solution after 30,000 FES, according to the graph.Fig. 6 The convergence to the best-so-far solution (Welded Beam)
The feasible best-known solution for Welded Beam has been obtained as 1.724852 in the literature. Most of the algorithms have reached feasible best-known solutions. However, the solution values obtained differ after the 5th digit after the comma, as shown in Table 11. It is worth noting that the solutions less than 1.724852 are infeasible for some constraints.Table 11 Comparisons for Welded Beam (Best-so-far solution)
Algorithm × 1 × 2 × 3 × 4 Objective
CSS [28] 0.20582 3.468109 9.038024 0.205723 1.724866
FA [67] 0.2015 3.562 9.0414 0.2057 1.73121
RO [68] 0.203687 3.528467 9.004233 0.207241 1.735344
MCSS [50] 0.20573 3.470489 9.036624 0.20573 1.724855
MOPM [74] 0.20573 3.470489 9.036624 0.20573 1.724852
ISA [75] 0.244330 6.219931 8.291521 0.244369 2.3812
GWO [76] 0.205676 3.478377 9.03681 0.205778 1.72624
TEO [79] 0.205681 3.472305 9.035133 0.205796 1.725284
SOA [80] 0.205408 3.472316 9.035208 0.201141 1.723485
PA [81] 0.02058 3.470495 9.036624 0.20573 1.724853
N2F [83] 0.20573 3.470489 9.036624 0.20573 1.724852
MPA [84] 0.205728 3.470509 9.036624 0.20573 1.724853
EO [85] 0.2057 3.4705 9.03664 0.2057 1.7549
SRO [86] 0.20573 3.470489 9.036624 0.20573 1.724852
CGWO [87] 0.20573 3.470499 9.036637 0.20573 1.724854
SMA [88] 0.2054 3.2589 9.0384 0.2058 1.69604
CGO [89] 0.198856 3.337244 9.191454 0.198858 1.670336
GTO [90] 0.20573 3.470489 9.036624 0.20573 1.724852
TLMPA [91] 0.20573 3.470489 9.036624 0.20573 1.724852
SBO [92] 0.175055 3.305377 9.248898 0.206137 1.699215
IGWO [93] 0.20573 3.47049 9.036624 0.20573 1.724853
CoSA [94] 0.205692 3.254453 9.03636 0.205733 1.695505
HS-WOA + [95] 0.20573 3.470489 9.036624 0.20573 1.724852
HS-WOA [95] 0.208079 3.442723 8.986502 0.208651 1.738146
AOS [96] 0.205730 3.470489 9.036624 0.205730 1.724852
LA [97] 0.2213 3.2818 8.7579 0.2216 1.8446
MGA [99] NA NA NA NA 1.672967
RSO [100] 0.205397 3.465789 9.034571 0.201097 1.722789
CPA [101] 0.188500 3.562000 9.134835 0.205245 1.723916
SCSO [102] 0.2057 3.2530 9.0366 0.2057 1.6952
AHO [103] NA NA NA NA 1.67
Proposed algorithm (PbA) 0.205715 3.470808 9.036624 0.20573 1.724872
In Table 12, the descriptive statistics for Welded Beam are reported. Table 12 indicates that the PbA achieves the best-known solution nearly (with a 2.04E-05 deviation, which is negligible).Table 12 Comparisons for Welded Beam (Descriptive Statistics)
Algorithm Best Mean Worst Std Dev
CSS [28] 1.724866 1.739654 1.759479 0.008064
FA [67] 1.73121 NA NA NA
RO [68] 1.735344 1.9083 NA 0.173744
MCSS [50] 1.724855 1.735374 1.750127 0.007571
MOPM [74] 1.724852 1.7249 1.749 1.11E-08
ISA [75] 2.3812 2.4973 2.67 1.02E-01
GWO [76] 1.72624 NA NA NA
TEO [79] 1.725284 1.76804 1.931161 0.058166
SOA [80] 1.723485 1.724251 1.727102 1.724007
PA [81] 1.724853 NA NA NA
N2F [83] 1.724852 1.725 1.726147 3.39E-04
MPA [84] 1.724853 1.724861 1.724873 6.41E-06
EO [85] 1.724853 1.726482 1.736725 0.003257
SRO [86] 1.724852 1.724852 1.724852 2.22E-11
CGWO [87] 1.724854 1.724854 1.724854 3.36E-16
SMA [88] 1.69604 NA NA NA
CGO [89] 1.670336 1.670378 1.670903 9.30E-05
GTO [90] 1.724852 NA NA NA
TLMPA [91] 1.724852 NA NA NA
SBO [92] 1.699215 1.719856 1.743486 0.014826
IGWO [93] 1.724853 NA NA NA
CoSA [94] 1.695505 1.724051 1.873922 0.047618
HS-WOA + [95] 1.724852 1.754853 1.848521 0.000249
HS-WOA [95] 1.738146 1.739235 1.948905 0.001349
AOS [96] 1.724852 1.725674 1.732516 0.024787
LA [97] 1.7351 1.8446 NA 0.1597
MGA [99] 1.672967 1.678791 1.687172 4.41E-03
RSO [100] 1.722789 1.725097 1.726987 0.015748
CPA [101] 1.723916 NA NA NA
SCSO [102] 1.6952 NA NA NA
AHO [103] 1.67 1.67 1.67 1.15E-14
Proposed Algorithm (PbA) 1.724872 1.799315 2.278059 0.12
Tension/Compression Spring Design
The Tension/Compression Spring Design Problem is an optimization benchmark that minimizes the weight [107]. There are three variables and four constraints. Its figure and model are given in Fig. 7 and Eq. 10, respectively.10 Minimizefx→=x3+2x2x12Subjecttog1x→=1-x23x371785x14≤0g2x→=4x22-x1x212566x2x13-x14+15108x12-1≤0g3x→=1-140.45x1x22x3≤0g4x→=x1+x21.5-1≤0x1∈0.05,1;x2∈0.25,1.3;x3∈2,15
Fig. 7 Tension/Compression Spring Design [105]
The experimental results for Tension/Compression Spring Design are given in Table 13 as descriptive statistics. Maximum FES is limited to 30,000, and the minimum and the average FES values are also reported as well.Table 13 Experimental results of Tension/Compression Spring Design
Best 0.012665 Average iteration 227.43
Mean 0.013404 Minimum FES 11,970
Worst 0.01705 Average FES 28,646.73
Standard deviation 0.0013 Maximum FES 30,120
Standard error 0.0002
The best-so-far solution for Tension/Compression Spring Design obtained by the PbA is given in Table 14. As is seen in Table 14, all constraints are satisfied.Table 14 Best-so-far solution for Tension/Compression Spring Design
Objective x1 x2 x3
0.012665 0.05182 0.359887 11.105579
Constraints g1(x) g2(x) g3(x) g4(x)
− 8.18448E-10 − 1.77694E-07 − 4.059998 − 0.725529
A graphic is given in Fig. 8 to visually express the algorithm's convergence to the global minimum value. It shows the objective function values obtained according to the FES value in the run reaching the global minimum within 30 trials. It is seen that the best-so-far solution has been obtained at the very beginning of FES values.Fig. 8 The convergence to the best-so-far solution (Tension/Compression Spring Design)
According to Table 15, the feasible best-known solution is 0.012665 reported in the literature. When the digits of the solutions reaching the value of 0.012665 are compared, it is evident that the PbA also reached the value of the best-known solution. It is worth noting that the solutions less than 0.012665 are infeasible to some extent.Table 15 Comparisons for Tension/Compression Spring Design (best-so-far solution)
Algorithm × 1 × 2 × 3 Objective
CSS [28] 0.051744 0.358532 11.165704 0.012638
RO [68] 0.05137 0.349096 11.7679 0.012679
MCSS [50] 0.051627 0.35629 11.275456 0.012607
MOPM [74] 0.051718 0.357418 11.248016 0.012665
ISA [75] NA NA NA 0.012665
GWO [76] 0.05169 0.356737 11.28885 0.012666
TEO [79] 0.051775 0.358792 11.16839 0.012665
SOA [80] 0.051065 0.342897 12.0885 0.012645
PA [81] 0.051727 0.35763 11.235724 0.012665
MPA [84] 0.051725 0.357570 11.239196 0.012665
EO [85] 0.05162 0.355054 11.387968 0.012666
SRO [86] 0.051689 0.356723 11.288648 0.012665
CGO [89] 0.051663 0.356078 11.326575 0.012665
TLMPA [91] 0.051681 0.356533 11.299823 0.012665
SBO [92] 0.051598 0.354523 11.418801 0.012665
HS-WOA + [95] 0.05192 0.362288 10.969723 0.012666
HS-WOA [95] 0.053446 0.399928 9.173312 0.012764
AOS [96] 0.051690 0.356729 11.288297 0.012665
MGA [99] NA NA NA 0.012665
RSO [100] 0.051075 0.341987 12.0667 0.012656
CPA [101] 0.051741 0.357978 11.21548 0.012665
SCSO [102] 0.0500 0.3175 14.0200 0.012717
AHO [103] NA NA NA 0.0127
Proposed Algorithm (PbA) 0.05182 0.359887 11.105579 0.012665
The descriptive statistics for Tension/Compression Spring Design are listed in Table 16. As it is seen, the performance of the PbA is better than the solutions reached by other algorithms.Table 16 Comparisons for Tension/Compression Spring Design (Descriptive Statistics)
Algorithm Best Mean Worst Std Dev
CSS [28] 0.012638 0.012852 0.013626 8.3564e−5
RO [68] 0.012679 0.013547 NA 0.001159
MCSS [50] 0.012607 0.012712 0.012982 4.7831e−5
MOPM [74] 0.012665 0.012665 0.012665 1.87E-08
ISA [75] 0.012665 0.013165 0.012799 1.59E-02
GWO [76] 0.012666 NA NA NA
TEO [79] 0.012665 0.012685 0.012715 4.41E-06
SOA [80] 0.012645 0.012666 0.012666 0.001108
PA [81] 0.012665 NA NA NA
MPA [84] 0.012665 0.012665 0.012665 5.55E-08
EO [85] 0.012666 0.013017 0.013997 3.91E-04
SRO [86] 0.012665 0.012665 0.012668 1.26E-07
CGO [89] 0.012665 0.012670 0.012719 1.09E-05
TLMPA [91] 0.012665 NA NA NA
SBO [92] 0.012665 0.012687 0.012723 1.77E-05
HS-WOA + [95] 0.012666 0.012745 0.012827 0.000105
HS-WOA [95] 0.012764 0.012816 0.012918 0.000121
AOS [96] 0.012665 0.012738 0.013597 0.000121
MGA [99] 0.012665 0.012666 0.012667 5.65E-07
RSO [100] 0.012656 0.012666 0.012668 0.057894
CPA [101] 0.012665 NA NA NA
SCSO [102] 0.012717 NA NA NA
AHO [103] 0.0127 0.0129 0.0151 2.17E-04
Proposed Algorithm (PbA) 0.012665 0.013404 0.01705 0.0013
Himmelblau’s Function
Himmelblau proposed a nonlinear constrained optimization problem in 1972, and it is regarded as a mechanical engineering problem [108]. This well-known problem has five variables and six constraints. The model of the problem is given in Eq. 11.11 Minimizefx→=5.3578547x32+0.8356891x1x5+37.293239x1-40792.141Subjecttog1x→=85.334407+0.0056858x2x5+0.00026x1x4-0.0022053x3x5g2x→=80.51249+0.0071317x2x5+0.0029955x1x2+0.0021813x32g3x→=9.300961+0.0047026x3x5+0.0012547x1x3+0.0019085x3x40≤g1x→≤9290≤g2x→≤11020≤g3x→≤25x1∈78,102;x2∈33,45;x3,x4,x5∈27,45
The experimental results for Himmelblau’s Function are given in Table 17 as descriptive statistics. Maximum FES is limited to 30,000, and the minimum and the average FES values are also reported as well.Table 17 Experimental results of Himmelblau’s Function
Best − 31,025.546836 Average iteration 171.5
Mean − 30,986.343296 Minimum FES 4918
Worst − 30,642.489379 Average FES 21,415.3
Standard deviation 94.38 Maximum FES 30,106
Standard error 17.23
The solution for Himmelblau’s Function obtained by the PbA is given in Table 18. As it is seen, all constraints are within the defined range, which means that there are no violations.Table 18 Best-so-far solution for Himmelblau’s Function
Objective x1 x2 x3 x4 x5
− 31,025.546836 78 33 27.07115 44.999999 44.968769
Constraints g1(x) g2(x) g3(x)
91.999924 100.404691 20
In Fig. 9, a graphic is given in order to show the convergence of the algorithm to the global minimum visually. It shows the objective function values obtained according to the FES value in the run reaching the global minimum within 30 trials. According to Fig. 9, it is seen that the algorithm has achieved convergence of the best-so-far solution with less than 10,000 FES values.Fig. 9 The convergence to the best-so-far solution (Himmelblau)
In Table 19, the feasible best-known solutions obtained for Himmelblau’s Function are given. H-GSA-GA reaches the best-known solution with -31,027.64076. However, it would be better to mention that H-GSA-GA utilizes 20*Dimension as population size, which becomes 100.Table 19 Comparisons for Himmelblau’s Function (Best-so-far solution)
Algorithm × 1 × 2 × 3 × 4 × 5 Objective
CSA [69] 78 33 29.99616 45 36.77605 − 30,665.233
PSO-GA [70] 78 33 29.99525 45 36.77582 − 30,665.5389
ABC [71] 78 33 27.07098 45 44.969024 − 31,025.57569
PPA [72] 78 33 29.9952 45 36.7758 − 30,665.54
H-FPA [73] NA NA NA NA NA − 31,025.5654
OIO [77] NA NA NA NA NA − 31,025.50178
H-PSO-GA [78] 78 33 27.070951 45 44.969167 − 31,025.57471
H-GSA-GA [82] 77.961 32.99948 27.072836 45 44.973943 − 31,027.64076
CSA [94] 78 33 29.995256 45 36.775813 − 30,665.538672
Proposed Algorithm (PbA) 78 33 27.07115 44.999999 44.968769 − 31,025.546836
The descriptive statistics for Himmelblau’s Function are listed in Table 20. As seen, the performance of the PbA for Himmelblau's Function is considerably good.Table 20 Comparisons for Himmelblau’s Function (Descriptive Statistics)
Algorithm Best Mean Worst Std Dev
CSA [69] − 30,665.233 NA NA 11.6231
PSO-GA [70] − 30,665.5389 − 30,665.53697 − 30,665.48996 8.76E-03
ABC [71] − 31,025.57569 − 31,025.55841 − 31,025.49205 0.015353
PPA [72] − 30,665.54 NA NA NA
H-FPA [73] − 31,025.5654 NA NA NA
OIO [77] − 31,025.50178 − 31,024.5348 − 31,020.60517 1.2092
H-PSO-GA [78] − 31,025.57471 − 31,025.55782 − 31,025.49205 0.01526
H-GSA-GA [82] − 31,027.64076 − 31,026.07246 − 31,025.38705 0.01803
CSA [94] − 30,665.538672 − 30,625.97242 − 30,561.19298 35.52345
Proposed Algorithm (PbA) − 31,025.54684 − 30,986.3 − 30,642.48938 94.38
Discussion and conclusion
This study presents a new population-based evolutionary computation model for solving continuous constrained nonlinear optimization problems. The proposed algorithm assumes that candidate solutions in a defined search space are in interaction to survive through having better fitness values. The interaction between candidate solutions is limited with the closest neighbors by considering the Euclidean distance. The outstanding feature of the PbA is the MUPE which considers satisfied constraints rate and deviations from constraints besides objective function in a multiplicative manner. Another prominent feature in the PbA is the control mechanism for duplication, which is for satisfying Pauli’s Exclusion Principle in physics. PbA is structured as a memory-based algorithm inspired by Tabu Search and Elitism at some point. A database structure has been created to reduce the function evaluation load in the algorithm. This database can be thought of as a memory capability of the PbA. However, unlike in Tabu Search, this database is designed as a particle repository, not a banned list. On the other hand, the best solutions achieved are also recorded and kept separately. However, this does not include a specific ratio as in the Elitism approach; on the contrary, the best set is used as much as the population size. Although the PbA is inspired by natural facts and other algorithms in the literature, the primary goal is to achieve better results in a specific problem type, regardless of metaphors and similarities.
To show the performance of the PbA, the most common engineering design problems such as Pressure Vessel, Welded Beam, Tension Compression Spring Design, and Himmelblau’s Function are applied. The experimental studies have shown that the PbA performs well to handle constraints while minimizing objective functions, and the PbA has provided the best-known solutions in the literature. It should be pointed out that solution set size significantly impacts the results. For this reason, the PbA has been performed with the minimum set size listed in the comparison table. It is evident that, in the case of a more extensive set size, the best-known solutions can be reached more quickly in the PbA.
Limitations of this study should be noted as well. The performance of the proposed algorithm is limited by the real-world engineering design problems handled. Furthermore, parameter setting for importance scores in MUPE approach has been determined by trial and error which can be considered a disadvantage of the proposed algorithm. Apart from this, hardware qualifications such as central processing unit (CPU), computer data storage, and the motherboard can also be considered as limitations.
For further studies, different benchmark group problems (unconstrained, multi-objective, combinatorial, etc.) can be solved after some modifications of the PbA. Furthermore, the PbA can be integrated with other constraint handling methods. Modifications can achieve the desired result with less function evaluation value. It can be combined with various algorithms as a different hybrid algorithm. Moreover, as stated by Gambella et al. [109], the concept of optimization problems for machine learning presents novel research directions by considering machine learning models as complement approaches in addition to the existing optimization algorithms. For instance, the proposed algorithm can be implemented in any place where other evolutionary algorithms such as genetic algorithm have been utilized for itemset mining as shown in [110, 111]. Besides, it can be integrated with any deep learning algorithms to diagnose the disease as handled in [112].
Appendix
ABC Artificial bee colony algorithm
AHO Archerfish hunting optimizer
AOS Atomic orbital search
APO Artificial physics optimization
CFO Central force optimization
CGO Chaos game optimization
CGWO Chaotic grey wolf optimizer
CSA Cuckoo search algorithm
CoSA Cooperation search algorithm
CSS Charged system search
CPA Colony predation algorithm
DOA Dingo optimization algorithm
EFO Electromagnetic field optimization
EM Electromagnetism-like mechanism
EO Equilibrium optimizer
FA Firefly algorithm
FES Function evaluations
GIO Gravitational interaction optimization
GSA Gravitational search algorithm
GTO Group teaching optimization algorithm
GWO Grey wolf optimizer
H-FPA Hybrid flower pollination algorithm
H-GSA-GA Hybrid GSA-GA algorithm
HO Hysteretic optimization
H-PSO-GA Hybrid PSO-GA algorithm
HS-WOA Hybrid social whale optimization algorithm
IGWO Improved grey wolf optimizer
ISA Interior search algorithm
LA Lichtenberg algorithm
MCSS Magnetic charged system search
MGA Material generation algorithm
MOA Magnetic optimization algorithm
MOPM Modified oracle penalty method
MPA Marine predators algorithm
MUPE Multiplicative penalty-based method
N2F Nuclear fission-nuclear fusion algorithm
OIO Optics inspired optimization
PA Pathfinder algorithm
PbA Penalty-based algorithm
PPA Plant propagation algorithm
PSO-GA Advanced particle swarm-assisted genetic algorithm
RO Ray optimization
RSO Rat swarm optimizer
SBO Smell bees optimization algorithm
SCSO Sand cat swarm optimization
SMA Slime mould algorithm
SOA Seagull optimization algorithm
SRO Search and rescue optimization algorithm
TEO Thermal exchange optimization
TLMPA Teaching–learning based marine predator algorithm
Acknowledgements
There are no relevant financial or non-financial competing interests to report. The authors would like to thank the anonymous reviewers who contributed to the paper through their comments. This study has been derived from a Ph.D. thesis titled as "Nature-Inspired Evolutionary Algorithms and a Model Proposal" which is prepared by Gulin Zeynep Oztas under the supervision of Sabri Erdem. Therefore, we are also grateful to the doctoral dissertation committee members for their supports.
Author contribution
GZO: Investigation, Software, Writing – Original Draft, Writing – Review & Editing. SE: Conceptualization, Methodology, Supervision, Writing – Review & Editing.
Data availability
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Codes of the proposed algorithm are available at https://github.com/gulinoztas/repulsive-forces.git. For further information one can get contact with the corresponding author.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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==== Front
Auton Robots
Auton Robots
Autonomous Robots
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1573-7527
Springer US New York
10074
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Article
That was not what I was aiming at! Differentiating human intent and outcome in a physically dynamic throwing task
http://orcid.org/0000-0002-9951-3513
Surendran Vidullan [email protected]
1Vidullan Surendran
is a doctoral student in Aerospace Engineering at the Pennsylvania State University. His work focuses on human intent recognition, particularly robots using surface cues to determine human intent in the context of various physical tasks. His other areas of interest include autonomous aerial vehicles, computer vision, and intelligent IoT automation. His alma mater is the University of Southampton, UK where he graduated with an MEng in aerospace engineering working on the design of an autonomous Lunar vehicle that could complete the Google Lunar XPRIZE. Currently he is the President of the Penn State Autonomous Robotics Competition Club which participates in aerial vehicle competitions held all over the World.
Wagner Alan R. [email protected]
2Dr. Alan R. Wagner
currently holds a position as an assistant professor within the Aerospace department at Penn State and is a co-funded hire with the Penn State’s Rock Ethics Institute. Previously Dr. Wagner was a senior research scientist at Georgia Institute of Technology’s Research Institute and is a member of the Institute of Robotics and Intelligent Machines. His research interest include the development of algorithms that allow a robot to create categories of models, or stereotypes, of its interactive partners, creating robots with the capacity to recognize situations that justify the use of deception and to act deceptively, and methods for representing and reasoning about trust. Application areas for these interests range from military to healthcare. Dr. Wagner’s research has won several awards including being selected for by the Air Force Young Investigator Program. His research on deception has gained significant notoriety in the media resulting in articles in the Wall Street Journal, New Scientist Magazine, the journal of Science, and described as the 13th most important invention of 2010 by Time Magazine. His research has also won awards within the human-robot interaction community, such as the best paper award at RO-MAN 2007. Dr. Wagner received his Ph.D. in computer science from Georgia Institute of Technology. He also holds a master’s degree in computer science from Boston University and a bachelor’s degree in psychology from Northwestern University.
1 grid.29857.31 0000 0001 2097 4281 301C Engineering Unit C, Pennsylvania State University, University Park, 16801 USA
2 grid.29857.31 0000 0001 2097 4281 234B Hammond Building, Pennsylvania State University, University Park, 16801 USA
3 12 2022
117
2 10 2020
27 10 2022
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Recognising intent in collaborative human robot tasks can improve team performance and human perception of robots. Intent can differ from the observed outcome in the presence of mistakes which are likely in physically dynamic tasks. We created a dataset of 1227 throws of a ball at a target from 10 participants and observed that 47% of throws were mistakes with 16% completely missing the target. Our research leverages facial images capturing the person’s reaction to the outcome of a throw to predict when the resulting throw is a mistake and then we determine the actual intent of the throw. The approach we propose for outcome prediction performs 38% better than the two-stream architecture used previously for this task on front-on videos. In addition, we propose a 1D-CNN model which is used in conjunction with priors learned from the frequency of mistakes to provide an end-to-end pipeline for outcome and intent recognition in this throwing task.
Keywords
Intent recognition
Human robot interaction
Surface cues
Computer vision
==== Body
pmcIntroduction
Robots designed to assist humans should be capable of dynamically varying their behaviour in response to the human’s needs. Prediction of intent allows for efficient task planning by reasoning about what is being done and why (Sukthankar et al., 2014). Liu et al. showed that, in a collaborative scenario where humans are unable to explicitly communicate their intent, inference of human partner goals improved perceived and objective performance of a human-robot team, and that participants preferred to work with a robot that adapted to their actions (Liu et al., 2018). In addition, understanding intent in the context of a task informs us of deviations from normal operation allowing us to spot mistakes early. In a complex task with many steps this could help prevent failures by bringing such deviations to the attention of the person and solutions could be provided to mitigate future problems.
Here, intent is defined as an internal state vector of the human subject that is indirectly observable. We use the terms intent and goal interchangeably in this text. Actions, on the other hand, are the external, observable, manifestations of intent. We consider an example to differentiate between intents and actions. Consider, for example, a pick and place task where participants are asked to manipulate objects based on criteria such as colour, shape, or object type (Alikhani et al., 2020; Jois & Wagner, 2021; Lin & Chiang, 2015; Lamb et al., 2017). An intent or goal could be to complete the task in a specified amount of time. To achieve this intent and perform the task, the person must pickup objects, decide if they fit the imposed criteria, and move them to the appropriate locations within a set amount of time. This leads to sub-goals such as ‘pickup an object’, ‘determine what criteria it satisfies’, and ‘move it to the correct location’. In other words, intents are naturally hierarchical, contextual, and task dependent. Thus recognizing intent requires knowledge of the task.
On the other hand, actions are the observable physical interactions performed by the person to achieve these intents. Action recognition is typically concerned with identifying the physical motion performed by the person, for example, classifying the motion as a grasp, lift, move, or drop. Although action recognition is a key component necessary for recognizing intent, action recognition does not predict the intent unless there is a one-to-one correspondence between the intent and action. Mistakes preclude a one-to-one correspondence between the outcome of an action and the intent.
Humans are rarely perfect when executing complex real world tasks. Mistakes are common when the task is physical and dynamic. Mistakes can be attributed to incomplete information, misunderstandings, physical inability of the body to repeatedly and accurately replicate motion patterns, or a myriad of other factors. Little research has considered the challenge of recognizing intent during mistake riddled, physically dynamic tasks. For such tasks, relying on action recognition to determine intent ignores the possibility that the observed action is incongruent with the underlying intent. Yet, a person is usually aware of the errors they commit if they are able to observe the outcome of their action. We postulate that this awareness is expressed as observable surface cues such as body motion and facial expressions generated by the person. We then hypothesize that using surface cues will allow us to detect congruity between the subject’s intent and the outcome of their action. Used in conjunction with a known task model, this allows us to predict intent, or at the very least reduce the search space of possible intents.
This work focuses on predicting intent in the physically dynamic task of throwing in the presence of mistakes. When mistakes occur, the intent of a human thrower is different from the target the throw hits. The methods proposed for human intent recognition in a throwing task (Li et al., 2018, 2020; Zhang et al., 2019) omit throws that are mistakes and rely on predicting the outcome of the throw which is considered to be the subject’s intent. We argue that this is unrealistic as the inherent difficulty of a throwing task leads to a high percentage of mistakes. To this end, we contribute:A dataset consisting of 1227 throws generated by 10 different participants captured from 3 different viewpoints which includes mistakes1
Prediction of the outcome of a throw when the trajectory of the ball is only partially visible
Recognition of the presence of mistakes relying on the human’s reaction to the outcome
An end-to-end pipeline for intent prediction accounting for the possibility of mistakes
Measures of human performance on this task which can be used as a baseline comparison
Related work
Identifying key frames in the throwing motion and intent recognition relies on determination of human body pose. This can be achieved with a motion capture system or estimated from RGB-D (RGB with an added Depth channel) images. Image based methods have reduced accuracy, but are not restricted to operate within a tracked volume of space. They also forego the need for high performance sensors making them advantageous in robotic applications. AlphaPose (Fang et al., 2017) for instance, uses a spatial transformer architecture to generate two dimensional human pose from RGB images and, achieves 72.3 mean average precision (mAP) on the COCO dataset and 82.1 mAP on the MPII dataset. A commonly used closed source alternative is the Microsoft Kinect V2 which uses RGB and depth from its IR camera to estimate pose (Shotton et al., 2011).
Huang and Mutlu tracked human gaze to develop an anticipatory control method enabling robots to proactively perform tasks based on predicted intent (Huang & Mutlu, 2016). Gaze patterns from 276 episodes were used to train a support vector machine (SVM) classifier based on four features - number of glances, duration of first glance, total duration, and most recently glanced item. They report that their model predicts user intent approximately 1.8 s prior to human verbal request with an accuracy of 76%. Yang et al. proposed a task-based method that captured hand gestures and eye movement to recognize user intent, arguing that hand and eye movement represents a vast majority of nonverbal expressions of intent (Yang et al., 2016). Surendran and Wagner showed that surface cues in the form of upper body gestures could be used to determine if a human was trustworthy or not in the context of a card playing game involving deception (Surendran & Wagner, 2019). Their approach achieved prediction rates that were on par with humans performing the same task. More recently, they extended this work to use facial emotions as features for end-to-end prediction of deceptive intent (Surendran & Wagner, 2021).
Yu and Lee used multiple timescale recurrent neural networks to tackle the problem of intent recognition from recognised motions (Yu & Lee, 2015). Their experiment defined eight types of motion primitives and five intents that were related to drinking, moving, and pouring from a cup or a container. One of the strengths of this work is that they acknowledge that a time sequence of action primitives has to be considered to determine intent as many intents may share the same subsequence of actions. A limitation of their approach is that action sequences that map to an intent have to be pre-defined and known. This was acceptable for the tasks they explored, but is not reasonable for the throwing task where the sequence of primitives that are exhibited is unknown and varies between subjects.
Classification based on human cues generated from videos can be formulated as a time series classification task and can be tackled using algorithms such as nearest neighbour (Lee et al., 2012), dynamic time warping (Jeong et al., 2011), LSTM architectures (Karim et al., 2017) and recently, 3D convolutional networks (CNNs) and temporal CNNs suited for multi-channel data such as images (Akilan et al., 2019). A study with over three million automatically sampled experiments on 75 time series data-sets showed that single metric classifiers very rarely outperform dynamic time warping (Lines & Bagnall, 2015). This provides an empirical argument for ensembles models such as random forests and multi-branch neural networks.
In a task using overarm throws, Maselli et al. found that for most participants it was possible to predict the region where the ball would hit a target as early as 400–500 ms before release (Maselli et al., 2017). They were also able to predict which one of 4 targets were hit with an accuracy of 80% and that towards the end of the throwing action, the throwing arm motion provides the most information. This study was only concerned with where the ball struck the target and not where the participant intended to throw it. It effectively ignores mistakes and the intent of the subject but provides evidence that if extremely accurate joint predictions are available, motion alone can predict the outcome of a throwing task. This method, which used a 16 camera motion capture system to generate highly accurate joint positions, is not ideal for robotic applications in the wild.
Li et al. utilized a Kinect V2 stereo camera to predict the outcome of a throwing task with 9 targets (Li et al., 2020). The human pose estimates generated by the Kinect were used to determine the start of the throwing action. A single camera positioned head-on to the subject, similar to the setup shown in Fig. 1 was used to collect data. They also compared various pre-processing schemes such as K-random sampling of the input frames, using the entire clip, and a combination of both of these to overcome the problem of having frames in the video that were not relevant to the task. The model used for prediction of the throwing outcome was based on the two-stream architecture (Simonyan & Zisserman, 2014) which uses optical flow in conjunction with RGB images.
A majority of the published works that used a throwing task for intent recognition (Li et al., 2018, 2020; Zhang et al., 2019) excluded trials where the participant did not strike the target they were instructed to hit, i.e. mistakes. Excluding mistakes results in artificially mapping the thrower’s intent to the realized outcome. We argue that this exclusion reduces the real-world validity of the proposed intent recognition methods since in this task a significant percentage of throws result in mistakes. During our data collection we found that 47% of throws were mistakes and this is detailed in Sect. 3.2. Moreover, our attempts to reproduce the reported performance from (Li et al., 2020) were not successful and this is explored in Sect. 7.Fig. 1 Throwing task setup with relevant dimensions
Throwing task
We seek to study human intent recognition during physically dynamic tasks. We characterize physically dynamic tasks as tasks that require a rapid series of physical motions, tend to result in improved performance with training, and as a consequence, tend to result in a high rate of mistakes unless the person is highly trained. A throwing task is one example of a physically dynamic task. Throwing tasks tend to result in a high number of unforced errors unless the subject has extensive previous training. Our version extended the throwing task described in (Li et al., 2018) to include more participants, more camera angles, and our dataset included samples where the thrower made a mistake.
Experimental setup
The overall setup is shown in Fig. 1 which is annotated with the relevant dimensions. Three camera units placed at 0∘, 45∘, and 90∘ with respect to the participant allowed the capture of front-on, angled, and side-on images of a right handed thrower encompassing most of the commonly encountered camera viewpoints. A distance of 2.75 ms was used for the 45∘ and 90∘ camera units due to space restrictions, but this still allowed us to fit a 6ft tall subject with their arms extended vertically overhead in the camera frame. The 0∘ camera unit placed under the target 4 ms away replicates the setup used in related work (Li et al., 2018, 2020; Surendran & Wagner, 2021).
The target was a 3×3 grid with nine equally sized zones numbered as shown in Fig. 2. Each of the camera units consisted of an Intel RealSense D435 and a Raspberry Pi camera mounted as shown in Fig. 3. The D435 cameras were mainly used to capture wide angle RGB images of the subject at a resolution of 848×480 pixels and a frame rate of 30FPS. These camera were auto focused at infinity. The Raspberry Pi cameras, fitted with a 50 mm lens, were manually focused such that the participant’s upper body and face was captured at a higher resolution of 1080p and a frame rate of 30FPS. Sample images from the cameras can be seen in Fig. 5 (right).Fig. 2 3×3 target grid with dimensions and zone labels
Fig. 3 Dual camera setup consisting of the Intel D435 and a Pi camera fitted with a 50 mm lens. The Raspberry Pi 4 used to process images from the Pi Camera can be seen vertically mounted behind the cameras
The internal clocks of the three RealSense cameras were hardware synchronized to simultaneously trigger the frame capture. The Raspberry Pi cameras do not support this functionality and thus the software reported timestamp from each captured frame was used to approximately match them. To ensure the clocks of the three Raspberry Pis connected to the cameras had a common reference, we synchronized them to a local Network Time Protocol (NTP) server. Using the six timestamps (three of which are identical due to the hardware synced D435s), we are able to associate each RealSense frame to a corresponding frame from the Pi Cameras. As all cameras were run at 30FPS, at worst we expect to have a frame capture time skew of 33 ms between the Pi camera image and the D435 image.
Data collection
Fig. 4 Probability of intent target given observed outcome target in the presence of a mistake, i.e. the subject misses the target they aimed at. ‘Missed’ refers to the subject missing the target grid entirely, i.e. did not hit any of the 9 zones
IRB approval was obtained and 10 right-handed subjects were each compensated $15 USD to perform the throwing task for an hour. The subject pool consisted of 6 men and 4 women who were physically able, aged 25–35, with a recreational level of throwing proficiency. The participants ranged in height from 4ft 11in to 6ft 1in approximately. Subjects were asked to sign a consent form permitting the recording and sharing of the experiment before they began. The consent form explained the task, but did not mention anything related to intent recognition, mistakes, or their facial expressions and body movement being used for predictions. This was to minimize over-exaggerated reactions they might unconsciously perform in order to aid the study.
Subjects were instructed to place a foot in the vicinity of an ‘X’ mark affixed to the floor so as to stay within view of the cameras. They were told that they could use any overhand throwing motion to throw the ball. A reference of the target numbering was affixed above the target to assist the subject in case they forgot what each target zone was called. Each throwing trial consisted of the experimenter starting video collection and calling out the target zone the participant was to aim at. Once the subject threw the ball, the experimenter would stop video collection a couple seconds after the ball hit the target. In certain cases, where the subject was still noticeably reacting to the outcome of their throw, video collection was continued until a subjective assessment was made to determine when to stop video collection. After the recording was stopped, a generic buzzer sound was played to notify the subject that they were free to move away from the throwing location to pick up a ball for the next throw. Subjects were instructed to only take one ball at a time. Nine identical balls were used so that the subject could throw a ball at each one of the nine target zones before having to collect them. The experimenter sat behind a screen obscured from the subject’s field of view to minimize visual interaction with the subject. Even then, subjects had a tendency to look towards the general direction of the experimenter after completion of a throw.
The target aimed at was considered to represent the subject’s intent, whereas the target the ball actually struck was considered to be the outcome. A round was defined as all 9 target zones being selected as the intent exactly once. The sequence of intent targets was randomly generated each round to minimize learning effects and mitigate extraneous factors such as lighting variations from biasing the data. For example, if one target zone was aimed at multiple times before moving on and the lighting changed, one could differentiate between the targets solely based on image brightness. Learning cannot be completely eliminated as participants tend to improve with practice. Accuracy improvement with practice was counteracted by the decline in performance caused by fatigue over the course of the hour, but the size of these effects is unknown.
Ethical considerations
While collection of such data is predicated on obtaining IRB approval which also governs how the data is shared, the researchers involved who are intimately familiar with the information should carefully consider the privacy and equity issues inherent in its distribution; especially for datasets such as ours containing non-anonymized videos of the participants. With the advent of big data and psychology research conducted via mining social media data, there is an ongoing discussion in the community on best practices to protect the subjects when using publicly available video and social media data (Derry et al., 2010; Kraut et al., 2004; Legewie & Nassauer, 2018; Townsend & Wallace, 2017; Zimmer, 2017).
The subjects that participated in our research study are given the authority to revoke consent at any point which would result in the deletion of their data. But, once distributed, it is impossible to guarantee that other users of the dataset have deleted local copies of the data. This consideration affected how we chose to share the data. We only make the dataset available through explicit request which includes collecting information pertaining to who the users will be, how they will use the data, and how they will protect the data to ensure the privacy of the participants. This allows us to track the users and inform them when participants withdraw consent. We realise that this relies on trusting that the users granted access will follow the protocol, and in practice limits access to researchers belonging to trusted institutions since they can reasonably be expected to behave ethically. While this is in not in the spirit of democratizing science, we consider the ability of our subjects to withdraw consent paramount. An alternative is drafting a legally binding contract for users of the dataset which reduces the emphasis on trust potentially allowing access to a larger user base, but this is complicated by the global nature of research and lies outside the scope of expertise of the authors.
As practitioners implementing data driven models and generating datasets that might become a benchmark, we must consider data biases that can arise due to subject demographics. Since the majority of HRI research arises out of well funded labs in a few countries, there is an under-representation of certain races, genders, and cultures, leading to computational models trained on such data being discriminatory (Cheuk, 2021; Garcia, 2016; Zou & Schiebinger, 2018). This is a very difficult problem to overcome as recruiting numerous diverse subjects is extremely challenging and is something to be cognizant of when deploying models that are trained on our dataset.
Statistics
Table 1 Per subject throws, mistakes, and accuracy
Subject 1 2 3 4 5
Throws 135 200 63 117 82
Mistakes 78 56 38 56 61
Accuracy 0.42 0.72 0.40 0.52 0.26
Subject 6 7 8 9 10
Throws 99 135 135 153 108
Mistakes 69 63 35 64 62
Accuracy 0.30 0.53 0.74 0.58 0.43
Table 2 Mean (std-dev) probability of a mistake when aiming at each target zone (Round-off error results in a sum of 1.01)
0.11 (0.02) 0.12 (0.03) 0.12 (0.03)
0.11 (0.02) 0.11 (0.03) 0.10 (0.04)
0.12 (0.02) 0.11 (0.03) 0.11 (0.03)
Table 3 Number of times each target was hit, i.e. was the outcome target. 192 throws completely missed the target
1 2 3 4 5 6 7 8 9
115 107 95 129 150 141 97 115 86
In total, 1227 throws (mean = 123, std-dev = 37) were made with 192 throws completely missing the target grid and 582 throws resulting in mistakes. Table 3 shows the number of times a target zone was hit regardless of it being selected as the intent target. While the number of mistakes varied based on the participant’s skill level, the mean proportion of mistakes to valid throws over all participants was found to be 0.51 (std-dev = 0.15). Per subject counts are shown in Table 1. We can discount any significant bias towards a particular target zone since the probability of making a mistake was found to be independent of the participant’s intent target as shown in Table 2.
Using the frequency counts of the outcome target given a particular intent target, we calculate a prior probability of the intent target given an observed outcome. Figure 4 shows this matrix of probabilities for the aggregate data of all participants in the presence of a mistake. The diagonal elements are 0 since otherwise it would not be an erroneous throw. This representation allows us to infer that certain targets are highly unlikely to be the intent given a particular outcome, for example, zones 7 or 8 being the intent when the outcome was target zone 3. This makes intuitive sense as one is unlikely to hit the bottom left target zones when aiming at the top right target zone.
Computational pipeline
Given a video of a subject throwing a ball, we would like to predict the intent target. This requires us to determine if the throw is erroneous, which in turn requires the determination of the outcome from videos which only partially capture the trajectory of the ball.
Our approach uses RGB image data to (a) determine the target zone that will be struck, i.e. predict the outcome target (discussed in Sect. 4.3), and (b) predict the target that was being aimed at, i.e. the intent target (discussed in Sect. 4.4). We begin by determining the video frame that signals the end of the acceleration phase of the throwing action, referred to as the throw frame. This information is used to split the video into the throwing segment and the reaction segment. Assuming a subject’s reaction to the outcome would only be observable after they throw the ball, we can reduce the number of uninformative frames by using the throwing segment from the D435 camera which captures the entire subject to address problem (a), and the reaction segment from the Pi camera which provides higher resolution images of the subject’s upper body to address problem (b).
Generation of 2D pose
Fig. 5 Top left graph shows the filtered X,Y values of the throwing wrist along with the composite score for a sample captured by the 0∘ D435 camera. The score was scaled for graphing and the maximum value was observed at frame 77 denoting the throw frame. Bottom left shows the raw, interpolated, and filtered throwing wrist Y coordinate values illustrating the effect of preprocessing discussed in Sect. 4.1. Right shows the throw frame from all 6 cameras
Human pose was predicted using AlphaPose which is a deep learning based multi-person pose estimator (Fang et al., 2017). It outputs 26 joint key-points using the COCO dataset format which includes the location of the following joints: nose, eyes, ears, shoulders, elbow, wrist, hips, knees, ankles. Missing joints, resulting from one part of the body occluding another or low quality images, were linearly interpolated in the temporal direction. The 2D pixel pose estimates were not temporally stable as they are estimated on a frame-by-frame basis which varied slightly over the video even in frames with negligible movement. Moreover, interpolation can result in sudden jumps in joint position when there is excessive joint motion. A Butterworth filter with cutoff frequency of 2Hz was used to reduce high frequency noise over the temporal dimension due to its maximally flat response. The effect of filtering can be observed in Fig. 5 (bottom left).
Determination of throw frame
For the 0∘ cameras, we estimate the end of the acceleration phase of the throwing motion using the following heuristic:The magnitude of the velocity of the throwing arm wrist joint is expected to be sinusoidal going from a standstill (gather), to a minima (cocking), to a global maxima (acceleration), and then approach zero as the arm decelerates at the end of the action (deceleration/follow up).
The scoring metric used for the ith frame of a video containing n frames was,1 scorei=‖vi‖2-max(V)max(V),Vi=‖vi‖2,i=0,1,…,n
where vi denotes the velocity of the throwing wrist joint in the ith frame, and V is the vector containing the L2 norm of velocity for the entire throwing sample. Since this score uses velocity estimated from noisy joint pixel data, we used a Savitzky-Golay filter to fit a 2nd order polynomial using a convolution window length of 11 steps. The score along with the x and y pixel coordinates for a sample are shown in Fig. 5 (top left). From approximately frame 60–90 we observe the sinusoidal pattern that corresponds to the participant cocking their arm back, accelerating towards the target, and then slowing down during the follow through. At the end points, we tended to obtain spikes due to the filtering approach used. We thus ignore the first and last 10% of the frames when searching for the frame with the maximal score. In the example considered (Fig. 5), the score reached a peak at frame 77.Fig. 6 Top shows the LSTM model used to classify 2D pose data into one of 9 outcome classes. ‘Batch’ refers to the variable data batch size used during training/inference. Bottom shows the Multi-branch 1D CNN model used to detect congruence between outcome and intent using features from a pre-trained emotion model. A and B denote two input branches whereas C is the concatenated branch. The layer parameters are shown in Table 4
The 45∘ and 90∘ cameras are able to capture participant joint translation normal to the target grid plane, and thus we used the following heuristic:The distance between the wrist and the body would be at a maximum at the end of the acceleration phase due to maximal elbow extension.
This translates to finding the frame with the maximal signed offset between the x-pixel values of the throwing wrist joint and the hip joint. If only the wrist position is considered, there is a possibility of false positives whenever the subject moves backwards in the frame while throwing.
Figure 5 confirms that the applied heuristics are able to determine the end of the acceleration phase of the throwing action. The hardware synced D435 images all show the same frame from different viewing angels as expected. The prediction for the Rasberry Pi cameras differed slightly as these software synced cameras cannot guarantee frame capture at the exact same instant.
Inspection of the predicted throw frames revealed that the two most common sources of inaccuracy in throwing frame prediction were blurry image frames, and taller participants moving too far forward while throwing resulting in their wrist moving outside the camera frame. Unfortunately, this is commonly found in the Rasberry Pi camera data due to the zoom lens reducing the field of view, whereas the D435 cameras with their wide angle lenses were less affected by subject translation. We did not manually correct the erroneous predictions because our system is meant to be end-to-end autonomous.Table 4 Layer parameters for 1D CNN model
Input Conv1D Dropout Conv1D MaxPool
A Shape = (Batch, 30,7) c = 8, k = 3, s = 1 0.1 c = 16, k = 3, s = 1 k = 2
B Shape = (Batch, 30,7) c = 8, k = 9, s = 1 0.1 c = 16, k = 9, s = 1 k = 2
Concatenate Dropout Dense Dense
C Output = (Batch, 320) 0.1 n = 20, act: relu n = 2, act: softmax
Key: ‘c’ is channels, ‘k’ is kernel size, ‘s’ is stride, ‘n’ is number of units, ‘act’ is activation function. ‘A’, ‘B’ and ‘C’ refer to the model sections from Fig. 6 (bottom)
Outcome prediction
Here we try to predict the outcome target the subject struck irrespective of their intent. Focusing solely on the joint pose results in poor performance in outcome prediction as a multitude of throwing actions can result in an identical ball trajectory. Two identical throwing motions with a minimally varying release position would result in different outcomes. Detection of release position from the 30FPS camera streams was not possible since the fast throwing motions resulted in either blurry frames or the exact moment of release not being captured. The outcome prediction model overcomes this limitation by tracking the position of the ball starting from its initial position coincident with the throwing wrist joint and its trajectory after release until it leaves the camera’s field of view. This implicitly encodes the assumption that the wide range of throwing and follow through motions employed by the subjects is encoded by the position of the ball greatly reducing the dimensionality of our problem.
Due to the large amount of movement inherent in the throwing action, and the ball overlapping the subject in the 0∘ camera, dense optical flow could not be employed to track the position of the ball; The small moving object, that is the ball, was indistinguishable from background noise. We use the estimate of the throw frame number, Ntf to add robustness to this process. The ball is assumed to overlap the throwing wrist joint position for the frames numbered 0 to Ntf-10. Further, we assume that the ball is outside the field of view of the cameras for frames numbers greater than Ntf+5. For the frames in between these ranges, we convert our colour space to HSV, and threshold the image to detect regions with the same colour as our ball. The HSV colour space makes our threshold operation robust to varying lighting conditions compared to the RGB colour space. We filter the resultant binary image using the morphological operations of closing with a 3×3 kernel. Contours are then detected and the center of a rectangular bounding box enclosed around the largest detected connected region of pixels is used as the location of the ball in that frame.
The outcome target is predicted by using a feature vector containing the positions of the ball in the Ntf-5 to Ntf+5 frames. The position of the ball implicitly encodes the position of the throwing wrist joint position in these frames and thus our feature vector is of length 2 (x, y pixel position in image). An LSTM model was used to classify the feature vector into one of 9 target classes and its architecture is shown in Fig. 6 (top).
Intent prediction
This is a two-step process where we first recognize if the outcome is congruent with the intent and subsequently predict the intent of the participant. Images from the Pi camera provide a clearer view of the upper body and face of the subject for the surface cues we hope to extract. One second worth of frames (30 frames) from the reaction segment beginning 10 frames after the identified throw frame is used. The first 10 frames after the release of the ball are ignored as these capture the subject in the follow through phase of the throwing action. This method implicitly assumes that the subject visibly expresses their internal state and the most relevant information is obtained within one second of the completion of the throwing action.
Intent-outcome congruence
It is challenging to recognize or predict a subject’s reaction without a prior model of their behaviour. Humans express themselves using a large number of primitive gestures and combination of gestures. The datasets used for full body gesture recognition such as NTU RGB+D (Shahroudy et al., 2016), NTU RGB+D 120 (Liu et al., 2020), A Large Scale RGB-D Dataset for Action Recognition (Zhang et al., 2018), two-person interaction dataset (Yun et al., 2012), and others all consider everyday activities and are segmented to include only a primary gesture per video sample. They do not consider reactionary body gestures which is required for determining the participant’s reaction in our throwing task. Moreover, the problem of continuous gesture recognition and segmentation is an active area of research with problem specific knowledge used to segment gestures.
Using the full range of expressive gestures and human expression would be preferred, but given the limitations of current gesture recognition algorithms, we employed facial reactions. While limited, prediction of facial emotion based on front-on images is a well studied problem. Detection and cropping of faces in each frame was carried out using an implementation of FaceNet available through the OpenCV computer vision software library (Schroff et al., 2015). A CNN pre-trained on the FER 2013 dataset (Arriaga et al., 2017) which contains 35,685 images representing seven expressions, namely, happiness, neutral, sadness, anger, surprise, disgust, and fear was used to generate feature vectors from the images of the cropped faces. We modified the CNN by removing the output softmax classification layer and using the flattened weights from the last 2D global average pooling layer as our feature vector.
Our proposed solution relies on detecting the facial emotion response and using this to infer if the subject has committed a mistake (Surendran et al., 2021; Surendran & Wagner, 2021). By using a pre-trained facial expression model, we leverage priors learned from a much larger dataset and eliminate the need to label our throwing dataset. We employed a multi-branch 1D CNN model whose architecture is shown in Fig. 6 (bottom) and layer parameters are shown in Table 4. The binary outcome of the model corresponds to the observed outcome fulfilling the subject’s intent or the outcome being different from the intent indicating the presence of a mistake.
Prediction
The output of the intent-outcome congruence model informs how we predict the intent target. If the intent is congruent with the outcome, the throw did not result in a mistake and the intent target is predicted to be the same as the outcome target. Otherwise, we can rule out the observed outcome being the intent and are left with 8 possible target choices. We generated a-priori probabilities as discussed in Sect. 3.3 and use this distribution to predict the intent target. Given an outcome target, the target zone with the maximum probability is chosen as the intent target. If multiple intent targets have the same probability, then one of them is randomly selected.
While certain probabilities were calculated to be 0 as these events were not observed during data collection, this might not hold true during inference. Add-one smoothing was used to assign a minimal but non-zero probability to prevent the model from discounting target zones with a probability value of 0. We do not consider online updates of this probability matrix which would negate the need for this smoothing.
Human performance as a comparison
Table 5 Average human labeler performance on the tasks
0∘ Cam 45∘ Cam 90∘ Cam
Outcome (Accuracy) 0.43 0.23 0.29
Congruence (F1/MCC) 0.69/0.14 0.74/0.33 0.72/0.23
End-To-End (Accuracy) 0.33 0.16 0.25
Performance metric listed in parenthesis
Due to the limited literature exploring intent recognition on tasks that include mistakes, there is a dearth of models that can be used for comparison. We recruited two humans labelers to perform the tasks of outcome, intent-outcome congruence, and intent recognition. This provides another comparison baseline in addition to random chance.
The labelers were shown 50 randomly sampled throwing videos from the 1035 throws that hit the target grid to help them learn each participant’s tendencies, referred to as the learning phase. Then their performance was evaluated on 50 new videos randomly sampled from the dataset, referred to as the testing phase. The labelers were allowed to replay the video as many times as they wanted. They were asked to predict the outcome target, if the participant hit the correct target (intent-outcome congruence), and then predict the intent target. This process was repeated for the 0∘, 45∘, and 90∘ cameras ensuring the labelers saw the same video samples for all three views. Since the labelers were not provided the ground truth after each testing phase, seeing the same samples should not increase performance as a result of memorization of the correct answer. The testing phase used the same samples for the three views to prevent sample selection from skewing the results for the different views.
Once the human labelers completed the task, an informal interview revealed the strategies they employed. They said that they tried to use the trajectory of the ball and its position in the image to determine the outcome target. They also considered how fast the participant moved to extrapolate the ball’s trajectory once it left the frame. In samples where the ball immediately went out of frame, or when the participant’s limbs were not visible in the frame (commonly encountered in the 45∘ and 90∘ views), they expressed that ‘educated guesses’ were the only option. For the 45∘ and 90∘ views, the labelers mentioned that they primarily focused on predicting the row of the target grid the ball would strike as it was extremely difficult to predict the column due to the lack of depth data.
Both human labelers felt that barring a few subjects who had ‘no reactions’, they were confident in their ability to determine when a subject had missed the target. To predict the intent target, they tried to follow where the participant was aiming using eye gaze and body posture prior to the start of the throwing phase. In addition, they tended to assume that subjects would on average be inaccurate in the vertical axis rather than the horizontal axis. The heuristic is confirmed by the frequency data shown in Fig. 4.
Table 5 lists the performance metrics averaged over both human labelers. Overall, they outperformed all models considered. Comparing the best case human labeler performance to our models, outcome prediction accuracy was 0.43 compared to the model accuracy of 0.34, congruence had a MCC score of 0.33 compared to model MCC of 0.29, and intent prediction accuracy of 0.33 versus 0.25 for the model (Sect. 6.2 discusses why MCC was considered the appropriate metric for intent-outcome congruence). We attribute this to the human ability to use the participant’s body position prior to the throw, reason about the throwing motion employed, and extrapolate the ball’s trajectory once it has left the camera’s field of view. Human detection and interpretation of emotions and expressions is currently far superior to computational models. Finally, human ability to predict the ball’s position even when it is blurry in the image is superior to the computational models.
Results
All models were evaluated using 5-fold nested cross validation. Training was carried out on a system running Ubuntu 18 equipped with a Ryzen 1700, Nvidia 2080 S GPU, and 16GBs of RAM. All two-stream models were trained in Pytorch 1.5 with a batch size of 10, and the SGD optimizer with momentum of 0.9. The initial learning rates were 1.24e-2 for the RGB stream and 2.4e-4 for the flow stream. The learning rate was reduced to 10% of its value every 20 epochs. Training was stopped when the validation loss stagnated for 10 epochs to ensure convergence. The LSTM and CNN models were trained in Tensorflow 2.1 with a batch size of 5, Adam as the optimizer, and a learning rate of 2e–3. Training was stopped when the validation loss did not improve for 20 epochs. The mean value over all 5 folds is reported for all metrics unless otherwise specified.Table 6 Comparison of classification accuracy for outcome prediction using the D435 camera frames (mean/std-dev)
0∘ cam 45∘ cam 90∘ cam
LSTM (Ours) 0.339/0.06 0.219/0.01 0.251/0.02
Two-Stream(Li et al., 2020) 0.245/0.04 0.179/0.03 0.178/0.03
Human Labelers 0.43/- 0.23/- 0.29/-
Outcome prediction
Only the 1035 throws that struck one of the nine target zones were used. To account for the differing number of throws per participant, the throws were split on a per participant basis using 80% for the training set and 20% for the testing set. This ensured the number of throws per participant in the split sets were representative of the dataset. In addition, the splits were stratified using the outcome target to better represent the distribution in the dataset. For a perfectly balanced split, we would expect a mean of 0.11 and a std-dev of 0.0 for the percentage of samples belonging to each target zone that makes up the set. For the 5 splits used, the overall mean was 0.108 with an average std-dev of 0.019 which meant our dataset was balanced and had a similar number of samples for each outcome target. The training set was further split into a training and validation set using a 80:20 ratio to determine when to stop training the model. Using the testing set for this purpose can lead to over-fitting on the test set and an inflated accuracy metric.
Table 6 compares the model introduced in Sect. 4.3 to the Two-Stream scheme (Li et al., 2020), and the human labeler baseline. Predicting the majority class for the 5-folds would result in a mean accuracy of 0.14 (std-dev 0.005). The performance of Li et al.’s Two-Stream approach is discussed in detail in Sect. 7 and in summary our model improves performance by 33% over all 3 views compared to the Two-Stream approach. Our model was able to get closer to the human labeler accuracy in the 45∘ and 90∘ cases since these views made it hard for the labelers to perceive depth and use their knowledge of throwing actions to extrapolate ball trajectory. Figure 7 shows the proportion of test cases that were correctly predicted for each target zone. This illustrates that our model is able to differentiate ball trajectories in the X and Y axis and the accuracy is not a result of skewed performance on few target zones. The poor performance on target zone 9 can be attributed in part to the 45∘ and 90∘ camera being increasingly perpendicular to the ball trajectory which worsens depth determination from RGB camera images which are 2D projections of the 3D trajectory of the ball.Fig. 7 Mean accuracy over the 5-folds for each target zone. Ordered left to right showing grids for the 0∘, 45∘, and 90∘ D435 camera views
Predicting the outcome of the throwing task using only RGB data of the throwing motion is a very difficult problem. Inter-subject variation in the form of varying throwing actions and limb lengths, and intra-subject variation in the form of changing ball release speed, release point, and the use of multiple overhand throwing actions greatly increases the complexity of this problem. These variations, caused by differing body geometry, results in the inability to accurately predict the ball’s trajectory using body pose as current computer vision techniques lack the ability to precisely and consistently detect joint position with sub-millimeter accuracy in the absence of tracking cameras. Moreover, the same throwing action can result in different ball trajectories if the release point is minimally altered and it is not possible to accurately track the hand to determine the release point with our current setup.
Intent-outcome congruence prediction
In this case, the 5-folds for cross validation were created similar to outcome prediction using only the 1035 throws that struck one of the nine target zones. Throws from each participant were split using 80% for the training set and 20% for the testing set. Unlike outcome prediction, the splits were stratified using the dummy variable, congruence, defined as,2 congruence=1,outcome=intent0,outcome≠intent
This led to imbalanced folds where on average 63% of the cases belonged to the positive class in this binary classification problem. The training set was further split into a training and validation set using a 80:20 ratio.
When training our neural network, the loss function was biased using class weights calculated using the distribution of the training set to account for the imbalanced training set. When a binary classification dataset is imbalanced, the F1 score which computes the harmonic mean of the recall and precision can be used to evaluate the model. While we provide the F1 scores, we also discuss the Matthews Correlation Coefficient (MCC), also referred to as the phi coefficient, as it can be shown to be superior to the F1 score (Chicco & Jurman, 2020). In addition, the F1 score is not normalized and the score is not symmetric when the classes are swapped. MCC is easier to interpret with a score of -1 representing an inverse prediction, 0 an average random prediction, and +1 a perfect prediction. To illustrate the utility of the MCC score, consider that for a random classifier on this task, the mean MCC over all folds was 0.02 (std-dev 0.05) and the F1 score was 0.48 (std-dev 0.03). For a classifier that predicted only the negative class the MCC was 0 and the F1 score was 0.27 whereas for one that predicted only the positive class the MCC was 0 and the F1 score was 0.38. The MCC score correctly captures that these models are not predictive which is very hard to glean from the F1 scores. For the sake of completeness, we present the F1 scores in addition to the MCC.
Table 7 shows the metrics for the intent-outcome congruence model discussed in Sect. 4.4 compared against the human labelers. We do not compare to Li et al. as their work assumes that the intent target is always coincident with the outcome target and only perform what we refer to as outcome prediction.
Both the labelers and our model outperform a random average model which had an MCC of 0.02 and F1 score of 0.48, and a majority class predictor with MCC of 0 and F1 of 0.38. This provides evidence that the model is able to predict the congruence at a rate above chance and that the subject’s internal state change in response to the outcome of their action is expressed through facial emotions and can be captured using RGB cameras. Intent-Outcome congruence prediction is one where we expect humans to vastly outperform the algorithm. Surprisingly, our algorithm outperforms the human labelers in the front-on 0∘ camera view with an MCC of 0.29 compared to the humans at 0.14.
Our model performance degrades as we get more side-on and the camera moves away from capturing frontal videos of the subject. This degradation can be attributed to poor facial emotion recognition when the subject’s face is not captured head-on as the pre-trained emotion model and available facial emotion datasets are based on close-up frontal images of the face. Another major issue was that taller participants tended to move outside the field of view of the 45∘ and 90∘ cameras during their throwing action even though they were instructed to minimize translation towards the target. These two issues do not affect the 0∘ camera which captures front-on videos of the subject.Table 7 Intent-Outcome congruence MCC and F1 scores for the Pi camera frames (mean/std-dev)
0∘ cam 45∘ cam 90∘ cam
1D-CNN MCC 0.29/0.04 0.19/0.06 0.05/0.07
F1 0.62/0.02 0.58/0.03 0.48/0.06
Human MCC 0.14/– 0.33/– 0.23/–
Labelers F1 0.69/– 0.74/– 0.72/–
Intent prediction
For this experiment, the 80:20 train/test splits were stratified using the intent target and only trials where the subject hit one of the nine target zones were used. The resulting splits were balanced as the data collection procedure ensured subjects aimed at all nine target zones equally. Subjects were also equally likely to make a mistake regardless of target zone, hence ignoring trials where they completely missed the target did not introduce any significant imbalance in the splits. We therefore use accuracy as the evaluation metric.
Here we evaluate the performance of intent prediction using the probability matrix as described in Sect. 4.4.2 for only those data samples where incongruence is detected i.e. the outcome is not the intent. This allows us to evaluate performance in isolation of the outcome prediction pipeline as when incongruence is not detected, the intent prediction accuracy is directly tied to outcome prediction accuracy.
Three different probability distributions were considered: A uniform probability distribution used as a baseline, probabilities based on all trials in the training set, and specific probabilities generated for each subject calculated using only the trials they completed. Table 8 shows that using the entire dataset to generate the probabilities outperforms only considering subject specific trials. Both these methods perform far above random or using a uniform distribution. The low number of trials some subjects completed in the hour of data collection explains the poor performance of the subject specific model. With more data, we expect the accuracy of a subject specific model to improve. Humans tend to have biases in their movement patterns which would be reflected in hitting certain target zones more frequently. In the case of our throwing dataset, the higher accuracy of the model which uses the entire dataset suggests that the subjects had similar patterns of mistakes.Table 8 Effect of probability matrix on intent prediction accuracy (mean/std-dev)
Dataset Avg Subject Specific Uniform
0.451/0.05 0.374/0.05 0.113/0.03
Table 9 End-to-End accuracy for the three camera views (mean/std-dev)
0∘ cam 45∘ cam 90∘ cam
Ours 0.253/0.06 0.157/0.01 0.180/0.01
Labelers 0.33/– 0.16/– 0.25/–
End-to-end pipeline
Finally, we evaluate the performance of intent prediction on both samples that contain and do not contain mistakes in contrast to the previous section. That is, we evaluate the end-to-end system which uses the predicted outcome and intent-outcome congruence prediction to determine subject intent. For this experiment, we have to ensure that the same training/test split is used to train all the models to prevent data leakage. The training splits were stratified using the intent targets since this best represents the throwing task. The overall dataset probabilities were used for intent prediction. For the end-to-end system, the best accuracy was found to be 0.253 (std-dev 0.06) when the 0∘ camera was used.
Table 9 shows the end-to-end prediction accuracy for the various camera views with the D435 camera data used for outcome prediction and the Rasberry Pi camera data used for intent prediction. We found that the highest end-to-end intent prediction accuracy was obtained using the 0∘ camera view which corresponds to the view with the highest outcome prediction accuracy discussed in Sect. 6.1. This highlights the high degree to which the outcome prediction accuracy affects the accuracy of the end-to-end system, and when the outcome is predicted incorrectly, this has a cascading effect on intent prediction. The model outperforms a random predictor which has an accuracy of 0.11 in all cases. But, compared to the human labelers, we were only able to match their performance in the 45∘ view. This can be attributed to the superior labeler outcome prediction informed by learning outside of this task allowing them to infer ball trajectory from the videos better than the proposed outcome prediction model.
Comparison to closely related work
In this section we address the inability to replicate the model performance of the Two-Stream architecture reported by Li et al. and discuss,Choice of train/test splitting (Li et al., 2018).
Use of the test set to select the best model parameters during training (Li et al., 2020)
Differences in the dataset used in Li et al. (2020) and our throwing dataset
(A) Li et al. (2018) and (B) Li et al. (2020) use a 9 target experimental setup with a single camera pointed towards the subject which corresponds to the 0∘ camera in our version of the experiment. (A) explores data augmentation methods for improving performance while, (B) proposes the use of the two-stream deep learning architecture. In (A) a single human participant was used to create a dataset consisting of 256 training trials and 36 testing trials. In (B) a larger dataset was created using 6 human subjects each performing 90 throws to obtain 432 training samples and 108 testing samples, and introduces the two-stream architecture as an improved model over the CNN used in (A). Both (A) and (B) report an outcome prediction accuracy in the range of 50–75% for the data augmentation and sampling techniques they developed respectively. Our evaluation of the two-stream architecture on our dataset introduced in Sect. 3.2 resulted in much lower performance metrics listed in Table 6.
Inspection of the code used for (A) available from the project’s publicly available Github (Zhang, 2018) revealed an issue with the strategy used to create the train and test sets resulting in data leakage between these sets. In (A) the frames from all the throwing trial videos were extracted and collated to form a large dataset of images which was then shuffled and split into a train, validation, and test set. While this is a common way of creating splits for image recognition tasks, it is not appropriate for video classification as the training and testing sets would contain frames from the same video. To avoid data leaks, the videos must first be assigned to either the train or test set before extraction of the frames.
The code and data used for study (B), which is currently not publicly available, was obtained by contacting the authors. There was no data leak in (B) and the train/test sets were split appropriately on a per video basis. The code we received evaluated the model on the test set after each training epoch, saving the model with the highest accuracy on the test during the training phase. This overfits the model to the test set. A validation set should have been employed to avoid this issue and this method of parameter selection would severely impact the model’s ability to generalize to unseen data. From the code it was unclear if K-Fold cross validation was employed. Training the Two-Stream model using the code sent to us by the authors on the dataset used in (B) resulted in performance shown in Table 10 which is lower than that reported in (Li et al., 2020). This variation in performance can be attributed to the different train/test splits we generated and random initialization of the network parameters among other factors.
We conclude by evaluating the performance of our outcome prediction method on the dataset used in (B). We used 5 fold cross validation. For fair comparison, we also used the test set to select optimal model parameters. Table 10 shows that our method is able to match the accuracy of the two-stream model.Table 10 Accuracy of two-stream model introduced in (Li et al., 2020) compared to our method presented in Sect. 4.3
1 2 3 4 5
RGB stream 0.41 0.50 0.30 0.34 0.50
Flow stream 0.38 0.33 0.27 0.32 0.50
Avg. fusion 0.40 0.50 0.29 0.34 0.51
Our method 0.45 0.43 0.49 0.36 0.47
Shows our model is able to match performance on the dataset used by Li et al. (2020). Results shown for all 5-folds of cross validation
Fig. 8 Anonymized image showing the position of the ball in (Li et al., 2020) for each of the 9 target zones when thrown by a single participant. Even with the naked eye one can differentiate between the outcome targets especially which column of the target grid the ball might strike. Image at the top left represents target zone 1, while the image at the bottom right shows target zone 9
Fig. 9 Position of the ball for each of the 9 target zones for a single participant in our dataset showing the difficulty of determining the outcome target from the ball position in the frame. Image at the top left represents target zone 1, while the image at the bottom right shows target zone 9
Difference between our dataset and (B) Li et al. (2020)
The most striking difference is the speed at which the participants in (B) throw the ball. In our dataset participants threw the ball significantly faster as the only limitation placed on them was the use of an overhand throwing action. This resulted in many frames in our dataset containing a blurry ball and arm captures due to the joint and ball velocities even though both datasets captured images at 30FPS.
Another difference is the number of frames for which the ball was visible after release. On average the ball was visible for 4–6 frames after release in our dataset compared to 10–12 frames in (B). The Kinect V2 they used has a field of view (FoV) of 84.1x53.8 compared to the D435 with a FoV of 64x41. These factors made it easier to determine the outcome target based on the location of the ball in the camera frame in (B). Since their dataset is private, we include a graphical representation of the location of the ball and subject in the final frame before it leaves the camera field of view for the 9 target zones in Fig. 8. Compared to the location of the ball in our dataset, shown in Fig. 9, where the ball moves towards the top of the image, it is far easier to determine the outcome target in the version of the dataset used in (Li et al., 2020) based on ball position and size in pixels. Thus the Two-Stream architecture which uses majority voting of the individual frame predictions to predict the outcome target performs poorly as the location of the ball in the frame corresponding to each target zone becomes harder to separate. An LSTM on the other hand with input features containing the location of the ball is able to use temporal information of the ball’s trajectory to predict the outcome with higher accuracy.
Conclusion
Physically dynamic tasks introduce unique challenges from the perspective of intent recognition due to the increased number of unforced errors humans make while performing them. In our throwing dataset out of a total of 1227 throws, 582 were mistakes with the subjects completely missing the entire target grid in 192 of these mistakes. Prior work that considered the throwing task ignored throws that resulted in mistakes introducing a one-to-one correspondence between the subject’s intent and the outcome. In realistic situations, mistakes must be accounted for and the outcome cannot be considered to be the human’s intent. We propose a method that leverages the surface cue of facial expressions allowing us to predict when the subject believes they have committed a mistake. Using this information we inform our prediction of intent in the context of the throwing task.
We propose the use of an LSTM to predict the outcome from the partial ball trajectory and show that it outperforms the majority voting prediction used by the Two-Stream architecture previously used for this task. Our 1-D CNN which uses features learnt from a facial emotion dataset is able to outperform human labeler performance in predicting the presence of a mistake when given front-on videos. Using the output of these two models along with priors learnt from the frequency of mistakes, we provide an end-to-end system that takes as input a video of a throw and predicts the outcome and intent for a throwing task consisting of 1035 throws generated by 10 people.
While our end-to-end pipeline performs better than chance and matches human performance on the 45∘ camera view, it is not able to outperform the human labelers. The use of an emotion dataset with front-on facial images results in degraded performance as in the 45∘ and 90∘ views which does not affect the labelers. Although we have improved outcome prediction, vision based approaches under-perform when compared to motion capture systems. The main culprit is the resolution and precision by which both these methods estimate human joint position. The advantage of vision-based approaches is that they can be used on robots in the field unlike MOCAP systems that require expensive equipment and are constrained to a calibrated environment. We also show that a two-stream architecture for throwing tasks is ill-advised unless the location of the ball in the frames is well seperated for each target zone. When the position of the ball is not well differentiated, we propose the use of an LSTM that is able to leverage temporal information and extrapolate the trajectory of the ball to predict the target zone.
Since we use a subject’s reaction to the observed outcome to predict if a mistake is likely, it is not possible to predict the intent earlier than 30 frames after the completion of the task. We envision this pipeline to be utilized in applications where a robotic teammate would assist the human when it has detected that the outcome observed was not the intent of the human. In such tasks, prediction of the intent is only necessary before the next step of the task has to commence. For example, in our throwing task the robotic teammate might help by striking the correct target if the human missed the target. As long as there is about 1 s in addition to the time taken by the robot to perform the actions available to complete the task, this late prediction should be acceptable for a particular application. On the other extreme, if the task involves predicting the intent before the ball thrown by the human has hit the target, or before the human has reacted to the outcome, then our method which relies on capturing the reaction of the human would not be suitable.
Advancements in the prediction of temporally stable 3D poses from RGB-D data would help reduce joint position errors and improve performance of outcome prediction using 3D pose as input compared to 2D pose. Unfortunately due to the global COVID-19 pandemic we were extremely limited in our ability to conduct human subject research. Future work could test these ideas using additional human subjects with varied backgrounds and limb lengths as the type of cues exhibited could differ significantly. The advantage of using emotion cues is that these cues are largely agnostic to a person’s physical characteristics, but the same cannot be said for outcome prediction using human pose. Normalisation of lengths based on a reference length might overcome this but it is unclear if different body types inherently bias the types of surface cues exhibited. We must also consider that emotion cues likely vary with one’s culture, age, and gender, and this information is rarely available for the emotion datasets we transfer learn from.
We argue that changes to the task setup such as orientation of the target and number of targets would be unlikely to change the validity of the method developed as it is probable that subjects exhibit comparable reactions to the outcome of a throw. Even if the task type was changed to require a different physical action, for example rolling a ball towards targets, or pushing an object towards multiple targets, we believe our method would be able to predict outcome-intent congruence as long as the task meets the key criteria of being one where mistakes are likely. This arises from the hypothesis that the surface cues of facial expression and body gestures arises from the subject’s reaction to an uncertain outcome when performing a skill based action. It is possible that stronger cues are generated if an element of chance/luck in introduced to increases the uncertainty of the outcome. Inversely, when the outcome is certain, for example the task of placing the ball in one of many target boxes without time pressure, the intensity of the surface cues exhibited, if any at all, would be very low making them undetectable.
The adaptability of this technique is illustrated by the use of facial emotions as a feature to detect incongruence in a task that did not have dynamic motions but introduced uncertainty in the form of incomplete information. Surendran et al. (2021) showed that in a card game where the human intends to deceive the robot, there are patterns in the sequences of the perceived surface cues that can be used to detect incongruence which was then used to predict the intent to deceive on par with human performance on the task.
Future work should also consider variations that affect the difficulty of the task. Varying the distance to the target and sizing of the target grid can affect not only subject performance but model prediction accuracy. The order of the target zones aimed at were randomly selected to minimize increase in accuracy due to practice/learning effects. Participant accuracy would also be negatively affected by fatigue as time goes on. We did not attempt to quantify the effects of practice and fatigue on accuracy in our throwing task as this would require a longitudinal study with repeated data collection on the same subject to evaluate improvement in performance. A longitudinal study deriving from this research is another opportunity for future work as this would inform how an intent recognition system can adapt to a particular subject over time. Finally, fusion of images from multiple viewpoints to generate prediction could also improve performance by relying on the advantages of each view. This initial attempt at predicting intent using pose and emotion cues shows promise and at the very least provides a method that can help detect mistakes and the lack of congruence between the observed outcome and the expected outcome.
Declarations
Conflict of interest
The authors declare that they have no affiliations with or involvement in any organization or entity with any conflict of interest regarding the subject matter or materials discussed in this manuscript.
1 Request access at https://sites.psu.edu/real/datasets/.
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Sociocultural Issues and Epidemiology (M Fusaschi, Section Editor)
Policies and Practices on Out-of-Hospital Birth: a Review of Qualitative Studies in the Time of Coronavirus
http://orcid.org/0000-0002-8002-543X
Quattrocchi Patrizia [email protected]
grid.5390.f 0000 0001 2113 062X University of Udine, Udine, Italy
9 12 2022
113
12 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Purpose of Review
The purpose of this review is to summarize the current knowledge on out-of-hospital births (at home or in an independent birth center) in high-income countries in the time of coronavirus. Qualitative studies published between 2020 and 2022 providing findings on women’s and health providers’ perspectives and experiences, as well as policies and practices implemented, are synthetized.
Recent Findings
During the COVID-19 pandemic, the number of women choosing the home or a birth center to deliver has grown considerably. Main reasons for this choice include fear of contagion in facilities and restrictions during delivery and the post-partum period, especially women’s separation from their companion of choice and their newborn. Findings suggest that homebirth within a public model has several advantages in the experience of birth for both women and professionals during the pandemic period, maintaining the benefits of biomedicine when needed.
Summary
During the COVID-19 pandemic, the interest in out-of-hospital birth increased in high-income countries, and the number of women choosing the home or a birth center to deliver has grown considerably. This review aims to give a more in-depth understanding of women’s and health providers’ perspectives on and experiences of out-of-hospital birth services during this period. Twenty-five studies in different countries, including the USA, Canada, Australia, Switzerland, the Netherlands, the UK, Spain, Croatia, and Norway, were reviewed. Findings stress that out-of-hospital birth has allowed women to deliver according to their wishes and needs. In addition, the pandemic experience represents an opportunity for policy to better support and integrate out-of-hospital services in the health care system in the future.
Keywords
Homebirth
Birth center
Community birth
Out-of-hospital birth
COVID-19
==== Body
pmcIntroduction
Although out-of-hospital birth is still a controversial topic, evidence-based literature shows that in high-income countries, in low-risk women, and in well-integrated health systems, homebirth and independent birth centers are associated with fewer obstetrical interventions and equal safety compared to hospital births [1–6, 7••]. Sometimes, it is even safer than hospital birth, because it provides fewer unnecessary interventions, offers personalized care, and enhances women’s empowerment [2]. During the COVID-19 pandemic, the interest in out-of-hospital births increased in high-income countries, and the number of women choosing the home or a birth center to deliver has grown considerably. This review aims to give a more in-depth understanding of women’s and health providers’ perspectives on and experiences of out-of-hospital birth services during the pandemic period. It also aims to foment the debate on the desirable better integration among different models of care in childbirth in high-income countries.
Methods
To perform this study, a qualitative synthesis was conducted [8]. The objective was to identify papers relating to out-of-hospital births and COVID-19 published in English or Spanish between 1 January 2020 and 30 June 2022.
Search Strategy and Study Selection
The database search was conducted on PubMed and SciELO. Interdisciplinary approach was taken into account: both databases contain citations and abstracts of biomedical and social sciences literature. Qualitative approach is well-represented in these sources. The following key words were used: “out-of-hospital birth,” “homebirth,” “planned homebirth,” “birth centre,” and “Covid 19” or “Sars-Cov-2.” In Spanish, “parto domicilio/domiciliar/en casa and Covid 19/Sars-Cov-2,” “casa de parto/casa maternidad,” and “Covid 19/Sars-Cov-2” were used. The inclusion criteria comprised primary data analysis characterizing women’s and health care providers’ perspectives on and experiences of out-of-hospital birth during the pandemic, written in English or Spanish and considering high-income countries. A total of 78 articles were initially obtained by data search. Each title and abstract were screened for inclusion. Following deduplication (33), 20 articles were excluded according to the following exclusion criteria: research conducted in middle- and low-income countries (12), systematic reviews (2), guideline and protocol studies (2), and articles addressing other topics (4) (Fig. 1). Twenty-five studies were included in the review. They were carried out in 9 countries (Table 1).Fig. 1 Flow diagram of search and study inclusion
Table 1 Selected studies.
Source: author’s elaboration
Reference number Study Country Study aim Study population Methodology
11 Rauch S, Arnold L, Stuerner Z, Rauh J, Rost M. A true choice of place of birth? Swiss women’s access to birth hospitals and birth centers. PLoS One. 2022Jul6;17(7):e0270834. 10.1371/journal.pone.0270834. PMID: 35,793,367; PMCID: PMC9258807 Switzerland To analyze Swiss women’s choice between birth hospitals and birth centers 1,896,669 (99.8 of Swiss women of childbearing age) were included Spatial accessibility analysis, based on four data types: highly disaggregated population data, administrative data, street network data, addresses of birth hospitals and birth centers. If both birth settings were available within 30 min, a woman was considered to have a true choice
12 MacDorman MF, Barnard-Mayers R, Declercq E. United States community births increased by 20% from 2019 to 2020. Birth. 2022 Feb 25. 10.1111/birt.12627. Epub ahead of print. PMID: 35,218,065 USA To examine trends in community births from 2019 to 2020, and the risk profile of these births A total of 3,613,647 were analyzed Analysis of birth certificates transmitted to the National Center for Health Statistics. 2020 birth certificate data were compared with prior years’ data to analyze trends in community births by socio-demographic and medical characteristics
13 Vanderlaan J, Woeber K. Early perinatal workforce adaptations to the COVID-19 pandemic. J Perinat Neonatal Nurs. 2022 Jan-Mar 01;36(1):37–45. 10.1097/JPN.0000000000000617PMID: 35,089,176 USA To describe the system’s initial pandemic response from the perspectives of perinatal health workers and to identify opportunities for improved future preparedness A total of 181 nurses, midwives, and physicians Exploratory survey to identify perinatal practice changes and workforce challenges during the initial weeks of the COVID-19 pandemic. The survey included baseline data collection and weekly surveys
14 Grünebaum A, Bornstein E, Katz A, Chervenak FA. Worsening risk profiles of out-of-hospital births during the COVID-19 pandemic. Am J Obstet Gynecol. 2022. Jan;226(1):137–138. 10.1016/j.ajog.2021.11.1346. Epub 2021 Dec 10. PMID: 34,895,908; PMCID: PMC8660066 USA To evaluate changes of place of births and risk profiles before (2019) and during (2020) the COVID-19 pandemic 3,747,540 births in 2019 and 3,613,647 in 2020 Retrospective descriptive population-based cohort study that used the Centers for Disease Control and Prevention Natality online database for the years 2019 (before the pandemic) and 2020 (during the pandemic). Comparison of births in birth centers and home births with those in hospitals (births by midwives and births by others, such as doctors)
15 Strózik M, Szarpak L, Adam I, Smereka J. Determinants of place of delivery during the COVID-19 pandemic-internet survey in polish pregnant women. Medicina 2022, 58, 831. 10.3390/medicina5806083 Poland To determine the factors influencing the choice of place of delivery and the impact of the COVID 19 pandemic on these factors 517 women who gave birth during the pandemic or are about to give birth Survey questionnaire distributed via the Internet from 8 to 23 June 2021. Statistical analysis of measurable (quantitative) and non-measurable (qualitative) features. The analysis of the relationships between the qualitative variables was carried out with the use of cross tables with the use of chi-2 tests, Likelihood ratio chi-2, and the exact Fisher test. The strength of the compounds was measured using the Phi Yule coefficient. A correlation between quantitative variables was verified using Spearman’s rho test. A significance level of p < 0.05 was adopted, indicating the presence of statistically significant relationships or differences. Statistical analysis was performed using the SPSS 26 software
16 Applebaum J. Expanding certified professional midwife services during the COVID-19 pandemic. Birth. 2022 Apr 15:10.1111/birt.12643. 10.1111/birt.12643. Epub ahead of print. PMID: 35,429,017; PMCID: PMC9111869 USA To discuss issues surrounding the expansion of CPM services including safety, standardization of care, patient satisfaction, racial and income equity, and an overburdened health care system Discussed policy
17 Mikuš M, Sokol Karadjole V, Kalafatić D, Orešković S, Šarčević A. Increase of stillbirths and unplanned out-of-hospital births during coronavirus disease 2019 lockdown and the Zagreb earthquake. Acta Obstet Gynecol Scand. 2021Nov;100(11):2119–2120. 10.1111/aogs.14250. Epub 2021 Aug 26. PMID:34,448,194; PMCID: PMC8652766 Croatia To evaluate the effect of the first wave of COVID-19 pandemic and the Zagreb earthquake on perinatal outcomes in the largest Croatian maternity clinic at the University Hospital Center Zagreb Total single births 3277 (2029) and 2732 (2020) Retrospective study. The analysis covered the data of all pregnant women with singleton gestation admitted during the pandemic period from February 25 to December 31, 2020 (study group) and the corresponding prepandemic period in 2019 (comparison group)
18 Rice KF, Williams SA. Making good care essential: the impact of increased obstetric interventions and decreased services during the COVID-19 pandemic. Women Birth. 2021 Oct 27:S1871-5192(21)00,182–7. 10.1016/j.wombi.2021.10.008. Epub ahead of print. PMID: 34,774,446; PMCID:PMC8559154 Canada To examine the impact of pandemic policy changes on experiences of pregnancy and birth, thereby identifying barriers to good care; to inform understandings of medicalization, care, pregnancy, and subjectivity during times of crisis; and to critically examine the assumptions about pregnancy and birth that are sustained and produced through policy 65 pregnant people Qualitative descriptive study drawing on 67 in-depth interviews with people who were pregnant and/or gave birth in Canada during the pandemic. Constructionist standpoint and employed thematic analysis to derive meaning from study data
19 DeJoy SB, Mandel D, McFadden N, Petrecca L. Concerns of women choosing community birth during the COVID-19 pandemic: a qualitative study. J Midwifery Womens Health. 2021 Sep;66(5):624–630. 10.1111/jmwh.13290. Epub 2021 Oct 1.PMID: 34,596,940; PMCID: PMC8662103 USA To understand childbearing persons’ decision-making during the pandemic and to illuminate their experiences giving birth in community settings 17 pregnant women Semi-structural interviews, content analysis, and phenomenological approach
20 Preis H, Mahaffey B, Lobel M. The role of pandemic-related pregnancy stress in preference for community birth during the beginning of the COVID-19 pandemic in the United States. Birth. 2021 Jun;48(2):242–250. 10.1111/birt.12533. Epub 2021 Mar 6. PMID: 33,677,838; PMCID: PMC8250474 USA To quantitatively investigate psychological factors related to this birth preference 3896 pregnant women This study included 3896 pregnant women from the COVID-19 Pregnancy Experiences (COPE) Study who were anticipating a vaginal birth. COPE Study participants were recruited online between April 24 and May 15, 2020, and completed a questionnaire that included preference with respect to place of birth and psychological constructs: fear of childbirth, basic beliefs about birth, pandemic-related preparedness stress, and pandemic-related perinatal infection stress
21 Daviss BA, Anderson DA, Johnson KC. Pivoting to childbirth at home or in freestanding birth centers in the US during COVID-19: safety, economics and logistics. Front Sociol. 2021 Mar 26;6:618,210. 10.3389/fsoc.2021.618210. PMID: 33,869,572; PMCID: PMC8022486 USA To examine the intersections of safety, economic efficiency, insurance, liability, and birthing persons’ needs that have become critical as the pandemic has ravaged bodies and economies around the world Discuss policy
22 Gildner TE, Thayer ZM. Maternity care preferences for future pregnancies among United States childbearers: the impacts of COVID-19. Front Sociol. 2021Feb 18;6:611,407. https://doi.org/10.3389/fsoc.2021.611407. PMID: 33,869,560; PMCID:PMC8022446 USA To analyze how the pandemic may shape future maternity care preferences post-pandemic 1175 women participants Online convenience survey. Prenatal survey and postnatal survey 4 weeks after their due date
23 Grünebaum A, McCullough LB, Bornstein E, Klein R, Dudenhausen JW, Chervenak FA. Professionally responsible counseling about birth location during the COVID-19 pandemic. J Perinat Med. 2020 Jun 25;48(5):450–452. 10.1515/jpm-2020–0183. PMID: 32,401,227 USA Discuss policies and health providers recommendation Discuss policy
24 Noddin K, Bradley D, Wolfberg A. Delivery outcomes during the COVID-19 pandemic as reported in a pregnancy mobile app: retrospective cohort study. JMIR Pediatr Parent. 2021 Oct 4;4(4):e27769. 10.2196/27769. PMID: 34,509,975; PMCID: PMC8491643 USA To assess the incidence of key obstetrics outcomes (preterm delivery, cesarean sections, and home births) and length of hospital stay during the COVID-19 pandemic as compared to the 6 months prior 304,023 birth reports of women aged 18–44 years who delivered between October 1, 2019, and September 30, 2020, had singleton deliveries, and completed a birth report in the Ovia Pregnancy mobile app Retrospective cohort study. Women were assigned to the prepandemic cohort if they delivered between October 2019 and March 2020, and the pandemic cohort if they delivered between April and September 2020. Gestational age at delivery, delivery method, delivery facility type, and length of hospital stay were compared
25 Nelson A, Romanis EC. The medicalisation of childbirth and access to homebirth in the UK: COVID-19 and beyond. Med Law Rev. 2021 Dec 6;29(4):661–687. 10.1093/medlaw/fwab040. PMID: 34,668,011; PMCID: PMC8574542 United Kingdom To explore how the law has perpetuated the medicalisation of childbirth, and outline why this may limit the ability of birthing persons to access and opt for homebirth Low and policies analysis
26 Van Manen ELM, Hollander M, Feijen-de Jong E, de Jonge A, Verhoeven C, Gitsels J. Experiences of Dutch maternity care professionals during the first wave of COVID-19 in a community based maternity care system. PLoS One. 2021 Jun 17;16(6):e0252735. 10.1371/journal.pone.0252735. PMID: 34,138,877; PMCID: PMC8211230 The Netherlands To present the opinions and experiences of maternity care professionals with the organization of maternity care during the COVID-19 pandemic; and outline the opportunities for the long-term organization of maternity care 495 respondents:
364community midwives
75 hospital-based midwives
34 obstetricians
22 resident obstetrics
Online survey. Multinomial logistic regression analyses were used to investigate associations between the respondents’ characteristics and answers. The data were imported from Survalyzer and analyzed using IBM SPSS Statistics for Windows, version 26
27 Oparah JC, James JE, Barnett D, Jones LM, Melbourne D, Peprah S, Walker JA. Creativity, resilience and resistance: black birthworkers’ responses to the COVID-19 pandemic. Front Sociol. 2021 Mar 25;6:636,029. 10.3389/fsoc.2021.636029. Erratum in: Front Sociol. 2021 May 13;6:695,303. PMID: 33,869,584; PMCID: PMC8022614 USA To present the experiences of Black birthworkers supporting pregnant and birthing people and new mamas during the first 6 months of the COVID-19 pandemic 38 participants (2 midwives, 2 lactation consultants, 7 community health workers, 23 doulas, and 2 obstetric/gynecologists) Narratives of Black birthworker were collected and analyzed. Participants were invited to participate in one of four sharing circles, held virtually over Zoom. Sharing circles were attended by 8–12 participants. A set of guiding questions were asked in the Zoom chat and each participant shared their experience. Conversations were taped, transcribed, and analyzed using Dedoose qualitative research software
28 Greenfield M, Payne-Gifford S, McKenzie G. Between a rock and a hard place: considering “freebirth” during COVID-19. Front Glob Womens Health. 2021 Feb 18;2:603,744. 10.3389/fgwh.2021.603744. PMID: 34,816,178; PMCID: PMC8594025 United Kingdom To provide real-time data to capture the lived experiences of expectant families during COVID-19 1700 respondents. The survey was open to those in the third trimester of pregnancy, and the partners of pregnant women and people who were in these circumstances A mixed-methods online survey was carried out over 2 weeks between 10 and 24th April 2020. 1700 responses were received
29 Homer CSE, Davies-Tuck M, Dahlen HG, Scarf VL. The impact of planning for COVID-19 on private practicing midwives in Australia. Women Birth. 2021. Feb;34(1):e32-e37. 10.1016/j.wombi.2020.09.013. Epub 2020 Sep 23. PMID: 32,994,144; PMCID: PMC7510523 Australia To explore the experience of privately practicing midwives in relation to the response to planning for the COVID-19 pandemic 103 privately practicing midwives An online survey was distributed through social media and personal networks to privately practicing midwives in Australia in April 2020
30 Verhoeven CJM, Boer J, Kok M, Nieuwenhuijze M, de Jonge A, Peters LL. More home births during the COVID-19 pandemic in the Netherlands. Birth. 2022 May 12. 10.1111/birt.12646. Epub ahead of print. PMID: 35,554,962 The Netherlands To examine whether the course of pregnancy and birth and accompanying outcomes among low-risk pregnant women changed in the COVID-19 pandemic compared to the prepandemic period 5913 women, 2963 (50.1%) of them were pregnant in the COVID-19 pandemic, whereas 2950 (49.9%) were pregnant in the prepandemic period. They were healthy women, with a singleton pregnancy, who gave birth from 24 weeks of gestation onward, and had at least one appointment with a primary care midwife after 24 weeks of gestation Observational study. Analysis of data from the Dutch Midwifery Case Registration System (VeCaS). Differences in the course of pregnancy and birth, and accompanying maternal and neonatal outcomes, were calculated between women pregnant during the initial months of the COVID-19 pandemic (March 1 to August 3, 2020) and the prepandemic period (March 1–August 3, 2019)
31 Davis-Floyd R, Gutschow K, Schwartz DA. Pregnancy, birth and the COVID-19 pandemic in the United States. Med Anthropol. 2020 Jul;39(5):413–427. https://doi.org/10.1080/01459740.2020.1761804Epub 2020 May 14. PMID: 32,406,755 USA To show the changes that have occurred in birth practices across the USA as a result of the pandemic 41 members of the listservs of the Council on Anthropology and Reproduction, REPRONETWORK, and birth practitioners, including midwives, doulas, and obstetricians Queried via e-mail members of the listservs of the Council and birth practitioners between March 27 and April 11, 2020. Content analysis
32 Premkumar A, Cassimatis I, Berhie SH, Jao J, Cohn SE, Sutton SH, Condron B,Levesque J, Garcia PM, Miller ES, Yee LM. Home birth in the era of COVID-19: counseling and preparation for pregnant persons living with HIV. Am J Perinatol. 2020 Aug;37(10):1038–1043. 10.1055/s-0040–1,712,513. Epub 2020 Jun 4. PMID:32,498,092; PMCID: PMC7416217 USA Discuss experience and recommendations for counseling and preparation of pregnant persons living with HIV who may be considering home birth or at risk for unintentional home birth due to the pandemic; discuss issues associated with implementing a risk mitigation strategy involving high-risk births occurring at home during a pandemic Persons living with HIV who may be considering home birth or at risk for unintentional home birth due to the pandemic Analysis of components of counseling for pregnant persons living with HIV who are choosing home birth and literature
33 Costa Abós S, Behaghel M. Parir en casa en tiempos de coronavirus, Musas. 2020;5(2): 4–22. 10.1344/musas2020.vol5.num2.1 Spain To present women’s experience of giving birth 1 woman giving birth at home In-depth interview and content analysis
34 Combellick JL, Basile Ibrahim B, Julien T, Scharer K, Jackson K, Powell Kennedy H. Birth during the COVID-19 pandemic: what childbearing people in the United States needed to achieve a positive birth experience. Birth. 2022 Jun;49(2):341–351. 10.1111/birt.12616. Epub 2022 Feb 25. Erratum in: Birth. 2022 Jul 13;: PMID: 35,218,067; PMCID: PMC9111370 USA To identify what childbearing people needed to achieve a positive birth experience during the pandemic 707 participants from 46 states and the District of Columbia completed the questionnaire, with 394 contributing qualitative data about their experiences. Participants were who gave birth during the COVID pandemic from 3/1/2020 to 11/1/2020 Mixed-methods, cross-sectional study. Participants were sampled via a web-based questionnaire that was distributed nationally. Descriptive and bivariate statistics were analyzed. Thematic and content analyses of qualitative data were based on narrative information provided by participants. Qualitative and convergent quantitative data were reported
35 Monteblanco AD. The COVID-19 pandemic: a focusing event to promote community midwifery policies in the United States. Soc Sci Humanit Open. 2021;3(1):100,104. 10.1016/j.ssaho.2020.100104. Epub 2021 Jan 1. PMID: 34,173,508; PMCID: PMC7775796 USA To theorize that the COVID-19- disrupted health care system and the heightened visibility of community midwives may create a “focusing event,” or policy window, which may enable midwives and their advocates to shift policy Discuss policies
Data Extraction
Twenty-five studies were included in the review (Table 1). Full texts were analyzed. A thematic synthesis approach [9] was used to synthetize the data. It was based on an initial coding of the texts and the subsequent development of first-order descriptive categories, a second order of analytical themes, and a third order of domains (Table 2). ATLAS.ti qualitative data analysis software was used to code and synthetize the studies into categories and themes. The analysis synthetizes findings from research conducted in the following countries: the USA (15 studies), Canada (1), Australia (1), Switzerland (1), the Netherlands (2), the UK (2 studies), Spain (1), Poland (1), Croatia (1). Sixteen studies included women, 4 studies included health providers (especially midwives), 1 study included both women and health providers, and 4 studies discussed policies and laws.Table 2 Analysis: codes, categories, and domains.
Source: author’s elaboration
Third order: domains Second order: themes Studies First order: codes
Data Increase of delivery in out-of-hospital birth
Increase of interest in out-of-hospital birth
[12–15, 17, 18, 21, 22, 24, 25•, 26–28, 30, 32, 33] Increase number of out-of-hospital births
Increase interest in out-of-hospital birth
Increase interest in freebirth
Increase according to women and pregnant persons’ profile
----Race/ethnicity
----Gender
----Socio-economics status
----Medical condition
Midwives perspectives and experience Midwives’ perceptions on use of out-of-hospital birth services
Midwives’ perceptions on interest in out-of-hospital birth
Midwives’ experiences/role on out-of-hospital birth
[13, 16, 19, 21, 24, 26, 27, 29, 31, 33–35] More questions
More consultants
More births
Hospital-based midwives experience
Community-based midwives experience
Women’s and pregnant persons’ perspective and experience Reasons for the choose homebirth [15–22, 25•, 26–28, 30–33] Fear of being infected in hospital setting
Restrictions
Fear of interventionism/unnecessary practices
Fear for lack of support
Women’s experiences [10, 14, 16, 19, 21, 23, 26, 27, 31–34] Women’s satisfaction
Safety (perception of)
Risk (perception of)
Increasing in risk profile
Policy Barriers to out-of-hospital birth [11, 12, 19, 21, 22, 25•, 33–35] Spatial accessibility
Costs
Laws and policies
Protocols
Preference for the future
Recommendations [11, 18, 20–22, 25•, 29, 31–35]
Quality Assessment
Qualitative studies were assessed for quality using the JBI Critical Appraisal Checklist for Qualitative Research (QARI) tool [10]. Threshold for inclusion was confirmation of questions 2, 3, 4, 5, 8, and 10.
Findings
The studies included in this review show the perspective and experience of women regarding home birth during the COVID-19 pandemic [11–24, 25•, 26–35]. A few case protocols or policies are also discussed [17, 19, 25•, 34]. In the qualitative synthesis, the following themes emerged as significative during the pandemic: (1) increased use of and interest in homebirth and independent birth centers by pregnant women (16 studies); (2) midwives’ perceptions and role (10 studies); (3) reasons of the preference of giving birth in an out-of-hospital setting (17 studies); (4) women’s experiences (10 studies); (5) barriers to access a no hospitalized birth (9 studies); (6) recommendations (12 studies).
Themes were aggregated into four domains: (1) data, (2) midwives’ perspectives and experiences, (3) women’s perspectives and experiences, and (4) policies (Table 2).Data
Increase of delivery in homebirth and independent birth centers. During the COVID-19 pandemic, more women desired and had a home birth. Most of the studies show a significant increase of out-of-hospital births during the pandemic period [12–15, 17, 22, 24, 25•, 26, 27, 30]. In the USA in 2020, one out of every 50 births (2.0%) was a community birth [2]. Community birth increased in every states in the USA, from 19.5 to 30% [12, 14, 24]. Homebirth increased from 23.3 to 30%, and birth center birth increased from 9.2 to 13.2% (2, 4]. Increases occurred for all racial and ethnic groups, particularly non-Hispanic Black mothers [12–14, 24]. An increase between 20 and 30% of out-of-hospital births is reported also in Poland, in the Netherlands, in the UK, in Australia, and in Croatia [15, 17, 25•, 26, 29, 31]. In Croatia during the pandemic period, the overall prevalence of unplanned out-of-hospital births was 0.4%, against the annual out-of-hospital birth rate reported in the last decade, consistently around 0.05–0.10% of all singleton gestations [17].
Midwives’ perspectives and experiences
The perceptions of community midwives and midwives working in hospital-based care regarding the increasing birth rate in their country are reported [16, 19, 21, 24]. Midwives also reported increased interest in or desire for out-of-hospital birth, increase in the number of enquiries by women relating to homebirth, more confidence in giving birth at home, and better-informed choices about the place of birth [16, 19, 21, 24]. Women with high-risk pregnancies, such as those living with HIV, are increasingly investigating the option of home birth, according to the midwives’ experiences [24]. Findings also show the positive role of community midwives in supporting birthing women during the pandemic and their ability to find innovative ways to offer care in the pandemic situation. Flexibility and their ability to work when supplies or institutional support is limited were particularly useful during this period [13, 16, 19, 26, 27, 29, 31, 33–35]. Changes reported in their practices included more wearing of personal protective equipment (masks and gloves); sanitizing their workspace; fewer in-persons visits or childbirth classes; more video calls, phone calls, and virtual prenatal and post-partum visits; and sharing online documents to inform women [26, 27, 31, 35]. Strategies were developed to contrast the lack of PPE, for instance homemade sanitizer and cloth masks [29]. Some difficulties emerged, such as financial strain for independent midwives, due to the loss of job for many parents because of the pandemic [16, 27], and the inability to support women who needed transfer from home to hospital because of the restrictions (health professionals were seen as “support people” or visitors, not as professionals) [29, 31].
Women’s perspectives and experiences: the reasons for the choice 3.1 Motivations/reasons for the preference of giving birth in an out-of-hospital setting. More women have chosen out-of-hospital birth due to (a) the perception of the hospital as a more dangerous place in the time of pandemic (greater chance of becoming infected) [15, 17, 20, 30]; (b) the restrictions implemented in facilities [15, 16, 18–20, 22, 26–28, 30, 31], especially restriction on birth partners and visitors, being separated from the newborn after birth, and restriction on doulas; and (c) fear of unnecessary intervention in response to the pandemic stresses and uncertain condition (i.e., unnecessary induction of labor, cesarean section, etc.) or lack of support [18, 26, 27, 30]. Interest in “freebirth” (giving birth without a professional present) is also reported, particularly for lesbian, bisexual, pansexual, and queer women [28, 31]. Many women had a preexistenting desire for community birth and used the pandemic to justify or consolidate their choice [19, 33].
3.2 Women’s satisfaction. Women who choose to give birth at home or in an independent birth center reported significantly higher satisfaction: they reported to be better informed and less stressed during pregnancy; receiving care in their home kept them safe; fear of contagion was better managed; more autonomy and self-efficacy were also reported [10, 16, 19, 21, 27, 34]. Increases in the risk profiles in community birth (increase of women giving birth to twins, preterm births, breeched newborns, post-cesarean delivery, or persons living with HIV) were also reported [14, 23, 32, 33].
Policies 4.1 Evidence reported some logistic, financial, and legal barriers to access an out-of-hospital birth setting, preventing women from a true choice [11, 12, 19, 21, 22, 25•]. Limited accessibility of birth centers (birth setting not close to the women’s home), high costs, and suspended services due to the emergency were reported during the pandemic period.
4.2 Recommendations. According to many studies, the pandemic is an opportunity to restructure reproductive health care, particularly to better support out-of-hospital births [11, 18, 20, 22, 25•, 29–33, 35]. Findings stressed the pandemic served as a positive example of the need to recognize and better integrate in the broader health system home birth services and birth centers. This involves rethinking laws, policies, and practices in order to offer a real choice to all women regarding the model and place of birth. This is recommended due to the positive impact of out-of-hospital services in women’s and midwives’ experiences and in clinical outcomes.
Discussion
The impact of the COVID-19 pandemic had a profound effect on childbearing women, their families, and midwives [36••]. Evidence shows that restrictions and measures taken during the period disrupted the quality of care provided to women during labor and childbirth and respectful maternity care [37] and impacted the choice of the place of birth. On the one hand, fear of being infected or ill led some to perceive hospitals as no longer “safe” places for mothers and newborns. This occurred even if the risk was defined by scientific evidence as contained for pregnant women [38].
On the other hand, the implementation of rigorous protocols in a standardized way (in most cases, for all deliveries and birthing women) discouraged many women from delivering in hospitals and caused them to take interest in alternative models of care. The WHO, since the beginning of the emergency and throughout the pandemic period, has repeatedly recommended not to separate women in labor from their newborn and their companion of choice, even when suspected of or infected with SARS-CoV-2 [38]. Despite these recommendations, separation of mother–partner–child has been implemented all over the world [39]. The impact on the mother and newborn in terms of well-being and “positive birth” [40] has emerged in the literature [41, 42], as well as the lack of exercise of human rights in childbirth and the loss of women’s autonomy in reproductive health [43, 44].
Qualitative studies on out-of-hospital birth carried out between 2020 and 2022 in different countries are discussed within this context. The pandemic has accelerated the demand for homebirth and birth centers, increasing in the last decades in high-income countries (Macdormen and Declerq 2019 [45]. Women’s needs and expectations—well investigated in high-income countries also before the pandemic [46–49]—were highlighted during the COVID-19 emergency, involving more women and parents. The increasing rate of using homebirth and birth centers shows that out-of-hospital births have been a fundamental “safety valve” to manage fear, uncertainty, and stress during pregnancy and birth for both women and midwives; it has also offered women the possibility to maintain certain autonomy and freedom of choice in the reproductive process. This calls for novel social and political awareness for accessing different models of care (hospitalized or not) as a human right in daily life and as an efficient response strategy for present or future emergencies involving health systems. A novel policy effort to better support and integrate out-of-hospital services in health care systems is urgent in high-income countries. Lessons learned from these experiences during the pandemic represent an opportunity to rethink our models of care in childbirth, focusing on women’s needs and contrasting abuse and disrespect that can turn into forms of obstetric violence, which is well known in research [50–56] and recently addressed in the debate of international bodies [57–59]. Expanding biomedical concepts of safety and risk, while also considering social, cultural, and family dimensions—as clearly emerge from women giving birth at home or in birth centers also before the pandemic, is taken into account in this perspective [54, 60].
Conclusion
Interest in out-of-hospital births has increased during the COVID-19 pandemic. More women have delivered at home or in an independent birth center. Main reasons for this choice are fear of contagion in facilities and standardized protocols, such as restrictions during delivery and the post-partum period, especially women’s separation from their companion of choice and their newborn. Research findings suggest that homebirth and birth centers have conferred several advantages for both women and professionals during the pandemic period, maintaining the benefits of biomedicine when needed. This calls for renewed support for out-of-hospital models of care within a public model of care.
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The author declares no competing interests.
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| 0 | PMC9735103 | NO-CC CODE | 2022-12-14 23:28:32 | no | Curr Sex Health Rep. 2022 Dec 9;:1-13 | utf-8 | Curr Sex Health Rep | 2,022 | 10.1007/s11930-022-00354-7 | oa_other |
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SN Bus Econ
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Springer International Publishing Cham
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10.1007/s43546-022-00361-9
Original Article
Crisis transmission degree measurement under crisis propagation model
http://orcid.org/0000-0002-2356-3717
Belghith Imen Bédoui [email protected]
1
Hallara Slaheddine [email protected]
2
Jilani Faouzi [email protected]
3
1 Higher Institute of Taxation and Finance, University of Susa, Tunis, Tunisia
2 grid.265234.4 0000 0001 2177 9066 Tunisian Higher Institute of Management, University of Tunis, Tunis, Tunisia
3 grid.12574.35 0000000122959819 Faculty of Economics and Management of Tunis, University of Tunis El Manar, Tunis, Tunisia
9 12 2022
2023
3 1 723 9 2020
10 10 2022
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
In this paper, we propose a new approach to studying the spread of financial crises, their effects, and origins. To do this, an empirical measure of the degree of crisis transmission is introduced in the context of a crisis propagation model that corresponds to a multifactorial switching model with random endogenous transition variable. The latter is modeled as a diffusion process and allows us to determine whether crisis transmission is perfect, partial, or weak and whether it is due to contagion or interdependence effects. In addition, the model takes into account the relative impact of idiosyncratic and global factors in crisis and non-crisis periods, as well as any lag in the crisis transmission process. We used the genetic algorithm as an empirical method, because it uses probabilistic rather than deterministic transition rules, which is appropriate for our work. Our results suggest that the subprime crisis is perfectly or partially transmitted to developed markets and interdependence effects are due to most of them. However, the transmission to emerging markets is only partial or weak and, in most cases, due to contagion effects. Moreover, the significance of the coefficients of idiosyncratic factors was not related to crisis effects. For many countries, these coefficients were higher than the coefficients of the global factors, while crisis transmission was due to contagion effects. Our results exceed those of alternative studies on crisis transmission and provide important portfolio and risk management insights. By understanding the crisis transmission mechanism, investors and risk managers can make appropriate decisions to hedge against market downturns and reduce risk out of the country.
Supplementary Information
The online version contains supplementary material available at 10.1007/s43546-022-00361-9.
Keywords
Crisis transmission
Crisis transmission degree
Crisis transmission magnitude
Idiosyncratic and global factors
Multifactorial switching regimes model
Diffusion process
Crisis effects
Developed, emerging and frontiers markets
JEL Classification
C3
C4
C6
F3
F6
issue-copyright-statement© Springer Nature Switzerland AG 2023
==== Body
pmcIntroduction
Financial and currency crises have hit the world’s financial markets in recent years. The causes and repercussions of financial crises have been the subject of numerous financial studies. A typical characteristic of these crises is that they can spread quickly from one market to another and can cause financial instability. However, the results were not always convergent in determining their beginning and ending dates and their transmission mechanism.
Financial crises are not necessarily problematic; while they may be detrimental to some markets, they may also be advantageous to others. Whether or these countries were interconnected due to macroeconomic factors, investment- related issues surfaced when shocks resulting from country-specific crises were conveyed from one country to another. For instance, Fratzscher et al. (2014) stated that subprime crisis was transmitted to other countries because of the deterioration of their domestic factors and not specifically because of the relationships that they had with the United States. Even in the instance of the COVID-19 crisis, which did not originate in the financial sector, suddenly binding financial frictions powerfully amplified the initial impulse. The main question that arises is how can we measure crisis transmission magnitude, impacts, and origins?
In this study, we model the evolution of stock market indices as a switching multifactorial model within transmission and no-transmission crises situations, and thus, we avoid the need to define their timing exogenously. Our model specifically aims to measure the degree of crisis transmission and establish whether the transmission of the under consideration crisis is perfect, partial, or weak. Additionally, our model analyzes the relative importance of local and global factors in each of these settings to determine whether the crisis transmission is due to contagion or interdependence effects measured by estimated coefficient of idiosyncratic factor generated by the crisis market.
In specifically, by modeling stock market indices as a multifactorial switching model with a random endogenous transition variable, we suggest a new strategy to analyze the crisis transmission process and identify its scale, consequences, and origins. This variable, which is expressed as a diffusion process, measures the magnitude of crisis transmission degree.
Our formulation is unique in that the change from a crisis to a non-crisis regime is described as a stochastic process as opposed to a deterministic one (as was the case of probabilistic models). Since the size of a crisis’ transmission degree and magnitude and the relative weights of the crisis’ originating causes depend on one other, this fact serves as the foundation for our core concepts of measuring crisis transmission degree and pinpointing its origin.
The contributions of the paper are as follows. First, our multifactorial switching model benefits from switching models, which provide the opportunity to account for various financial states or regimes (Benigno et al. 2020; Barthlemy and Marx 2017; Coe 2002), as well as from multifactorial models, which are adaptable and suitable to describe various financial aspects.
Second, the transition variable in our created model, which measures the degree of crisis transmission, is modeled as a diffusion process rather than a deterministic one. This measurement allows to ascertain whether a crisis is completely transmitted, partially transmitted, or weakly transmitted, as well as whether it is caused by contagion or interdependence effects.
Third, in both crisis and non-crisis periods, our created model takes into account the relative weights of local and global factors. However, their weights differ depending on whether there is a crisis or not. By modeling stock market indices as multifactorial switching model with a random endogenous transition variable, we do not have to specify exogenously crisis and non-crisis periods. The model’s structure takes these into consideration, allowing us to avoid issues with determining crisis periods.
Researchers, foreign investors, and financial risk managers can all get a better understanding of financial contagion and its mechanism by quantifying crisis transmission magnitude, identifying its effects, and pinpointing its source. Studying crises transmission degree may also have significant ramifications. In times of crisis, investors need to adjust their portfolios dependent on the severity of the crisis. In reality, the markets appear to be more connected during these times, which can restrict the benefits of diversification process.
In our study, we take into account the instance of the subprime crisis, which spread quickly throughout international financial markets, caused global financial catastrophes, and finally led to the collapse of the financial system (Fratzscher et al. 2014). Numerous financial risk managers, international investors, and academics have been inspired by this financial crisis to research the crisis transmission process and reduce risks from the crisis originating country. Therefore, a key area of study in the field of international finance is the study of financial contagion and its mechanism.
Since many real-world financial issues might be complicated and call for the employment of an effective and reliable optimization strategy, we employed the genetic algorithm as our empirical methodology. It is a valid approach to many practical problems in finance which can be complex and thus require the use of an efficient and robust optimization technique. It attempts to solve difficult problems by evolving an initial set of potential solutions into better solutions through an iterative process.
Our empirical findings demonstrated that the developed model performed better than the competing crisis transmission research. We found that the subprime crisis transmission to many developed markets was perfect or partial and was caused, in the majority of cases, by interdependence effects. The emerging markets, however, did not see strong crisis transmission for major cases and it was due to contagion effects. Recent findings from behavioral finance studies (i.e., Engstrom et al. 2019; Huynh et al. 2020; Foglia et al. 2021) can be used to explain paper findings, particularly the occurrence of contagion effects in the crisis transmission process.
The remainder of the paper is organized as follows: the literature review for the framework of our model is presented in Sect. 2. The methodology and data for empirical modeling are presented in Sect. 3. Section 4 provides empirical findings. Section 5 brings the paper to a close.
Literature overview
There is already a large body of recent financial literature that attempts to pinpoint crises transmission channels and their effects (see, e.g., Huang and Xu 2021; Otrok et al. 2020; Agosto et al. 2020; Engstrom et al. 2019; Hansen et al. 2019; Christou et al. 2019; Alexakis and Pappas 2018)). From a thorough literature review, two main approaches on financial crises transmission may be identified.
The first one known as investor-induced channels (pure contagion) explains financial crises transmission by the rational or irrational investor’s behavior (Masson 1998; Forbes et al. 2001; Pritsker 2000). Wealth constraints and portfolio rebalancing behavior are the commonly recognized channels of investor-induced contagion (Kodres and Pritsker 2002; Yuan 2005). Changes in risk appetite are frequently seen as an important determinant of asset prices’ dynamics. The behavioral finance literature (Lemmon and Portniaguina 2006; Baker and Wurgler 2006) developed “sentiment indices” to examine financial market anomalies. Foglia et al. (2021) recently proposed a new approach to estimate investor’s sentiments and their implications for the global financial markets. They constructed a cross-country sentiment indices entitled “feverish sentiment” and explored its ability to predict stock volatility (return). They found that investor’s sentiment positively predicted the stock volatility and negatively anticipated the returns at the onset of COVID-19. While, the habit models with time-varying risk aversion started to emerge in the “structural” dynamic asset pricing literature (Campbell and Cochrane 1999) with the recent variants using structural asset pricing models (Huynh et al. 2020; Engstrom et al. 2019; Xu 2017; Bakshi and Wu 2010). Recent equilibrium frameworks have demonstrated that comoving country risk aversion is potentially important in explaining international comovements (Miranda-Agrippino and Rey 2020; Hoerova et al. 2021).
Other approaches explained the existence of crises transmissions by the already existing economic and financial relations: fundamental-induced channels (shift contagion) (Rose et al. 1996; Glick and Rose 1999; VanRijckeghem and Weder 2001; Kichian et al. 2006; Kumagai et al. 1003; Jayech 2016; HortaP and Martins 2008; among many others). Econometric approach was devised by Flavin and Panopoulou (2010) that made it possible to examine both shift and pure contagion within a same framework. They found a statistical evidence of both types of contagion in developed and emerging markets. According to Samitas et al. (2011a), the contagion effect was caused by behavioral reasons rather than changes in macro-fundamentals.
Numerous studies have examined the empirical characteristics of the transmission channels of the financial crisis, and these studies were distinguished by the diversity of their empirical methodology. The first empirical studies including those of King and Wadhwani (1990, Baig and Goldfajn (1999), Forbes et al. (2001), Forbes and Rigobon (2002), and Butler and Joaquin (2002) were interested in examining the stock market correlations during crisis and non-crisis periods. When there was a considerable increase in the correlation coefficient during a crisis, it was thought that there was a greater degree of crisis transmission between the two markets. These studies were suffering from omitted variables, heteroscedasticity and endogeneity problems. Some authors proposed multivariate approach González-Hermosillo et al. (2005b), DCC test (Rigobon 2003), and DCC GARCH (Khemiri et al. 2010) to correct heteroscedasticity effects. In a recent study, Zorgati and Lakhal (2020) used adjusted and local correlation measures, based on the polynomial local regression, and found that simple and adjusted correlations were not enough to explain the spatial effect of contagion. Bentes et al. (2021) employed the EGARCH technique to develop the volatility spillover effect. The results revealed that gross domestic product and money supply were the most significant factors influencing the volatility spillover effect among pan-Asian countries.
Other studies, including those of Masulis et al. (1990), Ito et al. (1990), Edwards (1998), Longin and Solnik (1995), Nelson (1991), and Jagannathan et al. (1993), were based on the ARCH processes and their extensions to study the transmission of external crises volatilities to stock markets. Dedi and Yavas (2017) distinguished between “volatility transmission” and “volatility persistence” in crisis and non-crisis periods using GARCH and ARMA processes. Many extensions of ARCH process were given: EGARCH (Nelson 1991; GJR-GARCH (Jagannathan et al. 1993), SWARCH (Hamilton and Susmel 1994), NEAR-GARCH (Sun and Zhou 2014), and FIAPARCH (Kenourgios and Dimitriou 2015). Results depended on the choice of crisis and non-crisis periods, on global and idiosyncratic factors (Longin and Solnik 1995), and on spillovers persistence (Dedi and Yavas 2017). Many other empirical tests on crises transmissions were developed such as co-skewness, co-volatility, and co-kurtosis (Hsiao and Morley 2015; Fry-McKibbin and Hsiao 2015; Castro et al. 2016).
Similarly, some studies (namely those of Favero and Giavazzi (2002), Longin (1996), Bae et al. (2003), Kaminsky and Reinhart (2000, 2003) were based on asymmetric adjustments and no linearities to model crises transmissions. The basic idea was that the crises transmission process between financial markets could be nonlinearly different between periods of extreme movements of markets returns and quiet periods (González-Hermosillo et al. 2005a). Rose et al. (1996) employed probability-based models on the leading economic indicators. Vector autoregression (VAR) analysis was used by Baig and Goldfajn (1999) for five selected markets during the Asian crisis period. Calvo and Reinhart (1996) used Principal Component Analysis (PCA) to check contagion effect on stock and bond market.
Based on Extreme Values Theory (EVT), Longin and Solnik (2001) modeled multivariate distribution to determine asymptotic distribution of conditional correlation tails. Bae et al. (2003) used extreme return co-exceedances test, and found that extreme negative return strongly supported the contagion effect. Founded results show that extreme shocks are nonlinear (Kaminsky and Reinhart 2003; Markwat et al. 2009; Xu 2012; Belanes et al. 2015). These approaches, however, differed in modeling extreme values. They required choosing a critical threshold value based on a sample-estimated data, which could have different classifications for different sample periods.
To address issues with the estimation of correlation coefficients that suffered from biases due to heteroscedasticity, endogeneity, and omitted variables difficulties, other methodologies that concentrated on analyzing changes in asset market returns were developed. Forbes and Rigobon (2002) used heteroscedasticity-adjusted correlation coefficient test and found higher interdependence in the state of contagion effect during the crisis period. Martin et al. (2000) introduced latent factor model, which not only provided the sign of crisis transmission effect but also the size of crisis effects. According to Pericoli et al. (2010) and Harvey et al. (2005), the use of factor models allows to solve bias problems. Fedderke and Marinkov (2018) resolved problems of bias caused by heteroscedasticity, endogeneity, and omitted variables by checking idiosyncratic and common factors’ effects in subprime Asiatic and European crises transmissions.
Whereas, some authors, including Ramchand and Susmel (1998) and Ang and Bekaert (1999), used the switching models to study the evolution of financial assets’ income. These models took into account changes in means and conditional co-variances and moments of higher orders of financial asset returns, using a single state variable to refer to two different states at the same time (Brooks et al. 2011; Chen et al. 2011). Those models were largely criticized by many authors (Hubrich and Tetlow 2014; Adel and Jaghoubbi 2011) because of their limited contributions in studying contagion and interdependence phenomena. Recently, Otrok et al. (2020) developed a perturbation-based solution method for solving the endogenous regime-switching model. They analytically showed how to capture the effects of endogenous transition probabilities on the policy functions characterizing optimal behavior. They also indicated that these effects would be missed by linear approximation. The developed solution method could be used with a wide range of endogenous regime-switching models in which the probability of being infected depended on agents’ decisions as in Rebelo et al. (2020).
Copula models have been widely used to describe the dependence between financial markets (e.g., Aissa et al. 2011; Samitas et al. 2011b; Abbara and Zevallos 2014; Chen et al. 2015; Gomez-González et al. 2015; Fonseca and Ignatieva 2019; Fenech and Vosgha 2019; Ouyang and Zhang 2020). With a copula model, any multivariate distribution could be estimated by separately estimating the marginal distribution and the copula function. Copula models were also used to study financial contagion phenomena [e.g., Jayech (2016) and Lakhal et al. (2019)]. However, most of them neglected some aspects of the complex dependence between markets, such us nonlinearity, asymmetry, time-varying patterns, and upper and lower tail dependence. In this regard, Li et al. (2021) construct a DMC-EVT model to describe the joint return distribution of the exchange rate in different forex markets and estimate the dependence coefficient between those markets. Wavelet-copula-GARCH approach proposed by Alqaralleh and Canepa (2021) investigated the occurrence of cross-market linkages during the COVID-19 pandemic. They revealed evidence of long-run interdependence between the studied markets before the start of the COVID-19 pandemic in December 2019. However, after the beginning of the health crisis, strong evidence of pure contagion among stock markets was detected.
Chiodi et al. (2021) proposed to study the dynamics of financial contagion by means of a class of point process models employed in the modeling of seismic contagion. The proposal extended network models recently introduced to model financial contagion, in a space–time point process perspective. The extension helped improve the assessment of the credit risk of an institution, taking into account the contagion spillover effects. Econometric measures of systemic risk based on bivariate approach were proposed in particular by Adrian and Covar (2011), Engle et al. (2012) and Brownlees and Engle (2012). A different stream of research considered systemic risks as exogenous, and explained them by causal factors. This is the approach proposed, in particular, by Ang and Longstaff (2012) and Peltonen et al. (2014), who explained whether the default probability of an institution depended on a set of exogenous risk sources or not.
Trying to address the multivariate nature of systemic risk, researchers proposed financial network models, which were able to combine the rich structure of networks [e.g., Battiston et al. (2009) and Gallegati et al. (2012)] with a more parsimonious approach that could estimate contagion effects from the dependence structure among market prices. Seminal contributions in this frame work were made by Lo et al. (2012) and Diebold and Yilmaz (2014), who derived contagion measures based on Granger-causality tests and variance decompositions. Then, Giudici and Spelta (2016), Hadji-Misheva et al. (2020), and Sarlin et al. (2020) extended this methodology by introducing correlation network models. They find that the proposed approach improves predictive accuracy as well as model explainability.
All of these used approaches were criticized in terms of empirical methodology, empirical hypotheses, or used data. Similarly, the obtained results were varied and even contradictory sometimes because of the nature of used data and the problems of identifying crises dates. Moreover, these studies did not give precisions on the magnitude of studied crises and their effects. They mainly explained how a shock, which was initially specific to a country, could be transmitted to other countries having similar or different conditions and markets’ structures. In this paper, we not only explain crisis transmission process in terms of its mechanism but also in terms of its effects and origins. We give more insights on financial crisis transmission magnitude and effects.
Model framework and used data
Many of empirical studies cited above suffered from heteroscedasticity, endogeneity, and omitted variables. Different empirical methodologies were used to solve those problems. According to Pericoli et al. (2010), Harvey et al. (2005), and Fedderke and Marinkov (2018), the use of factor models allowed to solve bias problems by checking idiosyncratic and common factors’ effects namely in crisis context. Martin et al. (2000) introduced latent factor model which not only provided the sign of crisis transmission effect but also the size of crisis effects. However, those studies focused on estimating and analyzing volatility process and parameter’s stability to examine crisis transmission process. Our first structure approach is related to Dungey and Martin’s latent factors’ framework to avoid bias problems by taking into account the common and idiosyncratic factors’ effects.
The stock market indices are presumed to evolve in response to global (common) and idiosyncratic factors. Common factors are supposed to affect all countries. Idiosyncratic ones are only related to the individual countries. However, in contrast to many existing crises transmission models, the factors are not assumed to be observed directly. In fact, latent factor models provided a desirable alternative circumventing the need to choose specific indicators to proxy economic fundamentals Dooley (2000) and Edwards (2000). This model type was adopted previously for equity markets (Forbes and Rigobon 2002; Sentana et al. 1994), currency markets Dungey (1999), Mahieu and Schotman (1994), and fixed interest markets (Gregory and Watts 1995; Martin et al. 2000).
In the following, we present the empirical steps followed to develop our model. We begin by studying econometrically the initial structure’s factors shown below arising from two factors models developed to study asset pricing mechanism which depends on specific and common factors (Sentana et al. 1994; Martin et al. 2000). Then, we give and explain the adjustments made to develop our final model.
The first structure’s factors below have origins in the two factor models developed particularly for the equity markets, where equity market returns depend on common and country-specific shocks (see, for example, Sentana et al. (1994)1 Ri,t=λiGt+δiIi,t,
i = 1…N; N is the number of markets, i.e., number of stock market indices considered; Ri,t: stock market indices i at time t; Gt: common factors for all asset markets considered; λi: measures the effect of the common factors on stock market indices performance i at time t. These effects are supposed to be positive λi ≥ 0; Ii,t: idiosyncratic factors relative to stock market index i at time t; δi: measures the relative importance degree of idiosyncratic factors in determining the volatility of the stock market index i at time t; this degree is supposed to be positive δi ≥ 0.
To test the specification quality of this first structure’s factors, on which based our modeling strategy, we applied the Ramsey Reset test using “Stata”. The latter allowed us to test the specification quality of the model and the existence of omitted variables. This test was performed over a period characterized by the occurrence of the subprime crisis, spreading from September 2005 to June 2010.
We considered three frontier markets (Jordan, Morocco, and Tunisia), eight emerging markets (Mexico, Indonesia, Malaysia, Thailand, Turkey, Brazil, Poland, and Greece), and 11 developed markets (United States of America, Germany, Japan, Canada, Denmark, France, Hong Kong, Singapore, Portugal, United Kingdom, and Switzerland).1
The proxy variable of the common factor considered for the subprime crisis corresponds to global stock returns as it can be a possible source of portfolio risk in international stock returns, and it is important for both investment practitioners and academic researchers. The proxy variable for idiosyncratic factor is the ratio of money supply at the national level reported by the exchange reserves. The higher the ratio, the more likely considered market is vulnerable to a confidence crisis. Indeed, this ratio reflects the ability of banking system to deal with its domestic engagements, mainly during a currency crisis. In the crisis situation, the higher exchange reserves of a country are, the more it will be able to deal with the massive convertibility requests of the national currency to the foreign one.
Ramsey reset test was applied to considered model over the whole period for developed, emerging, and frontier countries. Obtained results (see Appendix) provided an F-Fischer less than 10% for developed countries and higher than 10% for emerging and frontiers ones. The null hypothesis of absence of omitted variables and good model specification cannot be accepted for developed countries, while it can be accepted for emerging ones. Thus, we cannot conclude for bad specification model. H0 was accepted for some countries and rejected for others. This can be due to data nature, i.e., the instability of model coefficients between crisis and no-crisis periods. Thus we applied a Chow test to see if the rejection of H0 could be explained by existing nonlinearities in stock market indices’ evolutions.
Hence, a Chow test was applied over the two periods to find explanation of Ramsey Reset test results and the existence of nonlinearities in stock market indices’ evolutions. In fact, the whole period can be divided into crisis and non-crisis periods. We tried to find if the rejection of H0 hypothesis was due to the existence of structural breaks that caused the instability of the model parameters, between the two sub-periods. The application of the Chow test provided F-Fischer’s below 10%. Therefore, we cannot accept the H0 hypothesis of coefficient’s stability between the two sub-periods. This may be due to empirical problems related to identifying crises periods on which depends on the results’ robustness.
The results of tests applied to model 1 led us to review its structure and to find explanations for obtained results. Consequently, the second empirical step of our proposed approach consists in taking into account the crisis transmission effects by adding the idiosyncratic factor effects of originating crisis market. In fact, in the literature on crises transmissions, the different definitions of crises transmissions led researchers to develop different methods. It has become common practice for studies to adhere to a single definition which coheres with the method used. In this paper, crisis occurrence is referred as the transmission of shocks due to crisis from one market to another (or a group of markets) which cannot be explained by the fundamental channels. Accordingly, crisis transmission process and effects play crucial role for making major economic decisions at international level.
Crises effects are represented by the transmission of unanticipated local shocks to other countries or markets.2 This definition is consistent with that of Masson (1999a; b; ; 1998) which classified financial shocks in common shock (or shocks) “Spillovers” due to some identifiable channels, local shocks, and contagion.
The second discussed structure’s factors will be tested in crisis periods. It corresponds to the first structure’s factors tested above in non-crisis situations, but to which we added idiosyncratic factor effects of originating crisis market: US market. It corresponds to transmission factor of subprime crisis to considered markets: the US interest rate. Thus, the possibility of shocks transmission in crisis periods is modeled as follows:2 Ri,t=λiGt+δiIi,t+γijIj,t,
Ij,t idiosyncratic shocks relative to market j. γij measures the effects of idiosyncratic factor of the crisis source country, j to market i; j = 1 · · · N − i and i ≠ ,. We suppose that γij ≥ 0; thus, market i will be positively affected by shocks issued from market j. The variable proxy of idiosyncratic factor of the crisis source country is the US interest rate.
We applied the Ramsey Reset test on model 1 in a no-crisis periods and on model 2 in crisis periods for all countries. Results show that the H0 hypothesis cannot be rejected in all cases. There is no omitted variables and no specification problems. Thus, the two factors structures can be considered for the rest of our modeling approach. Our basic idea being to develop a unique model allowing to combine those two extreme situations without having to specify periods of crises and no crises periods.
Existing empirical studies of crises transmission are generally confronted to the problem of specifying crisis and non-crisis periods. They had to compare crisis and non-crisis results. According to González-Hermosillo et al. (2005b) and Dungey and Tambakis (2003), the choice of crisis and non-crisis periods is generally done ad-hoc. There are some authors who opted for a rational choice Forbes and Rigobon (2002) and Gonzalez-Hermosillo et al. (2002), those who were based on journals and staff papers of IMF Glick and Rose (1999) and VanRijckeghem and Weder (2001), and those based on heteroscedasticity and DCC test. Ho (2004) and Bae et al.’s (2003) works were based on data characteristics using the critical threshold procedure. The large diversity of used techniques can affect results accuracy and effectiveness. So that, in our approach, we will use switching regimes models to avoid problems related to specifying crisis and non-crisis periods exogenously.
One drawback of all of these procedures is that they cannot adequately determine crisis and non-crisis periods. The results are generally divergent and thus largely arguable. It is also clear that whatever technique is used to determine the crises dates, and it will always be a subject to criticism. To overcome this, and based on the Chow test results, we used a regime-switching model, which allowed us to take into account the existence of nonlinearities. Moreover, the extreme situations of no-transmission shocks and perfect transmission shocks are taken into consideration by the model’s structure. This idea comes from the fact that, in reality, the financial markets are experimenting intermediate cases, i.e., partial transmission shocks.
Thus, to address this issue, we consider the following multifactorial switching model with endogenous transition variable3 described by the following equation as the third modeling approach step:3 Ri,t=(1-αij,t)(λiGt+δiIi,t)+αij,t(λi′Gt+δi′Ii,t+γijIj,t).
Assuming that
Hypothesis 1: all factors are independentEIi,t,Ij,t=0;i≠j.E(Ii,t,Gt)=0∀i.
Hypothesis 2: Crisis transmission is defined as the positive effect of unanticipated shocks issued from a market j in crisis and transmitted to market i.
Hypothesis 3: Contrary to the assumption made by Dungey et al. (2005) (Gonz´alez-Hermosillo B. Dungey M. et al. 2005a), we assume in our model that the impacts or weights of common and idiosyncratic shocks are not the same in crisis and no-crisis periods. This assumption is particularly justified by the fact that in reality, the idiosyncratic and global shocks do not necessarily have the same weights in crisis and no-crisis periods.
In this model, αij,t is the endogenous transition variable. It can be interpreted as a measure of crisis transmission degree from country j to countries i, thus:
If αij,t = 0, then Ri,t is entirely determined by (λiGt + δiIi,t); this is the case of no-crisis transmission. That is regime 2.
If αij,t = 1 ,then Ri,t is entirely determined by (λi′Gt+δi′Ii,t+γijIj,t); it is the case of perfect crisis transmission. That is Regime 1.
If αij,t∈]0,1[, then the transmission of crises at time t is only partial “mild transmission crisis”. Stock market indices are determined by a combination of the effects of common factors and idiosyncratic factors related to the stock index of market i and those of market j.
As the matter of fact, the transition variable αij,t can be considered as a random variable. This is justified by the fact that we cannot know and predict followed trajectory of crisis transmission degree. We assume that αij,t follows a stochastic process and not a deterministic one as was the case of works on integration phenomena (see Hardouvelis et al. (2006), Bekaert and Harvey (1997) and Bekaert and Harvey (1995). A particularly important example of stochastic process was the Brownian motion.
According to this and assuming that our random variable αij,t has zero mean,4 we can say that αij,t follows a brownien process with Gaussian distribution having a zero mean and a variance σ2ij,t, with σ2ij,t ≠ σ2ji,t.
Clearly, αij,t ∼ N (0, σij,t).
Being considered as a brownien motion, αij,t can be written as a stochastic differential equation. This equation allows to model random trajectory. In our case, the random phenomenon corresponds to crisis diffusion from one market to another4 dαij,tαij,t=μdt+σij,tdWt.
The first term of this equation is called drift and corresponds to instantaneous average. The second term is called volatility or diffusion term and corresponds to instantaneous standard deviation. This differential equation corresponds to differential form of stochastic integral. One of its solution is called diffusion process.
The stochastic integral can give meaning to the following integral equation:5 αij,t=α0+∫t0αij,tμdt+∫t0αij,tσij,tdWt.
Equation (5) corresponds to Itô process and than can be expressed as follows:6 αij,t=α0expμ-σij,t22t+σij,tWt,
αij,t is the unique solution of the Eq. (5) and corresponds to a diffusion model entirely determined by its volatility σij,t.
Thus, the model corresponds to simultaneous equations system (3) and (6)7 Ri,t=(1-αij,t)(λiGt+δiIi,t)+αij,t(λi′Gt+δi′Ii,t+γijIj,t)αij,t=α0expμ-σij,t22t+σij,tWt.
The particularity of our specification given above is that the transition between the two regimes (crisis and non-crisis) is considered as a random process rather than a deterministic one (i.e., Otrok et al. 2020). Thus, our main contribution consists in analyzing crises transmission process based on a multifactorial switching model with a random endogenous transition parameter which is αij,t. Our proposed model fits well with stock market indices, and does not rely on the preliminary specification of crisis and non-crisis periods. It rather lets the structure of the model explain those events. Moreover, it allows us to characterize the magnitude of crisis transmission effects by giving a measure of crisis transmission degree. The structure of the model also jointly captures the effects of global and idiosyncratic factors in crisis and non-crisis periods.
Our approach provides a number of contributions to the literature. First, we propose a multifactorial switching model that takes into account the nonlinear evolution of stock market indices and integrates a diffusive component corresponding to (αij,t) process. In this model, the transition parameter (αij,t) cannot interpret as a probability measure as was the case of studies using switching models (namely studies of the integration phenomenon), since the model is developed in crisis context. Accordingly, we cannot consider (αij,t) as a measure of crisis occurrence probability, and thus, it cannot be modeled as probabilistic model as was the case for the major works focusing on studying unpredictable situations or evolutions (i.e., probit and logit models). Besides, (αij,t) is determined endogenously by model’s structure.
In addition, our model has the advantage of giving an idea about the extent of crisis transmission. The coefficient αij,t measures the crisis transmission degree and allows us to find if it is perfect, partial, or weak. Furthermore, our proposed model makes a distinction between interdependence and contagion effects. More clearly, estimated values of αij,t are compared to the differences between the theoretical and the observed values of the stock market indices. Thus, the possible increase in αij,t will not necessarily be due to the existence of contagion effects. It will be so only if this increase is accompanied by widening gaps between theoretical and observed stock market indices5, and in this case, γij will be interpreted as a measure of contagion. If the difference is not important, it will be interpreted as interdependence effects and γij will correspond to a measure of interdependence effects. By establishing whether crisis transmission degree is due to interdependence or contagion effects, our multifactorial regime- switching model provides important insights on portfolio and risk management. The coefficient γij measures contagion or interdependence effects.
A specific feature of this model is that it avoids having to distinguish between contingent and non-contingent crises, because these two cases are already taken into account by the model’s structure. Model (3) particularly allows us to avoid problems related to exogenous determination of crisis periods. In particular, modeling stock market indices as a switching model allows us to take into account crisis and non-crisis periods at the same time thanks to the model’s structure. Therefore, we do not have to specify crisis and non-crisis periods.
Finally, to the best of our knowledge, there is no-crisis transmission study that allowed to determine a measure of crisis transmission degree based on a multifactorial switching model. Thus, our paper presents the advantage of giving more clarifications about the crisis transmission process and magnitude which were generally missed by previous works focusing on the transmission process.
However, the effects of a crisis triggered in a country j on the financial situation of a country i may be detected with some delay which is due to the crisis transmission magnitude. Indeed, the crisis transmission degree of certain countries begins by being lower and increases thereafter with some delay. In the following section, we present empirical methodology we used and the obtained empirical results for the case of subprime crisis.
Results
For the empirical study of our model, we used an optimization program based on genetic algorithm method. This program is developed within the Matlab software.
Genetic algorithms
Genetic algorithms are problem-solving methods that mimic the process of natural evolution. These algorithms utilize the concepts of natural selection (crossing, mutation, selection, etc.) to determine the best solution for a problem. In particular, they require a few assumptions to treat very complex problems that would take a long time to solve, and that is why, they are very important and are convenient for our multifactorial regime-switching model with an endogenous diffusion component. According to Girard (2006), the genetic algorithms seem to be advantageous at two levels. On one hand, they have the characteristic of being based only on performance values of the function to be optimized and in any case on its derivative.
On the other hand, the genetic algorithm needs not to know the nature of the problem to be optimized. It just needs to know all the numeric values or yet the solutions to which must converge. These latter must necessarily take into account the constraints on setting system parameters. Genetic Algorithm is a heuristic function for optimization, where the extreme of the function (i.e., minimal) cannot be established analytically.
As mentioned by Pereira (2000), genetic algorithms are especially suitable for complex problems characterized by large solution spaces, multiple optima, non-differentiability of the objective function, and other irregular features. In this work, the transition variable αij,t is modeled as a brownien process. The use of genetic algorithms allows to respond to this objective giving that they do not use deterministic transition rules. They belong to the class of evolutionary algorithms, which attempt to solve difficult problems by evolving an initial set of potential solutions into better solutions through an iterative process. This is achieved through a process referred to as natural selection or survival of the fittest, which is based on Charles Darwin’s theory of evolution.
In our case, we seek to find the best combination values of parameters (α0,σij,t,λi,δi,λ′,δ′,γij) allowing to minimize the difference between the observed values of stock market indexes and the corresponding theoretical values, determined from Eq. (7).
The function to be optimized is therefore presented as follows:
Minimize[Ri,t-[(1-αij,t)(λiGt+δiIi,t)+αij,t(λi′Gt+δi′Ii,t+γijIj,t)]].
Under constraints:αij,t∈[0,1]α0>0σij,t>0γij≥0λi≥0λi′≥0δi≥0δi′≥0.
Note here that αij,t is included in the objective function through its expression given by (6).
Empirical study: case of subprime crisis
Empirical estimations of equations system (7) provided monthly estimated values of crisis transmission degree denoted by αij,t and of model parameters (λ, δ, λ′, δ′ and γ), that is, we can determine theoretical values of stock market indices.
We can establish if crisis transmission is caused by contagion or interdependence effects by calculating the discrepancies between observed and theoretical values of stock market indices. The outcomes of the transmission of the subprime crisis for developed, emerging, and frontier markets are presented and analyzed in the section that follows.
Presentation and analysis of empirical results for developed countries
The estimated coefficients of idiosyncratic factors in the model are greater than those of global factors for the case of developed countries (with the exception of the UK and France), in both crisis and non-crisis periods. Stock market indices appear to be more influenced by local variables than by global ones. However, the changes in the proportional weights of those components vary from market to market and from a crisis to a non-crisis period.
Otherwise, the estimated values of idiosyncratic factors’ coefficients γij are linked to the originating crisis country, in this case, the USA. The crisis transmission effects, which could be associated with interdependence or contagion effects, are measured by γij.
We were able to classify all industrialized countries into three sub-groups after conducting an initial global analysis of the results. The first category included markets where the crisis was perfectly transmitted. The second one brings together markets where the crisis’ transmission was partial. The final group brings together markets where a weak transmission crisis occurred.
The first subgroup: perfect crisis transmission
The crisis transmission in the cases of Denmark, United Kingdom, Japan, and Canada was perfect. For those countries, the α estimated values, specifically during the peak transmission period, are close to 1.
The predicted values specifically hit two peaks in Denmark. A 0.91 peak was reached in September 2007 and a 0.84 peak was reached in January 2008. This demonstrates that the subprime crisis had both immediate and delayed effects on the Denmark market condition. When compared to its normal evolution level, the apparent increase in the estimated level of α appeared extremely considerable (between 0.5 and 0.6). It should be mentioned that the level of did, however, grow into a new wave between 0.8 and 0.6 after the crisis. There were no significant discrepancies between the theoretical and observed levels of the stock market indices that coincided with the gains seen in September 2007 and January 2008.
Therefore, we can conclude that the rising estimate of α represents a nearly perfect transmission of the crisis that increased Denmark and America’s level of dependence on one another. Since the average discrepancy between the theoretical and observed values of stock market indices was low (on the order of 10.01%), this transmission was not the result of contagion effects but rather of interdependence ones. Thus, the estimated value of the parameter γ (2.16) measures the dependence degree between Denmark and the United States of America.
The projected monthly values of α for the United Kingdom change virtually monotonically over considered period (September 2005 to June 2010). In actuality, these values varied between a very small range of 0.59 and 0.68. The dependency between the United Kingdom and the United States of America persisted during the crisis period, even though α continuing to develop practically in the same manner. Additionally, whether there was a crisis or not, the observed values of stock market indices continued to evolve in accordance with their theoretical values. In comparison to its estimated values for the other countries, the γ estimated coefficient’s value is relatively high (54.69). This highlights how crucial the degree of dependence between the United Kingdom and the United States of America.
In the case of Japan, the coefficient α, which had fluctuated around 0.4 prior to the crisis, hit a maximum threshold of 0.72 in June 2007. The perfect transmission of the crisis to Japan was partial but almost immediate. As a result, the delay effect was absent. This perfect transmission of the crisis appeared to be due to the dependency between Japan and the United States of America rather than to the existence of a contagion effect. This was further supported by the very close evolutions of calculated and observed values of stock market indices during the studied period. The typical discrepancy was 6.33%. A measurement of the level of dependance between the United States of America and Japan was supplied by the estimated value of the γ coefficient.
The evolution of the monthly estimated values of the parameter α for Canada, however, attained two maximum values over the time period under consideration. A first peak of roughly 0.82 in June 2008 which was the period of full crisis, and a second peak of roughly 0.77 in November 2009 in the post-crisis period. This suggested that the subprime crisis may have indirectly reached Canada and may have had some effects. Moreover, the discrepancies between the theoretical and the observed values of the stock market indices were not too large (11.05% on average). The estimated value of the parameter γ which was 3.25 could not be interpreted as a measure of contagion. The perfect transmission of the subprime crisis to Canada was due to dependence rather than contagion effects.
The second subgroup: partial crisis transmission
Transmission of the subprime crisis is only partially felt in Germany, Switzerland, Hong Kong, France, and Singapore. Estimated values of α are in the range of 0.5.
In the case of Germany, the maximum α value reached is 0.6 particularly in crisis situations (the mean average across the period was 0.422). The percentage error is too small (8.8% on average throughout the time period under consideration). Alternatively put, the theoretical values of stock market indices were too close to the observed ones. The crisis did not cause an increase of the gap between the theoretical and the observed values of stock market indices.
Thus, dependance consequences were what caused the crisis to spread. The coefficient of γ was a measurement of dependence effects as opposed to contagion effects. However, α reached its peak in January 2009, indicating a slight delay in the subprime crisis’ transmission to Germany. As a result, our model enabled us to evaluate the crisis transmission degree as well as account for the potential existence of a particular delay impact.
For Switzerland, α reached its maximum in October 2007, i.e., at the beginning of subprime crisis. Accordingly, the transmission of the crisis to Switzerland was done almost instantly. However, the magnitude of this transmission was not very important. Moreover, the crisis transmission was partial, since the jump observed in the evolution of α compared to its habitual level was not too high. α fluctuated around the value of 0.4 before the crisis, reflecting a normal dependence between Switzerland and the United States of America. The small and surge increase of the evolution of α showed that the partial crisis transmission was mainly due to the importance of the dependence level especially in times of crisis. This was confirmed by the fact that the monthly differences between theoretical and observed values of stock market indices were moderate and disproportionate to estimated increases of α. Thus, the parameter γ can be considered as a measure of the dependence degree of Swiss stock market indices on American idiosyncratic factors.
In the instance of Hong Kong, the estimated values of α changed between 0.3 and 0.4 until rising to 0.5 in July 2007. It subsequently significantly dropped to a minimum value of 0.10 after that. Thus, the period in which the parameter α grew coincided with the period of the crisis, but was not followed by a significant change in the percentage discrepancies between theoretical and observed stock market indices, which had an average value of 7.77% over the course of the period (September 2005 to June 2010). Since interdependence effects rather than contagion effects were responsible for the partial spread of the subprime crisis to Hong Kong, the estimated value of γ related to a measure of the interdependence degree.
The transmission of the subprime crisis to France was also partial, since the maximum level attained in June 2009 by the parameter α was 0.445. This indicates that the crisis’ propagation may have been delayed in some way. Prior to the crisis, the parameter α had evolved to be approximately 0.3. The partial transmission of the subprime crisis to France was also due to the importance of the dependence degree between France and the United States of America, especially because there were no large deviations between calculated and observed values of stock market indices. The coefficient γ was estimated at (1.14) and measured the dependence effect of the French stock market indices to the Americans ones.
In Singapore’s case, the estimated level of α peaked at 0.64 in October 2007 after fluctuating between 0.49 and 0.3 and then declined to 0.13 as a minimum after October 2007. It should be noted that starting in June 2010, the parameter α increased until it reached a value of 0.5. In this instance, we can draw the conclusion that the subprime crisis had indirect impacts on the nation at the end of 2010. The maximum values reached by the α parameter in October 2007 and June 2010 were, however, accompanied by considerable gaps between theoretical and real values of stock market indices. These values peaked in October 2007 at 33.52% and fell over the next time period to reach 21.10% in June 2010. Since the increase of the parameter was quite large compared to its usual values and that this increase was accompanied by proportional growth of the gap between theoretical and observed stock market indices values, it follows that the partial transmission of the subprime crisis to Singapore was caused by contagion effects rather than interdependence ones. The estimated value of the parameter γ, 2.68, can be interpreted as a measure of contagion effects on stock market indices.
The third subgroup: weak crisis transmission
In the case of Portugal, the weight of the global factor increased in crisis period compared to its value during the non-crisis period. However, the stock market indices were less dependent on the idiosyncratic factor in crisis period than in non-crisis period. The effect of the idiosyncratic factor in determining stock market indices was greater than the global one in both crisis and non-crisis periods.
The maximum value reached by α is 0.24 in December 2007, after fluctuating around 0.20 before that date. This demonstrated the modest increase of α relative to its typical pre-crisis level. Estimated values declined after the crisis to lower levels (0.13) at the end of the entire period (September 2005 to June 2010). The evolution of α estimated values denoted a low transmission of sub- prime crisis to Portugal. This transmission can be explained by the dependence effects between the two countries rather than by contagion, because the differences between calculated and observed values of stock market indices are not very important. The estimated value of γ (5, 656) can be used to gauge how dependent Portugal and the United States of America are on one another.
Presentation and analysis of empirical results for emerging and frontiers countries
In both crises and non-crises periods, the estimated coefficients of idiosyncratic factors in the model were higher than global factors, for the major countries under consideration. Stock market indices seemed to be largely dependent on local factors’ effects rather than on global ones. However, the evolutions of the relative weights of those factors varied from one market to another and from crisis to non-crisis periods.
The estimations of the model in the case of emerging and frontier countries and the analyzed results allowed us to identify three sub-groups. A first one regroups markets where crisis transmission was perfect. The second set regroups markets where crisis transmission was partial. The last group deals with markets where there was a weak crisis transmission.
The first subgroup: perfect crisis transmission
For the examples of Brazil and Mexico, where the α estimated values were very near to 1, specifically during the peak transmission period, the crisis transmission was perfect.
For Brazil, the dependence degree of stock market indices on global factors decreased during the crisis period but increased in proportion to the idiosyncratic factors. However, the relative weights of the idiosyncratic factors were more important than the global ones in determining the stock market indices in both crisis and non-crisis periods.
Brazil is unique in that its crisis transmission degree has reached two peaks. A first level of (0.8) reached in May–July 2007 and a second peak of (0.77) was reached in October 2008. These findings supported the idea that the subprime crisis had a direct effect during the crisis, and an indirect or delayed effect corresponding to the consequences perceived after the crisis. Additionally, these increases were quite large compared to the usual level of α that was around (0.6) before these periods and around (0.4) afterward. They were also accompanied, by deviations between theoretical and observed values of stock market indices which also reached the maximum levels over the period when α increased too. The percentage of the overall average gap was (25.29%). Therefore, we can conclude that this situation of perfect subprime crisis transmission to Brazil was due to the existence of financial contagion effects. The estimated value of γ corresponded to a measure of the contagion effect.
In the case of Mexico, the relative weight of both global and idiosyncratic factors decreased in crisis period. However, the idiosyncratic factors were more important than the global ones in setting the Mexican stock market indices, as with most emerging and frontier countries. The subprime crisis seemed to have been nearly perfectly transmitted to Mexico. In reality, the estimated values of α fluctuated between (0.4) and (0.65) before increasing to (0.728) in December 2007. Following that, it fell and stayed between (0.54) and (0.35). During the crisis, there were substantial discrepancies between theoretical and observed stock market indexes that accompanied the evolution of α. The average monthly discrepancy percentage is (31.654%). Here, a measurement of contagion effects is given by the estimated value of the parameter γ.
The second subgroup: partial crisis transmission
In the cases of Poland, Greece, and Jordan, the transmission of the subprime crisis was only partial. Estimated values of α were in the range of 0.5.
In the case of Poland, between May 2007 (the start of the crisis) and December 2007, α reached a level of (0.43). The two dates are similar enough to show the existence of certain subprime crisis delayed repercussions. Because the increase of α was not accompanied by an appreciable discrepancies between theoretical and observed stock market indices, it was also concluded that this was an instance of partial crisis transmission to Poland. γ coefficient was considered as a measure of dependence degree between Poland and the United States of America.
For Greece, the highest level of estimated value of α was (0.555) in February 2008. After fluctuating between (0.37) and (0.27), these numbers began to rise since November 2007 and after February 2008. The estimated values of α decreased back to their pre-crisis levels after reaching the value of (0.555). However, compared to its customary level, this increase was not very important and was not accompanied by appreciable discrepancies between theoretical and observed values of stock market indices. The significance of the monthly average percentage (21, 708%) over the entire period was due to the importance of the monthly average percentage difference (from February 2010 to June 2010). The start of the Greek crisis falls inside this time frame. These differences could be explained by the domestic conditions of Greece rather than by the external ones. Thus, it can be said that the partial transmission of the subprime crisis to Greece was due to interdependence, rather than contagion effects. Therefore, we can interpret the estimated value of γ (30.44) as a measure of the dependence degree.
In the case of Jordan, the monthly estimation values of α increased significantly in August 2007, peaking at a value of (0.6). In fact, they changed between (0.2) and (0.3), rising in June 2007 and declining in December 2007. This increase was accompanied by a rise in the percentage gap between theoretical and observed stock market indices, which reached 41.286% in May 2007. This corresponded to a case of partial crisis transmission, due to the existence of contagion effects. The estimated value of γ (1, 955) corresponded to a measurement of contagion effects.
The third subgroup: weak crisis transmission
This group consists of Indonesia, Malaysia, Morocco, Tunisia, Turkey, and Thailand. These nations share the common trait that, while the weights of idiosyncratic factors decreased during the crisis period, the weights of global factors grew as compared to their levels during the non-crisis period. In both crisis and non-crisis periods, the dependence of stock market indices on the idiosyncratic factors was more important than on the global ones.
The estimated α parameter’s evolution in the instance of Indonesia ranged from (0.16) to (0.22) in September and October 2008 before returning to normal values. The increase of α compared to its regular level was not very important, but was accompanied by a relatively large increase in the gap between theoretical and observed values of stock market indices. The overall average throughout considered period was (28.71%). Therefore, we can conclude that the low transmission of the subprime crisis was due to financial contagion effects. Accordingly, the γ parameter corresponded here to a measure of contagion.
The scenario of Malaysia was fairly similar to that of Indonesia, with the exception that the maximum value reached by the estimated parameter of transmission degree in May 2008 was (0.19). This was also accompanied by a relatively large increase in error percentage. The global average over the entire period was (13.02%). The subprime crisis transmission to Malaysia was also low and was due to the existence of contagion effects.
In the instance of Morocco, the changes in the monthly predicted values ranged between two similar values (0.22) and (0.16). This evolution remained unchanged during the crisis. The theoretical stock market indices evolved differently than the ones that were actually observed, though. There was a gap between these two series in crisis period, which was not followed by a notable rise in α. Before the crisis transmission degree peaked at a value of (0.22), the gap started to grow slightly. This instance of the subprime crisis’s low-delayed transmission was caused by a contagion process that started even before the transmission process. γ can be used as a proxy for the spread of contagion between Morocco and the United States of America.
In the case of Turkey, the monthly estimations of the α parameter did not differ significantly between the crisis and non-crisis periods. In fact, over the whole period, α fluctuated in a constrained range between (0.18) and (0.12). The same holds true for the monthly percentage differences between the theoretical and observed stock market indices. This leads us to conclude that there was a low crisis transmission, which was due to interdependence effects between Turkey and the United States of America, measured by the estimated value of γ (4, 857).
Given that the maximum value reached by the parameter α was (0.05), Tunisia appeared to be lightly impacted by the subprime crisis with a low crisis transmission. In addition, in crisis period, the very low maximum values of α were not accompanied by particularly large differences between theoretical and observed values of stock market indices. Thus, the estimated value of γ (16,593) measured the degree of dependence between Tunisia and the United States of America.
Even during the financial crisis, Thailand’s stock market returns gap was not very significant. The estimated values of the parameter α did not exhibit a specific evolution during the crisis period. These values ranged from (0.09) to (0.119). Therefore, this was a case of a very low crisis transmission due to the effects of interdependence relations between the two countries. Estimated value of γ, (0.86), was a measure of the dependence degree between Thailand and the United States of America.
Conclusions
Economic stability is seriously threatened by the financial crisis transmission phenomena that was observed in developed, emerging, and frontier markets. Therefore, it was essential for policymakers, financial regulators, and international investors to investigate the crisis transmission process and its mechanism to formulate regulations and build strategies accordingly. The phenomenon of crisis transmission in this study was defined as the spreading of unanticipated local shocks to other countries or markets. With a multifactorial switching model and a random endogenous transition parameter that was treated as a diffusing process, we offered a novel technique. Our main goal was to identify whether the subprime crisis transmission was perfect, partial, or weak and to ascertain whether it was caused by contagion or interdependence effects. The constructed model allowed us to capture the effects of idiosyncratic and global factors between crisis and non-crisis periods without having to specify them exogenously.
In our model, we provided a measurement of subprime crisis transmission degree to a select group of developed, emerging, and frontier countries. Many financial risk managers, foreign investors, and academics were inspired by this financial crisis to research how and why crises spread as well as what steps may be taken to reduce risk from the crisis originating country.
We can observe from the results that the genetic algorithm just slightly reduced precision. Our empirical analysis demonstrated that the developed model outperformed the competing studies on crisis transmission. It did this by measuring the degree of crisis transmission with more accuracy, which allowed for a more accurate examination of the financial crisis’s spread by determining whether it was caused by contagion or interdependence effects.
The analysis’ findings showed that, in many situations, interdependence effects were to blame for the subprime crisis’ whole or partial transmission to developed markets (except for Singapore). With the exception of Greece, Tunisia, and Turkey, crisis transmission was minimal for emerging markets and was caused by contagion effects. Therefore, a higher crisis transmission degree was not always associated with the presence of contagion effects in the crisis transmission process. Estimated values were high, while crisis transmission was caused by interdependence effects for some countries.
Furthermore, the significance of the coefficients of idiosyncratic characteristics was unrelated to the effects of the crisis. These coefficients were higher for many countries than the ones associated with global issues, but the spread of crises was caused by contagion effects.
For investors to develop risk-hedging strategies during and after crisis situations, these findings offer crucial insights. Investors should increase the percentage of assets in markets that were not impacted by contagious effects during the financial crises and decrease the percentage of assets related to the USD in contagious markets (Singapore, Brazil, Mexico, Jordan, Indonesia, Malaysia, and Morocco) to lower the risk of financial losses.
This had important implications for designing effective policies that would prevent or mitigate risk issued from the crisis originating country. Policy-makers should carry out some short-term isolation policies, such as capital controls or central bank interventions, to isolate these contagious countries from the crisis source country. Moreover, some short-term stabilizing policies, such as tighter monetary policy, should be warranted during crisis periods.
By understanding the crisis transmission process, investors and risk managers can make appropriate decisions to hedge against market downturns. Besides, determining the role of the relative effects of global and idiosyncratic factors in explaining stock market indices evolution in crisis and non-crisis periods, can help risk manager to orientate their decisions and their strategic measures.
The approach we recommended is also applicable to the creation and estimation of capital price models. It can also be used to prevent problems with asymmetric information transmissions by assessing the degree of information transfer between investors and supporting them in making suitable judgments at the right moments. Conclusions concerning significant elements influencing financial frictions, analysis of potential policy, and structural real-time forecasting all depend heavily on our findings. The COVID-19 issue, the global financial system, and the great depression can all be understood using the glasses provided by our model.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 3884 KB)
Author contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by IBB, SH and FJ. The first draft of the manuscript was written by IBB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
The authors did not receive support from any organization for the submitted work.
Availability of data and materials
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Conflict of interest
The authors have no relevant financial or non-financial interests to disclose.
Consent for publication
The authors hereby consent to publication of the work.
1 This market classification is that made by Morgan Stanley Capital International: MSCI.
2 This definition corresponds to those adopted by Fratzscher et al. (2014) and González-Hermosillo et al. (2005a).
3 According to Lo et al. (2005), the advantage of switching models compared to ARCH and GARCH processes is their ability to reflect the occurrence of extreme events and the fact that regime changes can be considered as breaks. They also help to account for unobservable variables that can affect the endogenous variables.
4 We assume that αij,t has zero mean, because the values it can take are very low (between 0 and 1), and therefore, its average over the period will be low and than its effect is assumed to be negligible.
5 Crisis periods are generally marked by a widening gap between theoretical and observed values of stock market indices.
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J Ped Endosc Surg
Journal of Pediatric Endoscopic Surgery
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Abstracts
Abstracts of 39th National Pediatric Surgeons Congress and 12thNational Pediatric Urology Congress (Minimal Access Surgery Section) Kuşadası, Turkey November 2–5, 2022
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J Youth Adolesc
J Youth Adolesc
Journal of Youth and Adolescence
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Springer US New York
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Empirical Research
Identity Formation, Body Image, and Body-Related Symptoms: Developmental Trajectories and Associations Throughout Adolescence
http://orcid.org/0000-0002-9091-5540
Vankerckhoven Lore [email protected]
1Lore Vankerckhoven
is a doctoral student at KU Leuven. Her major research interests include the associations between identity and psychopathology in adolescents.
Raemen Leni 1Leni Raemen
is a doctoral student at KU Leuven. Her major research interests include the transdiagnostic value of identity in psychopathology.
Claes Laurence 12Laurence Claes
is a Full Professor at KU Leuven and the University of Antwerp (UA). Her major research interests include the associations between identity/personality and psychopathology, more specific, non-suicidal self-injury, eating disorders, and addictions.
Eggermont Steven 1Steven Eggermont
is a Full Professor at KU Leuven. His major research interests include media effects and the associations with mental health.
Palmeroni Nina 1Nina Palmeroni
obtained a PhD in Psychology at KU Leuven. Her major research interests include identity functioning, body image, and eating disorder symptoms.
Luyckx Koen 13Koen Luyckx
is Associate Professor at KU Leuven and research fellow at the University of the Free State, Bloemfontein, South Africa (UNIBS). His major research interests include identity development and its associations with psychopathology, both in community adolescents and emerging adults and in adolescents/emerging adults with a chronic illness.
1 grid.5596.f 0000 0001 0668 7884 Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium
2 grid.5284.b 0000 0001 0790 3681 Faculty of Medicine and Health Sciences (CAPRI), University of Antwerp, Antwerp, Belgium
3 grid.412219.d 0000 0001 2284 638X UNIBS, University of the Free State, Bloemfontein, South Africa
9 12 2022
119
16 9 2022
26 11 2022
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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Emerging evidence highlights the intricate link between identity and one’s body, however, integrative longitudinal research on this identity-body interplay is lacking. The current study used three-wave longitudinal data (Time 1: N = 403; 52.1% female; Mage = 14.85, SD = 0.89, range = 13–19 years) spanning two years (2019–2021; T1 and T2 being pre-pandemic, T3 peri-pandemic) to identify identity trajectory classes and examine their co-development with negative and positive body image and various body-related variables (i.e., sociocultural pressures, internalization of appearance ideals, self-objectification, appearance comparison, and eating disorder symptoms). First, four identity classes emerged using latent class growth analysis (achievement, moratorium, carefree diffusion, and troubled diffusion). Second, using multigroup latent growth curve modeling, adolescents in less adaptive identity trajectory classes (i.e., engaging less in pro-active processes and more in ruminative processes) displayed higher levels of negative body image and body-related symptoms. The current study testified to the clinically meaningful associations linking identity formation to adolescents’ body image and other body-related symptoms.
Keywords
Identity functioning
Body image
Adolescence
Trajectory classes
==== Body
pmcIntroduction
Identity formation is a lifelong developmental task which is especially prominent during adolescence and emerging adulthood (Erikson, 1968). Erikson has already mentioned that feeling at home in one’s body is one of the most important concomitants of achieving an optimal identity. In the past few years, research has pointed to the intricate link between identity functioning and one’s body. However, integrative research is lacking as research on personal identity and one’s body has developed mainly in isolation (Nelson et al., 2018). Further, research has mainly focused on negative body image instead of adopting a holistic perspective on the body with attention to positive body image as well. To broaden the understanding of the link between identity and one’s body, the current study used three-wave longitudinal data spanning two years to (1) identify different identity trajectory classes (based on five interrelated commitment and exploration-processes) among adolescents and examine if these trajectory classes differ on gender, age, and body mass index (BMI) at baseline; and (2) examine how these identity trajectory classes are related to differential development in negative and positive body image and various body-related variables and symptoms (i.e., sociocultural pressures and internalization of appearance ideals, self-objectification, appearance comparison, and eating disorder symptoms).
Identity Formation
Erikson (1968) described identity formation as a central developmental task throughout the life span. Especially during adolescence and emerging adulthood, youth are challenged to resolve life-defining questions. During this identity quest, adolescents may go through an identity crisis in which they contemplate decisions concerning their future lives. This identity crisis may result in identity synthesis which is characterized by adhering to a set of coherent ideals and future goals, or alternatively, in sustained feelings of identity confusion in which a sense of purpose is lacking (Erikson, 1968).
To operationalize Erikson’s ideas on identity formation, the identity status paradigm was proposed by Marcia (1966) to identify behavioral markers of one’s underlying identity structure. Marcia focused on the decision-making processes of exploration (of different identity alternatives) and commitment (adhering to one or more identity alternatives). Marcia derived four identity statuses based on the levels of engagement in exploration and commitment: achievement (characterized by high commitment after high exploration), foreclosure (characterized by high commitment but without prior exploration), moratorium (high exploration and low commitment), and diffusion (low commitment and low exploration).
Due to societal changes in Western societies (e.g., prolonged education), young people may postpone long-term identity commitments (Arnett, 2000). Consequently, identity formation has been extended into emerging adulthood as individuals re-evaluate their prior commitments. These societal changes call for a rethinking of existing models. Luyckx et al., 2008 developed a dynamic process-oriented identity model with five processes to capture identity formation. According to this model, the search for one’s identity may start with a broad exploration of various identity alternatives (exploration in breadth), presumably followed by making identity choices (commitment making). Afterwards, these identity choices may be evaluated in-depth by discussing them with significant others or by considering personal values and standards (exploration in depth). Exploration in depth may result in identification with commitments, as the individual feels convinced about their commitments, or alternatively, the process can cycle back to renewed exploration if the individual does not identify with the commitments. However, some individuals continue to explore without engaging into long-term commitments and get stuck in their identity search. As such, this model distinguishes pro-active exploration (in breadth and in depth) from ruminative exploration which inhibits achieving a stable identity.
By using person-centered techniques on longitudinal data emerging from the dynamic process-oriented identity model, different identity trajectory classes resembling Marcia’s identity statuses could be identified. The advantage of this typological approach is that researchers could gain insight into subgroups of individuals, both those who are more resilient in their identity quest and those who experience more difficulties and are more vulnerable over time. This approach has already been used in community samples of adolescents (12–18 years at baseline), college students (17–29 years at baseline), and employees (21–40 years at baseline). Five identity trajectory classes have been consistently identified: achievement, foreclosure, moratorium, carefree diffusion, and troubled diffusion (Luyckx et al., 2013; Raemen et al., 2022). As expected, across studies, individuals in the achievement class displayed high scores on all identity processes, except for low scores on ruminative exploration. Individuals in the foreclosure class scored moderate to high on commitment processes (not as high as achievement) and low on all exploration processes. Individuals in the moratorium class scored low to moderate on commitment processes, and high on exploration processes. Individuals in the carefree diffusion class displayed low scores on commitment and pro-active exploration processes and moderate to low scores on ruminative exploration. Individuals in the troubled diffusion class scored low on commitment processes, low to moderate on exploration in depth and in breadth, and high on ruminative exploration. These identity trajectory classes were mainly based on consistent differences in initial levels of commitment and exploration processes (i.e., intercepts) and less so in rates of changes over time (i.e., slopes), as differences in slopes were less indicative to differentiate trajectory classes in a specific sample. Furthermore, previous studies have found significant differences in gender and age between the trajectory classes. With regard to gender, girls were more likely to be situated in statuses characterized by higher scores on pro-active and ruminative exploration processes (i.e., moratorium and troubled diffusion), whereas boys were more likely to be situated in statuses characterized by lower scores on exploration processes (i.e., foreclosure and carefree diffusion) (Raemen et al., 2022; Verschueren et al., 2017). With regard to age, older individuals were more likely to be situated in statuses characterized by higher levels of both commitment and pro-active exploration processes (i.e., especially achievement) (Raemen et al., 2022; Verschueren et al., 2017).
Given that the search for a personal identity can be accompanied by certain challenges and difficulties, the COVID-19 pandemic and its vast impact on everyday life may have made this developmental task even more demanding. Research worldwide has investigated adolescents’ mental health in relation to the pandemic and testified to the serious negative outcomes adolescents were confronted with (Jones et al., 2021). These studies have emphasized the specific vulnerability of adolescents, given that they are faced with the challenging task of constructing a personal identity. Given that one’s identity develops in close interaction with the social context and peers become increasingly important during this developmental stage, adolescents are highly sensitive to social interactions (Erikson, 1968; McElhaney et al., 2008). As such, adolescents’ mental health and their identity formation process could have been affected by the social isolation measures imposed during the pandemic (Cover, 2021).
Identity and the Body
Besides the process of identity formation, adolescents’ bodies undergo a range of apparent changes (Wertheim & Paxton, 2012). Adolescents go through these maturation processes whilst the opinion of others and social acceptation by peers becomes increasingly important (McElhaney et al., 2008). This may result in a heightened consciousness of the body and appearance, becoming a central aspect of adolescents’ lives. As a result, the prevalence of youth struggling with a negative body image is alarmingly high (Bucchianeri et al., 2013). Given that identity formation and body image both come to the fore during adolescence and emerging adulthood, theorists call for an increasing integration of both research fields (Daniels & Gillen, 2015). The current study aims to investigate the associations between identity and a range of interrelated body-related variables and processes that have been forwarded in multifactorial models such as Stice’s (2001) dual-pathway model. More specifically, in the current study, identity formation will be linked to the body perfect ideal upheld in society and the sociocultural pressures individuals may experience in attaining these ideals, the processes of self-objectification and appearance comparison, and, finally, body image and disturbed eating behaviors.
An important contributor to negative body image is the, often unrealistic, body perfect ideal youth are confronted with, typically encouraging girls to be thin and boys to be lean and muscular (Dittmar et al., 2007; Slater et al., 2012). These body perfect ideals are communicated through sociocultural pressures (e.g., media, parents, and peers), which may result in the internalization of appearance ideals (Thompson et al., 1999; Thompson & Stice, 2001). In the past years, research from various theoretical frameworks, such as the identity disruption model (Vartanian et al., 2018) and the identity styles model (Berzonsky, 1988), has revealed that identity formation in youth may impact the vulnerability to turn to appearance ideals. The identity disruption model linked negative early life experiences to body dissatisfaction and disordered eating via self-concept clarity (a concept closely related to identity diffusion) and sociocultural pressures. Results indicated that lower self-concept clarity was associated with higher internalization of appearance ideals and more frequent appearance comparisons, which were associated with greater body dissatisfaction. Greater body dissatisfaction, in turn, was associated with higher levels of disordered eating. From this perspective, individuals with low self-concept clarity are thought to be more vulnerable to turn to external sources to derive a sense of self (Vartanian et al., 2018). Relatedly, research from the identity styles framework indicated that adolescents who attach more importance to expectations and norms in their environment (i.e., the normative identity style) seemed more vulnerable to develop a rather maladaptive attitude towards beauty and eating. In contrast, adolescents who were information-oriented and engaged in pro-active identity exploration seemed to distance themselves from body perfect ideals and were therefore less vulnerable to internalizing these appearance ideals. In other words, individuals who actively search for information and are critical towards their environment (i.e., the information-oriented identity style) seemed less likely to turn to externally oriented identity building blocks which are provided by society (Verstuyf et al., 2014). In line with these findings, researchers have already stated that a healthy identity development may fulfill a protective role against appearance ideals internalization (Corning & Heibel, 2016).
Internalization of appearance ideals may lead to self-objectification, a self-perspective in which you look at your own body as an object and evaluate yourself based on its appearance (Lindner & Tantleff-Dunn, 2017). Previous findings demonstrated that self-objectification is a risk factor for various negative outcomes including body shame, body dissatisfaction, appearance anxiety, and disordered eating (Tiggemann, 2011). Little is known about the interplay between self-objectification and identity formation (Daniels & Gillen, 2015). However, theorists presume that self-objectified individuals may choose appearance-related identity alternatives, which may impact one’s choices concerning leisure activities (e.g., dance, gymnastics,…), education and profession (e.g., fashion, hostess job, hairdresser,…) (Calogero, 2011).
Self-objectification was found to be bidirectionally associated with appearance comparison (Lindner et al., 2012; Tylka & Sabik, 2010), a process in which adolescents compare their appearance to the appearance of others as a way to evaluate themselves (Festinger, 1954). As mentioned earlier, the identity disruption model indicated that individuals with low self-concept clarity were more susceptible to engage more frequently in appearance comparison to define their sense of self, which has been confirmed in other studies as well (Shahyad et al., 2018; Vartanian et al., 2018). When adolescents compare themselves to idealized media images or peers who are thought to be more attractive, appearance comparison may lead to negative outcomes, such as a negative body image (Yang et al., 2018). Negative body image is primarily characterized by body image disturbance (Burychka et al., 2021). Body image disturbance can be manifested in an underestimation or overestimation of body size (i.e., perceptual disturbance) and/or body dissatisfaction or overevaluation of body size and weight (i.e., affective disturbance) (Cornelissen et al., 2013; Dakanalis et al., 2016). However, body image is a multidimensional concept covering both negative and positive body image (Burychka et al., 2021). Positive body image was initially understood as the opposite concept of negative body image (Smolak, 2012; Tylka, 2012). However, a growing body of evidence points out that negative and positive body image are two distinct constructs (Tylka, 2018). Positive body image covers acceptance, respect, and favorable opinions towards one’s own body despite incongruences with media-promoted appearance ideals (Tylka & Wood-Barcalow, 2015a).
During the past decade, there has been a growing interest in the interplay between identity and body image (Daniels & Gillen, 2015). Erikson (1968) has already highlighted the intricate link between identity and one’s body in adolescence. During this developmental stage, the focus on one’s body and appearance may be so strong that it becomes a central identity aspect (Arnett, 2000). In line with this theorizing, recent studies have confirmed the salience of one’s body to define oneself as a person (Kling et al., 2018). One of the initial studies demonstrated a positive relationship between identity distress and negative body image (Kamps & Berman, 2011). Studies in adolescents revealed a positive association between identity processes (interpersonal exploration and commitment processes) and body esteem (Wängqvist & Frisén, 2013). Furthermore, decreasing body esteem predicted lowered identity coherence in emerging adulthood over time (Nelson et al., 2018). Further, identity functioning predicted body dissatisfaction over time, whereas body dissatisfaction also predicted maladaptive identity functioning over time (Palmeroni et al., 2020; Verschueren et al., 2018). Questions concerning the association between identity and positive body image, however, remain largely unanswered, indicating the need to address this topic.
Finally, negative body image is known to be a key element in the onset and maintenance of eating disorder symptoms, such as drive for thinness and bulimia (binge eating, purging) (Shagar et al., 2017). Eating disorder symptoms are highly prevalent in adolescence and contribute to the development and maintenance of clinical eating disorders (Croll et al., 2002). Theorists have forwarded identity formation as a contributing factor in the development and maintenance of eating disorder symptoms. Individuals searching for one’s identity may turn to eating disorder symptoms to define themselves, what may result in a more fragile identity (Corning & Heibel, 2016). Consequently, when the body is used to derive a sense of identity, this may result into the continuation of eating disorder symptoms to maintain this fragile personal identity (Cunningham et al., 2016; Verschueren et al., 2019). Otherwise, eating disorder symptomatology may also represent avoidance strategies to deal with identity-related difficulties (Wheeler et al., 2001). In a recent study, community adolescents who committed to their identity choices reported lower levels of drive for thinness and bulimia (Raemen et al., 2022). Previous studies in community adolescents further indicated that experiencing identity problems was associated with increased drive for thinness and bulimia (Palmeroni et al., 2020; Vartanian et al., 2018). Relatedly, patients with an eating disorder reported more identity problems compared to community controls (Verschueren et al., 2017). Furthermore, researchers have found an increasing amount of evidence for bidirectional effects between identity formation and eating disorder symptomatology (Palmeroni et al., 2021; Verschueren et al., 2019). In sum, identity formation and eating disorder symptomatology seem to reciprocally influence each other.
Current Study
Despite the fact that identity formation and body image both come to the fore during adolescence, integrative longitudinal research on this identity-body interplay in adolescents is lacking. The current study aimed to fill this gap by investigating the role of identity towards the body in adolescent boys and girls over time. The hypotheses and analyses of this study were preregistered at Open Science Framework. The first main goal was to investigate if the different identity trajectory classes that were found in previous studies could be replicated in the current study. Subsequently, since previous studies have found gender and age differences in identity formation, the current study explored whether there were gender and age differences among adolescents in different identity trajectory classes. Additionally, as drastic bodily changes and related weight change are prominent during adolescence, this study investigated if adolescents in different identity trajectory classes also differed on adjusted BMI at baseline. Second, this study aimed to investigate how these identity trajectory classes were related to differential development in negative and positive body image and various body-related variables (i.e., sociocultural pressures and internalization of appearance ideals, self-objectification, appearance comparison, and eating disorder symptoms).
Methods
Participants
A total of 403 students (52.1% female), with a mean age of 14.85 years (SD = 0.89; range 13–19) participated at Time 1. At Time 2, 329 students participated (retention rate = 81.64%); and at Time 3, 138 students participated (retention rate = 34.24%). Times 1 and 2 (early 2019 and, 2020, respectively) took place prior to the COVID-19 pandemic, Time 3 (early 2021) during the pandemic. Participants with and without complete data were compared using Little’s (1988) Missing Completely At Random (MCAR) test including all study variables at all three time-points simultaneously, which indicated that data were most likely missing completely at random (χ² = 800.49; p = 0.73). With regard to the preliminary analyses conducted in SPSS, The Expectation-Maximization (EM) algorithm was used to estimate missing data. With regard to the primary analyses conducted in MPLUS, the full information maximum likelihood (FIML) procedure (Muthén & Muthén, 2012) was used to handle cases with missing values (Enders, 2010).
Procedure
The data used in the current study were obtained in a longitudinal questionnaire study which was conducted at three annual measurement points between February 2019 and May 2021. The study was approved by the Social and Societal Ethics Committee of KU Leuven. Originally, students from four secondary schools in Flanders (Belgium) participated in the study, but data from only one school were used for the current paper, as the data collection in the other schools was not performed at all three measurement waves for logistic reasons and due to the COVID-19 pandemic. Prior to the data collection, all participants signed an informed consent form after receiving active parental consent which was required for minor participants. At Times 1 and 2, the data collection was conducted during school hours. All students filled out the self-report questionnaires and returned their completed questionnaires in a sealed envelope. Participants who were absent from school at the time of data collection were invited by e-mail to complete the questionnaires online (Qualtrics). At Time 3, data collection was done online using Qualtrics given that researchers were not allowed to collect data in schools due to the COVID-19 pandemic. At Times 2 and 3, students who had graduated or changed schools were also contacted by e-mail to participate online. Participants could win a voucher or a cinema ticket for their participation.
Measures
Adjusted body mass index
Based on students’ self-reported height and weight, their BMI (weight in kilogram/height*height in meters) was calculated. Given that the sample mainly included high school students under the age of 18 years, the adjusted BMI [(BMI/Percentile 50 of BMI for age and gender) × 100] was calculated based on the growth charts of a representative Flemish sample, to account for age and gender in the interpretation of BMI-scores.
Identity
Identity processes were assessed with the 25-item Dimensions of Identity Development Scale (DIDS; Luyckx et al., 2008). This questionnaire includes five subscales (exploration in breadth, exploration in depth, ruminative exploration, commitment making, and identification with commitment), each being measured by five items. All items were rated on a 5-point rating scale, ranging from 1 (completely disagree) to 5 (completely agree), and for each dimension mean scores were used. Example items are: ‘I think about the direction I want to take in my life’ (exploration in breadth), ‘I think about the future plans I have made’ (exploration in depth), ‘I keep looking for the direction I want to take in my life’ (ruminative exploration), ‘I decided on the direction I want to follow in life’ (commitment making), and ‘My plans for the future offer me a sense of security’ (identification with commitment). Cronbach’s alpha’s at Times 1, 2, and 3 were 0.83, 0.85, and 0.83, respectively, for exploration in breadth, 0.75, 0.82, and 0.78 for exploration in depth, 0.82, 0.85, and 0.82 for ruminative exploration, 0.88, 0.91, and 0.96 for commitment making, and 0.86, 0.88, and 0.88 for identification with commitment.
Body image
Negative body image or body dissatisfaction was evaluated by the body dissatisfaction subscale of the Eating Disorder Inventory-3 (EDI-3; Garner, 2004), which gives an indication of the degree to which an individual feels unsatisfied with his/her own body shape and believes that certain body areas are too large or big. The scale consists of 9 items that were rated on a 6-point Likert scale ranging from 1 (never) to 6 (always). An example item is: ‘I think that my stomach is too big’. Cronbach’s alpha’s were 0.90, 0.90, and 0.91 at Times 1, 2, and 3 respectively. Positive body image was assessed with the Body Appreciation Scale-2 (BAS-2; Tylka & Wood-Barcalow, 2015a). Positive body image entails favorable opinions towards one’s body, acceptance of one’s body despite incongruences with body perfect ideals, body competence, and integrity and respect towards the body (Tylka & Wood-Barcalow, 2015a). This scale consists of 10 items, which were rated on a 5-point Likert-scale ranging from 1 (never) to 5 (always). An example item is: ‘I respect my body’. Cronbach’s alpha’s at Times 1, 2, and 3 were 0.92, 0.94, and 0.94, respectively.
Sociocultural pressures and internalization of societal appearance ideals
Sociocultural pressures and internalization processes were assessed with the 22-item Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4; Schaufer et al., 2015). The questionnaire includes five subscales, of which three subscales address the perceived appearance pressures from family, parents and media and two subscales address internalization of societal appearance ideals: internalization of the thin ideal and internalization of the muscular ideal. Each of the first three subscales consists of four items scored on a 5-point Likert scale ranging from 1 (definitely disagree) to 5 (definitely agree). Each of the last two subscales consists of 5 items, rated on a 5-point Likert scale ranging from 1 (definitely disagree) to 5 (definitely agree). The current study focused on the total scale score of the first three subscales, representing sociocultural pressures in general, and distinct scale scores for internalization of appearance ideals. Example items are: ‘I feel pressure from my peers to improve my appearance’ (sociocultural pressures), ‘I want my body to look very thin’ (internalization of the thin ideal), and ‘It is important for me to look athletic’ (internalization of the muscular ideal). Cronbach’s alpha’s at Times 1, 2, and 3 were 0.90, 0.89, and 0.91, respectively, for sociocultural pressures, 0.90, 0.90, and 0.93 for internalization of the thin ideal, and 0.91, 0.90, and 0.90 for internalization of the muscular ideal.
Self-objectification
The process of self-objectification was measured by the Self-Objectification Beliefs and Behaviors Scale (SOBBS; Lindner & Tantleff-Dunn, 2017), which gives an indication of the degree to which an individual internalizes an observer’s perspective on the body and values the appearance of the body over physical abilities and what one thinks and feels. The scale consists of 14 items that were rated on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). An example item is: ‘Looking attractive to others is more important to me than being happy with who I am inside’. Cronbach’s alpha’s at Times 1, 2, and 3 were 0.91, 0.91, and 0.92, respectively.
Appearance comparison
The process of appearance comparison was evaluated by the five-item Physical Appearance Comparison Scale (PACS; Thompson et al., 1991). Items were rated on a 5-point Likert scale ranging from 1 (never) to 5 (always). An example item is: ‘At parties or other social events, I compare my physical appearance to the physical appearance of others’. Cronbach’s alpha’s were 0.80, 0.77, and 0.80 at Times 1, 2, and 3, respectively.
Eating disorder symptoms
Drive for thinness and bulimia were measured by means of the Eating Disorder Inventory-3 (EDI-3; Garner, 2004), which is a valid and reliable survey for questioning eating disorder symptomatology in non-clinical populations (Van Strien & Ouwens, 2003). The two symptom scales that were included, drive for thinness and bulimia, measure some of the central characteristics of an eating disorder. Each scale included 7 items and all items were scored on a 6-point Likert scale ranging from 1 (never) to 6 (always). Example items are: ‘I feel extremely guilty after overeating’ (drive for thinness) and ‘I eat when I am upset’ (bulimia). Cronbach’s alpha’s at Times 1, 2, and 3 were 0.91, 0.92, and 0.93, respectively, for drive for thinness, and 0.78, 0.78, and 0.88 for bulimia.
COVID-19
The impact of the COVID-19 pandemic at T3 of the data collection was assessed with two sets of seven self-constructed items. The first set of items assessed the pandemic’s negative and/or positive influence on different life aspects (e.g., social life, physical and mental health etc.), rated on a scale from -3 (strong negative impact) to +3 (strong positive impact). The second set of items measured the pandemic’s influence on a person’s negative affect (e.g., I feel scared), rated on a 7-point Likert scale ranging from 1 (completely disagree) to 7 (completely agree). Cronbach’s alpha’s were 0.81 and 0.86, respectively. Exploratory factor analysis (EFA) indicated a one-factor solution based on the eigenvalues and a scree plot for each set of seven items. The factor which contained the first set of items explained 48.25% of the variance with factor loadings from 0.511 to 0.881. The factor which contained the second set of items explained 54.58% of the variance with factor loadings from 0.517 to 0.810.
Statistical Analyses
First, it was investigated if the study variables were related to missing data. Of the 403 adolescents who entered the study, 138 participated at the final measurement wave (133 participants participated at all time-points, 178 missed 1 time-point, and 92 missed 2 time-points). To address differential attrition, a quasi-Poisson regression analysis was conducted to predict the number of missed waves by gender, age, COVID-19 variables, and main study variables. Only the demographic variables gender and age were associated with missingness, with both male gender (B = 0.447, p < 0.001) and higher age (B = 0.176, p = 0.003) being associated with a higher number of missed waves.
Second, latent class growth analysis (LCGA) on all five identity processes simultaneously was used to identify identity trajectory classes (Luyckx et al., 2013). The path from the linear slope to the indicator at Time 1 was fixed to 0 so that the mean intercept would represent the initial mean level. Given the equally spaced measurement intervals, subsequent linear slope pattern coefficients were fixed at 1, and 2 for Time 2 and Time 3, respectively. To account for non-normality, the models were estimated with maximum likelihood estimation with robust standard errors (MLR). LCGA solutions with one to six classes were estimated. Several criteria were used to decide on the number of classes (Masyn, 2013). These criteria did not always clearly indicate a single best-fitting model. Hence, it was important to balance objective fit with parsimony and interpretability to arrive at a meaningful solution (Johnson et al., 2007). First, the Akaike Information Criterion (AIC)1, the Bayesian information criterion (BIC), and the sample size-adjusted BIC (SABIC) for a solution with k classes had to be lower (at least 10 points; Kass & Raftery, 1995) than for a solution with k-1 classes, suggesting that adding classes improved model fit. Second, classification quality was assessed by entropy (E), a standardized summary measure of classification accuracy. Entropy ranges from 0.00 to 1.00, with values of 0.75 or higher indicating accurate classification (Reinecke, 2006). Third, a significant p-value for the Lo-Mendell-Rubin likelihood ratio test (LMR-LRT) and the bootstrap likelihood ratio test (BLRT) indicated added value of k classes over k-1 classes. Finally, the theoretical interpretability and meaningfulness of the classes were evaluated. If a solution with k classes emerged in which certain classes were difficult to interpret or did not add a meaningful class as compared to the more parsimonious solution with k-1 classes, the latter, more parsimonious solution was chosen. In line with this reasoning, all classes had to include at least 5% of the sample.
Third, assuming that the classification accuracy of the selected class solution was adequate, individuals were assigned to the trajectory class for which their posterior probability of group membership was highest (Luyckx et al., 2011). Age, adjusted BMI, and gender differences at baseline among the trajectory classes were examined. For age and adjusted BMI, a one-way multivariate analysis of variance (class membership as fixed factor and adjusted BMI/age as dependent variables) was performed with Tukey HSD post-hoc tests. For gender, a chi² cross-tabulation was performed and standardized residuals were inspected to determine significant discrepancies between observed and expected frequencies within each cell (i.e., an absolute value exceeding |2|).
Next, to examine whether the classes differed in their developmental trajectories of body-related variables and symptoms, multigroup latent growth curve (LGC) modeling was used. First, unconstrained LGC models with intercepts and linear slopes (again estimated using MLR and with linear slope terms fixed to 0, 1, and 2) freely estimated across identity trajectory classes were estimated for each outcome variable separately, resulting in nine unconstrained models. Adequate model fit was reflected by a root mean square error of approximation (RMSEA) below 0.08, a standardized root mean square residual (SRMR) below 0.10, a comparative fit index (CFI) above 0.90, and a χ²-value as small as possible (given that models were estimated using the MLR estimator, this study focused on the Yuan-Bentler scaled chi²). Next, the models were re-estimated with intercepts constrained equal across classes; and finally, slopes were constrained equal across classes. If these constrained models provided a significantly poorer fit to the data compared to the baseline unconstrained model (χ²-values of the constrained vs. unconstrained models were compared), these findings suggested that the trajectory classes differed from one another on at least some of the parameters tested. As a result, follow-up multigroup models estimated which intercepts or slopes could be held equal across each possible pair of classes. As such, it could be determined which specific trajectories differed from one another in terms of mean intercepts and slopes (Raymaekers et al., 2020).
Finally, exploratory analyses2 were conducted to examine whether identity development was associated with the impact of the COVID-19 pandemic (assessed at Time 3). Associations between identity development and the impact of COVID-19 were examined by conducting a multivariate analysis of variance (MANOVA) with the identity trajectory classes as fixed factor. As follow-up exploratory analyses, univariate LGC modeling was performed on the five identity dimensions to assess how the latent trajectories of these dimensions were related to COVID-19 measures. In doing so, intercepts and slopes of the identity dimensions (with the intercept being set at the final time-point by fixing the linear slope terms to −2, −1, and 0 for Times 1-3, respectively) were regressed on the items related to COVID-19.
Results
Preliminary Analyses
Table 1 presents means and standard deviations at the three time-points. Table 2 provides Pearson correlations at Times 1-3. Commitment making was significantly positively associated with drive for thinness at Time 1. Identification with commitment was negatively related to drive for thinness at Time 1 and Time 3, to bulimia and sociocultural pressures at Time 1, to internalization of the thin ideal, appearance comparison, and self-objectification at Time 1 and Time 2, and to negative body image at each time-point. Identification with commitment was positively related to positive body image at each time-point. Exploration in breadth was positively associated with drive for thinness and internalization of the muscular ideal at Time 1 and Time 2, with sociocultural pressures and self-objectification at Time 2, with internalization of the thin ideal at Time 1 and Time 3, and with appearance comparison at each time-point. Exploration in depth was positively related to internalization of the thin ideal at Time 1 and the muscular ideal at Time 2, and to drive for thinness, bulimia, sociocultural pressures, appearance comparison, and self-objectification at Time 1 and Time 2. Finally, ruminative exploration was positively related to all outcome variables at each time point, except for a negative relationship with positive body image.Table 1 Descriptive Statistics of Study Variables at Times 1-3
Time 1 Time 2 Time 3
Variable M (SD) M (SD) M (SD)
Commitment making 3.37 (0.86) 3.32 (0.90) 3.18 (1.08)
Identification commitment 3.37 (0.78) 3.31 (0.82) 3.41 (0.72)
Exploration breadth 3.48 (0.78) 3.63 (0.73) 3.80 (0.64)
Exploration depth 3.06 (0.78) 3.13 (0.84) 3.49 (0.74)
Ruminative exploration 2.73 (0.88) 2.82 (0.91) 3.06 (0.87)
Drive for thinness 2.42 (1.24) 2.41 (1.27) 2.64 (1.33)
Bulimia 1.96 (0.80) 2.08 (0.86) 2.11 (0.98)
Negative body image 3.03 (1.23) 3.07 (1.81) 3.19 (1.18)
Positive body image 3.48 (0.82) 3.53 (0.83) 3.49 (0.80)
Sociocultural pressures 1.88 (0.92) 1.92 (0.87) 2.26 (0.99)
Internalization thin ideal 2.76 (1.32) 2.83 (1.34) 3.07 (1.41)
Internalization muscular ideal 2.88 (1.23) 2.90 (1.20) 2.90 (1.15)
Appearance comparison 2.62 (0.93) 2.71 (0.87) 2.92 (0.86)
Self-objectification 2.64 (0.77) 2.67 (0.76) 2.86 (0.75)
Table 2 Pearson correlation coefficients between Identity Processes and Body-related variables at Times 1-3
Commitment making Identification with commitment Exploration in breadth Exploration in depth Ruminative exploration
Variable
Drive for thinness
T1 0.10* −0.14** 0.12* 0.15** 0.30**
T2 0.07 −0.08 0.14* 0.18** 0.17**
T3 0.04 −0.18* 0.13 0.02 0.24**
Bulimia
T1 −0.03 −0.17** 0.06 0.14** 0.35**
T2 0.05 −0.07 0.10 0.15** 0.23**
T3 0.04 −0.16 0.08 0.12 0.29**
Negative body image
T1 0.00 −0.26** 0.04 0.06 0.33**
T2 −0.07 −0.26** −0.04 −0.01 0.18**
T3 0.01 −0.24** 0.11 −0.05 0.25**
Positive body image
T1 0.06 0.31** 0.05 0.05 −0.34**
T2 0.06 0.27** 0.04 0.04 −0.19**
T3 0.05 0.28** 0.00 0.14 −0.28**
Sociocultural pressures
T1 0.05 −0.13** 0.06 0.18** 0.32**
T2 0.08 −0.05 0.15** 0.15** 0.22**
T3 0.04 −0.11 0.08 0.07 0.24**
Internalization of thin app
ideal
T1 0.02 −0.19** 0.15** 0.11* 0.32**
T2 −0.06 −0.16** 0.04 0.10 0.24**
T3 0.02 −0.12 0.18* 0.07 0.26**
Internalization of Muscular ideal idideal
muscular ideal
T1 0.06 0.01 0.12* 0.08 0.17**
T2 0.11 0.08 0.16** 0.15** 0.16**
T3 0.07 0.11 0.15 0.11 0.20*
Appearance comparison
T1 −0.05 −0.14** 0.13** 0.14** 0.31**
T2 −0.07 −0.11* 0.15** 0.20** 0.26**
T3 −0.10 −0.15 0.18* 0.10 0.36**
Self-objectification
T1 0.01 −0.16** 0.08 0.17** 0.37**
T2 −0.01 −0.15** 0.11* 0.18** 0.30**
T3 −0.05 −0.16 0.15 0.02 0.37**
*p < 0.05, **p < 0.01, ***p < 0.001
Identifying Identity Trajectory Classes
Table 3 presents the results of LCGA on the five identity dimensions, including all AIC, BIC, SABIC, entropy, LMR-LRT, and BLRT values, as well as the trajectory group prevalence. Because of a lower AIC, BIC, and SABIC value, the four-class solution (AIC = 9365.235; BIC = 9597.174; SABIC = 9413.134) was preferred over the three-class solution (AIC = 9539.072; BIC = 9727.022; SABIC = 9577.887). The four-class solution had an adequate entropy value (E = 0.809) and although the LMR-LRT value of the four-class solution was not significant (p = 0.173), the BLRT-value was significant (p < 0.001). Additionally, in the five-class solution, one of the classes consisted of only 6% of the sample and the classes were theoretically more difficult to interpret. Hence, the more parsimonious four-class solution was chosen.Table 3 Results of Latent Class Growth Analysis on the Five Identity Dimensions
Trajectory Group Prevalence (%)
AIC BIC SABIC Entropy LMR-LRT BLRT 1 2 3 4 5 6
1 Class 10488.713 10588.686 10509.359 / / / 100
2 Class 9777.829 9921.791 9807.559 0.786 p < 0.001 < 0.001 46 54
3 Class 9539.072 9727.022 9577.887 0.784 p = 0.080 < 0.001 27 26 47
4 Class 9365.235 9597.174 9413.134 0.809 p = 0.173 < 0.001 35 27 29 9
5 Class 9240.253 9516.180 9297.236 0.809 p = 0.099 < 0.001 21 25 16 32 6
6 Class 9185.968 9505.883 9252.035 0.831 p = 0.049 < 0.001 5 38 9 23 3 22
AIC Akaike Information Criterion, BIC Bayesian Information Criterion, SABIC Sample size-adjusted BIC, LMR-LRT Lo-Mendell-Rubin Likelihood Ratio Test, BLRT Bootstrapped Likelihood Ratio Test. The four class solution (in italics) was selected
Table 4 provides the estimates of mean intercepts and mean slopes for all trajectory classes of the four-class solution. Partially in line with hypotheses, class 1 (35%) resembled achievement and included adolescents scoring relatively high on both commitment and exploration processes, except for ruminative exploration. Whereas identity processes remained rather stable over time, exploration in breadth tended to increase over time. Class 2 (27%) was labeled carefree diffusion and consisted of adolescents scoring relatively low to moderate on all dimensions. All identity processes remained rather stable over time. Class 3 (29%) resembled moratorium and included adolescents scoring relatively low on both commitment processes and high on all exploration processes. Both pro-active as well as ruminative exploration processes tended to increase over time. Finally, class 4 (9%) resembled troubled diffusion and consisted of adolescents scoring low on all identity processes, except for ruminative exploration. All three exploration dimensions substantially increased over time, hence this class was labeled more specifically as troubled diffusion-increasing exploration.Table 4 Parameter Estimates of the Four Class Solution
Total sample Identity Trajectory Class
Parameters Achievement Carefree diffusion Moratorium Troubled diffusion-increasing exploration
Commitment making
mean intercept 3.382*** 4.072*** 3.274*** 3.052*** 2.128***
mean slope −0.084** −0.072 −0.093 −0.074 −0.170
Identification commitment
mean intercept 3.354*** 4.008*** 3.254*** 3.030*** 2.200***
mean slope 0.007 −0.048 0.009 0.035 0.077
Exploration in breadth
mean intercept 3.480*** 3.893*** 2.982*** 3.729*** 2.630***
mean slope 0.160*** 0.097* 0.054 0.119* 0.571***
Exploration in depth
mean intercept 3.028*** 3.560*** 2.545*** 3.134*** 2.089***
mean slope 0.194*** 0.121 0.110 0.215*** 0.366*
Ruminative exploration
mean intercept 2.714*** 2.472*** 2.351*** 3.275*** 2.940***
mean slope 0.152*** 0.103 0.015 0.141* 0.571***
*p < 0.05, **p < 0.01, ***p < 0.001
Further analyses indicated that the classes did not differ on age at Time 1 (F(3) = 2.27, p = 0.08), but differed on gender (χ²(3) = 20.16, p < 0.001). Based on an inspection of the standardized residuals, male adolescents were significantly overrepresented in the carefree diffusion class (61.1% boys), whereas female adolescents were overrepresented in the moratorium class (67.5% girls). Finally, the classes did not differ on adjusted BMI (F(3) = 0.400, p = 0.75).
Associations with Body Image and Body-Related Symptoms
Table 5 provides all the baseline parameter estimates of multigroup LGC modeling. For sociocultural pressures, an adequate fit was found for the unconstrained model [χ²(8) = 13.21, p = 0.10; RMSEA = 0.08; CFI = 0.97; SRMR = 0.05]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(5) = 41.19, p < 0.001], indicating that the classes differed from one another on initial levels of sociocultural pressures. Adolescents in carefree diffusion experienced significantly lower levels of sociocultural pressures compared to adolescents in the other classes. Further, although levels of sociocultural pressures increased significantly in achievement and troubled diffusion-increasing exploration, model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(5) = 6.47, p = 0.26], indicating that the classes did not differ from one another in terms of changes over time.Table 5 Baseline Parameter Estimates of Multigroup Latent Growth Curve Modeling
Identity Trajectory Class
Parameters Achievement Carefree diffusion Moratorium Troubled diffusion-increasing exploration
Drive for thinness
Mean intercept 2.458***b 2.016***a 2.660***b 2.579***b
Mean slope 0.069 −0.014 0.070 0.059
Bulimia
Mean intercept 1.925***ac 1.761***a 2.230***b 2.016***bc
Mean slope 0.095* 0.002 0.108* 0.032
Negative body image
Mean intercept 2.905***a 2.709***a 3.325***b 3.486***b
Mean slope 0.070 −0.028 0.010 0.039
Positive body image
Mean intercept 3.619***b 3.600***b 3.357***a 3.127***a
Mean slope 0.017 0.077 0.034 0.014
Sociocultural pressures
Mean intercept 1.885***b 1.526***a 2.117***b 1.921***b
Mean slope 0.163*** 0.058 0.079 0.203*
Internalization thin ideal
Mean intercept 2.770***b 2.284***a 3.047***b 3.062***b
Mean slope 0.112 0.011 0.046 0.193
Internalization muscular ideal
Mean intercept 2.988*** 2.781*** 2.948*** 2.663***
Mean slope 0.104 0.035 −0.009 −0.096
Physical appearance comparison
Mean intercept 2.598***b 2.262***a 2.946***c 2.717***bc
Mean slope 0.103bc 0.000ab −0.023a 0.223**c
Self-objectification
Mean intercept 2.645***b 2.332***a 2.872***c 2.744***bc
Mean slope 0.062 0.080 0.002 0.142
Within rows, intercepts and slopes differ at p < 0.05 if they have different superscripts (letters a, b, or bc). Parameters without superscripts do not differ significantly from one another. *p < 0.05, **p < 0.01, ***p < 0.001
For internalization of the thin ideal, the unconstrained model did not provide an adequate fit across all indices [χ²(6) = 15.94, p = 0.01; RMSEA = 0.13; CFI = 0.95; SRMR = 0.10]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 28.45, p < 0.001], indicating that the classes differed from one another on initial levels of internalization of the thin ideal. Adolescents in carefree diffusion were less likely to internalize the thin ideal compared to adolescents in the other classes. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 0.36, p = 0.95], indicating that the classes did not differ from one another in terms of changes over time.
For internalization of the muscular ideal, the unconstrained model provided, except for the SRMR-value, an adequate fit [χ²(6) = 7.64, p = 0.27; RMSEA = 0.05; CFI = 0.99; SRMR = 0.11]. Analyses indicated that both intercepts and slopes could be constrained as equal among the classes [Δχ²(3) = 2.87, p = 0.41; Δχ²(3) = 1.63, p = 0.65], indicating that the classes did not differ from one another on initial levels of internalization of the muscular ideal or in terms of changes over time.
For self-objectification, the unconstrained model provided, except for the SRMR-value, an adequate fit [χ²(7) = 10.14, p = 0.18; RMSEA = 0.07; CFI = 0.98; SRMR = 0.14]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 32.60, p < 0.001], indicating that the classes differed from one another on initial levels of self-objectification. Adolescents in achievement reported significantly lower levels of self-objectification compared to moratorium, whereas adolescents in carefree diffusion reported the lowest levels of self-objectification. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 1.11, p = 0.78], indicating that the classes did not differ from one another in terms of changes over time.
For appearance comparison, an adequate fit was found for the unconstrained model [χ²(9) = 2.82, p = 0.97; RMSEA = 0.00; CFI = 1.00; SRMR = 0.03]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 42.71, p < 0.001], indicating that the classes differed from one another on initial levels of appearance comparison. Adolescents in achievement reported significantly lower levels of appearance comparison than in moratorium, whereas adolescents in carefree diffusion reported the lowest levels of appearance comparison. Constraining slopes as equal among classes resulted in a significantly decreased model fit as well [Δχ²(3) = 7.93, p = 0.05], indicating that the classes differed from one another in terms of changes over time. Appearance comparison increased significantly more over time for adolescents in achievement compared to adolescents in moratorium. Adolescents in troubled diffusion-increasing exploration experienced the largest increases in appearance comparison, with changes over time significantly different from those in moratorium and carefree diffusion.
For negative body image, an adequate fit was found for the unconstrained model [χ²(6) = 2.86, p = 0.83; RMSEA = 0.00; CFI = 1.00; SRMR = 0.03]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 25.94, p < 0.001], indicating that the classes differed from one another on initial levels of negative body image. Adolescents in achievement and carefree diffusion experienced significantly lower levels of negative body image compared to adolescents in moratorium and troubled diffusion-increasing exploration. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 1.79, p = 0.62], indicating that the classes did not differ from one another in terms of changes over time.
For positive body image, an adequate fit was found for the unconstrained model [χ²(7) = 11.48, p = 0.12; RMSEA = 0.08; CFI = 0.98; SRMR = 0.07]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 16.24, p < 0.001], indicating that the classes differed from one another on initial levels of positive body image. Adolescents in achievement and carefree diffusion experienced significantly higher levels of positive body image compared to adolescents in moratorium and troubled diffusion-increasing exploration. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 0.48, p = 0.92], indicating that the classes did not differ from one another in terms of changes over time.
For drive for thinness, an adequate fit was found for the unconstrained model [χ²(7) = 8.44, p = 0.30; RMSEA = 0.05; CFI = 0.99; SRMR = 0.04]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 20.56, p < 0.001], indicating that the classes differed from one another on initial levels of drive for thinness. Adolescents in carefree diffusion reported significantly lower levels of drive for thinness compared to the other classes. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 2.89, p = 0.41], indicating that the classes did not differ from one another in terms of changes over time.
Finally, for bulimia, an adequate fit was found for the unconstrained model [χ²(6) = 6.64, p = 0.36; RMSEA = 0.03; CFI = 1.00; SRMR = 0.05]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(2) = 25.20, p < 0.001], indicating that the classes differed from one another on initial levels of bulimia. Adolescents in achievement reported significantly lower levels of bulimia compared to moratorium, whereas adolescents in carefree diffusion scored lower compared to moratorium and troubled diffusion-increasing exploration. Further, although bulimia increased significantly for adolescents in achievement and moratorium, model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(2) = 5.50, p = 0.06], indicating that the classes did not differ from one another in terms of changes over time.
Associations with the Impact of the COVID-19 Pandemic
Given that the items assessing the pandemic’s influence on different life aspects showed non-significant correlations with the identity dimensions, only the results regarding the items assessing the pandemic’s influence on a person’s negative affect are discussed. With regard to the associations between identity development and the impact of COVID-19, significant differences between the identity classes on the impact of COVID-19 on a person’s negative affect were found (F = 10.858, p < 0.001, η2 = 0.194). Post-hoc analyses indicated that adolescents in carefree diffusion (M = 3.19; SD = 1.35) experienced the least influence by COVID-19 on their negative affect as compared to adolescents in achievement (M = 4.21; SD = 1.35), moratorium (M = 4.65; SD = 0.94), and troubled diffusion-increasing exploration (M = 4.78; SD = 0.59) (p < 0.05). Finally, Table 6 shows positive associations between the initial levels of all exploration processes and changes over time in ruminative exploration with the impact of COVID-19 on negative affect.Table 6 Beta regression coefficients of the Identity Processes regressed on COVID-19 items and values of explained variances
Impact of COVID-19
ß R2
Commitment making
mean intercept −0.17 0.03
mean slope −0.21 0.18
Identification commitment
mean intercept −0.10 0.02
mean slope −0.05 0.08
Exploration in breadth
mean intercept 0.33** 0.10
mean slope 0.08 0.01
Exploration in depth
mean intercept 0.28* 0.07
mean slope −0.01 0.00
Ruminative exploration
mean intercept 0.54*** 0.31***
mean slope 0.27* 0.10
*p < 0.05, **p < 0.01, ***p < 0.001
Discussion
According to Erikson (1968), feeling at home in one’s body is crucial to developing a strong personal identity. During the past decade, research findings have supported Erikson’s theoretical thinking and pointed out the complex interplay between identity and the body. However, research on personal identity and one’s body has developed mainly in isolation and has primarily focused on negative body image (Daniels & Gillen, 2015; Nelson et al., 2018). To broaden the understanding of the link between identity and one’s body, the current study examined identity trajectory classes throughout adolescence and investigated how these identity trajectory classes were associated with differential development in negative and positive body image and body-related variables. Four identity trajectory classes emerged, partially in line with expectations. Additionally, evidence was found for the developmental association linking identity formation to adolescents’ body image and body-related variables. These results emphasize the need to target adolescents struggling with their identity development, as they may be more vulnerable for body image problems and other body-related symptoms.
Identity Trajectory Classes throughout Adolescence
Partially consistent with previous studies (Luyckx et al., 2013; Raemen et al., 2022), four identity trajectory classes were identified: achievement, carefree diffusion, moratorium, and troubled diffusion-increasing exploration. Although identity trajectory classes were differentiated primarily in terms of initial levels of the identity dimensions, some differential changes over time were also observed. Interestingly, relatively high and/or increasing levels of exploration were uncovered in the identity trajectory classes, which was in contrast with previous findings. This finding might be explained by the younger age group of this study and the COVID-19 pandemic at Time 3, as initial levels of all exploration processes and changes over time in ruminative exploration were associated with the impact of COVID-19. It is plausible that adolescents became more self-doubting and questioning due to the pandemic, as their known identity building blocks (e.g., hobbies, contact with peers, etc.) were substantially affected, for instance, by lockdown measures. Further, the current study could not identify a separate foreclosure trajectory class. However, readers should note that adolescents in carefree diffusion made commitments to a certain degree, somewhat resembling characteristics of foreclosed individuals. However, the levels of their commitment processes were not elevated enough to label this class as foreclosure. Importantly, it is not uncommon that not all identity trajectory classes are identified in each specific study (see, e.g., the study by Hatano & Sugimura (2017) that also did not identify a longitudinal foreclosure class), possibly due to sample characteristics or context-specific factors such as the COVID-19 pandemic (Fig. 1).Fig. 1 Observed mean trends for the five identity processes in the identified identity trajectory classes. CM Commitment making, IC Identification with commitment, EB Exploration in breadth, ED Exploration in depth, RE Ruminative exploration. “*” indicates significant changes over time
First, with respect to the four trajectory classes obtained, and in line with previous longitudinal research (Luyckx et al., 2013; Raemen et al., 2022), adolescents in the achievement trajectory class pro-actively explored identity options and they were able to make strong commitments and identify with these commitments, without being inhibited by ruminative exploration. Although these adolescents identified with their identity choices, they increasingly kept exploring their identity options in breadth over time. Based on their engagement in commitment and pro-active exploration processes, this achievement trajectory class seemed to be a prime example of an adaptive identity search (Schwartz et al., 2011).
Second, also in line with previous research, adolescents in the carefree diffusion trajectory class developed tentative commitments to a certain degree, but without systematically exploring different identity options. They seemed unmotivated to fully engage themselves in their identity quest (Schwartz et al., 2011). These carefree-diffused adolescents also did not seem to ruminate about their identity search.
Third, as expected, adolescents in the moratorium trajectory class kept exploring different identity options in breadth and in depth, without making strong commitments or identifying with these choices. Adolescents in moratorium seemed to worry about their tentative commitments and their search for alternative identity building blocks. In terms of changes over time, they increasingly explored identity options in both an adaptive and maladaptive way. This moratorium trajectory class may reflect less adaptive identity functioning to some extent, as these adolescents seemed to lack a strong identity foundation (Schwartz et al., 2016).
Finally, an identity trajectory class resembling troubled diffusion-increasing exploration was identified. As expected, troubled-diffused adolescents worried about identity issues, hindering them from adequate identity work, as indicated by limited engagement in pro-active exploration and commitment processes. Whereas carefree-diffused adolescents seemed unmotivated to engage in identity development, troubled-diffused adolescents seemed to be unable to translate their worries into a proactive identity search. However, in contrast to expectations (Luyckx et al., 2013; Raemen et al., 2022), troubled-diffused adolescents increasingly tried to explore identity options in breadth and in depth over time. In other words, they tried to engage proactively in their identity quest, but at the same time they felt overwhelmed by this process (Schwartz et al., 2011). Consequently, based on these substantial increases in exploration processes over time, this trajectory class was labeled as troubled diffusion-increasing exploration. These increasing levels of exploration might again be linked to the COVID-19 pandemic. Although troubled-diffused individuals did not differ from adolescents in achievement and moratorium on the impact of COVID-19, troubled-diffused adolescents reported the strongest impact of COVID-19 on their negative affect. Moreover, increases over time in ruminative exploration were positively associated with the impact of COVID-19, meaning that the stronger someone experienced impact of the pandemic, the more someone was likely to ruminate about life choices, and vice versa.
Subsequently, results showed gender differences among the identity classes at Time 1, as female adolescents were overrepresented in moratorium and male adolescents were overrepresented in carefree diffusion, as expected (Raemen et al., 2022; Verschueren et al., 2017). Further, as expected, the identity trajectory classes did not differ on adjusted BMI, indicating that the evaluation of the body (i.e., body image) might be a more important factor to identity functioning than body shape in itself (Nelson et al., 2018). Finally, in contrast with previous research (Raemen et al., 2022; Verschueren et al., 2017), no age differences were found among the identity trajectory classes. This finding might be explained by the younger age group, as there might be more differentiation at a slightly older age (Luyckx et al., 2013). Late adolescence and emerging adulthood indeed offer many opportunities for pro-active identity exploration in various domains of life, possibly resulting in more inter-individual differences (Arnett, 2000).
Identity Trajectory Classes and Differential Development in Body Image and Body-Related Variables
The results provided a nuanced picture of the co-development of identity and the body, and findings were dependent on which specific body-related variables the study focused on. In line with expectations, the levels of negative and positive body image and body-related variables differed among identity trajectory classes. These findings suggested that adolescents in identity trajectory classes reflecting less adaptive identity functioning, such as moratorium and troubled diffusion-increasing exploration, displayed higher levels of negative body image and body-related symptoms and lower levels of positive body image. Although class differences were primarily found on the initial levels of the external variables, some differential changes over time were also observed.
In line with hypotheses, adolescents in moratorium and troubled diffusion-increasing exploration showed the least adaptive functioning. In addition to their arduous identity search, they seemed more vulnerable to sociocultural pressures and internalization of the thin ideal. Consistent with previous research (Corning & Heibel, 2016), these findings seem to indicate that adolescents who are lacking a strong identity foundation and get stuck in ruminatively exploring different identity options, are more prone to internalize appearance ideals (and especially the thin ideal) to derive a sense of identity. In line with this tenet, these adolescents seemed also more likely to self-objectify and engage in appearance comparison to evaluate themselves. These findings can also be understood from the identity styles model which focuses on individual differences in cognitive styles underlying the identity exploration process (Berzonsky, 1988). Especially the diffuse-avoidant identity style, in which individuals adopt an evasive and procrastinatory orientation toward decision making, is associated with internalizing appearance ideals. In line with this, adolescents in moratorium and troubled diffusion-increasing exploration seemed to avoid or procrastinate their identity choices by continuing to ruminatively explore identity options without making strong commitments. As a result, these adolescents may turn to the body perfect ideal in the expectation that they will achieve happiness and success when they reach this ideal or as a way to avoid coping with their identity issues (Verstuyf et al., 2014; Wheeler et al., 2001). Moreover, troubled-diffused adolescents seemed vulnerable to increasingly engage in appearance comparison over time, which might be associated with their strong increases in pro-active and ruminative exploration over time. Because these adolescents lack a stable sense of identity when they begin to increasingly explore identity alternatives, they may be even more vulnerable to being guided by extrinsic goals and societal ideals, resulting in increased engagement in appearance comparison (Duriez et al., 2012). Subsequently, adolescents in these identity trajectory classes experienced higher levels of negative body image and lower levels of positive body image, confirming the established interplay between identity and one’s body image (Palmeroni et al., 2020; Verschueren et al., 2018). Interestingly, given that the interplay between identity and adolescents’ positive body image is still understudied, these findings suggested that identity formation indeed might be associated with one’s positive body image as well. Finally, adolescents in moratorium and troubled diffusion-increasing exploration seemed more vulnerable to develop eating disorder symptoms (i.e., drive for thinness and bulimia). These results are in line with previous research (Palmeroni et al., 2020; Raemen et al., 2022), indicating that adolescents who are searching for a personal identity without making strong commitments may turn to eating disorder symptoms as identity substitutes.
Based on the idea that achievement may be the most adaptive identity trajectory class, these adolescents were expected to also behave most adaptively in terms of body image and body-related behaviors (Luyckx et al., 2013). With regard to self-objectification, appearance comparison, negative and positive body image, and bulimia, adolescents in achievement indeed displayed better scores as compared to adolescents in moratorium and/or troubled diffusion-increasing exploration. However, with regard to sociocultural pressures, internalization of appearance ideals, and drive for thinness, adolescents in achievement did not behave differently from adolescents in moratorium and troubled diffusion-increasing exploration. Thus, adolescents in achievement also seemed to turn to socially available identity building blocks, such as appearance ideals, in their search for a strong personal identity. Interestingly, adolescents in carefree diffusion generally displayed the most adaptive scores regarding body image and body-related variables. This finding might be explained by the fact that male adolescents were overrepresented in carefree diffusion and, more importantly, that carefree-diffused adolescents were less concerned about their identity quest. Given the identity-body interplay, it is possible that carefree-diffused adolescents were doing better in terms of body-related symptoms in the short term, because their limited identity search might made them more immune to sociocultural pressures regarding appearance (Corning & Heibel, 2016). In other words, when individuals seem unmotivated to fully engage in their identity search and to explore identity options, they may be less vulnerable to turn to socially constructed appearance ideals as identity building blocks as well. This finding highlights the importance to focus also on the specific content of the identity exploration and commitment processes. However, the identity questionnaire used in the current study focused broadly on the degree to which adolescents engaged in exploration and commitment processes with respect to their future plans and lifestyle (without detailing what these plans and lifestyle exactly entail). Adolescents who are more involved in pro-active exploration or commitment processes, for instance, may commit to rather pathological identity content (such as being excessively thin). Furthermore, the lack of a strong personal identity might make these carefree diffused individuals more vulnerable in the long run for developing pathological symptoms, as an integrated identity tends to become increasingly important for one’s well-being throughout the twenties (Kling et al., 2018; Luyckx et al., 2013).
Practical Implications
Although no strong conclusions for clinical practice can be made, the current findings may have several implications for the prevention and intervention of body image problems and other body-related symptoms in adolescents. As the current study confirms the intricate link between identity and one’s body in adolescence, it seems important to target adolescents who are struggling with their identity development, as they may be more vulnerable to also struggle with their body image and other body-related symptoms. In other words, when identity development becomes even more challenging (e.g., due to a pandemic), it is important for clinicians to be aware of bodily concerns as well. Further, besides clinicians, the immediate social environment may promote pro-active identity exploration and may support adolescents in committing to healthy identity choices. For instance, research has demonstrated that positive youth development (PYD) interventions in schools or other communities can have a beneficial impact on identity formation (Eichas et al., 2017). More concretely, schools can organize exercises with students to guide students in sharing life stories, discovering personal strengths, co-constructing life goals, and strategies for achieving these goals (Eichas et al., 2014). Findings suggested that such PYD interventions, focusing on expanding and enhancing personal potentials and meaningful aspect of one’s life, can empower adolescents to define who they are and what they wish to achieve in life (Eichas et al., 2017). Relatedly, families and peers may also stimulate adolescents to reflect on their intrinsic life goals and to explore different aspects of the self that are not only related to body and appearance. In this way, adolescents may end up developing a more diversified and intrinsically oriented sense of self as a resource against the confrontation with the body perfect ideal. Finally, as associations between identity formation and positive body image have been found, it might be helpful to strengthen a positive body image in adolescents. It is known that reducing negative body image and enhancing positive body image might prevent or reduce eating disorder symptoms, and that body image and pressures regarding appearance ideals might impact identity formation as well (Palmeroni et al., 2021; Palmeroni et al., 2020). Hence, strengthening positive body image besides reducing negative body image and appearance-related pressures might positively impact eating disorder symptomatology and identity development. As body ideals are socially constructed, both the direct social environment (i.e., parents, teachers, and peers) and the larger community might have a crucial role in adolescents’ enhancement of healthy attitudes towards the body and appearance. For example, given that body acceptance by others can positively affect one’s body image, it might be helpful for adolescents if parents, teachers, and peers would provide positive and accepting messages related to one’s body (Andrew et al., 2016).
Limitations and Suggestions for Future Research
Some limitations should be considered. First, although the three-wave longitudinal design was a strength of the current study, the time span was limited to a period of only two years, which does not allow us to draw conclusions about long-term functioning. Investigating adolescents over a longer time period could give us a greater insight into the co-development of identity and the body during adolescence. Second, the study faced a large drop-out on the third measurement wave, which is presumably due to the fact that this last measurement wave took place during the COVID-19 pandemic. Third, the current study exclusively made use of self-report questionnaires, which is the preferred way to assess subjective processes. However, self-reports might be influenced by memory recall, and, inaccurately high correlations among the study variables could occur as a result of shared method variance (Tylka, 2012). Combining this method with a multi-method or multi-informant approach might provide additional information and is advised for future studies. Relatedly, future research could also benefit from investigating this identity-body interplay from a narrative identity approach and focusing on the content of one’s identity (Skhirtladze et al., in press). From this point of view, it would be interesting to investigate whether sociocultural pressures and appearance ideals are equally embedded into one’s identity in the different statuses; or, similarly, what the different motives are behind the thin versus the muscular appearance ideal. Finally, although gender-adjusted measures assessing appearance ideals internalization (i.e., thin ideal and muscular ideal) were included (Schaefer et al., 2015), this study solely focused on disturbed eating behaviors aiming at achieving the thin ideal instead of also focusing on eating behaviors related to the muscular ideal such as eating more carbohydrates or using steroids. Moreover, the EDI-3 subscale (Garner, 2004) that assesses negative body image seems to focus primarily on women’s physical features and bodily concerns (Tylka, 2012). Hence, these findings might be an underestimation of body image concerns and body-related symptoms in adolescent boys, as no significant differences for internalization of the muscular ideal were found. Future research should include additional measurements that can assess the full spectrum of bodily concerns across gender.
Conclusion
The complex longitudinal associations between identity formation and one’s body in adolescence have remained largely understudied. Addressing these gaps, the current study provides insight into this identity-body interplay by investigating identity trajectory classes among adolescents and the co-development with body image and body-related variables. In sum, the current findings indicated that distinct identity pathways throughout adolescence emerge, characterized by differential levels of underlying exploration and commitment processes. Adolescents in identity trajectory classes reflecting less adaptive identity functioning, such as moratorium or troubled diffusion, displayed higher levels of negative body image and body-related symptoms and lower levels of positive body image. Finally, adolescents included in these less adaptive identity trajectory classes also experienced a stronger impact of the COVID-19 pandemic on their negative affect. Overall, the current study confirms that identity formation is intricately linked to adolescents’ body image and other body-related symptoms. Both future research and prevention or intervention programs are encouraged to take identity formation into account in relation to body image problems and other body-related symptoms in adolescents.
Authors’ Contributions
L.V. conceived of the study, participated in its design and coordination, performed the statistical analyses and drafted the manuscript; L.R. helped with the data collection, participated in the design of the study, the interpretation of the data and helped to draft the manuscript; L.C. conceived of the study, participated in the design of the study, the interpretation of the data and helped to draft the manuscript; S.E. participated in the design of the study and helped to draft the manuscript; N.P. oversaw the data collection and helped to draft the manuscript; K.L. conceived of the study, participated in its design and coordination, performed the statistical analysis and helped to draft the manuscript. All authors read and approved the final manuscript.
Data availability
The dataset analyzed during the current study are not publicly available but are available from the corresponding author (L.V.) on reasonable request.
Compliance with Ethical Standards
Conflict of Interest
The authors declare no competing interests.
Ethical Approval
The study was approved by the Social and Societal Ethics Committee of KU Leuven (G-2018 08 1303).
Informed Consent
Written informed consent was provided by all participants included in the study and the parents of minor students provided active parental consent as well.
1 The AIC, SABIC, and LMR-LRT were requested by a reviewer as additional criteria, and such, were not mentioned in the preregistration of the manuscript.
2 Analyses were conducted on a limited sample, given that the students had to have participated at the third measurement point. These analyses were not preregistered.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Wheeler HA Adams GR Keating L Binge eating as a means for evading identity issues: The association between an avoidance identity style and bulimic behavior Identity: An International Journal of Theory and Research 2001 1 2 161 178 10.1207/S1532706XID0102_04
Yang C Holden SM Carter MDK Webb JJ Social media social comparison and identity distress at the college transition: A dual-path model Journal of Adolescence 2018 69 92 102 10.1016/J.ADOLESCENCE.2018.09.007 30278321
| 36484894 | PMC9735114 | NO-CC CODE | 2022-12-14 23:28:32 | no | J Youth Adolesc. 2022 Dec 9;:1-19 | utf-8 | J Youth Adolesc | 2,022 | 10.1007/s10964-022-01717-y | oa_other |
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J Youth Adolesc
J Youth Adolesc
Journal of Youth and Adolescence
0047-2891
1573-6601
Springer US New York
36484894
1717
10.1007/s10964-022-01717-y
Empirical Research
Identity Formation, Body Image, and Body-Related Symptoms: Developmental Trajectories and Associations Throughout Adolescence
http://orcid.org/0000-0002-9091-5540
Vankerckhoven Lore [email protected]
1Lore Vankerckhoven
is a doctoral student at KU Leuven. Her major research interests include the associations between identity and psychopathology in adolescents.
Raemen Leni 1Leni Raemen
is a doctoral student at KU Leuven. Her major research interests include the transdiagnostic value of identity in psychopathology.
Claes Laurence 12Laurence Claes
is a Full Professor at KU Leuven and the University of Antwerp (UA). Her major research interests include the associations between identity/personality and psychopathology, more specific, non-suicidal self-injury, eating disorders, and addictions.
Eggermont Steven 1Steven Eggermont
is a Full Professor at KU Leuven. His major research interests include media effects and the associations with mental health.
Palmeroni Nina 1Nina Palmeroni
obtained a PhD in Psychology at KU Leuven. Her major research interests include identity functioning, body image, and eating disorder symptoms.
Luyckx Koen 13Koen Luyckx
is Associate Professor at KU Leuven and research fellow at the University of the Free State, Bloemfontein, South Africa (UNIBS). His major research interests include identity development and its associations with psychopathology, both in community adolescents and emerging adults and in adolescents/emerging adults with a chronic illness.
1 grid.5596.f 0000 0001 0668 7884 Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium
2 grid.5284.b 0000 0001 0790 3681 Faculty of Medicine and Health Sciences (CAPRI), University of Antwerp, Antwerp, Belgium
3 grid.412219.d 0000 0001 2284 638X UNIBS, University of the Free State, Bloemfontein, South Africa
9 12 2022
119
16 9 2022
26 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Emerging evidence highlights the intricate link between identity and one’s body, however, integrative longitudinal research on this identity-body interplay is lacking. The current study used three-wave longitudinal data (Time 1: N = 403; 52.1% female; Mage = 14.85, SD = 0.89, range = 13–19 years) spanning two years (2019–2021; T1 and T2 being pre-pandemic, T3 peri-pandemic) to identify identity trajectory classes and examine their co-development with negative and positive body image and various body-related variables (i.e., sociocultural pressures, internalization of appearance ideals, self-objectification, appearance comparison, and eating disorder symptoms). First, four identity classes emerged using latent class growth analysis (achievement, moratorium, carefree diffusion, and troubled diffusion). Second, using multigroup latent growth curve modeling, adolescents in less adaptive identity trajectory classes (i.e., engaging less in pro-active processes and more in ruminative processes) displayed higher levels of negative body image and body-related symptoms. The current study testified to the clinically meaningful associations linking identity formation to adolescents’ body image and other body-related symptoms.
Keywords
Identity functioning
Body image
Adolescence
Trajectory classes
==== Body
pmcIntroduction
Identity formation is a lifelong developmental task which is especially prominent during adolescence and emerging adulthood (Erikson, 1968). Erikson has already mentioned that feeling at home in one’s body is one of the most important concomitants of achieving an optimal identity. In the past few years, research has pointed to the intricate link between identity functioning and one’s body. However, integrative research is lacking as research on personal identity and one’s body has developed mainly in isolation (Nelson et al., 2018). Further, research has mainly focused on negative body image instead of adopting a holistic perspective on the body with attention to positive body image as well. To broaden the understanding of the link between identity and one’s body, the current study used three-wave longitudinal data spanning two years to (1) identify different identity trajectory classes (based on five interrelated commitment and exploration-processes) among adolescents and examine if these trajectory classes differ on gender, age, and body mass index (BMI) at baseline; and (2) examine how these identity trajectory classes are related to differential development in negative and positive body image and various body-related variables and symptoms (i.e., sociocultural pressures and internalization of appearance ideals, self-objectification, appearance comparison, and eating disorder symptoms).
Identity Formation
Erikson (1968) described identity formation as a central developmental task throughout the life span. Especially during adolescence and emerging adulthood, youth are challenged to resolve life-defining questions. During this identity quest, adolescents may go through an identity crisis in which they contemplate decisions concerning their future lives. This identity crisis may result in identity synthesis which is characterized by adhering to a set of coherent ideals and future goals, or alternatively, in sustained feelings of identity confusion in which a sense of purpose is lacking (Erikson, 1968).
To operationalize Erikson’s ideas on identity formation, the identity status paradigm was proposed by Marcia (1966) to identify behavioral markers of one’s underlying identity structure. Marcia focused on the decision-making processes of exploration (of different identity alternatives) and commitment (adhering to one or more identity alternatives). Marcia derived four identity statuses based on the levels of engagement in exploration and commitment: achievement (characterized by high commitment after high exploration), foreclosure (characterized by high commitment but without prior exploration), moratorium (high exploration and low commitment), and diffusion (low commitment and low exploration).
Due to societal changes in Western societies (e.g., prolonged education), young people may postpone long-term identity commitments (Arnett, 2000). Consequently, identity formation has been extended into emerging adulthood as individuals re-evaluate their prior commitments. These societal changes call for a rethinking of existing models. Luyckx et al., 2008 developed a dynamic process-oriented identity model with five processes to capture identity formation. According to this model, the search for one’s identity may start with a broad exploration of various identity alternatives (exploration in breadth), presumably followed by making identity choices (commitment making). Afterwards, these identity choices may be evaluated in-depth by discussing them with significant others or by considering personal values and standards (exploration in depth). Exploration in depth may result in identification with commitments, as the individual feels convinced about their commitments, or alternatively, the process can cycle back to renewed exploration if the individual does not identify with the commitments. However, some individuals continue to explore without engaging into long-term commitments and get stuck in their identity search. As such, this model distinguishes pro-active exploration (in breadth and in depth) from ruminative exploration which inhibits achieving a stable identity.
By using person-centered techniques on longitudinal data emerging from the dynamic process-oriented identity model, different identity trajectory classes resembling Marcia’s identity statuses could be identified. The advantage of this typological approach is that researchers could gain insight into subgroups of individuals, both those who are more resilient in their identity quest and those who experience more difficulties and are more vulnerable over time. This approach has already been used in community samples of adolescents (12–18 years at baseline), college students (17–29 years at baseline), and employees (21–40 years at baseline). Five identity trajectory classes have been consistently identified: achievement, foreclosure, moratorium, carefree diffusion, and troubled diffusion (Luyckx et al., 2013; Raemen et al., 2022). As expected, across studies, individuals in the achievement class displayed high scores on all identity processes, except for low scores on ruminative exploration. Individuals in the foreclosure class scored moderate to high on commitment processes (not as high as achievement) and low on all exploration processes. Individuals in the moratorium class scored low to moderate on commitment processes, and high on exploration processes. Individuals in the carefree diffusion class displayed low scores on commitment and pro-active exploration processes and moderate to low scores on ruminative exploration. Individuals in the troubled diffusion class scored low on commitment processes, low to moderate on exploration in depth and in breadth, and high on ruminative exploration. These identity trajectory classes were mainly based on consistent differences in initial levels of commitment and exploration processes (i.e., intercepts) and less so in rates of changes over time (i.e., slopes), as differences in slopes were less indicative to differentiate trajectory classes in a specific sample. Furthermore, previous studies have found significant differences in gender and age between the trajectory classes. With regard to gender, girls were more likely to be situated in statuses characterized by higher scores on pro-active and ruminative exploration processes (i.e., moratorium and troubled diffusion), whereas boys were more likely to be situated in statuses characterized by lower scores on exploration processes (i.e., foreclosure and carefree diffusion) (Raemen et al., 2022; Verschueren et al., 2017). With regard to age, older individuals were more likely to be situated in statuses characterized by higher levels of both commitment and pro-active exploration processes (i.e., especially achievement) (Raemen et al., 2022; Verschueren et al., 2017).
Given that the search for a personal identity can be accompanied by certain challenges and difficulties, the COVID-19 pandemic and its vast impact on everyday life may have made this developmental task even more demanding. Research worldwide has investigated adolescents’ mental health in relation to the pandemic and testified to the serious negative outcomes adolescents were confronted with (Jones et al., 2021). These studies have emphasized the specific vulnerability of adolescents, given that they are faced with the challenging task of constructing a personal identity. Given that one’s identity develops in close interaction with the social context and peers become increasingly important during this developmental stage, adolescents are highly sensitive to social interactions (Erikson, 1968; McElhaney et al., 2008). As such, adolescents’ mental health and their identity formation process could have been affected by the social isolation measures imposed during the pandemic (Cover, 2021).
Identity and the Body
Besides the process of identity formation, adolescents’ bodies undergo a range of apparent changes (Wertheim & Paxton, 2012). Adolescents go through these maturation processes whilst the opinion of others and social acceptation by peers becomes increasingly important (McElhaney et al., 2008). This may result in a heightened consciousness of the body and appearance, becoming a central aspect of adolescents’ lives. As a result, the prevalence of youth struggling with a negative body image is alarmingly high (Bucchianeri et al., 2013). Given that identity formation and body image both come to the fore during adolescence and emerging adulthood, theorists call for an increasing integration of both research fields (Daniels & Gillen, 2015). The current study aims to investigate the associations between identity and a range of interrelated body-related variables and processes that have been forwarded in multifactorial models such as Stice’s (2001) dual-pathway model. More specifically, in the current study, identity formation will be linked to the body perfect ideal upheld in society and the sociocultural pressures individuals may experience in attaining these ideals, the processes of self-objectification and appearance comparison, and, finally, body image and disturbed eating behaviors.
An important contributor to negative body image is the, often unrealistic, body perfect ideal youth are confronted with, typically encouraging girls to be thin and boys to be lean and muscular (Dittmar et al., 2007; Slater et al., 2012). These body perfect ideals are communicated through sociocultural pressures (e.g., media, parents, and peers), which may result in the internalization of appearance ideals (Thompson et al., 1999; Thompson & Stice, 2001). In the past years, research from various theoretical frameworks, such as the identity disruption model (Vartanian et al., 2018) and the identity styles model (Berzonsky, 1988), has revealed that identity formation in youth may impact the vulnerability to turn to appearance ideals. The identity disruption model linked negative early life experiences to body dissatisfaction and disordered eating via self-concept clarity (a concept closely related to identity diffusion) and sociocultural pressures. Results indicated that lower self-concept clarity was associated with higher internalization of appearance ideals and more frequent appearance comparisons, which were associated with greater body dissatisfaction. Greater body dissatisfaction, in turn, was associated with higher levels of disordered eating. From this perspective, individuals with low self-concept clarity are thought to be more vulnerable to turn to external sources to derive a sense of self (Vartanian et al., 2018). Relatedly, research from the identity styles framework indicated that adolescents who attach more importance to expectations and norms in their environment (i.e., the normative identity style) seemed more vulnerable to develop a rather maladaptive attitude towards beauty and eating. In contrast, adolescents who were information-oriented and engaged in pro-active identity exploration seemed to distance themselves from body perfect ideals and were therefore less vulnerable to internalizing these appearance ideals. In other words, individuals who actively search for information and are critical towards their environment (i.e., the information-oriented identity style) seemed less likely to turn to externally oriented identity building blocks which are provided by society (Verstuyf et al., 2014). In line with these findings, researchers have already stated that a healthy identity development may fulfill a protective role against appearance ideals internalization (Corning & Heibel, 2016).
Internalization of appearance ideals may lead to self-objectification, a self-perspective in which you look at your own body as an object and evaluate yourself based on its appearance (Lindner & Tantleff-Dunn, 2017). Previous findings demonstrated that self-objectification is a risk factor for various negative outcomes including body shame, body dissatisfaction, appearance anxiety, and disordered eating (Tiggemann, 2011). Little is known about the interplay between self-objectification and identity formation (Daniels & Gillen, 2015). However, theorists presume that self-objectified individuals may choose appearance-related identity alternatives, which may impact one’s choices concerning leisure activities (e.g., dance, gymnastics,…), education and profession (e.g., fashion, hostess job, hairdresser,…) (Calogero, 2011).
Self-objectification was found to be bidirectionally associated with appearance comparison (Lindner et al., 2012; Tylka & Sabik, 2010), a process in which adolescents compare their appearance to the appearance of others as a way to evaluate themselves (Festinger, 1954). As mentioned earlier, the identity disruption model indicated that individuals with low self-concept clarity were more susceptible to engage more frequently in appearance comparison to define their sense of self, which has been confirmed in other studies as well (Shahyad et al., 2018; Vartanian et al., 2018). When adolescents compare themselves to idealized media images or peers who are thought to be more attractive, appearance comparison may lead to negative outcomes, such as a negative body image (Yang et al., 2018). Negative body image is primarily characterized by body image disturbance (Burychka et al., 2021). Body image disturbance can be manifested in an underestimation or overestimation of body size (i.e., perceptual disturbance) and/or body dissatisfaction or overevaluation of body size and weight (i.e., affective disturbance) (Cornelissen et al., 2013; Dakanalis et al., 2016). However, body image is a multidimensional concept covering both negative and positive body image (Burychka et al., 2021). Positive body image was initially understood as the opposite concept of negative body image (Smolak, 2012; Tylka, 2012). However, a growing body of evidence points out that negative and positive body image are two distinct constructs (Tylka, 2018). Positive body image covers acceptance, respect, and favorable opinions towards one’s own body despite incongruences with media-promoted appearance ideals (Tylka & Wood-Barcalow, 2015a).
During the past decade, there has been a growing interest in the interplay between identity and body image (Daniels & Gillen, 2015). Erikson (1968) has already highlighted the intricate link between identity and one’s body in adolescence. During this developmental stage, the focus on one’s body and appearance may be so strong that it becomes a central identity aspect (Arnett, 2000). In line with this theorizing, recent studies have confirmed the salience of one’s body to define oneself as a person (Kling et al., 2018). One of the initial studies demonstrated a positive relationship between identity distress and negative body image (Kamps & Berman, 2011). Studies in adolescents revealed a positive association between identity processes (interpersonal exploration and commitment processes) and body esteem (Wängqvist & Frisén, 2013). Furthermore, decreasing body esteem predicted lowered identity coherence in emerging adulthood over time (Nelson et al., 2018). Further, identity functioning predicted body dissatisfaction over time, whereas body dissatisfaction also predicted maladaptive identity functioning over time (Palmeroni et al., 2020; Verschueren et al., 2018). Questions concerning the association between identity and positive body image, however, remain largely unanswered, indicating the need to address this topic.
Finally, negative body image is known to be a key element in the onset and maintenance of eating disorder symptoms, such as drive for thinness and bulimia (binge eating, purging) (Shagar et al., 2017). Eating disorder symptoms are highly prevalent in adolescence and contribute to the development and maintenance of clinical eating disorders (Croll et al., 2002). Theorists have forwarded identity formation as a contributing factor in the development and maintenance of eating disorder symptoms. Individuals searching for one’s identity may turn to eating disorder symptoms to define themselves, what may result in a more fragile identity (Corning & Heibel, 2016). Consequently, when the body is used to derive a sense of identity, this may result into the continuation of eating disorder symptoms to maintain this fragile personal identity (Cunningham et al., 2016; Verschueren et al., 2019). Otherwise, eating disorder symptomatology may also represent avoidance strategies to deal with identity-related difficulties (Wheeler et al., 2001). In a recent study, community adolescents who committed to their identity choices reported lower levels of drive for thinness and bulimia (Raemen et al., 2022). Previous studies in community adolescents further indicated that experiencing identity problems was associated with increased drive for thinness and bulimia (Palmeroni et al., 2020; Vartanian et al., 2018). Relatedly, patients with an eating disorder reported more identity problems compared to community controls (Verschueren et al., 2017). Furthermore, researchers have found an increasing amount of evidence for bidirectional effects between identity formation and eating disorder symptomatology (Palmeroni et al., 2021; Verschueren et al., 2019). In sum, identity formation and eating disorder symptomatology seem to reciprocally influence each other.
Current Study
Despite the fact that identity formation and body image both come to the fore during adolescence, integrative longitudinal research on this identity-body interplay in adolescents is lacking. The current study aimed to fill this gap by investigating the role of identity towards the body in adolescent boys and girls over time. The hypotheses and analyses of this study were preregistered at Open Science Framework. The first main goal was to investigate if the different identity trajectory classes that were found in previous studies could be replicated in the current study. Subsequently, since previous studies have found gender and age differences in identity formation, the current study explored whether there were gender and age differences among adolescents in different identity trajectory classes. Additionally, as drastic bodily changes and related weight change are prominent during adolescence, this study investigated if adolescents in different identity trajectory classes also differed on adjusted BMI at baseline. Second, this study aimed to investigate how these identity trajectory classes were related to differential development in negative and positive body image and various body-related variables (i.e., sociocultural pressures and internalization of appearance ideals, self-objectification, appearance comparison, and eating disorder symptoms).
Methods
Participants
A total of 403 students (52.1% female), with a mean age of 14.85 years (SD = 0.89; range 13–19) participated at Time 1. At Time 2, 329 students participated (retention rate = 81.64%); and at Time 3, 138 students participated (retention rate = 34.24%). Times 1 and 2 (early 2019 and, 2020, respectively) took place prior to the COVID-19 pandemic, Time 3 (early 2021) during the pandemic. Participants with and without complete data were compared using Little’s (1988) Missing Completely At Random (MCAR) test including all study variables at all three time-points simultaneously, which indicated that data were most likely missing completely at random (χ² = 800.49; p = 0.73). With regard to the preliminary analyses conducted in SPSS, The Expectation-Maximization (EM) algorithm was used to estimate missing data. With regard to the primary analyses conducted in MPLUS, the full information maximum likelihood (FIML) procedure (Muthén & Muthén, 2012) was used to handle cases with missing values (Enders, 2010).
Procedure
The data used in the current study were obtained in a longitudinal questionnaire study which was conducted at three annual measurement points between February 2019 and May 2021. The study was approved by the Social and Societal Ethics Committee of KU Leuven. Originally, students from four secondary schools in Flanders (Belgium) participated in the study, but data from only one school were used for the current paper, as the data collection in the other schools was not performed at all three measurement waves for logistic reasons and due to the COVID-19 pandemic. Prior to the data collection, all participants signed an informed consent form after receiving active parental consent which was required for minor participants. At Times 1 and 2, the data collection was conducted during school hours. All students filled out the self-report questionnaires and returned their completed questionnaires in a sealed envelope. Participants who were absent from school at the time of data collection were invited by e-mail to complete the questionnaires online (Qualtrics). At Time 3, data collection was done online using Qualtrics given that researchers were not allowed to collect data in schools due to the COVID-19 pandemic. At Times 2 and 3, students who had graduated or changed schools were also contacted by e-mail to participate online. Participants could win a voucher or a cinema ticket for their participation.
Measures
Adjusted body mass index
Based on students’ self-reported height and weight, their BMI (weight in kilogram/height*height in meters) was calculated. Given that the sample mainly included high school students under the age of 18 years, the adjusted BMI [(BMI/Percentile 50 of BMI for age and gender) × 100] was calculated based on the growth charts of a representative Flemish sample, to account for age and gender in the interpretation of BMI-scores.
Identity
Identity processes were assessed with the 25-item Dimensions of Identity Development Scale (DIDS; Luyckx et al., 2008). This questionnaire includes five subscales (exploration in breadth, exploration in depth, ruminative exploration, commitment making, and identification with commitment), each being measured by five items. All items were rated on a 5-point rating scale, ranging from 1 (completely disagree) to 5 (completely agree), and for each dimension mean scores were used. Example items are: ‘I think about the direction I want to take in my life’ (exploration in breadth), ‘I think about the future plans I have made’ (exploration in depth), ‘I keep looking for the direction I want to take in my life’ (ruminative exploration), ‘I decided on the direction I want to follow in life’ (commitment making), and ‘My plans for the future offer me a sense of security’ (identification with commitment). Cronbach’s alpha’s at Times 1, 2, and 3 were 0.83, 0.85, and 0.83, respectively, for exploration in breadth, 0.75, 0.82, and 0.78 for exploration in depth, 0.82, 0.85, and 0.82 for ruminative exploration, 0.88, 0.91, and 0.96 for commitment making, and 0.86, 0.88, and 0.88 for identification with commitment.
Body image
Negative body image or body dissatisfaction was evaluated by the body dissatisfaction subscale of the Eating Disorder Inventory-3 (EDI-3; Garner, 2004), which gives an indication of the degree to which an individual feels unsatisfied with his/her own body shape and believes that certain body areas are too large or big. The scale consists of 9 items that were rated on a 6-point Likert scale ranging from 1 (never) to 6 (always). An example item is: ‘I think that my stomach is too big’. Cronbach’s alpha’s were 0.90, 0.90, and 0.91 at Times 1, 2, and 3 respectively. Positive body image was assessed with the Body Appreciation Scale-2 (BAS-2; Tylka & Wood-Barcalow, 2015a). Positive body image entails favorable opinions towards one’s body, acceptance of one’s body despite incongruences with body perfect ideals, body competence, and integrity and respect towards the body (Tylka & Wood-Barcalow, 2015a). This scale consists of 10 items, which were rated on a 5-point Likert-scale ranging from 1 (never) to 5 (always). An example item is: ‘I respect my body’. Cronbach’s alpha’s at Times 1, 2, and 3 were 0.92, 0.94, and 0.94, respectively.
Sociocultural pressures and internalization of societal appearance ideals
Sociocultural pressures and internalization processes were assessed with the 22-item Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4; Schaufer et al., 2015). The questionnaire includes five subscales, of which three subscales address the perceived appearance pressures from family, parents and media and two subscales address internalization of societal appearance ideals: internalization of the thin ideal and internalization of the muscular ideal. Each of the first three subscales consists of four items scored on a 5-point Likert scale ranging from 1 (definitely disagree) to 5 (definitely agree). Each of the last two subscales consists of 5 items, rated on a 5-point Likert scale ranging from 1 (definitely disagree) to 5 (definitely agree). The current study focused on the total scale score of the first three subscales, representing sociocultural pressures in general, and distinct scale scores for internalization of appearance ideals. Example items are: ‘I feel pressure from my peers to improve my appearance’ (sociocultural pressures), ‘I want my body to look very thin’ (internalization of the thin ideal), and ‘It is important for me to look athletic’ (internalization of the muscular ideal). Cronbach’s alpha’s at Times 1, 2, and 3 were 0.90, 0.89, and 0.91, respectively, for sociocultural pressures, 0.90, 0.90, and 0.93 for internalization of the thin ideal, and 0.91, 0.90, and 0.90 for internalization of the muscular ideal.
Self-objectification
The process of self-objectification was measured by the Self-Objectification Beliefs and Behaviors Scale (SOBBS; Lindner & Tantleff-Dunn, 2017), which gives an indication of the degree to which an individual internalizes an observer’s perspective on the body and values the appearance of the body over physical abilities and what one thinks and feels. The scale consists of 14 items that were rated on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). An example item is: ‘Looking attractive to others is more important to me than being happy with who I am inside’. Cronbach’s alpha’s at Times 1, 2, and 3 were 0.91, 0.91, and 0.92, respectively.
Appearance comparison
The process of appearance comparison was evaluated by the five-item Physical Appearance Comparison Scale (PACS; Thompson et al., 1991). Items were rated on a 5-point Likert scale ranging from 1 (never) to 5 (always). An example item is: ‘At parties or other social events, I compare my physical appearance to the physical appearance of others’. Cronbach’s alpha’s were 0.80, 0.77, and 0.80 at Times 1, 2, and 3, respectively.
Eating disorder symptoms
Drive for thinness and bulimia were measured by means of the Eating Disorder Inventory-3 (EDI-3; Garner, 2004), which is a valid and reliable survey for questioning eating disorder symptomatology in non-clinical populations (Van Strien & Ouwens, 2003). The two symptom scales that were included, drive for thinness and bulimia, measure some of the central characteristics of an eating disorder. Each scale included 7 items and all items were scored on a 6-point Likert scale ranging from 1 (never) to 6 (always). Example items are: ‘I feel extremely guilty after overeating’ (drive for thinness) and ‘I eat when I am upset’ (bulimia). Cronbach’s alpha’s at Times 1, 2, and 3 were 0.91, 0.92, and 0.93, respectively, for drive for thinness, and 0.78, 0.78, and 0.88 for bulimia.
COVID-19
The impact of the COVID-19 pandemic at T3 of the data collection was assessed with two sets of seven self-constructed items. The first set of items assessed the pandemic’s negative and/or positive influence on different life aspects (e.g., social life, physical and mental health etc.), rated on a scale from -3 (strong negative impact) to +3 (strong positive impact). The second set of items measured the pandemic’s influence on a person’s negative affect (e.g., I feel scared), rated on a 7-point Likert scale ranging from 1 (completely disagree) to 7 (completely agree). Cronbach’s alpha’s were 0.81 and 0.86, respectively. Exploratory factor analysis (EFA) indicated a one-factor solution based on the eigenvalues and a scree plot for each set of seven items. The factor which contained the first set of items explained 48.25% of the variance with factor loadings from 0.511 to 0.881. The factor which contained the second set of items explained 54.58% of the variance with factor loadings from 0.517 to 0.810.
Statistical Analyses
First, it was investigated if the study variables were related to missing data. Of the 403 adolescents who entered the study, 138 participated at the final measurement wave (133 participants participated at all time-points, 178 missed 1 time-point, and 92 missed 2 time-points). To address differential attrition, a quasi-Poisson regression analysis was conducted to predict the number of missed waves by gender, age, COVID-19 variables, and main study variables. Only the demographic variables gender and age were associated with missingness, with both male gender (B = 0.447, p < 0.001) and higher age (B = 0.176, p = 0.003) being associated with a higher number of missed waves.
Second, latent class growth analysis (LCGA) on all five identity processes simultaneously was used to identify identity trajectory classes (Luyckx et al., 2013). The path from the linear slope to the indicator at Time 1 was fixed to 0 so that the mean intercept would represent the initial mean level. Given the equally spaced measurement intervals, subsequent linear slope pattern coefficients were fixed at 1, and 2 for Time 2 and Time 3, respectively. To account for non-normality, the models were estimated with maximum likelihood estimation with robust standard errors (MLR). LCGA solutions with one to six classes were estimated. Several criteria were used to decide on the number of classes (Masyn, 2013). These criteria did not always clearly indicate a single best-fitting model. Hence, it was important to balance objective fit with parsimony and interpretability to arrive at a meaningful solution (Johnson et al., 2007). First, the Akaike Information Criterion (AIC)1, the Bayesian information criterion (BIC), and the sample size-adjusted BIC (SABIC) for a solution with k classes had to be lower (at least 10 points; Kass & Raftery, 1995) than for a solution with k-1 classes, suggesting that adding classes improved model fit. Second, classification quality was assessed by entropy (E), a standardized summary measure of classification accuracy. Entropy ranges from 0.00 to 1.00, with values of 0.75 or higher indicating accurate classification (Reinecke, 2006). Third, a significant p-value for the Lo-Mendell-Rubin likelihood ratio test (LMR-LRT) and the bootstrap likelihood ratio test (BLRT) indicated added value of k classes over k-1 classes. Finally, the theoretical interpretability and meaningfulness of the classes were evaluated. If a solution with k classes emerged in which certain classes were difficult to interpret or did not add a meaningful class as compared to the more parsimonious solution with k-1 classes, the latter, more parsimonious solution was chosen. In line with this reasoning, all classes had to include at least 5% of the sample.
Third, assuming that the classification accuracy of the selected class solution was adequate, individuals were assigned to the trajectory class for which their posterior probability of group membership was highest (Luyckx et al., 2011). Age, adjusted BMI, and gender differences at baseline among the trajectory classes were examined. For age and adjusted BMI, a one-way multivariate analysis of variance (class membership as fixed factor and adjusted BMI/age as dependent variables) was performed with Tukey HSD post-hoc tests. For gender, a chi² cross-tabulation was performed and standardized residuals were inspected to determine significant discrepancies between observed and expected frequencies within each cell (i.e., an absolute value exceeding |2|).
Next, to examine whether the classes differed in their developmental trajectories of body-related variables and symptoms, multigroup latent growth curve (LGC) modeling was used. First, unconstrained LGC models with intercepts and linear slopes (again estimated using MLR and with linear slope terms fixed to 0, 1, and 2) freely estimated across identity trajectory classes were estimated for each outcome variable separately, resulting in nine unconstrained models. Adequate model fit was reflected by a root mean square error of approximation (RMSEA) below 0.08, a standardized root mean square residual (SRMR) below 0.10, a comparative fit index (CFI) above 0.90, and a χ²-value as small as possible (given that models were estimated using the MLR estimator, this study focused on the Yuan-Bentler scaled chi²). Next, the models were re-estimated with intercepts constrained equal across classes; and finally, slopes were constrained equal across classes. If these constrained models provided a significantly poorer fit to the data compared to the baseline unconstrained model (χ²-values of the constrained vs. unconstrained models were compared), these findings suggested that the trajectory classes differed from one another on at least some of the parameters tested. As a result, follow-up multigroup models estimated which intercepts or slopes could be held equal across each possible pair of classes. As such, it could be determined which specific trajectories differed from one another in terms of mean intercepts and slopes (Raymaekers et al., 2020).
Finally, exploratory analyses2 were conducted to examine whether identity development was associated with the impact of the COVID-19 pandemic (assessed at Time 3). Associations between identity development and the impact of COVID-19 were examined by conducting a multivariate analysis of variance (MANOVA) with the identity trajectory classes as fixed factor. As follow-up exploratory analyses, univariate LGC modeling was performed on the five identity dimensions to assess how the latent trajectories of these dimensions were related to COVID-19 measures. In doing so, intercepts and slopes of the identity dimensions (with the intercept being set at the final time-point by fixing the linear slope terms to −2, −1, and 0 for Times 1-3, respectively) were regressed on the items related to COVID-19.
Results
Preliminary Analyses
Table 1 presents means and standard deviations at the three time-points. Table 2 provides Pearson correlations at Times 1-3. Commitment making was significantly positively associated with drive for thinness at Time 1. Identification with commitment was negatively related to drive for thinness at Time 1 and Time 3, to bulimia and sociocultural pressures at Time 1, to internalization of the thin ideal, appearance comparison, and self-objectification at Time 1 and Time 2, and to negative body image at each time-point. Identification with commitment was positively related to positive body image at each time-point. Exploration in breadth was positively associated with drive for thinness and internalization of the muscular ideal at Time 1 and Time 2, with sociocultural pressures and self-objectification at Time 2, with internalization of the thin ideal at Time 1 and Time 3, and with appearance comparison at each time-point. Exploration in depth was positively related to internalization of the thin ideal at Time 1 and the muscular ideal at Time 2, and to drive for thinness, bulimia, sociocultural pressures, appearance comparison, and self-objectification at Time 1 and Time 2. Finally, ruminative exploration was positively related to all outcome variables at each time point, except for a negative relationship with positive body image.Table 1 Descriptive Statistics of Study Variables at Times 1-3
Time 1 Time 2 Time 3
Variable M (SD) M (SD) M (SD)
Commitment making 3.37 (0.86) 3.32 (0.90) 3.18 (1.08)
Identification commitment 3.37 (0.78) 3.31 (0.82) 3.41 (0.72)
Exploration breadth 3.48 (0.78) 3.63 (0.73) 3.80 (0.64)
Exploration depth 3.06 (0.78) 3.13 (0.84) 3.49 (0.74)
Ruminative exploration 2.73 (0.88) 2.82 (0.91) 3.06 (0.87)
Drive for thinness 2.42 (1.24) 2.41 (1.27) 2.64 (1.33)
Bulimia 1.96 (0.80) 2.08 (0.86) 2.11 (0.98)
Negative body image 3.03 (1.23) 3.07 (1.81) 3.19 (1.18)
Positive body image 3.48 (0.82) 3.53 (0.83) 3.49 (0.80)
Sociocultural pressures 1.88 (0.92) 1.92 (0.87) 2.26 (0.99)
Internalization thin ideal 2.76 (1.32) 2.83 (1.34) 3.07 (1.41)
Internalization muscular ideal 2.88 (1.23) 2.90 (1.20) 2.90 (1.15)
Appearance comparison 2.62 (0.93) 2.71 (0.87) 2.92 (0.86)
Self-objectification 2.64 (0.77) 2.67 (0.76) 2.86 (0.75)
Table 2 Pearson correlation coefficients between Identity Processes and Body-related variables at Times 1-3
Commitment making Identification with commitment Exploration in breadth Exploration in depth Ruminative exploration
Variable
Drive for thinness
T1 0.10* −0.14** 0.12* 0.15** 0.30**
T2 0.07 −0.08 0.14* 0.18** 0.17**
T3 0.04 −0.18* 0.13 0.02 0.24**
Bulimia
T1 −0.03 −0.17** 0.06 0.14** 0.35**
T2 0.05 −0.07 0.10 0.15** 0.23**
T3 0.04 −0.16 0.08 0.12 0.29**
Negative body image
T1 0.00 −0.26** 0.04 0.06 0.33**
T2 −0.07 −0.26** −0.04 −0.01 0.18**
T3 0.01 −0.24** 0.11 −0.05 0.25**
Positive body image
T1 0.06 0.31** 0.05 0.05 −0.34**
T2 0.06 0.27** 0.04 0.04 −0.19**
T3 0.05 0.28** 0.00 0.14 −0.28**
Sociocultural pressures
T1 0.05 −0.13** 0.06 0.18** 0.32**
T2 0.08 −0.05 0.15** 0.15** 0.22**
T3 0.04 −0.11 0.08 0.07 0.24**
Internalization of thin app
ideal
T1 0.02 −0.19** 0.15** 0.11* 0.32**
T2 −0.06 −0.16** 0.04 0.10 0.24**
T3 0.02 −0.12 0.18* 0.07 0.26**
Internalization of Muscular ideal idideal
muscular ideal
T1 0.06 0.01 0.12* 0.08 0.17**
T2 0.11 0.08 0.16** 0.15** 0.16**
T3 0.07 0.11 0.15 0.11 0.20*
Appearance comparison
T1 −0.05 −0.14** 0.13** 0.14** 0.31**
T2 −0.07 −0.11* 0.15** 0.20** 0.26**
T3 −0.10 −0.15 0.18* 0.10 0.36**
Self-objectification
T1 0.01 −0.16** 0.08 0.17** 0.37**
T2 −0.01 −0.15** 0.11* 0.18** 0.30**
T3 −0.05 −0.16 0.15 0.02 0.37**
*p < 0.05, **p < 0.01, ***p < 0.001
Identifying Identity Trajectory Classes
Table 3 presents the results of LCGA on the five identity dimensions, including all AIC, BIC, SABIC, entropy, LMR-LRT, and BLRT values, as well as the trajectory group prevalence. Because of a lower AIC, BIC, and SABIC value, the four-class solution (AIC = 9365.235; BIC = 9597.174; SABIC = 9413.134) was preferred over the three-class solution (AIC = 9539.072; BIC = 9727.022; SABIC = 9577.887). The four-class solution had an adequate entropy value (E = 0.809) and although the LMR-LRT value of the four-class solution was not significant (p = 0.173), the BLRT-value was significant (p < 0.001). Additionally, in the five-class solution, one of the classes consisted of only 6% of the sample and the classes were theoretically more difficult to interpret. Hence, the more parsimonious four-class solution was chosen.Table 3 Results of Latent Class Growth Analysis on the Five Identity Dimensions
Trajectory Group Prevalence (%)
AIC BIC SABIC Entropy LMR-LRT BLRT 1 2 3 4 5 6
1 Class 10488.713 10588.686 10509.359 / / / 100
2 Class 9777.829 9921.791 9807.559 0.786 p < 0.001 < 0.001 46 54
3 Class 9539.072 9727.022 9577.887 0.784 p = 0.080 < 0.001 27 26 47
4 Class 9365.235 9597.174 9413.134 0.809 p = 0.173 < 0.001 35 27 29 9
5 Class 9240.253 9516.180 9297.236 0.809 p = 0.099 < 0.001 21 25 16 32 6
6 Class 9185.968 9505.883 9252.035 0.831 p = 0.049 < 0.001 5 38 9 23 3 22
AIC Akaike Information Criterion, BIC Bayesian Information Criterion, SABIC Sample size-adjusted BIC, LMR-LRT Lo-Mendell-Rubin Likelihood Ratio Test, BLRT Bootstrapped Likelihood Ratio Test. The four class solution (in italics) was selected
Table 4 provides the estimates of mean intercepts and mean slopes for all trajectory classes of the four-class solution. Partially in line with hypotheses, class 1 (35%) resembled achievement and included adolescents scoring relatively high on both commitment and exploration processes, except for ruminative exploration. Whereas identity processes remained rather stable over time, exploration in breadth tended to increase over time. Class 2 (27%) was labeled carefree diffusion and consisted of adolescents scoring relatively low to moderate on all dimensions. All identity processes remained rather stable over time. Class 3 (29%) resembled moratorium and included adolescents scoring relatively low on both commitment processes and high on all exploration processes. Both pro-active as well as ruminative exploration processes tended to increase over time. Finally, class 4 (9%) resembled troubled diffusion and consisted of adolescents scoring low on all identity processes, except for ruminative exploration. All three exploration dimensions substantially increased over time, hence this class was labeled more specifically as troubled diffusion-increasing exploration.Table 4 Parameter Estimates of the Four Class Solution
Total sample Identity Trajectory Class
Parameters Achievement Carefree diffusion Moratorium Troubled diffusion-increasing exploration
Commitment making
mean intercept 3.382*** 4.072*** 3.274*** 3.052*** 2.128***
mean slope −0.084** −0.072 −0.093 −0.074 −0.170
Identification commitment
mean intercept 3.354*** 4.008*** 3.254*** 3.030*** 2.200***
mean slope 0.007 −0.048 0.009 0.035 0.077
Exploration in breadth
mean intercept 3.480*** 3.893*** 2.982*** 3.729*** 2.630***
mean slope 0.160*** 0.097* 0.054 0.119* 0.571***
Exploration in depth
mean intercept 3.028*** 3.560*** 2.545*** 3.134*** 2.089***
mean slope 0.194*** 0.121 0.110 0.215*** 0.366*
Ruminative exploration
mean intercept 2.714*** 2.472*** 2.351*** 3.275*** 2.940***
mean slope 0.152*** 0.103 0.015 0.141* 0.571***
*p < 0.05, **p < 0.01, ***p < 0.001
Further analyses indicated that the classes did not differ on age at Time 1 (F(3) = 2.27, p = 0.08), but differed on gender (χ²(3) = 20.16, p < 0.001). Based on an inspection of the standardized residuals, male adolescents were significantly overrepresented in the carefree diffusion class (61.1% boys), whereas female adolescents were overrepresented in the moratorium class (67.5% girls). Finally, the classes did not differ on adjusted BMI (F(3) = 0.400, p = 0.75).
Associations with Body Image and Body-Related Symptoms
Table 5 provides all the baseline parameter estimates of multigroup LGC modeling. For sociocultural pressures, an adequate fit was found for the unconstrained model [χ²(8) = 13.21, p = 0.10; RMSEA = 0.08; CFI = 0.97; SRMR = 0.05]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(5) = 41.19, p < 0.001], indicating that the classes differed from one another on initial levels of sociocultural pressures. Adolescents in carefree diffusion experienced significantly lower levels of sociocultural pressures compared to adolescents in the other classes. Further, although levels of sociocultural pressures increased significantly in achievement and troubled diffusion-increasing exploration, model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(5) = 6.47, p = 0.26], indicating that the classes did not differ from one another in terms of changes over time.Table 5 Baseline Parameter Estimates of Multigroup Latent Growth Curve Modeling
Identity Trajectory Class
Parameters Achievement Carefree diffusion Moratorium Troubled diffusion-increasing exploration
Drive for thinness
Mean intercept 2.458***b 2.016***a 2.660***b 2.579***b
Mean slope 0.069 −0.014 0.070 0.059
Bulimia
Mean intercept 1.925***ac 1.761***a 2.230***b 2.016***bc
Mean slope 0.095* 0.002 0.108* 0.032
Negative body image
Mean intercept 2.905***a 2.709***a 3.325***b 3.486***b
Mean slope 0.070 −0.028 0.010 0.039
Positive body image
Mean intercept 3.619***b 3.600***b 3.357***a 3.127***a
Mean slope 0.017 0.077 0.034 0.014
Sociocultural pressures
Mean intercept 1.885***b 1.526***a 2.117***b 1.921***b
Mean slope 0.163*** 0.058 0.079 0.203*
Internalization thin ideal
Mean intercept 2.770***b 2.284***a 3.047***b 3.062***b
Mean slope 0.112 0.011 0.046 0.193
Internalization muscular ideal
Mean intercept 2.988*** 2.781*** 2.948*** 2.663***
Mean slope 0.104 0.035 −0.009 −0.096
Physical appearance comparison
Mean intercept 2.598***b 2.262***a 2.946***c 2.717***bc
Mean slope 0.103bc 0.000ab −0.023a 0.223**c
Self-objectification
Mean intercept 2.645***b 2.332***a 2.872***c 2.744***bc
Mean slope 0.062 0.080 0.002 0.142
Within rows, intercepts and slopes differ at p < 0.05 if they have different superscripts (letters a, b, or bc). Parameters without superscripts do not differ significantly from one another. *p < 0.05, **p < 0.01, ***p < 0.001
For internalization of the thin ideal, the unconstrained model did not provide an adequate fit across all indices [χ²(6) = 15.94, p = 0.01; RMSEA = 0.13; CFI = 0.95; SRMR = 0.10]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 28.45, p < 0.001], indicating that the classes differed from one another on initial levels of internalization of the thin ideal. Adolescents in carefree diffusion were less likely to internalize the thin ideal compared to adolescents in the other classes. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 0.36, p = 0.95], indicating that the classes did not differ from one another in terms of changes over time.
For internalization of the muscular ideal, the unconstrained model provided, except for the SRMR-value, an adequate fit [χ²(6) = 7.64, p = 0.27; RMSEA = 0.05; CFI = 0.99; SRMR = 0.11]. Analyses indicated that both intercepts and slopes could be constrained as equal among the classes [Δχ²(3) = 2.87, p = 0.41; Δχ²(3) = 1.63, p = 0.65], indicating that the classes did not differ from one another on initial levels of internalization of the muscular ideal or in terms of changes over time.
For self-objectification, the unconstrained model provided, except for the SRMR-value, an adequate fit [χ²(7) = 10.14, p = 0.18; RMSEA = 0.07; CFI = 0.98; SRMR = 0.14]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 32.60, p < 0.001], indicating that the classes differed from one another on initial levels of self-objectification. Adolescents in achievement reported significantly lower levels of self-objectification compared to moratorium, whereas adolescents in carefree diffusion reported the lowest levels of self-objectification. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 1.11, p = 0.78], indicating that the classes did not differ from one another in terms of changes over time.
For appearance comparison, an adequate fit was found for the unconstrained model [χ²(9) = 2.82, p = 0.97; RMSEA = 0.00; CFI = 1.00; SRMR = 0.03]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 42.71, p < 0.001], indicating that the classes differed from one another on initial levels of appearance comparison. Adolescents in achievement reported significantly lower levels of appearance comparison than in moratorium, whereas adolescents in carefree diffusion reported the lowest levels of appearance comparison. Constraining slopes as equal among classes resulted in a significantly decreased model fit as well [Δχ²(3) = 7.93, p = 0.05], indicating that the classes differed from one another in terms of changes over time. Appearance comparison increased significantly more over time for adolescents in achievement compared to adolescents in moratorium. Adolescents in troubled diffusion-increasing exploration experienced the largest increases in appearance comparison, with changes over time significantly different from those in moratorium and carefree diffusion.
For negative body image, an adequate fit was found for the unconstrained model [χ²(6) = 2.86, p = 0.83; RMSEA = 0.00; CFI = 1.00; SRMR = 0.03]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 25.94, p < 0.001], indicating that the classes differed from one another on initial levels of negative body image. Adolescents in achievement and carefree diffusion experienced significantly lower levels of negative body image compared to adolescents in moratorium and troubled diffusion-increasing exploration. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 1.79, p = 0.62], indicating that the classes did not differ from one another in terms of changes over time.
For positive body image, an adequate fit was found for the unconstrained model [χ²(7) = 11.48, p = 0.12; RMSEA = 0.08; CFI = 0.98; SRMR = 0.07]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 16.24, p < 0.001], indicating that the classes differed from one another on initial levels of positive body image. Adolescents in achievement and carefree diffusion experienced significantly higher levels of positive body image compared to adolescents in moratorium and troubled diffusion-increasing exploration. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 0.48, p = 0.92], indicating that the classes did not differ from one another in terms of changes over time.
For drive for thinness, an adequate fit was found for the unconstrained model [χ²(7) = 8.44, p = 0.30; RMSEA = 0.05; CFI = 0.99; SRMR = 0.04]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(3) = 20.56, p < 0.001], indicating that the classes differed from one another on initial levels of drive for thinness. Adolescents in carefree diffusion reported significantly lower levels of drive for thinness compared to the other classes. Model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(3) = 2.89, p = 0.41], indicating that the classes did not differ from one another in terms of changes over time.
Finally, for bulimia, an adequate fit was found for the unconstrained model [χ²(6) = 6.64, p = 0.36; RMSEA = 0.03; CFI = 1.00; SRMR = 0.05]. Constraining intercepts as equal among classes resulted in a significantly decreased model fit [Δχ²(2) = 25.20, p < 0.001], indicating that the classes differed from one another on initial levels of bulimia. Adolescents in achievement reported significantly lower levels of bulimia compared to moratorium, whereas adolescents in carefree diffusion scored lower compared to moratorium and troubled diffusion-increasing exploration. Further, although bulimia increased significantly for adolescents in achievement and moratorium, model comparison indicated that slopes could be constrained as equal among the classes [Δχ²(2) = 5.50, p = 0.06], indicating that the classes did not differ from one another in terms of changes over time.
Associations with the Impact of the COVID-19 Pandemic
Given that the items assessing the pandemic’s influence on different life aspects showed non-significant correlations with the identity dimensions, only the results regarding the items assessing the pandemic’s influence on a person’s negative affect are discussed. With regard to the associations between identity development and the impact of COVID-19, significant differences between the identity classes on the impact of COVID-19 on a person’s negative affect were found (F = 10.858, p < 0.001, η2 = 0.194). Post-hoc analyses indicated that adolescents in carefree diffusion (M = 3.19; SD = 1.35) experienced the least influence by COVID-19 on their negative affect as compared to adolescents in achievement (M = 4.21; SD = 1.35), moratorium (M = 4.65; SD = 0.94), and troubled diffusion-increasing exploration (M = 4.78; SD = 0.59) (p < 0.05). Finally, Table 6 shows positive associations between the initial levels of all exploration processes and changes over time in ruminative exploration with the impact of COVID-19 on negative affect.Table 6 Beta regression coefficients of the Identity Processes regressed on COVID-19 items and values of explained variances
Impact of COVID-19
ß R2
Commitment making
mean intercept −0.17 0.03
mean slope −0.21 0.18
Identification commitment
mean intercept −0.10 0.02
mean slope −0.05 0.08
Exploration in breadth
mean intercept 0.33** 0.10
mean slope 0.08 0.01
Exploration in depth
mean intercept 0.28* 0.07
mean slope −0.01 0.00
Ruminative exploration
mean intercept 0.54*** 0.31***
mean slope 0.27* 0.10
*p < 0.05, **p < 0.01, ***p < 0.001
Discussion
According to Erikson (1968), feeling at home in one’s body is crucial to developing a strong personal identity. During the past decade, research findings have supported Erikson’s theoretical thinking and pointed out the complex interplay between identity and the body. However, research on personal identity and one’s body has developed mainly in isolation and has primarily focused on negative body image (Daniels & Gillen, 2015; Nelson et al., 2018). To broaden the understanding of the link between identity and one’s body, the current study examined identity trajectory classes throughout adolescence and investigated how these identity trajectory classes were associated with differential development in negative and positive body image and body-related variables. Four identity trajectory classes emerged, partially in line with expectations. Additionally, evidence was found for the developmental association linking identity formation to adolescents’ body image and body-related variables. These results emphasize the need to target adolescents struggling with their identity development, as they may be more vulnerable for body image problems and other body-related symptoms.
Identity Trajectory Classes throughout Adolescence
Partially consistent with previous studies (Luyckx et al., 2013; Raemen et al., 2022), four identity trajectory classes were identified: achievement, carefree diffusion, moratorium, and troubled diffusion-increasing exploration. Although identity trajectory classes were differentiated primarily in terms of initial levels of the identity dimensions, some differential changes over time were also observed. Interestingly, relatively high and/or increasing levels of exploration were uncovered in the identity trajectory classes, which was in contrast with previous findings. This finding might be explained by the younger age group of this study and the COVID-19 pandemic at Time 3, as initial levels of all exploration processes and changes over time in ruminative exploration were associated with the impact of COVID-19. It is plausible that adolescents became more self-doubting and questioning due to the pandemic, as their known identity building blocks (e.g., hobbies, contact with peers, etc.) were substantially affected, for instance, by lockdown measures. Further, the current study could not identify a separate foreclosure trajectory class. However, readers should note that adolescents in carefree diffusion made commitments to a certain degree, somewhat resembling characteristics of foreclosed individuals. However, the levels of their commitment processes were not elevated enough to label this class as foreclosure. Importantly, it is not uncommon that not all identity trajectory classes are identified in each specific study (see, e.g., the study by Hatano & Sugimura (2017) that also did not identify a longitudinal foreclosure class), possibly due to sample characteristics or context-specific factors such as the COVID-19 pandemic (Fig. 1).Fig. 1 Observed mean trends for the five identity processes in the identified identity trajectory classes. CM Commitment making, IC Identification with commitment, EB Exploration in breadth, ED Exploration in depth, RE Ruminative exploration. “*” indicates significant changes over time
First, with respect to the four trajectory classes obtained, and in line with previous longitudinal research (Luyckx et al., 2013; Raemen et al., 2022), adolescents in the achievement trajectory class pro-actively explored identity options and they were able to make strong commitments and identify with these commitments, without being inhibited by ruminative exploration. Although these adolescents identified with their identity choices, they increasingly kept exploring their identity options in breadth over time. Based on their engagement in commitment and pro-active exploration processes, this achievement trajectory class seemed to be a prime example of an adaptive identity search (Schwartz et al., 2011).
Second, also in line with previous research, adolescents in the carefree diffusion trajectory class developed tentative commitments to a certain degree, but without systematically exploring different identity options. They seemed unmotivated to fully engage themselves in their identity quest (Schwartz et al., 2011). These carefree-diffused adolescents also did not seem to ruminate about their identity search.
Third, as expected, adolescents in the moratorium trajectory class kept exploring different identity options in breadth and in depth, without making strong commitments or identifying with these choices. Adolescents in moratorium seemed to worry about their tentative commitments and their search for alternative identity building blocks. In terms of changes over time, they increasingly explored identity options in both an adaptive and maladaptive way. This moratorium trajectory class may reflect less adaptive identity functioning to some extent, as these adolescents seemed to lack a strong identity foundation (Schwartz et al., 2016).
Finally, an identity trajectory class resembling troubled diffusion-increasing exploration was identified. As expected, troubled-diffused adolescents worried about identity issues, hindering them from adequate identity work, as indicated by limited engagement in pro-active exploration and commitment processes. Whereas carefree-diffused adolescents seemed unmotivated to engage in identity development, troubled-diffused adolescents seemed to be unable to translate their worries into a proactive identity search. However, in contrast to expectations (Luyckx et al., 2013; Raemen et al., 2022), troubled-diffused adolescents increasingly tried to explore identity options in breadth and in depth over time. In other words, they tried to engage proactively in their identity quest, but at the same time they felt overwhelmed by this process (Schwartz et al., 2011). Consequently, based on these substantial increases in exploration processes over time, this trajectory class was labeled as troubled diffusion-increasing exploration. These increasing levels of exploration might again be linked to the COVID-19 pandemic. Although troubled-diffused individuals did not differ from adolescents in achievement and moratorium on the impact of COVID-19, troubled-diffused adolescents reported the strongest impact of COVID-19 on their negative affect. Moreover, increases over time in ruminative exploration were positively associated with the impact of COVID-19, meaning that the stronger someone experienced impact of the pandemic, the more someone was likely to ruminate about life choices, and vice versa.
Subsequently, results showed gender differences among the identity classes at Time 1, as female adolescents were overrepresented in moratorium and male adolescents were overrepresented in carefree diffusion, as expected (Raemen et al., 2022; Verschueren et al., 2017). Further, as expected, the identity trajectory classes did not differ on adjusted BMI, indicating that the evaluation of the body (i.e., body image) might be a more important factor to identity functioning than body shape in itself (Nelson et al., 2018). Finally, in contrast with previous research (Raemen et al., 2022; Verschueren et al., 2017), no age differences were found among the identity trajectory classes. This finding might be explained by the younger age group, as there might be more differentiation at a slightly older age (Luyckx et al., 2013). Late adolescence and emerging adulthood indeed offer many opportunities for pro-active identity exploration in various domains of life, possibly resulting in more inter-individual differences (Arnett, 2000).
Identity Trajectory Classes and Differential Development in Body Image and Body-Related Variables
The results provided a nuanced picture of the co-development of identity and the body, and findings were dependent on which specific body-related variables the study focused on. In line with expectations, the levels of negative and positive body image and body-related variables differed among identity trajectory classes. These findings suggested that adolescents in identity trajectory classes reflecting less adaptive identity functioning, such as moratorium and troubled diffusion-increasing exploration, displayed higher levels of negative body image and body-related symptoms and lower levels of positive body image. Although class differences were primarily found on the initial levels of the external variables, some differential changes over time were also observed.
In line with hypotheses, adolescents in moratorium and troubled diffusion-increasing exploration showed the least adaptive functioning. In addition to their arduous identity search, they seemed more vulnerable to sociocultural pressures and internalization of the thin ideal. Consistent with previous research (Corning & Heibel, 2016), these findings seem to indicate that adolescents who are lacking a strong identity foundation and get stuck in ruminatively exploring different identity options, are more prone to internalize appearance ideals (and especially the thin ideal) to derive a sense of identity. In line with this tenet, these adolescents seemed also more likely to self-objectify and engage in appearance comparison to evaluate themselves. These findings can also be understood from the identity styles model which focuses on individual differences in cognitive styles underlying the identity exploration process (Berzonsky, 1988). Especially the diffuse-avoidant identity style, in which individuals adopt an evasive and procrastinatory orientation toward decision making, is associated with internalizing appearance ideals. In line with this, adolescents in moratorium and troubled diffusion-increasing exploration seemed to avoid or procrastinate their identity choices by continuing to ruminatively explore identity options without making strong commitments. As a result, these adolescents may turn to the body perfect ideal in the expectation that they will achieve happiness and success when they reach this ideal or as a way to avoid coping with their identity issues (Verstuyf et al., 2014; Wheeler et al., 2001). Moreover, troubled-diffused adolescents seemed vulnerable to increasingly engage in appearance comparison over time, which might be associated with their strong increases in pro-active and ruminative exploration over time. Because these adolescents lack a stable sense of identity when they begin to increasingly explore identity alternatives, they may be even more vulnerable to being guided by extrinsic goals and societal ideals, resulting in increased engagement in appearance comparison (Duriez et al., 2012). Subsequently, adolescents in these identity trajectory classes experienced higher levels of negative body image and lower levels of positive body image, confirming the established interplay between identity and one’s body image (Palmeroni et al., 2020; Verschueren et al., 2018). Interestingly, given that the interplay between identity and adolescents’ positive body image is still understudied, these findings suggested that identity formation indeed might be associated with one’s positive body image as well. Finally, adolescents in moratorium and troubled diffusion-increasing exploration seemed more vulnerable to develop eating disorder symptoms (i.e., drive for thinness and bulimia). These results are in line with previous research (Palmeroni et al., 2020; Raemen et al., 2022), indicating that adolescents who are searching for a personal identity without making strong commitments may turn to eating disorder symptoms as identity substitutes.
Based on the idea that achievement may be the most adaptive identity trajectory class, these adolescents were expected to also behave most adaptively in terms of body image and body-related behaviors (Luyckx et al., 2013). With regard to self-objectification, appearance comparison, negative and positive body image, and bulimia, adolescents in achievement indeed displayed better scores as compared to adolescents in moratorium and/or troubled diffusion-increasing exploration. However, with regard to sociocultural pressures, internalization of appearance ideals, and drive for thinness, adolescents in achievement did not behave differently from adolescents in moratorium and troubled diffusion-increasing exploration. Thus, adolescents in achievement also seemed to turn to socially available identity building blocks, such as appearance ideals, in their search for a strong personal identity. Interestingly, adolescents in carefree diffusion generally displayed the most adaptive scores regarding body image and body-related variables. This finding might be explained by the fact that male adolescents were overrepresented in carefree diffusion and, more importantly, that carefree-diffused adolescents were less concerned about their identity quest. Given the identity-body interplay, it is possible that carefree-diffused adolescents were doing better in terms of body-related symptoms in the short term, because their limited identity search might made them more immune to sociocultural pressures regarding appearance (Corning & Heibel, 2016). In other words, when individuals seem unmotivated to fully engage in their identity search and to explore identity options, they may be less vulnerable to turn to socially constructed appearance ideals as identity building blocks as well. This finding highlights the importance to focus also on the specific content of the identity exploration and commitment processes. However, the identity questionnaire used in the current study focused broadly on the degree to which adolescents engaged in exploration and commitment processes with respect to their future plans and lifestyle (without detailing what these plans and lifestyle exactly entail). Adolescents who are more involved in pro-active exploration or commitment processes, for instance, may commit to rather pathological identity content (such as being excessively thin). Furthermore, the lack of a strong personal identity might make these carefree diffused individuals more vulnerable in the long run for developing pathological symptoms, as an integrated identity tends to become increasingly important for one’s well-being throughout the twenties (Kling et al., 2018; Luyckx et al., 2013).
Practical Implications
Although no strong conclusions for clinical practice can be made, the current findings may have several implications for the prevention and intervention of body image problems and other body-related symptoms in adolescents. As the current study confirms the intricate link between identity and one’s body in adolescence, it seems important to target adolescents who are struggling with their identity development, as they may be more vulnerable to also struggle with their body image and other body-related symptoms. In other words, when identity development becomes even more challenging (e.g., due to a pandemic), it is important for clinicians to be aware of bodily concerns as well. Further, besides clinicians, the immediate social environment may promote pro-active identity exploration and may support adolescents in committing to healthy identity choices. For instance, research has demonstrated that positive youth development (PYD) interventions in schools or other communities can have a beneficial impact on identity formation (Eichas et al., 2017). More concretely, schools can organize exercises with students to guide students in sharing life stories, discovering personal strengths, co-constructing life goals, and strategies for achieving these goals (Eichas et al., 2014). Findings suggested that such PYD interventions, focusing on expanding and enhancing personal potentials and meaningful aspect of one’s life, can empower adolescents to define who they are and what they wish to achieve in life (Eichas et al., 2017). Relatedly, families and peers may also stimulate adolescents to reflect on their intrinsic life goals and to explore different aspects of the self that are not only related to body and appearance. In this way, adolescents may end up developing a more diversified and intrinsically oriented sense of self as a resource against the confrontation with the body perfect ideal. Finally, as associations between identity formation and positive body image have been found, it might be helpful to strengthen a positive body image in adolescents. It is known that reducing negative body image and enhancing positive body image might prevent or reduce eating disorder symptoms, and that body image and pressures regarding appearance ideals might impact identity formation as well (Palmeroni et al., 2021; Palmeroni et al., 2020). Hence, strengthening positive body image besides reducing negative body image and appearance-related pressures might positively impact eating disorder symptomatology and identity development. As body ideals are socially constructed, both the direct social environment (i.e., parents, teachers, and peers) and the larger community might have a crucial role in adolescents’ enhancement of healthy attitudes towards the body and appearance. For example, given that body acceptance by others can positively affect one’s body image, it might be helpful for adolescents if parents, teachers, and peers would provide positive and accepting messages related to one’s body (Andrew et al., 2016).
Limitations and Suggestions for Future Research
Some limitations should be considered. First, although the three-wave longitudinal design was a strength of the current study, the time span was limited to a period of only two years, which does not allow us to draw conclusions about long-term functioning. Investigating adolescents over a longer time period could give us a greater insight into the co-development of identity and the body during adolescence. Second, the study faced a large drop-out on the third measurement wave, which is presumably due to the fact that this last measurement wave took place during the COVID-19 pandemic. Third, the current study exclusively made use of self-report questionnaires, which is the preferred way to assess subjective processes. However, self-reports might be influenced by memory recall, and, inaccurately high correlations among the study variables could occur as a result of shared method variance (Tylka, 2012). Combining this method with a multi-method or multi-informant approach might provide additional information and is advised for future studies. Relatedly, future research could also benefit from investigating this identity-body interplay from a narrative identity approach and focusing on the content of one’s identity (Skhirtladze et al., in press). From this point of view, it would be interesting to investigate whether sociocultural pressures and appearance ideals are equally embedded into one’s identity in the different statuses; or, similarly, what the different motives are behind the thin versus the muscular appearance ideal. Finally, although gender-adjusted measures assessing appearance ideals internalization (i.e., thin ideal and muscular ideal) were included (Schaefer et al., 2015), this study solely focused on disturbed eating behaviors aiming at achieving the thin ideal instead of also focusing on eating behaviors related to the muscular ideal such as eating more carbohydrates or using steroids. Moreover, the EDI-3 subscale (Garner, 2004) that assesses negative body image seems to focus primarily on women’s physical features and bodily concerns (Tylka, 2012). Hence, these findings might be an underestimation of body image concerns and body-related symptoms in adolescent boys, as no significant differences for internalization of the muscular ideal were found. Future research should include additional measurements that can assess the full spectrum of bodily concerns across gender.
Conclusion
The complex longitudinal associations between identity formation and one’s body in adolescence have remained largely understudied. Addressing these gaps, the current study provides insight into this identity-body interplay by investigating identity trajectory classes among adolescents and the co-development with body image and body-related variables. In sum, the current findings indicated that distinct identity pathways throughout adolescence emerge, characterized by differential levels of underlying exploration and commitment processes. Adolescents in identity trajectory classes reflecting less adaptive identity functioning, such as moratorium or troubled diffusion, displayed higher levels of negative body image and body-related symptoms and lower levels of positive body image. Finally, adolescents included in these less adaptive identity trajectory classes also experienced a stronger impact of the COVID-19 pandemic on their negative affect. Overall, the current study confirms that identity formation is intricately linked to adolescents’ body image and other body-related symptoms. Both future research and prevention or intervention programs are encouraged to take identity formation into account in relation to body image problems and other body-related symptoms in adolescents.
Authors’ Contributions
L.V. conceived of the study, participated in its design and coordination, performed the statistical analyses and drafted the manuscript; L.R. helped with the data collection, participated in the design of the study, the interpretation of the data and helped to draft the manuscript; L.C. conceived of the study, participated in the design of the study, the interpretation of the data and helped to draft the manuscript; S.E. participated in the design of the study and helped to draft the manuscript; N.P. oversaw the data collection and helped to draft the manuscript; K.L. conceived of the study, participated in its design and coordination, performed the statistical analysis and helped to draft the manuscript. All authors read and approved the final manuscript.
Data availability
The dataset analyzed during the current study are not publicly available but are available from the corresponding author (L.V.) on reasonable request.
Compliance with Ethical Standards
Conflict of Interest
The authors declare no competing interests.
Ethical Approval
The study was approved by the Social and Societal Ethics Committee of KU Leuven (G-2018 08 1303).
Informed Consent
Written informed consent was provided by all participants included in the study and the parents of minor students provided active parental consent as well.
1 The AIC, SABIC, and LMR-LRT were requested by a reviewer as additional criteria, and such, were not mentioned in the preregistration of the manuscript.
2 Analyses were conducted on a limited sample, given that the students had to have participated at the third measurement point. These analyses were not preregistered.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36494547 | PMC9735115 | NO-CC CODE | 2022-12-14 23:28:32 | no | Br Dent J. 2022 Dec 9; 233(11):969-971 | latin-1 | Br Dent J | 2,022 | 10.1038/s41415-022-5256-9 | oa_other |
==== Front
Energy Effic
Energy Effic
Energy Efficiency
1570-646X
1570-6478
Springer Netherlands Dordrecht
10076
10.1007/s12053-022-10076-3
Original Article
Estimating implicit discount rate for energy efficiency investment using the contingent valuation method: a case study in South Korea
Park Jiyong [email protected]
1
Woo JongRoul [email protected]
2
http://orcid.org/0000-0002-7909-6679
Jin Taeyoung [email protected]
1
1 grid.467726.6 0000 0004 0647 3546 District Heating and Power Research Team, Korea Energy Economics Institute, 405-11 Jongga-ro, Jung-Gu, 44543 Ulsan, South Korea
2 grid.222754.4 0000 0001 0840 2678 Energy Environment Policy and Technology, Graduate School of Energy and Environment, Korea University, 145 Anam-Ro, Sungbuk-Gu, Seoul, 02841 South Korea
6 12 2022
2022
15 8 6729 1 2022
26 11 2022
© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
This study measures the implicit discount rate (IDR) for energy efficiency investment at the household level. Our pioneering attempt to use the contingent valuation method suggests fresh insights into relieving the possible problems induced when the IDR is estimated using multiple price list and open-ended questions. Using the survey data from 2392 respondents in South Korea, we measured the IDR for appliances with high energy efficiency. The measurement ranges from 21.80 to 25.94%, implying the overestimation in existing literature. This study contributes to the literature by determining the role of cognition and experience in energy efficiency investment. Cognition has a statistically significant negative impact on IDR and depends on the appliance type, whereas risk preference has no meaningful impact. Energy efficiency improvement experiences are the critical factor in reducing IDR, that is, promoting energy efficiency investment, especially for recently introduced appliances. Overall, our finding suggests that information that induces high cognition on the cost–benefit analysis and energy efficiency labeling can lower IDR and thus promote energy efficiency. Our study also suggests that targeting energy consumers who have experience in energy-saving campaigns or programs could be a priority because such experiences are crucial to IDR reduction.
Keywords
Contingent valuation method
Implicit discount rate
Energy efficiency investment
Cognitive reflection test
issue-copyright-statement© Springer Nature B.V. 2022
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pmcIntroduction
Climate change is a critical threat to the future and should be addressed for the next generation (Chan, 2018). Energy production and usage have been mentioned as a main contributor to greenhouse gas (GHG) emission, accounting for 87% of world emissions (IEA, 2020). The energy sector devotes global efforts to mitigate GHG emissions with various measures, such as renewable energy source adoption and consumption curb through demand management. Especially in advanced countries, energy-related carbon emissions have been successfully mitigated through clean energy development (IEA, 2020). However, energy-related GHG emissions are projected to increase in developing economies (EIA, 2019), keeping the current status of the energy-climate issue to be an international issue.
Although energy consumption involves GHG emissions, policymakers cannot call for drastic energy reduction because energy also plays a vital role in economic growth (Apergis & Payne, 2012). According to the energy-growth nexus theory, a significant relationship exists between energy consumption and economic growth (Apergis & Payne, 2009). Under the circumstances that energy consumption is essential for economic growth, scholars have attempted to determine how the environment is conserved without reducing the production factor.
IEA (2019) emphasized that energy efficiency is the first fuel, which should be prioritized to address climate change. Energy efficiency improvement can save energy consumption that is deeply related to carbon emissions, as mentioned above. Naturally, 10% improvement in energy efficiency is directly connected to 10% reduction of energy consumption, assuming the absence of the energy rebound effect (T. Jin & Kim, 2019). Accordingly, energy efficiency improvement can mitigate carbon emissions by reducing energy usage involving GHG. If energy-related emissions become zero by making energy transition to clean energy mix, energy efficiency improvement might be an ineffective tool for coping with climate change. However, renewable expansion with the energy transition policy will overburden the electricity system. Energy efficiency improvement can also be an effective tool to mitigate it (X. Jin et al., 2017). According to Karatasou et al. (2014), energy policy for efficiency must be established because energy efficiency with consumer behavior change takes a long time. At this point, how to improve energy efficiency with consumer behavior correction must be determined.
To address the climate problem, the Paris Agreement in 2015 demands the parties to submit the modified action plan every 5 years. In 2020, Korea also constructed a long-term low GHG emission development strategy. As a result, the Korean government declared the “2050 Carbon–Neutral Strategy” that emphasizes the innovation of energy efficiency as a tool for carbon–neutral. Specifically, the supply of appliances with high energy efficiency has been listed in the policy goals. Moreover, the role of households in energy efficiency improvement becomes important (Lakić et al., 2021).
The supply program supported by determinants of adopting appliances with high energy efficiency in the household sector should be planned to magnify the policy impact on energy efficiency. This study measures the implicit discount rate (IDR) of consumers on energy efficiency investment, in the context of South Korea. The estimated IDR can show consumers’ evaluation of the future value of energy reduction benefit induced by energy efficiency investment. The energy efficiency policy, which does not reflect the IDR of household consumers, may be ineffective (Solà et al., 2021). Additionally, policymakers can diversify policy design and evaluation according to the IDR results. This also promotes the outcome of energy efficiency policy.
This study contributes to the literature on several points. First, we introduce the contingent valuation method (CVM), which is frequently adopted to measure the willingness-to-pay (WTP) or willingness-to-accept (WTA), to estimate the IDR of household energy efficiency investors (Woo et al., 2019). This can supplement the shortcoming of multiple price list (MPL) that can be a representative method to estimate IDR in that MPL elicits interval responses rather than “point” valuations (Andersen et al., 2006).1 Additionally, the IDR depends on the appliance type and trend. Second, we confirm that the energy efficiency improvement experiences are the additional determinants of IDR. The experiences lower IDR, and thus, it leads to the energy efficiency investment, which demonstrates the useful information to make energy efficiency policy. Finally, the cognitive reflection test (CRT) is adopted as a proxy of cognition to determine the impact of cognition on IDR. Our novelty can be focused in that we estimate IDR with CVM combining behavior economics and cognition psychology, suggesting fresh insight in energy efficiency investment field.
The rest of the paper is organized as follows. The “Literature survey” section introduces the existing literature about IDR, especially focusing on the energy field. The “Methodology” and “Empirical results” sections present the estimation methods and empirical results, respectively. Finally, the “Conclusion and policy implications” section presents the conclusions and policy implications.
Literature survey
For the household sector, electricity consumption is expected to increase, whereas energy consumption will decrease, owing to the enlargement and enhancement of house appliances, with electrification policy (Jihyo Kim et al., 2016). Appliances with high energy efficiency are more expensive than general ones, but they can reduce the future cost of energy consumption in the lifetime of appliances. The results of cost–benefit analysis on highly energy-efficient appliances revealed that most appliances with high energy efficiency are more cost-effective than the general ones (Ellis et al., 2007).
However, an energy efficiency gap exists between energy efficiency investment and consumer purchase behavior. Gerarden et al., (2015) explained why the energy efficiency gap has induced much higher IDR for energy efficiency investment than general purchase of goods among consumers. Because of the gap in time between cost and benefit, a consumer with high IDR must underestimate the future benefit from energy reduction. According to Stadelmann, (2017), existing literature covering IDR has overestimated IDR because estimated IDR includes irrational behavior and market failure.
Studies on IDR estimation have been based on purchasing data of consumers. For instance, Hausman, (1979) and Train, (1985) have attempted to estimate IDR for appliance purchase, but they derived seriously overestimated IDR. To measure precise IDR on energy efficiency investment, several scholars have developed the survey techniques and estimation methods. Recently, Haq & Weiss, (2018) conducted a meta-analysis based on 21 research papers covering IDR for energy efficiency investment in households. Studies investigating IDR for energy efficiency investment have commonly derived much higher IDRs than market interest rate. Additionally, they concluded that the IDR depends on socio-demographic factors such as income and the type and price of highly energy-efficient appliances.
According to Sanstad & McMahon, (2008), who reviewed IDR of energy decision-making, personal IDRs have huge gap and are widely distributed with a range from 17 to 300%. The IDR has been found to exhibit time-variant characteristics and depend on equipment type; thus, the IDR is hard to be generalized (Frederick et al., 2003). The other study on the IDR for energy efficiency investment found large deviations of IDRs, according to the estimated standard deviation of 23% (Newell & Siikamki, 2015).
From the experimental studies on IDR with survey data, Schleich et al., (2016) defined three categories on IDR determinants. The first category is personal preferences, including time, risk, and environmental-friendly preferences. The second category is the building block of IDR, that is, predictable irrational behavior explained by limited rationality, carelessness, and biases. The third determinant category denotes external barriers such as lack of information.
Existing literature on the IDR has commonly concluded that the estimated IDR depends on household income and equipment (Busic-Sontic et al., 2017). Kubiack, (2016) investigated the literature on IDR for energy efficiency investment and found a negative relationship between estimated IDR and annual income from the empirical results of 13 studies. The negative relationship between IDR and income has been explained: high-income level represents a low credit limitation, risk-loving, time-preference endurance, and high awareness of energy-environmental issues (DEFRA, 2010).
The IDR for thermal shell investments depended on household income, ranging from 0.4 to 88% (Little, 1984). Moreover, energy investors have relatively low IDR for fuel switching on the heating system, ranging from 14 to 56%, that also depended on income level (Berkovec et al., 1983). Also, existing literature revealed that the IDRs for energy efficiency investment are also heterogeneous by socio-demographic factors, such as education level and cultural background (Kubiack, 2016).
Wang et al., (2021) did not investigate the IDR using survey data, but they adopted econometric analysis. Nonetheless, they determined that labeling of high energy efficiency on appliances, especially in the case of refrigerator, increases the purchase of appliances. This result implies that the labeling of energy efficiency on appliances decreases the IDR of energy investors (Z. Wang et al., 2019). To control the effects from labelling, we collected the survey data of labelling confirmation when purchasing that is included as individual self-awareness variable.
Meanwhile, Lakić et al., (2021) surveyed Slovenian households to investigate the willingness to invest in more efficient heating controls which can be elicited into the IDRs. The estimated IDRs ranged from 29.8 to 47.3%, which is close to our results. Likewise, the IDRs are found to depend on socioeconomic factors, such as gender and marriage. Kim & Nam, (2021) conducted a Korean case study to determine whether time, risk, and social preferences affect energy efficiency investment using the probit model. They concluded that risk and social preferences are determinants of energy efficiency investment, whereas time-preference partially affects it.
The literature introduced above have mostly adopted CVM method to elicit the IDR for energy efficiency investment. Damigos et al., (2021) conducted a stated preference survey in Greece to estimate IDRs used in energy efficiency decisions. They concluded that the IDRs for energy efficiency investment ranged from 92 to 136%, which seems to be highly overestimated by the problem of open-ended questions of CVM. In the same study, choice experiment (CE) was conducted to show the distribution of IDR ranging from − 10 to 60%, and mean IDR is equal to 5.5%. It implies that IDR for energy efficiency investment is not robust to the method. In addition, it was suggested that open-ended question CVM may have more consistency than CE to elicit WTP (Brouwer et al., 2017). Compared to open-ended question, the dichotomous choice (DC) method can take the advantage that the probability of strategic response bias is low in the dichotomous choice option. Therefore, we decided to adopt the DC CVM model.
Nevertheless, CE was frequently adopted as the empirical method to derive IDR for energy efficiency investment. Revelt & Train, (1998) attempted to find out households’ choice of appliance efficiency level with repeated choice questions indicating CE method. While this study was not to derive IDR, they concluded that household prefer to invest high-efficiency appliances with the loan. Heinzle, (2012) found implicit WTP in energy efficiency investment can be increased by the energy efficiency label, tackling the importance of information in the energy efficiency investment of household sector. The implicit discount rate for TV was estimated with the range from − 4.95 to + 5.96%, implying that CE method may underestimate IDR of investing high-efficiency appliances (Damigos et al., 2021).
Min et al., (2014) conducted case study on light bulbs of experimental studies with CE method to emphasize the importance of labeling in similar to the study of Heinzle, (2012). This study results in the changes from 560 to 100% of IDR that induced by shown operating cost when purchasing high-efficiency appliances. Davis & Metcalf, (2016) derived same results that energy efficiency labels can promote energy efficiency investment from experimental research with CE method. While the multi-country CE study of Schleich et al., (2022) was not for energy efficiency, the preferences for new heating systems across countries have been investigated and heterogeneity of countries can be controlled in the CE study, implying the adaptability of CE method to apply consumer choice study on energy efficiency preference.
Lastly, Solà et al., (2021) reviewed the literature covering energy efficiency investment at the household level. Their research drew the consensus between existing studies. The underinvestment in energy efficiency can be induced by market failure, including informational failure, behavioral failure, and other factors. Therefore, the energy efficiency policy needs to be diversified with the consideration of characteristics and promotion purpose to promote energy efficiency investment.
As summarized above, the IDR for energy efficiency investment has been addressed by many scholars and its estimation methods. Although the MPL and open-ended question survey have been used to measure IDR and its determinants, the existing literature tended to overestimate the IDR for energy efficiency investment at the household sector because of the nature of questionnaires. To overcome this problem, we adopt the CVM method to elaborate the IDR question to respondents.
Methodology
Theoretical framework
Highly energy-efficient appliances take advantage of energy cost savings through its long-run usage, despite the high price. In this paper, energy efficiency investment indicates the decision-making of energy consumers who purchase appliances with high energy efficiency and recover the purchasing cost through energy cost savings in the long-term years of usage (Miller, 2015).
Assuming that an investment decision-making of enterprises is affected by several factors, energy efficiency investment of households is also derived by a combination of economic factors and personal characteristics. Existing literature has defined the economic factors affecting decision-making of energy efficiency investment with the following objective function of cost minimization (T. Gerarden et al., 2015; T. D. Gerarden et al., 2017; Stadelmann, 2017).1 minT(C)=KE+∑tTOE,PEt×Dr,t
where T(C) and KE denote the total cost of energy efficiency investment and appliance purchase cost that is the initial investment cost. OE,PE indicates annual energy cost discounted by discount function (Dr,t). E and PE are energy consumption and energy price, respectively. Finally, r and T represent the discount rate and lifetime of appliances, respectively.
Energy consumer decides on energy efficiency investment by comparing the initial investment cost for highly energy-efficient appliances and future energy cost reduction for the appliance’s lifetime. The investment potential rises in the initial investment cost-cutting or the increase in benefits from future energy cost reduction. Future energy cost reduction can be affected by future energy price increase and low IDR, which in turn increase the benefit of energy efficiency investment.
The appliance purchase cost, KE, is an incremental cost presented by the price gap between highly energy-efficient and general appliances. This is determined by energy consumption (E), with an inverse proportion relationship. The high energy efficiency indicates the reduction in energy consumption and the increase in the appliance purchase cost, which reduces the possibility of energy efficiency investment. Alternatively, the adoption of appliances with high energy efficiency reduces future energy cost (OE,PE). Energy cost reduction depends on personal discount rate that is demonstrated by IDR, reflecting personal characteristics of how much weight the future value. High IDR causes people to underestimate future benefits from the energy cost reduction, which is connected to the low chance of energy efficiency investment.
CVM method
This study adopts a CVM to estimate the IDR of household energy consumers. The CVM is well-known as a valuation method to measure the value of non-market goods based on the survey data. In general CVM analysis, a structured questionnaire suggests a hypothetical situation change to ask direct question of WTP or WTA to respondents. Especially for the energy field, the CVM is often used to determine the WTP and WTA about renewable preference, energy supply security evaluation, and social value (Jinsoo Kim & Kim, 2015; Junghun Kim et al., 2018; K. Kim et al., 2015; Lee & Cho, 2020).
There are several forms to organize questions for deriving the WTP information from respondents such as open-ended, payment card, and dichotomous choice formats (Welsh & Poe, 1998). For most respondents, answering the open-ended WTP questions is difficult because they are not an expert on this field (Loomis, 1990). By this reason, many CVM studies have constructed the questionnaire consisting of dichotomous choice question. The CVM with dichotomous questions has few biases and reliability (Yoo & Kwak, 2002). The dichotomous choice question suggests two options of yes or no to respondents based on a certain level of WTP. Based on the survey results of dichotomous choice, the interviewer can calculate the WTP through the econometric analysis assuming the consumer utility function with logit and probit model (Lee & Cho, 2020).
Bishop & Heberlein, (1979) and Hanemann, (1985) proposed the two dichotomous choice question methods: a single-bounded dichotomous choice (SBDC) and a double-bounded dichotomous choice (DBDC). The two methods differ in terms of question times: SBDC questions just once, whereas DBDC does twice. Among the two methods, DBDC model is used in this study.
In the DBDC model, if the respondents choose the answer “yes” in the initial question of WTP, the twice WTP question is followed. Alternatively, when the respondents say “no” in the initial question, the follow-up question goes to the half WTP. Most literature covering CVM has adopted the DBDC model rather than SBDC because the SBDC tends to be statistically more inefficient than the DBDC (Cameron & Quiggin, 1994).
Hanemann, (1984) suggested using the indirect utility function measured by the Hicksian compensation surplus that can be observed from the discrete choice survey data. In the survey system, energy consumers, that is, respondents, are assumed to behave to maximize their own utilities. By using the utility difference approach, we can present the indirect utility function of respondents as follows.2 u1,m-A;S+ε1≥u0,m;S+ε0
where u denotes indirect utility function. The first term in utility function expressed in one or zero means whether purchase a product or not. In this study, state 1 means purchasing the highly energy-efficient appliances. m and A are each respondent’s income and WTP, respectively. The energy consumers respond to question based on their income (m) and socio-economic characteristics of themselves (S). ε indicates the disturbance assuming identical and independent distribution that influences consumer’s decision-making. Equation (2) expresses that the respondents check “yes” when the utility gap between the adoption and non-adoption of appliances with high energy efficiency is bigger than the random error gap (ε0-ε1).
In the CVM literature, zero value of WTP has been questionable problem. Even though the CVM survey uses the DBDC structure that questions twice, the WTP becomes zero value of the respondent selecting “no” several times in a row. In real, sometimes most CVM respondents express their WTP of zero (Lim et al., 2014). Some studies decided to exclude the respondents of zero WTP. If the WTP estimation omits a part of respondents, the WTP will be biased and overestimated. To overcome this problem, the spike model that can handle the zero WTP value was introduced (Kriström, 1997).
Since we use DBDC spike model, the possible outcomes of DBDC question can be categorized into five combinations: “no–no (IiNN),” “no-yes (IiNY),” “yes–no (IiYN),” “yes-yes–no (IiYYN),” and “yes-yes-yes (IiYYY).” The I denotes the indicator function that shows 1 value in case that the respondents answer the combination to the survey as presented in Eq. (3). For instance, if a respondent answered “no” to the initial question of WTP and “yes” to follow-up question, the indicator function (IiNY) presents 1, the others are zero. Our empirical analysis is based on the DBDC spike model to estimate the IDR of household energy efficiency investors considering zero IDR value. The third follow-up question in case that the respondent answers “yes-yes” is intended to confirm either the devoid IDR or at least a positive IDR of potential energy efficiency investors.IiNN=1ifIDR>AiN0otherwise
IiNY=1ifAi<IDR≤AiN0otherwise
IiYN=1ifAiY<IDR≤Ai0otherwise
IiYYN=1if0<IDR≤AiY0otherwise
3 IiYYY=1ifIDR=00otherwise
In this study, we adopt the DBDC spike model to estimate the IDR of household energy consumers for energy efficiency investment with handling the zero WTP problem that respondents may express the none of investment. The log-likelihood function for the DBDC spike model can be expressed as follows:4 lnL=∑i=1NIiNNln1-GAiN+IiNYlnGAiN-GAi+IiYNlnGAi-GAiY+IiYYNlnGAiY-G0+IiYYYlnG0
where Ai indicates the IDR of energy efficiency investor in the initial question. AiY and AiN are the follow-up questions when the response to the initial bid was “yes” or “no,” respectively. For the spike model, logistic distribution function (G∙) is assumed to follow a half logistic distribution as follows.5 GA=1+exp(a-bA)-1ifA>01+exp(a)-1ifA=00ifA<0
where a and b are the parameters to be estimated by a logit. The maximum likelihood estimator (MLE) is used to estimate the parameters. The mean IDR can be calculated using Eq. (6).6 meanIDR=1bln[1+exp(a)]
Advantages of CVM for IDR estimation
The MPL has three possible disadvantages. (1) It only elicits interval responses, rather than “point” valuations. (2) The subjects can switch back and forth from row to row, implying potentially inconsistent preferences. (3) It could be susceptible to framing effects, as subjects are drawn to the middle of the ordered table irrespective of their true values (Andersen et al., 2006).
One of the main disadvantages of complex methods for eliciting risk preferences is that, depending on the population, a significant number of subjects will fail to understand the procedure. This reduces the reliability of the risk preference measure and can bias the results. With the standard MPL method, individuals are typically allowed to switch freely between options A and B as they progress down the decision rows. As such, participants may make inconsistent decisions either by switching more than once or making “backward” choices—starting with option A and switching to B (Dave et al., 2010; Holt & Laury, 2002).
Depending on the participant pool, this problem could be significant. For example, Jacobson & Petrie, (2009) found that in a sample of Rwandan adults, 55% made inconsistent choices; Charness & Viceisza, (2012) found that 75% of farmers from rural Senegal made inconsistent choices (51% switched more than once and 24% always chose option A). This poses an obvious problem because the inference of risk preferences, and in turn, parameter estimation, requires a unique switch point, and such inconsistent behavior is difficult to rationalize under standard assumptions on preferences (Gary Charness et al., 2013).
The problems addressed above can be solved and alleviated by applying CVM. The CVM can take advantage of eliciting WTP with successive “point” questions. The second problem, that is, switching-back problem, also does not occur in CVM because the second and third questions are followed according to the response of the former question. To mitigate the problem of MPL and elaborate the estimation of the IDR, we adopt the CVM method with well-designed survey to measure IDR for energy efficiency investment.
Survey form and data descriptions
The survey for CVM is designed to investigate the determinants of IDR of household energy efficiency investors. According to Schleich et al., (2016), the IDR is determined by preferences, predictable rational behavior, and external barriers to energy efficiency factors. To consider these determinants in a microsurvey system, we add the questionnaire to ask risk preference, experience, and cognition. The survey is constructed into four parts. First, the IDR questions are conducted for four home appliances: TV, air conditioner, dehumidifier, and air cleaner. In the second part, to measure the priority of consumers under the consideration of risk, the survey consists of the questions about risk on high energy efficiency investment and general efficiency investment.
Third, we attempt to control the impact of cognition on energy efficiency investment with the CRT results. The third part is elaborated with the questions to measure the cognitive power of each energy efficiency investor. Finally, general socioeconomic information, the current status of home appliance usage, and energy efficiency improvement experiences of energy efficiency investors are investigated. Survey questions are summarized in Appendix 2.
We set based an initial value of IDR as 50% of IDR only except high energy efficiency TV. Other than the CVM study estimating WTP, our analysis targets the IDR estimation, which is bounded 0 to 100. To determine the impact of initial suggestion on IDR, we diversify the initial value of 30% and 40% in addition to the initial base value. The lowest initial IDR is 30%, derived by considering the prices of actual high energy efficiency appliances and household electricity charge level. The follow-up question is designed to depend on the initial suggestion. According to Arrow et al., (1993), the best way to conduct the CVM survey is through face-to-face interaction. However, conducting offline survey was unsuccessful due to the COVID-19 pandemic. We collect the survey data with interned responded by 2392 effective respondents.
When we build up the questionnaire, it was not certain that the respondents are aware of the concept of interest rate. The discount rate or interest rate to estimate the investment returns such as payback period would be not familiar to the respondents. Therefore, in the questionnaire, the IDR bid are presented together with the underlying payback period and financial returns with energy efficiency investments based on the current electricity charge level so that the respondents can recognize that the suggested IDR can be translated into the energy efficiency investment and financial returns.
The demographic characteristics of survey respondents are presented in Table 1. Our socioeconomic factor investigation of each potential energy efficiency investor include age, gender, dwelling type, number of family members, education level, monthly income, and monthly electricity consumption. Overall, the demographic factors of respondents are regularly distributed. The age we use is not discrete but continuous variable. Although the tenant, the actual resident, pays the bill for energy in South Korea, the energy efficiency investment decision may depend on home ownership; hence, the variable can be a critical factor. Other factors such as monthly income and electricity consumption are directly connected to the willingness to invest of household energy consumers.Table 1 Demographic factors of respondents
Characteristics Group Number of respondents (N = 2392) Percentage (%)
Age 38.09 (average)
Gender Male 1191 49.79
Female 1201 50.21
Dwelling type Own 1452 60.70
Rent 773 32.32
Etc 167 6.98
Number of family members 1 465 19.44
2 388 16.22
3 627 26.21
4 746 31.19
Over 5 160 6.66
Etc 6 0.25
Education level Lower than high school 43 1.80
High school 351 14.67
University 1,688 70.57
Graduate school 310 12.96
Monthly income (KRW 10,000) Lower than 200 517 21.61
200–300 673 28.14
300–400 494 20.65
400–500 264 11.04
500–600 195 8.15
600–1000 204 8.53
Over 1000 45 1.88
Monthly electricity consumption (kwh) 0–100 129 5.39
100–200 374 15.64
200–300 548 22.91
300–400 426 17.81
400–500 169 7.07
500–600 44 1.84
Over 600 21 0.88
Unknown 681 28.47
Other than the demographic factors, we conduct an additional survey to measure the abovementioned other factors: risk preference, experience, and cognition. The risk preference for energy efficiency investment is measured by MPL, the results of which are presented in Table 2. One of the most important contributions of this research is to attempt to control the individual cognition reflecting individual decision-making process and heterogeneity, which measured by CRT, in the empirical analysis (Dohmen et al., 2010; Sajid & Li, 2019). Based on the behavior economic theory, the individual cognition can be classified into systems 1 and 2. The system 1 indicates quick but imprecise decision-making person, whereas a person with time-taking and precise decision-making falls to system 2 (Frederick, 2005). The existing literature has shown that a person with system 2 tends to have low IDR for time and risk preferences. Table 3 summarizes the results of CRT. In the questionnaire, CRT part consists of three questions. The CRT variable denotes the number of correct answers by the respondents, indicating that the higher CRT variable is, the higher cognition of respondents is.Table 2 Risk preferences of respondents
Risk preference Level Number of respondents (N = 2392) Percentage (%)
Risk-loving 1 176 7.36
2 440 18.39
3 115 4.81
4 186 7.78
Risk-neutral 5 345 14.42
Risk-averse 6 239 9.99
7 22 9.49
8 187 7.82
9 127 5.31
10 350 14.63
Group 1 indicates extreme risk-loving whereas group 10 denotes extreme risk-aversion.
Table 3 CRT results of respondents
Cognition level Number of respondents (N = 2392) Percentage (%)
0 993 41.51
1 487 20.36
2 453 18.94
3 459 19.19
Group 1 indicates extreme risk-loving whereas group 10 denotes extreme risk-aversion.
Moreover, the self-awareness of energy consumption pattern and energy efficiency investment experience can be determinants of IDR (Stadelmann, 2017). The last part of survey was constructed to investigate them. The summarization of the survey results for self-awareness of energy consumption pattern and energy efficiency investment experience are suggested in Appendix 1.
Lastly, Table 4 shows the results of the survey for IDR eliciting questions. We conduct the survey for four home appliances with high energy efficiency. As described in Eq. (3), the IDR estimation has reverse form with traditional WTP estimation. The answer to the initial bid was “yes” which can be translated into high willingness to invest, which indicates lower IDR. That is, successive “yes” presents the low IDR, and energy investors are willing to invest the highly energy-efficient appliances. Although the final question of a traditional DBDC CVM is to ask the zero WTP with successive “no” responses, a three-time successive “yes” translates into zero IDR in our analysis. Unlike the literature concerned about zero WTP, our survey results show a few respondents expressing zero IDR (about 0.2% of sample), so that the estimated mean IDR has few chances of underestimation.Table 4 IDR eliciting question results
Response IDR level Television Air conditioner Dehumidifier Air cleaner
No/no IDR>AiN 288 238 327 306
No/yes Ai<IDR≤AiN 165 187 206 201
Yes/no AiY<IDR≤Ai 319 311 326 317
Yes/yes/no 0<IDR≤AiY 1615 1656 1529 1565
Yes/yes/yes IDR=0 5 5 4 3
Empirical results
The survey to investigate IDR of household energy efficiency investors is conducted with a questionnaire consisting of IDR questions on four home appliances, risk preferences, CRT, awareness, experiences, and demographic factors. MLE examines the potential IDR of energy efficiency investment. Table 5 presents the mean IDR results and its determinants. The empirical results were estimated by the extension of Eq. (4) with addition of determinants of IDR. The dependent variable denotes the rejection rate of bidding. Therefore, the estimated coefficients of covariate represent the impact of covariate on estimated IDR. In the conventional CVM, the dependent variable should be the acceptance rate of bidding converse to our study.Table 5 Mean IDR with covariates
Variables Estimated coefficient
TV Air conditioner Dehumidifier Air cleaner
Mean IDR 23.30% 21.80% 25.94% 24.91%
95% Confidence interval2 [22.44, 24.19] [21.00, 22.63] [24.96, 26.96] [24.00, 25.88]
Risk preference − 0.0413 − 0.0157 − 0.0092 0.0348
Gender 0.1165 0.4010a 0.3250a 0.3448a
Age 0.0041 0.0346c 0.0195a 0.0248b
Number of family members 0.1360a 0.0201 − 0.0069 − 0.0327
Education level 0.0875 0.1191 − 0.0284 0.1607
Dwelling type − 0.6191c − 0.3739 − 0.4165b − 0.1820
Monthly income 0.0563 − 0.0600 0.0391 − 0.0588
Monthly electricity consumption − 0.0544 − 0.0447 0.0175 0.0502
Cognition (CRT) − 0.1833b − 0.3825c − 0.3129c − 0.3919c
Current home appliance usage − 0.0848 0.0221 − 0.3676a − 0.8390c
Purchasing plan 0.2767 0.0251 − 0.3783a − 0.3294
Self-awareness of energy consumption pattern
Confirming energy efficiency level when purchasing 0.0211 − 0.0672 0.0164 0.0264
Confirming electricity charge when paying 0.0192 0.0046 − 0.0261 − 0.00002
Participating in energy-saving program − 0.0190 0.0536 0.0497 0.0770a
Considering fuel cost in heating and cooling 0.0588 0.0990 0.0558 0.1397b
Multi-tap usage 0.1497b 0.0075 − 0.0078 − 0.1112a
Turn-off the unnecessary light − 0.1892c − 0.1966b − 0.1005 − 0.1396a
Energy efficiency improvement experiences
Adopting appliances with high energy efficiency 0.1425 − 0.4990b − 0.4011b − 0.4156b
Replacing windows and doors − 0.1373 − 0.0766 − 0.1273 − 0.0566
Setup insulator 0.0305 0.5053b − 0.1538 − 0.0293
Constant − 6.3631c − 6.3327c − 5.3351c − 5.9910c
IDR in initial bid 0.0760c 0.0738c 0.0770c 0.0769c
Log likelihood − 430.7413 − 378.5375 − 447.7442 − 432.7499
a, b, and c denote rejection of the null hypothesis at 10%, 5%, and 1% significance level, respectively.
For estimating the mean IDR, we use the model without additional explanatory variables. The empirical results to measure mean IDR are statistically significant at the 1% significance level for all home appliances. The acceptable IDRs for TV, air conditioner, dehumidifier, and air cleaner are derived as 23.30, 21.80, 25.94, and 24.91%, respectively. The potential household energy investor’s IDR for energy efficiency investment is in the 20%, which is slightly lower than the IDR estimated from the existing literature.
In addition, the IDR depends on the appliances; relatively higher IDRs are observed for recently introduced appliances, dehumidifier, and air cleaner than the ones of TV and air conditioner. For recently introduced appliances, risk and uncertainty affected by the absence of information increase the IDR of energy efficiency investors. Moreover, the purchasing power for recently introduced appliances is much higher than older ones; the consumers decide to purchase the appliances according to the attraction and performance, rather than energy efficiency. The other consistent evidence also supports it. The current home appliance usage decreases the IDR for dehumidifier and air cleaner. It means that the information and experiences on new appliances can lower the IDR and are the critical factors for energy efficiency investment. The estimated coefficients for the IDR in initial bid variable are statistically significant at 1% significance level for all appliances. The variable indicates the first offer IDR in the questionnaire. As mentioned above, we diversify the initial IDR into 30%, 40%, and 50%. The questionnaire was randomly allocated to the respondents to avoid anchoring effect of initial bid. The positive and statistically significant parameters denote that the first offer IDR positively affects the mean IDR.
Although the determinants of IDR are slightly different from each other for four house appliances, the IDR in general is affected by gender, age, dwelling type, cognition, energy-saving, and experiences. The IDR increases when the household energy efficiency investor is male and dwells in rent. Age affects the IDR positively, indicating that old age is conservative for the energy efficiency investment, whereas the cognitive power is negatively related to the IDR. Note that energy-saving program and energy efficiency experiences can reduce the IDR for energy efficiency investment; therefore, they are essential factors to consider for the residential energy efficiency improvement policy. Alternatively, demographic factors, such as income and electricity consumption, have no meaningful information to explain the IDR of potential energy efficiency investors.
It was surprising that the socio-demographic factors intended to control the heterogeneity across households have not affected the estimated IDR. We assume that the regulated electricity price in Korea may result in this cautiously. Electricity is recognized as the essential goods, since the price and income elasticity are considerably small compared to the other general goods (Fabra et al., 2022). Furthermore, regulated electricity price in Korea makes the share of energy costs of household budget to be smaller (Jihyo Kim et al., 2022), implying that income and monthly consumption are not the determinants of IDR. The low electricity cost cognition of households in Korea can be observed in the literature covering willingness-to-pay (Huh et al., 2015).
For the impact of cognition by appliance, CRT is found to reduce the IDR for energy efficiency investment. Furthermore, the CRT has a much negative impact on IDR for recently introduced appliances rather than familiar ones, such as TV. This implies that individual cognition level highly affects the adoption of new and highly energy-efficient appliances. For the familiar appliance, energy consumers are used to it and have learned information. Otherwise, for recently introduced appliances, energy consumers decide of purchasing through information delivery and promotion. In the process, the cognition measured by CRT seems to affect energy efficiency investment.
Also, the electricity consumption and operating hours may implicitly explain different IDR across the appliances, whereas we attempted to explain the reason to derive different IDR with the experience and recognition of the appliances, which may appear in the form of consumer utilities. In addition, it is highly affected by the marketing and circumstances of appliances in Korea. In Korea, the air conditioner and TV are regarded as the essential home appliances, implying estimated lower IDR. Furthermore, dehumidifier and air cleaner that have been introduced in relatively recent were derived to have bigger barrier in energy efficiency investment than TV and air conditioner, emphasizing the importance of experiences and cognition in energy efficiency investment in household.
Overall, we presume that energy efficiency investment behaviors can be affected by the awareness of environmental issues such as carbon neutrality around the world recently. In addition, the recent policy trend that increases electricity charge in Korea to reflect the fuel cost of generation sector may affect the willingness to invest in energy efficiency to avoid increased energy cost through energy savings from energy efficiency improvement. It would be better to include questions why the zero WTP and the determinants of IDR in household appliances. In case of estimating IDR, we suggest that the research consider including the questions into the questionnaire so that the empirical research can detect the barriers of energy efficiency investments in household.
Conclusion and policy implications
Our study suggests a new approach for assessing the IDR for energy efficiency investment by adopting the CVM method, which is frequently used to estimate the WTP of non-market goods. Our CVM analysis is based on data derived from 2392 online survey respondents. The DBDC method is adopted to elicit the IDR of potential energy efficiency investors in household sector. We aim to derive IDR, not WTP; hence, our survey form is a reverse of the survey for eliciting WTP. Traditional CVM for WTP regards “no–no-no” as zero WTP, whereas our CVM takes zero IDR from three-time successive “yes” question.
Our empirical results are robust to zero WTP problem (in our analysis, zero IDR problem) due to few zero IDR respondents. We found that the IDR for household energy efficiency investment is around 20%, depending on the appliances. The estimated IDR is relatively smaller than the ones of existing literature. We adopt the CVM method to provide specific information to respondents; therefore, the IDR of potential energy efficiency investors seems to be diminished by the risk reduction from information security. The statistical insignificance of risk preference variable indirectly proves it. Moreover, the socio-demographic factors of the survey respondents are regularly distributed. To determine the additional determinants of IDR for energy efficiency investment other than demographic factors, few surveys are conducted for risk preference, CRT, self-awareness, and experiences. Risk preference is found to have no significant impact on the IDR, whereas CRT, energy-saving program participation, and experiences reduce the IDR. It implies that cognition, experience, and information are critical factors for adopting highly energy-efficient appliances in the household sector.
The other major finding is that the estimated IDRs vary according to appliances. Moreover, energy efficiency investors have relatively higher IDRs for the recently introduced appliances, such as dehumidifier and air cleaner, than traditional ones, such as air conditioner and TV. This can be explained by the impact of the current home appliance usage variable. The estimated parameters for dehumidifier and air cleaner have statistically significant and negative effect on IDR, emphasizing the importance of information and experiences in energy efficiency investment.
The existing literature drew the results that cognition can reduce investment IDR, which is in line with our results that cognition can break down the barrier of high energy efficiency investment. It implies that the cost–benefit and energy efficiency labeling that provides information to consumer can lead to energy efficiency investment by increasing the cognition of potential energy efficiency investors. Consistent with these results, for self-awareness of energy consumption patterns, the consumer with a tendency to confirm the energy efficiency level is a potential energy efficiency investor having low IDR.
Energy efficiency improvement experiences can also reduce the IDR of investors, especially for participating in energy-saving program. Experiences of energy efficiency improvement induce perception, advancing the adoption of appliances with high energy efficiency. Using CVM to measure IDR can be shorthanded in that the estimated IDR depends on the initial suggestion, which may be occurred by the “anchoring effect” in behavioral economics. Nevertheless, policymakers did not take advantage of CVM in modifying the discount rate resented in the current energy efficiency support program.
The estimated IDRs are the criteria that is the basis of energy efficiency investment decisions. Energy efficiency policy can also be established using IDR, by providing the initial investment cost and energy efficiency improvement acceptable for energy consumers. The IDR should be reflected in efficiency policy to draw natural energy efficiency investment and thus supply the highly energy-efficient appliances in household sector. Otherwise, efficiency policy through support fund has limits of budget and effectiveness, eventually leading to regulation-based policy.
The estimated IDR depends on appliances. Especially for recently introduced appliances, energy consumers tend to have high IDR. Energy efficiency policy should extend the range to diffuse information for energy-efficient appliances and to increase chances to experience appliances with high energy efficiency because the barriers of newly introduced appliances come from them. Furthermore, the energy efficiency policy taking the IDR into account can synergize the existing policy because the experiences in energy efficiency improvement and energy-saving program reduce IDR.
Our study has several limits. We applied DBDC CVM model to estimate the IDR on household appliances. Although we attempted to avoid the anchoring effect by allocating initial bid randomly, still the initial bid was limited to range from 30 to 50% of IDR. To overcome this, we need to extend the experiments that have widen initial bid range with a lot of respondents. In addition, there is no comparison since IDRs on household appliances with high energy efficiency in Korea have not been investigated. The open-ended question would be a good control group for comparison. In addition, the follow-up questions are required in the IDR research to find out the determinants of willingness-to-investment other than socio-demographic factors. Lastly, high energy efficiency appliances have own characteristics. For example, the monthly electricity saving by adopting high energy efficiency appliances depends on the appliance, despite same energy efficiency level. This is because of the difference in the using intensity between appliances. The IDR estimation study would benefit from reflecting it in the questionnaire.
Consequently, the IDR should be diversified in energy efficiency policy according to the socio-demographic factors and appliance types. Second, to secure the effectiveness of supportive policy for energy efficiency investment, the level of subsidies is determined through a bottom-up approach based on consumer’s decision-making on energy efficiency investment. After then, the level of subsidies is adjusted in consideration of consumer income and education level. In this basis, the IDR should be reduced by campaigns such as specialized education.
Appendix 1
Table A1
Table A1 Additional explanatory variables: self-awareness and energy efficiency investment experiences
Variables Contents Level Number of respondents (%)
Current status of home appliances usage Air cleaner Yes 1481 (61.91%)
No 911 (38.09%)
Washing machine Yes 2338 (97.74%)
No 54 (2.26%)
Clothes dryer Yes 767 (32.07%)
No 1625 (67.93%)
Air conditioner Yes 2209 (92.35%)
No 183 (7.65%)
Refrigerator Yes 2345 (98.04%)
No 47 (1.96%)
Television Yes 2179 (91.10%)
No 213 (8.9%)
Dehumidifier Yes 1063 (44.44%)
No 1329 (55.56%)
Clothes manager Yes 363 (15.18%)
No 2029 (84.82%)
Purchasing plan (within 3 years) Air cleaner Yes 888 (33.78%)
No 1584 (66.22%)
Washing machine Yes 635 (26.55%)
No 1757 (73.45%)
Clothes dryer Yes 795 (33.24%)
No 1597 (66.76%)
Air conditioner Yes 585 (24.46%)
No 1807 (75.54%)
Refrigerator Yes 649 (27.13%)
No 1743 (72.87%)
Television Yes 675 (28.22%)
No 1717 (71.18%)
Dehumidifier Yes 578 (24.16%)
No 1814 (75.84%)
Clothes manager Yes 862 (36.04%)
No 1530 (63.96%)
Self-awareness of energy consumption pattern Confirming energy efficiency level when purchasing 1 30 (1.25%)
2 16 (0.67%)
3 27 (1.13%)
4 51 (2.13%)
5 178 (7.44%)
6 178 (7.44%)
7 474 (19.82%)
8 518 (21.66%)
9 920 (38.46)
Confirming Electricity charge when paying 1 36 (1.51%)
2 48 (2.01%)
3 57 (2.38%)
4 84 (3.51%)
5 246 (10.28%)
6 274 (11.45%)
7 407 (17.02%)
8 437 (18.27%)
9 803 (33.57%)
Participating in energy saving program 1 342 (14.30%)
2 138 (5.77%)
3 186 (7.78%)
4 158 (6.61%)
5 414 (17.31%)
6 283 (11.83%)
7 298 (12.46%)
8 234 (9.78%)
9 339 (14.17%)
Considering fuel cost in heating and cooling 1 40 (1.67%)
2 27 (1.13%)
3 40 (1.67%)
4 68 (2.84%)
5 228 (9.53%)
6 255 (10.66%)
7 561 (23.45%)
8 461 (19.27%)
9 712 (29.77%)
Multi-tap usage 1 57 (2.38%)
2 40 (1.67%)
3 60 (2.51%)
4 79 (3.30%)
5 252 (10.54%)
6 263 (10.99%)
7 436 (18.23%)
8 433 (18.10%)
9 772 (32.27%)
Turn-off the unnecessary light 1 19 (0.79%)
2 18 (0.75%)
3 38 (1.59%)
4 53 (2.22%)
5 156 (6.52%)
6 215 (8.99%)
7 437 (18.27%)
8 480 (20.07%)
9 976 (40.80%)
Energy efficiency improvement experiences Adopting appliances with high energy efficiency Yes 1725 (72.12%)
No 667 (27.88%)
Replacing windows and doors Yes 1248 (52.17%)
No 1144 (47.83%)
Setup insulator Yes 1861 (77.80%)
No 531 (22.20%)
In level column, 1 indicates “not at all,” whereas 9 “really does.”
Appendix 2 Survey questions to elicit the implicit discount rate
This is a question related to your energy efficiency investment decision making.
there are devices with general efficiency (A) and devices with high energy efficiency (B). The purchase price of device A is 300,000 KRW, and the annual energy cost is 100,000 KRW. The purchase price of device B is 400,000 KRW, and the annual energy cost is 80,000 KRW.Between the two devices, except for the difference in purchase price and annual energy cost, all other conditions are the same, the lifetime of home appliances is generally 10 years. This means that no matter which device you choose, you will be using this appliance for 10 years.
If you use a low-purchase general efficiency device (A), you will pay more energy costs than the high-energy-efficiency device (B) every year for 10 years. Energy cost can be reduced compared to device (A). For example, if you purchase a high energy efficiency device (B) instead of a general efficiency device (A), you can save an energy cost of 20,000 KRW annually for the next 10 years by investing an additional 100,000 KRW.
Q1. (All respondents) If you purchase an energy-efficient TV (Air conditioner, Dehumidifier, Air cleaner), the purchase price is 100,000 KRW more expensive than a regular-efficiency TV (Air conditioner, Dehumidifier, Air cleaner), but you can save 5.1 (3.3, 4.3) million KRW in energy costs annually for the next 10 years. This means that by investing 100,000 KRW initially, you get an interest rate of 50 (30, 40)%. Do you want to buy a high-efficiency TV (Air conditioner, Dehumidifier, Air cleaner)?Yes (Purchase) – go to Q2
No (Do not purchase) – go to Q4
Q2. (Respondent who answered that they purchase in Q1.) If you purchase an energy-efficient TV (Air conditioner, Dehumidifier, Air cleaner), the purchase price is 100,000 KRW more expensive than a general-efficiency TV (Air conditioner, Dehumidifier, Air cleaner), but you will save 2.8 (2.0, 2.4) million KRW in energy costs annually for the next 10 years. can. This means that by investing 100,000 KRW initially, you get an interest rate of 25 (15, 20)%. Do you want to buy a high-efficiency TV (Air conditioner, Dehumidifier, Air cleaner)?Yes (Purchase) – go to Q3
No (Do not purchase)
Q3. (Respondents who answered that they purchase in Q2.) So, are you willing to purchase at the lowest energy saving cost listed above?
* Since you answered in Q2 that you are willing to purchase if there is a cost savings of 2.8 (2.0, 2.4) KRW, you must respond with an amount of 2.8 (2.0, 2.4) KRW or less.
Q4. (Respondent who answered no in Q1.) Then, you can save 100,000 KRW (6.1, 8.1) in energy costs annually for the next 10 years. This means that by investing 100,000 KRW initially, you get an interest rate of 100 (60, 80)%. Do you want to buy a high-efficiency TV (Air conditioner, Dehumidifier, Air cleaner)?Yes (Purchase)
No (Do not purchase) – go to Q5
Q5. (Respondent who answered no in Q4.) So, do you have no intention of purchasing a high-efficiency TV (Air conditioner, Dehumidifier, Air cleaner) at all?Not at all
Yes(purchase) – go to Q6
Q6. (Respondents who answered that they intend to purchase in Q5.) So, are you willing to purchase at the lowest energy saving cost listed above?
* Since you answered in Q4 that you do not intend to purchase even if there is a cost savings of KRW 100,000 (6.1, 8.1), you must respond with an amount exceeding KRW 100,000 (6.1, 8.1).
DeclarationsDeclarations
Conflict of interest
The authors declare no competing interests.
1 The disadvantages of MPL are elaborated in “Advantages of CVM for IDR estimation”.
2 The 95% confidence interval is calculated using the Monte Carlo simulation suggested by Krinsky and Robb (1986).
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735117 | NO-CC CODE | 2022-12-14 23:28:32 | no | Energy Effic. 2022 Dec 6; 15(8):67 | utf-8 | Energy Effic | 2,022 | 10.1007/s12053-022-10076-3 | oa_other |
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Endocrine
Endocrine
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Original Article
Assessment of the reporting quality of randomised controlled trials for vitamin D supplementation in autoimmune thyroid disorders based on the CONSORT statement
Christos Vrysis 1
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Eirini Beneki [email protected]
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Elias Zintzaras 134
Chrysoula Doxani 1
1 grid.410558.d 0000 0001 0035 6670 Department of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, 41222 Larissa, Greece
2 grid.414122.0 0000 0004 0621 2899 State Department of Cardiology, Hippokrateion Hospital, 114 Vasilissis Sofias avenue, Athens, Attica Greece
3 grid.67033.31 0000 0000 8934 4045 Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA USA
4 grid.67033.31 0000 0000 8934 4045 Pharmacology and Drug Development Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA USA
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Background—Purpose
Randomized controlled trials (RCTs) are the cornerstone of evidence-based medicine, yet their quality is often suboptimal. The Consolidated Standards of Reporting Trials (CONSORT) statement is a list of advice to upgrade the quality of RCTs. The aim of this study was the assessment of the quality of RCTs for vitamin D supplements in thyroid autoimmunity according to the revised CONSORT 2010 checklist.
Methods
Databases were searched for RCTs involving patients with autoimmune thyroid disorders (AITDs) who received vitamin D supplements published from 2011 to 2021. A list of 37-items was used and adherence ≥75% was considered of optimal quality. The primary outcome was the mean CONSORT adherence of studies. Secondary outcomes were the estimation of compliance per CONSORT item and the examination for possible determinants of the reporting quality.
Results
Thirteen eligible trials were finally included. The mean compliance was 61.15% ± 14.86%. Only threeof the studies (23%) achieved a good reporting quality (≥75%), while ten (77%) were presented with inadequate reporting (<75%). Randomization and blinding were mainly poorly reported. Impact Factor (IF) of journal was associated with the reporting quality in the univariate analysis [p = 0.033, OR = 1.65, 95%CI = (1316, 1773)]. Sample size (p = 0.067), number of authors (p = 0.118) and number of citations (p = 0.125) were marginally not significant. None of the factors showed significant results in multivariate analysis. Reporting quality and IF were strongly positively correlated [Pearson’s r = 0.740, p = 0.04].
Conclusion
This study shows that mean CONSORT adherence of RCTs for Vitamin D supplementation in AITDs is moderate, reflecting that study quality and transparency could be improved with better adherence to CONSORT rules.
Keywords
CONSORT
Randomized controlled trials
Vitamin D supplementation
Autoimmune thyroid disease
Hashimoto disease
Graves’ disease
==== Body
pmcIntroduction
The prevalence of Autoimmune thyroid diseases (AITDs) is about five percent which rendersthem the most common amongautoimmune disorders with a continuing rise in incidence. Thefemale populationis at a greater riskof developing thyroid autoimmunity than men [1]. The most common AITDs are Hashimoto thyroiditis (HT), Graves’ disease (GD) among the general population and post-partum thyroiditis (PPT) in pregnant women.AITDare caused by multiple factors, involving both environmentaland genetic factors [2–4].
Vitamin D is a secosteroidal hormone precursor and has been identified as a key hormone inthe musculoskeletal, nervous system and insulin sensitivity [5–7]. Several studies have reported a low vitamin D status in AITD, indicating an association between vitamin D deficiency and thyroid autoimmunity [8–13]. On the other hand, a small number of studies,showed no significant association between AITDs and vitamin D deficiency [14–17]. These pieces of evidence led several researchers to examine the effectiveness of vitamin D supplementation in the prevention/treatment of this group of conditions [18, 19]. The results are conflicting, so the potential of vitamin D in thyroid diseases treatmentneeds to be clarified.
Double-blind RCTs are considered to be the highest ranked mean of evidence-based medicine and their results are crucial in the formulation of the therapeutic guidelines [20]. RCTs represent better the whole strategy and philosophy of the research [21].
Readers have access to a plethora of articles, so there is a need for a tool to assess the guidance of RCTs [22].
In 1996, an international group of experts created the CONSORT (Consolidated Standards of Reporting Trials) Statement [23]. Two revisions followed in 2001 and 2010with detailed explanation and elaboration documents [24, 25]. This statement is an evidence-based set of advice, including a checklist of 37 items and a flow diagram whose reporting ensures the avoidance of failing to include important information [25]. For that reason, an increasing number of journals endorse compliance with the CONSORT statement to improve reporting standards [26].
The quality of RCTshas beeninvestigated in a variety of specialties [27–31]. Our team, in a previous study concerning anticoagulant versus antiplatelet medication for venous thromboembolism prophylaxis, the average CONSORT compliance score was found to be 59.69% (38–83%). Only one RCT achievedmore than 75% of the CONSORT items (83%) [32].
To our knowledge, no published study has evaluated the quality of RCTs for vitamin D supplement in thyroidautoimmunity based on the CONSORT statement. The most recent study published in December 2021 was a meta-analysis focusing on cases of Hashimoto disease and the evaluation was conducted using the Cochrane CollaborationRisk of Bias tool Statistical analysis [19].
The purpose of this study is to evaluate the reporting quality of RCTsfor vitamin D supplementation in autoimmune thyroid disorders according to Consortstatement covering a period from January 2011, onwards following the release of the updated CONSORT 2010 guidelines in March 2010, until December 31st, 2021.
Methods
Data sources and search strategies
An electronic structured literature search was organized using the following databases MEDLINE/PubMed, Cochrane library and Google Scholar. We attempted to identify relevant RCTs published within the time period from January 2011 onwards following the release of the updated CONSORT 2010 guidelines in March 2010, until December 31st, 2021.
The implemented combination of the following terms is reproduced:
(((((“Vitamin D”[Mesh] OR “Ergocalciferols”[Mesh] OR “Vitamin D Response Element”[Mesh] OR “Vitamin D-Binding Protein”[Mesh] OR “Vitamin D Deficiency”[Mesh] OR “Receptors, Calcitriol”[Mesh] OR “Vitamin D3 24-Hydroxylase”[Mesh] OR “vitamin D-binding protein-macrophage activating factor” [Supplementary Concept] OR “Cholecalciferol”[Mesh] OR “MED4 protein, human” [Supplementary Concept] OR “vitamin D binding protein 2, primate” [Supplementary Concept] OR “vitamin D binding protein 1, primate” [Supplementary Concept] OR “vitamin D response element-binding protein 2” [Supplementary Concept] OR “vitamin D 1-alpha hydroxylase” [Supplementary Concept] OR “vitamin D3 glucosiduronate” [Supplementary Concept]) OR (“Calcitriol”[Mesh] OR “25-O-ethyl-calcitriol” [Supplementary Concept] OR “22-dehydro-1,25-dihydroxy-24-dihomovitamin D3” [Supplementary Concept] OR “24,24-difluoro-1,25-dihydroxy-26,27-dimethylvitamin D3” [Supplementary Concept] OR “1,25-dihydroxyvitamin D3-23,26-lactol” [Supplementary Concept] OR “Vitamin D supplementation”)) AND (“Hashimoto Disease”[Mesh] OR “Hypothyroidism, Autoimmune” [Supplementary Concept])) OR (“Thyroiditis”[Mesh] OR “Postpartum Thyroiditis”[Mesh] OR “Thyroiditis, Autoimmune”[Mesh] OR “Thyroiditis, Chronic” [Supplementary Concept])) OR “Hypothyroidism”[Mesh]) OR (“anti-thyroid autoantibodies” [Supplementary Concept] OR “Autoantibodies”[Mesh] OR Graves’ disease OR Hyperthyroidism OR postpartum thyroiditis).
In order to restrict the search in PubMed, the “Randomized Controlled Trial”filter for study type, the “English” filter for language and lastly the “Humans”species filterwere used.
Eligibility of studies
Inclusioncriteria:Published from January 1st 2011 until December 31st, 2021
Parallel groupRCTs
One group was randomized to receive calcitriol or other Vitamin D analogs
They recruit patients with autoimmune thyroid disease
Exclusion criteria:Non-randomized studies
Reviews
Pilot studies
Non-human studies
Studies with crossover design
Economic analyses
Small pilot studies
Study protocols
Articles not in English
Reporting assessment tool
The revised CONSORT checklist was used, which includes a 37-item questionnaire [25]. The CONSORT elaboration and explanationstatementguided the process [33]. CONSORT offersrecommendations for eachpart of an RCT, such as title, introduction, methods, results, discussion or other information, coveringall aspects of an optimal clinical trial [34].
The immediate period (until December 31st2010) following the publication of the latest revision of CONSORT statement (Mar 2010) was not included in the assessment. This decision was made to provide authors with enough time to abide by the revisedrecommendations.
Methodological evaluation
During the evaluation process, the selected articles were reviewed one by one according to the revised CONSORT version of 2010.Each item was appraised one of the following scores: ‘yes’ 1 point when adequately reported, ‘no’ or ‘unclear’ 0 points when inadequately reported or absent. When an item was reported in a different section of the trial, it was considered as a positive response.Regarding items on the CONSORT check- list with statements such as “When applicable” (7b), “If done” (11a)or “If relevant” (11b) they were checked as “non-applicable” if the answer was definite yes or no; then the answer of these items wasanalyzed accordingly.This resulted in a score range from 0 to 37.
Additional information included publication year,journal ranking [5-year Impact Factor (IF)published in 2020 by Clarivate Analytics via Journal Citation Reports], reporting of funding sources, number of authors, continent of first author, sample size, number of citations.
Outcome measures and Statistical analysis
The period from January 2011until December 31st, 2021 was assessed.It was decided that the remaining part of 2020 would not be evaluated in order to provide a sufficient time for authors to conform with the newest recommendations.The primary outcome measure was the mean CONSORT adherence of the included RCTs.Compliance above 75% with the CONSORT items was regarded as cut-off [31, 32]. We investigated the adherence of each itemseparately and the existence of possible determinant factors were also investigated.
All parameters were analyzed as categorical variables:IF (<2.86, ≥2.86 based on the median of our sample), sample size (≥82, <82 based on the median of our sample), citations (≥ 5, <5 based on the median of our sample), number of authors(≥7, <7 based on the median of our sample), funding source(yes/no), Covid-19 pandemic(earlier/in the course of). Pearson’s chi squared test (or Fisher’s exact test) was used for univariate analysis.A relaxed p-value of 0.20 was established arbitrary as a cut-off value in order to enter the binary logistic regression. A strict P value of 0.05 was set to be important for the multivariate analysis. Odds ratios (ORs), 95% confidence intervals (95% Cls) and P value are presented. An additional analysis was performed in order to examine a possible linear correlation between IF and reporting quality.SPSS v.26 package was used for statistical analysis.
Ethical view
No approval from any Ethical committee was sought, since this study analyzed existing data from publicly available sources.
Results
Initially, 8196 studies were obtained through the selected databases(Pubmed, Cochrane library and Google scholar). After removal of duplicated items, 6467 records were remained. Following evaluation of title and abstracts, 20 potentially eligible articles were identified. Finally, the full-text of these studies were examined and 13 studies were included in further assessment. Fig. 1 describes the five steps of the search strategy in a PRISMA flow diagram.Fig. 1 Flow diagram
CONSORTadherence
The mean compliance to the CONSORT statement for RCTs was calculated at 61.15% with SD = 14.86% (Median = 62%, minimum & maximum adherence were 38% and 86% respectively). Among the studies, only 3 (23%) achieved a good reporting quality (≥75% of the items), while 10 (77%) presented with inadequate reporting (< 75% of the items). The mean proportion of adherence to the CONSORT statement for each study are presented in Table 1 and Fig. 2.Table 1 List of randomized controlled trials along with the CONSORT (Consolidated Standards of Reporting Trials) score
Article Medical Journal Year Mean compliance score (%)
Chahardoli et al. [42] Hormone and Metabolic Research 2019 62
Nodehi et al. [43] European Journal of clinical nutrition 2019 65
Anaraki et al. [44] Journal of research in medical sciences 2017 51
Anaraki et al. [45] Journal of research in medical sciences 2017 65
Simsek et al. [46] Journal of research in medical sciences 2016 44
Chaudhary et al. [47] Indian Journal of endocrinology and metabolism 2016 52
Behera et al. [48] Nigerian medical journal 2020 38
Laugesen et al. [49] Endocrine 2019 84
Laugesen et al. [50] Thyroid 2019 86
Mei et al. [51] Annals of palliative medicine 2021 57
Knutsen et al. [52] Journal of the Endocrine Society 2017 76
Purnamasari et al. [53] Asian Journal of Pharmaceutical and Clinical Research 2017 72
Ucan et al. [54] International Journal for vitamin and nutrition research 2016 43
Fig. 2 Distribution of the total CONSORT (Consolidated Standards of Reporting Trials) scores of the 13 studies
Adherence per CONSORT item was estimated (Table 2, Fig. 3). Specially, 5 of the 37 items of the checklist (13.5%) were reported in all (100%) of the articles and only 16 of the 37 items of the checklist (43.2%) were reported by 75% or more of the studies. Among methodological items, randomization process (items 8a and 8b) and blinding (items 10 and 11a) were mainly inadequately reported. In contrast, a structured abstract (item 1b) was reported adequately (77%) among the studies and is considered of crucial importance, taking into account that most readers base their decision to acquire or not a full text on its abstract.Table 2 Adherence per CONSORT (Consolidated Standards of Reporting Trials) item
Item No Checklist item Compliance (%)
Title and abstract 1a Identification as a randomised trial in the title 61
1b Structured summary of trial design, methods, results, and conclusions 77
Introduction 2a Scientific background and explanation of rationale 100
2b Specific objectives or hypotheses 100
Methods 3a Description of trial design (such as parallel, factorial) including allocation ratio 92
3b Important changes to methods after trial commencement (such as eligibility criteria), with reasons 61
4a Eligibility criteria for participants 92
4b Settings and locations where the data were collected 92
5 The interventions for each group with sufficient details to allow replication, including how and when they were actually administered 85
6a Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed 85
6b Any changes to trial outcomes after the trial commenced, with reasons 31
7a How sample size was determined 46
7b When applicable, explanation of any interim analyses and stopping guidelines 70
8a Method used to generate the random allocation sequence 46
8b Type of randomization; details of any restriction (such as blocking and block size) 70
9 Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 38
10 Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions 7.7
11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how 38
11b If relevant, description of the similarity of interventions 31
12a Statistical methods used to compare groups for primary and secondary outcomes 100
12b Methods for additional analyses, such as subgroup analyses and adjusted analyses 46
Results 13a For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analyzed for the primary outcome 92
13b For each group, losses and exclusions after randomization, together with reasons 70
14a Dates defining the periods of recruitment and follow-up 77
14b Why the trial ended or was stopped 0
15 A table showing baseline demographic and clinical characteristics for each group 100
16 For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 85
17a For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) 15
17b For binary outcomes, presentation of both absolute and relative effect sizes is recommended 23
18 Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory 70
19 All-important harms or unintended effects in each group 23
Discussion 20 Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses 92
21 Generalizability (external validity, applicability) of the trial findings 31
22 Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence 100
Other information 23 Registration number and name of trial registry 70
24 Where the full trial protocol can be accessed, if available 15
25 Sources of funding and other support (such as supply of drugs), role of funders 77
Fig. 3 Correlation (scatter-plot) between reporting quality and IF (Impact Factor)
Determinants of reporting quality
According to univariate analysis high IF of journal was the only with superior statistical significance (p < 0.05). Large sample size, great number of authors, existence of funding source was all associated with an adequate p value (p < 0.20) in order to enter binary logistic regression. Results are summarized at Table 3.Table 3 Univariate analysis of possible determinants of reporting quality
Parameter OR 95% CI P value
IF of journal (>2.86 = median) 1.65 1.316–1.773 0.033
Funding source (yes/no) 2 0.115–34.822 0.631
Covid-19 pandemic (earlier/in the course of) 0.8 0.587–1.091 0.4
Citations (>5 = median) 8 0.459–139.290 0.125
Sample size (>82 = median) 1.016 0.994–1.039 0.067
Number of authors (>7 = median) 1.07 0.547–2.093 0.118
OR odds ratio, 95% CI 95% confidence interval, IF impact factor
The four predictors of the univariate analysis were entered into a multivariable model. None of these was associated significantly with adequate reporting. Particularly, the journal impact factor (p = 0.150) failed to demonstrate significant effect, whereas the effect of number of citations (p = 0.650), sample size (p = 0.161) and number of authors (p = 0.892) persisted inadequately. Results of binary logistic regression are illustrated at Table 4.Table 4 Multivariate analysis of possible determinants of reporting quality
Parameter OR 95% CI P value
IF of journal 2.500 0.717–8.712 0.150
Citations 1.127 0.673–1.888 0.650
Sample size 1.026 0.990–1.064 0.161
Number of authors 1.069 0.410–2.782 0.892
OR odds ratio, 95% CI 95% confidence interval, IF impact factor
Finally, an additional analysis (Fig. 3) discovered the occurrence of satisfactory positive linear corellation between reporting quality and IF
[Pearson’s correlation (r = 0.740, p = 0.004)].
Discussion
CONSORT adherence
The present study evaluated the reporting quality of RCTsthat examined the effect of vitamin D supplement in thyroid autoimmunity according to 2010 CONSORT statement. The conclusion is that the overall CONSORT adherence is far from optimal, with the mean compliance equal to 61.15%. The number and sample size of RCTs based on our subjectis smaller than that of other endocrinological diseases probably due to rising interest of researchers in the last decade [35–37]. We collected and analyzed 13 articles referring to 1174 randomized participants. Only three of them showed compliance above 75%.
Furthermore, 16 of 37 checklist items (43.2%) were addressed by 75% or more. The report of crucial methodological characteristics like randomization (item 9: allocation concealment method—38%; item 10: implementation—7.7%) and blinding (item 11a: who was blinded—38%) was found to be suboptimal. Unclear or absent description of randomization and blinding degrades RCTs due to complicated risk of bias [38]. Also, inadequate explanation of adverse effects in their articles (item 19: harms or unintended effects—23%) will probably misguide the medical approach of the physicians and may even give wrong advice to their patients. Item 14b (Why the trial ended or was stopped—0%) was the least reported item.On the contrary, it is hopeful that significant items such as trial design (item 3a – 92%) and report of the interventions for each group (item 5–85%) achieved a strong representation.
Determinants of reporting quality
Univariate analysis suggested thatlarger sample size,higher number of authors,the presence of funding wereall associated with abetter reporting quality but not statistically significant. Only RCTs of high-ranked medical journals showed superior adherence to the CONSORT statement giving statistically significant results (p < 0.05) and additionally a strong linear correlation (r = 0.740). IF was previously studied and a number of studies demonstrated an important association between IF and reporting quality [28, 29, 32, 34]. This is because journals with a higher IF have more strictrules for the publication of studies.
Despite the indications of univariate analysis, logistic regressionof possible determining factors canceled the previous effectof impact factor in the reporting quality of RCTs.In any case, we have to make referenceto commercial funding. It is crucial that our study comes in harmony with previous showing non-significant impact in scientific information [28, 38–40].
In one hand, the reporting quality of RCTs for Vitamin D supplementation in autoimmune thyroid disorders appeared not to be affected by Covid-19 pandemic. On the other hand, several fields of research are being lured away from their main area of interest to the pandemic, including the possibility that other health topics are ignored or not done properly [41]. It is important to highlight that literature search involved three databases: PubMed/MEDLINE, Cochrane Library and Google scholar creating a source of 8196 studies and increasing the overall efficacy of search strategy. As is well known, CONSORT statement is free and the methodology of current study is easily accessible.
However, our results must be interpreted with skepticism and some points need to be addressed. Vitamin Dsupplementation in autoimmune thyroid disorders is not a field well studied by the research community. As a result, the number of RCTs we analyzed, is quiet low. Moreover, articles not published in English orreleased beyond the time limit were excluded. The researcher was not blinded to journal and all items were rated as equal. So, the methodological analysis becomes more susceptible to subjectivity as certain items like flow diagram, randomization and blinding are more important than others.
Considering the increasing number of publications, investigators are recommended to report their RCTs according to the CONSORT statement and the CONSORT statement should be implemented in the editorial process. The improvement of the quality of RCTs could assist to reach more conclusive results, to minimize biased conclusions, to elucidate better the clinical significance of RCTs, and to direct more specifically future medical research.
Conclusion
To the best of our knowledge, the present study is the first to evaluate the reporting quality of RCTs for Vitamin D supplementation in autoimmune thyroid disorders according to 2010 CONSORT statement. The results we obtained were discouraging. It is our feeling that our subject is generally badly reported. Taking into account the controversial role of VitD supplementation on the prevention and/or treatment of AITD and the increasing number of publications, we concluded that the compliance with CONSORT guidelines becomes essential in order to provide more reliable and consistent answers to scientific question.
Author contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by V.C., B.E., E.Z. and D.C. The first draft of the manuscript was written by Vrysis Christos and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36462148 | PMC9735118 | NO-CC CODE | 2022-12-14 23:28:32 | no | Endocrine. 2022 Dec 3;:1-9 | utf-8 | Endocrine | 2,022 | 10.1007/s12020-022-03270-x | oa_other |
==== Front
Mol Biol
Mol Biol
Molecular Biology
0026-8933
1608-3245
Pleiades Publishing Moscow
8413
10.1134/S0026893322060218
Mammalian Genome Editing
Structural Elements of DNA and RNA Eukaryotic Expression Vectors for In Vitro and In Vivo Genome Editor Delivery
Zagoskin A. A. 1
Zakharova M. V. 1
Nagornykh M. O. [email protected]
12
1 grid.470117.4 Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, 142290 Pushchino, Russia
2 grid.510477.0 Sirius University of Science and Technology, Sirius, 354349 Sochi, Russia
9 12 2022
2022
56 6 950962
18 5 2022
25 6 2022
28 6 2022
© Pleiades Publishing, Inc. 2022, ISSN 0026-8933, Molecular Biology, 2022, Vol. 56, No. 6, pp. 950–962. © Pleiades Publishing, Inc., 2022.Russian Text © The Author(s), 2022, published in Molekulyarnaya Biologiya, 2022, Vol. 56, No. 6, pp. 1023–1038.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Gene editing with programmable nucleases opens new perspectives in important practice areas, such as healthcare and agriculture. The most challenging problem for the safe and effective therapeutic use of gene editing technologies is the proper delivery and expression of gene editors in cells and tissues of different organisms. Virus-based and nonviral systems can be used for the successful delivery of gene editors. Here we have reviewed structural elements of nonviral DNA- and RNA-based expression vectors for gene editing and delivery methods in vitro and in vivo.
Keywords:
expression DNA vector
IVT RNA
mRNA-based delivery
genome editing
Cas9
ZFN
TALEN
GENE THERAPY
NANOPARTICLES
issue-copyright-statement© Pleiades Publishing, Inc. 2022
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pmcINTRODUCTION
Currently there are three main variants of genetic editors, i.e., ZFN, TALEN, and CRISPR/Cas systems. The use of these systems involves the creation of vectors for the expression of the above proteins. Currently, viral and nonviral expression vectors are widely used. Nonviral vectors include DNA-based vectors and synthetic mRNAs. In general, the structure of DNA-based vectors for genome editing differs little from the expression vectors of other therapeutic recombinant proteins. In both, there are structural elements, such as promoters, enhancers, poly(A) sequences, selective markers, replication initiation sites, etc. Differences in structure relate to specific elements necessary for the functioning of genome editors, and each editing system has its characteristics. In most cases, a nuclear localization signal is merged with the sequence of the genome editor, and the CRISPR-Cas-carrying vectors contain promoters for RNA polymerases II and III because it is necessary to obtain guide RNA in addition to proteins.
RNA molecules can also be used as expression vectors for the synthesis of therapeutic proteins and genetic editing of cellular DNA. This delivery method has several significant advantages over DNA vectors. When using RNA, the probability of integration of the vector or its parts into the genome is extremely small, which almost totally excludes mutagenic events. Another significant advantage is that RNA in combination with lipid nanoparticles is a biodegradable carrier. In addition, there is no need for RNA to penetrate the cell nucleus because the translation of the transgene occurs immediately after entering the cytoplasm. Finally, the transient nature of transgene expression with RNA is better controlled, which avoids excessive production of transgenes, such as gene editor molecules, and reduces the risk of non-specific editing of the cell genome. It is necessary to note the main disadvantages of using artificial RNA carriers, which are primarily caused by the instability of RNA and the high immunogenicity of foreign RNA, which is associated with the mechanisms of antiviral immunity formed by the evolution of eukaryotes.
The potential for biomedical use of synthetic mRNAs was demonstrated in 1990 in an experiment on the expression of various proteins in skeletal muscle cells of mice. However, problems with extracellular and intracellular stability, RNA immunogenicity, and the complexity of large-scale production have slowed down the spread of the use of synthetic mRNAs for therapeutic purposes. Currently, the synthesis of single-stranded RNA molecules in vitro is a widespread laboratory procedure, which is actively used for both the study of RNA and the preparation of RNA-based drugs. This method is applicable for the biochemical and molecular analysis of RNA, the study of RNA-protein interactions, the structural analysis of complexes, the creation of RNA aptamers, the synthesis of functional mRNAs for expression, and the production of small RNAs that affect gene expression (e.g., guide RNAs for gene editors). In addition, in vitro synthesized RNAs have played an important role in the development of RNA vaccines, the CRISPR/Cas9, ZFN, and TALEN genome editing tools, pluripotent stem cells, and diagnostic methods based on RNA amplification.
In this review, we will consider the main structural elements of DNA- and RNA-based expression vectors including those used in gene editing and the methods for in vitro and in vivo delivery of these vectors.
STRUCTURAL ELEMENTS OF DNA- AND RNA-BASED EXPRESSION VECTORS FOR DELIVERY OF GENOME EDITORS
Promoters
A promoter is a nucleotide sequence that is recognized by an RNA polymerase complex and specifically binds this complex, thus leading to the initiation of transcription of the nucleotide sequence located below the promoter. Mammalian cells contain several types of RNA polymerases, each of which interacts with specific promoters. Most often, researchers are interested in promoters that can interact with RNA polymerase II. This enzyme is responsible for the synthesis of mRNAs, which are templates for the synthesis of polypeptides [1]. The functioning of any promoter is due to the interaction of proteins that are part of RNA polymerase with certain nucleotide motifs in the promoter. The structure of mammalian promoters, which interact with RNA polymerase II, contains about ten different motifs, i.e., MTE, BREu, BREd, XCPE1 and others, and the most well-known motifs are the initiator and TATA box [2]. Most motifs have a fixed position on the promoter relative to the transcription start point. However, CpG islands, for example, can be located at different positions.
Both the position of motifs and their composition are important for the structure of promoters. Based on these two parameters, promoters are divided into two types: scattered and focused promoters. The scattered type most often includes promoters that ensure the expression of housekeeping genes. They often lack an initiator and the TATA box but contain a large number of CpG islands. These promoters provide stable moderate expression of the gene under control. As an example, we can consider the promoter of the human phosphoglycerate kinase (hPGK) gene, which contains a large number of CpG islands but lacks the TATA box and the initiator sequence. In contrast, focused promoters often have few CpG islands but there are motifs, for example, an initiator and a TATA box, which provide strong interaction with RNA polymerase complexes [3]. These promoters usually provide intracellular expression at a high level in a short time. Promoters of this type are often found in the genomes of viruses. The promoters of the focused type include the promoter of the SV40 virus or the promoter of the human EF1a gene. Since researchers want to achieve a high level of expression of recombinant proteins when creating vectors, they use promoters of the focused type.
In practice, it turns out that many promoters of this type have a viral nature, for example, the SV40 or cytomegalovirus (CMV) promoters. Sometimes, there is a need for an RNA product whose structure differs from that of mRNA. In particular, this product is necessary for obtaining a guide RNA for the CRISPR/Cas genome editing system. For this purpose, a promoter that interacts with RNA polymerase III is used, e.g., the U6 promoter [4]. In addition to promoters that provide stable expression, there are also induced promoters, which can be both scattered and focused types and include a regulatory element to control expression [5]. Examples are the Tet-On inducible system or the thermoinducible Hsp70 promoter. These promoters can be advantageous when the synthesized protein is cytotoxic or it is necessary to give time to the cell culture to grow before expressing the target gene.
Another type of promoter, which have much in common with inducible promoters, are tissue-specific promoters. They can belong to both the scattered and focused types but contain a motif or motifs, which specifically interact with some protein. In most cases, the protein is a tissue-specific transcription factor. Since gene expression under the control of these promoters occurs strictly in a certain type of tissue, they are used for genetic editing in vivo [6]. For example, the SLPI promoter, which is active in some types of carcinomas, ensures a low level of expression of the gene encoding the inhibitor of leukoprotease secreted in the liver. Promoters come in different ‘strengths’, i.e., they provide different levels of gene expression. They can promote both stable gene expression and expression in a certain type of tissue under the action of a certain inductor. They can have different sizes ranging from hundreds to thousands of nucleotides. It is necessary to select these parameters based on the needs of the experiment.
Enhancers
Enhancers increase the level of gene expression by increasing the local concentration of transcription factors. Like promoters, enhancers perform their function using a variety of motifs that attract transcription factors [7]. Enhancers are most often located in the genome far from the controlled promoter; the promoter and enhancer may even be located on different chromosomes [8]. At the same time, due to the DNA architecture, the enhancers are located near the controlled promoter that is a prerequisite for enhancer function. In vectors, however, enhancers are located before the promoter. Eukaryotic enhancers most often have a fairly large size; therefore, viral variants of these elements with a small size have found wide application. For example, the CMV enhancer [9] is widely used, which is merged with both viral and eukaryotic promoters. Most of the currently used vectors contain an enhancer for increasing the level of expression of the target gene.
Untranslated Sequences
Translation of the polypeptide begins with the AUG initiator codon (start codon). For successful initiation, the start codon must be in a certain nucleotide surrounding, i.e., the Kozak sequence. This motif is quite conservative; in higher eukaryotes, it is represented by the GCC(A/G)CCATGG sequence, which contains especially important nucleotides at positions –3 and +4 [10]. The Kozak sequence functions through interaction with the 40S subunit of the ribosome and translation initiation factors. During mRNA scanning, the ribosome is delayed on the secondary structure formed by the Kozak sequence, thus increasing the probability of translation initiation [11]. When creating a vector, the Kozak sequence is embedded directly before the gene because the absence of this sequence significantly reduces the translation efficiency. The poly(A) tail on the 3' end of mRNA significantly increases both the stability of mRNA and the efficiency of translation. To attach the poly(A) tail in the mRNA structure, the plasmid should include the polyadenylation signal, i.e., the conservative sequence with the AATAAA motif followed by a GT-rich region. mRNA without the poly(A) tail undergoes rapid degradation by cellular nucleases, which negatively affects the overall efficiency of transgene expression [12]. Therefore, the inclusion of the polyadenylation signal in the expression cassette after each protein-coding sequence is also a mandatory step in creating a vector that expresses a recombinant protein.
Selective Marker
A selective marker helps to successfully select transformed cells. Often, antibiotic resistance genes are used because this allows one to quickly select transfected cells by their survival after adding the appropriate antibiotic to the nutrient medium. Moreover, the presence of the antibiotic resistance gene makes it possible to be sure that the plasmid will not be eliminated by the cell over time because the cell needs to express the antibiotic resistance gene for survival under constant antibiotic pressure. To save space, the selective marker can be expressed along with the transgene in the same reading frame using the 2A peptide or IRES element [13]. However, it should be taken into account that the expression level under the control of the IRES element is significantly lower than under the control of the promoter. In addition to resistance genes, fluorescent proteins, such as GFP, are also used as a marker of selection in eukaryotic cells. In this case, transformants are selected using cellular sorters. This approach is appropriate when it is necessary to temporarily express a transgene, followed by elimination (preferably) of the plasmid from the cell to prevent load on the translational apparatus [14]. In particular, this approach is used when creating plasmids that carry gene editors. The fluorescence proteins make it possible to select transformants; genetic editors work for a short time, followed by degradation of the plasmid. There is also a ‘bacterial’ part in the plasmids, which is necessary to obtain a large amount of the plasmid before transfection of eukaryotic cells. A prokaryotic selective marker is present in the bacterial part; most often it is the ampicillin resistance gene. This gene allows Escherichia coli cells to be cultured on an ampicillin-containing medium and, more importantly, to retain the plasmid in the cell.
Signal Peptide
It is often not enough to express the target gene; it is also necessary to ensure the secretion of a protein from the cell or its entry into the appropriate compartment for functioning. For this purpose, there are signal peptides encoded by the 5'-terminal region of the nucleotide transgene sequence. As a result, the synthesized protein is delivered to the cellular compartment, determined by the signal peptide. Genetic editors are usually merged with nuclear localization signals, which leads to the delivery of the synthesized editor to the cell nucleus, where it exhibits its activity [15].
Replication Start Point
Another important component of the bacterial part of the vector is the replication start point (origin) of replication. This is the start point of the synthesis of plasmid copies in a bacterial cell. In fact, this is a regulatory site that influences the number of copies of the plasmid in the cell. There are low-copy and high-copy replication origins. Researchers most often need to obtain a large number of copies of the plasmid; therefore, the high-copy ColE1 origin of replication has become widespread [16].
DNA-Based Expression Vectors to Deliver Genome Editors
Summarizing the above, the map of the base vector for the expression of recombinant therapeutic proteins can be schematically represented as follows. The base vector must have a bacterial part, which should consist of a replication origin to obtain a large number of copies of the plasmid in E. coli and a prokaryotic selective marker of the vector resistance in E. coli cells. The ‘eukaryotic’ part of the vector should contain a fused enhancer and promoter to control the expression of a certain target protein, the Kozak sequence at the 5' end of the sequence encoding the protein, and the polyadenylation signal with a terminator on the 3' end. If the vector is to be used in vitro, it is necessary to have a eukaryotic selective marker (such as an antibiotic resistance gene) controlled by a second promoter because this marker is also a protein. The Kozak and poly(A) sequences are also needed (Fig. 1).
Fig. 1. The structure of the base vector for eukaryotic expression of therapeutic proteins. (1) Replication origin; (2) prokaryotic selective marker; (3) prokaryotic promoter; (4) eukaryotic enhancer; (5 and 9) the eukaryotic promoters specifically interacting with RNA polymerase II; (6 and 10) Kozak sequences; (7) target protein gene; (8 and 12) polyadenylation signals; (11) eukaryotic selective marker.
The vectors presented in the work of Zou J. et al. can be considered as examples of the structure of vectors that carry the ZFN-based gene editor [17]. The authors proposed a vector that contains a target gene, i.e., a sequence encoding a chimeric protein that consists of the FokI nuclease domain and zinc fingers that direct the nuclease to the desired part of the genome. In addition, there is a nuclear localization signal, which is located on the 5' end of the protein-coding sequence. As a marker of selection, the vector contains the gene for resistance to blasticidin, which provides rapid selection of transfected cells. In other respects, it is a typical vector for the synthesis of recombinant proteins (Fig. 2a). Editors can be directed not only to the cell nucleus but also to the mitochondria [18]. Since the compartment in which the editing should take place was not the nucleus, the transport signal into the mitochondria was placed at the N-end of the protein. The synthesized protein entered the mitochondria, where FokI endonuclease activity was manifested.
Fig. 2. The structure of vectors for the expression of gene editors in eukaryotic cells. (a) The expression vectors for genome editing using ZFN and TALEN are very similar, only element 8 differs. Targeting is carried out by zinc fingers in the first case and the effector DNA-binding domain in the second case. (1) Replication origin; (2) prokaryotic selective marker; (3) prokaryotic promoter; (4) eukaryotic enhancer; (5 and 11) eukaryotic promoters which specifically interact with RNA polymerase II; (6 and 12) Kozak sequences; (7) nuclear localization signal peptide; (8) zinc fingers/effector DNA-binding domain; (9) FokI endonuclease; (10, 14) polyadenylation signal; (13) eukaryotic selective marker; (b) Genome editing using CRISPR/Cfs. (1) Replication origin; (2) prokaryotic selective marker; (3) prokaryotic promoter; (4) eukaryotic enhancer; (5 and 10) eukaryotic promoters, which specifically interact with RNA polymerase II; (6 and 11) Kozak sequences; (7) signal peptide of nuclear localization; (8) Cas protein with endonuclease activity; (9 and 13) polyadenylation signals; (12) eukaryotic selective marker; (14) U6 promoter, which specifically interacts with RNA polymerase III; (15) guide RNA sequence.
The targeting to the target site in the TALEN-based technology is provided by effector DNA-binding domains, and the cleavage is performed by the FokI nuclease domain. Effector DNA-binding domains are rather conservative small regions that consist of 33–34 amino acid residues with variable residues at positions 12 and 13 that promote interaction with DNA. The sequential arrangement of these domains makes it possible to recognize different motifs in DNA. In this case, a chimeric protein is synthesized that consists of the TALEN domain and FokI nuclease connected by a spacer. Consequently, the vector for the expression of the TALEN-based gene editor will also not differ from the base vector that provides the synthesis of recombinant proteins because the entire editor is one large protein [19] (Fig. 2a). As an example, we can consider the work of Kim Y.H. et al., who tried using the TALEN-based gene editor to change the set of antigens on the surface of erythroid progenitor cells, thus obtaining universal group I blood from the blood of any other group [20]. A nuclear localization signal was attached to the TALEN-encoding nucleotide sequence; on the whole, however, this vector can be called standard, except for one feature, i.e., it lacks a eukaryotic selective marker but this is due to the specificity and requirements of the experiment. The disadvantages of ZFN- and TALEN-based systems include the complexity of creating recognition domains and, sometimes, the inability to choose modules for recognizing the nucleotide sequence. The advantage of these systems is the relatively small size of the expression vector.
Unlike ZFN and TALEN, the CRISPR/Cas-based genetic editor is a complex consisting of a Cas endonuclease and a guide RNA, which is the main feature of the expression vector of the CRISPR/Cas editor [21]. The structure of synthesized guide RNA significantly differs from RNAs synthesized by RNA polymerase II. The guide RNA lacks the cap and poly(A) tail, characteristic components of mRNA. The synthesis of guide RNA is provided by RNA polymerase III; therefore, the vector must include a promoter that can interact with this polymerase. The human U6 promoter is most often used for this purpose [22]. As to the rest, the composition of the vector should be the same as that of a typical vector for the synthesis of recombinant proteins (Fig. 2b). As an example, we can consider a vector from Gabriel C.H et al. [23]. The authors used a CRISPR/Cas-based editor to knock out genes. They used GFP as a selective marker, which was expressed from the same reading frame as the Cas9 protein. To obtain two proteins, the 2A peptide was placed between Cas9 and GFP. Another difference was that the promoter, which controlled the expression of Cas9, was not merged with the enhancer, and, instead of that, an intron was placed next to the promoter. This element can also enhance the expression of the target product.
Thus, it can be stated that the expression vector may include various functional elements in addition to the standard elements. If it is necessary to place the plasmid DNA into viral particles, the vector must contain sites that specifically interact with the viral capsid. Transgene expression can also be modulated by certain regulatory elements. Ultimately, the choice of elements depends on either the requirements of the experiment or the therapeutic application.
STRUCTURAL ELEMENTS OF SYNTHETIC mRNAs FOR DELIVERY OF GENOME EDITORS
Structure of Natural mRNAs
mRNA is synthesized in the nucleus and undergoes various modifications, followed by translation in the cytoplasm. After modification of the 5' and 3' termini, mRNA becomes functionally active. The transcribed mRNA undergoes splicing and two significant modifications. 7-Methylguanosine is attached to 5'-triphosphate in pre-mRNA through a 5'–5' bond with the formation of a so-called cap structure. This structure protects mature mRNA from degradation and promotes nuclear transport and efficient translation. The second modification is the post-transcriptional addition of the poly(A) tail (100–250 adenosine residues) to the 3' end of the RNA molecule. The addition of the poly(A) tail imparts stability to the mRNA molecule, promotes the export of mRNA to the cytosol, and participates in the formation of a translationally competent ribonucleoprotein complex along with the 5'-cap structure. Mature mRNA forms a ring structure (closed loop) and connects the cap to the poly(A)tail through the cap-binding eIF4E protein (eukaryotic translation initiation factor 4E) and poly(A)-binding protein (PABP), which interact with eIF4G (eukaryotic translation initiation factor 4G). Thus, the main requirements for functional mRNA are the presence of the cap (7-methylguanosine) at the 5' end and the poly(A) tail at the 3' end [24].
Transcription and Capping of Synthetic mRNAs
Transcription is one of the main biological processes underlying the central dogma of molecular biology. DNA-dependent RNA polymerases, which perform this stage of transmission of genetic information, are common in all forms of life. As a rule, these enzymes are intricate multisubunit complexes, which transcribe prokaryotic and eukaryotic genes in vivo. mRNA is synthesized in vitro by bacteriophage polymerases (T7, T3, and SP6), one-unit enzymes whose activity requires only Mg2+ ions. The DNA molecule (PCR fragment or linearized plasmid), which contains the sequence of the corresponding promoter, acts as a template for in vitro transcription. The enzyme promotes the synthesis of a complementary RNA molecule, followed by dissociation of the transcription complex at the end of the process. The DNA template and the enzyme can be reused in the following reactions. The yield of synthesized mRNA can reach milligram quantities in this process. After transcription, RNA is treated with DNase I to remove the DNA template and is purified before capping. This method makes it possible to obtain RNA with 5'-triphosphate termini in a high yield. The resulting RNAs need to be supplied with the cap structures [25].
For effective translation of synthetic mRNA, it must transformed into mature mRNA by attaching the cap and poly(A) tail during or after the RNA synthesis in separate reactions catalyzed by capping enzymes and poly(A)-polymerase, respectively (Fig. 3). Additionally, modified internal bases or modified cap structures can be included in artificial RNA molecules, which can increase the stability and translational activity of the final molecule. Depending on the chosen copying strategy, two variants of in vitro transcription are used. The standard synthesis with enzymatic capping after the transcription reaction (post-transcriptional capping) or the inclusion of a cap analog during transcription (co-transcriptional capping). The strategies of the in vitro mRNA synthesis depend on the desired scale of synthesis.
Fig. 3. The structure of synthetic mRNA. (1) Cap structure; (2) 5'-untranslated regions; (3) open reading frame encoding the transgene; (4) 3'-untranslated area; (5) poly(A) tail.
Post-transcriptional mRNA capping is often performed using enzymes of the smallpox vaccine virus. This enzyme complex converts the 5'-triphosphate ends of transcripts in vitro into m7G-cap structures. The cap system of the smallpox vaccine virus includes three active parts (RNA triphosphatase, guanylyl transferase, and guanine-N7 methyltransferase), which are necessary for the formation of the complete cap structure (m7Gppp5'N) using GTP and S-adenosyl methionine, the donor of the methyl group. Additionally, 2'-O-methyltransferase can be included in the same enzymatic reaction, which leads to the formation of the cap 1 structure by methylation of the 2'‑O-position of the nucleotide following the cap. This reaction is a natural modification of many eukaryotic mRNAs [26].
During transcriptional copying, the cap analog is embedded in RNA as the first nucleotide of the synthesized molecule. The cap analog is introduced into the transcription reaction along with four standard nucleoside triphosphates in a 4 : 1 ratio of optimized cap to GTP. This makes it possible to initiate the formation of a significant number of cap-containing transcripts among the synthesized RNA molecules. As a result, a mixture of transcripts is formed, of which ~80% are capped and the rest have the 5'-triphosphate termini. The decrease in the total yield of RNA products is caused by a lower concentration of GTP in the reaction. In the case of co-transcriptional capping, several synthetic cap analogs are used. The most common analogs are the standard cap, 7-methylguanosine (m7G), and the symmetric cap analog (ARCA), also known as 3'-O-me-7-meGpppG. The standard m7G cap analog can be embedded in the RNA molecule in both the forward and reverse orientation, which significantly reduces the overall level of translation of mRNA. ARCA is methylated at the 3'-position of m7G, which makes it possible to embed this cap analog only in the direct orientation and obtain a pool of capped mRNAs with a translational activity of 100%. The yield of the products in this reaction is lower than in the transcription reaction without synthetic cap analogs. The ARCA cap structure can be converted to the cap 1 structure using cap-dependent 2'-O-methyl transferase and S-adenosylmethionine in the subsequent enzymatic reaction [27]. It should also be noted that several other synthetic cap analogs with improved properties have been synthesized including the cap 1 analog from Trilink Biotechnologies (United States).
Modified Nucleotides and Optimization of the Nucleotide Composition of Synthetic mRNAs
Natural RNAs, as a rule, tend to mature not only from the 5' and 3' ends but also by modifying certain nucleotides inside the molecule. The use of modified nucleotide analogs in synthetic mRNAs is considered the most effective way to avoid activation of cellular sensors (TLR3, TLR7, TLR8, PKR), which trigger an immune response to foreign (usually viral) RNAs. This means that RNA can be synthesized in vitro using a mixture of modified nucleoside triphosphates instead of natural triphosphates of A, G, C, and U. Modified nucleotides, such as naturally occurring 5‑methylcytosine and/or pseudouridine (including N1-methylpseudouridine) are most often used instead of C and U, respectively [28]. It has been shown that the use of modified nucleoside triphosphates for mRNA synthesis significantly increases the stability of mRNAs in the cell, the efficiency of their translation, and reduces the cellular immune response to these mRNAs. This is especially important in some therapeutic applications of mRNA, e.g., in gene editing, protein replacement therapy, or differentiation of stem cells using mRNA-encoded transcription factors. For example, the expression of the ZFN gene editor in mouse lung tissues was significantly higher when using synthetic mRNAs that contain modified nucleotides than when using unmodified mRNA [29]. It is important to note that the choice of nucleotides can affect the overall yield of the mRNA synthesis in vitro. It is possible to obtain mRNA with the desired modification. Transcripts with the replacement of one or more nucleotides can be capped post-transcriptionally or co-transcriptionally by including ARCA or another cap analog. It should also be noted the importance of chromatographic purification of the final mRNAs to minimize the nonspecific immune response [30]. Another factor affecting the efficiency of synthetic RNA translation is the optimization of the composition of the transgene codons taking into account both the organism and the type of tissues and cells. During optimization, some rare codons are replaced by synonymous ones, which are translated more efficiently. Most often, this leads to increased translation and enhances the stability of RNA. However, this approach is not always suitable for therapeutic proteins. In some cases, for the correct folding of proteins encoded by synthetic mRNAs, it is necessary to reduce the translation rate at certain regions of the sequence; therefore, the value of codon optimization in such situations is ambiguous [31].
5'- and 3'-Untranslated Regions in Synthetic mRNAs
The stability and translational activity of mRNA in the cell are largely determined by the 5'- and 3'-untranslated regions (UTR). These regulatory regions flank the coding sequence of the transgene mRNA. They contain various motifs and form secondary structures that determine the stability of mRNA, recognition of mRNA by ribosomes, and interaction with components of the translational apparatus [32]. The inclusion of these sequences in synthetic mRNA can improve the translation and stability of mRNA. Many UTRs, which enhance mRNA translation, are natural. For example, UTR in mRNAs of alpha and beta globins are widely used to create synthetic mRNAs. Moreover, the stabilizing effect can be enhanced by sequentially placing two copies of 3'-UTR of beta-globin. UTRs of human heat shock protein 70, albumin, and alphavirus proteins have similar effects on synthetic mRNAs [33].
Synthetic UTRs developed in the laboratory can be used as an alternative to natural UTRs. For example, the de novo constructed 5'-UTR sequence with a length of only 14 nucleotides provides an expression level comparable to that characteristic for 5'-UTR of human alpha-globin [34]. Modern screening technologies allow experimental selection of UTRs with improved properties [35].
Poly(A) Tail of Synthetic mRNAs
The polyadenylated 3'-terminal region of mRNA, the so-called poly(A) tail, is an important structural element that determines the lifespan of mRNA molecules. With some exceptions, the poly(A) tails of most natural mRNA molecules in mammalian cells are up to 250 nucleotides long, and they gradually shorten during the lifetime of mRNA in the cell. In addition, the poly(A) tail plays an important role in translation, specifically in the formation of a translationally active mRNA complex with translation factors [36]. The size of the tail affects the stability of mRNA, thus preventing 3'-exonuclease degradation. Therefore, it is desirable to include poly(A) tails of approximately 100–120 nucleotides in length in synthetic mRNAs. It has been experimentally shown that a length of the poly(A) tail of more than 120 nucleotides significantly increases recombination events in bacterial cells involving this sequence. As a result, this affects the stability of the plasmid, which is used as a template for the mRNA synthesis in vitro and reduces the yield of the plasmid during its development in bacterial culture. Polyadenylation of mRNA in vitro can be carried out by either the enzymatic attachment of a poly(A) tail to the capped mRNA using recombinant poly(A) polymerase or the encoding of this sequence in a plasmid vector [25]. Polyadenylation by a separate enzyme adds an extra stage to the process of the mRNA synthesis and does not allow accurate control of the number of nucleotides included in all molecules during the reaction. Therefore, the second approach, which involves the use of a plasmid for encoding poly(A) tail, is more suitable for the industrial production of therapeutic mRNAs.
Synthetic mRNAs to Deliver Genome Editors
The safe nonviral delivery of genome editors opens new prospects for the therapeutic application of gene editing of therapeutic mRNAs. This approach worked well during the COVID-19 pandemic. The combination of mRNA and lipid nanoparticles ensures the safe expression of antigenic or therapeutic proteins in vivo, which has been confirmed by the results of clinical and preclinical trials. In recent years, successful experiments on genomic editing have been carried out with the use of synthetic mRNAs. The transtiretin (Ttr) gene was edited in the liver of mice, which led to a decrease in the level of the TTR serum protein by more than 97% [37]. The authors used an original delivery system based on lipid nanoparticles, which made it possible to simultaneously pack Cas9-encoding mRNAs along with guide RNAs [37]. Intravenous co-delivery of Cas9 mRNA and guide RNA led to DNA editing in liver, kidney, and lung tissues in mice [38]. The use of nanoparticles of a different composition ensured the effective release of RNA inside the cells in the reducing medium. The authors of [39] have shown effective knockout of the reporter gene in embryonic kidney cells, accumulation of intravenously injected mRNA-bearing nanoparticles in liver tissues, and successful knockout of the target gene (up to 20% of the serum level). Recently, the possibilities of gene editing using the RNA delivery platform have been shown by the example of correction of muscular dystrophy in muscle cells obtained from a wide range of donors. The safe delivery of gene editors using the synthetic RNA platform in terms of embedding the transgene into the genome has been confirmed, and the high efficiency of the editing with the possibility of dosing SpCas9 activity has also been shown [40]. The therapeutic potential of delivering gene editors using lipid nanoparticles that contain synthetic RNAs has been shown. In this case, knockdown of the Angptl3 gene in the mouse liver, which was performed to reduce the level of the ANGPTL3 protein, led to a decrease in blood lipid levels and correction of hypercholesterolemia. Researchers noted a significant duration of the therapeutic effect (up to 100 days after a single injection), the absence of nonspecific editing in several of the most possible places, and a lack of hepatotoxicity [41].
METHODS OF DELIVERY OF DNA- AND RNA-BASED EXPRESSION VECTORS IN VITRO AND IN VIVO
The successful application of genome editing tools requires not only correctly designed expression vectors, but also effective and safe delivery methods for carriers of genetic information to cells in vitro or to certain tissues in vivo. These methods are divided into three main types (Table 1). The first is biological transfection with the use of viral vectors or virus-like particles. The second and the third methods are the use of physical and chemical transfection. In this review, we do not consider viral transgene delivery vectors; we will focus only on physical and chemical transfection methods for the delivery of nucleic acid-based expression vectors.
Physical Transfection Methods
Electroporation. Electroporation, or electrotransfection, is the most common physical transfection method. Traditionally, electrotransfection is carried out in vitro in a cuvette with suspended cells; however, this method is also applicable in vivo. A cellular suspension that contains the DNA plasmid or mRNA of interest is placed between two electrodes. A medium with cells is subjected to a series of short electrical pulses, which leads to a sharp change in the voltage on the cell membrane (reaching a critical threshold between 250 and 500 mV) and the appearance of pores in the cell membrane for penetration of nucleic acid into the cytosol. DNA and RNA move in an electric field from the anode to the cathode [42]. Interestingly, larger pores in the cell membrane are formed from the side of the anode, which also contributes to the penetration of fairly large nucleic acid molecules into the cell. When the electrical impulses are terminated, the pores gradually relax and close. Electrotransfection is a very effective method for DNA and RNA delivery; unfortunately, a large number of cells die during this procedure.
It should also be noted that there are differences in the efficiency of transfection of different cell lines. The classical version of transfection can be used only for suspensions of cells; adhered cells cannot be modified. However, Maschietto et al. recently proposed an electrotransfection method that circumvents this limitation [43]. The authors proposed the use of plates for cell cultivation, the bottom of which is covered with microelectrodes. The plates are chips for electroporation, which are supplied with arrays of thin-film capacitive microelectrodes. Each individual microelectrode is an octagonal structure formed by highly conductive p-type silicon, which is covered with a layer of silicon oxide 15 nm thick. Cells grow on the surface of these electrodes, which makes it possible to use significantly lower currents without losing the efficiency of transfection. It is claimed that, in this case, the efficiency of transfection of CHO-K1 cells, reaches 60–80% without a high mortality rate of cell culture after the procedure. It was also possible to transfect differentiated neurons after six days of cultivation, although with low efficiency of ~10%. To apply this approach in vivo, it was necessary to develop several electrodes suitable for use in various organs and tissues [44]. In general, this method is well accepted for use in clinical practice due to its simplicity and relatively few side effects. Kawasaki et al. proposed electroporation for the successful delivery of the CRISPR/Cas genetic editor in utero [45]. Thus, transfection by electroporation is at the moment a very effective and cheap approach to the delivery of nucleic acids to cells both in vitro and in vivo, which is limited only by the availability of equipment.
Gene gun: the principle of operation and application. Like electroporation, this approach is applicable to the delivery of both plasmid DNA and mRNA. Initially, this method was used to modify plant cells; however, its potential is much wider. Using a gene gun, various cell types can be modified both in vitro and in vivo. The method is based on the high-speed bombardment of cells with complexes of heavy metal particles of about 1 µm in size coated with nucleic acids. At first, tungsten particles were used; however, this metal is toxic to cells, so it is often replaced with biologically inert gold particles [46]. Particles can be accelerated in different ways. Currently, the most common acceleration method is the use of a short pulse of an inert gas, e.g., helium. The dispersed particles penetrate the cell membrane and deliver genetic material to various cellular compartments. Nucleic acids can enter either the cytosol, nuclei, or other organelles. Plastids and mitochondria can be modified using this approach. The main limitations when using biolistics for in vivo transfection are the size of the equipment and the depth of penetration of particles into the body. This approach is used mainly for the transfection of epithelial and subcutaneous muscle tissues because of their accessibility [47].
The main advantages of this method include its high efficiency, the possibility of delivering several plasmids or mRNAs simultaneously, a wide range of modification objects, and the possibility of modifying differentiated cells and cells growing in adhesive culture. But there are also a number of disadvantages. The first is the high cost of the gene gun with relatively cheap further operation of the device. The second significant drawback is the high cellular mortality during the transfection procedure. However, as reported by O’Brien and Lummis, the use of lower pulse pressure (about 345 kPa) significantly reduces the degree of cell damage [48]. The gene gun delivery method continues to evolve. The important advantages of this method include versatility and applicability to cells of different types, while its use is constrained by the high cost of equipment. It is likely that reduction in cost will attract more attention to this method.
Sonoporation for DNA and RNA delivery in vitro and in vivo. The sonoporation method promotes the transfer of nucleic acids by exposing cells to ultrasound waves, which results in effects such as cavitation, radiation pressure, and micro-flows. Cavitation, i.e. the appearance and collapse of micro-bubbles of air, provides a very high local pressure and an increase in temperature, thus leading to a violation of the integrity of the cell membrane if the bubble collapses at the cell surface. Nucleic acid penetrates through these pores under the influence of other effects that occur during low-frequency ultrasound treatment [49]. There is also the method of plasmid DNA delivery using a combination of sonoporation and microfluidic technologies, hereinafter referred to as the method of acoustofluidic sonoporation. Belling et al., the authors of this method, state that it is possible to transfect a large number of cells at a high speed. In this method, a mixture of cells and plasmid DNA is treated with ultrasound while passing through a capillary. Researchers report that they managed to achieve a transfection rate of about 200 000 cells/min in the case of the Jurkat cell line, with cell viability after the procedure being about 80% [50]. This method is an effective and affordable analog of physical transfection methods, although it is necessary to study the effects of ultrasound on cells, especially on cell nuclei, which are also susceptible to local damage as a result of cavitation. Sonoporation is also used for transfection in vivo but its effectiveness, in this case, is significantly lower than in vitro. Nevertheless, the use of this approach made it possible to successfully deliver a CRISPR/Cas-based genetic editor for the treatment of male pattern baldness. The researchers directed the genetic editor to the SRD5A2 gene using a combination of nanoliposomal particles as a vehicle and sonoporation as an ‘activator’ of particles, for delivery. Under the action of cavitation, the particles burst and delivered plasmid vectors directly to the cells of the hair follicles [51].
Phototransfection. Laser transfection works by the local destruction of the cell membrane. The laser beam is focused under a microscope on the cell membrane in a 1–2 µm area, followed by a series of gentle high-intensity pulses, which leads to local destruction of the membrane. In this case, plasmid DNA from the nutrient medium penetrates into the cell [52]. The duration of radiation is femtoseconds, the used wavelength can vary significantly and depends, as a rule, on the available equipment, and power in the range of 50–100 mW is recommended [53]. However, the method has a low transfection efficiency (~25%) and a significantly lower throughput compared to the previously considered methods. Therefore, it is more suitable for point transfection. One of the advantages of phototransfection is the applicability of the method to cells that grow in both suspension and adhesive culture. The low cytotoxicity of this approach is also noted, which may be important for the transfection of single cells [54].
Chemical Transfection Methods
Transfection with calcium phosphate. Transfection with calcium phosphate was one of the first methods of cell transfection in vitro [55]. The method is based on the cellular absorption of complexes that consist of plasmid DNA and calcium phosphate. These complexes are prepared by mixing CaCl2 with DNA, followed by the addition of a buffer that contains phosphorus compounds, for example, HEPES [56], which leads to precipitation of the desired complexes. The resulting complexes are adsorbed on the cells from the nutrient medium. The main advantages of this method are its simplicity and low cost. The disadvantages include the relatively low efficiency of transfection, especially of differentiated cells, the relatively high level of cytotoxicity, and applicability only in vitro [57]. The method was proposed in the 1970s but is still widely used, and attempts are being made to optimize it to increase its effectiveness [58].
Transfection with poly-L-lysine. This method is also based on the creation of complexes of nucleic acids and a carrier, which are absorbed by the cell. The carrier is a polymer consisting of lysine amino acid residues. A molecule that contains ~10 lysine residues has a positive charge, which makes it possible to form complexes with negatively charged nucleic acid molecules. The complex of poly-L-lysine with nucleic acid also has a total positive charge, which provides its interaction with the cell membrane. In such the ‘classic’ version, this method of DNA delivery has a number of disadvantages. First, the microparticles are absorbed by lysosomes, followed by degradation, which negatively affects the overall transfection efficacy. Second, the poly-L-lysine complex itself has pronounced cytotoxicity [59]. However, these disadvantages can be compensated for by using additional agents. Thus, the addition of an endosomolytic agent, e.g., glycerin, to the cellular medium before transfection solves the problem of the release of poly-L-lysine complexes from endosomes. Modification of poly-L-lysine with PLGA (polylactide-co-glycolide) reduces cytotoxicity and increases the overall efficiency of transfection. If necessary, poly-L-lysine complexes can be targeted to certain cell types by attaching signal sequences to the polymer for binding to surface cell receptors. Similarly, some studies solve the problem of absorption of the poly-L-lysine complex by endosomes [60]. One of the main advantages of this method is its easy modification for the needs of the experiment and application both in vivo and in vitro. However, this method does not provide the highest level of transfection. In addition, the resulting complexes have different sizes, which can also affect the effectiveness of transfection.
Transfection with polyethylenimine. Polyethylenimine (PEI) is a polymer with high cationic potential due to its large number of amino groups. It is possible to synthesize linear or branched PEI molecules [61] of a given size and with various modifications. PEI interacts with negatively charged nucleic acids, thus forming complexes that are ready for transfection. The interaction with a negatively charged cell membrane is caused by the total positive charge of the complex. Unlike poly-L-lysine complexes, PEI complexes leave endosomes quite easily due to the ‘proton sponge’ or buffering effects [62]. All this leads to a high efficiency of transfection, which is the main advantage of this method. The main disadvantage of PEI is its cytotoxicity, which is directly proportional to the particle size and the efficiency of transfection. Neutral hydrophilic copolymers, such as polyethylene glycol, are added to the complexes to reduce their cytotoxicity [63]. Transfection with PEI has found wide application in vitro as an effective approach to transgene delivery. However, this approach is of little use for the delivery of genetic material in vivo.
Transfection with chitosan. Chitosan is a polysaccharide that consists of repeating units of D-glucosamine and N-acetyl-D-glucosamine. At pH 6.5, chitosan is protonated and becomes soluble in water. After processing, it acquires a high positive charge. Like other cationic polymers, chitosan forms complexes with negatively charged nucleic acids. This polymer contains two hydroxyl groups, which are easily modified for the tasks of the researcher [64]. The mechanism of chitosan penetration into cells is the same as that of PEI or poly-L-lysine complexes. Unlike other polymers, chitosan has low cytotoxicity. However, the efficiency of transfection with this polysaccharide is significantly lower than in other transfection methods. Transfection with chitosan is considered a promising alternative to the use of PEI. Its low cytotoxicity and the possibility of modification make chitosan a fairly convenient platform. Although studies are being performed to improve the efficiency of transfection using this polymer, an acceptable level of efficiency of PEI has not yet been achieved [65].
Lipofection. Lipofection is based on the delivery of DNA and RNA in lipid complexes. Positively charged lipids and negatively charged nucleic acids are used to create complexes. As an example, we can consider the first commercially available drug Lipofectin®, which consists of the positively charged DOTMA lipid and the neutral DOPE lipid. To date, transfection is performed using various lipids, which differ in properties and degree of impact on cells. In particular, lipids, such as DOTAP and DODAP for the preparation of the YSK05 liposomes are significantly less cytotoxic than Lipofectin® components, and the MVLBG2 lipid dendrimer has a high positive charge, which promotes its effective interaction with DNA [66]. Lipid vesicles that contain DNA or RNA are formed when mixing nucleic acid and cationic lipids. The total charge of the vesicle should be positive to provide interaction with the cell membrane due to electrostatic forces. Vesicles are absorbed by cells by endocytosis.
Lipofection provides a high level of cell transfection in vitro, but lipid vesicles have high cytotoxicity, especially if we consider a classic variant, such as Lipofectin® [67]. Another disadvantage is the high heterogeneity of the size of the vesicles. It is believed that this heterogeneity negatively affects the transfection efficacy. However, the simplicity of the chemical synthesis and modification of cationic lipids make this approach very flexible. For example, it is possible to obtain lipid nanoparticles (LNP), which are ‘dissolved’ in the lysosomes at a decreased pH value, thus increasing the efficiency of transfection. These LNPs are produced using ionizable lipid, polyethylene glycol, auxiliary phospholipid, and cholesterol. The key component is an ionizable lipid that is neutral at physiological pH values, but after penetration into the endosome with internal acidic pH, acquires a positive charge. A change in the particle charge leads to the destruction of endosomes and the release of nucleic acids [68]. This approach was used in vivo for the knockdown of the Angptl3 gene in the liver of mice [41]. Lipofection, despite its pronounced cytotoxicity, allows transfection to be performed with high efficiency. In addition, the possibility of modifying each unit of the cationic lipid and the complex as a whole makes this method very flexible.
Table 1. Methods of delivery of DNA- and RNA-based expression vectors in vitro and in vivo
Method Principle Advantages Disadvantages
Electroporation Penetration of nucleic acids occurs under the influence of a series of short electrical pulses Simplicity of the procedure; low cost; wide range of electrodes; applicability both in vitro
and in vivo
Specialized equipment is required; the procedure is accompanied by cell/tissue damage
Biolistics Metal particles coated with nucleic acid molecules are dispersed by an inert gas pulse and penetrate the cell membrane High transfection efficiency; possibility of simultaneous delivery of different vectors; a wide range of modification objects; applicability both in vitro and in vivo High cost of the gene gun and subsequent operation; high level of cell damage as a result of the transfection procedure; limited number of tissues available in vivo
Sonoporation Transfer of nucleic acids due to exposure of cells to ultrasound waves High rate and efficiency of transfection in vitro; high cell survival; applicability both in vitro
and in vivo
Availability of equipment; limited use and lower efficiency in vivo
Phototransfection Local destruction of the cell membrane by short laser pulses The method is applicable to cells growing both in suspension and in adhesion; low level of cytotoxicity Applicable only in vitro; low efficiency of transfection relative to other physical methods; low bandwidth; labor intensity
Calcium phosphate Absorption by cells of complexes that consist of nucleic acids and calcium phosphate Simplicity of the procedure;
low cost
Low transfection efficiency; pronounced cytotoxicity; applicability only in vitro
Poly-L-lysine Absorption by cells of complexes that consist of nucleic acids and poly-L-lysine Easily modified for the needs of the experimenter; applicability both in vivo and in vitro Low transfection efficiency; different sizes of the resulting complexes; pronounced cytotoxicity of unmodified poly-L-lysine complex
Polyethyleneimine Absorption by cells of complexes that consist of nucleic acids and polyethyleneimine High efficiency of transfection
in vitro
High cytotoxicity; applicability mainly in vitro
Chitosan Absorption by cells of complexes that consist of nucleic acids and chitosan Low cytotoxicity; applicability both in vivo and in vitro Low transfection efficiency
Lipofection Absorption by cells of complexes that consist of nucleic acids and a mixture of lipids High transfection level; applicability both in vivo and in vitro; easy modification for the experimental needs High cytotoxicity; different sizes of the resulting complexes
CONCLUSIONS
In this paper, we have considered the structural elements of expression vectors based on DNA and synthetic mRNAs and the methods for their delivery both in vitro and in vivo. Optimization of the structural components of these vectors makes it possible to effectively express therapeutic proteins and gene editing tools both in cells and in tissues for successful implementation of gene therapy. The choice of appropriate vector platforms, their structural elements, and transgene delivery methods make it possible to solve a wide range of experimental biomedical and therapeutic tasks, which is confirmed by a growing amount of scientific data and the results of preclinical and clinical trials on the use of gene editors for the correction of hereditary and acquired pathologies.
FUNDING
The work was supported by the program of Ministry of Higher Education and Science of the Russian Federation (agreement no. 075-10-2021-113, ID of the project RF-193021X0001).
COMPLIANCE WITH ETHICAL STANDARDS
The authors state that there is no conflicts of interest. This article does not contain any studies involving humans or animals as objects of research.
Translated by A. Levina
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| 0 | PMC9735121 | NO-CC CODE | 2022-12-14 23:28:32 | no | Mol Biol. 2022 Dec 9; 56(6):950-962 | utf-8 | Mol Biol | 2,022 | 10.1134/S0026893322060218 | oa_other |
==== Front
Nat Rev Immunol
Nat Rev Immunol
Nature Reviews. Immunology
1474-1733
1474-1741
Nature Publishing Group UK London
815
10.1038/s41577-022-00815-z
Perspective
Unique properties of tissue-resident memory T cells in the lungs: implications for COVID-19 and other respiratory diseases
http://orcid.org/0000-0001-7233-9466
Carbone Francis R. [email protected]
grid.1008.9 0000 0001 2179 088X Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria Australia
9 12 2022
17
22 11 2022
© Springer Nature Limited 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Tissue-resident memory T (TRM) cells were originally identified as a tissue-sequestered population of memory T cells that show lifelong persistence in non-lymphoid organs. That definition has slowly evolved with the documentation of TRM cells having variable terms of tissue residency combined with a capacity to return to the wider circulation. Nonetheless, reductionist experiments have identified an archetypical population of TRM cells showing intrinsic permanent residency in a wide range of non-lymphoid organs, with one notable exception: the lungs. Despite the fact that memory T cells generated during a respiratory infection are maintained in the circulation, local TRM cell numbers in the lung decline concomitantly with a decay in T cell-mediated protection. This Perspective describes the mechanisms that underpin long-term T cell lodgement in non-lymphoid tissues and explains why residency is transient for select TRM cell subsets. In doing so, it highlights the unusual nature of memory T cell egress from the lungs and speculates on the broader disease implications of this process, especially during infection with SARS-CoV-2.
In this Perspective, Francis Carbone considers the unique characteristics of the tissue-resident memory T (TRM) cell populations that develop in the lungs. He discusses how the different properties of lung TRM cells may affect immunity to lung infections, including SARS-CoV-2.
Subject terms
Viral infection
Immunology
==== Body
pmcIntroduction
Memory T cells can show a range of persistence within non-lymphoid compartments. Many lymphocytes move freely through the various organs unimpeded before exiting the tissue via the draining lymphatic vessels1–3. Recognition of antigen leads to their transient retention4 while physical barriers may slow the return of cells to the circulation5. Finally, a subset of T cells is specialized for purely localized patterns of immune surveillance6,7 and only poorly exits the tissues, if at all8. These tissue-resident memory T (TRM) cells9 have a cell-autonomous limitation in their recirculation capacity10–12 and show a superior ability to control localized infections in a number of settings13–15. In this Perspective, I detail the transcription networks that define sequestered TRM cells, identifying CD103+CD8+ memory T cells as the key population of memory CD8+ T cells that encompasses all the hallmarks of permanent tissue residency. Finally, I describe how these archetypical TRM cells show an unusual pattern of egress from the lungs and discuss how this impacts the course of respiratory infections, including SARS-CoV-2.
Identifying tissue-resident memory T cells
TRM cells were initially identified as a distinct, sessile T cell subset that coexisted alongside tissue-emigrating T cells8. This was a break from the prevailing understanding of tissue T cells based on early lymphocyte circulation experiments5,16,17. At that time, the widely accepted view was that these T cells were simply recirculating memory cells that either happened to be found in non-lymphoid tissues in large numbers18–20 or, alternatively, were trapped by some sort of gating mechanisms or by structural barriers such as the basement membrane that lines epithelia5. The identification of a unique TRM cell subset meant that non-lymphoid tissues contained at least two populations of memory T cells, each with its own distinct phenotype and functional properties. One was a recirculating subset that at the time was thought to comprise effector memory T (TEM) cells17 and the other, the newly identified permanently resident TRM cell population.
A major challenge from that point onwards has been distinguishing non-migrating TRM cells from recirculating memory T cells, largely because of the phenotypic overlap between these populations. For example, TRM cells do not express CC-chemokine receptor 7 (CCR7) — a receptor required for entry into lymphoid tissues and the marker that was originally used to differentiate TEM cells (identified as CCR7-negative) from lymphoid-tissue-constrained central memory T (TCM) cells (identified as CCR7-positive)17. Separately, CD69 had been proposed to be a pan-TRM cell identifier21, yet it is upregulated by both antigen-specific and nonspecific stimuli22 and a substantial fraction of migratory T cells express this molecule once in the tissues23. Compounding the confusion is the extensive heterogeneity seen in both circulating and tissue-resident memory T cell populations24–27, expanded by a history of natural infection28. Therefore, although combinations of surface markers can cover a range of TRM-like tissue cells, it would be fair to say that to date there remains no unifying phenotypic identifier for this population.
CD103+CD8+ TRM cells: the archetypical TRM cell
Although it has proven difficult to identify TRM cells by definitive phenotypic means, therapeutic and experimental interventions can eliminate all circulating T cells from the blood, leaving long-term tissue residents as the only memory T cells remaining in non-lymphoid compartments. Two approaches have proven particularly useful in this regard. The first exploits T cell responses against a transplantation mismatch to selectively eliminate cells in the circulation29–31 whereas the second uses a more versatile cytolytic antibody-based technique for the same purpose27,32,33. Of additional importance is the in vivo infusion of labelling antibodies before tissue analyses to exclude cells that are simply in the vasculature34. This technique eliminates confounding contributions by blood-borne cells and is critical when examining highly vascularized organs such as the lung, although it does not identify TRM cells per se.
One of the striking features of the mouse TRM cells that remain after circulating T cells are depleted from the tissues is the dominance of a population of CD8+ T cells expressing the CD103 (also known as αE integrin) subunit of the αEβ7 integrin complex23,33. CD103+ TRM cells are highly enriched in the environmentally exposed epithelia of the skin, small intestine and female reproductive tract8,10,35. At these epithelial sites, interaction between αEβ7 and its abundantly expressed target ligand E-cadherin36 probably plays a role in cell adhesion and retention. However, CD103+CD8+ TRM cells are also found in non-epithelial tissues such as the brain12,37, and although CD103 has variously been implicated as being important for TRM cell development38–40, its expression is not ubiquitous37 and therefore not mandatory for all forms of T cell residency. Nonetheless, tissue-lodged CD103+CD8+ memory T cells are highly resistant to equilibration across parabiotic pairs41, are uniquely spared from elimination by the approaches mentioned above23,30, selectively survive for prolonged periods in transplanted tissues in mice8,33 as well as in humans42,43 and persist independently of antigen recognition15,37. Moreover, CD103+CD8+ memory T cells are usually not found in secondary lymphoid organs15,44 — with one striking exception45,46 to be described in detail below. Thus, although not all TRM cells express CD103, the balance of evidence argues that CD103+CD8+ tissue T cells are true TRM cells, making this an easily identifiable archetypical population and an ideal reductionist means for delineating tissue residency mechanisms.
RUNX3 and TGFβ in CD8+ TRM cell development
Early experiments in mice comparing the transcriptomes of CD103+CD8+ TRM cells isolated from a range of organs with those of their circulating counterparts provided some of the first insights into the transcription networks critical for TRM cell development and survival10,39. Not surprisingly, genes associated with tissue egress were found to be downregulated in TRM cells, including Ccr7 and the genes encoding the sphingosine-1-phosphate receptors S1PR1 and S1PR510,11. Without the downregulation of these receptors, the precursors of TRM cells return to the circulation, thereby dampening TRM cell development11,47. Other genes that come into play are those involved in dealing with local metabolite availability7,48,49 and those that prolong T cell survival23, with both sets of genes necessary to maintain a long-lived sequestered T cell population. Further experiments fleshed out how transcription factors control the various networks, such as the involvement of KLF2, which modulates the expression of S1PR1 and CCR711. Following this, key upstream gene regulators were identified, such as T-bet and EOMES23,50 as well as BLIMP1 and the BLIMP1 homologue HOBIT51,52; of note, BLIMP1 and HOBIT are also involved in the development of innate-like lymphocytes that permanently reside in mouse tissues, such as natural killer cells and natural killer T cells51. Most recently, an overarching transcription factor has come into focus. RUNX3 has been identified as contributing to TRM cell formation, and it directly or indirectly regulates BLIMP1 and KLF2 expression as well as modulating downstream retention components53. This contribution is particularly striking as RUNX3 is a pivotal player in CD8+ T cell development and functionality54,55.
As the network analyses evolved, one commonality to emerge was the involvement of TGFβ in TRM cell development and survival in a range of tissues and organs23,40,56–58. TGFβ appears to use a non-canonical signalling pathway59 that controls much of the CD8+ TRM cell gene expression signature60. It has been shown to facilitate tissue entry via selectin upregulation61 and can regulate a broad range of transcription regulators and cytokine-driven survival factors during CD8+ TRM cell development11,23,50. Combined, there is now a wealth of data regarding the tenets of transcriptional control of TRM cell formation, which largely pivots around a TGFβ–RUNX3 axis, at least in the case of the mouse CD8+ TRM cell subset.
TRM cell re-entry into the circulation
Although TRM cells were originally shown to persist in non-lymphoid organs in quasi-perpetuity8, there have been subsequent descriptions of TRM cell egress with the resultant ‘ex-TRM cells’ ultimately being incorporated into the circulation33,41,62. CD8+ TRM cell numbers show an intrinsic decline in organs such as the lung and liver30,41, but not in tissues such as the skin and small intestine, where the cells effectively remain in place for life once lodged8,41. However even for these fixed populations, TRM cells can be forced to leave using in situ antigen stimulation via peptide challenge33,44. Such active dislodgement is not universal, with CD103+CD8+ TRM cells sometimes remaining resident in the tissue even after multiple rounds of cell division initiated by local infection8,63,64. Perhaps tellingly, when CD103+CD8+ TRM cells are selectively dislodged by intervention, the resultant ex-TRM cells appear to adopt a phenotype intermediate between those of upstream resident memory T cells and conventional recirculating memory T cell populations, with a CD103 expression status that is either undefined or reported to be transient33,44. Moreover, when these same cells are directly isolated from non-lymphoid compartments, they are inferior in their capacity to enter the circulation compared to counterparts extracted from lymphoid organs33,65.
It remains difficult to reconcile these conflicting results, but studies on CD8+ TRM cells in the liver and recent revelations regarding the basis for CD4+ T cell residency provide valuable insight that might explain egress variability. Although much more is known about CD8+ TRM cells, there are many examples of CD4+ TRM cell-type counterparts13,27,66. Comparisons make it clear that the two are unrelated in terms of mechanistic underpinnings and they can exhibit quite distinct patterns of tissue residency even in the same organ29,67. As noted above, the archetypical CD103+CD8+ TRM cells use a set of TGFβ-driven transcriptional networks to shut down tissue egress, upregulate survival factors and tailor metabolic pathways. By contrast, few of these networks have been associated with CD4+ TRM cell residency, which instead relies on retention mechanisms variously operating via cell aggregation, antigen-specific T cell activation and chemotactic agents68,69 (Fig. 1). The reason why CD4+ and CD8+ TRM cells are likely to differ at the mechanistic level is the pivotal role RUNX3 plays in TRM cell development and survival53. This transcription factor is repressed in CD4+ T cells by the opposing gene regulator ThPOK (also known as ZBT7B), which is itself a lineage-determining factor70,71. Although natural RUNX3 upregulation can convert CD4+ T cells to an unconventional CD8αα+ intraepithelial regulatory T cell population with CD8+ TRM cell-like qualities72, the intrinsic paucity of RUNX3 expression in conventional CD4+ TRM cells results in low CD103 levels in these cells and more transient tissue residency as a direct consequence of their inability to access the RUNX3-mediated pathways downstream of TGFβ signalling53,73.Fig. 1 Subtypes of tissue-resident memory T cells based on transcription profiles.
The mechanism promoting permanent residency in non-lymphoid tissues for the CD103+CD8+ tissue-resident memory T (TRM) cell population involves a RUNX3-driven transcriptional network that is downstream of TGFβ receptor signalling53,60. This transcription programme is missing in CD4+ TRM cells as a consequence of deficiencies in RUNX3 expression73. Instead, these populations use a combination of cell aggregation and extrinsic chemokine networks for tissue retention68,69. The typical CD103+CD8+ TRM cell transcription programme is also missing in CD103− liver-like TRM cells because of deficiencies in TGFβ engagement65.
Somewhat analogous to their CD4+ tissue-resident T cell counterparts, mouse liver CD8+ TRM cells are also deficient in CD103 expression74. These cells show medium-to-long-term tissue residency74, but not the almost lifelong persistence of TRM cells in organs such as skin and small intestine41,65. Although the liver T cells are fully capable of responding to TGFβ, local requirements negate this capacity, resulting in an immature or less differentiated CD103− TRM cell population (Fig. 1) with an inferior term of residency combined with more flexible reprograming compared to mature CD103+ TRM cell counterparts65. Collectively, the results show that although CD103− TRM cells can reside in tissues for a considerable period, they can exhibit a range of spontaneous egress and reprogramming capabilities because of deficiencies in TGFβ-mediated maturation. Given the heterogeneous nature of tissue-resident T cells, including variable CD103+ T cell content across different organs37 and the known recruitment of recirculating T cells by the peptide stimulation used for TRM cell dislodgement32, it is possible that less differentiated populations analogous to the liver CD103− TRM cells may preferentially contribute to the egress process. Regardless, although some TRM cells can leave the tissues and enter the circulation, the balance of data argues that for the archetypical CD103+CD8+ TRM cells, this process is not constitutive and when it does happen, it usually results in cells that do not phenocopy their direct upstream antecedents.
TRM cells in the lungs
From the discussion above, it can be reasonably argued that because they fully engage the TGFβ–RUNX3 residency programme, mouse CD103+CD8+ tissue T cells fit the original TRM cell definition8; specifically, they form a distinct subset of memory T cells that remains lodged in peripheral compartments in virtual perpetuity. However, there is one organ where the CD103+CD8+ T cells do not abide by this rule, and its uniqueness has important disease implications. Unlike the situation in other tissues, CD103+CD8+ TRM cells in the lung do not require local antigen stimulation for dislodgement45. Also unusually, the egressing memory T cells retain cell surface expression of CD103 post-exit, meaning that the lung-draining lymph nodes are unique in having a substantive subset of memory CD8+ T cells with this marker45,46. Lung CD103+CD8+ TRM cells are fully mature and unremarkable in terms of their TGFβ requirement for development and survival58. They also express the gene signatures associated with tissue residency10,12, including a cluster of TRM cell-associated transcription factors, namely HOBIT, NR4A1, aryl hydrocarbon receptor (AhR) and BHLHE407,51,75,76. In all critical aspects, they resemble TRM cells from other tissues, meaning that their exit from the lung is probably an organ-specific feature rather than due to a cell-intrinsic programme. Such a mechanistic distinction is important, as it would suggest that the egress process would probably capture TRM cells beyond the archetypical CD103+CD8+ subset that was used to define this phenomenon and would do so regardless of where they fall on a maturation and term-of-residency continuum.
Exacting experiments by Stolley and colleagues45 proved that the resultant draining lymph node-resident memory T cells were indeed constitutively derived from upstream lung tissue counterparts, possibly dislodged as a consequence of virus-induced tissue damage77,78 or the interruption of tonic TGFβ signalling needed to retain TRM cells in tissues79. Although the resultant lymph node accumulation offers an additional avenue to maintain regional protection45,80, memory T cell exit helps to explain one of the intriguing conundrums associated with immune protection in the lungs. It has long been known that T cell immunity in the lung wanes over time, with this first reported for respiratory infections with influenza virus and Sendai virus in mice81,82. This decline in lung-based immunity occurs despite virus-specific memory cells persisting in the circulation30,82–84. Non-TRM cell-based mechanisms were originally proposed to describe the behaviour of lung T cell populations81,85–87, variously confounded by blood-borne cells that are particularly problematic when dealing with this highly vascularized organ34. More recently, it was shown that the waning local immunity correlates with declining lung TRM cell numbers in mouse after influenza virus infection83,84 and in humans after respiratory syncytial virus challenge88. Although other mechanisms have been posited to account for this TRM cell attrition, such as the selective death of lung TRM cells30,84 or the disappearance of structures associated with focal damage67, none exclude concurrent tissue egress. Once lost, lung TRM cells are difficult to replace in the absence of renewed infection owing to the strict antigen recognition requirements for effective lodgement67,83,89, which are optional in many other tissues37 including the upper respiratory tract90. Overall, a range of mechanistic overlays would imply that losing TRM cells over time is important for this organ — for example, to limit ongoing damage to its delicate oxygen-exchange architecture91.
Finally, the natural decay of lung TRM cells stands in stark contrast to what is seen elsewhere in the body, where CD103+CD8+ TRM cell populations can remain tightly contained (Fig. 2). CD103+CD8+ TRM cells show long-term persistence in organs such as the brain, skin and cervicovaginal tissue8,39,92, despite the loss of their CD103− counterparts. The extent to which these spatial and temporal restrictions can operate was dramatically illustrated by experiments that lodged CD103+CD8+ TRM cells in a small patch of skin, thus confining effective protection to just that location while leaving the remainder of the torso under the inferior control of memory cells in the blood8,63. By contrast, lung TRM cell residency is unstable and transient, resulting in surveillance that is increasingly dependent on recirculating populations over time, with a concomitant decline in local T cell immunity.Fig. 2 Selective and constitutive egress of lung CD103+CD8+ TRM cells.
Inflammation associated with infection of tissues such as skin, small intestine and reproductive tract (left panels) and lung (right panels) leads to the recruitment of a variety of CD4+ and CD8+ T cells that combat the invading pathogens (part a). These populations include effector memory T (TEM) cells that continuously recirculate between non-lymphoid organs and blood as well as tissue-resident memory T (TRM) cell precursors (not shown). Following resolution of the infection (part b), most of the recruited T cells exit or die, leaving local immunosurveillance to recirculating TEM cells and the more potent TRM cells. Over time, some TRM cell subsets selectively disappear (part c, left panel), resulting in a resident population highly enriched in long-lived CD103+CD8+ TRM cells that afford long-term local immunity against re-infection (part d, left panel). In the lungs, CD103+CD8+ TRM cells are gradually lost after the infection has resolved and instead accumulate in the proximal draining lymph nodes (part c, right panel) leaving the lower respiratory tract deficient in CD103+CD8+ TRM cells and thus susceptible to re-infection (part d, right panel).
TRM cell lung egress and immunity to SARS-CoV-2
At the time of this writing and nearly three years since the emergence of the SARS-CoV-2 virus in late 201993,94, the COVID-19 pandemic continues to be a major challenge in many parts of the world. Despite reports showing that circulating antiviral T cell immunity can be cross-reactive against emerging variants95, long lived96,97 and associated with better disease outcomes98,99, immunity from combinations of COVID-19 vaccination and SARS-CoV-2 infection has been found to steadily decline100,101. One possible contributor may be that anti-SARS-CoV-2 tissue-resident T cells that are pivotal for immune protection show the same type of numerical decay as reported for mouse CD103+CD8+ TRM cells. Employing strategies that slow TRM cell loss102 could be advantageous, as might approaches that circumvent the lung altogether. The upper respiratory tract, especially the nasal mucosa, is a prime target with respect to the latter possibility as it does not show the TRM cell decline that is intrinsic to the lung90. Alternatively, it may be that TRM cells are actually counterproductive, leading to tissue damage. This is especially poignant because repeated antigen encounters extend the durability of CD103+CD8+ TRM cells in the lung102, yet a recent report found that experiencing successive SARS-CoV-2 infections progressively increases the risk of adverse health outcomes103. In terms of their potential to contribute to tissue damage, TRM cells have an innate immune alarm and recruitment function32,104, and the innate response has been shown to be a key mediator of COVID-19-associated lung pathology105,106.
Conclusion
Overall, TRM cells provide superior protection against tissue-localized infection, primarily because of constraints in their migration capabilities. Despite proving to be long-lived and effective in a range of different infectious diseases, lung TRM cells have an unusual propensity for tissue exit reflected in a decay in local T cell immunity. Such a feature may have evolved to protect this organ against long-term damage or may simply be a by-product of some unique anatomical feature intrinsic to lung function. Given the ability of TRM cells to respond to infection with an immediacy unmatched by the blood-based memory populations, there is a need to focus on their deposition in the different compartments of the respiratory system, especially in settings or sub-regions that support their long-term survival.
Acknowledgements
The author wishes to thank L. Mackay, L. Wakim and T. Gebhardt for insightful discussions.
Peer review
Peer review information
Nature Reviews Immunology thanks J. Harty, M. Hassert and J. Schenkel for their contribution to the peer review of this work.
Competing interests
The author declares no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36494455 | PMC9735123 | NO-CC CODE | 2022-12-14 23:28:32 | no | Nat Rev Immunol. 2022 Dec 9;:1-7 | utf-8 | Nat Rev Immunol | 2,022 | 10.1038/s41577-022-00815-z | oa_other |
==== Front
Curr Breast Cancer Rep
Curr Breast Cancer Rep
Current Breast Cancer Reports
1943-4588
1943-4596
Springer US New York
469
10.1007/s12609-022-00469-9
Breast Cancer Disparities (LA Newman, Section Editor)
Disparities in Time to Treatment for Breast Cancer: Existing Knowledge and Future Directions in the COVID-19 Era
Fasano Genevieve A.
Bayard Solange
Gillot Tamika
Hannibal Zuri
Pedreira Marian
Newman Lisa [email protected]
grid.5386.8 000000041936877X Department of Surgery, New York-Presbyterian-Weill Cornell Medicine, New York, NY USA
6 12 2022
19
31 10 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Purpose of Review
Despite significant advances in detection and treatment for breast cancer, the breast cancer mortality rate for Black women remains 40% higher than that for White women. Timely work-up and treatment improve outcomes, yet no gold standard exists for which to guide providers.
Recent Findings
A large body of literature demonstrates disparities in time to treatment for breast cancer, and most studies show that Black women receive treatment later than their White counterparts. The COVID-19 pandemic has been projected to worsen these disparities, but the extent of this impact remains unknown.
Summary
In this review, we describe the available evidence on disparities in time to treatment, potential drivers, and possible mitigation strategies. Future research must address how the COVID-19 pandemic has impacted the timely treatment of breast cancer patients, particularly populations vulnerable to disparate outcomes. Improved access to multidisciplinary breast programs, patient navigation services, and establishment of standards for timely treatment are necessary.
Keywords
Disparities
Breast cancer
Cancer screening
Time to treatment
==== Body
pmcIntroduction
Despite advances in screening/early detection and systemic therapy, breast cancer remains a leading cause of cancer death among women and is the most commonly diagnosed malignancy in women after skin cancer [1]. While overall mortality from breast cancer has improved in recent decades, disparities persist and mortality rates are 40% higher among African American compared to White American women [2]. Additionally, African American women are more likely to present at a younger age and with later stage disease; they are also more likely to have biologically aggressive tumors such as high-grade disease and estrogen-receptor-negative tumors [1]. Compounding these biological differences in breast cancer presentation are additional factors such as socioeconomic status and reduced access to high-quality, timely treatment among Black women. Prolonged time to treatment of newly diagnosed breast cancer has been associated with lower overall and disease-specific survival [3, 4•]. However, heterogeneity exists regarding the definition of a treatment delay, as there is no current standard for time to treatment. To date, several studies have characterized racial disparities in time to treatment and provide retrospective data on how this may explain discrepancies in survival [4•, 5–10]. In this review, we aim to summarize the current literature regarding disparities in time to treatment for breast cancer and the impact on survival, identify directions for future study considering the COVID-19 pandemic, and propose potential strategies to mitigate these time to treatment disparities.
Time to Treatment Impacts Survival
One of the difficulties in improving disparities in time to treatment is that there are currently no universally established benchmarks defining optimal intervals for initiating treatment following detection of a breast cancer. For example, time to treatment from the first diagnostic imaging study to core needle biopsy and time from the first positive needle biopsy to initial breast cancer surgery are included in quality measures developed by the National Consortium of Breast Centers [11]. Additionally, the Commission on Cancer (CoC) includes several measures regarding timely treatment for benchmark performance in CoC-accredited cancer programs [12] (Table 1). Evidence for these recommendations is driven by analyses of large national datasets that demonstrate that longer time to treatment is associated with worse outcomes, including reduced overall and disease-specific survival [3, 13–15]. Streamlining these definitions for providers would strengthen quality improvement efforts.Table 1 Commission on Cancer (CoC) quality measures in time to treatment for breast cancer
Commission on Cancer (CoC) quality measures in time to treatment for breast cancer
----Radiation therapy is administered within 1 year of diagnosis for women under age 70 receiving breast conservation surgery for breast cancer
----Combination chemotherapy is recommended or administered within 4 months (120 days) of diagnosis for women under age 70 with AJCC T1cN0M or stage IB–III hormone receptor-negative breast cancer
----Tamoxifen or third-generation aromatase inhibitor is recommended or administered within 1 year of diagnosis for women with AJCC T1cN0M0 or stage IB–III hormone receptor-positive breast cancer
----Radiation therapy is recommended or administered following any mastectomy within 1 year of diagnosis for women with ≥ 4 positive regional lymph nodes
A large population-based study of SEER-Medicare data comprised of more than 94,000 patients showed that overall survival diminished with progressively increasing intervals of treatment delay (≤ 30, 31–60, 61–90, 91–120, and 121–180 days) in time to surgery. In an analysis of the National Cancer Database (NCDB), the overall mortality hazard ratio was 1.10 for each increasing time interval [3]. For patients requiring neoadjuvant chemotherapy, a delay of more than 61 days from breast cancer diagnosis to initiation of neoadjuvant chemotherapy was associated with an increased risk of death [13]. Regarding adjuvant chemotherapy, multiple studies demonstrate adverse outcomes with initiation of therapy more than three months after diagnosis [14, 15].
These data suggest that ensuring timely treatment for breast cancer patients is relevant to the goal of optimizing outcomes.
Disparities in Time to Treatment
Disparities in time to treatment for breast cancer have been well documented over the last two decades. Currently, a large body of data exists that is driven predominantly by retrospective studies, ranging from single institutional studies to investigations of large national datasets. Most find that regardless of the first treatment modality, racial and ethnic minorities, particularly Black women, experience prolonged treatment delays compared to White women (Table 2).Table 2 Recent studies evaluating disparities in time to treatment for breast cancer
Study Design Setting and number of subjects Main findings
Babatunde (2021) Retrospective cohort South Carolina Central Cancer Registry (SCCCR) and Office of Revenue and Fiscal Affairs (RFA), 2002–2010, n = 2155 • Black women received surgery, chemotherapy, and radiotherapy later than White counterparts
• Unadjusted mean time to surgery from diagnosis was longer for Blacks
Benefield (2021) Population-based study with in-home interview Carolina Breast Cancer Study Phase III, 2008–2013, n = 437 • After adjusting for stage, Black women with hormone receptor-positive/HER2- high-grade tumors were more likely to experience a treatment delay
Bleicher (2017) Retrospective cohort National Cancer Database, 2004–2015, n = 622,793 • After adjusting for all other variables, factors that nearly or more than doubled odds of having > 90 days between diagnosis and surgery included Black race and Hispanic ethnicity
Bustami (2014) Retrospective cohort study NYU and Morristown Medical Center tumor registry, 2007–2011, n = 3071 • Longest median time to surgery observed for African American patients and longer absolute difference between African American compared to Whites with difference less pronounced for Asian/other compared to White
Champion (2020) Retrospective cohort National Cancer Database, 2004–2015, n = 903,008 • After adjustment, Hispanic White women had longer time to surgery compared to non-Hispanic White women, regardless of treatment sequence
• No significant racial differences in time to surgery among Hispanic patients
Doe (2020) Retrospective cohort Henry Ford Health System, 2015–2017, n = 541 • Mean time to treatment was significantly longer for Blacks than Whites both before and after implementation of multidisciplinary approach (MDC)
• Before MDC, significantly more White patients were treated ≤ 60 days than Black and significantly more Black patients were treated > 60 days but this difference no longer appeared after MDC
Eaglehouse (2019) Retrospective cohort Department of Defense Central Cancer Registry and Military Health System Data Repository, 1998–2008, n = 4887 • In multivariable models, NHB women had longer time to surgery than NHW women
• Regarding survival, addition of time to surgery to multivariable model did not substantially attenuate the HR estimates compared with adjusted model—NHB had higher risk for all-cause death compared to NHW women
Foy (2018) Retrospective cohort James Cancer Hospital, 2005–2014, n = 4593 • Mean number of days between diagnosis and treatment was significantly greater for Black women
• Proportion of Black women with more than 90 days between diagnosis and treatment onset was significantly greater than White women
George (2015) Retrospective cohort NJ State Cancer Registry, 2005–2010, n = 575 • Median time to surgery was 29 days for White vs. 32 days for Black with 92% of White compared to 80% of Black patients receiving surgery within 2 months of diagnosis
• Black patients more likely to experience surgical delay more than 3 months
• In models adjusted for situational barriers, Black patients at increased risk for both diagnostic and surgical delay compared to Whites
Halpern (2016) Retrospective cohort study Medicaid data, 2006–2008, n = 7452 • Black Medicaid beneficiaries were more likely to experience delays for breast-conserving surgery and outpatient and inpatient mastectomy
Hoppe (2019) Retrospective cohort National Cancer Database, 2004–2014, n = 546,351 • Black women had significantly longer times to first treatment, time to surgery, chemotherapy, radiation, and endocrine therapy than White women
• Despite private insurance, Black women still had longer time to surgery than White patients
Jackson (2021) Retrospective cohort National Cancer Database, 2010–2016, n = 378,499 • Median time from diagnosis to first surgery was longer for Black women than White
• 30.6% of Black women had surgery > 60 days from biopsy compared to 18.0% White
• On multivariable logistic regression, Black race associated with increased odds of surgery > 60 days from diagnosis
Khanna (2017) Retrospective cohort Boston Medical Center, 2004–2014, n = 1130 • Black women had longer time to treatment compared to all other race groups and significance primarily driven by comparison of Black vs. White
• On multivariate model with race/ethnicity, marital status, stage, and first treatment delivered, race/ethnicity was the only independent predictor of time to treatment
Khorana (2019) Retrospective cohort National Cancer Database, 2004–2013, n = 1,368,024 • On multivariable analysis, race was one of the several predictors of delay
• Black race was associated with increased time to initiation compared to White
• Increased time to initiation was associated with worsened survival in stage I and II breast cancer
Lamb (2018) Retrospective cohort Methodist University Hospital, 2002–2012, n = 3072 • Black women with stage 0, I, II, and III breast cancer all had significantly longer median time to surgery than White women
Polverini (2016) Retrospective cohort National Cancer Database, 2004–2012, n = 420,792 • As time to surgery increased, the percentage of Medicaid and uninsured patients and patients of Black or Hispanic race increased
• Overall, only time to surgery > 12 weeks was associated with significantly shorter survival
• When stratified by stage, stage I patients treated at 8 to < 12 weeks and > 12 weeks as well as stage II patients treated > 12 weeks had decreased overall survival compared with patients treated within 4 weeks
Reeder-Hayes (2019) Retrospective cohort Carolina Breast Cancer Study, unknown timeline, n = 2659 • Women with delayed treatment initiation were significantly more likely to be Black
• Black women more frequently experience delayed treatment
• Even in fully adjusted models, Black women had almost twice the frequency of delayed initiation compared to White women
• After adjustment for age, receptor status, grade, and tumor size, a nonsignificant trend association with recurrence risk was suggested for patients with delayed initiation
Examining time to treatment among early-stage breast cancer patients, Hoppe and colleagues analyzed over 540,000 patients within the National Cancer Database (NCDB). Black patients were found to have a significantly longer time to first treatment (35.5 days vs. 28.1 days) compared to White patients. This trend continued when stratified by treatment modality: surgery (36.6 days vs. 28.8 days), chemotherapy (88.1 days vs. 75.4 days), radiation (131.3 days vs. 99.1 days), and endocrine therapy (152.1 days vs. 126.5 days). Subset analysis among patients with private insurance found that the disparity remained, although it was reduced by 1.2 days [10].
In another NCDB study, time to surgery, defined as date of biopsy to first surgery, was examined among a cohort of 378,499 patients. Jackson et al. found that the odds of receiving surgery more than 60 days after diagnosis were higher among non-Hispanic Blacks (NHB) (OR 1.77, 95% CI 1.64–1.91) compared to non-Hispanic Whites. Specifically, 30.6% of NHB women had surgery more than 60 days after diagnosis compared to only 18% of White women [16•].
For patients undergoing primary surgical therapy for breast cancer, many factors may impact the interval from diagnosis to surgery such as genetic testing, consultation with a plastic surgeon for consideration of all surgical options such as contralateral prophylactic mastectomy (CPM) and reconstruction, and obtaining multiple oncology treatment opinions [3]. Recent work has found that racial and ethnic minorities are in fact less likely to undergo CPM and less likely to have genetic testing which would potentially reduce the odds of surgical delay for this patient population [17, 18]. However, most studies have nonetheless found that Black women tend to experience longer time to surgery than their White counterparts [5, 10, 16•, 19–23].
The role that other socioeconomic factors play in the treatment delays has been well studied, particularly the impact of insurance status. Analyzing patients from Phase 3 of the Carolina Breast Cancer Study, Reeder-Hayes et al. found that women with the longest treatment durations were more likely to be Black, younger, have a lower income, be uninsured or have Medicaid, be less educated, and have a higher stage at diagnosis [24]. Another study of 420,792 breast cancer patients from the NCDB undergoing primary surgical therapy found that as time to surgery increased, the percentage of Medicaid and uninsured patients also increased [8]. Importantly, other work has shown that higher Medicaid reimbursements for breast conserving surgery are associated with a decreased time from diagnosis to surgery [25]. These studies suggest that the etiology of these disparities is multifactorial and that insurance status clearly plays an important role.
Potential Mitigation Strategies
Potential strategies to mitigate disparities in time to treatment for breast cancer include a multidisciplinary approach to breast cancer care and utilization of patient navigators.
Recent work by Doe et al. sought to examine whether a multidisciplinary approach to breast cancer care may improve disparities in time to treatment. In their analysis of 541 patients, mean time to treatment was significantly longer for Blacks than Whites among patients both before and after implementation of the multidisciplinary care program (MDC). Although the gap in time to treatment between races was shortened in the MDC group from 18.7 days to 8.5 days, the improvement did not achieve statistical significance [26]. These data suggest that a multidisciplinary approach to breast cancer treatment may be one potential method to reduce disparities but additional confirmatory studies are needed.
Other data have shown that with the use of patient navigation services, time from initial presentation to definitive treatment can be reduced. For example, in their analysis of patients at an urban safety net hospital, Haideri et al. found that 67% of women in the pre-navigation group received treatment within 60 days of presentation vs. 75% in the navigator group [27].
While minority patients have historically been underrepresented in National Cancer Institute (NCI)-designated cancer centers, one study elucidates how among certain communities comprised of predominantly minority patients, disparities may be reduced. For example, Parsons et al. retrospectively reviewed patients treated at an NCI-designated cancer center where 50% of the population identifies as Hispanic. On multivariate Cox proportional hazards modeling adjusting for age, cancer and treatment characteristics, and sociodemographic factors, no difference in time to treatment was found between Hispanic versus non-Hispanic White patients [28]. This finding underscores the importance of improving access to care at NCI-designated cancer centers particularly among communities where at least 50% of the population identifies as either Hispanic, Black, or other.
Disparities also appear to be less pronounced among patients treated within the U.S. military healthcare system. Outcomes of 6577 patients from the Department of Defense (DoD) central tumor registry demonstrate more equal access to treatment. Specifically, wait time from diagnosis to treatment was significantly shorter for Black women. Additionally, Black women have improved survival when treated at a DoD facility compared to within the general population. These findings are likely explained by the fact that military personnel have unique characteristics and similarities in education, lifestyle, and socioeconomic status that is more consistent among race groups. This includes equal wage and housing policies that may contribute to less inequity compared to that seen within the general population. This work is further evidence that disparities are driven by more than just race, but also social determinants of health [29]. Furthermore, U.S. military healthcare system may serve as a model for providing more equitable care.
Impact of the COVID-19 Pandemic on Time to Treatment
The COVID-19 pandemic has been the catalyst for a tremendous amount of research in understanding and addressing healthcare disparities in the United States. This has been largely driven by the disproportionate impact of the COVID-19 mortality on racial and ethnic minorities which mirrors disparities seen with cancer. For example, in recent data from the Kaiser Family Foundation, Black, Hispanic, and American Indian/Alaska Native people are at least twice as likely to die from COVID-19 as their White counterparts. These disparities are also seen with respect to hospitalization rates [30].
Beginning in the spring of 2020 in the Northeast, widespread shelter-in-place mandates were enacted to curb the spread of COVID-19. Simultaneously, large healthcare systems underwent a major reorganization to allocate resources toward pandemic management. These measures included diversion of resources and personnel and suspension of routine healthcare including cancer screenings. At this time, surgeons were faced with a necessary surgical pause, to conserve personal protective equipment, and in some institutions transform operating rooms toward caring for COVID-19 patients [31, 32].
In response to this, the American College of Surgeons developed a set of guidelines for the triage and prioritization of surgery relative to illness severity and time sensitivity [33]. Additionally, the American Society of Breast Surgeons, the National Accreditation Program for Breast Centers, the Commission on Cancer, and the National Comprehensive Cancer Network assembled a COVID-19 Pandemic Breast Cancer Consortium to establish guidelines for the treatment of breast cancer patients during this unprecedented time [34]. Treatment recommendations were based on various features including clinical stage, biologic and phenotype characteristics, and patient-related factors.
As a result, many breast cancer patients who would have been eligible for immediate surgery were now having their surgery postponed. While these guidelines were well intentioned, they may have inadvertently exacerbated disparities in time to treatment for surgery for Black patients [35•]. For example, previous studies have quantified the absolute difference in median time to surgery for Black versus White patients undergoing primary surgery. The majority demonstrate that Black patients consistently have surgery later than their White counterparts [5, 10, 16•, 19, 21–23].
Thus far, the impact of the COVID-19 surgical pause on outcomes for breast cancer patients remains unknown. Few studies have sought to quantify patient-reported delays in treatment and have identified patient factors that increase the odds of a delay. For example, one study of breast medical oncology patients from February 1, 2020, to April 30, 2020, who were scheduled for outpatient appointments found that 42.6% of patients had a COVID-19-related delay and/or change in treatment plan. The median COVID-19-related delay in systemic therapy was 24.5 days, and the median COVID-19-related delay for surgery and radiation was 47 and 55 days, respectively. On univariate analysis, Black/African American, Asian, and Other race groups were more likely to experience a COVID-19-related delay and/or change compared to White patients; however, on multivariate modeling, race and ethnicity were not associated with a delay [36•]. Another survey of breast cancer survivors in the United States found that race had no significant effect on patient-reported delays in care [37].
Future Directions
Future work is needed to characterize the impact of these widespread surgical delays, especially among vulnerable populations. Specifically, studies are needed that characterize time from diagnosis to surgery for breast cancer patients. Studies must be designed to account for social determinants of health such as financial stress, education, travel time to a healthcare facility, and geographical features specific to the pandemic, such as local lockdowns and suspensions of elective surgery.
While a large body of data exists documenting disparities in time to treatment for breast cancer, a paucity of data exists for mitigation strategies. Designing targeted interventions for more equitable breast cancer care is complex and should include the following (Fig. 1):Increased implementation of multidisciplinary breast programs at hospitals with a large volume of breast cancer patientso Multidisciplinary breast cancer programs should be designed to provide comprehensive but efficient breast cancer care. Enabling patients to be seen by multiple disciplines on a single day can help overcome barriers to timely treatment by minimizing the number of visits. Additionally, coordination between disciplines such as surgery, medical oncology, radiation oncology, plastic surgery, and genetic counseling at a single site can streamline care for patients and improve communication about individualized treatment plans.
Increased funding for patient navigation services, particularly among hospitals treating a large population of medically underserved patientso Patient navigation services have been shown to improve outcomes and reduce treatment intervals for patients requiring complex cancer care [38]. Since the expanded use of telehealth services since the COVID-19 pandemic, expansion of navigation services to include telehealth visits will be prudent to increase access [39]. However, considering the digital divide, this will require expanded resources to improve broadband internet services and education to familiarize patients with use of electronic communication methods. For example, orientation to the methods of communication available through the electronic medical record can empower patients to obtain enhanced follow-up and coordination of care.
Establishment of standards for time to treatment to enhance awareness among providerso More visibility on how time to treatment is an essential element of cancer care that improves outcomes is needed, particularly among providers caring for a large proportion of racial minorities and Medicaid or underinsured patients. By establishing standards for acceptable treatment intervals from presentation to diagnosis, diagnosis to treatment, and delivery of adjuvant therapies, providers will have metrics to adhere to, similar to the monitoring of adverse events.
Fig. 1 Strategies for improving disparities in treatment delays in the COVID-19 era
Conclusions
In conclusion, disparities in time to treatment for breast cancer have been well documented. While most studies have found significant differences in the interval from diagnosis to treatment for racial and ethnic minorities and Medicaid or uninsured patients, more work is needed to investigate the impact that the COVID-19 pandemic has had on the diagnosis and treatment of breast cancer patients, particularly among vulnerable populations. Mitigating differences in treatment delays is complex but should include more widespread availability of multidisciplinary breast programs and patient navigators, as recent data have indicated their potential to improve disparities.
Acknowledgements
We acknowledge the expertise and literature search assistance of Michelle R. Demetres of the Weill Cornell Medicine Samuel J. Wood Library.
Declarations
Ethics Approval and Consent to Participate
This article does not contain any studies with human or animal subjects performed by any of the authors.
Conflict of Interest
The authors declare no competing interests.
This article is part of the Topical Collection on Breast Cancer Disparities.
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| 0 | PMC9735127 | NO-CC CODE | 2022-12-14 23:28:32 | no | Curr Breast Cancer Rep. 2022 Dec 6;:1-9 | utf-8 | Curr Breast Cancer Rep | 2,022 | 10.1007/s12609-022-00469-9 | oa_other |
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Asia-Pac Financ Markets
Asia-Pacific Financial Markets
1387-2834
1573-6946
Springer Japan Tokyo
9386
10.1007/s10690-022-09386-4
Original Research
The Stock Performance of Green Bond Issuers During COVID-19 Pandemic: The Case of China
Jin Jiongye 1
http://orcid.org/0000-0003-2964-0733
Zhang Jianing [email protected]
12
1 grid.507057.0 0000 0004 1779 9453 College of Business and Public Management, Wenzhou-Kean University, 325060 Wenzhou, China
2 grid.507057.0 0000 0004 1779 9453 Center for Big Data and Decision-Making Technologies, Wenzhou-Kean University, 325060 Wenzhou, China
5 12 2022
120
14 5 2022
31 8 2022
14 9 2022
© The Author(s), under exclusive licence to Springer Japan KK, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
The green bond (GB) is a new financial product in the green finance field that has recently become a corporate social responsibility (CSR) tool for organizations. Previous studies show that high-CSR firms receive more trust from shareholders during a financial crisis. This paper aims to assess the stock performance of publicly listed Chinese companies that issued GBs during the COVID-19 pandemic. The bond sample covers 2016–2019 and consists of 67 listed issuers. The paper uses the event study method based on the market and Fama-French (1993) three-factor models. Our results show that GB issuers exhibited significantly positive cumulative abnormal stock returns on the official announcement dates of the COVID-19 outbreak. The positive cumulative abnormal returns are mainly driven by non-financial GB issuers rather than financial GB issuers. The results reflect the attitudes of investors toward GB-issuing companies primarily in the context of the crisis and contribute to the development of green finance policies.
Keywords
Stock market
COVID-19
Green bond
CSR
Event study
JEL Classifications
G01
G12
G32
Q5
http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China 71772111 Zhang Jianing Student Partnering with Faculty Research Program of Wenzhou-Kean UniversityWKUSPF202222 Zhang Jianing Internal Research Support Program of Wenzhou-Kean UniversityIRSPG202206 Zhang Jianing
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pmcIntroduction
Environmental protection has become a global concern. Transitioning to a low-carbon economy is a crucial strategy to combat climate change. Green finance, also called climate finance, is rising to achieve the climate challenge by mobilizing the capital of the financial market for environmentally friendly projects. The green bond (GB) is one of the emerging green financial products and is also a fixed-income asset (Ferrer et al., 2021). To promote the financing and transparency of sustainable development projects, the International Capital Market Association published the Green Bond Principles, according to which GBs are intended to support projects with “environmental benefits.”1 This environmental purpose makes the most significant difference between GBs and conventional bonds. As part of corporate social responsibility (CSR), the company that issues GBs should disclose relevant information to the public to ensure the funds are used for qualified green projects.1 This action can help the issuing company build positive public perception; at the same time, it has to bear a considerable reputation risk stemming from possible violations of green guidelines.
Over the past decades, the GB market has witnessed rapid growth. The worldwide cumulative issuance of GBs grew from $0.8 billion in 2007 to $1 trillion at the end of 2020; the annual growth rate is around 95%.2 At the end of 2020, China approached 1.4 trillion yuan of GBs.3 Corporate bond issuance accounts for the largest share among all entities. Hence, Chinese corporates act as vital participants in the GB market. This market is expected to have tremendous potential thanks to the global mission of CO2 emission reduction expressed by the Paris Agreement, which planned to increase investment in renewable energy by $110 trillion by 2050.4 As the large emitter of greenhouse gases in the world, China actively joined the Paris Agreement. The 1st issuer of GB in China was published in 2015 by the wind energy firm Xinjiang Goldwind Science and Technology.5 So far, China has the largest GB market worldwide. Because of the lack of an international standard for identifying green assets, the definition of “green” varies among countries. Therefore, this paper will only discuss GBs issued by China after 2015 and focus on Chinese listed corporate issuers.
The GB market is a relatively young segment that started growing only in 2015. Academic research about it, therefore, is limited. Most scholars have focused on testing the pricing model of GBs (Hyun et al., 2021; Agliardi & Agliardi, 2021), the hedging effect of GBs compared to other assets (Jin et al., 2020), the link between GBs and other financial assets (Reboredo, 2018; Nguyen et al., 2021), and investors’ perception of “green” (Zerbib, 2019; Sangiorgi & Schopohl, 2021). Considerable research has been undertaken in management and finance to examine the global relationship between CSR and corporate performance. Flammer (2013), for example, argued that corporates’ eco-friendly and CSR activities would have a minimal positive effect on stocks, while eco-harmful activities would have an apparent adverse effect. However, few studies have discussed the stock performance of corporates issuing GBs, especially the impact of GBs on stock performance during the COVID-19 pandemic.
This paper studies the impact of the COVID-19 pandemic on GB issuers using the event study method. To improve the accuracy of event date selection for the pandemic, we set two event dates: December 31, 2019, and March 11, 2020. The market model’s event study reports an upward trend of cumulative abnormal returns (CARs) within the event window [-10, 10] for both event dates. Furthermore, there are significantly large positive CARs from the second day after the announcement to the tenth day. It indicates that the sample GB issuers generally have positive abnormal stock performance either when the pandemic breaks out in China or spreads out worldwide. However, by dividing the sampled companies into financial institutions and non-financial firms, the results of the CARs are different. After the event date, there are significant positive CARs for the non-financial issuers but negative CARs for the financial issuers in two cases. These results suggest that GB issuers in the financial sector are shocked by the COVID-19 crisis, while non-financial companies enjoy positive abnormal stock returns and more trust from investors regardless of whether it is the early or the late stage of the pandemic. To better test the results, the paper uses the Fama-French (1993) three-factor model to estimate the CAR values of the two event dates. Under the Fama-French model, the first event results are the opposite of the results based on the market model, but they are similar for the second event. The opposite results suggest that the positive CARs in the market model may be driven by small or value stocks. To summarize, for the whole sample, the pandemic positively impacts financial GB issuers’ CARs around the event dates. The non-financial issuers have positive CARs, while the financial issuers have negative CARs.
For market participants and policymakers, it is crucial to understand the stock performance of GB issuers during the COVID-19 pandemic. The pandemic tends to negatively impact the global stock market (Erdem, 2020) and positively impact the GB market (Yi et al., 2021; Lee & Lu, 2021) also revealed that CSR companies were less affected by the COVID-19 outbreak than non-CSR companies. The impact of the COVID-19 pandemic on the stock market might be moderated by GB issuance and other CSR activities. This study can help policymakers gauge the effectiveness of climate policies, develop a sustainable financial market, and construct a green financial system. Regarding investors, as a new interdisciplinary financial product, the GB is essential for investment portfolio diversification and hedging capability in the financial field and combating global climate change.
The remainder of this paper is structured as follows. Section 2 reviews the relevant literature and develops our hypotheses. The data concerning the sample and the methodology are presented in Sect. 3. Section 4 discusses the study’s results, and Sect. 5 concludes the paper.
Literature Review
Recent developments in green finance have led to an interest in the GB market. Important topics include the benefits of GBs as a CSR tool, the relationship between GBs and other financial markets, and the impact of the COVID-19 pandemic on the stock market and the GB market. This literature review focuses on these topics in the following subsections.
GB and CSR
The growth of the GB market is in line with the practice of CSR by organizations (Febi et al., 2018). CSR has long been a question of great interest across many fields. Previous research has established that high CSR participation can help the financial performance of corporations. For example, Mumtaz & Yoshino (2021) indicate that initial public offerings by greener firms have better long-term performance. Several researchers (e.g., Heinkel et al., 2001; El Ghoul et al., 2011) suggest that CSR activities can help corporations reduce capital costs.
Furthermore, with the development of green finance, some studies have investigated the link between CSR and GBs. Paranque & Revelli (2019) analyze the ethical value of issuing GBs through qualitative research on their social impacts. Under a transparent green financial regulatory regime, GBs are an effective intermediary for companies to exchange financing for social development (Paranque & Revelli, 2019) and financial benefits (Tang & Zhang, 2020; Flammer, 2018; Agliardi & Agliardi, 2021). For companies, the issuance of GBs positively impacts their credit quality (Agliardi & Agliardi, 2021) and CSR scores (Zhou & Cui, 2019). Regarding institutional investors, survey evidence from Krueger et al., (2020) shows that they consider the climate risk and prefer investment in environmental, social, and governance (ESG) oriented assets and that investors’ sentiments affect GB returns and volatility (Pham & Huynh, 2020; Pineiro-Chousa et al., 2021).
However, the effectiveness of CSR on a corporation’s financial performance has been subject to considerable scrutiny. An asymmetric pattern seems to exist in which firms that increase environmental friendliness do not create shareholder value (Fernando et al., 2017), while eco-harmful activities negatively affect stock values (Flammer, 2013). Investors also avoid eco-friendly companies (Fernando et al., 2017). Similarly, Kruger (2015) proposes a small negative stock response to a firm’s positive CSR news. Cui & Docherty (2020) find that ESG events only impact the stock market in the short term, with no long-term effect, suggesting that “greenness” may have no close relationship with financial outcomes.
The Link Between GBs and Other Financial Assets
Another significant discussion concerning GBs is the link between these bonds and other financial assets over different time horizons (Reboredo, 2018; Reboredo & Ugolini, 2020; Reboredo et al., 2020; Nguyen et al., 2021; Ferrer et al., 2021; Pham, 2021; Liu et al., 2021). This discussion also considers hedging effects and diversification benefits. Reboredo & Ugolini (2020) prove that GBs are closely linked to the currency and fixed-income markets while weakly tied to the energy market. Supporting this statement using different empirical methodologies, Ferrer et al., (2021) find connections among GBs, Treasury bonds, and high-quality corporate bonds, while they find little connection among GBs, stocks, oil, and clean energy markets. Furthermore, Pham (2021) finds that GBs and green stocks are closely linked only during extreme market conditions. In other words, GBs have significant volatility spillovers from other markets. The diversification advantages of GBs with the stock market are confirmed by Reboredo (2018), Reboredo & Ugolini (2020), Reboredo et al., (2020), and Pham (2021). Consequently, GBs are vital hedging instruments in other markets, such as the commodity market (Naeem et al., 2021a) and the energy market (Jin et al., 2021).
For companies, the issuance of GBs positively impacts the issuer’s stock price (Tang & Zhang, 2020; Flammer, 2013; Zhou & Cui, 2019; Baulkaran, 2019) examined the stock reaction to the announcement of GB issuance. The CARs are positive and significant, consistent with Tang and Zhang’s (2020) findings. Wang et al., (2020) also revealed positive announcement stock returns for Chinese GB new issues, consistent with the stakeholder value maximization theory that corporate engagement in sustainable financing practice increases firm value in the long run and thus is favored by shareholders. However, Lebelle et al., (2020) show that the stock market reacts negatively to the announcement of international GB issuances.
The above review shows that GBs bring diversification and value-enhancing benefits to firms. The literature discusses the stock price responses to issuing GBs and the hedging benefits of these bonds. The impact of a GB on a corporation in China, particularly in the context of COVID-19, is unexplored.
The Impact of the COVID-19 Pandemic on the Stock Market and the GB Market
Since the beginning of the COVID-19 health crisis in 2020, researchers have widely investigated this phenomenon. Many scholars have focused on the stock market, while others have concentrated on the pandemic’s global impact (Erdem, 2020; Ramelli & Wagner, 2020; Zhang et al., 2020; Ashraf, 2020; Narayan et al., 2021; Engelhardt et al., 2021a, b). Some researchers have studied specific countries or regions (Al-Awadhi et al., 2020; Rahman et al., 2021; Sun et al., 2021; He et al., 2020; Lee & Lu, 2021). For example, Erdem (2020) and Ashraf (2020) use panel data from several countries to examine the global negative stock influence of COVID-19. Al-Awadhi et al., (2020), Sun et al., (2021), and He et al., (2020) clarify the different consequences of the COVID-19 pandemic on various Chinese industries. Their findings show the overall negative impact of the outbreak on the stock market. However, pharmaceutical, IT, and agricultural companies exhibit resilience during the pandemic.
Regarding the global shock of COVID-19 on the financial market, few studies have investigated how the pandemic influences the effectiveness of the hedging role of GBs. Using the event study method, Yi et al., (2021) found that COVID-19 disrupts Chinese green financing. They find that the COVID-19 pandemic has significantly impacted China’s GB market and greatly increased the CAR of the GBs. Naeem et al., (2021b) show that the GB market is more efficient during the pandemic. Taghizadeh-Hesary et al., (2021) also reveal that GBs in Asia tend to show higher returns than those in Europe and North America.
Based on investors’ pursuit of stability rather than return in times of crisis, some researchers (Lins et al., 2017; Engelhardt et al., 2021a, b) focus on evaluating the financial performance of firms practicing CSR activities during a crisis. Their findings show similar results. Lins et al., (2017) found that high-CSR firms obtained more trust and stock returns even during the financial crisis of 2008–2009. Engelhardt et al., (2021a, b) note the higher stock returns and lower volatility in high-ESG-related European firms during the COVID-19 pandemic. Moreover, Lee & Lu (2021) use the event study approach to compare CSR- and non-CSR-practicing companies’ stock reactions to the COVID-19 outbreak in Taiwan. They indicate that CSR-practicing companies were less affected by the outbreak and that their stock prices recovered faster than non-CSR-practicing companies.
Overall, the COVID-19 pandemic appears to hurt stock markets but positively impacts GBs and high-CSR firms. Therefore, the following hypothesis is proposed:
Hypothesis 1
Chinese corporations that issue GBs have positive abnormal stock returns during the COVID-19 pandemic.
Financial vs. Non-financial Firms
Foerster & Sapp (2005) have pointed out that it is common practice in many empirical studies in finance to exclude financial services firms from the samples. The standard argument for this exclusion is that financial services firms differ from typical firms because they tend to have much greater leverage and increased sensitivity to financial risks. For example, Fama & French (1993) explicitly exclude financial firms because of their high leverage. Since the primary purpose of financial institutions issuing GBs is to obtain funding, increase their capital liquidity, and invest in other firms’ projects (Tang & Zhang, 2020), the greenness of the bond project may be reduced, making the market reactions less trustworthy. Therefore, this study separates the non-financial issuers from the financial service issuers to further test whether they have different stock performances.
Taghizadeh-Hesary et al., (2021) pointed out that the Asian GBs market is dominated by the banking sector, representing 60% of all issuance. Given that bonds issued by this sector tend to show lower returns than average, they recommend different tax policies for the bonds issued by the banking sector. Lebelle et al., (2020) split their sample into financial and non-financial GBs. They show that financial GBs issuers experience significantly lower CARs than non-financial corporations in response to the announcement of GB issuances. Considering the lower abnormal returns for financial firms, we propose the following hypothesis.
Hypothesis 2
The positive impact of the COVID-19 pandemic on the stock performance of GB issuers is mainly driven by non-financial firms.
Data and Methodology
Data and Sample
This study employs three data sources: the WIND economic database, the China Stock Market & Accounting Research (CSMAR) database, and the Central University of Finance and Economics (CUFE) database. From the WIND database, we obtained information on all existing GBs in the current Chinese market. This information included bond ID, bond name, issuer, nature of the issuing company (private or state-owned, publicly listed or not), coupon rate, and debt rating. The data includes the GBs issued from mainland China and are not classified by bond types. The Chinese CSI300 stock market index daily returns and the sample companies’ daily stock returns from March 11, 2019, to April 10, 2020, were also obtained from WIND.
From the CSMAR database, we downloaded the sample of 1,607 Chinese GBs issued in mainland China from 2016 to 2019, containing bond ID, issuer name, issuer rating, bond characteristics (e.g., par value, bond nature, and bond credit level), and project investment. The information on GBs from WIND was matched and merged with that from CSMAR, using bond ID to identify the issuers’ attributes and filter out the listed firms. By excluding the private issuers, Hong Kong-listed companies, repeat information, and bonds with missing important information (e.g., issue price, par value, bond credit level), 273 GBs and 67 issuers remained. Of the 67 issuers, 20 are financial institutions, and 47 are public companies in other industries. Finally, the daily Fama-French three-factor indexes are retrieved from the CUFE database.
Methodology
The event study method is a standard research method in finance to test the effect of a specific event or policy by looking at the abnormal performance (Kothari & Warner, 1997). Following Huang and Liu’s (2021) and Tang and Zhang’s (2020) model, we use the event study approach to examine the impact of the COVID-19 pandemic on Chinese GB-issuing companies. The event window selection is variable to test the impact during a limited time interval and border times. Furthermore, the paper use models of abnormal returns to measure the sample’s excess returns within the event window. In order to estimate the expected return (ER) and abnormal return (AR), the market model is used based on the following calculations,1 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{i,t}={\alpha }_{i}+{\beta }_{i}{R}_{m,t}+{\mu }_{i,t},$$\end{document}
2 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${E(R}_{i,t})={\widehat{\alpha }}_{i}+{\widehat{\beta }}_{i}{R}_{m,t},$$\end{document}
3 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$A{R}_{i,t}={R}_{i,t}-E\left({R}_{i,t}\right),$$\end{document}
where \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$E{\left(R\right)}_{i,t}$$\end{document} is the expected return of firm \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$i$$\end{document} on the t-th day based on the estimation window. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{m,t}$$\end{document}indicates the excess return of market index m on the t-th day, and α, β, and µ denote the intercept, the slope of the market model, and a random error term, respectively. In Eq. (3), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$A{R}_{i,t}$$\end{document}represents the abnormal return of the listed company \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$i$$\end{document} on the t-th day, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{i,t}$$\end{document} is the stock return of the firm \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$i$$\end{document} on the t-th day.
CARs are computed as follows:4 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$CA{R}_{i,T}=\sum _{t={t}_{1}}^{t={t}_{2}}A{R}_{i,t},$$\end{document}
5 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$AA{R}_{t}=\frac{1}{N}\sum _{i=1}^{n}A{R}_{i,t},$$\end{document}
6 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$CAA{R}_{T}=\frac{1}{N}\sum _{i=1}^{n}AA{R}_{i,T},$$\end{document}
where \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$CA{R}_{i,T}$$\end{document} is the cumulative abnormal return of company \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$i$$\end{document} with the time interval T [t1, t2], from initial moment t1 to final moment t2. In Eq. (5), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$AA{R}_{t}$$\end{document} calculates the average abnormal return of all the GB-issuing listed firms on the t-th day, where N is the number of the firms (from 1 to n). Similarly, in Eq. (6), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$CAA{R}_{T}$$\end{document} is the cumulative average abnormal return of all the companies in the sample within the time interval T on the t-th day.
Table 1 Descriptive of chinese GBs issuers
Variables N Mean StdDev Min Max Skewness Kurtosis
\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{i,t}$$\end{document} 15,631 -0.3356 2.1765 -10.1266 43.9394 0.6659 19.1548
\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{m,t}$$\end{document} 15,631 0.0396 1.2880 -7.8809 3.8608 -1.1190 10.3250
E(R) 15,631 -0.1858 1.9751 -12.8163 4.1960 -2.7517 13.0970
AR 1,386 -0.0347 2.3473 -10.9260 17.1436 1.1465 11.1253
CAR 1,386 -0.5474 9.3571 -23.6497 55.5644 2.1368 8.3158
CAAR 15,631 -0.7608 12.3881 -18.5594 72.4265 3.1129 18.2403
The table reports descriptive statistics for the sample of 67 Chinese public companies that issued GBs from 2016 to 2019. The dataset of stock closing prices and market stock returns is obtained from the WIND database. Using the event study approach, we select two event dates when t = 0. One was December 31, 2019, when the news of the COVID-19 outbreak in Wuhan was announced. Another event day is March 11, 2020, when the World Health Organization declared the COVID-19 pandemic. The estimation event window is [-200, -20]. The event window is [-10, 10]. The raw returns (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{i,t}$$\end{document}) are calculated from daily stock closing prices. The Chinese CSI300 stock market index return is considered the daily market return (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{m,t}$$\end{document}). The expected return (E(R)) is the expected return within the predicted event window based on the market model. The abnormal returns (AR) equal raw returns minus the expected return based on a market model. The cumulative abnormal returns (CAR) are the sums of each company’s abnormal returns within the event window.
To accurately study the investors’ response to the outbreak, we choose two different news points as event days. On December 31, 2019, it was officially confirmed that the novel virus originated from a Wuhan seafood market. Following this announcement, news of the pandemic attracted significant attention, affecting investors’ attitudes toward the sampled companies. On March 11, 2020, World Health Organization declared a global pandemic outbreak of the novel coronavirus (COVID-19) (Cucinotta & Vanelli, 2020). The event window is ten days before and after the announcement date (t = 0). Specifically, the event window interval T is [-10, 10]. The estimation window is defined as [-200, -20] to avoid confounding effects. Table 1 shows the summary statistics of the stock performance of the Chinese GB issuers in our sample.
We used the t-test method to test the event study results, investigating whether the COVID-19 crisis impacted the firms’ stock performance. The calculation is based on the following equations,7 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$T\text{-}tes{t}_{AA{R}_{t}}=\frac{AA{R}_{t}}{S\left(A{R}_{i,t}\right)/{\sqrt{N}}^{{\prime }}},$$\end{document}
8 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$T\text{-}tes{t}_{CAA{R}_{T}}=\frac{CAA{R}_{T}}{S\left(AA{R}_{i,T}\right)/{\sqrt{N}}^{{\prime }}},$$\end{document}
where S is the standard deviation. Finally, the study focuses on the CAR results of two events to investigate the cumulative stock price influence of the COVID-19 pandemic on Chinese GB issuers in the event window.
Results and Discussions
Main Results
Figure 1 presents the CAR trend for Chinese GB-issuing companies impacted by the COVID-19 pandemic during the event window [-10, 10]. Figure 1 shows a positive and rising trend of CARs of all the companies during the event window of the announcement date, December 31, 2019. The exact values and t-test results are presented in Table 2, which shows that all the companies have significant small positive CARs at the announcement date. From the second to the tenth day after the event date, CARs remain significantly positive. This result suggests that COVID-19 positively impacts the stock performance of Chinese companies that issued GBs.
Fig. 1 CARs of the first event on December 31, 2019
Table 2 CARs in the early COVID-19 period (December 31, 2019)
Event Date: 2019/12/31
Event window CAR t value
[-10, 10] 2.7831*** 2.9072
[-5, 5] 1.8259*** 2.7824
[-4, 4] 1.3683*** 3.1704
[-3, 3] 1.0157*** 2.6756
[-2, 2] 0.2171 0.7791
[-1, 1] -0.1902 -1.0877
[0] 0.2206* 1.6857
[-10, 0] 1.4550*** 2.8427
[-5, 0] 0.8354* 1.9352
[-2, 0] -0.1755 -0.8591
[-1, 0] -0.0606 -0.3413
[-10, -1] 1.2343** 2.3636
[-5, -1] 0.6147 1.3700
[0, 1] 0.0911 0.6251
[0, 2] 0.6132*** 2.8399
[0, 3] 1.2902*** 3.6384
[0, 4] 1.7241*** 4.4815
[0, 5] 1.2111** 2.4610
[0, 10] 1.5488** 2.1970
[1, 5] 0.9905** 2.1339
[1, 10] 1.3282* 1.9632
The table reports the event study result on the event date, December 31, 2019, when the official news announced the epidemic in Wuhan, China. The event study method utilizes the market model based on the estimation event window [-200, -20] and event window [-10, 10]. The CARs are sums of each GB issuing company’s abnormal returns within the event window. ***-stat. sig. at 1% level. **-stat. sig. at 5% level. *-stat. sig. at 10% level
The second event day was March 11, 2020, when China passed the pandemic’s peak, but World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic (Cucinotta & Vanelli, 2020). Figure 2 shows a continuous upward trend of CARs during the event window of the second event date [-10, 10]. Furthermore, the detailed results in Table 3 show significantly positive CAR values lasting from one day after the event to the tenth day. CARs on the event day are also significantly positive. It indicates that all the companies have better stock performance in the late COVID-19 pandemic period than in the early period
Fig. 2 CARs of the second event on March 11, 2020
Table 3 CARs in the late COVID-19 period (March 11, 2020)
Event Date: 2020/3/11
Event window CAR t value
[-10, 10] 9.8649*** 7.7556
[-5, 5] 6.0783*** 7.2432
[-4, 4] 5.1156*** 6.9490
[-3, 3] 4.8605*** 7.9611
[-2, 2] 2.1348*** 3.3409
[-1, 1] 0.0977 0.1772
[0] 0.8507*** 3.3875
[-10, 0] 3.6833*** 3.4898
[-5, 0] 0.7136 1.2133
[-2, 0] 1.0540** 2.3293
[-1, 0] -0.2516 -0.5662
[-10, -1] 2.8325*** 2.8921
[-5, -1] -0.1371 -0.2600
[0, 1] 1.2000*** 3.2378
[0, 2] 1.9315*** 4.1305
[0, 3] 4.3786*** 8.9198
[0, 4] 5.1299*** 8.3202
[0, 5] 6.2154*** 9.0313
[0, 10] 7.0323*** 9.8905
[1, 5] 5.3647*** 7.4515
[1, 10] 6.1816*** 8.4943
The table reports the event study result on the second event date, March 11, 2020, when the WHO declared the COVID-19 pandemic. The event study method utilizes the market model based on the estimation event window [-200, -20] and event window [-10, 10]. The CARs are sums of each GB issuing company’s abnormal returns within the event window. ***-stat. sig. at 1% level. **-stat. sig. at 5% level. *-stat. sig. at 10% level
Analyzing Financial and Non-financial GB-Issuers in the Event Windows
As discussed in Sect. 2.4, financial firms might behave differently from non-financial firms due to their high leverage. To better understand the impact of the COVID-19 pandemic on GB-issuing companies, we divide the 67 firms into financial and non-financial companies to determine whether the company’s financial nature affects the results.
A comparison of the abnormal performance of GB issuers in the financial and non-financial sectors is presented in Table 4, where the CARs are based on the first event date, December 31, 2019. For non-financial firms, the CARs are negative two days before the event. The value is statistically positive at the 10% level on the announcement day and becomes significantly positive at the 1% level from the second day to the tenth day after the event. It indicates that the pandemic positively impacts the non-financial GB issuers’ stock, and these firms may have a relatively significant hedging effect during the initial stage of the crisis.
For the financial companies, the CARs are positive but insignificant on the first event day, similar to the non-financial companies’ situation. However, the CARs change to negative values from the second day to the tenth day after the event date. These opposite results reflect the better stock performance of the non-financial companies during the initial COVID-19 outbreak. This result is consistent with the literature that financial firms show lower CARs than non-financial firms in response to GB issuances (Lebelle et al., 2020). It also suggests that investors may have had less trust and confidence in financial GB issuers after the COVID-19 outbreak because financial issuers tend to have high leverage and might dilute the greenness of the bond project. As Tang & Zhang (2020) pointed out, corporate GBs are used to finance issuers’ projects, and project eligibility criteria are specified. In contrast, financial institutions issue GBs to make green loans and invest in other firms to finance other firms’ projects and will only define general criteria for selecting green projects. This practice contributes to further reduction of the greenness of the bond project.
Table 4 CARs of financial and non-financial issuers on December 31, 2019
Event Date: 2019/12/31
Event window Non-financial Financial Difference
CAR t value CAR t value
[-10, 10] 4.0973*** 3.3604 -0.6483 -0.6492 4.7456
[-5, 5] 2.7348*** 3.3603 -0.5474 -0.6467 3.2822
[-4, 4] 1.8601*** 3.5582 0.0840 0.1229 1.7761
[-3, 3] 1.4712*** 3.1717 -0.1738 -0.3056 1.6450
[-2, 2] 0.5881 1.6516 -0.7516** -2.6040 1.3397
[-1, 1] -0.1656 -0.9766 -0.2543 -0.5522 0.0887
[0] 0.2386* 1.7751 0.1738 0.5362 0.0648
[-10, 0] 1.3356** 2.1983 1.7666* 1.8169 -0.4310
[-5, 0] 0.9031* 1.7784 0.6585 0.7822 0.2446
[-2, 0] -0.0387 -0.1494 -0.5326* -1.8564 0.4939
[-1, 0] -0.0953 -0.6449 0.0300 0.0575 -0.1253
[-10, -1] 1.0971* 1.7217 1.5927* 1.7499 -0.4956
[-5, -1] 0.6646 1.2329 0.4846 0.5863 0.1800
[0, 1] 0.1683 1.0063 -0.1105 -0.3729 0.2788
[0, 2] 0.8654*** 3.2318 -0.0452 -0.1488 0.9106
[0, 3] 1.8964*** 4.2691 -0.2926 -0.8766 2.1890
[0, 4] 2.3225*** 4.7615 0.1615 0.4439 2.1610
[0, 5] 2.0702*** 3.3199 -1.0320** -2.7987 3.1022
[0, 10] 3.0002*** 3.4215 -2.2410*** -5.6906 5.2412
[1, 5] 1.8316*** 3.1572 -1.2058*** -3.0264 3.0374
[1, 10] 2.7617*** 3.3082 -2.4148*** -6.0568 5.1765
The table reports the event study results on the event date, December 31, 2019, by dividing the sample companies into financial and non-financial companies. The estimation and event windows are [-200, -20] and [-10, 10], respectively. The CARs are sums of each GB issuing company’s abnormal returns within the event window. ***-stat. sig. at 1% level. **-stat. sig. at 5% level. *-stat. sig. at 10% level
Table 5 reports the comparison for the second event date, March 11, 2020. For the non-financial issuers, the results are similar to those in Table 4. There is a significant positive abnormal stock performance after the announcement day and on the event day. For the financial issuers, there are negative CAR values from the event date to the tenth day after the event, which contrasts with the situation of the non-financial companies. Similar to the first event, the stock price of the financial institution issuers deteriorates after the spread of the COVID-19 outbreak, while the stock performance of the non-financial corporate GB issuers improves. Non-financial companies include firms from multiple sectors, such as manufacturing and energy. After the production of non-financial companies resumes, investors still show higher levels of trust in non-financial GB issuers.
Table 5 CARs of financial and non-financial issuers on March 11, 2020
Event Date: 2020/3/11
Event window Non-financial Financial Difference
CAR t value CAR t value
[-10, 10] 9.8649*** 5.5450 3.0089*** 4.0464 6.8560
[-5, 5] 6.0783*** 5.7358 -3.6570** -2.8551 9.7353
[-4, 4] 5.1156*** 5.4645 0.5231 0.5042 4.5925
[-3, 3] 4.8605*** 6.3724 -0.4650 -0.4667 5.3255
[-2, 2] 2.1348*** 2.7596 -0.1097 -0.1099 2.2445
[-1, 1] 0.0977 0.1304 -2.9611*** -5.2061 3.0588
[0] 0.8507** 2.5134 -0.7679*** -3.3633 1.6186
[-10, 0] 3.6833** 2.4865 5.1526*** 10.0655 -1.4693
[-5, 0] 0.7136 0.9101 0.4193 0.5871 0.2943
[-2, 0] 1.0540* 1.7452 -0.5529 -1.0102 1.6069
[-1, 0] -0.2516 -0.4142 -2.8407*** -6.7480 2.5891
[-10, -1] 2.8325** 2.0550 5.9205*** 11.4508 -3.0880
[-5, -1] -0.1371 -0.1968 1.1872* 1.7249 -1.3243
[0, 1] 1.2000** 2.3936 -0.8883** -2.2435 2.0883
[0, 2] 1.9315*** 3.5518 -0.3247 -0.4180 2.2562
[0, 3] 4.3786*** 7.5678 -0.8127 -0.9525 5.1913
[0, 4] 5.1299*** 6.7319 -1.7444* -1.8099 6.8743
[0, 5] 6.2154*** 7.4058 -4.8442*** -4.1359 11.0596
[0, 10] 7.0323*** 7.2811 -2.9115*** -4.0171 9.9438
[1, 5] 5.3647*** 5.9481 -4.0763*** -3.8596 9.4410
[1, 10] 6.1816*** 6.1548 -2.1436*** -3.3038 8.3252
The table reports the event study results on the event date, December 31, 2020, by dividing the sample companies into financial and non-financial companies. The estimation and event windows are [-200, -20] and [-10, 10], respectively. The CARs are sums of each GB issuing company’s abnormal returns within the event window. ***-stat. sig. at 1% level. **-stat. sig. at 5% level. *-stat. sig. at 10% level
Alternative Models
To conduct robustness checks, we choose the Fama-French three-factor model (Fama & French, 1993). We used this as an alternative method to reestimate expected stock returns and obtain new CAR values. Doing so allowed us to investigate whether the conclusions of the event studies based on two different return models were the same. Using the Fama-French three-factor model, the abnormal return is calculated as follows:9 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{i,t}={\alpha }_{i}+{\beta }_{i1}{R}_{m,t}+{\beta }_{i2}{SMB}_{t}+{\beta }_{i3}{HML}_{t}+{\epsilon }_{i,t},$$\end{document}
10 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${E(R}_{i,t})={\widehat{\alpha }}_{i}+{\widehat{\beta }}_{i1}{R}_{m,t}+{\widehat{\beta }}_{i2}{SMB}_{t}+{\widehat{\beta }}_{i3}{HML}_{t},$$\end{document}
11 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$A{R1}_{i,t}={R}_{i,t}-E\left({R}_{i,t}\right),$$\end{document}
where \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\beta }_{i1}$$\end{document}, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\beta }_{i2}$$\end{document}, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\beta }_{i3}$$\end{document} are estimated by regressing company i’s returns on three factors—daily market excess returns, firm size factor, and book-to-market—in the estimation windows [-200, -20]. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{m,t}$$\end{document} indicates the excess return of the market index. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$HM{L}_{t}$$\end{document} and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$SM{B}_{t}$$\end{document} are the high-minus-low book-to-market and the small-minus-big size factors on day t, respectively. Fama & French (1993) sort firms into six portfolios based on large/small market-capitalization and large/intermediate/small book-to-market ratios. HML is the difference between the simple average of the returns on the two high book-to-market portfolios and the average of the returns on the two low book-to-market portfolios. SMB is the difference between the simple average of the returns on the three small-capitalization portfolios and the simple average of the returns on the three big-capitalization portfolios. AR1 is the abnormal return based on Fama-French three-factor model. CARs are calculated based on Eq. (4) in the methodology section.
Table 6 Fama-French CARs on December 31, 2019
Event Date: 2019/12/31
Event window All companies Non-financial Financial
CAR t value CAR t value CAR t value
[-10, 10] -5.6778*** -6.6533 -5.6778*** -5.0131 -4.3197*** -4.1698
[-5, 5] -5.7793*** -9.4432 -5.7793*** -7.3421 -1.9438** -2.3555
[-4, 4] -2.8272*** -6.7031 -2.8272*** -5.3985 -2.2468*** -3.2427
[-3, 3] -3.3614*** -8.3588 -3.3614*** -6.8045 -2.3031*** -3.6186
[-2, 2] -1.5800*** -5.4908 -1.5800*** -4.3873 -1.418*** -4.1644
[-1, 1] -1.4064*** -7.1920 -1.4064*** -7.4386 -0.8139 -1.6614
[0] -0.2952** -2.2645 -0.2952** -2.1418 0.1704 0.5692
[-10, 0] -2.3477*** -4.3402 -2.3477*** -3.9391 -4.136*** -3.5648
[-5, 0] -2.3215*** -5.5133 -2.3215*** -4.7203 -4.152*** -5.0353
[-2, 0] -0.4468* -1.8957 -0.4468* -1.6991 -4.4139*** -11.439
[-1, 0] -0.2749 -1.3912 -0.2749* -1.7748 -3.0383*** -5.4515
[-10, -1] -2.0524*** -3.7832 -2.0524*** -3.2655 -4.3064*** -4.0284
[-5, -1] -2.0262*** -4.6384 -2.0262*** -3.8639 -4.3224*** -5.372
[0, 1] -1.4267*** -8.9261 -1.4267*** -8.212 2.3949*** 6.836
[0, 2] -1.4284*** -6.3254 -1.4284*** -5.2719 3.1663*** 7.5524
[0, 3] -2.2872*** -6.6641 -2.2872*** -5.2414 3.2849*** 6.5506
[0, 4] -1.7902*** -5.2114 -1.7902*** -4.1084 3.6366*** 6.7631
[0, 5] -3.7531*** -8.3245 -3.7531*** -6.4253 2.3786*** 4.1057
[0, 10] -3.6253*** -6.0883 -3.6253*** -4.6396 -0.0133 -0.0212
[1, 5] -3.4579*** -8.1581 -3.4579*** -6.4627 2.2082*** 3.6392
[1, 10] -3.3301*** -5.7843 -3.3301*** -4.4678 -0.1837 -0.2801
The table reports the event study results on the event date, December 31, 2019, using the Fama-French three-factor model. The estimation and event window are [-200, -20] and [-10, 10], respectively. The CARs are sums of each GB issuing company’s abnormal returns within the event window. ***-stat. sig. at 1% level. **-stat. sig. at 5% level. *-stat. sig. at 10% level
Table 6 presents the Fama-French CAR values for the first event date, December 31, 2019, and compares the results for the financial institutions and non-financial firms. Based on the Fama-French three-factor model, the CAR results for the first event are very different from those obtained with the market model. In this case, all the firms suffer a significantly negative shock after the COVID-19 outbreak. Specifically, under the Fama-French model, the financial institution issuers exhibit significantly positive abnormal stock returns, while the non-financial corporate issuers have significantly negative abnormal stock returns. After adding more risk factors, the sampled companies have different benchmarks when estimating the expected returns. Thus, the outperformance of CARs in the market model might be driven by size or value effects (driven by small stocks or high book-to-market stocks) and disappears once the additional risk factors are considered.
Table 7 Fama-French CARs on March 11, 2020
Event Date: 2020/3/11
Event window All companies Non-financial Financial
CAR t value CAR t value CAR t value
[-10, 10] 4.3361*** 3.5675 4.3361** 2.5405 3.3070*** 4.9569
[-5, 5] 2.8168*** 3.5616 2.8168*** 2.7780 -2.5859** -2.4947
[-4, 4] 2.5350*** 3.6002 2.5350*** 2.8389 1.2344 1.3504
[-3, 3] 2.3789*** 4.2613 2.3789*** 3.3931 -0.5077 -0.5861
[-2, 2] 1.6355*** 2.6603 1.6355** 2.1906 -0.1638 -0.1759
[-1, 1] 0.1988 0.3641 0.1988 0.2676 -2.6417*** -4.8281
[0] 0.4863* 1.9661 0.4863 1.4589 -0.8493*** -3.6697
[-10, 0] -0.3714 -0.358 -0.3714 -0.2561 5.3835*** 8.5929
[-5, 0] -0.8609 -1.5427 -0.8609 -1.1589 1.9257** 2.7765
[-2, 0] 0.7287 1.6534 0.7287 1.2357 -0.5557 -1.0570
[-1, 0] -0.0181 -0.0412 -0.0181 -0.0300 -2.7113*** -6.6197
[-10, -1] -0.8577 -0.8885 -0.8577 -0.6344 6.2328*** 10.0401
[-5, -1] -1.3472** -2.6349 -1.3472** -2.0158 2.7751*** 4.1289
[0, 1] 0.7032* 1.9442 0.7032 1.4337 -0.7797** -2.0930
[0, 2] 1.3932*** 3.0835 1.3932** 2.6439 -0.4574 -0.6260
[0, 3] 2.6076*** 5.6863 2.6076*** 4.7763 -1.2946 -1.6864
[0, 4] 3.0756*** 5.2334 3.0756*** 4.2011 -2.0195** -2.3036
[0, 5] 4.1640*** 6.3018 4.1640*** 5.0746 -5.3609*** -5.0889
[0, 10] 5.1938*** 7.4264 5.1938*** 5.4444 -2.9258*** -4.1981
[1, 5] 3.6777*** 5.2341 3.6777*** 4.1062 -4.5116*** -4.7723
[1, 10] 4.7075*** 6.4990 4.7075*** 4.6930 -2.0765*** -3.3645
The table reports the event study results on the event date, March 11, 2020, using the Fama-French three-factor model. The estimation and event window are [-200, -20] and [-10, 10], respectively. The CARs are sums of each GB issuing company’s abnormal returns within the event window. ***-stat. sig. at 1% level. **-stat. sig. at 5% level. *-stat. sig. at 10% level
The Fama-French reestimation results for the second event date, March 11, 2020, are presented in Table 7. They are similar to the market model for the pandemic mitigation scenario. All the firms show significantly positive abnormal returns after the event date, with financial firms being significantly negatively affected on the fourth and fifth day after the event. Therefore, the positive abnormal returns are more robust during the late than the early COVID-19 periods.
Although most event studies utilized the market model and the Fama-French model to estimate the expected return and subsequent abnormal return (Kothari & Warner, 1997; Lebelle et al., 2020), the market model used for computing abnormal returns could have been adjusted by adding another exogenous variable to account for global shocks if any. Since the United States dominates the international financial market, we adopted S&P 500 index returns as our exogenous variable. After adding this additional risk factor, our results are shown in Table A1. The CARs based on [-10, 10] event days around March 11, 2020, show significantly positive numbers for all the companies and the non-financial companies but a negative and insignificant number for the financial companies. Such an observation is consistent with our results for the market model and the Fama-French model.
Conclusion
GB is an emerging financial product related to CSR and green finance. China has the biggest GB market in the world. The impact of GB issuances and CSR activities on company share prices has been widely researched but remains controversial. Several studies investigate this topic in the context of the COVID-19 pandemic, but there is still a gap in research on the pandemic’s impact on the stock performance of the companies that have issued GBs. This study fills this gap by exploring such an impact on Chinese GB issuers.
We select two event days and discuss the stock price performance of 67 Chinese GB-issuing firms during the pandemic using an event study methodology. Furthermore, we divide the sample into financial and non-financial companies, and we use the market model and the Fama-French three-factor model to compare the estimated abnormal return results. Our findings show that (1) at the early period of the pandemic, the two return models present different results, suggesting that the outperformance in the market model is mainly driven by small or value stocks. (2) at the late period of the pandemic, the two return models present similar results, with GB issuers having significantly positive abnormal stock returns and non-financial issuers performing better.
The different results for the non-financial and the financial companies are consistent with Sun et al., (2021) and He et al., (2020), who indicate that different industries are affected by the COVID-19 pandemic to different degrees. However, this study only distinguishes between the financial and non-financial sectors because of its small sample size. Future research could discuss whether companies issuing GBs have different stock market performances across various industries. Furthermore, this study employs the market and Fama-French three-factor models in the event study methodology. Future research could consider the results of other models, such as the four-factor model and the generalized autoregressive conditional heteroskedasticity model.
Appendix
Table A1 Adjusted Market Model CARs on March 11, 2020
Event Date: 2020/3/11
Event window All companies Non-financial Financial
CAR t value CAR t value CAR t value
[-10, 10] 2.8551** 2.5338 2.8551* 1.8194 -0.5347 -0.8199
[-5, 5] -1.8907** -2.6163 -1.8907* -1.9727 -9.7520*** -11.3658
[-4, 4] -1.5201** -2.3504 -1.5201* -1.8120 -4.5731*** -5.5696
[-3, 3] -2.7517*** -4.8575 -2.7517*** -3.8403 -6.8436*** -7.6581
[-2, 2] -2.4366*** -4.3795 -2.4366*** -3.5471 -3.8229*** -4.9124
[-1, 1] 0.7692 1.4259 0.7692 1.0472 -1.7969*** -3.2759
[0] 0.5065** 2.0199 0.5065 1.5104 -0.9392*** -3.8562
[-10, 0] 3.3196*** 3.3377 3.3196** 2.388 6.5774*** 12.3916
[-5, 0] 0.6095 1.0651 0.6095 0.8086 1.2933* 1.7309
[-2, 0] -0.1398 -0.3229 -0.1398 -0.2423 -1.2405** -2.3536
[-1, 0] 0.3600 0.8037 0.3600 0.5875 -1.9147*** -4.5503
[-10, -1] 2.8130*** 3.0327 2.8130** 2.1693 7.5165*** 12.6637
[-5, -1] 0.1030 0.1982 0.1030 0.1534 2.2325*** 2.9423
[0, 1] 0.9157** 2.5904 0.9157* 1.9103 -0.8214** -2.2058
[0, 2] -1.7903*** -4.3088 -1.7903*** -3.6219 -3.5216*** -5.6654
[0, 3] -1.0775** -2.3616 -1.0775* -1.9114 -5.5441*** -7.9918
[0, 4] -2.1638*** -3.9330 -2.1638*** -3.1108 -8.1481*** -10.3352
[0, 5] -1.9938*** -3.1506 -1.9938** -2.5083 -11.9846*** -12.1342
[0, 10] 0.0421 0.0601 0.0421 0.0451 -8.0512*** -9.7888
[1, 5] -2.5003*** -3.7023 -2.5003*** -2.8549 -11.0454*** -13.0885
[1, 10] -0.4644 -0.6461 -0.4644 -0.4729 -7.1120*** -9.9187
The table reports the event study results on the event date, March 11, 2020, using an adjusted market model. The estimation and event window are [-200, -20] and [-10, 10], respectively. The CARs are sums of each GB issuing company’s abnormal returns within the event window. ***-stat. sig. at 1% level. **-stat. sig. at 5% level. *-stat. sig. at 10% level
Acknowledgements
This work was supported by the National Natural Science Foundation of China [No. 71772111], the Student Partnering with Faculty Research Program of Wenzhou-Kean University [No. WKUSPF202222], and the Internal Research Support Program of Wenzhou-Kean University [No. IRSPG202206].
Declaration
Conflict of Interest
The authors have no potential conflicts of interest to declare.
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| 0 | PMC9735128 | NO-CC CODE | 2022-12-14 23:28:32 | no | Asia-Pac Financ Markets. 2022 Dec 5;:1-20 | utf-8 | null | null | null | oa_other |
==== Front
J Soc Econ Dev
J Soc Econ Dev
Journal of Social and Economic Development
0972-5792
2199-6873
Springer India New Delhi
213
10.1007/s40847-022-00213-0
Research Paper
Development impact bonds in developing countries: an emerging innovation for achieving social outcomes
http://orcid.org/0000-0003-0595-0913
Mishra Alok Kumar [email protected]
1
Dash Aruna Kumar [email protected]
2
1 grid.18048.35 0000 0000 9951 5557 School of Economics, University of Hyderabad, Gachibowli, Hyderabad, Telangana 500 046 India
2 Department of Economics, IBS Hyderabad, IFHE University, Shankerpally Road, Donthanpally, 501 203 India
6 12 2022
127
26 9 2022
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This research focuses on the development of impact bonds (DIBs), a newly emerging alternative financial innovative product for financing social results in developing countries. DIBs are an agreement between several parties working towards a development goal. The idea of DIBs has not been thoroughly investigated. The various dimensions of DIBs, including their structure, evolution, conduct, and performance, are the focus of this research. This study examines the idea of DIBs specifically concerning developing countries based on an analytical review of grey literature. According to our research, when it comes to DIBs, policymakers have prioritised their policies more towards health, followed by employment and training, education, poverty reduction, and agriculture.
Keywords
Development impact bonds
Social welfare
Public–private partnership
Results-based finance
SDGs
JEL Classification
O30
O35
==== Body
pmcIntroduction
Developing countries face enormous challenges accelerating economic growth and development through adequate infrastructure finance. Most of these countries face gross mismatches of functions and finances at all their federal structures. The revenue and official aid sources alone are insufficient to meet the excess demand of social challenges such as widespread poverty, unemployment, food security, and lack of health care services and education. In developing countries, the global investment in sustainable development goals is falling short of the target to close an estimated US$2.5 to 3 trillion annual financing gap (Zhan and Santos-Paulino 2021). The COVID-19 global pandemic shocks through different waves and lockdown of the economy have exacerbated the progress made in the last 7 years in United Nations Sustainable Development Goals (UN SDG) investment. This poses considerable risks and challenges to delivering the 2030 Agenda for Sustainable Development. Therefore, governments of developing countries are looking for innovative models to finance their public agendas without incurring substantial higher costs for society. In the contemporary context, the development impact bonds (hereafter DIBs) have been seen as alternative innovated instruments for the achievement of the UN SDGs because of their ability to connect private financing with developmental challenges and by shifting the risks that the public sector cannot afford (Carè 2021).
A new business model called DIBs was created to address the complicated social issues that face international development. Impact bonds are creative performance-based agreements that service providers, outcome funders, and investors enter to address social or environmental issues. They are a type of public–private collaboration that pays back investment for producing an effect. Investors receive rewards if providers accomplish predetermined results, but they forfeit their investment if providers fall short of expectations or fail. DIBs are financial instruments used to support development initiatives with funds from private investors who receive a return if the initiative is successful and is funded by a third-party donor. The intended measurements are established up front and independently verified. The greater emphasis on outcomes over inputs allows for more room for innovation, local problem-solving, and adaptation in DIBs (Center for Global Development).
This paper explores the potential innovative financing mechanism for developing impact bonds in developing countries. Significantly, the paper makes an earnest effort to understand whether impact bonds can be considered the vehicle for innovative finance. How are impact bonds performing across the dimensions of success such as political feasibility, outcome funder administrative capacity, service provider capacity, data availability, legal feasibility, and the efficiency of the deals in terms of cost–benefit analysis? The paper also tries to analyse whether there is a demand for impact bonds and the impact bonds achieve something besides outcomes. The research is based on the systematic and scientific analytical review of literature, feature analysis, international and national best practices, and case study analysis. The paper contributed to the limited literature on the DIBs by clearly defining the concept, key players, structure, development, conduct, and performance measurement. The paper also contributed to the literature by analysing the future potential impact bonds and the possibility of innovative potential derivatives as a mechanism for solving social challenges in developing countries.
Impact investing is an innovative investment technique seeking financial and social returns. Different names familiarise impact bonds in the context of other countries. For instance, the Social Impact Bonds (hereafter SIBs) are called Pay for Success (PFS) in the USA and Social Benefit Bonds (SBBs) in Australia. Since 2010, SIBs have been increasing globally, spreading austerity and addressing the challenges of leveraging funds for financing social welfare services in the developed world (Alenda-Demoutiez 2020). In this finance model, private parties invest in socially desirable interventions and are repaid by the government with interest only if the agreed-upon result is attained and verified.
In simple terminology, SIBs are arrangements or contracts where results determine payments and are positively correlated with desired outcomes. So far, SIBs have been developed on only three continents: Europe, North America, and Australia (Gustafsson-Wright et al. 2015). The UK launched the first SIB in 2010 to reduce prison recidivism among short-term male prisoners. Since then, above 140 deals have been found or launched (Social Finance Database 2021). These SIBs are used in developed and developing countries to address social issues, including providing high-quality preschool education, avoiding foster care placement, increasing youth employment, and enhancing infrastructure facilities to access health care and education by a larger mass. Though the UK tops in the number of SIBs, Australia, the USA, Canada, Israel, and several European nations like Portugal, Germany, Netherlands, Austria, and Belgium have joined the race to design, launch, and implement SIBs. In 2016, over 56 SIBs (31 in the UK, 11 in the USA, 8 in Europe, 3 in Australia, 2 in Canada, and 1 in Israel) and two DIBs were designed. Over 60 are being negotiated. Half of these are concentrated in developing countries (Financing 50 years of solutions for Sustainable development, UNDP).
DIBs are used for SIB implanted in low- and middle-income countries. DIBs can be considered an innovative technique for social impact financing in the future. DIBs are relatively new financial instruments introduced in 2012 that use private funding to support shared goals. DIBs are a bilateral agreement between the government and private investors ready to pre-finance the government for the social welfare programme. According to the project’s success, the government repays the investors (principal + coupons). The rationale behind DIBs is routed on the idea to promote development projects in developing countries by using financial resources provided by third parties, such as donors, philanthropic organisations, and development or international agencies that are more willing to take higher risks to generate more significant social impact (DIBs Working Group 2013).
The very structure of DIBs is different from conventional fixed income securities as DIBs do not offer a fixed rate of coupon to the investors throughout the bond’s life. Instead, repayment is solely tied to the results of an undertaking. Hence, from the investor’s point of view, the DIBs are mapped under the high-risk instruments for investors compared to conventional bonds. For instance, if the desired result is not obtained, the investors do not receive anything from the government. As a result, the investors will lose part, or all of their principal invested. In DIBs, the investors support social projects and benefit when results are achieved. The overall risk stemming from the DIBs is being shared among investors, outcome funders, and national Governments.
Different economies are increasingly adopting SIBs and DIBs across various sectors (Clifford and Jung 2016; OECD 2019). DIBs usage is specific to developing countries (Carmody et al. 2011; DIBs Working Group 2013). DIBs are an extension of SIBs (Hughes and Scherer 2014) and are based on the principle of sharing risk between donors and a stringent result-based payback regime. It shifts the risk to private players. They incentivise socially desirable projects which would be neglected if left to the mercy of traditional funding models. DIBs planning started in 2012. The first two DIBs launched in 2015 were meant for sustainable agriculture in Peru and the education of girls in India (Government Outcomes Lab 2021). The silver line between a SIB and a DIBs is the funder. The outcomes funder is usually the Government for a SIB, whereas a DIB is typically a donor such as a bilateral cooperation agency, multilateral aid agency, or philanthropic funding (Instiglio 2014). The other difference between DIBs and SIBs is that while SIBs solely apply to domestic financing, DIBs can involve foreign funding (Clarke et al. (2018). More clearly, in a social impact bond, the outcome funder is the government, while in DIBs, it is a third party, such as a donor or foundation.
This is the first study highlighting the more significant number of DIBs in practice and the DIBs’ policy areas of intervention to the best of our knowledge. The rest of the paper is organised as follows. Section II presents the very funding structure of the DIBs and the potential benefits associated with it. Section III highlights the analytical review of the grey literature of DIBs. Section IV has undertaken a feature analysis of the DIBs in practice, followed by the conclusion in Section V.
Why use DIBs as a funding structure?
This section aims to understand the analytical framework of the DIBs. We have also explored the multiple dimensions of DIBs like the production criterion, the agents related to DIBs like public, private, local, and international, the production and validation criterion, market construction, valuation, and the measurement of the outcomes.
Unlike SIBs, in the case of DIBs, investing agencies are full or joint-outcome funders. DIBs are not considered conventional bonds since repayment is outcome-based, and investors are paid only after attaining the desired social outcome. The risk and return profile of each DIB is different. DIBs are more like an equity investment than a debt investment in most cases. The DIBs’ beauty is transferring the risk from public agencies to private actors. DIBs garner private capital for funding various socially desirable outcomes that are subject to market failures and are not adequately supported by the government due to political, operational, and financial constraints. DIBs induce investors to improve the projects’ performance since returns are pegged to the outcomes of such projects. DIBs incentivise programme funding for a more extended time period, say 5–10 years, to enable service providers to build the foundation for scaling up interventions. It supplements service providers with funds and allows them to undertake result-based contracts. Further, it addresses taxpayers’ resistance and instils public confidence as repayment occurs from taxpayers’ money only after desired results are achieved and verified. The potentials of framing DIBs to finance the developmental needs include focussed outcomes, performance-driven management, incentivising collaborations, effective monitoring and robust evaluation, investment in prevention, mitigating risk for government, achieved scale, the crowd in private investment, and sustainable impact.
DIBs have the potential to leverage funds by improvising the collaborations between different development stakeholders, namely government or public agencies, private groups, and non-profit organisations, especially in resource-starved economies. These tools are outcome-based and desirable to address budget constraints and offset the lacunae in traditional financing models. The fundamental structure of the DIBs has enormous potential to provide a joint platform to the private sector, civil organisations, governments, and donors in a way each player contributes towards achieving the social outcomes as depicted in Fig. 1.Fig. 1 Development impact bond structure.
Source: Author's Compilation
In Fig. 1, the DIBs structure comprises four actors: investor, service provider, outcome evaluator, and outcome funder. The critical information of DIBs involves location, focus, upfront capital commitment, outcome funding, and the internal rate of return (IRR). The outcome of DIBs is encompassed by the evaluation method, target, allocated outcome payment, outcome, and an impact indicator. However, the precise structure and nature of a DIBs depend on the stakeholders involved, their corresponding objectives for using the DIBs, and the organisational and regulatory requirements in place. The donor agencies usually set up an outcome fund to build a challenge fund for the most lucrative DIBs proposals. The outcome funders typically belong to foundations or philanthropists, bilateral, multi-laterals, intergovernmental financial institutions (IFI), governments, and investment funds. DIBs investment funds ought to be established by investors to channelise funds from banks, development finance institutions, impact investing firms, institutional investors, trusts, and IFIs. They want to invest in anticipating financial and social returns. The service providers of the DIBs are non-profitable organisations, international organisations, non-governmental organisations, development organisations, charities, impact investors, and community organisations. Technical support is extended by social consultancy organisations, think tanks, law firms, universities, and other advisory organisations. The evaluators of the DIBs are research institutes, academics, and professional firms. The different steps in implementing and completing DIBs include (i) signing of contracts and collection of investment funds, (ii) transfer of investment to the concerned service providers, (iii) implementation of interventions, (iv) evaluation of results independently, (v) verification of results, transfer of outcome-based funds to investors, and (vi) repayment of investment along with interest rate.
DIBs: analytical review of grey literature
The purpose of this section is twofold. First, it tries to explore the launch of DIBs across the globe from 2015 to 2021. Second, it highlights the policy areas of intervention of DIBS and the areas where policy intervention has not been done. This study explores the literature and attempts to understand the concept of DIBs concerning developing economies. This section is dedicated to reviewing DIBs studies by practitioners and academicians. However, these studies often lack clarity on the working and effectiveness of DIBs. This paper draws inferences from recent publications to reflect upon DIBs’ structure, application, functioning, and challenges. The concept seems to have been grossly neglected by scholars. To our knowledge, there have been no case studies regarding successful DIBs.
Seventeen DIBs were launched between 2015 and 2021, focussing on health care, employment and training, education, poverty reduction, and agriculture. Out of seventeen DIBs thrown, seven DIBs are concentrated in the health care sector via quality improvements for child and maternal health care, regaining physical mobility, and receiving good-quality cataract surgeries. The health care sector receives more attention so far as DIBs are concerned. Three DIBs are related to employment and training. Sectors related to education, poverty reduction, and agriculture attract only six DIBs (each sector carries only two). DIBs targeting economic empowerment are Asháninka Impact Bond, which supports the agricultural sector, and Village Enterprise DIBs, catalysing entrepreneurial activities to create employment opportunities. Only one DIB highlights child and family welfare in Chile. We believe child and family welfare DIBs will be focussed more on the post-COVID-19 pandemic era.
The global impact bond
As of 26 January 2022, 229 impact bonds had been launched globally (refer to Table 1). Of these, 212 are SIBs and 17 are DIBs. The purpose and classifications of IBs are employment and skill development or training, health, child and family welfare, homelessness, education, criminal justice, poverty reduction, and agriculture. It may be said that IBs policy areas are confined only in above-mentioned eight areas. Out of eight areas, we find that 65 IBs are launched in the area of employment and training, followed by child and family welfare (42), health (36), homelessness (33), education (30), and so on. It is noteworthy that only 3 IBs had been launched for poverty reduction and agriculture. Many IBs had been established for employment and training as developed countries are hungry for innovation.Table 1 IBs, SIBs, and DIBs launched per area of intervention
Policy area Number of IBs launched Number of SIBs launched Number of DIBs launched
Employment and training 65 62 3
Child and family welfare 42 41 1
Health 36 29 7
Homelessness 33 33 0
Education 30 28 2
Criminal justice 17 17 0
Poverty reduction 3 1 2
Agriculture 3 1 2
Total intervention 229 212 17
Source: Authors’ elaboration from Government outcomes labs https://golab.bsg.ox.ac.uk and Brookings Global Impact Bond Database
Of 212 SIBs launched, 201 SIBs were found in high-income countries and only 11 SIBs were launched in low- and middle-income countries (refer to Table 2). Hence, it may be said that a more significant number of SIBs are found in developed countries as compared to low- and middle-income countries. The UK tops the list with 89 globally launched SIBs. Next on the list is the USA (27), followed by the Netherlands (17) and Portugal (16), and so on. From Table 2, we observe that the number of SIBs issued in developing countries is way lesser than SIBs launched in developed countries. As shown in Table 1, the IBs covered several areas of intervention. A significant chunk of IBs pertained to employment and training, child and family welfare, health, etc. As far as several SIBs projects are concerned, the area of intervention is highest for employment and training (62), followed by child and family welfare (41), health (29), and so on. The DIBs policy area is more towards health (7), followed by employment and training (3).Table 2 SIB launched worldwide
S. No. Country Number of SIBs launched Income levels Region
1 The UK 89 High income Europe and Central Asia
2 The USA 27 High income North America
3 The Netherlands 17 High income Europe and Central Asia
4 Portugal 16 High income Europe and Central Asia
5 Australia 14 High income East Asia and Pacific
6 France 10 High income Europe and Central Asia
7 Russian Federation 5 Low and middle income Europe and Central Asia
8 Canada 4 High income North America
9 Belgium 4 High income Europe and Central Asia
10 Finland 4 High income Europe and Central Asia
11 Germany 3 High income Europe and Central Asia
12 Japan 3 High income East Asia and Pacific
13 Colombia 3 Low and middle income Latin America and Caribbean
14 Israel 2 High income Middle East and North Africa
15 South Korea 2 High income East Asia and Pacific
16 New Zealand 2 High income East Asia and Pacific
17 South Africa 2 Low and middle income Sub-Saharan Africa
18 Argentina 1 Low and middle income Latin America and Caribbean
19 Austria 1 High income Europe and Central Asia
20 Sweden 1 High income Europe and Central Asia
21 Switzerland 1 High income Europe and Central Asia
22 United Arab Emirates 1 High income Middle East and North Africa
Total number of SIBs launched 212
Source: Compiled by the authors by collecting information from Government outcomes labs https://golab.bsg.ox.ac.uk. Income levels and regions are classified by the World Bank Open Data
Further, we wanted to know in developed countries which regions attract a more significant number of SIBs (refer to Fig. 2). We find that a more substantial number of SIBs are issued for Europe and Central Asia (151), followed by North America (31) and East Asia and Pacific (21). It is worth mentioning that the South Asia region has not launched any SIBs. From Fig. 2, it is clear that SIBs are confined to developed nations only.Fig. 2 Regionwise SIB launched.
Source: Compiled by the authors by collecting information from Government outcomes labs https://golab.bsg.ox.ac.uk. Regions are classified by the World Bank Open Data
Figure 3 presents the number of DIBs launched in a particular country from 2015 to 2021. The blue-coloured area (represented by light blue and dark blue) indicates the number of research works carried out for a specific country from 2015 to 2021. The dark, blue-coloured area represents the more significant number of studies conducted in a particular country. In contrast, the light blue-coloured area represents a smaller number of research works carried out for a specific country. Grey-coloured area indicates that no study has been carried out in a particular country. From Fig. 3, it is seen that more DIBs are launched in developing countries as compared to developed countries.Fig. 3 Country-wise DIBs project launched from 2015 to 2021.
Source: Compiled by the authors by collecting information from Government outcomes labs and Brookings Global Impact Bond Database
DIBs in practice: a feature analysis
Seventeen DIBs were launched between 2015 and 2021, and the duration of DIBs varies between 10 months and 5 years (refer to Table 3). Though seventeen DIBs were found, only two, namely Asháninka Impact Bond and Educate Girls DIBs, have been completely implemented, and investors have been paid based on the results delivered by the projects. Fifteen of the seventeen DIBs are underway and believed to make result-based payments to the investor in 2022 and 2023. The DIBs completion process is delayed due to the COVID-19 pandemic, which brought life to virtually a standstill.Table 3 Timeline, location, and policy area (DIBs launched 2015–2021)
Name of the project DIB launched country DIB focussed area DIB launched (year) Project duration in years Stage of development
Asháninka Impact Bond Peru Agriculture 2015 < 1 year (10 months) Complete
Educate Girls DIB India Education 2015 3 years Complete
Utkrisht Impact Bond India Health 2017 4 years Implementation
Village Enterprise DIB Uganda and Kenya Poverty reduction 2017 3 years Implementation
ICRC Programme for Humanitarian Impact Investment (PHII) Mali, Nigeria, Democratic Republic of Congo Health 2017 5 years Implementation
Cataract DIB Cameroon Health 2017 5 years Implementation
Mozambique Malaria DIB Mozambique Health 2017 3 years –
Palestine Type II Diabetes DIB Palestine Health 2017 3 years –
Quality Education India DIB India Education 2018 4 years Implementation
Cameroon Kangaroo Mother Care Development Impact Bond (KMC DIB) Cameroon Health 2018 3 years Implementation
Peru Climate-Smart Agriculture DIB Peru Agriculture 2018 4 years –
Cambodia Rural Sanitation Development Impact Bond Cambodia Poverty Reduction 2019 4 years Implementation
Finance for Jobs (F4J) Palestine Employment and training 2019 2 years Implementation
Children literary Development Impact Bond Chile Child and family welfare 2019 3 years Implementation
In their hands Kenya Health 2020 2 years Implementation
Skill India Impact Bond India Employment and training 2021 – Implementation
The Refugee Impact Bond Jordan and Lebanon Employment and training 2021 4 years Implementation
Source: Information is collected by the authors from Gustafsson-Wright et al. (2017), CGD Policy Paper, 133, and government outcomes labs https://golab.bsg.ox.ac.uk
Table 4 displays the countrywide DIBs issued globally. The country with the highest number of DIBs launched globally is India (4), followed by Cameroon, Peru, and Palestine (2 DIBs each), and so on. We explored the DIBs investment launched projects per country’s income classification (Table 4). According to the World Data Bank, countries are classified into six categories: high income, middle income, low and middle income, lower middle income, and upper middle income. We find that DIBs investment projects are confined to low- and middle-income countries (World Data Bank). Out of seventeen DIBs, only one DIB is launched in Chile, which falls under higher-income country as classified by the World Bank. Hence, it can be said that DIBs are confined to developing countries only so far. It is noteworthy that Palestine issued two DIBs, such as finance for jobs and Type II diabetes, but the country is not classified by the World Bank so far as income level is concerned.Table 4 DIB launched worldwide as per income levels
S. No. Country Income levels Number of DIBs launched
1 India Low and middle income 4
2 Cameroon Low and middle income 2
3 Peru Low and middle income 2
4 Palestine Not classified by World Bank 2
5 Cambodia Low and middle income 1
6 Uganda and Kenya Low and middle income 1
7 Kenya Low and middle income 1
8 Chile High income 1
9 Nigeria, Mali, and Democratic Rep. of Congo Low and middle income 1
10 Jordan and Lebanon Low and middle income 1
11 Mozambique Low and middle income 1
Total number of DIBs launched 17
Source: Information is collected by the authors from Gustafsson-Wright et al. (2017), CGD Policy Paper, 133 and government outcomes labs https://golab.bsg.ox.ac.uk
We tried to find out which region in the world attracts more DIBs. The World Bank classifies seven regions, and we find that DIBs investment projects are confined to only three provinces out of seven regions (refer to Fig. 4): Latin America and Caribbean, South Asia, and Sub-Saharan Africa. It may be said that several DIBs projects are confined to developing countries.Fig. 4 Regionwise number of DIBs issued in the World.
Source: Compiled by the authors. The authors collect information from Government outcomes labs and Brookings Global Impact Bond Database
Our study is an exploratory analysis to develop the base for an alternate paradigm in finance. The global financial crisis of 2007–2008 prompted scholars to shift from the mainstream proposed alternate finance paradigm. The current study accepts such proposals regarding innovative alternate finance and adopts a qualitative approach to analysing seventeen DIBs case studies. The empirical materials based on the case study analysis method are used to understand the implementation and effectiveness of DIBs in financing and bettering education, health, and poverty reduction outcomes. Our study analyses 17 DIBs models, scrutinised as per the following critical angles: (i) projects outcome, (ii) financial terms—outcome funding, (iii) service and beneficiaries—target population, (iv) number of beneficiaries, (v) DIBs issued towards achieving SDGs, (vi) target population, (vii) service provider, (viii) investor, etc. The case study method is advantageous to generate insights that may lead to new and elaborate theories, specifically on the matters for which knowledge is still fragmented (Corbin and Strauss 1990; Strauss and Corbin 1997). The study can contribute towards building the body and base of knowledge regarding DIBs. The case studies have been analysed based on solid theory, techniques, and procedures rigorously using updated public data. However, regarding DIBs, data availability and usage are significant challenges. Public data can improvise the scale of similar approaches, promote research, and devise policy recommendations worldwide.
Table 5 presents 17 case studies of DIBs launched in different geographical areas worldwide. From Table 5, it is visible that DIBs differ in their degree and areas of funding. For instance, DIBs vary from 0.11 million US$ to 27.6 million US$. Asháninka Impact Bond cost was 0.11 million US$, whereas the Humanitarian Impact Bond involves the highest cost of 27.6 million US$. Table 5 presents an overview of the cases analysed.Table 5 Interventions, outcomes, and outcome funding (DIBs launched 2015–2021)
DIB issued Goal/support Outcomes Outcome funding (Max) Maximum returns Service and beneficiaries—target population—(value) Beneficiaries
Asháninka Impact Bond To support an existing agricultural project Improve sales, yield, and sustainability practices by farmers 0.11 M USD $110,000 (return of principal) The target population included Asháninka families (typically 2 adults and 5 children) 931
Educate Girls DIB To increase the enrolment rate of girls and improve the learning of boys and girls in the rural area of Bhilwara in Rajasthan The first DIB to be launched in a developing country in the education sector and the first to surpass both target outcomes. Improve school enrolment and test scores 0.42MUSD 15% IRR Out-of-school girls in Rajasthan. Educate Girls compiled and maintained a census of out-of-school girls in treatment villages, which IDinsight validated each year 7300
Utkrisht Impact Bond Support improved quality of maternal and newborn care Health facilities reach accredited quality standards 8 M USD 8% IRR (UBSOF) 15% (implementation partnership) Private facilities across Rajasthan. Scale: Less than 100 beds, minimum of 20 deliveries per month 600,000
Village Enterprise DIB Support poor households to set up micro-enterprises Increase incomes and living standards 5.2 M USD – Individuals living in extreme poverty (less than $1.90 PPP per day) 18,000
ICRC Programme for Humanitarian Impact Investment (PHII) Provide physical rehabilitation services Construct new facilities and improve the ratio of staff to persons regaining mobility 27.6 M USD – Individuals with physical disabilities living in Mali, Nigeria, and the Democratic Republic of Congo are victims of war, natural disasters, congenital impairments, or disabling diseases such as polio 3600
Cameroon Cataract Bond Supported improved access to eye surgery at a new hospital Provide high-quality and sustainable eye surgeries for the poorest patients 2.5 M USD 8% MICEI has two target groups: low-income and middle-income patients, to operationalise the cross-subsidisation pricing model 18,000
Mozambique Malaria DIB Malaria interventions through a pay-for-performance mechanism Indoor Residual Spraying prevention programme 4 M USD 0.05% – –
Palestine Type II Diabetes DIB DIB aims to prevent and delay the onset development of T2DM among prediabetic women in 4 refugee camps in the Ramallah and al-Bireh Governorate, West Bank, by funding a lifestyle modification programme – 0.15 M USD – – 150
Quality Education India DIB Provide free private school access for children, staff training, and leadership development Address gap in children’s expected and actual learning level 11 M USD 7% IRR Primary school-aged children 300,000
Cameroon Kangaroo Mother Care Development Impact Bond (KMC DIB) Identify a path to scale for and expand quality Kangaroo Mother Care to five regions in Cameroon to reduce infant mortality levels Increase in access to quality KMC (Kangaroo Mother Care) 2.43 M USD – Implemented across five regions in Cameroon, targeting low birth weight (LBW) or preterm newborns 2200
Peru Climate-Smart Agriculture DIB To increase incomes and environmental sustainability through the (i) increase in productivity and quality of the cocoa and coffee produced; (ii) upgrade Kemito Ene (currently an association) into a cooperative with a clear path for sustainability; (iii) strengthen the community governance over land use and conservation efforts The project seeks to implement a Climate Smart Agriculture Development Impact Bond (CSA-DIB) to increase farmer productivity, access high-value markets, and improve environmental management to capture CO2 and preserve forest landscapes 3.04 M USD – –
Cambodia Rural Sanitation Development Impact Bond The DIB is the first in the water, sanitation, and hygiene sector and aims to end open defecation in 1600 villages across six provinces in Cambodia Villages achieve Open Defecation Free (ODF) status 10 M USD – Rural communities across six provinces in Cambodia: Svay Rieng, Kandal, Prey Veng, Kampong Thom, Siem Reap, and Oddar Meanchey 1600
Finance for Jobs (F4J) The DIB will target an estimated cohort of 1500 Palestinian job seekers aged 18–29 years (at least 30% will be women) Enhancing the skills of the Palestinian workforce in a more market-driven way through training and job matching to foster improved job outcomes 5 M USD – 1500 Palestinian job seekers aged 18–29 years (at least 30% will be women) 1500
Children's literary development Impact Bond Improve children’s literary (reading and writing) skills living in vulnerable contexts in the Estacion Central commune of Santiago de Chile Level of children’s skill in reading comprehension, reading aloud, and writing, measured by tests the children take 0.3 M USD – Participants must meet the following criteria: (1) children enrolled in NT2, 1st, or 2nd grade (primary school), (2) have a score of 70% or more in the School Vulnerability Index (IVE), SIMCE Test –
In their hands The DIB aims to expand the availability and uptake of sexual and reproductive health services among adolescents in Kenya Normalise adolescent sexual health and increase uptake of teenage-friendly health services through nudges 6.2 M USD 0.02% IRR adolescent girls (15–19 years old) 193,000
Skill India Impact Bond SDG Goal 8 Millions of Indians have lost their jobs during the COVID-19 pandemic. The attention of the impact bond is to address the youth employment crisis and precisely that for young women The youth will be taught through training and provided access to wage employment in COVID-19 recovery sectors such as retail, apparel, and logistics 14.4 M USD – Unemployed youth 50,000
The Refugee Impact Bond SDG-1, 5, 8, 10 To catalyse a paradigm shift in livelihood responses to refugee crises This will support 4380 refugees and host population trainees and provide 3400 business start-up grants in Jordan 12 M USD ARR 0.051 Jordanians and refugees 4380
Source: Compiled by the authors. The authors collect information from Gustafsson-Wright et al. (2017), CGD Policy Paper, 133, and government outcomes labs https://golab.bsg.ox.ac.uk
Table 6 highlights the target population, service provider, investor, and outcome from 2015 to 2021. The explanation of the specific DIBs is appended below.Table 6 Target population, service provider, investor, and the outcome achieved (DIBs launched 2015–2021)
Name of the DIB launched Target population Commissioner (outcome funder) SERVICE provider Investor Outcome evaluator Outcome
Asháninka Impact Bond Asháninka families (typically 2 adults and 5 children). Indigenous Asháninka live near the Ene River in the Peruvian Amazon The Common Fund for Commodities (CFC) Rainforest Foundation U.K. (RFAK) with local partner organisations in Peru: Central Asháninka del Río Ene (CARE) and Kemito Ene Cocoa Co-operative Schmidt Family Foundation The Royal Tropical Institute, KIT
Educate Girls DIB Eligible out-of-school girls and children in government primary schools Children's Investment Fund Foundation Educate Girls UBS Optimus Foundation ID-Insight (a) Enrolment of girls aged 7–14 in primary education (b) Improvement in quality of education for girls and boys in grades 3–5
The Utkrisht Impact Bond Private health facilities in Rajasthan and the mothers and newborns they serve Merck for Mothers and USAID Hindustan Latex Family Planning Promotion Trust (HLFPPT) and Population Services International (PSI) UBS Optimus Foundation and co-investment from the implementation manager (Palladium) and service providers (HLFPPT and PSI) Mathematica Policy Research Improved quality of delivery care in private institutions. Reductions in maternal and newborn mortality. Impact the quality of approximately 600,000 institutional deliveries over 5 years
Village Enterprise DIB Households living in extreme poverty (less than $1.90 per day) Department for International Development, UK DFID, USAID, USA Village Enterprise (self-managing) ID-Insight Increase in household income, proxied through consumption and assets
ICRC Programme for Humanitarian Impact Investment (PHII) Persons with physical disabilities in Mali, Nigeria, and the Democratic Republic of Congo La Caixa Foundation and governments of Belgium, Italy, the UK, and Switzerland International Committee of the Red Cross (Physical Rehabilitation Programme) Munich Re, Lombard Odier pension fund and charitable foundations, and others Philanthropy Associates Staff Efficiency Ratio (SER)
Cameroon Cataract Bond Low-income patients and middle-income patients with cataracts in urban and rural areas in Cameroon The Fred Hollows Foundation, Conrad N. Hilton Foundation, Sightsavers Magrabi ICO Cameroon Eye Institute (MICEI) US International Development Finance Corporation (DFC) Bond Manager: Volta Capital 1. Number of cataract surgeries 2. Quality of surgeries with at least 50% of surgeries achieving a good outcome 3. Financial sustainability
Mozambique Malaria DIB Maputo Province, Mozambique Goodbye Malaria, underwritten by Nandos and other corporates Lubombo Spatial Development Initiative (LDSI) II TBD Independent M&E expert Prevalence and incidence rates
Palestine Type II Diabetes DIB For the pilot DIB, the target population is prediabetic women above 40 years old within 4 refugee camps in the Ramallah and al-Bireh Governorate, West Bank Currently in discussion with a potential outcome funder Juzoor for Health and Social Development Bank of Palestine TBD OUTCOME METRICS: TBD but will include weight loss
Quality Education India DIB Primary school-aged children in India Michael & Susan Dell Foundation (MSDF), The Mittal Foundation, and The Ellison Foundation Gyan Shala, Kaivalya Education Foundation (KEF) and Society for All Round Development (SARD), Pratham InfoTech Foundation UBS Optimus Foundation Grey Matters India, Dalberg Consultants OUTCOME METRIC: Improvement in numeracy and literacy learning
Cameroon Kangaroo Mother Care Development Impact Bond (KMC DIB) Five regions in Cameroon target low birth weight or preterm newborns Ministry of Public Health, Cameroon (drawing on funds from the Global Financing Facility); Nutrition International Kangaroo Foundation Cameroon (lead service provider); Kangaroo Foundation Colombia (Technical advisor); 10 partnering hospitals (including the KMC Centre of Excellence in the hospital Laquintinie in Douala) Grand Challenges Canada IRESCO Enhanced transparency and accountability
Peru Climate-Smart Agriculture DIB Asháninka cocoa and coffee producers and Asháninka communities Multilateral Investment Fund—Inter-American Development Bank (43%), others TBD RFUK is working with two local partners Common Fund for Commodities and a California based impact investment fund- subject to due diligence and board approval TBD Economic impact of cocoa improvement (in USD) Economic impact of coffee improvement (in USD) Social sustainability—good governance (number of hectares of forest conserved/no deforestation)
Cambodia Rural Sanitation Development Impact Bond Rural communities across six provinces in Cambodia: Svay Rieng, Kandal, Prey Veng, Kampong Thom, Siem Reap, and Oddar Meanchey IDE The Stone Family Foundation USAID Villages achieve Open Defecation Free (ODF) status
Finance for Jobs 1500 Palestinian job seekers aged 18–29 years (at least 30% will be women) World Bank Group Trust Fund for Gaza and West Bank (TFGWB), World Bank Group State and Peacebuilding Fund (SPF) DAI Global PIF, EBRD, FMO, Semilla de Olivo Ramallah-based management team Likely to be a mixture of training outputs and employment outcomes
Children's literary Development Impact Bond Cohort within 11 targeted schools Fundacion Colunga, Fundacion Larrain Vial, Fundacion Mustakis, Fundacion Viento Sur Fundacion Crecer con Todos Fundacion San Carlos de Maipo
In their hands Adolescent girls (15–19 years old) DFID In Their Hands (ITH) Children’s Investment Fund Foundation
Skill India Impact Bond Unemployed youth. 60% of the target population will be women and girls Government to be 50% outcome funders and the rest through private sector grants and philanthropies INDIGO-ORG-1287, Apollo MedSkills Ltd. MSDF British Asian Trust Increase in job retention rates; and increase in income levels
The Refugee Impact Bond Jordanians and refugees IKEA Foundation Near East Foundation DFC Survival of business after 10 months. Improvement in household spending on basic needs after 24 months
Source: Compiled by authors by looking at various reports
Asháninka impact bond was launched in 2015. It is a pioneer in Latin America for supporting sustainable practices in cocoa and coffee production by the Asháninka community. DIBs were designed to support an existing agricultural project in Peru, and the project helped enhance the yield and sales and promoted sustainable practices.
Educate Girls DIBs Educate Girls DIBs was launched in India in 2015, and it was the world’s first DIBs based on education and aimed at supporting 15,000 girls’ education in Rajasthan. Around 40% of girl students leave schools before completing the fifth grade in this state. The programme’s target was to raise the enrolment ratio for girls, improve learning outcomes, and promote quality education in rural areas of Rajasthan. The DIBs targeted to support more than 7000 children in Rajasthan who are 6–14 years old. Along with improving girls’ education, the DIBs aimed at reducing the gender gap in education. These DIBs reached their target outcomes in 2018 and improved school enrolment and test scores of students in grades 3–5.
The Utkrisht Impact Bond, aiming to provide improved health care, cover up to 600,000 pregnant ladies and newborns of Rajasthan, is the first of its kind in the world. The expected outcome is that health facilities reach accredited quality standards.
The Village Enterprise DIBs for alleviating poverty in Sub-Saharan Africa is also the first. The aim is to assist poor households in setting up micro-enterprises, and the expected outcome is to increase incomes and living standards. The Village Enterprise DIBs microenterprise development programme aims to create more than 4000 sustainable micro-enterprises to uplift more than 12,000 poverty-ridden households of rural Kenya and Uganda. The target population belongs to the poorest of the poor category and has no prior idea or business operation experience.
ICRC Programme for Humanitarian Impact Investment (PHII) was launched to expand and improve the quality of physical rehabilitation services for physically disabled people needing mobility devices. This bond aims to provide physical rehabilitation services. The expected outcome is the construction of new facilities and improving the staff ratio to people gaining mobility back.
Cameroon Cataract Bond aims to provide better facilities regarding eye surgery at new hospitals. The expected outcome is making high-quality eye surgeries available, especially for poor patients. The Cameroon Cataract Bond is a pay-for-performance loan designed to provide funding to build a hospital to prevent blindness through cataract surgeries. The ultimate goal is to make the hospital self-sufficient after 5 years.
Mozambique Malaria DIB Internationally, Mozambique ranked 6th in malaria burden. This DIB is a part of the PPP initiative between the government, the Global Fund, and MOSASWA launched to increase funds and efficiency of interventions to tackle malaria.
The Palestine Type II Diabetes DIB is designed to delay and prevent T2DM among prediabetic women in four refugee camps in the Ramallah and al-Bireh Governorate. It funds a lifestyle-changing intervention comprising nutrition and physical exercises. A pilot DIB targeting 100 prediabetic women is designed. An assessment of its success would scale up interventions to address T2DM throughout Palestine.
Quality Education India DIB is designed to provide access to free education in private schools, leadership training, staff development, and expected outcomes. Further, it addresses the gap between the actual and expected learning outcomes. Quality Education India DIB aims to enhance educational outcomes for over three lakhs primary school students from 2018 to 2022. Quality Education India DIB shifts the focus from the achievement of inputs to outcome achievement. The QEI DIB aims to support the education crisis in India. It funds three high-performing service providers to boost learning outcomes based on grade appropriation for about 300,000 primary school children over 4 years. Educate Girls DIB and Quality Education India DIB aim to improve the quality of schooling and education and boost attendance rates (Quality Education India 2018).
Cameroon Kangaroo, Mother Care DIBs, aims to implement Kangaroo Mother Care (KMC) in about ten hospitals in Cameroon. KMC aims to provide continuous skin-to-skin contact, breastfeeding for infants, and early discharge and follow-up. Cameroon Kangaroo Mother Care Development Impact Bond (KMC DIB) was extended by 6 months due to COVID-19. KMC is globally recommended and proven effective for babies born before time or small. Under this intervention, KMC was rolled out in ten hospitals in Cameroon, spread across five regions. The expected outcome was a verifiable and significant improvement in health conditions of LBW infants. Intermediate results are an extended duration of skin-to-skin care, exclusive breastfeeding, and weight gain above average within 40 weeks of gestational age.
Peru Climate-Smart Agriculture DIB This DIB is designed to address the low-income and environmental impacts of cocoa and coffee cultivation by over 4000 Asháninkas residing along the Río Ene Basin in the Central Jungle of Peru. This innovative funding mechanism aims to support agroforestry systems and organise a cooperative of the Asháninka communities to better market their cocoa and coffee. This project is an attempt towards scaling up a pilot DIB implemented in 2015 (see factsheet on the “Sustainable Cocoa and Coffee Production DIB”).
Cambodia Rural Sanitation Development Impact Bond Cambodia has seen significant progress in increasing rural sanitation coverage over the last 15 years, with national coverage rates rising from 20 to 74.6% in 2020. The Royal Government of Cambodia has now set the ambition of eradicating open defecation by 2025 as part of its National Action Plan for Rural Water Supply, Sanitation, and Hygiene II. However, realising universal sanitation coverage in Cambodia is more challenging as the focus shifts to the poorest, the most marginalised, and the hardest to reach populations. This DIB is the first one in the water, sanitation, and hygiene sector and aims to end open defecation in 1600 villages across six provinces in Cambodia.
Finance for Jobs (F4J) This impact bond is designed to improvise the workforce’s skills in Palestine. It is designed to strengthen the collaboration between education and training providers and the private sector. This would ensure that workforce is trained with the requisite skills to meet the needs of the private sector.
Children's literary Development Impact Bond This DIB is designed to improve children’s reading and writing skills in the Estacion Central commune of Santiago de Chile in collaboration with the Ministry of Education's “language and communication program”. This intervention runs throughout the academic year and helps children read and write and develop their vocabulary, comprehension skills, and creative writing abilities.
On the hand' the DIB programme is designed to address the sexual well-being of adolescent girls in the age group of 15–19 years of Kenya. This programme aims at health care that is teenage-friendly. It intends to reduce unwanted pregnancies and bring an end to unsafe abortions. The programme draws inferences from behavioural economics and incentivises positive health behaviours in the form of vouchers and rewards. Teenagers in Kenya are now better aware, connected, educated, and informed than they ever were with the traditional sex education provided at school. Now, teenagers are better aware of contraception (around 97%), and most of them use social media and networking platforms. However, despite these interventions, Kenya is globally ranked highest in teenage pregnancy rates, unsafe abortions and related injuries, and HIV infections.
Skill India Impact Bond This DIB targets to cover 50,000 youth over 4 years in India. Of this, 60% would be girls and women. The youth will be trained with requisite skills and provided access to jobs in COVID-19 recovery sectors, including logistics, apparel, retail, etc. Indian youth face challenges in terms of poor post-training placement rates and retention. Merely 27% of women are employed, with the majority in the informal sector (around 93%).
The Refugee Impact Bond The Syrian conflict has displaced more than 11 million people. Six million refugees have settled in five neighbouring countries, including Lebanon and Jordan. 85% of Syrian refugees live in urban areas, and 6 in 10 refugees live in extreme poverty. Women and young people are the most vulnerable. Lebanon has the largest refugee population per capita in the World, and Jordan is the fifth largest. This puts a strain on local economies and infrastructure. Refugees and host communities are also struggling to access safe and dignified work, essential services, and affordable housing.
We identified 16 research papers from 2014 to 2021 based on DIBs. Care has been taken to maintain the quality, and, in this context, we have ignored the documents that appeared in books and magazines, which may be one of the limitations of our study. Table 7 reports the distribution of selected studies, publication venues, and impact factors of the journals.Table 7 Publication venues and distribution of selected studies
Publication venue Type No. of studies Impact factor (2020) Publisher Indexed in
BMC Pregnancy and Childbirth Journal 2 3.007 BioMed Central Ltd. Scopus, SCIE
Journal of International Development Cooperation Journal 2 – Hiroshima University –
PLoS neglected tropical diseases Journal 1 4.411 PLoS Scopus
Journal of Urban Affairs Journal 1 3.377 Routledge Scopus
Acta Tropica Journal 1 3.112 Elsevier Scopus
Acta Paediatrica Journal 1 2.299 Wiley –
Journal of Human Rights Journal 1 0.694 Carfax Publishers Scopus
African Journal of Business Management Journal 1 – Academics Journal –
Childhood Education Journal 1 – Routledge Scopus
Enterprise Development and Microfinance Journal 1 – Practical Action Publishing Scopus
Scientific Annals of Economics and Business Journal 1 – Alexandru Ioan Cuza-University of Iasi Scopus
Mathematica Policy Research Report Journal 1 – KIPP –
World Bank Legal Review Journal 1 – World bank –
Mirovaya ekonomika i mezhdunarodnye otnosheniya Journal 1 – Department of Global Problems and International Relations of the RAS Scopus, WoS, ESCI
Impact factors are as per 2020 Journal Citation Reports (Clarivate Analytics 2020), which Thomson Reuters released
Conclusion
Very little is known regarding DIBs’ potential, effectiveness, value for money, performance, and impact. This lack of information may be attributed to the minimal number of DIBs that have completed the entire implementation process and have provided outcome-based returns to investors. Case studies published on Peru’s Asháninka Impact Bond and India’s Educate Girls DIBs are the only sources to analyse the impact of DIBs. Despite being highly desirable and sought after, very few DIBs have been launched. This paper attempts to frame the knowledge base and encourage extensive usage of impact bonds.
DIBs have surfaced as an innovative tool to complement the traditional policy financing techniques, especially in economies challenged by budget constraints and social issues. They can be helpful when government interventions are not strong enough to address market failures. This study highlights the launching of DIBs across the globe from 2015 to 2021 by considering recently available information. Further, we attempted to address the policy areas of intervention of DIBs and SIBs. We find that policy authorities have prioritised their policies more towards health, followed by employment and training, education, poverty reduction, and agriculture so far as DIBs are concerned. It is noteworthy that none of the DIBs focuses on the plastic bag ban.
This is the first study that highlights the more significant number of DIBs in practice and the DIBs policy areas of intervention to the best of our knowledge. Though the number of DIBs is increasing YoY, it is still shallow compared to SIBs. Though seventeen DIBs have been launched in developing countries, only two have delivered the desired result, and the remaining projects are in pipelines. DIBs result outcomes are delayed due to the COVID-19 pandemic. We expect that a more significant number of DIBs may deliver the desired effect once the pandemic becomes endemic. DIBs are like newborn babies, and their impact is complicated to address with the limited available information. The effectiveness of DIBs in addressing social needs should be analysed further. The lack of knowledge challenges the explorative nature of the study. Future studies may consider enlarging the DIBs’ samples and integrating them with other business models to derive better conclusions in general. Further studies may focus on resolving current challenges associated with DIBs and how data are used in DIBs and outcome-based financing to improve service delivery and measure impact.
Authors’ contribution
All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by AKD and AKM. The first manuscript draft was written by AKM, and all authors commented on previous versions. All authors read and approved the final manuscript.
Funding
The author(s) received no financial support for this article’s research, authorship, and/or publication.
Declarations
Conflict of interest
The authors reported no potential conflict of interest.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Gustafsson-Wright E, Gardiner S, Putcha V (2015) The potential and limitations of impact bonds: lessons from the first five years of experience worldwide. Global economy and development brookings. http://docplayer.net/17409565-The-potential-and-limitations-of-impact-bonds.html
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| 0 | PMC9735130 | NO-CC CODE | 2022-12-14 23:28:32 | no | J Soc Econ Dev. 2022 Dec 6;:1-27 | utf-8 | J Soc Econ Dev | 2,022 | 10.1007/s40847-022-00213-0 | oa_other |
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Eur Arch Psychiatry Clin Neurosci
Eur Arch Psychiatry Clin Neurosci
European Archives of Psychiatry and Clinical Neuroscience
0940-1334
1433-8491
Springer Berlin Heidelberg Berlin/Heidelberg
36484844
1523
10.1007/s00406-022-01523-4
Original Paper
Antidepressant effects of prolonged intermittent theta-burst stimulation monotherapy at the bilateral dorsomedial prefrontal cortex for medication and standard transcranial magnetic stimulation-resistant major depression: a three arm, randomized, double blind, sham-controlled pilot study
Cheng Chih-Ming 123
http://orcid.org/0000-0002-0670-1153
Li Cheng-Ta [email protected]
1234
Jeng Jia-Shyun 35
Chang Wen-Han 36
Lin Wei-Chen 123
Chen Mu-Hong 123
Bai Ya-Mei 123
Tsai Shih-Jen 123
Su Tung-Ping 1237
1 grid.260539.b 0000 0001 2059 7017 Institute of Brain Science, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan
2 grid.260539.b 0000 0001 2059 7017 Division of Psychiatry, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan
3 grid.278247.c 0000 0004 0604 5314 Department of Psychiatry, Taipei Veterans General Hospital, Beitou District, No. 201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
4 grid.37589.30 0000 0004 0532 3167 Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan
5 grid.415011.0 0000 0004 0572 9992 Department of Psychiatry, Kaohsiung Veterans General Hospital, Pingtung Branch, Pingtung, Taiwan
6 grid.37589.30 0000 0004 0532 3167 Graduate Institute of Statistics National Central University, Taoyuan, Taiwan
7 grid.413846.c 0000 0004 0572 7890 Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan
9 12 2022
110
30 5 2022
15 11 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
The dorsomedial prefrontal cortex (DMPFC) plays a pivotal role in depression and anxiosomatic symptom modulation. However, DMPFC stimulation using a double-cone coil has demonstrated inconsistent results for antidepressant efficacy. No study thus far has investigated the antidepressant and anti-anxiosomatic effects of prolonged intermittent theta-burst stimulation (piTBS) bilaterally over DMPFC. Furthermore, head-to-head comparisons of antidepressant effects between standard iTBS and piTBS warrant investigation. This double-blind, randomized, sham-controlled trial recruited 34 patients with highly treatment-resistant depression (TRD) unresponsive to antidepressants and standard repetitive transcranial magnetic stimulation (rTMS)/piTBS. These patients were randomly assigned to one of three monotherapy groups (standard iTBS, piTBS, or sham), with treatment administered bilaterally over the DMPFC twice per day for 3 weeks. The primary outcome was the overall changes of 17-item Hamilton Depression Rating Scale (HDRS-17) over 3-weeks intervention. The changes in Depression and Somatic Symptoms Scale (DSSS) as the secondary outcome and the anxiosomatic cluster symptoms as rated by HDRS-17 as the post-hoc outcome were measured. Multivariable generalized estimating equation analysis was performed. Although no differences in overall HDRS-17 changes between three groups were found, the antidepressant efficacy based on DSSS was higher in piTBS than in iTBS and sham at week 3 (group effect,p = 0.003, post-hoc: piTBS > iTBS, p = 0.002; piTBS > sham, p = 0.038). In post-hoc analyses, piTBS had more alleviation in anxiosomatic symptoms than iTBS (group effect, p = 0.002; post-hoc, p = 0.001). This first randomized sham-controlled study directly compared piTBS and iTBS targeting the DMPFC using a figure-of-8 coil and found piTBS may fail to demonstrate a significant antidepressant effect on overall depressive symptoms, but piTBS seems superior in alleviating anxiosomatic symptoms, even in depressed patients with high treatment resistance. This Trial registration (Registration number: NCT04037592). URL: https://clinicaltrials.gov/ct2/show/NCT04037592.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00406-022-01523-4.
Keywords
Dorsomedial prefrontal cortex
Prolonged intermittent theta-burst stimulation
Repetitive transcranial magnetic stimulation
Treatment refractory depression
Anxiosomatic cluster symptoms
http://dx.doi.org/10.13039/501100011912 Taipei Veterans General Hospital V108D44-003-MY3-1 Li Cheng-Ta http://dx.doi.org/10.13039/501100004663 Ministry of Science and Technology, Taiwan MOST 106-2314-B-075-034 -MY3 108-2321-B-075-004-MY2 Li Cheng-Ta http://dx.doi.org/10.13039/501100015811 Brain Research Center, National Yang-Ming University 108BRC-B502 Li Cheng-Ta
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pmcBackground
Repetitive transcranial magnetic stimulation (rTMS) is a Food and Drug Administration–cleared treatment option for treatment-resistant depression (TRD). The standard protocol involves high-frequency (e.g., 10-Hz) rTMS targeting of the left dorsolateral prefrontal cortex (DLPFC) and has been found to have a response rate of 40–60% and a remission rate of approximately 30% [1–3]. Theta-burst stimulation (TBS), a pattern-specific form of rTMS, has been found to achieve a more rapid and intensive plasticity effect on the synapses than conventional rTMS [4, 5]. Both the standard protocol (i.e., intermittent TBS [iTBS]; 600 pulses for 6 weeks) and the prolonged iTBS protocol (i.e., piTBS; 1800 pulses for 2 weeks) over the left DLPFC have demonstrated similar antidepressant effects compared with the standard 10 Hz rTMS protocol [2, 3, 6].
Although the DLPFC is reported to play an important role in treatment refractoriness [1, 7, 8], the pathophysiology of TRD remains largely unknown. Compared to the DLPFC, the dorsomedial prefrontal cortex (DMPFC) is considered another, and perhaps more important, core brain region in major depressive disorder (MDD). For instance, extensive gray matter reduction has been observed in the DMPFC of patients with multiple depressive episodes [9, 10], and more severe depression has been noted in patients with brain lesions in the DMPFC [9, 11, 12]. Moreover, misplacing the deep brain stimulation electrode to inhibit the DMPFC region has been found to elicit immediate dysphoric responses [9, 13]. Ketamine administration rapidly increased synapse formation in the medial prefrontal cortex (PFC), which were associated with the rapid antidepressant effects of ketamine [14]. However, the effects were blocked if the medial PFC was infused with rapamycin, a selective mTOR inhibitor [14]. Many large resting-state functional MRI (rsfMRI) studies have also shown that patients with MDD have a dysregulated DMPFC, a critical hub anteriorly located in the default mode network(DMN), especially those with recurrent depressive episodes [15–17]. Recently, the DMPFC, proposed to be an antidepressant target, is likely to be correlated with anxiosomatic symptoms in depression [9, 18]. By analyzing the correlation between rsfMRI and each item in different depression symptom scales, Siddiqi et al. divided depression symptom maps into two distinct clusters and found that the DMPFC is the distinct circuit-based target for treating anxiosomatic symptoms [18].
Several case reports and open-label studies have demonstrated the preliminary antidepressant effectiveness of bilateral DMPFC stimulation in TRD patients, but the few related sham-controlled trials have failed to demonstrate the antidepressant effects of DMPFC stimulation in TRD patients [19–24]. More sham-controlled studies were warranted to confirm the clinical efficacy of DMPFC stimulation. MDD is a heterogeneous disorder, and the refractoriness might be caused by different pathophysiology. In literature, MDD could be further defined as two or four connectivity-based bio-subtypes, such as mainly DLPFC-related or DMPFC-related dysregulation [18, 25], which might respond distinctly to the different neuromodulation treatments. Moreover, previous positron emission tomography (PET) findings have indicated that TRD patients resistant to standard DLPFC- rTMS treatment demonstrate low glucose metabolism in the DMPFC region [1]. Whether TRD patients resistant to antidepressants and standard DLPFC-rTMS/piTBS respond to bilateral DMPFC stimulation warrants further investigation. Last, to our knowledge, whether piTBS (i.e., 1800 pulses) outperforms standard iTBS (i.e., 600 pulses) has yet to be evaluated in a sham-controlled study.
In this double-blind, randomized, sham-controlled trial, we compared the antidepressant and anti-anxiosomatic efficacy among standard iTBS, piTBS, and sham protocols applied bilaterally to the DMPFC in TRD patients resistant to antidepressants and standard DLPFC stimulation. We hypothesized that piTBS two times per day for 3 weeks would provide higher clinical efficacy than iTBS and sham treatment.
Methods and Materials
Subjects
Adults aged 21 to 70 years and diagnosed with recurrent MDD based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria were eligible in the current double-blind, sham-controlled trial. Depressed patients with the failed response to adequate dose and duration of antidepressant treatments as well as one complete left-sided DLPFC rTMS/piTBS treatment course [1, 3, 6] in the current episodes and with at least moderate severity defined by the Clinical Global Impression – Severity score (CGI-S) and ≥ 18 of the 17-item Hamilton Depression Rating Scale (HDRS-17). The psychiatric comorbidity diagnoses would be established after thorough medical history taking and a semistructured interview by administering the Mini-International Neuropsychiatric Interview (MINI) [26]. We excluded schizophrenia, bipolar, organic brain and neurological disorders. During the study period and one week before receiving brain stimulation treatment, the recruited patients were required to be antidepressant-free for at least one week. There was no patient receiving fluoxetine before entering the trial. The study was performed under the Declaration of Helsinki and was approved by the local Ethics Review Committee. All participants had provided written informed consent. The study was preregistered in the ClinicalTrials.gov (Registration number: NCT04037592). Sample size calculation was performed using the G*Power (version 3.1.9.2) [27]. The estimated parameters used to reject the null hypothesis included the population means of the experimental and sham groups being equal with a probability (power) of 0.8, and the type I error probability associated with this test’s null hypothesis was 0.1. The expected effect size of 0.82 was based on the literature [6, 22]. The number of twenty participants required in each group was predetermined before the study.
Study overview and brain stimulation parameters
The study included two phases. First, a one-week screening period was performed to ensure the patients met the recruitment criteria and were medically stable. Second, those patients were randomized 1:1:1 to each intervention group (Group A standard iTBS; Group B, piTBS; Group C, sham iTBS). An independent research assistant conducted a computerized random number generator with block randomization methods (block size of 9).
Treatment sessions were given twice every weekday over three weeks. Each session would start at stimulating left DMPFC and then right DMPFC. The intersession interval was 15 min [19, 28, 29]. The parameters of standard iTBS (group A, 600 pulses) and piTBS (group B, 1800 pulses) followed the published protocols [6]. In short, the iTBS parameters were three-pulse 50 Hz bursts administered at 5 Hz with 80% active motor threshold. In the sham group (group C) patients were randomly assigned to receive the same parameter as standard iTBS or piTBS groups but all delivered by a sham coil, which improved the blinding process by mimicking the somatosensory and auditory effects of active protocols without actual stimulation of the brain [3]. All treatment coils were 70-mm figure-of-8 coils (Magstim® Double 70-mm Stimulating Coil 9925–00 and Magstim® Placebo Coil). Neuro-navigation computer software with an infrared system (Brainsight, Rogue Research, Inc., Montreal, QC) was used to guide the coil to target the bilateral DMPFC, following the location coordinate (X 0, Y + 30, Z + 30) from the literature [22, 30].
Study goals and efficacy assessments
Symptomatic ratings of participating patients were collected using HDRS-17 [31], Depression and Somatic Symptoms Scale (DSSS) [32], Young Mania Rating Scale (YMRS) [33] and CGI severity[34], which were applied at baseline (W0; before the first brain stimulation) and at the end of treatment weeks 1 (W1), 2 (W2), and 3 (W3). The primary outcome was the changes of the HDRS-17 score after 3 week intervention.
On the basis of previous studies, in the further post-hoc analysis, we divided HDRS-17 symptoms into two distinct clusters of symptoms—namely anxiosomatic and dysphoric—to analyze the anti-anxiosomatic effect of DMPFC stimulation [18]. The anxiosomatic cluster symptoms comprised nine items derived from HDRS-17: early insomnia, middle insomnia, slowness or retardation, psychic anxiety, autonomic anxiety, gastrointestinal symptoms, somatic symptoms, genital symptoms, and hypochondriasis. The remaining eight HDRS items were clustered as dysphoric symptoms. Percent improvement of anxiosomatic symptom at each time-point relative to the baseline value was analyzed. Previous research team found that symptom change, but not baseline symptom severity, resulted in a two-cluster solution [18].
For patient-reported outcomes, the depression subscales of the DSSS were assessed to determine subjective antidepressant efficacy as the secondary outcome. Safety was evaluated at each treatment session by recording adverse events and inquiring about preidentified symptoms such as headache, dizziness, seizure, or manic shifting.
The DSSS is a simple and self-administered scale with 22 items, and it has been demonstrated to have good reliability and validity for depression, with high correlation with HDRS outcomes [32] (detail in Supplementary material). Compared to the conventional scales, the DSSS evaluates somatic symptoms more accurately [32, 35]. DSSS items were grouped into two domains: a depression subscale (DS) and somatic subscale (SS). The DS score was analyzed as the dependent variable, and the SS score was evaluated as the covariate.
Other clinical measurement and covariates evaluation at baseline
The treatment resistance may influence the antidepressant response, not only on sham treatment but active rTMS/TBS treatment [6]. The impact of the following refractory factors on the efficacy of DMPFC stimulation was analyzed. Maudsley Staging Method (MSM) was used to measure the degree of refractoriness [6, 36]. In addition, the history of previous three antidepressant treatment failures compared with ≤ 2 antidepressant failures was confirmed as a significantly poor predictor for standard rTMS/iTBS intervention [37, 38].The number of comorbid anxiety disorders, i.e., generalized anxiety disorder, panic disorder and agoraphobia, diagnosed by MINI evaluation, was summed for each participant. Comorbid anxiety can reduce treatment efficacy in TRD patients across different modalities, including TMS [37–40]. Last, suicidality was measured by the suicidal scale of the MINI [37], and categorized by low (suicidal score ≤ 5), moderate (score 6–9), and high (score ≥ 10) in the further post-hoc analysis.
Statistical methods
One-way ANOVA and Fisher's chi-square test compared the continuous and categorical (sex, education, lifetime antidepressant failure, and MINI_Suicidality) baseline characteristic variables among groups for a relatively small sample. For primary and secondary outcomes measures, generalized estimating equations (GEE) methods were done for longitudinal, repeated and within-subject correlated data [41]. An autoregressive model of order 1 (AR-1) was set regarding the working correlation matrix. The dependent variables were the total score of HDRS-17, the percentage improvement of anxiosomatic cluster symptoms and the depression subscale of DSSS, while the independent factors were time (baseline, week 1, week 2 and week 3). The percentage improvement of dysphoric cluster symptoms and somatic subscales of DSSS, and CGI severity were considered as within-subject factors. Moreover, dysphoric cluster symptoms, somatic subscales of DSSS and CGI severity were treated as time-varying covariates correlated with one of our main outcomes: improvement of anxiosomatic symptoms or depression subscales of DSSS. Group was set as a between-subject factor. The least significant difference (LSD) correction was used for post-hoc analyses when the main effect of the group was significant. All statistical analysis of demographic and clinical data was performed using IBM SPSS Statistics 21 (IBM Corp., Armonk, NY). A value < 0.05 was considered statistically significant.
Results
In total, 45 patients with severe TRD who had failed responses to antidepressants (the median of antidepressant failures of 4.5 trials) and one completed left-sided DLPFC-rTMS or DLPFC-piTBS treatment course for current episodes were recruited (Figure S1). Of these, only 34 patients agreed to enter the study; they were randomized to three treatment groups: standard iTBS (n = 11), piTBS (n = 12), and sham (n = 11). All the patients completed treatments between August 2019 and December 2020 and could tolerate the active or sham treatments. Six patients experienced temporary headaches, for which analgesic intervention was not required (standard iTBS, n = 2; piTBS, n = 3; sham, n = 1; p = 0.606). Five patients reported temporary dizziness (standard iTBS, n = 1; piTBS, n = 3; sham, n = 1; p = 0.457). No events of seizure or manic shifting were reported. Total YMRS scores of each group at baseline and W3 were 0.0 ± 0.0 and 0.4 ± 0.8 in the standard iTBS, 0.1 ± 0.3 and 0.3 ± 0.8 in the piTBS, as well as 0.0 ± 0.0 and 0.0 ± 0.0 in the sham group.
The baseline demographic variables did not differ between the three groups; these included depression refractoriness, number of lifetime antidepressant treatment failures(≥ 3), and several depression scale scores (Table 1). Our patients had a mean age of 46.2 years and a female preponderance and all had moderate-to-severe treatment refractoriness (100%, 34/34, MSM score ≥ 7). Most of the patients also had considerable clinical illness severity, three or more antidepressant treatment failures (88.2%, 30/34), and a high prevalence of comorbid anxiety disorder (64.7%, 22/34).Table 1 Demographic and clinical characteristics at baseline
Total 600iTBS 1800iTBS Sham p value
Age 46 ± 16 46 ± 15 46 ± 18 47 ± 16 p = 0.995
Sex (female, %)* 20 (58.8%) 6 (54.5%) 7 (58.3%) 7 (63.6%) p > 0.999
Education (≤ 12 / > 12 Years)* 12/22 4/7 4/8 4/7 p > 0.999
MSM severity 10 ± 2 10 ± 2 10 ± 2 10 ± 1 p = 0.916
Duration of illness, years 11 ± 10 11 ± 12 14 ± 9 10 ± 8 p = 0.622
Lifetime Antidepressant failure ≥ 3* 30 (88.2%) 8 (72.7%) 12 (100.0%) 10 (90.9%) p = 0.121
MINI suicidality* (low/moderate/high) 22/3/9 8/1/2 7/1/4 7/1/3 p = 0.971
80% aMT, left, % 62 ± 10 61 ± 10 62 ± 9 62 ± 12 p = 0.963
80% aMT, right, % 63 ± 11 64 ± 10 62 ± 11 62 ± 12 p = 0.898
HDRS-17 (BL) 24 ± 5 24 ± 5 25 ± 6 24 ± 4 p = 0.625
Anxiosomatic subscale (BL) 13 ± 3 12 ± 4 14 ± 3 12 ± 3 p = 0.142
Dysphoric subscale (BL) 12 ± 3 12 ± 2 12 ± 4 12 ± 3 p = 0.832
DSSS_DS (BL) 22 ± 7 22 ± 4 21 ± 9 23 ± 7 p = 0.853
DSSS_SS (BL) 12 ± 7 9 ± 6 14 ± 8 14 ± 7 p = 0.112
CGI-S 5 ± 1 5.00 ± 1 5.00 ± 1 5 ± 1 p = 0.951
Comorbidity (GAD/panic disorder/agoraphobia) 20/4/2 7/1/0 6/1/0 7/2/2
iTBS intermittent theta burst stimulation, MSM maudsley staging method for refractoriness, MINI mini international neuropsychiatric interview, aMT active motor threshold, expressed as a percentage of maximum stimulator output, HDRS-17 (BL) 17-item Hamilton depression rating scales (Baseline), DSSS depression and somatic symptoms scale, DS depression subscale, SS somatic subscale, CGI-S clinical global impression–severity, GAD generalized anxiety disorder
*Fisher’s chi-square test
Clinician-rated depression change during the 3-week treatment period as the primary outcome
A GEE analysis was performed to evaluate antidepressant efficacy between Group (G) and Time (T) on the HDRS-17 total score during the 3-week treatment period after adjustments for MSM refractoriness, CGI severity, MINI suicidality, antidepressant failure ≥ 3 and the number of anxiety disorder. The result revealed a significant main effect of T and a significant interaction between G and T (G × T, p = 0.020; T, p < 0.001; G, p = 0.375). However, post-hoc comparison with LSD correction indicated no differences in the estimated HDRS score at W3 between the three groups (Fig. 1).Fig. 1 HDRS-17 scores before and after 3 week DMPFC stimulation among the three patient groups no significant difference was found in estimated HDRS score at week 3 among the three groupsa. Each group demonstrated improvement after receiving DMPFC stimulation. Analyzed by GEE with adjustment of MSM refractoriness, suicidal risk level, CGI, the number of anxiety disorder, and lifetime antidepressant failure. HDRS Hamilton depression rating Scale, DMPFC dorsomedial prefrontal cortex, GEE generalized estimating equation, MSM Maudsley staging method, CGI clinical global impression
Improvement in anxiosomatic-related HDRS symptoms during the 3-week treatment period as the post-hoc outcomes
On the basis of the findings of Siddiqi et al. [18], we further analyzed the improvement in anxiosomatic and dysphoric cluster symptoms after bilateral DMPFC stimulation. Our GEE analysis results demonstrated no interaction between G and T (G × T, p = 0.965) but a significant G effect (p = 0.002) and a trend T effect (p = 0.073) on percent improvement in anxiosomatic symptoms after adjustments for MSM refractoriness, CGI severity, MINI suicidality, antidepressant failure ≥ 3, and percentage improvement of dysphoric symptoms. The results of the post-hoc comparison with LSD correction demonstrated piTBS led to a larger anti-anxiosomatic effect than iTBS did (p = 0.001), but this effect was not statistically larger than that of the sham treatment (p = 0.108; Fig. 2).Fig. 2 Percent improvement in anxiosomatic cluster symptoms after 3 week DMPFC stimulation among the three patient groups The percent improvement in anxiosomatic symptoms relative to baseline values demonstrated a significant group effect (p = 0.002). Overall, prolonged iTBS led to much more anxiosomatic symptom improvement than did standard iTBS (p = 0.001), and demonstrated a non-significant reduction of the anxiosomatic symptoms compared with sham intervention(p = 0.108) a. Standard iTBS presented a more minor improvement of anxiosomatic symptoms than sham treatment (p = 0.015) a. a: Analyzed by GEE with adjustment of MSM refractoriness, suicidal risk level, CGI, lifetime antidepressant failure, and the changes of dysphoric cluster symptoms. DMPFC dorsomedial prefrontal cortex, GEE generalized estimating equation, MSM Maudsley Staging Method, CGI Clinical Global Impression
Self-reported depression change during the 3-week treatment period as the secondary outcomes
Another GEE analysis was applied for the antidepressant efficacy between G and T on the DS scores of DSSS during the 3 week treatment after adjustments for SS score, MSM refractoriness, CGI severity, MINI suicidality, antidepressant failure ≥ 3 and the number of anxiety disorder. The results revealed a significant main effect of G and T (G,p = 0.003;T,p = 0.034) but not of interaction between G and T (G × T,p = 0.395). Post hoc comparison after LSD correction indicated that the estimated DS score after piTBS was significantly lower than that after standard iTBS (p = 0.002) or sham treatment (p = 0.038) after 3 weeks (Fig. 3). In addition, covariates such as the number of anxiety disorders (p = 0.035), antidepressant failure ≥ 3 (p = 0.022), MINI suicidality (p = 0.002), CGI severity (p < 0.001), and SS score (p < 0.001), but not MSM treatment refractoriness (p = 0.172), had effects on the estimated DS score.Fig. 3 Baseline depression subscale of DSSS and estimated depression subscale after 3 week DMPFC stimulation among the three patient groups Prolonged iTBS demonstrated improved antidepressant efficacy compared with the standard iTBS and sham interventionsa. a Analyzed by GEE with adjustment of MSM refractoriness, suicidal risk level, CGI, the number of anxiety disorder, lifetime antidepressant failure, and the changes of somatic subscale of DSSS. DSSS depression and somatic symptoms scale, DMPFC dorsomedial prefrontal cortex, GEE generalized estimating equation, MSM Maudsley Staging Method, CGI Clinical Global Impression
Effects of the covariate on antidepressant efficacy in the piTBS group as the post-hoc outcomes
To further evaluate the influence of these covariates in the antidepressant effect of piTBS, another GEE analysis was conducted in the piTBS group. All participants in the piTBS group experienced at least three antidepressant treatment failures; therefore, we could not evaluate the impact of antidepressant treatment experience for this group. The number of anxiety disorders (p = 0.001),MSM refractoriness(p < 0.001),CGI severity (p < 0.001),and MINI suicidality(p < 0.001) showed significant effects on antidepressant efficacy. Mild baseline suicidality was associated with higher antidepressant efficacy than were moderate and severe baseline suicidality(both p < 0.001;estimated DS scores after piTBS: mild = 16.69 ± 10.74; moderate = 26.12 ± 9.78; severe = 26.59 ± 9.52). TRD comorbid with one anxiety disorder benefited more from piTBS intervention than TRD without a comorbid anxiety disorder (estimated DS scores after piTBS: 21.98 ± 10.05 vs. 24.28 ± 9.97, respectively, p = 0.001).
Discussion
This is the first randomized, double-blind, and sham-controlled study to bilaterally modulate the DMPFC using the piTBS protocol (1800pulses/session) with a figure-of-8 coil in high-resistant depressed patients who have failed to respond to antidepressants and one complete standard DLPFC- rTMS or piTBS treatment. The behavioral effects related to standard iTBS and piTBS were also compared directly. Although the study failed to demonstrate a difference in the primary outcome regarding overall clinician-rated antidepressant effect, the self-reported antidepressant effect in the piTBS group was superior to the standard iTBS and sham group. Compatible with our hypothesis and the findings of Siddiqi et al., patients who received two daily piTBS sessions demonstrated much more alleviation of their anxiosomatic and depressive symptoms than did those receiving standard iTBS over 3 weeks. However, in these highly refractory patients, moderate-to-high suicidality was a poor predictor for DMPFC-piTBS intervention. In general, DMPFC-piTBS with a relatively low stimulus strength and relatively focal stimulation was well tolerated and safe in the TRD patients.
Our findings are in line with the rsfMRI results of Siddiqi et al. and those of recent trials on patients with psychiatric disorders other than TRD: the anti-anxiosomatic effect of DMPFC stimulation is much better than its antidysphoric effect [18, 42, 43]. In their pilot trial for anorexia nervosa, Woodside et al. found that DMPFC-rTMS led to significant improvements on the eating disorders examination global scales and comorbid anxiety severity on the Beck Anxiety Inventory, but no such improvement was noted for depression measured using the HDRS-17 [42]. In the earlier trial for refractory binge–purge behaviors, the same research team observed similar results: the responders exhibited considerable anxiety-related improvements, but to a lesser extent improvement to depression symptoms [43].
Other studies found that compared with the sham intervention, DMPFC-piTBS did not lead to a considerable HDRS improvement [19–21]. Dunlop and colleagues found that compared with sham stimulation, two daily sessions of 20 Hz or 1 Hz stimulation on bilateral DMPFC over 3 weeks did not improve depressive symptoms, as defined by the HDRS-17 [20]. Moreover, Bodén et al. found that twice-daily standard iTBS bilaterally targeting the DMPFC over 10 days did not lead to more reduction in the self-reported Montgomery Åsberg Depression Rating Scale (MADRS) score than sham treatment [19]. Different scales might reveal varied treatment outcomes to some extent. For instance, an early 10-Hz-rTMS randomized controlled trial using 5-cm defined DLPFC as the stimulation location method, which was recently found to be a relatively anxiosomatic neuromodulation target, found that the modality provided a greater reduction in HDRS score than in MADRS scores. This difference may be indicative of a non-significant superiority of rTMS compared with a sham intervention if the MADRS is used [18, 44]. Hence, a suitable measurement for depression and somatic symptoms in TRD patients is needed to appropriately evaluate the clinical efficacy of bilateral DMPFC stimulation, the anxiosomatic circuit-based treatment, to prevent false-negative results [18]. The MADRS is a unidimensional scale focused on dysphoric symptoms, and the HDRS is a relatively multidimensional scale combining the evaluation of anxiety and somatic symptoms [45]. Compared to MADRS and HDRS, the DSSS emphasizes depression and somatic symptoms simultaneously and reasonably resolves the limitation of the poor evaluation of somatic symptoms [35]. In the current study, using the DSSS scales, we found that piTBS exhibited higher antidepressant efficacy than either the standard iTBS or sham intervention did. In particular, we noted that piTBS might benefit TRD patients with a comorbid anxiety disorder more than those without an anxiety disorder. We also found that piTBS delivered a superior anti-anxiosomatic effect to standard iTBS. Our findings supported the role of bilateral DMPFC stimulation in symptom-specific treatment targets in the literature [18]. Additional randomized controlled trials on bilateral DMPFC stimulation to validate our findings are warranted.
In contrast to other DMPFC stimulation studies, we used figure-of-8 coil instead of double-cone coil, which was believed to stimulate the anterior cingulated cortex or deeper regions of the DMPFC [19–24]. As mentioned before, the composite targeting atlas derived through rsfMRI and depressive symptoms indicated that a focal superficial figure-of-8 coil targeting DMPFC might have effect in treating depression [18]. Our previous PET findings also supported this conjecture: TRD patients exhibited significantly more decreased glucose metabolism in the bilateral superficial DMPFC than non-TRD and healthy participants [8]. Patients who didn’t respond to DLPFC-rTMS demonstrated lower baseline metabolic activity at the bilateral superficial DMPFC than the responders [1]. Compared to the figure-of-8 coil, the double-cone coil exhibits a considerably deep electrical field penetration, which may simultaneously modulate the DMN (i.e., the MPFC) and salience network (i.e., dorsal anterior cingulate). Our results provide evidence that only stimulating a superficial area of the DMPFC leads to antidepressant and anti-anxiosomatic effects, without the expense of higher and broader induced electrical fields in the superficial cortical regions and the risk of optical nerve excitation [46]. Whether DMPFC stimulation using a double-cone coil can demonstrate higher clinical efficacy than stimulation using a figure-of-8 coil needs further investigation.
We found that the higher the total number of pulses was, the higher was the clinical efficacy (600 pulses v.s. 1800 pulses) even in patients with severe TRD. However, the patients’ depression refractoriness might limit the degree of improvement. Compared to previous studies, the patients in current study had a higher treatment refractoriness [2, 19–24]. Our piTBS patients all had a history of ≥ 3 antidepressant treatment failures that were confirmed to have considerably decreased antidepressant efficacy in the Three-D trial. [37, 38, 47]. These patients were requested not to take antidepressants during the DMPFC trial. However, this potential synergistic interaction between TMS and pharmacological interventions remains elusive because of the heterogeneity of concomitant TMS studies [48, 49]. Notably, the DLPFC-piTBS monotherapy in our previous study exhibited similar antidepressant efficacy with add-on DLPFC-standard iTBS in the Three-D trial [2, 3]. Moreover, our recruited participants had experienced < 25% HDRS-17 improvements in their previous DLPFC-rTMS or DLPFC-piTBS treatment. Following the lesson of limited improvements in switching between medications from the STAR*D trial, except for further optimization of DMPFC-TMS parameters, these highly refractory patients might need to find another brain target for TMS stimulation or receive other intensive therapies beyond TMS.
The dropout rate was low in our study, echoing that rTMS treatment is a treatment with relatively high tolerability and acceptability. In the literature, the dropout rates of active or sham rTMS were around 7.5% [50]. Detailed informed study process, re-checking the patients' availability before trial, encouragement during the trial, the property of self-pay rTMS treatment without insurance coverage in Taiwan, and the high motivation if participants decide to receive the treatment during the COVID-pandemic might further lower the dropout rate.
Surprisingly, the standard iTBS demonstrated lower anxiosomatic symptoms reduction than the sham treatment, which might imply the DMPFC-standard iTBS protocol used in the current study might some extent exacerbate the anxiosomatic symptoms or inhibit the anti-anxiosomatic placebo effect. Using a similar protocol of twice-a-day subthreshold standard iTBS targeting at DMPFC, Struckmann et al. found active standard iTBS decreased the functional connectivity between left DLPFC and right insula compared with the sham intervention [19, 51]. However, another study found the strength of functional and structural connectivity between left DLPFC and insula was positively correlated with the antidepressant efficacy of rTMS [52]. The results of the two studies mentioned above echo our finding of less anti-anxiosomatic efficacy of standard iTBS than sham intervention. Additionally, previous studies found that placebo response might be associated with DMN activity [53–55]. Whether standard iTBS and piTBS have distinct contributions to the neurocircuitry within DMN needs further investigation.
The current pilot study has some limitations. First, no consensus on the symptom components of anxiosomatic cluster symptoms exists; nonetheless, here, we combined all HDRS-17 items mentioned in anxiosomatic clustering–response maps across HDRS-24 and HDRS-28 datasets as anxiosomatic cluster symptoms [18]. Second, the current sample size was relatively small, which may have affected the results and reduced the between-group difference. Patient recruitment was mainly limited by the COVID-19 pandemic. Recruiting TRD patients without pharmacological intervention and maintaining the scheduled treatment frequency were difficult. Further research with a larger sample size to confirm the present results is warranted. Third, regarding the blinding process, none of the participants reported they surely knew which study group they were assigned to, although quantitative analysis did not perform. Finally, the twice-daily session design and intersession interval of 15 min to promote plasticity were validated based on the literature [19, 20, 23, 28, 29]. However, whether longer intersession intervals or more intensive protocols (e.g., 10 sessions per day) would yield improved clinical effects remains unknown [56, 57]. Additional systematic studies optimizing the intersession interval and number of sessions per day are needed.
Conclusion
This randomized sham-controlled study, for the first time, directly compared the clinical efficacy of piTBS and standard iTBS targeting the DMPFC using a figure-of-8 coil. PiTBS may fail to demonstrate a clinician-rated antidepressant effect, but piTBS seems superior in alleviating anxiosomatic symptoms and self-reported depressive symptoms than standard iTBS and sham, even in depressed patients with high treatment resistance. TRD patients with severe anxiosomatic symptoms or even comorbid eating disorders may benefit from this circuit-based neuromodulation. However, TRD patients with moderate-to-severe suicidality may require a more powerful treatment modality.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 130 KB)
Acknowledgements
We would like to thank all the patients who kindly participated in this study and all the research assistants, physicians, and staff who assisted with the study and imaging procedures.
Funding
This study was sponsored by grants from Taipei Veterans General Hospital (V108D44-003-MY3-1, V111B-019), Taipei Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST111-G1-2-1), and the Ministry of Science and Technology (MOST 106–2314-B-075–034 -MY3; 108–2321-B-075–004-MY2). In addition, this work was supported by the Brain Research Center (108BRC-B502), National Yang-Ming University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Neither of the aforementioned organizations had any role in the study design, data collection, analysis, interpretation of results, writing of the report, or ultimate decision to submit the paper for publication.
Data availability statement
The data are not publicly available due to restrictions of local IRB regulations.
Declarations
Conflict of interest
The authors declare that they have no conflicts of interest. All authors have no financial relationships relevant to this article to disclose.
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| 36484844 | PMC9735131 | NO-CC CODE | 2022-12-14 23:28:32 | no | Eur Arch Psychiatry Clin Neurosci. 2022 Dec 9;:1-10 | utf-8 | Eur Arch Psychiatry Clin Neurosci | 2,022 | 10.1007/s00406-022-01523-4 | oa_other |
==== Front
Ann Oper Res
Ann Oper Res
Annals of Operations Research
0254-5330
1572-9338
Springer US New York
5062
10.1007/s10479-022-05062-y
Original Research
Who’s watching? Classifying sports viewers on social live streaming services
http://orcid.org/0000-0001-7774-7995
Liu Haoyu 1
http://orcid.org/0000-0003-4894-293X
Tan Kim Hua 1
http://orcid.org/0000-0002-2405-0737
Wu Xianfeng [email protected]
2
1 grid.4563.4 0000 0004 1936 8868 Nottingham University Business School, The University of Nottingham, Nottingham, NG8 1BB UK
2 grid.28703.3e 0000 0000 9040 3743 Faculty of Architecture, Civil, and Transportation Engineering, Beijing University of Technology, No. 100 Pingle Yuan, Chaoyang District, Beijing, 100124 China
3 12 2022
123
2 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
The newly emergent social live streaming services (SLSSs) provide the sport consumers with a synchronised and more interactive viewing experience. In order to help the sport SLSSs firms understanding and engaging with the viewers effectively, this research aims to classify the sports SLSS viewers based on their engagement behaviour, and identify the perceived value and value contribution of each group of viewers. Firstly, 52,545 sports SLSSs viewers’ viewing duration time is predicted by a feedforward neural network. Second, the predicted viewing duration time and other extracted viewer behavioural data (number of messages, number of virtual gifts, and value of virtual gifts) are analysed through two-step clustering in SPSS, and classified viewers into four types. Semi-structured interviews were then conducted to understand how each type of viewer co-creates value. The results identified four groups of viewers, namely content consumers, super co-creators, co-creators, and tourists, and identified their distinct value co-creations and perceived value. This study sheds light on combining engagement behaviour and value co-creation literature to classify the sports viewers in the context of SLSSs. This understanding assists the decision-making processes of marketers and operators to promote viewers’ co-creation effectively.
Keywords
Social live streaming services
Value co-creation
Viewing engagement behaviour
Neural network
Sports viewers classification
university of nottinghamgrant ID: 16415 Liu Haoyu http://dx.doi.org/10.13039/501100010031 postdoctoral research foundation of china grant ID: 2021M693038 Wu Xianfeng
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pmcIntroduction
The absence of live sport throughout the COVID-19 pandemic has been felt strongly by sport fans across the world. Most major sporting events at the international and national levels have been cancelled, delayed, or played in empty stadiums. Fans have been missing out on the physical game that offers communal experiences. The entire sports ecosystem needs new ways to deal with threats to fan attendance and engagement. However, video streaming presents new opportunities to generate revenue and maintain fan engagement. In response to this COVID-19 crisis, sport event organisers have adopted social live streaming services (SLSSs), such as YouTube and Facebook live, to supercharge the fan communal experience through providing rich, real-time, and immersive experiences of watching events online (Kim & Kim, 2020). In 2020, Twitch attracted 7 million unique streamers, with over 30 million followers, who create and stream sporting events and games on the platform (Twitch, 2020). Therefore, live streaming platforms are not just an extra stream of revenue, but play a central role in connecting with all ages of fans during crises (Neureiter, 2021).
Compared with the traditional social media that uses second screens to interact, these newly emergent services provide the sport event consumers with a synchronised viewing experience (Lu & Chen, 2021). The sport viewers can interact in real time with streamers and other viewers when they are watching the sport events through sending real-time messages and sending virtual gifts to express their personal feelings about a sport event instantly (Li et al., 2018a, 2018b; Liu et al., 2022a, 2022b). Given its increasing importance and rapidly evolving nature, sport SLSSs marketers should invest measurement of viewers’ consumption behaviours rather than demographic generalizations to acquire, engage, and retain customers sustainably (Westcott et al., 2018). The topic of conceptualising the types of users and their distinctive engagement behaviours in the context of online communities has been investigated extensively (Y. An et al., 2018; Liu et al., 2015; Westcott et al., 2018). For example, Wu and Yu (2020) revealed four groups of consumers who browse for information, adopting recommendations, consulting reviews, and conducting searches with different levels of goal-oriented or exploratory-based need-states. Van et al. (2016) adopted behavioural data acquired from posts and views from a large multinational corporation to explore the enterprise users’ groups and the motivations that underpin their usage behaviour. However, the live streaming communities are relationship-oriented online communities (Cheng et al., 2019) where there exist two levels of social contact—between streamers and viewers, and between viewers (Lin et al., 2021a, 2021b). In this kind of community, the real-time mutual interactions between streamers, viewers, and other viewers are important for facilitating the value co-creation of viewers. In line with the Service Dominant Logic (SDL), customers evaluate and decide the value of other actors’ contributions according to the specificity of their usage (Vargo & Lusch, 2008). That is to say that the value is always assessed and determined by the beneficiary based on their value-in-use (Tsiotsou, 2016). Consequently, different types of viewers can contribute to the community and acquire value distinctively according to their engagement behaviour. Given the novelty of SLSSs as a field of research, borrowing theories and concepts from the literature on online communities and value co-creation can benefit our understanding of the types of viewers and their value co-creation that exist in the usage context of SLSSs (Rishika et al., 2013; Singh et al., 2021). Classifying the viewers based on how they utilise the platform can help the sport SLSSs firms understand customer contributions and perceived value, and then engage with the viewers effectively.
Big data is currently available from both firm and consumer activities, making it possible to understand consumer behaviour (Grover et al., 2020; Kunz et al., 2017; Tan et al., 2015; Zhan & Tan, 2020) and consequently formulate more effective customer engagement strategies (Li et al., 2018a, 2018b; Liu et al., 2019; Mishra & Singh, 2018). In this research, we first predicted the viewing duration time and extracted other viewer behavioural data (number of messages, number of virtual gifts, and value of virtual gift) based on large-scale real viewers’ behavioural data on sports SLSSs. The predicted viewing duration time and other extracted viewer behavioural data were processed through two-step clustering analysis in SPSS to classify the viewers. 20 semi-structured interviews were then conducted to understand how each type of viewer co-creates value. This study aims to classify the sports SLSS viewers and identify the perceived value of their distinct value propositions. The following research questions underpin this study:RQ1 What are the groups of viewers that exist in sports SLSSs according to their distinct engagement behaviours?
RQ2 What are the contributions and perceived values of each type of viewer?
Literature review
Definition of engagement behaviour
In the social media literature, the most widely supported conceptualization of social media engagement behaviour is a behaviour-based model (Brooks et al., 2014; Dolan et al., 2016).The activities performed by customers on social media range from merely reading and commenting on posts to posting messages that show different levels of engagement (Vale & Fernandes, 2018). Van Doorn et al. (2010) state that customer engagement is a customer’s behavioural manifestations that have a brand or firm focus, beyond purchase, resulting from motivational drivers. Similarly, Vivek et al. (2012) define ‘consumer engagement’ as the intensity of an individual’s participation and connection with the organization's offerings. However, in SLSSs, the virtual gifting behaviour is a mixed function of engagement behaviour that is similar to ‘liking’ a social media post, but it is in the form of paid virtual gifts (Lu et al., 2018). During the live streaming, a viewer can purchase and send a virtual gift to a streamer to express their emotions. Therefore, the virtual gifting is both a transactional and community-related behaviour. Therefore, this research adopts a holistic definition of customer engagement behaviour provided by Kumar et al. (2010) and defines customer engagement behaviour in sport SLSSs as a mechanism that allows customers to add value both directly (transactional behaviour) and indirectly (non-transactional behaviour) to organisations.
Typology of customer engagement behaviour on social media
Existing typologies of social media users’ behaviours usually categorise behaviours based on two criteria: usage and user types. Among the typologies that classify social media behaviours into usage types based on the engagement level, Muntinga (2011) define these behaviours as consuming, contributing, and creating. These dimensions correspond to a path of gradual engagement with brands on social media, from low (passive) to high (active) activities. Consuming behaviour is where consumers passively receive company—and consumer-related content. The contributing behaviour is the medium level of consumer activity, which reflects the consumer’s contribution to a company’s content through participation. Researchers pay a lot of attention to consumer actions such as "Like", share, and comment. The creating behaviour includes consumer creation of different types of content. Building on this, Dolan et al. (2016) capture not only the intensity, but also the valence of brand-related activities by considering positively and negatively valenced engagement. Positively valenced engagement levels can be low (consuming), medium (positive contribution), or high (co-creation). Negatively valenced engagement levels can be low (detaching), medium (negative contribution), or high (co-destruction). Uhrich (2014) expand the behavioural view into a customer-to-customer value co-creation context through a series of qualitative research approaches, including in-depth interviews, naturalistic observation, and netnography. He identified five types of customer value co-creation practices: associating and dissociating, engaging and sharing, competing, intensifying, and exchanging. Usage typologies, however, are limited in the sense that the result is largely dependent on the researchers’ understanding and interpretation. Meanwhile, users engaging on social media may act out multiple types of behaviours at the same time. A single type of engagement behaviour cannot represent the whole behaviour of a group of users.
The usage typologies are thus oversimplifications of reality, whereas user typologies that classify behaviour into user types are not because they assume people engage in more than a single behaviour at the same time and with the analysis of intrinsic motivations. For instance, Pongsakornrungsilp and Schroeder (2011) focus on value creation in a particular type of co-consuming group: an online football fan community. They demonstrate that consumers can play dynamic roles in the value co-creation as providers (creative posters, brand warriors, and moderators) and beneficiaries. These roles of social media users represent the behavioural nature of social media engagement. Van Osch et al. (2016), based on the core-periphery theory, reveal four groups of enterprise users according to their posting and viewing behaviours. These four groups are core-users, promoters or super-promoters, and peripheral users.
However, the above typologies of customer engagement behaviours are based on the non-transactional behavioural manifestations (Yoshida et al., 2018). SLSSs have emerged as a new form of participatory social media that enables viewers to interact with each other and the streamers. In the study of live streaming services, both the non-transactional and transactional features of customer engagement have been identified (Busalim, Ghabban, & Hussin, 2021;Qian et al., 2022; Lin et al., 2021a, 2021b; Clement et al., 2021). Studies have found that, in general, SLSSs have explored the users’ information behaviours, including broadcasting, watching, rewarding, and chatting (Scheibe et al., 2016). Hilvert-Bruce et al. (2018) explain four types of live stream viewer engagement, including emotional connectedness, time spent, time subscribed, and donation, via an international online self-report survey of Twitch users. The donation behaviour is highlighted to be a transactional engagement that represents a customer engagement behaviour of financial donation to the streamer (via PayPal) or charities. Similarly, Lu et al. (2018) highlighted a mixed function of paid virtual gifting, whereby a viewer can purchase and send a gift to a streamer during the live stream. This new and innovative function has led to the emergence of a new monetization model in live streaming.
Value co-creation of viewers engagement behaviour
Many studies have discussed the reason for customers engaging in different behaviours. In the literature published over the last decade, studies of brand-related social media have been considered both self-directed (consuming) and others-oriented (contributing and co-creating) behaviours (Dolan et al., 2016; Muntinga et al., 2011). In line with the service dominant logic, studies have focused on value co-creations, and suggest that customers access and integrate resources to create value for themselves and others (Akaka et al., 2013).
On the one hand, actors within a system co-create value with their contributions. For example, at a sports stadium, fans and spectators contribute to the atmospherics through their behaviour (e.g., by singing battle chants) and their appearance (e.g., wearing fan merchandise) (Uhrich & Benkenstein, 2012). When it turns to the online community, customers can also contribute to the community, such as by contributing knowledge, comments, and information, by acting as a provider (Pongsakornrungsilp & Schroeder, 2011).
However, on the other hand, although the customer can make the contribution, they cannot create value, but rather value propositions, because the contribution of customers may only be a potential input for the value creation of other actors. According to SDL, actors integrate the service providers’ value propositions (competencies and capabilities) to acquire co-created value perceptions (Horbel et al., 2016; Vargo & Lusch, 2016). In this way, the value is always assessed and determined by the beneficiary based on the specificity of their usage, which is called value-in-use (Vargo et al., 2008; Woratschek et al., 2014). Value-in-use is the “customers' experiential evaluation of service proposition in accordance with their individual motivation, specialized competencies, actions, processes, and performances” (Ranjan & Read, 2016: 293). Beneficiaries can acquire a unique perceived use value through enjoying usage (Merz et al., 2018; Ranjan & Read, 2016).
In the SLSSs context, viewers engage with different actors (streamers, other viewers, and the platforms) through gifting and real-time messaging for value co-creation (Guan et al., 2022). For example, viewers sending real-time messages to cheer for players can contribute to the live streaming room atmosphere, which can influence the other viewers’ perceptions. Besides, the viewers can also perceive value from other actors’ contributions. For instance, viewers watching the players’ on-pitch performance listen to the streamer’s commentary and discuss with other viewers to acquire perceived epistemic value on SLSSs (Horbel et al., 2016).
Given the fact that the SLSSs are a newly-emerged social media for sport event watching, in the literature there is lack of explanation about viewers’ engagement behaviours and related value co-creation in live streaming. The lack of a theoretical understanding of this phenomenon offers an opportunity to explore sport SLSSs. This research seeks to provide insights into the nature and dynamics of typifying consumers’ roles based on live streaming usage behaviour.
Methodology framework
This research adopts a two-phase approach to address the proposed research question of identifying sports viewers groups and value co-creation (see Fig. 1 below). Phase one is to classify the sports SLSSs viewers based on real behavioural data. In phase one, the viewers’ viewing duration time will be estimated by a feedforward neural network (FFNN) model while other viewer behavioural data (number of messages, number of virtual gifts, and value of virtual gift) will be extracted by the statistical functions in Microsoft Excel. The two-step clustering analysis is then carried out to classify the viewers according to the estimated and extracted indicators. Phase two is to unravel the value co-creation of viewer groups in the sport SLSSs. In this phase, a series of interviews with viewers were conducted. The transcripts of these interviews were analysed to obtain more in-depth qualitative insights into the different viewers’ self-reported behaviours, and the value co-creation of each group of viewers. The process of this research can be divided into five steps, which are behavioural data acquisition, indicator extraction, viewer segmentation, interview data acquisition, and value co-creation analysis. The analysis procedures are discussed in detail in the following sections.Fig. 1 The methodology framework
Cluster analysis of SLSSs viewer groups
Data acquisition
In the current study, the objective transaction data were used to study sports SLSSs viewers’ typologies since real behavioural data can better reflect the viewers’ characteristics compared to subjective survey data. The viewer behavioural data from the men’s singles finals match (Dec 16th 2019, 20:30 to Dec 16th 2019, 21:40) of a world level competition, the ITTF World Tour Grand Final 2019, were collected from China Sport, which is one of the top sports SLSSs in China. China Sport owns the live streaming copyright for a vast range of world-class sports events including table tennis, billiards (e.g., Snooker and nine-ball), basketball, badminton, fighting, racing, and so forth. China Sport provides high quality live streams of sporting events with an interactive viewing experience on their website, and Android and iOS apps. The collected viewers behavioural data includes viewers’ time of entry to the streaming room, real-time messaging time, virtual gifting time, and virtual gifting value. These data were allocated into three separate Microsoft Excel spreadsheets in chronological order. Summary statistics of the dataset are presented in Table 1.Table 1 Data collected from China Sport
Sheet No. Content Amount of ID
Sheet 1ID Real-time message text Sending time 3615
Sheet 2 ID Virtual gifting content Virtual gifts value Sending time 3668
Sheet 3 ID Enter time 88,711
Indicator extraction
Characteristic indicators of engagement behaviour
In this study, the criteria used to define the clusters are the viewers’ overall viewing duration time, the number of messages sent, the number of gifts sent, and the value of the gift’s during a single match. Practically, due to the chronological order of the original data, the data were sorted according to the user ID in order to execute the clustering analysis through SPSS.
Firstly, as the match time is from 20:30:00 to 21:20:59 (50 min/3000 s), we deleted the time data of year, month, and day, and recoded the time data in seconds. Some data were incomplete as some viewers had no entry time data but did have interaction data (entered the room before 20:30:00), and some viewers’ first interaction data appeared before their first entry data (entered the room more than once). Therefore, we add an entry time of 20:30:00 for these users and defined their number of entries as 1 for better caculation.
Next, a new sheet (sheet 4) in Excel was added in order to merge the same user IDs that appear in the different datasheets into one sheet. Based on the ID in column A of sheet 4, the number of real-time messages sent by each ID in sheet 1 is calculated by the COUNTIF function and allocated into column B. For example, ID ‘10,718,023’ appears six times in sheet 1. This means that ID ‘10,718,023’ sent six real-time messages. Then, in column C of sheet 4, the number of gifts sent by each ID in sheet 2 is also counted by the COUNTIF function. Afterwards, in column D of sheet 4, the value of the total number of virtual gifts sent by each ID was calculated by summing each ID’s total gifting price using the SUMIF function. Last, the VLOOKUP function was used to get the number of entrances of each ID in sheet 3 and allocate it to column F based on the ID in column A. In this step, three indicators, namely the number of messages, number of virtual gifts, and value of virtual gift, of each ID have been identified. In total, 52,545 users’ behavioural data were prepared for further clustering analysis.
After transforming these data, a vector database is created in Python to store the times of entry, the time of sending real-time messages and virtual gifts, the number real-time messages and virtual gifts, and the value of virtual gifts for each ID. In this way, when searching by a viewer ID, the ID-related data will be returned.
However, it is worth noting that the viewers’ leaving times are not recorded by this platform. This impacts the calculation of viewing duration time which is normally calculated by the subtracting the time of entry from leaving time. The reason is that the current SLSSs industry in China is applying PCU (Peak concurrent users) and ACU (Average concurrent users) as the evaluation criteria for operations quality (Pires & Simon, 2015). Therefore, the viewing duration times will be estimated by FFNN model. The following section will introduce the process of estimating the viewing duration time.
Predicting viewing duration time
This section is to estimate the viewing duration time based on the current data. The number of times a viewer enters the stream is n, the first entry time i is t0, and the second entry time i + 1 is t2 (1 ≤ i ≤ n). In the period between the first entry time, t0, to the second entry time, t2, the last interaction time (i.e., sending real-time message or sending a gift) is t1. However, the viewer may not have an interaction during this period, in which case t1 = t0.The user's exit time, tf, must be in the interval [t1, t2]. The upper bound of the user's viewing duration time is t2 − t0, while the lower bound of the user's viewing duration time is t1 − t0. Therefore, estimating the viewing duration time problem is transformed into an estimation of tf ∈ [t1, t2], and then the viewing duration time can be obtained from tf − t0 (see Fig. 2 below).Fig. 2 The timeline of viewer entry time
The descriptive statistics of the viewer behavioural data are detailed in Table 2. Among the 52,545 viewers, there are 50,507 viewers with no record of gifting and real-time messaging, which accounts for 96% of the total sample. This proportion is in line with the “80/20 principle”, whereby 80% of content in an online community is created by 20% of the users (Van et al., 2016). These 50,507 viewers’ behavioural data are lacking t1 and t2, which cannot be used to predict their viewing duration through their behaviours directly. Therefore, the average number of real-time messages and virtual gifts of all viewers in a certain period is used to represent the overall behaviour of the viewers in this period.Table 2 Descriptive analysis
Total Mean Max Min σ2
Entry times 89,289 1.693 47 1 11.11
Number of real-time messages 3614 0.0685 87 0 0.9213
Number of virtual gifts 3667 0.6951 189 1 3.665
Figure 3 (Panel A) illustrates the changes in the number of virtual gifts and the changes in the number of real-time massages sent in every 5-min interval. It can be observed that the real-time messages are more equally distributed than the number of virtual gifts. The real-time messages show peaks in the periods of 20:35–20:37, 21:02–21:05, and 21:15–21:17. On the other hand, the gifts show a concentrated distribution from 20:32 to 20:42, and 20:58 to 21:05. Figure 3 (Panel B) shows the trend of the number of virtual gifts, the number of real-time massages, and total value of the gifts. It can be observed that the trend of the number of gifts is consistently associated with the value of gifts. However, it is also worth noting that the value of the gift may not reflect the viewing time of the viewers, while the number of gifts can indicate the audience's activeness. Therefore, the following analysis does not consider the value of virtual gifts.Fig. 3 Trend analysis
According to the results of the descriptive data analysis in the previous stage, 2,038 viewers’ data meet the following requirements: (1) entered the live broadcast room at least twice, and (2) had an interaction in the live streaming room (i.e., real-time messaging or gifting). Therefore, these data are used to predict how long these viewers stay in the live streaming room.
The sigmoid function is used to explore the possibility of the viewers leaving the live streaming room from t1 to t2. The sigmoid function (Eq. 1) is an activation function of a neural network (Wanto et al., 2017). It has three characters: continuous, differentiated easily, and is a function that does not go down (Pramod, 2015). However, Li et al., (2021) pointed out that visiting duration time of viewers on live streaming platforms is highly correlated with viewers’ attachment to the streamers, which can be reflected by the intensity of the interaction. In this study, it is unlikely that the viewers would leaving the live streaming room immediately after having an interaction at t1 (point a), while the probability of users remaining in the live streaming room would decrease gradually when approaching to t2 (point b) (see Fig. 4 below). Therefore, we used the symmetric Sigmoid function (Eq. 2) in this analysis.Fig. 4 Sigmoid function and the symsigmoid function
1 Sigmoid:sx=11+e-x,
2 SymSigmoid:s^(x)=11+ex.
We assume that viewers could be influenced by the overall popularity of the live streaming room based on the following assumption: viewers are inclined to stay when there is attractive live streaming content, which is reflected by the number of viewers, the number of real-time messages, and the number of virtual gifts at any particular moment in time. Accordingly, three other probability functions are introduced to describe the probability of the users’ viewing durations. f(t) is used to measure the probability of continuously staying. The equations are as follows:3 f1t=N2N1,
4 f2t=N4N3,
5 f3t=N6N5,
6 pt=S(t)∏i=13fit,t∈(t1,t2),
7 tf=argmaxt∈(t1,t2)p(t).
N2 is the number of viewers who enter the broadcast room at a point in the interval [t1, t2], and N1 is the total number of viewers who enter the broadcast room in the interval [t1, t2]. N4 represents the number of real-time messages sent by the viewers at a point in the interval [t1, t2], and N3 represents the total number of real-time messages sent by the viewers in the live streaming room at [t1, t2]. N6 represents the number of virtual gifts sent by the viewers in the live streaming room at a certain moment, and N5 represents the total number of gifts sent by viewers in the live streaming room at [t1, t2]. p(t) is used to measure the probability of the duration time t is within the interval [t1, t2]. The moment when the viewer is most likely to leave the live streaming room is the moment when the probability of the viewer continually staying in the broadcast room is the lowest. We only need to minimise p(t), t ∈ (t1, t2) in order to get the leaving time, tf (Eq. 7). In total, the viewing duration times of 2038 viewers have been estimated. The 50 min of the match time is divided into ten 5-min intervals. And then these viewers were allocated into each of 5-min intervals according to their viewing duration time.
Based on the existing algorithm model and the calculated data of 2038 viewers, the feedforward neural network (FFNN) is trained to calculate the viewing duration time of the rest of the viewers and set up time labels. The FFNN is comprised of a 5-dimensional input layer, three hidden layers, and a 10-dimensional output layer (dividing the overall match time into 10 5-min intervals) are adopted. The interval range (t1, t2) of the rest of the viewers’ leaving time can be allocated into the 5-min intervals. The ReLu function (Agarap, 2018) is used as the activation function to extract the nonlinear characteristics of the input vector, and the cross entropy loss function (Martinez & Stiefelhagen, 2019) is used to calculate loss. 90% of the samples were randomly selected as the training set, while 10% were as the test set. The Fig. 5 shows the effect diagram of loss and training accuracy after training:Fig. 5 The training effect of the feedforward neural network
The accuracy of the training set was improved to more than 90% through multiple iterations of the convolutional neural network, and the accuracy of the original dataset reached 50%. According to the neural network algorithm above and the predicted interval (t1, t2) of the leaving time, tF, of all users can be estimated. Then, the designed algorithm, tF − t0, was used to calculate the viewing duration time of the of the remaining 50,507 viewers.
Clustering analysis
In this research, two-step clustering analysis using SPSS was employed to classify viewers according to the indicators in order to answer the first research question. Clustering analysis is an appropriate research technique for classification as it can identify and classify individuals according to similarities using a set of multivariate statistical techniques (Coppi et al., 2012; Hautbois et al., 2020). It enables both categorical and continuous data to be processed and analysed simultaneously (Hautbois et al., 2020). In this study, because there is a limited quantity virtual gifts and real-time messages, we transferred the data of gifts and real-time messages from continuous data into a categorical scale. The two-step clustering analysis in SPSS can automatically group the dataset based on its algorithm (Van Osch et al., 2016). The two-step clustering analysis involves two steps. In the first step, the software identifies the groupings by pre-clustering. In the second step, the software runs a standard hierarchical clustering algorithm (Norušis, 2011). The Schwarz’s Bayesian Information Criterion (BIC) will then define the best solution (Chiu et al., 2001). The BIC is need to above 0.0 and ranges from –1 to 1. It identifies the validity of the within-cluster distance and the between-cluster distance (Norušis, 2011).
The results of BIC indicate there are four clusters, and the value of BIC is between 0.5 and 1, which shows a high quality of the classification (see Fig. 6 below). The four distinct types of SLSSs viewers contained 21,445, 538, 637, and 17,109 viewers, corresponding to 54%, 1.6%, and 43.1% of the total viewers, respectively.Fig. 6 The test of classification
Table 3 below show the descriptive statistics for each cluster. Cluster 1 is the largest group of viewers in the sample, consisting of about 54% of all users. These viewers have the longest average viewing time, which is 36.982 min. However, they do not send real-time massages and gifts. Therefore, they are labelled “content consumers”. The second cluster of viewers is much smaller than the first group. This group consists of only 538 viewers, accounting for 1.4% of the total viewers. Although this group of viewers has a shorter viewing duration time (28.19 min) compared to cluster 1, they are actively engaging in sending messages and gifts. On average, each of these viewers sent 77 real-time messages and 538 gifts totalling 63.89 RMB in value. Compared with cluster 1, this group of viewers not only consumes the content, but they also contribute to other actors in the live streaming room by sending real-time messages and gifts. Therefore, we label this group of viewers “super co-creators”. The third cluster contains 637 viewers, making up 1.6% of the total viewership, which is just slightly higher than that of the cluster 2. Viewers in this cluster have a slightly shorter viewing time (27.393 min) than the second group. Despite being the biggest group that sends real-time messages, they were not sending virtual gifts when watching the sports games on SLSSs. Therefore, we named those in this group “co-creators” who contribute to the community by only sending real-time messages. The last cluster of viewers is labelled the “tourist cluster” as these viewers only spend an average of 1.75 min on viewing the live streaming sports event with no other engagement behaviour. These viewers are like tourists who visit different live streaming platforms but do not stay for long time. It is worth noting that this cluster makes up about 55% of all users of SLSSs.Table 3 Cluster analysis results
Cluster # Cluster label Viewing duration (Min.) Realtime message (N) Gifting (N) Gifting value (¥) Cluster size (N) Cluster size (%)
AVE Sending Sending AVE
1 Content consumers 36.982 0 0 0 28,374 54
2 Super co-creators 28.198 77 538 63.89 7,356 1.4
3 Co-creators 27.393 637 0 0 8,407 1.6
4 Tourists 1.753 0 0 0 22,646 43.1
Unravelling value co-creation of viewer groups
Interview data acquisition
In order to address the second research question and understand the value co-creation in each cluster of viewers, this research adopted semi-structured interviews. Semi-structured interviews were conducted with 20 viewers who are users of China Sport. The interview protocols were developed based on identifying how viewers co-create value with other actors: (1) the ways viewers engage in the live streaming room; (2) the motivation and perceived value of engagement. The questions originated from studies that examined value co-creation in a sports context, on social media, and live streaming (Horbel et al., 2016; Kunkel et al., 2017; Pongsakornrungsilp & Schroeder, 2011; Vale & Fernandes, 2018). As the questions were initially developed in English, they were then translated from English to simplified Chinese for this study. The translation steps followed the three stages of translation proposed by Kim et al. (2020). Firstly, two bilingual individuals translated the questionnaire into simplified Chinese. Secondly, another bilingual individual translated the questionnaire back to English. Thirdly, in order to establish the clarity and accuracy of the translated items, three Chinese-English students assessed the discrepancies between the original questions and the translated ones. The researchers interviewed each participant independently through WeChat video calls. The duration of these interviews ranged from 45 to 65 min.
All the interview transcripts were digitally recorded and transcribed into a spreadsheet. In terms of data analysis, the computer-assisted software, NVivo 12, was employed to categorise and decide the representatives of different viewer’s clusters (three super co-creators, six co-creators, nine content consumers, and two tourists). The interview results provide further insight into the value co-creation across the four distinct viewer groups. Figure 7 presents a summary of the results. According to the viewing duration time, the content consumers have the longest viewing times, which is followed by the super co-creators and co-creators. These three groups of viewers contribute value propositions to the community and have relatively more perceived value. However, the tourists have the shortest viewing duration and do not contribute to the community. The details of the analysis will be explained in the following sections.Fig. 7 Understanding the usage behaviours of viewer groups through qualitative analysis
Value co-creation analysis
Content consumers
The first group of viewers place high value on only consuming the provided content, which in this case is the sport event live streams. Therefore, this group of viewers is labelled “content consumers” who are only consuming the sports event contents while not directly creating any value to other viewers and platforms. Consumers emphasise that the knowledge acquisition and flow experience are their main motivation for viewing the sport event on SLSSs. For example, one respondent emphasised that concentration on the match can help them to gain more knowledge:My original intention to watch the sporting event here is to view and enjoy the players’ performances in a focused manner. I don’t send messages or virtual gifts as it might distract me. I sometimes even switch off the floating message function, and zoom into the screen to watch the videos, to avoid distractions. Therefore, I can learn how world-class players use skills and tactics to counter the different styles of their opponents and different solve problems in any situation.
Other viewers explained their behaviour and illustrated the perceived flow experience that is acquired from the new functions of China Sport. For example, one respondent stated that:I enjoy watching games on China Sport by using its new functions, such as the 360 degree and multi-angle views. I like viewing from the player’s angle. It makes me feel like I am a VIP who is sitting on the side, and the players are playing just in front of me. I don’t send real-time messages, but I do listen to the streamers and sometimes have a look at what other viewers are saying.
However, although this group of viewers does not contribute directly via real-time messages and gifting, they can indirectly influence other viewers’ behaviours and add value to the platform. In the age of the ‘attention economy’, viewers’ attention can be perceived as a kind of product, which is ‘eyeballs’, to attract advertisements and generate revenue (Webster & Ksiazek, 2012). In the current study, we also found that the content consumers can attract more viewers to enter the live streaming room. On a related note, one participant stated that “When I first came to the platform, I would choose a room with the most viewers. Now, if my favourite streamer is not on live, I would also go for the room with highest number of viewers”. This statement implies that viewers enter rooms to seek a sense of community, the strength of which is established by the number of viewers.
Super co-creator
Apart from knowledge acquisition, viewers in the super co-creator referred to their sending of messages and gifting behaviours in several ways. One such way is ‘endorsement’—sending virtual gifts and real-time messages to show their appreciation and admiration for the streamers. Another way is ‘fan-identification’—sending virtual gifts and real-time messages to show their commitment of the players and teams. The final way is ‘self-identification’—commentating on the sporting events by sending real-time messages to express their own knowledge of table tennis and build their reputation in the community.
On SLSSs, the viewers are provided with an opportunity to interact with streamers and other viewers by sending virtual gifts. When viewing the sports live streaming events, the viewers can purchase and send virtual gifts during the game time. The super co-creators share a mutual game experience with one another and create a party-like atmosphere in the virtual online community. Some viewers described sending virtual gifts as a way to show their appreciation and admiration for the streamer in front of all viewers of the stream:I am a fan of ‘Xiao Ma Ge’ as he is very professional when commentating on sport events. I like to listen to his commentary as I can acquire a lot of knowledge and information from him. I send virtual gifts to him to thank him for his hard work in providing useful information and, more importantly, to attract his attention. If he notices my gifts and responds to them, I feel very excited. I think we are very close.
There are also interviewees who stated that sending gifts is a way to cheer and express their support for the players. This is described by one of the interviewees as follows:I like to send gifts to celebrate when the Chinese team wins a game or when they are playing against a strong opponent. If Liu Shiwen is playing, I would send much more. I am her fan.
In this study, the results also reveal that the super co-creators are concerned with ‘self-identification’. The reason for sending real-time messages is to answer other viewers’ questions related to techniques, strategies, scores, the players styles, and so forth. This is in line with the view that consumers would like to present themselves in the online community to seek and develop influence and build an identity among the community of viewers (Thorbjørnsen et al., 2007). Due some streamers lacking professional knowledge of the sport, they could not truly satisfy the needs of the viewers who are professional players. Value co-creators want to improve the streamer’s level of expertise by commentating on the match. In this way, co-creators not only provide knowledge to the streamers and other viewers, but they can also feel satisfied by gaining a sense of self-identity through self-presentation.
Co-creators
Co-creators have a similar usage duration to consumers and super co-creators in terms of consuming content. However, co-creators do not co-create value in the same way as the other groups of viewers. Co-creators send an abundance of real-time messages to achieve their perceived values. Their motivations for sending real-time messages display some striking differences compared with super co-creators. Compared with super co-creators, co-creators have lower fan identification and less streamer endorsement, but they seek a relatively strong sense of community. A few respondents mentioned that they are not willing to pay for virtual gifts:I like to engage in the community through sending real-time messages. It makes me feel that I am part of the fan community. For example, when other viewers cheer for players, I would follow them by typing ‘go go go’, when I see 886 (bye bye) with the streamer’s name when the game finishes, I will copy them. I also attend streamers’ interactive quizzes by typing ‘1’ or ‘2’ to vote for guessing which player would win prize.
Similarly, other respondents noted that:I like the atmosphere of everyone cheering together. I think the purpose of live streaming is to get people to watch the games together and cheer. I have national pride. The sense of unity is a very important feeling that the live streaming can bring to me. As I can't be there to support the players, sending a real-time message on the live stream platform makes me feel like I am encouraging them. When I watch live sports platforms, sometimes my message will be selected and read out by the anchors, and I may have some opportunities to communicate with others who are fans like me.
Co-creator also look to acquire knowledge when watching sport live streams. However, they are not only passively listening to streamers, but also sending real-time messages to ask questions. Meanwhile, they are keen to communicate with streamers and other viewers to discuss the players’ techniques, skills, and strategies. There is a viewer mention that:If the streamer is a professional in table tennis and I am uncertain about something, I will send my questions by real-time messages. I also interact with other viewers. When the streamers don’t answer some of my questions, some viewers answer me by sending real-time messages. I can learn a lot in this way.
Apart from acquiring professional expertise from watching and interacting, co-creators expect to access more information about the sports equipment or players since such information may not be accessible elsewhere. As one of the respondents stated:I often send real-time messages to ask about a player’s background, past achievements, and equipment. In my opinion, this is a good way to get to know information about the players, especially young players.
Some respondents of the co-creators firmly believe that watching sport events on SLSSs is entertaining. For example, one comment illustrates their perceived value of enjoyment when viewing the sport events on SLSSs:There is a lot of contents in the real-time messages, such as expressions of love and hate between viewers. Although I am not often engaging in such debates, I like to watch other people quarrel.
Tourists
Tourists describe their behaviour in terms of looking for the right streamers. There can be more than a dozen streamers covering important matches at the same time, and viewers seek to choose a channel selectively to meet their particular viewing needs (Smith et al., 2013). Tourists are the nimblest group who most easily shift between streaming rooms and platforms to optimise content discovery and perceived value. Among those who were found to be tourists, 85% said that they are not very professional at table tennis and are newcomers to China Sport. They explain that they will choose the streaming room with the highest number of viewers at the beginning. They travel around different streaming rooms to try to find a suitable streamer who can meet their requirements. As one respondent stated:At the beginning, I would switch around, but I believe I would stay in one streamer’s room when I found a streamer that suits my taste. For me, the first element is to see whether the streamer is good at technical commentary. The second element is the style of the streamer. I would say that for me the importance is weighted at around 70% for their technical skills and 30% for their personality.
Furthermore, another respondent also mentioned that the appearance and interactivity of the streamers might also be a factor affecting whether or not their streaming room is chosen:When there are no important games on, I flick through different streaming rooms to find a beautiful female streamer. However, I will look for a streamer who is professional in table tennis when there is a semi-finals or finals being streamed.
Discussion
As a newly-emerged type of social media platforms, SLSSs provide the sport event consumers a more interactive community with a synchronised viewing experience. Although conceptualising the user groups and their distinctive engagement behaviours in the context of online communities has been investigated extensively, the distinctions between different sports SLSSs viewer groups remain unknown. This study has shed some light on using customer behavioural big data to classify viewers in the SLSSs and explore the value co-creation of each type of viewer to facilitate operations management and set up marketing strategies.
Implications for research
The findings of this study have several important implications for research of customer behaviour and value co-creation. Firstly, in this research, we estimate an FFNN model using a dataset of 52,545 viewers’ real behaviours from a popular live streaming platform in China to estimate their viewing duration time in this novel business context. Next, by combining the clustering analysis of viewers’ behavioural data (real-time messaging, gifting, gift value, viewing duration time) and interviews, this research is the first attempt to investigate and identify the different viewer groups by considering both the non-transactional and transactional features of customer engagement behaviour. The viewers’ behavioural data delivered insights into their engagement behaviour and revealed four distinct viewer groups: content consumers—longest viewing duration without real-time messaging and gifting; super-co-creators—relatively long viewing duration with real-time messaging and gifting; co-creators—relatively long viewing duration with only real-time messaging; and tourists—shortest viewing duration time and without messaging and gifting. This is in line with an earlier study on enterprise social media, which found that the majority of content is created by a minority of users. However, different from the ‘promoters’ identified by Van Osch, et al. (2016), who occasionally post, we found that the first and last group of viewers do not contribute content to the community. The clustering analysis is also an important preliminary step required for exploring the viewers’ value co-creation in the context of SLSSs.
Secondly, different from previous studies that simply consider the motivations of engagement behaviour, this study provides an insight into what values different groups viewers perceive from viewing live streams on SLSSs, and how they contribute to platforms and other viewers, through a qualitative empirical study. In line with SDL, this study adds to our understanding of what the value co-creations of different types of viewers are. Thus, this study extended theoretically the boundary of the value co-creation studies into the user segmentation studies in the context of SLSSs.
Furthermore, the findings of this study suggest there exists a novel viewer group—tourists—in the SLSSs setting. They do not contribute to the community but have the potential to transfer into other groups of viewers. The SLSSs should not only consider whether tourists contribute to the community, but rather consider how long they can stay in the streaming room. This is because, just like the content consumers identified in this study, the viewers’ attention can attract other viewers. A community on a platform can only boom once there is a consistent source of attention, frequent engagement with the provided content, and contribution of information to the platforms.
Implications for practice
Segmentation, targeting, and positioning are fundamental to any marketing or brand management strategy. To date, viewers of SLSSs have most frequently been treated as one homogeneous group by marketers developing online promotion strategies. This study reveals that there are at least four distinct segments within the overall sports SLSSs group that can be differentiated based on quantity and quality of usage. This study also has important implications for operations managers of the sport SLSSs, and the streamers on SLSSs. First, the current sports SLSSs industry in China is still lacking uniform standards for service performance. This leads to a problem for sports SLSSs of ineffective behavioural data management and storage. The proposed neural network algorithms to estimate viewing duration time are intended to provide a decision support tool for sports SLSSs firms. Meanwhile, the SLSSs platform should not only use the statistics of page views (PV) and daily active users (DAU) as these parameters can neither reflect the reasons behind the data rise and fall, nor can they be used to explore the real characteristics and value of users. The current study will allow sport SLSSs managers to understand the perceived value and contributions of each group of viewers in order to guide their operation strategy. Secondly, the previous literature has assumed the importance of encouraging people to interact and contribute knowledge to the social media community. This research argues that a large base of the content consumers is important for attracting ‘tourists’ to enter the live streaming room. Therefore, the sport SLSSs should consider how to increase the content consumers’ levels of stickiness and activity. Last, it seems that the tourists do not contribute value to the platforms and other viewers, but they are the potential fan base of the platform. The sport SLSSs could increase the diversity of streamers, as well as improve their level of professional sports knowledge by providing online tutorials.
Conclusion
In this research, we set out to investigate the viewers groups in sport SLSSs and their value co-creation by combining web behavioural data and interview data collected from the SLSSs users. This study applies a two-phase approach to address the research questions. The first phase identifies the viewers’ groups through clustering analysis of viewers’ behavioural data (viewing duration time, real-time messaging, gifting, and gifts value) from a major Chinese sports SLSS. The value co-creation of different viewers groups in the SLSS community is then unravelled using content analysis of the interview data. This study has found four groups of viewers: content consumers, super co-creators, co-creators, and tourists, thus answered the first research question. The distinct engagement behaviours and value co-creation of each of the groups have been analysed in order to address the second research question. We identified a new group of viewers who do not contribute to the sport SLSS community but has high level of streamer endorsement. Therefore, they may be transformed into one of the three other types of viewers by the effort of streamers.
This study has shed light on combining engagement behaviour and value co-creation literature to classify the user groups in the context of SLSSs. This understanding assists the decision-making processes of marketers and operators to enable viewers’ co-creation effectively. The main limitation of this study is that there is insufficient data to facilitate an analysis of engagement frequency and live streaming shopping behaviour. Whilst this study does provide some interesting insights, it would be valuable to conduct similar studies with more behavioural data. Quantitative data analysis is also encouraged to define the value co-creation of distinct type of viewers in the future.
Limitations and future work
In this study, there is a limited amount of gifting and messaging data, so the clustering analysis according to frequency failed. Therefore, future research could adopt approaches that use more behavioural data to analyse the viewers groups in terms of their usage frequency and duration. This would allow managers to design a strategy that is more accurate and effective. In addition, this study used customer behavioural big data from a sport live steaming service. As live streaming shopping has just been introduced by the sports SLSSs industry in China, the viewers’ behavioural data related to live streaming shopping is limited in this study. Therefore, future studies could be based on collecting viewers’ behavioural data related to live streaming shopping from similar sports SLSSs to examine viewers’ groups. Furthermore, the value co-creation of each type of viewer is examined by qualitative data from semi-structured interviews. Although the qualitative data offered enough knowledge of how each type of viewers co-create value in the community, future work may conduct quantitative study (e.g., survey) to provide a more comprehensive understanding.
Both organisations and consumers in the sport context have gradually accustomed themselves to the growing use of live streaming before and during the COVID-19 pandemic. In the future, sport live streaming platforms will adopt all kinds of technologies to improve their business performance and participation performance. Therefore, it is imperative for researchers to attach more importance to the research of the sport SLSSs use and customer engagement.
Acknowledgements
Special thanks to China Sport for helping with the empirical data for this paper. We also would like to thank employees at China Sport for their time.
Funding
This research was funded by Deng Yaping Sports Scholarship (Grant ID: 16415) and China Postdoctoral Science Foundation (Grant ID: 2021M693038).
Data availability
The dataset generated during the current study is not publicly available as it contains proprietary information that the authors acquired through a license. Information on how to obtain it and reproduce the analysis is available from the corresponding author on request.
Code availability
The code that supports the findings of this study are available from the corresponding author upon request.
Declarations
Conflict of interest
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Ethical approval
The study was conducted and approved by the Ethics Committee of the University of Nottingham.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735134 | NO-CC CODE | 2022-12-14 23:28:32 | no | Ann Oper Res. 2022 Dec 3;:1-23 | utf-8 | Ann Oper Res | 2,022 | 10.1007/s10479-022-05062-y | oa_other |
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SN Soc Sci
SN Soc Sci
Sn Social Sciences
2662-9283
Springer International Publishing Cham
585
10.1007/s43545-022-00585-4
Original Paper
Gender differences in the professional experiences of Iran specialists in American academia
Borquez Julio [email protected]
1
http://orcid.org/0000-0003-0729-7479
Amin Camron Michael [email protected]
2
1 grid.266717.3 0000 0001 2154 7652 Political Science, University of Michigan, Dearborn, MI USA
2 grid.266717.3 0000 0001 2154 7652 History, University of Michigan, Dearborn, MI USA
9 12 2022
2022
2 12 2729 9 2021
30 11 2022
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
The work on gender differences in academic life spans a wide array of colleges and universities, scholarly disciplines, and countries. Using a survey conducted in 2016 to capture “the state of the field” in Iranian Studies as US–Iran relations were in a brief thaw, this paper draws on some of these perspectives and explores gender differences in the professional experiences of Iranian Studies scholars working in the USA. Iranian Studies has grown and diversified in the USA since the 1960s. This expansion occurred despite disruptions in Iran itself and in US–Iranian relations since 1979, with many US-based Iran specialists having heritage connections to Iran. The survey, which is the first of its kind conducted among this particular academic community, covered a range of topics related to respondents’ academic and professional experiences, career outlook, and political activities. The results spotlight some notable differences—statistically significant differences in several cases—in the professional experiences of men and women in this academic field. Women respondents were more likely to be of junior rank or graduate students and were more likely than men to feel that gender identity influenced their professional milestones. Women were more likely to list the desire for social impact as a professional motivation than men. Women tended to feel less sanguine about the state of their careers, their professional environment, their career prospects, and the state of the Iranian Studies field as a whole. Some of these attitudes varied depending on their self-identification as Iranian, Iranian-American or American, while some held true across self-identification. These results mostly confirmed expectations based on similar research discussed in our literature review.
Keywords
Iranian Studies
Iranian-American
Gender
Academia
Survey
issue-copyright-statement© Springer Nature Switzerland AG 2022
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pmcIntroduction
An important body of research describes and explains differences in the professional experiences of women and men in academia. Some studies focus on discrepancies in hiring, salary, promotion, and tenure (Barbezat and Hughes 2005; Burke et al. 2005; Crothers, et al. 2010; Ginther and Hayes 2003; Webber and Canche 2015, 2018). Other work investigates different aspects of job satisfaction, such as work environment, relations with colleagues, and work-life balance (Berheide et al. 2020; Hesli and Lee 2013; Lapierre and Allen 2006; Machado-Taylor et al. 2014; Okpara et al. 2005; Webber and Rogers 2018). Research has also examined contrasts in professional socialization and aspiration (Angervall et al. 2018; Evers and Sieverding 2015). The work on gender differences in academic life spans an array of academic settings: from large research universities to small liberal arts colleges; from STEM fields to the humanities and social sciences; and in multiple countries.
This paper draws on some of these perspectives and explores gender differences in the professional experiences of Iranian Studies scholars working in the USA. This study is based on a survey of Iranian Studies specialists conducted in late 2016. It is important to note that the intent of the survey was not simply to capture attitudes in response to a particular set of circumstances at that time but also to measure attitudes regarding cumulative professional experiences that played out over years to that point. As we discuss in both the literature review and analysis of results, the circumstances of late 2016 were relevant, but professional attitudes should also be put in the context of different forms of social identity and setting (ethnicity, class, gender, religion, education, family circumstances, institutions of higher learning).
Research agenda
The analyses that follow will spotlight four sets of professional experiences and research questions. In some cases, we expect to see clear distinctions in the responses provided by men and women. In other cases, we expect gender differences to be modest, if not negligible.
Gender and professional profile
Iranian Studies cover a wide range of disciplines and academic specialties, and the scholarly focus of Iranian Studies has shifted over time, in response to changes in scholarly approaches and political developments involving Iran and US–Iran relations (Marandi and Tari 2018; Tari 2015). We know of no studies that have directly explored gender differences in the professional socialization and research concentrations in Iranian Studies specifically, though differences have been observed in Middle East Studies more broadly. One manifestation of this might show up in the research focus reported by men and women in Iranian Studies. We provide a descriptive profile of men and women in terms of research focus and stage of career. To the extent that men and women have responded to differently to changing currents in other academic fields, it would not be surprising to see a similar pattern in Iranian Studies.
Gender and professional/academic milestones
We asked respondents to offer views about the influence of gender on professional milestones such as obtaining an academic appointment, salary, and promotion. Studies from other academic disciplines consistently point to gender differences in these milestones, whether measured objectively (e.g., salary data) or by way of respondents’ subjective judgments. We expect our results, which are based on subjective judgments, to confirm previous research. That is, we expect to observe notable gender differences in perceptions about professional milestones.
Gender and professional satisfaction/professional outlook
A related line of inquiry focuses on gender differences in more overall expressions of professional satisfaction and assessments of Iranian Studies as an academic field. These judgments are less rooted in respondents’ personal professional experiences and are more reflective of their appraisals of professional environment. Based on previous research, we should expect some discernable gender differences, with women generally less satisfied with their professional settings. At the same time, the field of Iranian Studies has faced the challenges of academic standing and material support faced by other areas studies fields. In the case of Iranian Studies, these challenges are potentially salient enough to transcend gender lines and temper gender differences in survey responses.
Gender and motivations for research
Earlier studies of Middle East scholars uncovered an important political consciousness among women, one that set them apart from their male colleagues and one that animated their research interests. We might expect to see a similar pattern in the related community of Iranian Studies specialists. But as previously noted, the present study was conducted in the midst of the 2016 presidential election. It is reasonable to expect that Donald Trump’s aggressive rhetoric, some of which specifically targeted Iran and Iranians, would touch a nerve with Iranian Studies scholars across the board, men, and women alike.
Iranian Studies has grown and diversified in the USA since the1960s, when efforts began to develop the field under the auspices of several academic societies (incorporated as non-profits). The growth and diversity relate not just to the range of subfields that have joined the “classic” fields of history, literature, and language, but also the demographics of the field. More women and “region-related” scholars are visible at institutions and in the scholarly canon. This expansion occurred despite disruptions in Iran itself and in US–Iranian relations since 1979, with many US-based Iran specialists—in all career stages—having heritage connections to Iran. Moreover, the administration of the survey itself coincided with the 2016 U.S. presidential campaign and its immediate aftermath, defined by hardline rhetoric on immigration, the Muslim travel ban, and a burgeoning anti-Trump “resistance” movement (Meyer and Tarrow 2018). We wanted to understand how these conditions and trends might have shaped the professional experiences and outlooks of this distinct scholarly community. Accordingly, the survey, which is the first to focus on Iranian Studies as a subfield, covered a range of topics related to respondents’ academic and professional experiences, career outlook, and political activities. The results spotlight some notable differences—statistically significant differences in several cases—in the professional experiences of men and women in this academic field.
Literature review
The process of interpreting our survey data involves finding appropriate points of reference. Unfortunately, there is a paucity of research about the development and state of Iranian Studies as an academic field (For exceptions, see Marandi and Tari 2018; Tari 2015). But there is a rich body of such work on Middle Eastern studies. We have drawn on some of that literature in the development of our own research expectations and in the interpretation of our survey findings. In particular, we draw on Deeb and Winegar’s important study of anthropologists in Middle Eastern and North African Studies (MENA), Anthropology’s Politics (2015). Although Deeb and Winegar are looking at MENA more generally and anthropology more specifically, some of their results speak to gender differences in the academic and professional experiences of men and women in the field. To that extent, Deeb and Winegar provide a relevant and rigorous point of comparison. There are other important studies of Middle East Studies (Amanat and Bernhardsson 2007; Khalil 2008, 2014, 2016; Lockman 2005, 2007, 2016) and Iranian Studies (Foster 2007; Shannon 2017, 2018), but these focus on the connections between foreign policy and academia (including the institutional history of area studies programs), not the experiences of a category of scholars within American academia. Indeed, one reviewer of Lockman’s 2016 book noted the conspicuous absence of both women and region-related names from his account of the rise of Middle East Studies, less as a criticism of Lockman than as a recognition of the fact that the field in the USA was largely shaped by “Ivy League-educated, well-off, Protestant elite men (Miller-Idriss 2018, 715).”
Deeb and Winegar, by contrast, were grappling with the diversification of the cohorts of anthropologists working on the Arab World in more recent years. This has some resonance with our results. For example, women in our Iranian Studies survey are more likely than men to be graduate students, non-tenured, assistant professors, and associate professors. This has been observed in other contexts within the broader field of Middle East and North African (MENA) Studies and many fields in academia. In Anthropology’s Politics: Disciplining the Middle East (2015), Deeb and Winegar report that women’s presence in the field only began to rise circa 1990 and stood at 61% (much higher than MENA as a whole or Iranian Studies). In MENA, some 40% of scholars were “region-related” (i.e., had heritage connections to the Middle East). Their explanatory notes indicate further that 42.1% of women in MENA were likely to be employed as “contingent faculty” working at more than one institution (Deeb and Winegar, 7, 8, and, 207, n17). The balance of “region-related” specialists and non-tenured/junior faculty in Iranian Studies is different in our survey results compared to MENA as a whole. Roughly two-thirds of Iranian-American Iran specialists identified as Iranian or Iranian-American in our survey. If you combine the categories of adjunct, assistant professor, “academic staff,” and “other” in our survey, 34% of men and 33% of might be considered “contingent faculty.” If you pull out tenure-stream assistant professors, those numbers are 10% and 17.2%, respectively. This suggests that, compared to colleagues in MENA generally, Iranian Studies scholars are less likely to be outside of coveted tenure-stream opportunities within academia. At the same time, gender-based differences exist and, as we shall see, these are even more pronounced among graduate students and tenured faculty.
Looking more broadly at questions of gender equity in academia, research has made clear the persistent and considerable gender gaps in salary (Barbezat and Hughes 2005; Crothers et al. 2010; Webber and Canche 2015, 2018). These salary discrepancies are manifested in academics’ assessments of job satisfaction; although women express higher levels of satisfaction with their work and colleagues, men tend to be more satisfied with their pay and promotions (Okpara et al. 2005; Webber and Rogers 2018). Furthermore, the kind of institution where one works—research vs. teaching intensive—does not seem to provide a better experience of “work-life” balance from the perspective of women faculty in both settings (Berheide et al. 2020; Ward and Wolf-Wendel 2017; Webber and Rogers 2018).
Other studies have explored how student evaluations and even ostensibly gender-neutral policies, such as family leave, can have adverse impacts on women in American academia (Antecol et al. 2018; Boring 2017; Chávez and Mitchell 2020; MacNeill et al. 2015; Winslow 2010). So, an interesting question is whether women Iranian Studies in American academic have experiences that track with women in American academia generally (Toutkoushian et al. 2007) or in MENA, more specifically.
Our survey provides us with a useful initial look at the intersection of ethnicity and gender among “region-related” faculty in the field of Iranian Studies. Being region related, of course, runs along a spectrum that includes those perceived as “foreign” (and perhaps perceive themselves that way) in an American context (Skachkova 2007; Dedoussis 2007; Lin et al. 2009). Although the questionnaire was not wholly focused on these questions and was more broadly based in design, differences in attitudes based on gender and ethnic identity came into view in our results. There is, of course, a growing body of literature on Iranian-Americans, most of which considers specific geographical contexts (Amin 2017; Chaichian 1997; Hanassab 1998; Honey 1978; Mobasher 2012), major demographic trends (Bozorgmehr 1998; Bozorgmehr and Ketcham 2018; Elahi 2006 and 2008; Foltz 2009; Higgins 2004; Lotfalian 2009; Mahdi 1998; Modarres 1998; Ronaghy et al. 1976) and the intersection of culture and identity (Amine 2018; Bennett 2008; Darznik 2010; Hoffman 1989a, 1989b, Karim and Khorrami 1999; Karim 2006; Maghbouleh 2018; Malek 2006; Mostofi 2003; Motlagh 2008). Our project is the first to focus on the community of scholars that would include those working on Iranian-Americans or Iranians in the diaspora.
Methodology
Iranian Studies scholars constitute a “low incidence population” (Berry et al. 2018). It is a small community of academics, difficult to locate with sampling procedures developed for general population surveys. So, a critical task for our survey was to identify and contact the appropriate pool of respondents. We employed a “list sampling” approach in which a targeted list of individuals was assembled from multiple sources (Berry et al. 2018). This was complicated by the fact that Iranian Studies is a broad interdisciplinary field without clear boundaries; we ultimately contacted scholars from disciplines ranging from history to literature to political economy to cinema studies. Very few colleges and universities have dedicated Iranian Studies or Persian Studies departments, programs, or centers. Middle Eastern Studies and Arab-American Studies programs, while more common, are a less than perfect fit with the scope of Iranian Studies as an academic field. These circumstances made it more difficult to determine just who should be contacted and invited to participate in the survey.
We addressed this by assembling a list that drew mainly from three databases. Two key sources were the membership directories for the Middle East Studies Association and the Association for Iranian Studies; from these lists we selected individuals whose subfields/specialties appeared to fit a broad conception of Iranian Studies. These searches were supplemented by a search in JSTOR for peer-reviewed publications since 2000 that appeared to fall into the realm of Iranian Studies; the authors of those articles were added to the list. The lists were crosschecked to avoid duplicate names. This effort produced a roster of 262 Iranian Studies specialists in U.S. academia. We included all academic ranks from advanced graduate students to emeritus professors. Because Iranian Studies is a small scholarly community and because the assembled list had only 262 people, we did not draw a sample from this pool. Rather, we attempted to obtain information from the entire group.1 It is important to note that we did not presume the social identity of the scholars we contacted based on their name or any other factor. Our survey asked individuals to sort themselves initially by the categories Iranian, Iranian-American, American, or Other. As expected, a small group of respondents selected “Other” and shared (via text box) how they identified (e.g., Canadian, Japanese). Those respondents are not included in the results we present here. Respondents were also asked about the other ethnicities with which they identified (both those common in Iran and the wide range of possibilities in the USA), again with a “text box” option for “Other.” Additionally, we asked what religious traditions they were raised in and held to now. Our question on gender identification was non-binary and included a “prefer not answer” option. Only one person did not identify as male or female (selecting, the “prefer not to answer” option). Although this was not a priority for our research, it is interesting to note that breakdown of sub-ethnicities and religious identifications among our respondents were very similar to those in national surveys of Iranian-Americans and in Iranian census data.
We initially contacted the respondent pool via regular mail in September 2016. A brief letter was sent explaining the purpose and content of the study.2 We then followed up with a series of emails with links to a survey distributed via Qualtrics in October 2016. The survey window was opened in late October 2016, just ahead of the Middle East Studies Association Conference in November. The survey remained open until early December with two sets of reminder emails sent before the survey was closed. As an incentive for opening and completing the survey, people were offered a chance to win one of two $50 Amazon gift cards. Of the 262 individuals contacted, 109 opened the survey and 99 completed it. This yielded a response rate of 37.8%, a rate that is firmly in line with web surveys of this kind (Tourangeau et al. 2013). Nonetheless, a respondent pool of only 99 individuals means that the analyses that follow are largely descriptive in nature, as not all comparisons attain traditional levels of statistical significance. Again, there were some respondents who did not consider themselves primarily Iranian, Iranian-American, or American. Therefore, in some tables that analyze those distinctions among Iranian specialists in American US academic settings, n will be lower than 99.
The questionnaire consisted of 46 questions seeking information on professional life in academia, education history, social identity, and attitudes toward the field of Iranian Studies, political activity, as well as some basic demographic questions. Most of the survey questions used a closed-ended format with predetermined sets of response options, although respondents were occasionally provided invited to provide open-ended comments to elaborate on their answers (some of which we share in our analysis below). The complete survey questions used in this paper are included in Appendix A.
Results
Our analysis of the survey data addresses several dimensions of gender differences in professional experiences. First, we present a basic profile of men and women in Iranian Studies, covering areas of study, academic rank, involvement in professional associations, and academic leadership. Second, we examine how men and women see gender identity as an influence in professional milestones, such as admission to graduate study and obtaining an academic position. Third, we discuss gender differences in more general assessments of professional satisfaction and the state of Iranian Studies as a field. Fourth, we consider gender contrasts in motivations for pursuing graduate study in Iranian Studies and the contours of their current research agendas. We close with a short overview of personal information which also highlight some differences based on gender.
The analyses discussed here are basic crosstabulations that display contrasts in survey responses between men and women. Statistical significance of gender differences was determined by way of chi-square tests of independence. Attendant p-values are included in tables where results met standards thresholds of statistical significance (p ≤ 0.05).
Gender and professional profile
Our survey confirmed that there is a wide array of fields represented in Iranian Studies, ranging from history, literature, and language to the social sciences, art, and music. We asked respondents to list the fields that best describe their current research. The questionnaire included an extensive list of possible fields, and we invited people to provide their own descriptions if the list did not include their field. Respondents could mention more than one field, so the percentages in Table 1 do not add up to 100%. A third of our respondents mentioned only one field, but most mentioned two, three, or four fields, and one individual listed nine different fields under the overall Iranian Studies umbrella.Table 1 Fields that best describe the research you do now…
Field Men Women
Iranian History 70.0% 50.0%
Literature 26.0% 25.0%
Language 12.0% 19.4%
Middle East Studies 38.0% 22.2%
Iranian Studies 44.0% 22.2%
Social Sciences 28.0% 19.4%
Gender Studies 4.0% 38.9%
Religious Studies 10.0% 11.1%
Art/Music/Media 6.0% 19.4%
Other 10.0% 2.8%
(n) (50) (36)
Respondents could select more than one field, so percentages in each column will not add up to 100%
p ≤ . 01
In Table 1, we break down the research backgrounds reported by men and women in our sample. The contrasts between men and women are more pronounced in some subfields more than others, but the overall gender differences shown in Table 1 are statistically significant. Iranian history is the most frequently mentioned subfield by both men and women, though a larger proportion of men (70%) list history compared to women (50%). Men are more likely than are women to mention area studies—Middle Eastern Studies or Iranian Studies—as a field. By contrast, women are much more likely than are men to mention gender studies as a subfield; 38.9% of women listed gender studies, making it the second most frequently listed subfield among women. Almost a fifth of women (19.4%) of women list a concentration in art/music media, compared to only 6% of men. Because the women in the sample tend to be younger and at earlier stages in their careers, the gender differences in subfield choices may portend shifts in the focus of Iranian Studies in the coming years. What is important to note is that three years after this survey was complete, over 100 scholars petitioned the Association for Iranian Studies to enact a Diversity and Inclusion Policy with particular focus on the composition of AIS conference panels to achieve more gender diversity. On May 29th, 2019, the AIS Council adopted this policy and applied it to the 2020 conference planning process.3 The demand for this policy change was clearly anticipated in the results of our survey data.
Studies of gender effects on salaries and promotion in academia often find it difficult to statistically disentangle the impact of gender and seniority/academic rank. Our sample is also defined by a discernable overlap between gender and academic rank. The contrasts are shown in Table 2. Although similar percentages of men (76%) and women (70%) hold tenure-stream positions, over a third of men (36%) are full professors, compared to less than a tenth (8.6%) of women in the sample. One in five women are graduate students, compared to only 6% of men. The different distributions of academic rank for men and women are statistically significant.Table 2 Academic rank by gender
Rank Men Women
Adjunct 8.0% 2.9%
Assistant Prof 24.0% 14.3%
Associate Prof 16.0% 37.1%
Full Prof 36.0% 8.6%
Academic Staff – 2.9%
Grad Instructor/TA 6.0% 20.0%
Other 2.0% 11.4%
Retired 8.0% 2.9%
(n) (50) (35)
p ≤ . 01
As might be expected, not having a tenure-stream position can impact one’s professional experience and outlook even when key professional milestones in research or campus leadership are achieved. One female respondent shared this comment, “As a non-tenure track associate professor on a long-term contract, my position is tenuous. Whenever I have directed… the college’s interdisciplinary programs, my views are generally respected (by colleagues and administrators) and I have had major impact on programming at the college during those periods. Otherwise, my views and role are marginalized despite my professional activities and publications. I am the only person doing Iranian Studies at my institution and the marginality of my position reflects the (lack of) importance given to this field of study.” This comment underscores the variety of factors that can shape one’s attitudes toward their professional experiences and how one’s sense of agency and inclusion can vary significantly over the course a person’s career. Furthermore, it suggests that one’s local institutional experience is in dialogue with one’s field. Our remaining tables explore how these factors contribute to the different experiences of men and women in Iranian Studies in American academia.
Gender and professional milestones
The questionnaire featured a series of items in which respondents were asked if gender identity had influenced a set of professional milestones, such as acceptance to graduate school, obtaining an academic position, salary, promotion, and opportunities for academic leadership. Respondents were asked if gender identity had influenced these milestones a great deal, a lot, a moderate amount, a little, or none at all. Table 3 summarizes the perceptions of male and female respondents across seven different milestones.Table 3 Gender identity influences professional milestones?
[A] Acceptance to grad school** Men Women
Great Deal – –
A Lot – 9.7%
Moderate Amount 6.3% 32.3%
A Little 14.6% 16.1%
None at All 79.2% 41.9%
(n) (48) (31)
[B] Funding in grad school* Men Women
Great Deal – –
A Lot – 6.9%
Moderate Amount 6.3% 24.1%
A Little 10.4% 17.2%
None at All 83.3% 51.7%
(n) (48) (29)
[C] Obtain academic position** Men Women
Great Deal – 3.3%
A Lot – 23.3%
Moderate Amount 16.7% 20.0%
A Little 18.8% 16.7%
None at All 64.6% 36.7%
(n) (48) (30)
[D] Salary time of hire* Men Women
Great Deal – 10.0%
A Lot 4.2% 16.7%
Moderate Amount 12.5% 13.3%
A Little 12.5% 6.7%
None at All 70.8% 53.3%
(n) (48) (30)
[E] Promotion** Men Women
Great Deal – 13.8%
A Lot – 10.3%
Moderate Amount 4.3% 10.3%
A Little 8.7% 10.3%
None at All 87.0% 55.2%
(n) (46) (29)
[F] Academic leadership Men Women
Great Deal – 3.3%
A Lot 4.3% 20.0%
Moderate Amount 8.7% 10.0%
A Little 19.6% 20.0%
None at All 67.4% 46.7%
(n) (46) 30)
[G] Ability to publish* Men Women
Great Deal – –
A Lot 4.3% 16.1%
Moderate Amount 2.2% 12.9%
A Little 10.9% 12.9%
None at All 82.6% 58.1%
(n) (46) (31)
*p ≤ .05
**p ≤ .01
In every case, there are notable differences in the perceptions voiced by men and women. Men rarely state that gender identity has a great deal or a lot of influence, and over 60%-80% of men see gender identity having no influence at all. Women are much less likely to say that gender identity has no influence, and for several milestones, they feel that gender identity has a great deal or a lot of influence.
Stark gender differences can be seen in an early professional milestone, acceptance to graduate school (Table 3A). Over 40% of women felt that gender identity had at least a moderate amount of influence, while only about 6% of men shared that judgment. At the same time, nearly eight in ten men (79.2%) thought that gender identity had no influence at all, nearly double the percentage of women (41.9%) with a similar view.
Men and women also differed significantly in their perceptions of the influence of gender identity on obtaining an academic position (Table 3C). About a quarter of women felt that gender identity had a great deal or a lot of influence. Not a single male respondent shared that perception. By contrast, 64.6% of men thought that gender identity had no influence at all, compared to 36.7% of women.
A similar pattern is found in perceptions regarding the influence of gender identity on salary at time of hire (Table 3D). Over 25% of women stated that gender identity had a great deal or a lot of influence compared to only 4% of men. Seven in ten men saw no gender influence at all on initial salaries, a view expressed by only about half the women in the sample. This result is particularly interesting in the way it dovetails with other studies of gender gaps in academic salaries, as well as some research on salary compression. Although direct gender effects on salary compression were hard to isolate statistically in one study (Burke et al. 2005), the authors did acknowledge an impact of gender of initial salary levels. It is telling, but perhaps not surprising, that female academicians are aware of this condition in a way that men are not.
The contrasting perceptions of male and female Iranian Studies scholars extends to the remaining professional milestones in Table 3—promotion, academic leadership, and ability to publish. In the case of promotion (Table 3E) close to 90% of men felt that gender identity had no influence at all, and none of the men in the sample saw that gender identity might have a great deal or a lot of influence. Women, on the other hand were less likely (55.2%) to say that gender identity had no influence at all, while almost a quarter (24.1%) of women stated that gender identity had a great deal or a lot of influence.
A similar proportion of women (23.3%) also see gender identity as having a great deal or a lot of influence on opportunities for academic leadership (Table 3F). Again, in stark contrast, two-thirds of men (67.4%) see gender identity having no influence at all. It happens to be the case in our sample that women are less likely than are men (although the differences are not statistically significant) to hold/have held positions of academic leadership. Although this could be attributed, in part, to more seniority among men, it is clear that women in our sample do appear to have a different view of the professional climate for leadership opportunities.
Finally, men and women differ in their judgments about the influence of gender identity on the ability to publish (Table 3G). Both men and women generally see gender identity as having minimal influence, although men are still much more likely than are women to observe that there is not influence at all (82.6% of men vs. 58.1% of women). Only about 6% of men state that gender identity might have moderate or a lot of influence, a judgment offered by 29% of women. These distinct sets of perceptions have a parallel in other research that finds women in academia often pursuing (and being socialized to pursue) careers in teaching intensive colleges and universities, where the atmosphere for research and publishing can be quite challenging (Berheide et al. 2020; Webber and Rogers 2018).
One of the interesting areas of “pushback” from our respondents in the comment section had to do with our questions that attempted to isolate the influence of social identity of professional milestones. One woman respondent opined, “I have no idea how these factors influence people who are in a position to hire or promote me. That is something you would have to ask them.” There is an interesting implication here: why should Iran specialists (of any background) have to account for the biases of others? They should not, of course. But our survey was seeking to understand, in the most open-ended way possible, if Iran specialists perceived any bias against them in their professional lives. Another woman respondent wanted to underscore the effort she made to separate her personal identity as “an Iranian woman” from her professional identity, “I try to comment on what I actually now about, instead of turning my presumed identity into a speaker position.” Wherever these individual respondents are located in the larger pattern of responses, these comments suggest that it is something that they have to navigate even if they do not want to.
Gender and professional satisfaction
An important component of our questionnaire was a set of items that invited respondents to express their satisfaction or dissatisfaction with various elements of professional well-being. One question focused on Iranian Studies as a field, while three other questions dealt primarily with respondents’ personal professional satisfaction. All of these survey questions used a five-point response scale running from very satisfied through very dissatisfied. Table 4 presents breakdowns by gender. Overall, gender differences are modest, and never reach standard thresholds of statistical significance. As such, these results provide an interesting contrast to the gender differences found in views about professional milestones. The two sets of survey questions cover some similar territory, but in different ways. The milestone items refer to some specific stages and issues in academic life, while the satisfaction items are more general. The milestone questions also directly ask respondents to think about gender identity as a possible influence. The satisfaction questions offer less clearly defined cues. The differing formats and orientations of the survey questions can help discern how and when gender might be associated with perceptions of professional experiences.Table 4 Gender identity influences professional outlook
[A] State of your career right now Men Women
Very Satisfied 45.8% 34.4%
Somewhat Satisfied 37.5% 40.6%
Neutral 6.3% 9.4%
Somewhat Dissatisfied 4.2% 12.5%
Very Dissatisfied 6.3% 3.1%
(n) (48) (32)
[B] Prospects professional future Men Women
Very Satisfied 40.4% 25.8%
Somewhat Satisfied 27.7% 38.7%
Neutral 19.1% 12.9%
Somewhat Dissatisfied 10.6% 16.1%
Very Dissatisfied 2.1% 6.5%
(n) (47) (31)
[C] Professional environment Men Women
Very Satisfied 39.6% 28.1%
Somewhat Satisfied 33.3% 34.4%
Neutral 10.4% 21.9%
Somewhat Dissatisfied 8.3% 15.6%
Very Dissatisfied 8.3% –
(n) (48) (32)
[D] State of Iranian studies Men Women
Very Satisfied – –
Somewhat Satisfied 45.8% 31.3%
Neutral 22.9% 37.5%
Somewhat Dissatisfied 25.0% 21.9%
Very Dissatisfied 6.3% 9.4%
(n) (48) (32)
The data in Table 4A–C show that quite high percentages of both men and women state that they are either very satisfied or somewhat satisfied with the state of their careers right now, prospects for their professional future, and the professional environment where they work. Women are a bit more likely than are men to express some level of dissatisfaction with prospects for their professional future (Table 4B), but the “gender gap” here is just short of ten percentage points.
We are struck by the degree of expressed dissatisfaction about the state of Iranian Studies as a field, an outlook that appears to be very similar among the men and women in the sample (Table 4D). Men were more likely than women to say that they were somewhat satisfied with the state of Iranian Studies, while women—by a comparable margin—were more inclined than men to stake out a neutral stance on the state of the field. Identical percentages (31.3%) of men and women expressed some measure of dissatisfaction with the state of Iranian Studies as a field.
The relatively small gender differences found here are a bit at variance with the results of previous studies on professional satisfaction. One possible explanation is that earlier work has often found gender differences to be most pronounced in STEM fields, which are not represented in Iranian Studies. Another possible factor may be that the challenges facing Iranian Studies in recent years—the often insecure state of area studies on many campuses, and the political ferment surrounding Iranian Studies—are sufficiently salient that they motivate a consensus that crosses lines of discipline, seniority, and gender.
Gender and motivations for graduate study and research interests
Survey respondents were presented with lists of possible influences on their choice of graduate study and their current research interests. Respondents could select multiple items from the lists, and they had the opportunity to specify influences not included among the response options. Gender breakdowns are shown in Table 5. The overall profiles of influences specified by men and women are more similar than different, and the contrasts that are apparent do not achieve statistical significance. But those contrasts are nevertheless noteworthy, and they resonate with previous research on scholarly motivations.Table 5 Factors influencing research
[A] Choice of graduate study Men Women
Social Identity 6.0% 16.7%
Intellectual Interest 94.0% 86.1%
Undergraduate Study 12.0% 19.4%
Economic Opportunity 2.0% 5.6%
Career Goals 18.0% 13.9%
Social Impact 16.0% 27.8%
(n) (50) (36)
[B] Current research interest Men Women
Previous Research 64.0% 63.9%
Funding Opportunities 12.0% 11.1%
Ethic Identity 12.0% 2.8%
Gender Identity 4.0% 11.1%
Religious Identity 6.0% –
Social Impact 32.0% 47.2%
(n) (50) (36)
Respondents could select more than one factor, so percentages in each column will not add up to 100%
As seen in Table 5A, intellectual interest was mentioned by most everyone—94% of men and 86% of women—as a factor in their choice of graduate study. In stark contrast, economic opportunity was mentioned by almost no one—2.0% of men and 5.6% of women. Neither set of figures should come as a surprise, especially the latter set.
Women were a bit more likely than men (27.8% vs. 16.0%) to identify social impact as an influence in their choice of graduate study. Although the gender gap here is not immense, it is noteworthy that close to 30% of women placed a priority on their scholarly pursuits having a social impact.
This priority is even stronger as an influence on current research interests (Table 5B). Nearly half of the female respondents (47.2%) mentioned social impact as an influence on current research interests. A substantial percentage of men (32.0%) also listed social impact. Aside from previous research, social impact was the most commonly mentioned motivator among both men and women, and the 15 percentage difference between men and women is the largest gap found in Table 5B.
Deeb and Winegar (2015) found a clear political consciousness underlying the scholarly pursuits of MENA scholars, a consciousness that was particularly evident among women trained in the late 1960s/early 1970s. Among subsequent generations of MENA scholars, a connection between academic interests and political commitments was evident across gender.
We followed up on this observation with our own data, by further breaking down the contrasts shown in Table 5 by academic rank. The results are not shown here; the analysis strains our small sample, and in most cases, we have only a few respondents representing different combinations of gender and academic rank. But the patterns that we do find are suggestive, both confirming and updating Deeb and Winegar’s observations. Take, for instance, the gender gap for mentions of social impact as a motivator for choice of graduate study. We found that gap to be wider among full and associate professors, consistent with the generational patterns found by Deeb and Winegar. At the same time, we also found a considerable gender gap among current graduate students in the mention of social impact. Again, this is based on a mere handful of survey respondents, but it we do wonder if the current political climate at the time of the survey was encouraging a consciousness or urgency that was influencing the academic interests of rising Iranian Studies scholars. And similar to the patterns of subfield interests summarized in Table 1, we wonder if there is a glimpse here of a future change in focus and priorities in the field of Iranian Studies.
Conclusion and prospects for future research
The survey results reported here identified different professional experiences on the basis of gender and “region-related” ethnicity. Women in Iranian Studies in America academia were more likely to be of junior rank or graduate students. Women were more likely than men to feel that gender identity influenced their professional milestones. Women were more likely to list the desire for social impact as a professional motivation than men. Women tended to feel less sanguine about the state of their careers, their professional environment, their career prospects, and the state of the Iranian Studies field as a whole.
These findings raise a host of questions for further research. Do those differences translate into different epistemological patterns among these scholars? If so, do patterns emerge within the broader field of Iranian Studies, or, in parallel because other disciplinary or interdisciplinary scholarly networks are more welcoming to other lines of inquiry? What is the impact of Iranian Studies scholars who are in a position to train and mentor younger scholars? What is the impact of Iranian Studies on wider academic curricula? Does that connect to where Iranian Studies scholars find tenure-stream positions? The epistemological questions are probably best addressed through the writing of scholars themselves, but researchers might follow the lead of scholars like Zohreh T. Sullivan (2001) and interview academics to get a fuller sense of how their personal lives intersect with and inform their professional ones.
Oral histories and memoirs can further enrich our understanding of the personal and the professional among Iranian-American Iran specialists. But how relevant is the study of this “low incidence population” to the wider story of Iranian-Americans and the Iranian diaspora? How representative is the community of US-based Iranian-American Iranian Studies scholars of the Iranian-American community as a whole?
Our survey did probe other personal experiences—comparisons of their economic status growing up versus the present (i.e., 2016), highest level of education in Iran (as a proxy for immigration timing), use of Persian in different settings, and family life. Some suggestive results in our survey relate to three demographic features of Iranian-Americans noted in other research. Some of those findings are briefly noted here.
First, there are a range of ways Iranian-Americans self-identify and stay connected to Iran through Persian. In our survey, if a respondent went to high school in Iran, they tended to identify as Iranian or American, but not Iranian-American (which was the case for other levels of education completion in Iran). More women than men completed high school in Iran. Iranians and Iranian-Americans in our survey rarely use Persian in “non-professional settings” outside the home or in casual conversations “at work.” Women were a little more likely than men to use Persian at home or non-professional social settings outside the home. Those who identified as Iranian were nearly twice as likely to speak Persian at home compared to those who identified as Iranian-American (58.3% and 30% respectively). But both groups reported speaking Persian at home less than US census respondents 15 years earlier:According to the 2000 US Census, Persian language ranked 18th among the 20 languages frequently spoken in US households. More recent ACS data reveal that 82% of first- and 45% of second-generation Iranians speak Persian at home. (Bozorgmehr and Meybodi 2016, 102).
Iranian Studies specialists—whether they consider themselves Iranian or Iranian-American—are less likely than Iranian immigrants generally to speak Persian at home. Whether this reflects the assimilative effects of being in American academia or some other factor is hard to say without further study. Prioritizing Persian language education and access to Persian language education were important factors in Persian retention in (Bozorgmehr and Meybodi, 104–14). Iranian Studies scholars are not necessarily concentrated in areas where access to Persian language education is available for their children.
Second, in terms of marital status and income, our survey results suggest some similarity with of our academics and the broader population of Iranian-Americans. Men in our survey were more likely to be married and have children than women. Women and men were more similar than not in reporting their progress on a “socio-economic” ladder (comparing their present circumstances to when they grew up), with men reporting slightly lower “starting” points than women. Self-identified “Americans” reported lower starting points that Iranian or Iranian-Americans. This suggests that Iranian-American academics are more like the majority of Iranian-Americans who report incomes of $50,000 or higher (82%) and who have a college degree or higher (86%, Zogby 2020, 12).
Third, and returning to the issue of cultural similarity, nearly equal proportions of women and men in our survey (70.3% and 72.1%, respectively) reported being raised in some religious tradition. Those proportions declined noticeably in adulthood for both men and women, although women were more likely than men to state a current religious identification (40.5% compared to 31%). The largest religious group growing up was “Muslim” (31.9 and 33.3%, respectively, for men and women). This is comparable to the number of Iranian-Americans generally. The PAAIA 2020 National Opinion Survey in 2020 found that 36% of Iranian-Americans identified as Muslim (Zogby 2020, 12). The largest current religious identification for respondents in our survey was “No Religious Tradition” (37.8% and 43.8%, respectively, for men and women). Again, this is a little higher than the 30% of Iranian-Americans in the PAAIA survey who selected “agnostic” (12%), “atheist” (7%), and “other religion” (11%), but arguably comparable.
All this taken together, we think our results on gender and professional experience among Iranian-American Iran specialists are worth exploring in other professional and socio-economic subsets of Iranian-Americans and Iranian-Americans more generally. There is much left to be learned, both through follow-up survey research, as well as more intensive interviewing. In the years since the 2016 survey, several significant events have occurred that could impact the professional experiences of Iran specialists and their attitudes. First, as noted earlier, the Association for Iranian Studies implemented a Diversity and Inclusion policy in 2019 that impacted conference organization and outreach for leadership positions in AIS. Second, worsening relations between the USA and Iran had two disruptive effects on Iranian-Americans generally and, therefore, could also impact the professional priorities of Iran specialists in the USA. The implementation of the “Muslim Ban” from 2017 to 2021, for example, put Iranian-born graduate students in a precarious situation. The tightening of sanctions on Iran in 2018 as the US withdrew from the Joint Comprehensive Plan of Action (also known as the “Iran Nuclear Deal”) would have hindered those Iranian-Americans with transnational families from supporting each other financially or traveling to visit one another. The vulnerability of diaspora-based academics to being detained in Iran may also have impacted scholarly activity and research plans. Third, the lasting impact of the Covid-19 pandemic on life and academia in the USA is only beginning to be assessed. Were Iran specialists insulated from those effects or did they perceive differential impacts? That might find expression in their current attitudes about the field generally and their expectations about their careers. Are the gendered differences in pandemic impacts in American society, academic life playing out differently among members of this scholarly community? As we look to develop an updated survey on these issues in 2022, we will have the benefit of insights accorded us by the 2016 survey which gave us a snapshot of the field before all these developments came to pass.
Appendix A: text of survey questions used in analysis
Full text of survey questionnaire available at: https://drive.google.com/drive/folders/11Yb-7p7YgRDxEp2pjO4wO2ESx6TIU4up?usp=sharing.
Q2.1 Please select the fields that best describe the research you do now (select all that apply)
Iranian History, 1800–present.
Iranian History, 1500–1800.
Iranian History, Early Islamic Period to 1500.
Iranian History, Pre-Islamic.
Modern Persian Literature.
Traditional Persian Literature (Post-Islam).
Pre-Islamic Iranian Literature/Culture.
Persian Language Pedagogy.
Middle East Studies.
Iranian Studies.
Gender Studies.
Sociology.
Religious Studies.
Other (please specify).
Q2.8 What is your current academic rank?
Non-Tenured Instructor/Adjunct Professor.
Tenure-Stream Assistant Professor (or equivalent).
Tenured Associate Professor.
Tenured Professor.
Research Faculty (Non-Tenured).
Academic Staff (e.g., Library).
Graduate Instructor or Teaching Assistant.
Other.
Retired.
Q4.1 Please select the single ethnic heritage that best describes you.4
Iranian.
American.
Iranian-American.
Other (specify).
Q4.7 To which gender identity do you most identify?
Male.
Female.
Transgender Male.
Transgender Female.
Gender Variant/Non-Conforming.
Other.
Prefer Not to Answer.
Q5.7 How do you think your gender identity influenced the following professional milestones:A Great Deal A Lot A Moderate Amount A Little
None at All
Acceptance to Graduate School.
Level of Funding Received in Graduate School.
Ability to Obtain an Academic Position.
Salary Negotiations at Time of Hire Promotion.
Opportunities for Academic Leadership Positions.
Ability to Publish.
Q 5.12 How do you feel about …Very Somewhat Somewhat
Satisfied Satisfied Neutral Dissatisfied Dissatisfied
The state of your career right now.
The prospects for your professional future.
The professional environment where you work.
The state of Iranian Studies as a field.
Q5.1 Which factors influenced your choice of graduate study? (select all that apply)
Social Identity.
Intellectual Interest.
Undergraduate Study.
Economic Opportunity.
Career Goals.
Desire to Have Social Impact.
Other (specify).
Q5.2 Which factors influenced your current research interest? (select all that apply)
Previous Research.
Funding Opportunities.
Ethnic Identity.
Gender Identity.
Religious Identity.
Desire to Have Social Impact.
Other (specify).
Acknowledgements
The authors gratefully acknowledge the University of Michigan-Dearborn Office of Research Administration for the campus grant award. We also appreciate the hard work of our student research assistant, Mr. Brian Kudron, who assisted us with developing our respondent pool and formatting the survey instrument in Qualtrics.
Author contributions
Both authors developed the survey and reviewed data collaboratively. JB prepared the tables and evaluated results for statistical significance. CMA interpreted the results in the context of the academic literature on Iranian Studies, Middle East Studies, and Iranian Diaspora Studies. Both authors reviewed the literature on gender and ethnic bias in US academia and evaluated the results accordingly. Conclusions and discussions were written collaboratively.
Funding
Funding for this research was provided by University of Michigan-Dearborn Research Administration Campus Grant in 2016.
Data availability
The aggregate, anonymized data from the survey are available upon request to either author.
Declarations
Conflict of interest
Authors have on financial interests connected to this research or results.
Ethical research
The survey was judged “exempt not regulated” by the University of Michigan Institutional Review Board on October 6, 2016 [eResearch ID: HUM00114712] but still bound by the principles of Belmont Report for ethical research. All data collected were anonymized and reported in aggregate from with no individual information included. The survey instrument itself advised respondents of the intended use of the survey data.
1 A similar list sampling approach was taken in a 2013 survey of Iranian-American physicians in California. In that study, respondents were identified from several medical directories and professional association membership lists (Rashidian et al. 2016).
2 Experiments conducted in conjunction with surveys of faculty have shown that initial hardcopy mail contact can improve response rate as much as 10% over surveys that rely only on email contact (Tourangeau et al. 2013).
3 See “Diversity and Inclusiveness Policy,” About AIS at https://associationforiranianstudies.org/about (accessed on January 13, 2021).
4 It is important to note that this question was followed up by several refining questions on ethnic heritage and religious identification. Both “Iranian” and “American” are categories that subsume a lot of diversity and a couple of respondents actually took issue with the wording of the question (although they answered it). But, our study was intended to query if identifying as Iranian or Iranian-American had an impact on professional experience in a field devoted to the study of Iran.
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Springer Berlin Heidelberg Berlin/Heidelberg
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10.1007/s11553-022-01000-9
Originalarbeit
Vorstellungen vom Altsein bei Menschen mit geistiger Behinderung – Ergebnisse einer qualitativen Public-Health-Studie
Perceptions of being old in people with intellectual and developmental disabilities—results of a qualitative public health studyhttp://orcid.org/0000-0001-6912-7999
Habermann-Horstmeier Lotte [email protected]
1
Breinlinger Larissa 23
1 Villingen Institute of Public Health (VIPH), Klosterring 5, 78050 Villingen-Schwenningen, Deutschland
2 grid.21051.37 0000 0001 0601 6589 Fakultät Gesundheit, Sicherheit, Gesellschaft, Hochschule Furtwangen, Pflege- und Rehabilitationsmanagement, Furtwangen, Deutschland
3 Organisationskomitee der Special Olympics World Games 2023, Berlin, Deutschland
5 12 2022
116
27 7 2022
4 11 2022
© The Author(s), under exclusive licence to Der/die Autor(en), exklusiv lizenziert an Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2022, Springer Nature oder sein Lizenzgeber (z.B. eine Gesellschaft oder ein*e andere*r Vertragspartner*in) hält die ausschließlichen Nutzungsrechte an diesem Artikel kraft eines Verlagsvertrags mit dem/den Autor*in(nen) oder anderen Rechteinhaber*in(nen); die Selbstarchivierung der akzeptierten Manuskriptversion dieses Artikels durch Autor*in(nen) unterliegt ausschließlich den Bedingungen dieses Verlagsvertrags und dem geltenden Recht.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Hintergrund
Obwohl die Zahl der alten Menschen mit geistiger Behinderung (MmgB) in den letzten Jahrzehnten deutlich angestiegen ist, gibt es in Deutschland noch viel zu wenige, speziell auf ihre Bedürfnisse zugeschnittene Wohn- und Betreuungsangebote. Zudem ist unklar, wie MmgB sich ihr eigenes Alter vorstellen, und ob sie überhaupt dazu in der Lage sind, sich in das eigene Altsein hineinzuversetzen.
Methode
Die Grundlage dieser qualitativen Studie bilden leitfadengestützte Interviews mit 16 erwachsenen MmgB (10 Frauen, 6 Männer; Alter: 24 bis 59 Jahre; sprachliche Fähigkeiten: sehr gut bis mittel; Grad der geistigen Behinderung [GgB]: sehr leicht bis mittel; sozioemotionaler Entwicklungsgrad [SEO-Grad]: SEO 4 bis ≥ SEO 5). Die Interviews wurden einer strukturierenden Inhaltsanalyse nach Mayring unterzogen (induktives Vorgehen).
Ergebnisse
Bei den Proband:innen hatten der GgB, der SEO-Grad und die sprachlichen Fähigkeiten deutlichen Einfluss auf ihre Fähigkeiten, sich in ein zukünftiges Selbst hineinzuversetzen. Wie Menschen ohne Behinderung möchten jedoch fast alle – unabhängig vom GgB – auch im Alter dort wohnen bleiben, wo sie derzeit wohnen, mit ihren engsten Verwandten und Freunden zusammen sein und von den Personen betreut werden, die sie jetzt betreuen. Anders als Menschen ohne Behinderung reagierten fast alle recht gelassen bei der Vorstellung, im Alter aufgrund zusätzlicher Erkrankungen weitere Hilfen zu benötigen.
Schlussfolgerungen
Bei der Planung von Wohn- und Betreuungsangeboten sollen in Zukunft vermehrt die Bedürfnisse der MmgB mit einbezogen werden. Hierbei ist jedoch der Grad der intellektuellen, sozioemotionalen und sprachlichen Einschränkungen zu berücksichtigen. Dies wird u. a. auch eine größere Flexibilität hinsichtlich der Planung und Bereitstellung entsprechender Wohnmöglichkeiten und Hilfen erfordern.
Background
Although the number of elderly people with intellectual and developmental disabilities (IDD) has increased significantly in recent decades, there are still far too few offers for housing and care in Germany that are specially tailored to the needs and wishes of this group. In addition, it is unclear how people with IDD perceive their own age and whether they are even able to empathize with their future selves.
Methods
This qualitative study was based on structured interviews with 16 adults with IDD (10 women, 6 men; age: 24–59 years; language skills: very good to moderate; degree of intellectual disability: very mild to moderate; socioemotional stage of development: SEO 4 to ≥ SEO 5). Based on the interviews, a structuring content analysis according to Mayring was carried out using an inductive approach.
Results
There was strong evidence that the level of intellectual disability and socioemotional development, as well as the level of language skills may influence the ability of people with IDD to empathize with their future selves. However, like people without disabilities and regardless of the degree of their disabilities, in old age almost all of them would like to remain where they currently live, to be with their closest relatives and friends, and to be cared for by the people who are caring for them now. However, unlike people without disabilities, everyone reacted quite calmly to the idea of having to make use of additional tools or assistance in old age due to illness.
Conclusions
In the future when planning housing and care offers, the needs, ideas, and wishes of people with IDD should be included. In doing so, their degree of intellectual and socioemotional disability and their language skills must also be taken into account. This of course will require greater flexibility in the planning and providing of appropriate housing and care services.
Schlüsselwörter
Alter
Geistige Behinderung
Behinderungsgrad
Bedürfnisse im Alter
„Episodic future thinking“
Keywords
Old age
Disabled persons
Degree of disability
Needs in old age
Episodic future thinking
==== Body
pmcEinleitung und Problemstellung
Noch vor einigen Jahrzehnten lag die Lebenserwartung von Menschen mit geistiger Behinderung (MmgB) in vielen westlichen Ländern erheblich unter der der Durchschnittsbevölkerung. Aufgrund einer verbesserten medizinischen Versorgung und dank intensiver Betreuung haben sich jedoch die Chancen, ein höheres Lebensalter zu erreichen, auch für MmgB deutlich verbessert [7]. Es fehlt aber noch immer an Einrichtungen, die speziell auf die Bedürfnisse von alten MmgB eingestellt sind und über entsprechendes Fachpersonal verfügen [15]. Dass etwa 40 % der Betreuungskräfte in Behinderteneinrichtungen das zunehmende Durchschnittsalter der von ihnen betreuten MmgB und die damit verbundenen zusätzlichen Aufgaben als belastend erleben, ist daher nicht verwunderlich [17]. Unklar ist jedoch, ob MmgB in ihrem Alter überhaupt in solchen Einrichtungen betreut werden möchten und wie sie sich das eigene Alter(n) vorstellen. Nach dem aktuellen Bundesteilhabegesetz (BTHG) sollen alle MmgB ihre eigenen Vorstellungen im Rahmen von regelmäßig stattfindenden Besprechungen zur Ermittlung ihrer Teilhabebedarfe („personenzentrierte Gesamtplanung“) einbringen, sodass ihre Fähigkeiten, Fertigkeiten und Ressourcen sowie ihre individuellen Lebenslagen dort jeweils berücksichtigt werden können. Bislang gab es allerdings noch keine Untersuchungen dazu, ob MmgB überhaupt grundsätzlich dazu in der Lage sind, sich selbst in die Zukunft zu projizieren. Können sich alle MmgB das eigene Alter(n) vorstellen und auf dieser Basis dann auch Wünsche und Vorstellungen hinsichtlich des eigenen Altseins äußern? Oder sind ihre Möglichkeiten hierzu nicht vielmehr von der Art und dem Grad ihrer geistigen Behinderung abhängig? Erste Ergebnisse unserer vorgeschalteten explorativen Studie zum episodischen Zukunftsdenken (EFT) weisen darauf hin, dass sowohl der Grad der geistigen Behinderung als auch der Grad der sozioemotionalen Entwicklung sowie das Niveau der sprachlichen/narrativen Fähigkeiten, die Art der geistigen Behinderung und das Vorhandensein zusätzlicher neurokognitiver Störungen Einfluss auf die Fähigkeiten von MmgB haben könnten, sich in ein zukünftiges Selbst als alter Mensch hineinzuprojizieren [16].
Zielsetzung
Ziel der vorliegenden Untersuchung war es nun, mehr darüber zu erfahren, welche Vorstellungen MmgB vom eigenen Altsein haben und ob es ggf. Unterschiede in Abhängigkeit etwa von ihrem jeweiligen intellektuellen bzw. sozioemotionalen Entwicklungsgrad gibt. Antworten hierauf sollten im Rahmen einer qualitativen Studie mit Hilfe von fokussierten, teilstrukturierten Interviews gefunden werden, in denen nach den subjektiven Meinungen, Motiven und Einstellungen der Proband:innen zu diesem Thema gefragt wurde. Diese Interviewform bietet einen breiten Raum für freie Antworten, die von der subjektiven Wirklichkeit der Interviewten geprägt sind. Die grob strukturierte Interviewform erlaubt dabei eine bessere Vergleichbarkeit der Interviews. Durch das Festlegen von Fragenbereichen und durch konkrete Nachfragen können jedoch gleichzeitig eigene Hypothesen zum Thema überprüft werden. Die Auswertung ist bei einer Vorstrukturierung zudem weniger zeitaufwändig als beim rein narrativen Interview. Auf diese Weise sollten nun möglichst viele Aspekte hinsichtlich der Vorstellungen von MmgB vom eigenen Altwerden und Altsein sichtbar gemacht werden.
Methode
Stichprobenerstellung und Kontaktaufnahme
Das wichtigste Kriterium der konstruierten Stichprobenerstellung im Rahmen einer qualitativen Studie ist neben der klar definierten Reichweite die Repräsentanz [12, 18]. Um eine kontrastierende Stichprobenzusammenstellung zu erreichen, wurden daher aus der Gruppe „erwachsene Menschen mit geistiger Behinderung“ Personen ausgesucht, die möglichst unterschiedliche Merkmale dieser Grundgesamtheit repräsentieren sollten (Beschreibung der Studienteilnehmenden s. u.).
Der Kontakt zu den befragten MmgB wurde jeweils über eine Betreuungskraft hergestellt. Potenzielle Studienteilnehmer:innen wurden vorab mit einem kurzen, in einfacher Sprache verfassten Schreiben über das Vorhaben informiert. Sobald sich eine Person bereiterklärt hatte, an der Studie teilzunehmen, wurde von ihr bzw. den gesetzlich Betreuenden eine Einwilligungserklärung zur Studienteilnahme eingeholt. Abschließend wurden die Betreuungskräfte gebeten, wenn möglich zusammen mit dem Probanden/der Probandin, einen kurzen Fragebogen zur interviewten Person (Name, Alter und Geschlecht, Art und Grad der geistigen Behinderung, kommunikative Fähigkeiten, zusätzliche Erkrankungen oder psychische Störungen, Angaben zu Fähigkeiten, aus denen sich auf den sozioemotionalen Entwicklungsgrad der interviewten Person schließen ließ) auszufüllen. Bei der Terminvereinbarung wurden die Bedürfnisse und Wünsche der Studienteilnehmer:innen berücksichtigt.
Studienteilnehmende
Für die Teilnahme an der Studie konnten schließlich 10 Frauen und 6 Männer mit geistiger Behinderung im Alter von 24 bis 59 Jahren (Mittelwert [MW]: 43,06; Standardabweichung [SD]: ± 11,64 Jahre) gewonnen werden. Alle Personen stammten aus Süddeutschland, wo sie in verschiedenen stationären Behindertenwohneinrichtungen (n = 6) und Außenwohngruppen stationärer Einrichtungen (n = 6) betreut wurden bzw. in inklusiven Wohngemeinschaften (n = 2) und im ambulant betreuten Einzelwohnen (n = 2) lebten. Ursache der geistigen Behinderung war in einigen Fällen das Prader-Willi-Syndrom, das Down-Syndrom bzw. eine Autismus-Spektrum-Störung, meist wurde die Art der geistigen Behinderung jedoch nicht konkret angegeben. Zusätzlich zur geistigen Behinderung wiesen 2 Probandinnen eine körperliche Behinderung, 7 Proband:innen eine psychische Störung auf.
Da Menschen mit einer schwereren geistigen Behinderung in der Regel eingeschränkte kommunikative Fähigkeiten haben, können fokussierte Interviews nur mit Personen durchgeführt werden, die einen leichten bis mittleren Grad einer geistigen Behinderung aufweisen. Die sprachlichen Fähigkeiten der Studienteilnehmenden wurden von ihren Betreuungspersonen – in einzelnen Fällen gemeinsam mit den jeweiligen Proband:innen – auf einer intervallskalierten Antwortskala von „sehr gut“ (1) bis „sehr schlecht“ (5) ausschließlich als „sehr gut“ (1), „gut“ (2) oder „mittel“ (3) eingestuft. Den Grad der geistigen Behinderung schätzten die Betreuungskräfte (ggf. wieder gemeinsam mit der betreuten Person) auf einer Antwortskala von „sehr leicht“ (1) bis „sehr stark“ (5) ein. Alle Proband:innen wiesen einen Grad der geistigen Behinderung von „sehr leicht“ (1) bis „mittel“ (3) auf. Das sozioemotionale Leistungsniveau der Studienteilnehmenden wurde auf der Basis des SEO-Konzepts (sozioemotionaler Entwicklungsgrad) nach Došen [8] und Sappok/Zepperitz [27] anhand von 5 Aussagen zu zentralen Fähigkeiten aus den Bereichen „Umgang mit dem eigenen Körper“, „Umgang mit Bezugspersonen“, „Umgang mit Peers“, „Kommunikation“ und „Affektregulation“ ermittelt, die entsprechend dem Diagnostikinstrument SEED (Skala der emotionalen Entwicklung) im Verlauf der SEO-Entwicklungsstufe 5 erreicht werden [28]. Die Betreuer:innen schätzten auch hier die Fähigkeiten der Proband:innen anhand einer Antwortskala ein. Jeder angekreuzten Aussage wurde dann ein Punktwert zugeordnet. Antwortmöglichkeiten waren hier „Ja“ (1 Punkt [P.]), „Ja, mit leichten Einschränkungen“ (2 P.), „Ja, mit deutlichen Einschränkungen“ (3 P.), „Nein“ (4 P.). Die Einordnung in die SEO-Entwicklungsstufe ≥ 5 erfolgte dann, wenn bei den 5 Aussagen überwiegend (d. h. in mehr als der Hälfte der Fälle) „Ja“ bzw. „Ja, mit leichten Einschränkungen“ angekreuzt wurde und der errechnete durchschnittliche Punktwert bei ≤ 2,0 von 4 lag. Eine Einordnung in die SEO-Entwicklungsstufe 4 wurde dann vorgenommen, wenn überwiegend „Ja, mit deutlichen Einschränkungen“ bzw. „Nein“ angekreuzt wurde und der errechnete durchschnittliche Punktwert bei > 2,0 lag. Dem SEO-Grad 4,5 wurden Proband:innen dann zugeordnet, wenn zwar überwiegend „Ja“ bzw. „Ja, mit leichten Einschränkungen“ angekreuzt wurde, der durchschnittliche Punktwert aber bei > 2,0 lag. Die Einordnung in die SEO-Entwicklungsstufe 4 bzw. 4–5 erfolgte unter der begründeten Annahme, dass keiner der Studienteilnehmenden einen SEO-Grad ≤ 3 aufwies, da sich bei diesen Personen in den Angaben der Betreuungskräfte bzw. in den Interviews nur vereinzelt und nicht durchgängig Anhaltspunkte für ein typisches SEO-3-Verhalten zeigte (Beispiel für typisches SEO-3-Verhalten im Interview: „Kommuniziert überwiegend über das Hier und Jetzt.“). Das beschriebene Vorgehen erlaubt nur eine grobe Einordnung des sozioemotionalen Entwicklungsstandes der Proband:innen. Es wurde gewählt, da eine vollständige SEO-Testung für alle Beteiligten zu zeitintensiv gewesen wäre. Hierbei muss allerdings berücksichtigt werden, dass es bei MmgB durchaus auch ausgeprägte Diskrepanzen zwischen körperlichem, sozioemotionalem und intellektuellem Entwicklungsstand geben kann. Zur Einteilung der SEO-Grade s. a. [16].
Eine ausführliche statistische Beschreibung der Studienteilnehmenden, auch hinsichtlich ihrer sprachlichen/narrativen Fähigkeiten, des Grades ihrer geistigen Behinderung und des grob eingeschätzten Grades ihrer sozioemotionalen Entwicklung (SEO-Grad) zeigt Tab. 1.Nr Geschlecht Altersgruppe Art der Behinderung, Erkrankung Wohnform GdgB SEO-Grad Sprachliche/narrative Fähigkeiten
1 w 1 GB, PS aEW 2 5 1
2 m 1 GB, ASS, PS Stat 3 4–5 2
3 w 2 GB, PS Stat 2 5 1
4 m 2 GB, Trisomie 21 Stat 3 5 3
5 w 2 GB, ASS AWG 3 4 2
6 m 1 GB, ASS, PS AWG 1,5 4 2
7 w 2 GB Stat 3 4–5 2
8 w 2 GB AWG 3 5 2
9 w 2 GB Stat 1 4 1
10 m 1 GB, ASS, PS Stat 2 5 1
11 w 1 GB, Prader-Willy-Syndrom AWG 2 4–5 1
12 w 1 GB, PS AWG 2 5 1
13 m 1 GB, Trisomie 21 Ink 3 4 1
14 w 2 GB, KB AWG 2 4 3
15 m 1 GB, PS Ink 1 ≥ 5 1
16 w 1 (GB), ASS, KB aEW 1 ≥ 5 1
w weiblich, m männlich, GB geistige Behinderung, KB Körperbehinderung, PS psychische Störung, ASS Autismus-Spektrum-Störung, GdgB Grad der geistigen Behinderung, SEO-Grad Grad der sozioemotionalen Entwicklung, aEW ambulant betreutes Einzelwohnen, stat. Wohngruppe in stationärer Einrichtung, AWG Außenwohngruppe einer stationären Einrichtung, Ink. ambulant betreutes Wohnen in inklusiver Wohngemeinschaft
Leitfadenerstellung und Durchführung der Interviews
Die Interviews fanden im September und Oktober 2021 überwiegend als telefonische Befragungen oder über Videotelefonie (n = 4) statt. Die Personen mit geistiger Behinderung führten die Telefonate in einem ruhigen Raum selbstständig durch. Wenn gewünscht, war während der Interviews eine Betreuungskraft anwesend, um bei möglichen Kommunikationsproblemen zu unterstützen. Die Interviewdauer betrug zwischen 13 und 27 min (MW: 20 min 43 s, SD: ±4 min 52 s; Median 20 min 31 s). Die Interviews wurden mit Zustimmung der Proband:innen aufgezeichnet.
Der Interviewleitfaden wurde so gestaltet, dass mittels verschiedener Frageoptionen die relevanten Themenbereiche abgedeckt werden konnten, es gleichzeitig aber auch möglich war, dass die Befragten selbst Impulse setzen konnten. Daher konnten die Reihenfolge und die Anzahl der Fragen sowie die Frageoptionen in den Interviews leicht variieren [24]. Buchner [2] betont, dass dies besonders für die Interviewsituation bei MmgB wichtig ist, da hier oft eine situationsspezifische Modifikation des Vorgehens nötig ist, um das Gespräch aufrecht zu erhalten und ein möglichst breites Spektrum an Informationen zu gewinnen. Im Verlauf des Interviews wurden folgende Themenbereiche angesprochen (1) Erinnern an die Kindheit, (2) Vergleich der Kindheit mit der jetzigen Situation, (3) Vorstellungen vom Altsein (z. B. Charakteristika des Altseins, Einordnen des eigenen Alters etc.), (4) gesundheitliche Einschränkungen im Alter, (5) Wohnen im Alter, (6) Zeitgestaltung im Alter, (7) soziales Umfeld und Betreuung im Alter. Die einzelnen Fragenbereiche wurden jeweils zu Beginn mit Leitfragen bzw. Erzählaufforderungen eingeleitet (z. B. „Können Sie sich noch daran erinnern, wie Sie ein Kind waren?“). Falls die Proband:innen hierauf nur sehr knapp und einsilbig antworteten, wurden zusätzlich Aufrechterhaltungsfragen gestellt. Wenn auch dies nicht zum Ziel führte, wurde konkret nachgefragt. Es wurde dabei jeweils angestrebt, einen Bezug zur Situation des eigenen Altseins herzustellen. Nach dem Interview wurde den Studienteilnehmer:innen zugesichert, dass sie – wenn gewünscht – über die Ergebnisse der Studie informiert werden.
Datenbearbeitung, Datenanalyse und Gütekriterien
Die aufgezeichneten Interviews wurden im nächsten Schritt transkribiert und einer strukturierenden Inhaltsanalyse nach Mayring unterzogen [22]. Die Transkription der Interviews erfolgte durch Personen mit langjähriger Erfahrung im persönlichen Umgang mit MmgB. Basiselement der strukturierenden Inhaltsanalyse war die induktive Kategorienbildung. Hierbei wurde anhand von Textbausteinen durch Paraphrasierung und Abstrahierung bzw. Generalisierung der einzelnen Aussagen eine frühe Reduktion der Komplexität der Daten erreicht. Zudem wurde nach Gemeinsamkeiten und Unterschieden geschaut, um zentrale Themen in den Daten analytisch herauszuarbeiten. Auf dieser Basis wurden dann zentrale inhaltliche Kategorien identifiziert, die anschließend spezifiziert wurden. In einem Kodierleitfaden wurde definiert, welche Textbestandteile unter eine Kategorie fallen sollten. Darüber hinaus wurden konkrete Textstellen als Ankerbeispiele festgehalten. Wo ggf. Abgrenzungsprobleme zwischen Kategorien bestanden, wurden Kodierregeln formuliert, um eindeutige Zuordnungen zu ermöglichen [22]. Anschließend fand zur Kontrolle noch eine Rücküberprüfung statt, bei der das Kategoriensystem erneut mit dem Ausgangstext abgeglichen wurde [23]. Im Rahmen der Inhaltsanalyse wurde dann jede Kategorie im Hinblick auf die dort genannten Inhalte, die Häufigkeit ihrer Nennung und hinsichtlich eines möglichen Bezugs zu den Eigenschaften der Proband:innen (Alter, Geschlecht, Wohnform, Art und Grad der geistigen Behinderung, sprachliche/narrative Fähigkeiten, SEO-Grad) betrachtet.
Da die klassischen Gütekriterien aus der quantitativen Forschung (Objektivität, Reliabilität, Validität) hier nicht anwendbar waren, wurde stattdessen nach Transparenz, Intersubjektivität und Reichweite als häufig angegebene Gütekriterien der qualitativen Forschung geschaut [34]. Darüber hinaus wurden die Gütekriterien Gegenstandsangemessenheit und Regelgeleitetheit des Vorgehens nach Mayring [22] berücksichtigt.
Ergebnisse
Im Folgenden werden nun die von den Studienteilnehmer:innen angesprochenen Inhalte aus den 5 zentralen Themenbereichen (1) Vorstellungen vom Altsein, (2) gesundheitliche Einschränkungen im Alter, (3) Wohnen im Alter, (4) Zeitgestaltung im Alter und (5) soziales Umfeld und Betreuung im Alter zusammengefasst dargestellt. Dabei werden die einzelnen Abschnitte jeweils auch mit Zitaten unterlegt. Bei den Angaben zur Häufigkeit der Nennung einzelner Aspekte ist zu berücksichtigen, dass die Proband:innen oftmals mehrere Punkte angesprochen haben.
Vorstellungen vom Altsein
Elf der 16 Studienteilnehmer:innen gaben an, schon einmal über das Altern bzw. das Altsein nachgedacht zu haben, eine Person verneinte dies und 4 Proband:innen machten hierzu keine Aussage. Nur 5 Befragte mit stärkeren intellektuellen/sozioemotionalen Einschränkungen hatten schon einmal mit jemandem über das Altsein geredet. Meist war es die Mutter, in einem Fall die Schwester, von denen hier die Initiative ausging. Die meisten Studienteilnehmer:innen kannten jemanden, der ihrer Ansicht nach alt ist. Genannt wurden die Eltern (die in diesen Fällen zwischen 54 und 70 Jahre alt waren), die Großeltern (meist in den 80ern), Mitbewohner:innen in der Wohngruppe für ältere Menschen mit Behinderung und eine Physiotherapeutin in der Werkstatt. Ein Proband mit geringen kognitiven/sozioemotionalen Einschränkungen fragte hier zuerst, welches Alter denn gemeint sei:Interviewerin.1: Kennen Sie ältere Leute?
Proband (PB) 15: „Ehm … Ab was für’m Alter spricht ma dann …“
I.: Ja, das möchte ich Sie fragen? Ab wann ist man alt? Was meinen Sie?
PB15: „Ehm … (nachdenklich) Ab was is mer alt? Also gene … alt … wenn mer alt is? … Schwierig zu beantworte … Also meine Eltern sin jetzt … mein Vater is 64 und meine Mutter is 65. … Ich würd’ sagen, also jetzt von mei’m Gefühl her so … ich würde so ab 60 einstufen. … Also meine Meinung is, wie gesagt, so ab 60.“
Bei 5 Personen war es unklar, ob sie ihr Alter richtig einordnen konnten, eine Person gab hier keine Antwort. 10 Proband:innen schätzten das eigene Alter korrekt als jung, relativ jung oder „scho bissle alt“ (PB7) ein. Einige Personen mittleren Alters relativierten ihre Einschätzung, noch jung zu sein und erwähnten in diesem Zusammenhang z. B. ihre bereits vorhandenen Einschränkungen.I.: Und wie alt sind Sie?
PB1: „Ich werde jetzt kommenden Freitag siebenunddreißig.“
I.: Denken Sie, dass das alt ist?
PB1: „Wenn ich so meine Rückenbeschwerden manchmal […] betrachte, ja. … Ja, sag ma’s mal so, ich fühl mich schon irgendwie, schon noch so ziemlich jung, aber wenn halt meine Wehwehchen da sind, dann fühl ich mich schon manchmal alt.“
Auf die Frage, wie das denn ist, wenn man alt ist, nannten die Befragten überwiegend die zunehmenden Einschränkungen im Alter.I.: Wie ist es denn, wenn man alt ist? Was ist da anders als jetzt?
PB14: „Traurig. Ja.“
Betreuerin: Wenn ma alt wird, wie isch des?
PB14: „Nit gut. Weil älter.“
Insbesondere die Proband:innen mit geringeren kognitiven/sozioemotionalen Einschränkungen betonten, dass man dann noch mehr Krankheiten bekomme bzw. unter noch mehr gesundheitlichen Einschränkungen leide. Man werde unbeweglicher und habe (noch mehr) Schmerzen. Es gehe einem nicht mehr so gut, man brauche für manche Dinge länger und könne Vieles nicht mehr alleine machen. Man komme leicht ins Schwitzen, habe nicht mehr so viel Hunger und kriege Falten. Manche alten Menschen bekämen Alzheimer. Alte Menschen seien deswegen auf ärztliche Hilfe und auf Betreuung angewiesen, wären oft pflegebedürftig und brauchten meist Hilfsmittel wie einen Rollator oder Rollstuhl. Zwei dieser Proband:innen betonten, dass alte Menschen bzw. sie selbst im Alter dann in ein Altersheim oder in eine spezielle Wohngruppe für alte Menschen ziehen müssten.PB1: „Ja, das wäre auf jeden Fall, also Hilfe im hohen Alter oder ab ’nem gewissen Alter bräucht’ ich wahrscheinlich schon. … Also ich denke, so lang, dass ich alleine wohnen kann, bin ich glücklich. Aber wenn ich jetzt sagen muss, ich halt das jetzt hier in der Wohnung eh nicht mehr aus, oder es geht einfach nicht mehr und ich muss jetzt irgendwo hin, weil ich jetzt 24-h-Betreuung bräuchte, weil dann ist es halt so, dann muss ich mich halt dann auseinandersetzen. Aber zurzeit mach’ ich mir da über ’s Altwerden oder über ’s später in paar Jahren überhaupt gar keine so großen Gedanken net, weil vielleicht betrifft’s mich ja gar nicht so. … Oder nicht so schlimm, sag ich’s jetzt mal …“
PB15: „Ja, bissle schon und bissle Angst auch devor …“
I.: Warum haben Sie Angst davor?
PB15: „Dass … dass das mit der Gesundheit nachher nit mehr so funktioniere könnte und so … Dass Probleme auftreten in dem Alter werden, woran ich noch gar nicht gedacht habe.“
Manche Proband:innen waren der Ansicht, dass alte Menschen nicht mehr alleine rausgehen oder einkaufen gehen können, während andere meinten, dass man dann (nur) noch einkaufen und spazieren gehen, handarbeiten, basteln oder malen könne. Im Rahmen dieses Fragenbereichs wurde auch noch einmal konkret nachgefragt, ob man denn im Alter noch zur Arbeit bzw. in die Werkstatt geht. Neun Proband:innen war klar, dass man irgendwann in Rente gehen kann. Einige meinten, dass sie dann mehr Zeit haben würden. Andere befürchteten, dass es langweilig sei, wenn man nicht mehr zur Werkstatt gehen kann.PB12: „Eh alt ist, glaube ich, zum Teil so, dass man, wie soll ich’s sagen, ja da geht man dann in Rente, dann hat man viel Zeit für sich selber, ja.“
I.: Und finden Sie das gut, dass man dann in Rente geht und nicht mehr arbeiten muss?
PB12: „Ja, schon.“
I.: Wieso?
PB12: „Weil, man dann Zeit hat für sich selber.“
I.: Finden Sie das gut, dass man dann nicht mehr arbeiten muss, wenn man alt ist?
PB7: „Da wird’s ma bissle teils ganz langweilig, wenn i nichts mehr arbeiten dät.“
Es gab auch Studienteilnehmer:innen, die mit dem Begriff Rente nichts anfangen konnten. Eine Person war bereits aufgrund ihrer körperlichen/seelischen Einschränkungen in relativ jungem Alter berentet.
Alt werden wollten 10 der 16 Befragten. Einige ergänzten hier, dass sie gerne leben oder dass doch jeder Tag ein Geschenk sei, dass sie irgendwann schon, aber jetzt noch nicht alt werden wollen bzw. nur alt werden wollen, solange die Gesundheit mitmacht.I.: Möchten Sie denn gerne alt werden?
PB8: „Ja, klar.“
I.: Warum?
PB8: „Oh mei, ich fühl mich wohl.“
Eine Person wollte gerne 80 Jahre, eine andere 100 Jahre alt werden. 4 Personen betonten dagegen, dass sie generell jung bleiben oder nicht so schnell alt werden wollten, bzw. dass sie grundsätzlich nicht alt werden wollten, weil sie nicht sterben möchten oder weil man ja nicht wisse, was da alles auf einen zukomme.I.: Möchten Sie denn gerne alt werden?
PB9: „Naa, net so gern.“
I.: Warum?
PB9: „Weil ma net woaß, was dann alles auf ein zukommt.“
I.: Und was für Dinge können dann auf einen zukommen?
PB9: „Na, z. B. dass ma dann vielleicht nimmer so kann. Wie man will.“
In diesem Zusammenhang sprachen 4 Proband:innen – überwiegend mit nur geringeren kognitiven/sozioemotionalen Einschränkungen – von sich aus das Thema Sterben und Tod an.I.: Haben Sie sich früher schon mal Gedanken zum eigenen Altwerden gemacht?
PB2: „Hab ich auch schon mal gemacht.“
I.: Und was waren das so für Gedanken?
PB2: „Wie es aussieht, wenn man irgendwann nicht mehr lebt oder so, genau. Mhm, okay. Genau. Wie es dann zum Beispiel aussieht, ob man dann die wiedersieht oder so, keine Ahnung oder was auch immer.“
I.: Also verbinden Sie jetzt auch mit dem Altwerden, dass Sie dann sterben und was dann nach dem Tod passiert?
PB2: „Genau, genau.“
I.: Warum möchten Sie denn jetzt noch nicht alt werden?
PB7: „Weil, dann denk i wieder ans Sterben oder so. … Wenn i bissle erst 70 oder 75 … da denk i scho wieder an Tod oder so. Da will i no net so schnell mache … de Tod selber.“
I.: Sie verbinden dann das Altsein mit dem Tod?
PB7: „Ja.“
PB16: „Ja, ich denke, schon. Ich leb’ sehr, sehr gern’. Ich bin … lebensfroh, sag ich mal. Lebensbejahend. … Ich hoff’, ich werde alt. … Ich würde vielleicht dort hingehen wollen, in ein Hospiz, wenn ich sterbe. Vielleicht das dann schon, aber das ist jetzt mal was, wo ich auch große Schwierigkeiten hab’. Also mit dem Tod. Mit dem Gedanken. Sag’ ich mal. Also ich hoffe, das so weit wie möglich rauszögern zu können. Sag ich mal. Auch mit medizinischen Mitteln. Technischen Mitteln. Dass ich solang’ wie möglich leben kann.“
Die meisten Proband:innen erläuterten an dieser Stelle des Interviews noch von sich aus, wie sie ihr eigenes Altsein gestalten möchten. Fünf Personen erwähnten, dass sie dann in ein Haus bzw. eine Wohngruppe für ältere Menschen mit Behinderung ziehen werden bzw. möchten. Zwei der 4 Proband:innen mit den stärksten intellektuellen/sozioemotionalen Einschränkungen sagten, sie möchten im Alter die Natur genießen bzw. Kaffee trinken. Eine Person merkte an, dass das Älterwerden für Menschen mit Lernschwierigkeiten besonders schwer sei.PB13: „Weil behinderte Menschen mit Lernschwierigkeiten … ist das Älterwerden ein bisschen schwer. … Sehr schwer.“
Gesundheitliche Einschränkungen im Alter
Seheinschränkungen
Viele Teilnehmer:innen verbanden also bereits bei der ersten Frage das Altsein mit gesundheitlichen Einschränkungen. Auf die Frage, wie das für sie wäre, wenn sie im Alter nicht mehr so gut sehen könnten, meinten 11 der 16 Befragten, dass dies nicht so schön, nicht so gut, doof oder schlimm sei bzw. die Vorstellung ihnen Angst mache.PB12: „Ganz schwierig, also ja, also es schränkt halt wahnsinnig ein, denk i, und ich denk, dass es halt (…) eh sieht man halt nicht mehr/also kriegt halt nicht mehr so viel mit oder ja.“
PB15: „Also des wär’ schon weng schwierig, ja. Ja, die Vorstellung macht mir a bissle Angst. Weil, wenn i ni mehr richtig sehen kann, das würde ja bedeuten, ich wär’ dann auf Hilfe angewiesen.“
Dies waren fast ausschließlich Personen mit geringeren intellektuellen/sozioemotionalen Einschränkungen. Fast alle Personen mit einer mittleren geistigen Behinderung und einem SEO-Grad 4 konnten sich nicht in diese Situation hineinversetzen bzw. berichteten von jüngeren Menschen aus ihrem Umkreis, die schlecht sehen.I.: Manche können z. B. nicht mehr so gut sehen, wenn sie alt sind. Wie wäre das denn, wenn Sie nicht mehr so gut sehen könnten?
PB 14: „I seh’ gut“.
Es waren auch ausschließlich Personen mit geringeren Einschränkungen, die jemanden mit altersbedingten Seheinschränkungen kannten. Genannt wurden hier z. B. die Oma oder die Freundin der Mutter. Sechs Proband:innen kannten niemanden oder konnten hierzu nichts sagen. Auf die Frage, ob es denn im Fall einer Seheinschränkung im Alter Hilfsmittel gibt, mit denen die Situation verbessert werden könnte, nannten 6 Personen die Brille2, 2 die Lupe, eine Person Kontaktlinsen und eine weitere Person sprach allgemein von einer Sehhilfe. Genannt wurden darüber hinaus die Operation, Augentropfen, (Blinden)stock und (Blinden)hund. Die Personen, die jemanden mit altersbedingten Seheinschränkungen kannten, nannten hier meist die Hilfsmittel, die sie bei den betroffenen Personen gesehen hatten. Eine noch recht junge Frau mit sehr geringen Einschränkungen meinte, dass es dann, wenn sie alt sei, sicherlich neue Techniken gebe, um ihr zu helfen. Ein Mann mit stärkeren Einschränkungen war der Überzeugung, dass eine Heilung nur durch göttliche Hilfe möglich sei. Eine Frau wies zudem darauf hin, dass bei Personen mit Seheinschränkungen alles auf dem gleichen Platz stehen müsse. Zwei weitere Probandinnen würden in diesem Fall Betreuungskräfte um Hilfe bitten.
Höreinschränkungen
Auf die Frage, wie das für sie wäre, wenn sie im Alter nicht mehr so gut hören könnten, meinten nur 7 der 16 Befragten, dass dies nicht so gut, schwierig, schlecht oder doof sei bzw. dass ihnen die Vorstellung Angst mache. Auch hier waren es ausschließlich Personen mit leichteren Einschränkungen. Alle Personen mit einer mittleren geistigen Behinderung und einem SEO-Grad 4 konnten sich nicht in diese Situation hineinversetzen, erzählten von der eigenen Höreinschränkung in der Kindheit oder meinten, dass dies nicht schlimm sei. Bei dieser Frage gaben doppelt so viele Proband:innen an, jemanden mit einer solchen altersbedingten Einschränkung zu kennen als beim Thema Seheinschränkung. Genannt wurden Mutter, Vater, Oma, Opa, Tante und jemand aus dem Bekanntenkreis. Nur eine Person konnte hierzu nichts sagen. Unabhängig vom Behinderungsgrad gaben 11 Personen das Hörgerät als wichtiges Hilfsmittel bei Höreinschränkungen an.I.: Sie haben gerade eben gesagt, das Hörgerät [aus der Werbung] sieht man nicht. Wäre das für Sie wichtig, dass man das nicht sehen kann? Wenn Sie sowas brauchen würden?
PB15: „Eigentlich isch egal, Hauptsach’, durch des Hilfsmittel kann i gut hör’n.“
Eine Person mit geringen kognitiven Einschränkungen bemerkte hierzu, dass das Hören mit Hörgerät kein natürliches Hören sei. Genannt wurden darüber hinaus eine Operation, das Anwenden von Zeichen- bzw. Gebärdensprache, das Ablesen von den Lippen, lautes Sprechen und ein Telefon mit Lesevorrichtung. Auch hier wurde wieder darauf hingewiesen, dass es dann vielleicht schon eine neue, bessere Technik gebe bzw. dass man sich Hilfestellung von Betreuungskräften holen könne. Eine Person kannte keinerlei Hilfsmittel.
Geheinschränkungen
Auf die Frage, wie das für sie wäre, wenn sie im Alter nicht mehr so gut gehen könnten, meinten ebenfalls nur 7 der 16 Befragten, dass dies nicht so gut, schwierig, schlimm oder „beschissen“ sei. Für eine Person war die Vorstellung nicht so schlimm, eine andere Probandin meinte, mit Hilfsmitteln ginge das schon. Insgesamt 7 Proband:innen mit überwiegend stärkeren intellektuellen/sozioemotionalen Einschränkungen betonten, sie könnten noch gut laufen, berichteten allgemein davon, was man dann nicht mehr tun kann oder gingen gar nicht auf die Frage ein. Drei Probandinnen erzählten von ihren derzeit schon eingeschränkten Bewegungsmöglichkeiten.PB16: „Und dass ich, wenn ich mal einen Rollstuhl brauche, dann akzeptier’ ich das. Ich mein, ich saß schon mal im Rollstuhl. Also ich … ja, das ist jetzt nicht was völlig Neues für mich. Aber ich hoff’, dass ich, wie gesagt, auf den Beinen bleib und wenn es mit dem Rollator ist. Im Haus oder so. Und draußen im Rollstuhl. … Es gibt, glaub ich, sehr wenig Dinge, wo ich sagen würde, ich würde damit nicht leben können. Weil ich eben schon behindert bin. Da weiß ich’s schon. … Ja, wie man Hilfe bekommt.“
Anders als beim eingeschränkten Sehen und Hören nannte nur eine Probandin die Oma als Person mit altersbedingter Geheinschränkung. Mehrere Teilnehmer:innen berichteten von (jüngeren) Personen mit einer Gehbehinderung im unmittelbaren Umfeld oder bejahten, jemanden zu kennen, ohne näher darauf einzugehen. Unabhängig vom Behinderungsgrad gaben neun Personen den Gehwagen/Rollator als wichtiges Hilfsmittel bei Einschränkungen des Gehens an. Fünf Personen nannten darüber hinaus den Rollstuhl, eine Person den Gehstock, und eine Person sprach allgemein von anderen Fortbewegungsmitteln. Weitere Optionen waren für die Befragten, sich Hilfestellung von Betreuungskräften zu holen, von ihnen versorgt zu werden, zum Arzt zu gehen bzw. im Bett zu liegen. Fünf Proband:innen wiesen darauf hin, dass hier auch Krankengymnastik, sich fit halten, regelmäßig laufen oder Sport machen und gesunde Ernährung wichtig seien. Eine Person betonte, dass sie keine Hilfsmittel brauche.I.: Es gibt ja z. B. auch Hilfen. Wenn man z. B. einen Rollator nimmt oder so was. Haben Sie das schon Mal überlegt?
PB8: „Naa, so was brauch i net.“
Kognitive Einschränkungen
Für 10 der 16 Proband:innen wäre es nicht so gut, nicht so schön, „e bissele doof“, blöd, schwierig, schlimm, ganz schrecklich oder „Scheiße“, wenn sie im Alter nicht mehr so gut denken könnten wie jetzt. Eine Person sah das nicht als Problem an, 2 weitere Personen konnten sich dies nicht vorstellen bzw. erzählten von Menschen aus ihrer Umgebung mit Gedächtnisproblemen, und eine Person betonte, dass sie gut denken könne.PB6: „Mir passiert sowas gar nicht.“
PB8: „Also denken kann i schon noch gut. Ja. [….] Also, wissen Sie was, aber mein Gedächtnis funktioniert …“
Auch hier kannten nur 3 Proband:innen jemanden mit altersassoziierten kognitiven Einschränkungen (Oma, Onkel und – auf Nachfrage einer Betreuerin – eine ehemalige Mitbewohnerin). Vier Personen mit stärkeren kognitiven/sozioemotionalen Einschränkungen konnten hierauf keine Antwort geben bzw. betonten, sie kennen niemanden, der schlecht denken kann.PB2: „Für mich wäre das kein Problem.“
I.: Wieso wäre das kein Problem für Sie?
PB2: „Das weiß ich selber auch nicht.“
I.: Aber Sie fänden es nicht so schlimm, wenn Ihnen das passiert?
PB2: „Genau.“
I.: Wenn jemand schlecht denken kann, kann man dann etwas tun, dass er sich trotzdem gut fühlt?
PB2: „Ja.“
I.: Und was kann man da tun?
PB2: „Zum Beispiel Hilfe holen. … Beim Betreuer oder so.“
I.: Kennen Sie denn jemanden, der schlechter denken kann, weil er jetzt alt ist?
PB2: „Das weiß ich jetzt grad nicht.“
Neun Personen gaben unabhängig vom Behinderungsgrad und z. T. auf Nachfrage an, dass die wichtigste Hilfe hier die Unterstützung bzw. Hilfestellung sei. So könnten Betreuungskräfte z. B. immer wieder an Vergessenes erinnern. Mehrmals genannt wurden auch Gedächtnishilfen, Gedächtnistraining, Gedächtnisspiele und Sudoku. Einzelne Personen meinten auch, die Betroffenen sollten mehr Wasser trinken bzw. es gebe hierfür Medikamente, andere gaben Musik, Malen und Tiertherapie als Hilfsmöglichkeiten an. Weitere Möglichkeiten sahen die Befragten im Zeigen von Zuneigung, im Trösten und Helfen, dem Äußern „guter Worte“, dem gemeinsamen Kaffee trinken oder spazieren gehen. Ein Proband betonte, dass hier keine medizinische Hilfe möglich sei, eine andere Probandin, dass sie hoffe, dass es bis dahin auch hier neue Techniken geben werde. Mehrere Personen gaben keine Möglichkeiten der Hilfestellung an, sondern beschrieben, wie das ist, wenn man nicht mehr so gut denken kann oder sagten, dass sie auch jetzt schon manche Dinge vergessen.PB10: „Da wär’ ich durcheinander und verstreut, wenn ich nicht mehr g’scheit denken könnt. Dann kenn ich mich nimmer aus, wo vorne und hinten ist, welche Sache da … ist, da kenn ich mich nimmer aus.“
PB9: „Wenn ma’ was vergisst oder was, dann sag’n die Erzieher oder die Betreuer manches Mal: Du des und des hast vergessen. Des und des musst no’ mache.“
Eine Teilnehmerin mit stärkeren kognitiven/sozioemotionalen Einschränkungen meinte, die Betroffenen müssten dann im Bett liegen. Sehr viele und tiefgehende Gedanken hierzu hatte sich bereits eine Probandin mit nur leichten Einschränkungen gemacht:PB16: „Ich denke, ein angenehmes Leben wäre das Ziel. Wenn’s nur akzeptabel ist, das wäre zu wenig. Also das ist für die meisten Menschen zu wenig. Aber ich denke, die Menschen, die dement sind, sollten weiterhin gefördert werden. Also mit Musik z. B., also mit Tieren, Tier-Therapie gibt’s ja im Krankenhaus. Und man sollte noch schauen, was die Menschen früher gemacht haben. Was sie gern gemacht haben. Als Kinder. Was sie gegessen haben, was sie gespielt haben. Und dann das eben, zumindest mit Bildern arbeiten. Je nachdem, was sie dann können. Ich denk’, man kann viel machen. Man kann auch vorbeugen mit Denksport, mit Aufgaben oder so.“
Wohnen im Alter
Die Hälfte der Befragten möchte auch im Alter dort wohnen bleiben, wo sie derzeit wohnen (z. B. in ihrer Wohngruppe oder im ambulant betreuten Einzelwohnen). Vier Proband:innen würden dann gerne in eine Altersgruppe ihres Wohnheims oder ein spezielles Altersheim für MmgB ziehen. Einige wussten schon genau, welche Einrichtung bzw. Wohngruppe das sein soll.PB8: „Also wenn, dann würd ich in die Lebenshilfe rüberziehn, nach L. … Also zur E. nüber, wenn da dann noch n Platz frei ist.“
PB12: „Also bei uns ist es ja so, wenn ich in einer Einrichtung lebe, dann kommt man halt so ja in ein Altenstock. … Das ist, also bei uns ist es so in H., wo man für ältere Leut’, die dann da untergebracht sind.“
Genannt wurden zudem der Umzug in eine Parterrewohnung, in ein Mehrgenerationenhaus, nach Hause zu den Geschwistern und das Zusammenziehen mit der Freundin. Die wenig realistischen Möglichkeiten, im Alter nach Hause zu den Geschwistern zu ziehen bzw. mit der Freundin zusammenzuziehen, wurden von Personen mit einem mittleren Grad einer geistigen Behinderung und einem SEO-Grad 4 bzw. 4–5 geäußert. Den Umzug in eine Parterrewohnung bzw. in ein Mehrgenerationenhaus erwogen Personen mit einer leichten geistigen Behinderung und einem SEO-Grad ≥ 5. Unabhängig vom Behinderungsgrad war der Wunsch, auch im Alter dort wohnen zu bleiben, wo man derzeit wohnt. Den Umzug in eine Altersgruppe eines Behindertenwohnheims oder ein spezielles Altersheim für MmgB nannten v. a. Personen mit leichten bis sehr leichten kognitiven/sozioemotionalen Einschränkungen.
Keinesfalls in ein Altersheim wollten 7 Personen ziehen, während andererseits das Altersheim von 4 Personen durchaus als Wohnmöglichkeit im Alter erwogen wurde. Drei Personen konnten sich vorstellen, dann in einem Seniorenheim, nicht jedoch in einem Altersheim zu leben, wobei nicht klar wurde, wo sie hier den Unterschied sahen. Die z. T. sehr bestimmt und heftig geäußerte Aussage, nicht ins Altersheim zu wollen, wurde unabhängig vom Behinderungsgrad genannt. Als Gründe gaben die Proband:innen an, dass es dort zu langweilig sei und die Bewohner:innen dort nicht so gut betreut würden.PB1: „Weil ich manchmal auch schon mitbekommen hab, dass die im Altersheim, die Leute, nicht gut betreut werden, und das Essen nicht gut ist und, und die nicht so viel mit dene Bewohner auch machen, die Pflegekräfte. … Und ich bin halt eine, die wo des halt nicht so möchte, sag i jetzt a mal.“
PB4: „Deswegen wollt ich, […] ich geh deshalb nicht ins Altersheim sowas, sondern da drüben in Altersheim, dann langweiliger als hier in der Gruppe.“
Auf die Frage, wo sie denn gerne leben möchten, wenn es aufgrund einer schweren Erkrankung im Alter nicht mehr möglich sei, in ihrer jetzigen Wohnung bzw. einer Altenwohnung zu bleiben, antworteten jeweils vier Personen, dass sie dann nicht ins Alters- oder Pflegeheim bzw. nicht in ein Krankenhaus gehen möchten. Sechs Proband:innen würden dann in ein Altenpflegeheim oder ein Hospiz wechseln. Fast alle betonten jedoch, dass sie dies nur im Notfall tun würden oder wenn sie sterben müssten. Dies waren v. a. Personen mit einer leichten geistigen Behinderung und einem SEO-Grad ≥ 5. Auch hier gaben wieder einige Befragte an, dass sie dann in ihrer jetzigen Wohnung bleiben, ins Alters- oder Seniorenheim wechseln bzw. in eine Altersgruppe ihres Wohnheims oder ein spezielles Altersheim für MmgB ziehen würden. Dies waren überwiegend Personen mit etwas stärkeren kognitiven/sozioemotionalen Einschränkungen. Eine Person wünschte sich, dann in ein Haus zu ziehen, wo man gut aufgehoben ist und versorgt wird. Ein anderer Proband betonte, dass er in diesem Fall nicht zu den Eltern ziehen würde, um ihnen nicht zur Last zu fallen, ohne nachvollziehen zu können, dass die Eltern dann ja wahrscheinlich selbst nicht mehr leben würden.PB15: „Weil ich kann mir net vorstellen, bei meine Eltern wieder noch einzuzieh’n und mich von dene pflegen zu lassen, weil das wär für meine Eltern bestimmt au net leicht. Ich will ja, wie g’sagt, meiner Familie auch net zur Lascht fallen. Obwohl se für mich da sind. Aber da hätt i kein gutes Gefühl debei.“
Insbesondere bei der Frage nach dem gewünschten Aufenthaltsort im Fall einer schweren Krankheit im Alter wurde deutlich, dass sich Personen mit einem mittleren Grad einer geistigen Behinderung und/oder einem SEO-Grad 4 bzw. 4–5 deutlich schlechter in die beschriebene Situation hineinversetzen konnten. Sie tendierten dazu, auf Signalwörter in der Frage wie „krank“ oder „alt“ mit entsprechenden Begriffen wie „Krankenhaus“ bzw. „Altersheim“ zu antworten oder konnten sich gar nicht in die Situation hineinversetzen, alt und krank zu sein.I.: Da gibt es ja zum Beispiel die Möglichkeit, im Krankenhaus, im Altersheim oder im Hospiz betreut zu werden.
PB14: „Ja.“
Betreuerin: Also möchtest Du dann ins Krankenhaus?
PB14: „Nee. … G’sund.“
Zeitgestaltung im Alter
Ähnlich wie bei den Wünschen bezüglich des Wohnortes nannten Proband:innen auch bei der Frage, was sie im Alter gerne den ganzen Tag über machen möchten, oft die Dinge, mit denen sie aktuell ihre Zeit verbringen.I.: Und was wollen Sie dann machen, wenn Sie alt sind, den ganzen Tag?
PB2: „Das weiß ich noch nicht.“
I.: Was machen denn alte Leute so den ganzen Tag?
PB2: „Manche stricken. Genau, und ich tu ja stricken.“
I.: Also möchten Sie das dann auch machen, wenn Sie alt sind?
PB2: „Genau.“
I.: Und was werden Sie dann den ganzen Tag machen, wenn Sie alt sind?
PB7: „… ab und zu a Kunst malen und i war bei de Frau H. bei Lesegruppe scho dabei und was ham ma noch? Trauergruppe hab i bei der Frau H. scho gemacht.“
I.: Das wollen Sie dann auch machen, wenn Sie alt sind?
PB7: „Ja, Lesen ist bei mir […], Malen und das Lesen und sowas ist mei Hobby.“
I.: Sie wollen, wenn Sie alt sind, dann auch Ihre Hobbies machen.
PB7: „Ja, ganz genau.“
Andere beschrieben, was alte Menschen, die sie kennen, tagsüber tun. Nur Personen mit geringeren Einschränkungen waren dabei in der Lage zu berücksichtigen, dass man im Alter aufgrund gesundheitlicher Einschränkungen manche Dinge vielleicht nicht mehr tun kann.PB12: „Ja, also bei uns, wenn ich das so mitkrieg’, die geh’n spazieren und spielen […] so Spiele, dann ja, das ist halt ganz unterschiedlich, wie jeder halt, glaube ich, auch drauf ist oder halt wie man das noch machen kann.“
Einige Probandinnen wiesen darauf hin, dass es für sie die Möglichkeit gibt, auch im Alter noch an tagesstrukturierenden Maßnahmen teilzunehmen.PB9: „Wenn ich no kann, wie g’sagt, dann in die TENE3 geh’n. Wenn i no kann.“
Unabhängig vom Behinderungsgrad nannten die Proband:innen bei dieser Frage am häufigsten spazieren gehen bzw. raus gehen, etwas anschauen, Ausflüge machen oder in eine Ferienfreizeit fahren. Ebenfalls häufiger genannt wurden Handarbeiten wie Stricken und Häkeln (von Männern und Frauen), aber auch Spiele spielen, Kreuzworträtsel oder Sudoku lösen und (Zeitung‑)Lesen bzw. in die Lesegruppe gehen. Jeweils nur 1‑ oder 2‑mal angegeben wurden Schwimmen und Massage, Malen und Basteln sowie Musik, Hörbücher oder Radio hören, Filme anschauen und Fernsehen. Zwei Personen wollten im Alter v. a. Pause machen, d. h. für sich alleine im Zimmer sein bzw. viel nachdenken. Eine Person mit nur leichten Einschränkungen betonte, dass sie auch im Alter so lange wie möglich reiten und mit Tieren zusammen sein möchte. Zudem möchte sie ihre Online-Kontakte aufrechterhalten. Mehrere Proband:innen legten Wert darauf, dass sie auch im Alter gerne mit anderen Menschen bzw. mit Freunden zusammen sein, sich unterhalten oder gemeinsam Kaffee trinken möchten. Dies waren meist Personen, die schon einmal in einem Altersheim zu Besuch waren und es dort langweilig fanden.
Soziales Umfeld und Betreuung im Alter
Auf die Frage „Mit wem möchten Sie denn zusammen sein, wenn Sie alt sind?“ wurden v. a. Freunde, die beste Freundin oder der bzw. die Freund:in bzw. Partner:in genannt. Einige Personen blieben bei dieser Frage recht allgemein. Sie möchten im Alter gerne mit anderen Menschen, mit lieben Menschen oder mit Leuten zusammen sein, mit denen sie sich gut verstehen. Auch konkrete Mitbewohner:innen und Betreuungskräfte wurden hier mit ihren Namen genannt. Dass einige der Befragten große Probleme hatten, sich vorzustellen, dass auch ihr Umfeld mitaltern wird, wurde v. a. bei der Nennung der Eltern oder Geschwister deutlich. Eine Probandin sagte, sie habe sich noch keine Gedanken gemacht, mit wem sie im Alter zusammen sein möchte und wer sie dann (auch im Fall einer schweren Krankheit) betreuen soll.
Fast alle Befragten wollten im Alter von ihren Betreuungskräften oder von speziellen Pflegekräften versorgt werden. Auch hier wurden z. T. Namen der aktuellen Betreuer:innen bzw. Personen eines Fachdienstes genannt.PB1: „… aber im Großen und Ganzen möchte ich von dem Team, wo ich jetzt betreut werde, auch betreut werden.“
I.: Also wollen Sie da ja keine Veränderung haben bei der Betreuung.
PB1: „Nein, weil, ich bin mit dem Betreuer sehr zufrieden.“
Eine Probandin nannte ihre gesetzliche Betreuerin. Einige Proband:innen betonten, dass es jemand Bekanntes sein sollte, keine fremde Person. Es waren nicht nur Personen mit stärkeren Einschränkungen, die hier nicht berücksichtigten, dass die von ihnen genannten Personen (z. B. Verwandte wie Mutter oder Bruder) ebenfalls älter werden. Ein weiterer Proband meinte jedoch explizit, dass er dann von „den Jüngeren“ betreut werden möchte. Die Probandin, die im Alter gerne in einem Mehrgenerationenhaus leben möchte, wünschte sich, dass ihre Mitbewohner:innen dann für sie da sein könnten.
Auf die Frage, wer sie denn bei einer schweren Krankheit im Alter betreuen bzw. bei ihnen sein soll, gaben nur wenige Proband:innen Betreuungskräfte, Krankenpflegepersonal oder Ärzt:innen an. Einige nannten jedoch auch hier wieder Namen ihrer Betreuungskräfte oder äußerten sich sehr allgemein (gute Menschen; jemand, den ich kenne; die Zuständigen). Besonders häufig wurden hier enge Freunde sowie Verwandte wie Eltern, Geschwister, Oma oder Nichte genannt, bzw. es wurde explizit darauf hingewiesen, dass man in so einem Fall die Eltern nicht in Anspruch nehmen möchte.I.: Wenn Ihnen das passiert, wenn Sie so krank sind, dass sie nicht mehr in der WG bleiben können, wer soll dann bei Ihnen sein? Wer soll Sie da begleiten?
PB10: „Ja, meine Eltern sollen mich begleiten.“
I.: Wenn Sie alt sind, dann sind Ihre Eltern ja auch schon sehr alt und können das vielleicht nicht mehr.
PB10: „Mhm.“
I.: Fällt Ihnen da vielleicht jemand anderes ein, den Sie da bei sich haben wollen?
PB10: „Vielleicht Oma.“
I.: Aber die Oma ist ja dann noch älter.
PB10: „Mhm.“
Überraschenderweise schienen sich bei dieser Frage auch Personen mit sehr geringen intellektuellen/sozioemotionalen Einschränkungen nicht im Klaren darüber zu sein, dass die Eltern oder die Oma dann ebenfalls deutlich älter wären und somit für eine Betreuung bzw. Begleitung nicht mehr in Frage kämen.
Ergebnisdiskussion
Bedeutung der Fähigkeit zum Hineinversetzen ins eigene Altsein
Bislang war kaum etwas darüber bekannt, wie sich MmgB ihr eigenes Alter vorstellen. Insbesondere war unklar, ob sie grundsätzlich überhaupt dazu in der Lage sind, sich in ein zukünftiges Selbst hineinzuversetzen oder ob ihre Fähigkeit hierzu nicht vielmehr von der Art und vom Grad ihrer geistigen Behinderung abhängt. Im Rahmen einer ersten explorativen Studie [16] auf der Basis der hier diskutierten fokussierten Interviews konnten wir Anzeichen dafür finden, dass die Proband:innen mit leichter geistiger Behinderung, sehr guten sprachlichen/narrativen Fähigkeiten und einem SEO-Grad 5 im Durchschnitt eine deutlich bessere Fähigkeit aufwiesen, sich in zukünftige Situationen wie das eigene Altsein hineinzuversetzen (Fähigkeit zum EFT), als solche mit stärkerer geistiger Behinderung, eingeschränkteren sprachlichen Möglichkeiten und SEO-Grad 4. Es fanden sich zudem erste Hinweise darauf, dass auch Geschlecht, Alter und Art der Behinderung die EFT-Fähigkeit beeinflussen können. In der folgenden Diskussion wird dies an vielen Stellen ebenfalls deutlich, was die Resultate unserer ersten Studie nochmals unterstreicht. Welche Bedeutung die eingeschränkte Fähigkeit zum episodischen Zukunftsdenken bei MmgB hinsichtlich ihrer Fähigkeit zur aktiven Teilhabe an Maßnahmen der Gesundheitsförderung und an inklusiven Forschungs- und Public-Health-Projekten haben kann, wird zum Schluss dieser Arbeit diskutiert.
Vorstellungen vom Altsein und Einordnen des eigenen Alters
Nachdenken über das Altern und das Alt-Sein
Von alleine über das Altern und Alt-Sein nachgedacht hatten v. a. Proband:innen mit geringeren intellektuellen/sozioemotionalen Einschränkungen. Personen mit stärkeren Einschränkungen hatten sich hierzu nur dann Gedanken gemacht, wenn sie zuvor aus dem familiären Umfeld darauf angesprochen worden waren. Bezeichnenderweise ging die Initiative dann von weiblichen Familienangehörigen (Mutter, Schwester) aus. Insbesondere die Mütter haben nach Seltzer et al. [30] in der Regel eine besonders starke emotionale Bindung zu ihren erwachsenen Kindern mit geistiger Behinderung und kümmern sich deutlich intensiver als andere um die Aufrechterhaltung des Kontakts, auch wenn die Kinder bereits seit langem in einer Behinderteneinrichtungen leben. Es ist anzunehmen, dass sie das Thema „Was passiert mit Dir, wenn ich alt sein werde?“ spätestens dann ansprechen, wenn es absehbar ist, dass sie sich bald nicht mehr um ihr Kind kümmern können. Einige Angehörige hatten offenbar bereits eine Lösung hierfür gefunden (z. B. eine mögliche Betreuung in einer Wohneinrichtung für alte MmgB), mit denen ihre nun ebenfalls schon älteren Töchter einverstanden waren.
Einschätzen des eigenen Alters und des Alters anderer Personen
Bei der Einschätzung des eigenen Alters und des Alters anderer Personen (jung oder alt?) hatten Proband:innen mit stärkeren Einschränkungen Probleme. Personen mit geringeren Einschränkungen gelang das in der Regel recht gut. Sie konnten z. T. sogar erläutern, warum sie aufgrund ihres kalendarischen Alters eigentlich noch jung seien, sich aber andererseits – etwa aufgrund von körperlichen Einschränkungen oder im Vergleich zu noch jüngeren Leuten – manchmal schon etwas alt fühlten. Wie bereits in unserer explorativen Studie diskutiert [16], nimmt u. a. die Gedächtnisleistung bei normal entwickelten Kindern erst im Alter von drei bis fünf Jahren deutlich zu. Ursache hierfür ist die ontogenetisch relativ später Ausreifung einiger Endhirnbereiche (z. B. des Hippocampus; [31]). Das hat Folgen für die EFT-Fähigkeit, aber auch für die Fähigkeit, Zeit in ihrer Dauer einzuschätzen [9, 25] und dies dann mit gespeichertem Wissen (z. B. „Alte Menschen haben Falten.“) zu verknüpfen. Entsprechend zeigen die Antworten der SEO-4-Proband:innen4 deutlich, dass diese zwar durchaus bereits Anzeichen für das Alt-Sein nennen konnten (wie etwa die Falten), dass sie aber Probleme damit hatten, ihr Alter bzw. das Alter anderer Menschen einzuschätzen – was SEO-5-Personen hingegen gut gelang.
Altersbild
Die meisten der befragten Proband:innen verknüpften Alt-Sein mit gesundheitlichen Einschränkungen, mit dem Angewiesen-Sein auf Hilfe und damit, dass man dann nicht mehr alles machen kann. Auch bei Burke et al. [4] gab fast die Hälfte der befragten MmgB negative Ansichten über die Folgen des Alterns an. Anders als in der Literatur, die diese Konzentration auf körperliche bzw. psychisch-kognitive Einbußen und die daraus folgende Hilfebedürftigkeit als ein in unserer Gesellschaft weit verbreitetes negatives Altersbild (mit einer Minderbewertung des Alters; [1, 3]) bezeichnet, waren die Aussagen der Proband:innen hinsichtlich des Alters jedoch durchaus nicht immer negativ. Viele der Befragten wollten alt werden, meist in der Hoffnung oder Annahme, dass sie persönlich nicht oder nicht so stark von gesundheitlichen Einschränkungen betroffen sein werden. Dass sie dann möglicherweise nicht mehr in ihrer jetzigen Wohnung bleiben können und ggf. auf Hilfsmittel oder Hilfestellung angewiesen sein werden, betrachteten die meisten sehr pragmatisch. Einige meinten sogar dazu, dass ihnen diese Situation ja bekannt sei. Dies stimmt überein damit, dass auch bei Burke et al. [4] nur knapp 25 % der Befragten Bedenken oder Sorgen hinsichtlich des Älterwerdens hatten. Knapp zwei Drittel der Befragten meinten dort, dass alte Leute die meisten Sachen noch so tun können wie junge Leute (auch Sport und Bewegung sowie soziale Aktivitäten) und dass auch alte Menschen MmgB unterstützen und betreuen können. Nur wenige machten sich Sorgen wegen körperlicher Veränderungen oder Krankheiten bzw. dem Verlust der Unabhängigkeit. Allerdings sah sich eine große Mehrheit der Befragten wohl gar nicht in der Lage, die Frage nach möglichen Sorgen zu beantworten. Es könnte daher sein, dass an dieser Stelle v. a. Personen mit geringeren kognitiven/sozioemotionalen Einschränkungen antworteten, die diese Fragestellung besser nachvollziehen konnten.
Überraschenderweise verknüpften nur wenige Personen von sich aus das Thema „Alt-Sein“ mit „in Rente gehen/nicht mehr arbeiten müssen“. Bei einigen Aussagen schimmerte durch, dass man dann ja noch nicht so richtig alt sei. Einige wollten gerne länger arbeiten gehen, weil es sonst zu langweilig sei oder weil sie ja Geld verdienen müssten. Dass sie dann Rentenzahlungen bekommen, ohne arbeiten zu müssen, war diesen Personen unklar bzw. unverständlich. Bereits in einer früheren Studie zur Situation von MmgB während der COVID-19-Pandemie („coronavirus disease 2019“) war deutlich geworden, dass einige MmgB nicht verstehen, warum sie in manchen Situationen Geldleistungen bekommen, obwohl sie nicht arbeiten [14, 35] Schäper et al. [29] betonen in diesem Zusammenhang, dass insbesondere das Ausscheiden aus dem Arbeitsleben (meist aus der Werkstatt für behinderte Menschen [WfbM]) für viele MmgB zu einem Verlust der gewohnten Tagesstruktur und der bisherigen sozialen Kontakte führe. Es seien daher Maßnahmen nötig, die frühzeitig auf den Ruhestand vorbereiten, wie z. B. „die (Wieder)entdeckung von Hobbys und Freizeitaktivitäten fördern, aber auch die Etablierung zusätzlicher tagesstrukturierender Angebote“.
Verknüpfung mit Sterben und Tod
Nur wenige Proband:innen (überwiegend Personen mit geringen kognitiven/sozioemotionalen Einschränkungen) kamen von sich aus während des Interviews auf das Thema „Sterben und Tod“ zu sprechen und verknüpften dabei „alt sein“ mit „sterben müssen“. Auch in der umfangreichen Studie von Burke et al. [4] gaben nur 20 der 367 Studienteilnehmer:innen mit geistiger Behinderung an, dass es ihnen Sorgen bereite, wenn sie an das eigene Alter denken, da man dann ja sterben müsse.
Gestaltung des eigenen Alters
Es waren v. a. Personen mit leicht- bis mittelgradigen intellektuellen/sozioemotionalen Einschränkungen, die schon einmal mit ihren Angehörigen darüber gesprochen hatten, wo sie im Alter leben und betreut werden sollen, und die daher sehr konkrete, gleichzeitig aber auch wenig flexible Vorstellungen von ihrem zukünftigen Leben im Alter hatten (PB8: „… und zu der zieh ich dann auch. […] Weil, da beißt die Maus kein’ Faden ab.“; PB9: „Ich muss dann zu die Älteren später mal in’d Gruppen nauf.“). Aus der Art ihrer Aussagen hierzu lässt sich schließen, dass sie dabei meist die Vorstellungen der Angehörigen unreflektiert übernommen haben. Im Gegensatz dazu hatte sich z. B. die Probandin mit den geringsten intellektuellen/sozioemotionalen Einschränkungen bereits sehr intensive, eigenständige Gedanken über ihr eigenes Altern und ihre Lebensumstände im Alter gemacht. Bei den meisten Personen mit stärkeren Einschränkungen zeigte sich immer wieder, dass sie kaum oder nicht in der Lage waren, sich in diese Situation hineinzuversetzen.
Bedeutung von gesundheitlichen Einschränkungen im Alter
In Deutschland leiden mehr als 80 % der 75- bis 79-Jährigen Durchschnittsbevölkerung an mehreren chronischen Erkrankungen [26]. Ab einem Lebensalter von 85 Jahren berichten über 70 % der Menschen von Einschränkungen aufgrund von Störungen der Sinnesfunktionen (v. a. beim Sehen und Hören) bzw. der körperlichen Funktionen (u. a. Bewegungs- und kognitive Einschränkungen; [10]).
Verlässliche epidemiologische Daten zu gesundheitlichen Einschränkungen bei alten MmgB wurden in Deutschland bislang nicht erhoben. Eine Studie aus dem Jahr 1998 fand in Großbritannien bei älteren MmgB (> 65 Jahre) einen höheren Prozentsatz an Harninkontinenz, Immobilität, Hörstörungen, Arthrose, Bluthochdruck und zerebrovaskulären Erkrankungen im Vergleich zu jüngeren MmgB [5]. Zander betont, dass der individuelle Hilfebedarf von MmgB – insbesondere, wenn sie in einer Einrichtung leben – oftmals schon deutlich früher ansteigt als in der Durchschnittsbevölkerung [35]. Bereits seit längerem ist bekannt, dass etwa das Risiko, im Verlauf des Lebens eine Demenz zu entwickeln, bei Menschen mit Down-Syndrom erheblich größer ist als in der Durchschnittsbevölkerung. Die Erkrankung setzt hier viel früher ein, sodass schon im Alter von 55 bis 59 Jahren fast ein Drittel der Menschen mit Down-Syndrom betroffen ist. Die Demenz führt dann zu einer hohen Rate an vorzeitigen Todesfällen [6, 15].
In unserer Untersuchung konnten sich Proband:innen mit leichteren intellektuellen bzw. sozioemotionalen Einschränkungen deutlich besser in die Situation hineinversetzen, im Alter mit einer Seh‑, Hör‑, Geh- oder kognitiven Behinderung zu leben, als Personen mit stärkeren Einschränkungen. Diejenigen, die sich in die Situation zumindest ansatzweise hineinversetzen konnten, fanden diese Vorstellung nicht so schön bis schlimm oder sogar angstauslösend. Auch hier konnten sich dies Personen mit einem SEO-Grad 4 jedoch kaum oder überhaupt nicht vorstellen. Besonders deutlich zeigten sich die Unterschiede bei dem Versuch, sich in (zusätzliche) altersbedingte kognitive Einschränkungen hineinzuversetzen, am wenigsten deutlich war dies bei der Vorstellung von Höreinschränkungen im Alter. Die meisten Proband:innen gingen jedoch recht pragmatisch mit der Vorstellung um, irgendwann altersbedingt etwas nicht mehr so gut machen zu können, wie dies aktuell der Fall ist. Oftmals klang in ihren Antworten an, dass für sie entsprechende Einschränkungen aufgrund ihrer Behinderungen bereits etwas Normales, Bekanntes sind, mit denen man leben muss und kann. Sie nannten eine breite Palette an in der Regel adäquaten Hilfsmitteln bzw. Hilfsmöglichkeiten, wie sie sie beispielsweise bei Angehörigen gesehen hatten oder die sie und ihre Mitbewohner:innen bereits heute nutzten.
Vorstellungen vom Wohnen im Alter
Die meisten der befragten MmgB würden auch im Alter gerne in ihrem Zuhause bleiben, also weiterhin dort wohnen, wo sie derzeit leben (etwa in ihrer aktuellen Wohngruppe oder im ambulant betreuten Einzelwohnen). Damit unterscheiden sie sich kaum von der Durchschnittsbevölkerung. Nach einer für Deutschland repräsentativen Untersuchung möchten mehr als zwei Drittel der Befragten (Alter > 50 Jahre) mit 70 Jahren gerne noch zu Hause wohnen [19]. Dabei ist der von einer Probandin unserer Studie genannte Umzug in eine altersgerechte Parterrewohnung eine Option, die sich auch viele Menschen ohne Behinderung vorstellen könnten. Die von einer weiteren Probandin mit nur leichten Einschränkungen genannte Möglichkeit, im Alter in ein Mehrgenerationenhaus zu wechseln, ist auch für etwa ein Drittel der Durchschnittsbevölkerung eine akzeptable, wenn auch angesichts der niedrigen Zahl der derzeit deutschlandweit geförderten Mehrgenerationenhausprojekte, in der Praxis oft nicht umsetzbare Alternative. Deutlich weniger als ein Viertel der Durchschnittsbevölkerung möchte mit 70 Jahren in einem Pflegeheim, einer Seniorenresidenz oder im Betreuten Wohnen mit/ohne Pflegeheimanschluss leben. Für einen Teil der von uns befragten MmgB war die Vorstellung, im Alter in eine spezielle Gruppe oder ein spezielles Haus für alte MmgB zu ziehen, jedoch eine durchaus annehmbare oder sogar selbstverständliche Vorstellung. Insbesondere bei den Proband:innen mit stärkeren Einschränkungen war hierbei nicht klar, ob dies ihren eigenen Wünschen entsprach oder ob sie hier die Vorstellungen von Angehörigen oder Betreuungskräften unreflektiert übernommen haben. Überraschend war allerdings die Vehemenz, mit der es einige Proband:innen ablehnten, im Alter in ein Alters(pflege)heim für Menschen ohne geistige Behinderung zu wechseln. Angesichts der oft prekären Situation in vielen Altersheimen in Deutschland sind die hier angegebenen Gründe (schlechte Betreuung, dort ist es langweilig, Pflegekräfte können nicht mit MmgB umgehen) durchaus nachvollziehbar. Genannt wurden diese Argumente von Proband:innen mit geringeren Einschränkungen, die selbst schon einmal zu Besuch oder im Rahmen eines Praktikums im Altersheim waren bzw. die durch Angehörige von Missständen gehört hatten.
Selbst bei schwerer Krankheit im Alter konnten sich die meisten Befragten nicht oder nur für den Notfall vorstellen, in ein Alters- oder Pflegeheim bzw. Hospiz5 zu wechseln. Hier ist allerdings wieder zu berücksichtigen, dass es selbst den Befragten mit leichten Einschränkungen schwerfiel, sich in diese Situation hineinzuversetzen. Die Anmerkung eines Probanden mit geringen Einschränkungen, dass er in diesem Fall nicht zu den Eltern ziehen würde, weil er ihnen nicht zur Last fallen möchte, deutet auf das große Bedürfnis nach Nähe zu einer primären Bezugsperson im Krankheitsfall hin. Dieses Bedürfnis scheint so stark zu sein, dass es ihn die eigentlich vorhandene Fähigkeit vergessen lässt, hierbei das ebenfalls zunehmende Alter bzw. den dann schon möglichen Tod der Eltern zu berücksichtigen. Nach Strüber und Roth dominierte in dieser Situation wahrscheinlich die u. a. für das Bindungsverhalten zuständige, entwicklungsgeschichtlich und ontogenetisch ältere untere limbische Ebene des Gehirns (Amygdala etc.) über die bei dem Probanden nicht vollständig ausgereifte obere limbische Ebene (z. B. den ventromedialen präfrontalen Kortex; [31]).6
Die Realität alter MmgB sieht jedoch in vielen Fällen anders aus als von ihnen gewünscht. So lebten z. B. im Jahr 2014 in der Region Westfalen-Lippe (NRW) 21,0 % der MmgB, die 65 Jahre und älter waren, in (Alten‑)Pflegeeinrichtungen für nicht behinderte Menschen. Diese sind in der Regel nicht auf MmgB eingerichtet. Die meisten verbrachten dort einen deutlich längeren Lebensabschnitt als Menschen ohne geistige Behinderung [32]. Auch Zander betont, dass Menschen mit Behinderung, die in ein Altenpflegeheim ziehen, in der Regel 15 bis 20 Jahre jünger sind als die übrigen Bewohner:innen [35]. Nach Thimm et al. wurden in der NRW-Studie zudem knapp 60 % der altem MmgB in stationären Behinderteneinrichtungen betreut (hiervon 4,5 % in einer Außenwohngruppe), wobei unklar bleibt, wie viele dieser Einrichtungen über spezielle Angebote für ältere Bewohner:innen verfügten. Nur 8,0 % der alten MmgB lebten im ambulant betreuten Wohnen und 8,9 % selbstständig in einer eigenen Wohnung oder bei Angehörigen [32].
Vorstellungen der Zeitgestaltung im Alter
In Deutschland empfinden nur 34 % der 80- bis 85-jährigen Menschen ihren Alltag als abwechslungsreich. Es sind v. a. diejenigen, die ihren Gesundheitszustand als gut oder sehr gut bezeichnen. Zu den häufigsten Alltagsbeschäftigungen der über 80-jährigen Durchschnittsbevölkerung gehören das Fernsehen (78 %) und Zeitung lesen (67 %). Nur etwa die Hälfte der Personen kocht in diesem Alter noch regelmäßig (52 %) bzw. geht einkaufen (44 %). Jeweils gut 40 % sind häufig mit der Familie zusammen oder ruhen sich oft aus. Aktive Beschäftigungen wie gärtnern (37 %), Bücher lesen (27 %), Freunde und Bekannte treffen (24 %), basteln oder heimwerken (14 %), sich sportlich bewegen (12 %) und in Vereinen etc. aktiv sein (12 %) werden nur noch selten wahrgenommen. Für die stark eingeschränkte Alltagsgestaltung sind insbesondere Behinderungen aufgrund zunehmender gesundheitlicher Einschränkungen verantwortlich [11].
Ähnlich wie in der jüngeren Durchschnittsbevölkerung entsprachen die Vorstellungen unserer Proband:innen darüber, wie sie im Alter gerne ihre Zeit verbringen möchten, meist ihren aktuellen Vorlieben bzw. ihren aktuell üblichen Tätigkeiten. Diejenigen, die direkten Kontakt zu speziellen Gruppen für alte MmgB hatten oder wo es eine solche Wohn- bzw. Tagesstrukturgruppe im Haus gab, schilderten stattdessen meist die Tätigkeiten, die sie bei den alten Menschen dort sahen. Eine Reihe von Beschäftigungsmöglichkeiten, wie etwa das Spazierengehen, wurde von vielen Befragten unabhängig von ihrem Behinderungsgrad genannt. Andere Tätigkeiten – z. B. Online-Kontakte aufrecht erhalten – gaben nur Personen mit geringen Einschränkungen an. Auch wenn die meisten Proband:innen jeweils nur wenige Tätigkeiten nannten, zeigte sich insgesamt ein sehr breites Spektrum an Möglichkeiten, im Alter die Zeit zu verbringen. Dabei war jedoch nicht immer klar, ob sich die Befragten bei ihren Antworten in die Situation des Altseins hineinversetzt hatten oder stattdessen ihre aktuellen Freizeitbeschäftigungen nannten. Zudem kann nicht eindeutig gesagt werden, ob sie jeweils in der Lage waren zu berücksichtigen, dass sie im Alter evtl. bestimmte Tätigkeiten nicht mehr ausführen können. Nur einzelne Proband:innen wie PB12 wiesen klar darauf hin, dass man im Alter nur noch die Dinge tun kann, zu denen man in der Lage ist.
Mehrere Personen betonten, dass sie auch im Alter gerne mit anderen Leuten zusammen sein und sich mit ihnen austauschen möchten. Eine Probandin führte hier als Negativbeispiel die Situation in Altersheimen an, wo die Bewohner:innen ihrer Ansicht nach die meiste Zeit alleingelassen werden und keiner sinnvollen Beschäftigung nachgehen können. Dies war für sie ein wichtiger Grund dafür, dass sie keinesfalls in ein Altersheim umziehen möchte. Auch anderen Befragten war bewusst, dass es in Deutschland einen deutlichen qualitativen Unterschied hinsichtlich der Freizeitgestaltung in vielen Einrichtungen der Behindertenhilfe einerseits und der Altenpflege andererseits gibt.
Vorstellungen von sozialen Beziehungen und Betreuung im Alter
In der Durchschnittsbevölkerung nimmt die Zahl der sozialen Kontakte mit zunehmendem Alter parallel zur Verschlechterung des subjektiven Gesundheitszustands ab. Nur noch ein Viertel der 80- bis 85-Jährigen trifft sich regelmäßig mit Freunden oder Bekannten. Soziale Kontakte innerhalb der Familie bleiben meist länger bestehen. Allerdings geben auch hier fast 60 % der Menschen dieser Altersgruppe an, keine entsprechenden Beziehungen mehr zu pflegen. Im Alter nehmen sowohl die Anzahl als auch die Intensität der sozialen Beziehungen ab. Dabei sagen 70 % der Personen dieser Altersgruppe, dass sie eigentlich gerne unter Menschen sind [11].
Die sozialen Netzwerke von MmgB, die in Behinderteneinrichtungen leben, sind unabhängig vom Alter im Durchschnitt deutlich kleiner als die der Menschen ohne Behinderung. Engere Beziehungen bestehen meist nur zu den primären Bezugspersonen (i. d. R. zu den Eltern, deren zentrale Rolle später oft von Geschwistern übernommen wird) bzw. zu den unmittelbaren Betreuungskräften, ergänzt durch die Kontakte zu Mitbewohner:innen und durch Werkstattkontakte. Wie viele der dort lebenden MmgB eine Partnerschaft (meist innerhalb der Einrichtung) eingehen, ist unbekannt [14]. Nach Schäper et al. kommt es bei MmgB im Alter – insbesondere dann, wenn die primären Bezugspersonen verstorben sind – meist zu einer „Singularisierung“, also zu einem Abbau familiärer Unterstützung und zur Ausdünnung der sozialen Netzwerke [29].
Wie nicht behinderte Menschen möchten auch MmgB im Alter gerne mit Personen zusammen sein, die sie kennen und mögen. Die Mehrzahl der von uns befragten Proband:innen konnte sich allerdings nur schwer oder gar nicht vorstellen, dass ihr soziales Umfeld ebenfalls altern wird, sodass die Großeltern bzw. Eltern dann wahrscheinlich nicht mehr leben und auch ihre aktuellen Betreuungskräfte nicht mehr da sein werden. Besonders häufig war dies bei der Frage der Fall, wer denn im Alter bei schwerer Krankheit bei ihnen sein solle. Auch hier ist wieder davon auszugehen, dass in diesem Fall selbst bei den Personen mit leichteren sozioemotionalen Einschränkungen die untere limbische Ebene des Gehirns über die obere limbische Ebene dominierte, sodass eigentlich in Ansätzen vorhandene Fähigkeiten nicht zum Tragen kamen [31]. Immer wieder zeigte sich in den Antworten, dass v. a. die Proband:innen mit stärkeren sozioemotionalen Einschränkungen die Beziehungen zu den für sie zuständigen Betreuungskräften nicht als professionelle, distanziertere Beziehungen sahen, sondern als enge Freundschaften. Sie gingen davon aus, dass diese zweifellos auch bis ins Alter bestehen bleiben würden. Dies macht deutlich, dass es sich – anders als in der Sonderpädagogik in den letzten Jahrzehnten immer wieder thematisiert – bei den Beziehungen zwischen MmgB in Betreuungseinrichtungen und ihren Betreuungskräften eben nicht um rein professionelle Verhältnisse zwischen Erwachsenen handelt. Die Fähigkeiten und Bedürfnisse von MmgB in Einrichtungen sind stark von ihrem jeweiligen intellektuellen und sozioemotionalen Entwicklungsstand abhängig. Basierend auf der Maslowschen Bedürfnishierarchie [21] stehen bei MmgB und einem SEO-Grad 1–3 (bzw. 4) Sicherheit – vermittelt etwa durch die Anwesenheit bekannter Personen, zu denen ein Vertrauensverhältnis besteht – und das soziale Bedürfnis nach Nähe und Zuneigung im Vordergrund. Erst SEO-Grad-4-Personen beginnen langsam, soziale Regeln (wie etwa das Einhalten einer gewissen Distanz zu Betreuungskräften) zu verstehen und zu akzeptieren [28]. Betreuungskräften, die auf die Nähe-Bedürfnisse von Menschen mit stärkeren sozioemotionalen Einschränkungen eingehen, sollte daher nicht ein Mangel an Professionalität attestiert werden [33]. Im Gegenteil, es kann sich hierbei durchaus um ein professionelles Eingehen auf die jeweiligen Bedürfnisse der MmgB handeln.
Zusammenfassung der Ergebnisse
Wie in unserer vorgeschalteten explorativen Studie zum episodischen Zukunftsdenken [16] finden sich auch in der qualitativen Inhaltsanalyse nach Mayring deutliche Hinweise darauf, dass insbesondere der Grad der geistigen Behinderung und der Grad der sozioemotionalen Entwicklung sowie das Niveau der sprachlichen/narrativen Fähigkeiten Einfluss auf die Fähigkeiten von MmgB haben könnten, sich in ein zukünftiges Selbst als alter Mensch hineinzuprojizieren. Die Antworten der Personen mit entsprechend geringeren Einschränkungen waren in der Regel erkennbar durchdachter, fundierter und inhaltlich passender. Sie zeigten in unterschiedlicher Ausprägung Ansätze der Fähigkeit zum episodischen Zukunftsdenken und waren weniger im Hier und Jetzt verhaftet.
Dies hatte jedoch keinen Einfluss darauf, dass die meisten Proband:innen unabhängig vom Grad ihrer Einschränkungen direkt oder indirekt den Wunsch äußerten, dass ihre Lebensumstände auch im Alter so bleiben mögen, wie sie derzeit sind. Ähnlich wie Menschen ohne Behinderung möchten sie gerne dort wohnen bleiben, wo sie gegenwärtig wohnen, und auch von den Personen betreut werden, die sie jetzt betreuen. Ausnahmen bildeten hier nur Proband:innen, die gemeinsam mit Angehörigen bereits festgelegt hatten, wo sie im Alter betreut werden sollen, und Proband:innen mit geringen Einschränkungen, die nachvollziehen konnten, dass es im Alter Situationen geben kann, die einen Umzug in eine passende Pflegeumgebung unumgänglich machen. Fast alle Proband:innen möchten auch im Alter gerne den Kontakt zu ihren engsten Verwandten und Freunden aufrechterhalten. Hier zeigte sich jedoch deutlich, dass selbst Proband:innen mit geringeren Einschränkungen Probleme damit hatten nachzuvollziehen, dass diese Personen dann ebenfalls alt sein werden. Mit der Vorstellung, im Alter aufgrund zusätzlicher Erkrankungen weitere Hilfsmittel oder Hilfestellung in Anspruch nehmen zu müssen, gingen fast alle recht gelassen um, da dies bereits heute zu ihrem Alltag gehört. Bei der Frage, wie sie ihre Zeit im Alter gestalten möchten, nannten viele ihre derzeitigen Freizeitbeschäftigungen oder Beschäftigungsformen, die sie bei alten Menschen gesehen hatten. Personen mit geringeren Einschränkungen wiesen darauf hin, dass sie dann vielleicht aus gesundheitlichen Gründen einiges davon nicht mehr tun können.
Limitationen der Studie
Qualitative Studien, wie die vorliegende, erfassen bewusst die subjektive Sichtweise einer bestimmten Zielgruppe. Die klassischen Gütekriterien aus der quantitativen Forschung (Objektivität, Reliabilität, Validität) sind daher nicht anwendbar. Stattdessen wurden hier Transparenz, Intersubjektivität und Reichweite sowie Gegenstands-Angemessenheit und Regelgeleitetheit des Vorgehens als häufig angegebene Gütekriterien der qualitativen Forschung berücksichtigt.
Um mit MmgB mündliche Interviews durchführen zu können, müssen diese über eine ausreichende Kommunikationsfähigkeit verfügen. Daher kamen nur erwachsene Menschen mit einer leichteren geistigen Behinderung und entsprechenden kommunikativen Fähigkeiten als Proband:innen in Frage. Nicht eingeschlossen werden konnten Menschen mit einer schwereren geistigen Behinderung und/oder einem SEO-Grad < 4. Da bei den meisten MmgB keine über objektive Messverfahren erhobenen Werte zum Grad ihrer geistigen Behinderung und zum Grad ihrer sprachlichen/narrativen Fähigkeiten vorliegen, wurden diese Fähigkeiten von ihren Betreuungskräften subjektiv eingeschätzt. Auch der Grad der sozioemotionalen Entwicklung wurde anhand von Fragen zu den vorhandenen sozioemotionalen Fähigkeiten eingeordnet. Die Gewinnung der Proband:innen erfolgte nicht direkt, sondern über die Einrichtungen, in denen sie leben bzw. von denen sie ambulant betreut werden. Wie in anderen Studien [2] trafen auch hier Betreuungskräfte als ‚Gatekeeper‘ die Vorauswahl und sprachen die aus ihrer Sicht passenden Personen an. Leider konnten auf diese Weise keine MmgB im Alter von ≥ 60 Jahren für die Teilnahme gewonnen werden. Da die Anwesenheit einer Betreuungskraft während des Interviews zu sozial erwünschten Antworten führen kann und Betreuungskräfte bei Verständnisproblemen ggf. auch Antwortmöglichkeiten vorgeben können, wurden die Interviews abschließend daraufhin analysiert – mit dem Ergebnis, dass sich beides hier weitgehend ausschließen lässt. Leider war es aufgrund der technischen Ausstattung der Einrichtungen größtenteils nicht möglich, wie ursprünglich vorgesehen, alle Interviews per Videotelefonie durchzuführen. Dies hätte über die Sinneskanäle Hören und Sehen einen intensiveren Kontakt mit den Teilnehmenden ermöglicht, sodass evtl. noch zusätzliche Informationen hätten gewonnen werden können.
Fazit für die Praxis
Eine Konsequenz dieser Studie ist, dass in Zukunft die Bedürfnisse und Wünsche älterer Menschen mit geistiger Behinderung (MmgB) vermehrt in die Planung von Wohn- und Betreuungsangeboten einbezogen werden sollten, wobei jeweils der Grad ihrer intellektuellen und sozioemotionalen Einschränkungen zu berücksichtigen ist. Folglich muss dann auch die Bereitstellung entsprechender Wohnmöglichkeiten und Hilfen flexibler gehandhabt werden.
Die Berücksichtigung des jeweiligen Behinderungsgrades ist zudem bei allen Maßnahmen der aktiven Teilhabe von MmgB am alltäglichen Leben erforderlich. Dies gilt v. a. für die Gesundheitsförderung und inklusive Forschungs- und Public-Health-Projekte. Nur so können die Beiträge der MmgB richtig eingeordnet und eine Überforderung verhindert werden.
Wegen der weitreichenden Folgen hinsichtlich des Umgangs mit MmgB und ihrer Teilhabe am gesellschaftlichen Leben sollten die Forschungsergebnisse zudem durch weitere, umfangreichere qualitative und quantitative Studien überprüft werden.
Danksagung
Die Autorinnen bedanken sich herzlich bei allen Studienteilnehmer:innen und ihren Betreuungskräften, dass sie uns ihre Zeit für die Studie zur Verfügung gestellt haben.
Einhaltung ethischer Richtlinien
Interessenkonflikt
L. Habermann-Horstmeier und L. Breinlinger geben an, dass kein Interessenkonflikt besteht.
Alle beschriebenen Untersuchungen am Menschen oder an menschlichem Gewebe wurden mit Zustimmung der zuständigen Ethikkommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Die vorliegende Studie wurde am 23.08.2021 von der Ethikkommission einer Hochschule in Deutschland genehmigt. Alle Studienteilnehmenden und ihren gesetzlichen Betreuer/-innen wurden umfassend über die Durchführung der Studie aufgeklärt, ihre Einwilligung zur Studienteilnahme wurde eingeholt.
1 Im folgenden Text mit I. abgekürzt.
2 Eine Person wies darauf hin, dass es Brillen mit Lesefeld gebe.
3 TENE: Tagesstätte für Erwachsene nach dem Erwerbsleben.
4 Nach dem SEO-Konzept entspricht SEO 4 in sozioemotionaler Hinsicht einem Referenzalter von 3 bis 6/7 Jahre, SEO 5 einem Referenzalter von 6/7 bis 12 Jahre [8, 13, 27].
5 Nur eine Probandin mit geringen Einschränkungen kannte die Bedeutung des Begriffs ‚Hospiz‘. Andere hatten ihn schon einmal gehört, konnten aber nicht genau sagen, was damit gemeint ist.
6 Personen mit frühen Stresserfahrungen, wie sie bei MmgB sehr häufig vorkommen, weisen oft strukturelle und funktionelle Gehirnveränderungen auf. Typisch ist z. B. eine Volumenreduktion im lateralen und medialen präfrontalen Kortex, der eine wichtige Rolle bei kognitiven und emotionalen Kontrollfunktionen spielt [20].
==== Refs
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| 0 | PMC9735145 | NO-CC CODE | 2022-12-14 23:28:32 | no | Präv Gesundheitsf. 2022 Dec 5;:1-16 | utf-8 | null | null | null | oa_other |
==== Front
Nat Rev Methods Primers
Nat Rev Methods Primers
Nature Reviews. Methods Primers
2662-8449
Nature Publishing Group UK London
175
10.1038/s43586-022-00175-x
Primer
Liquid chromatography–tandem mass spectrometry for clinical diagnostics
http://orcid.org/0000-0003-1679-5453
Thomas Stefani N. 1
French Deborah 2
Jannetto Paul J. 3
Rappold Brian A. 4
http://orcid.org/0000-0001-9665-4786
Clarke William A. [email protected]
5
1 grid.17635.36 0000000419368657 Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN USA
2 grid.266102.1 0000 0001 2297 6811 Laboratory Medicine, University of California San Francisco, San Francisco, CA USA
3 grid.66875.3a 0000 0004 0459 167X Department of Pathology & Laboratory Medicine, Mayo Clinic, Rochester, MN USA
4 grid.419316.8 0000 0004 0550 1859 Research and Development, Labcorp, Burlington, NC USA
5 grid.21107.35 0000 0001 2171 9311 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD USA
8 12 2022
2022
2 1 967 10 2022
© Springer Nature Limited 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Mass spectrometry is a powerful analytical tool used for the analysis of a wide range of substances and matrices; it is increasingly utilized for clinical applications in laboratory medicine. This Primer includes an overview of basic mass spectrometry concepts, focusing primarily on tandem mass spectrometry. We discuss experimental considerations and quality management, and provide an overview of some key applications in the clinic. Lastly, the Primer discusses significant challenges for implementation of mass spectrometry in clinical laboratories and provides an outlook of where there are emerging clinical applications for this technology.
Tandem mass spectrometry is increasingly utilized for clinical applications in laboratory medicine. In this Primer, Thomas et al. discuss experimental considerations and quality management for implementing clinical tandem mass spectrometry in the clinic with an overview of some key applications.
Subject terms
Mass spectrometry
Medical research
issue-copyright-statement© Springer Nature Limited 2022
==== Body
pmcIntroduction
Mass spectrometry has been used since the mid-twentieth century in basic science laboratories and various industries for quantitative and qualitative analysis. For many years, the sophisticated instrumentation and specialized knowledge required to develop analytical methods, as well as the complexity of sample preparation, kept the use of mass spectrometry confined to highly specialized laboratories. However, the operation of the instruments has since been simplified, and the instruments themselves have become more robust, which has made the technology more accessible to a broader user base. Although mass spectrometry continues to be used in research applications for biomarker discovery and complex protein characterization, it is increasingly common to find these instruments in the routine clinical laboratory as well.
Mass spectrometric analysis is based on the separation of ions by their mass to charge ratio (m/z). There are several different types of mass analysers used for mass spectrometric analyses including quadrupole, magnetic sector, radio-frequency ion trap, time of flight (TOF), orbitrap and ion cyclotron resonance1. There are also numerous approaches to create ions in the gas phase prior to analysis by mass spectrometry including electron ionization, chemical ionization, electrospray ionization (ESI), photoionization, inductively coupled plasma and matrix-assisted laser desorption ionization2.
Mass analysers can be combined to perform tandem mass spectrometry (MS/MS), which is a relatively simple concept — two mass analyses occur in series, often with a fragmentation step in between. One approach to MS/MS is to combine two or more identical types of mass analysers in series, such as a triple quadrupole analyser or a TOF/TOF analyser. Alternatively, two (or more) types of mass analysers can be combined to create hybrid instruments for MS/MS; for example, a quadrupole and TOF combined to create Q-TOF analysers or a quadrupole and linear ion trap put together to form a Q-Trap instrument. For any of these configurations, mass spectrometry analysis is accomplished by performing the first mass analysis or filtering, passing selected ions into a collision cell where fragmentation occurs, followed by a second mass analysis. For some configurations that utilize a trapping mass analyser, several cycles of mass spectrometry and fragmentation can be performed to generate structural information for an unknown compound. MS/MS is useful for both qualitative determinations (for example, structural characterization or presence) and targeted quantitative analysis with the use of stable isotope-labelled standards.
In liquid chromatography, molecules are separated based on differential equilibrium between a mobile phase and a stationary phase — the equilibrium is driven by their solubility or strength of interaction with the mobile and stationary phases. Initially, analytes interact with functionalized particles (the stationary phase) and are eluted when they have a stronger interaction with the solvent flowing through the chromatographic column (the mobile phase) relative to the stationary phase. The optimal characteristics of the solvent and stationary phase are dependent on the analysis performed3. The use of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) aids the separation of the analyte(s) of interest from matrix components, improving sensitivity and imprecision and improving specificity by separating interferences, such as isobaric compounds, that cannot be differentiated by the mass spectrometer4.
The strength of LC-MS/MS lies in the high analytic selectivity that is inherent to this technique. For quantitative analysis, a specimen is pretreated via dilution or by purification to remediate some complexities of the matrix, and then injected onto the liquid chromatography system. The liquid chromatography eluent carrying the analyte is introduced into the source of the mass spectrometer, where gas phase ions are produced. The first mass analyser filters incoming ions, only allowing precursor ions to move forward towards the collision cell. In the collision cell, precursor ions are fragmented to product ions, which are analysed in the last stage of the tandem mass spectrometer. The resulting mass spectrum reflects the product ions only; when focusing only on particular precursor/product ion pairs, quantitative analyses can be performed using a technique called selected reaction monitoring.
Utilization of mass spectrometry in a clinical laboratory is very different from work performed in research laboratories owing to regulatory requirements in place for clinical testing to ensure robustness, reproducibility and accuracy, such as the Clinical Laboratory Improvement Amendment or accreditation requirements from the College of American Pathologists5. These regulations typically characterize LC-MS/MS tests as laboratory developed tests and establish specific requirements for performance of laboratory developed tests along with the quality management of the associated processes. It should be noted that additional regulation is looming, as there is pending legislation that would require submission of laboratory developed tests for review and approval by the US Food and Drug Administration (FDA)6 — however, this is both a fluid and a contentious topic and enactment of this legislation is not a given. In addition to regulatory requirements, there is also a time-sensitive element to this testing — patient diagnosis or treatment can be pending, waiting for the LC-MS/MS result to become available. These techniques of clinical LC-MS/MS will be the focus of the current Primer, with most examples utilizing ESI triple quadrupole-based mass spectrometry; a typical set-up for this LC-MS/MS system can be seen in Fig. 1.Fig. 1 Depiction of a liquid chromatography–tandem mass spectrometry system.
Electrospray ionization shown as the ion source with a triple quadrupole analyser.
This Primer includes an overview of some basic mass spectrometry concepts, focusing primarily on MS/MS using quadrupole mass analysers. We discuss experimental considerations and quality management, and provide an overview of some key applications for small molecules. We do not discuss other forms of MS/MS with non-quadrupole mass analysers, nor do we address metabolomics or proteomics. Lastly, the Primer discusses significant challenges for implementation of mass spectrometry in clinical laboratories and provides an outlook of where there are emerging clinical applications for this technology.
Experimentation
Sample preparation
Sample preparation is required before LC-MS/MS analysis. This can be simple (for example, dilution or protein precipitation) or more complex (for example, solid phase extraction (SPE), liquid–liquid extraction (LLE) or supported liquid extraction (SLE))7. Although simple sample preparation is rapid, sample extracts are not as clean as with more complex preparation. Extracts will still contain significant amounts of sample matrix that could cause issues with the robustness and reproducibility of the LC-MS/MS method. An internal standard is added in the same amount to all calibrators, quality control materials and patient samples as a first step in sample preparation to ensure that the internal standard goes through all steps of analysis along with the analyte of interest.
Samples can be diluted with water or a mobile phase before injection onto the LC-MS/MS system. The diluted sample should be centrifuged and/or filtered to remove particulates before injection. Dilutions are commonly used for urine drug analysis8,9 owing to the concentration of drugs in urine being high and the protein content normally being low. Although this technique is simple and fast, it cannot be used to concentrate analytes and no matrix is removed from the sample. To minimize matrix effects, it is recommended to use as high a dilution as possible while still retaining the required sensitivity7.
For protein precipitation, an organic solvent (such as acetonitrile) or acid (such as trichloroacetic acid) and sometimes a salt (for example, zinc sulfate) are added to a body fluid sample such as whole blood or serum/plasma in order to precipitate the proteins out of solution10. After centrifugation, the supernatant can be evaporated and reconstituted to concentrate the analyte if required8. Although this technique is simple, only a fraction of proteins are removed; this may result in issues with robustness and reproducibility. Protein precipitation is a sample preparation strategy often employed for therapeutic drug monitoring (TDM) owing to the requirement for a fast turn-around time for such assays11–13.
SPE uses a sorbent, for which there are various mechanisms of interaction, to retain the analyte(s) while matrix components are washed away before the analyte(s) are eluted7. The sorbent is commonly conditioned with elution solvent and equilibrated with buffer prior to addition of the sample. Mixing the sample with an application buffer will maximize retention of the analyte(s) to the sorbent. The sorbent can be washed with additional solvents to remove matrix and other compounds before the measurand(s) are released from the sorbent bed using an elution solvent. This elution mixture can be evaporated and reconstituted in an appropriate injection matrix7. SPE can be optimized for the analyte(s) in the method based on the buffers and the wash solutions used, and creates a cleaner sample extract with the ability to concentrate the analyte(s). However, SPE is complex and time-consuming. This technique is commonly used for analysis of urine and serum drugs and steroid hormones14–17.
LLE involves use of an organic solvent (such as hexane/ethyl acetate) that can separate hydrophobic analytes from the aqueous body fluid phase. Samples are mixed with the organic solvent to allow the analytes of interest to partition into the organic phase, which is then transferred to a clean vessel. Once evaporated, the analytes are reconstituted in an LC-MS/MS-compatible solvent7. This extraction method creates a sample extract in which analytes can be further concentrated and so is commonly applied in analysis of steroid hormones18,19. However, it is time-consuming and fairly complex to perform. SLE uses the same principle as LLE but the partition is performed in solid media rather than in liquid. The sample mixed with a buffer is allowed to disperse into a sorbent bed (commonly diatomaceous earth) and is then eluted using an organic solvent mixture (for example, ethyl acetate and hexane) as the hydrophobic analyte(s) partition preferentially into the solvent. SLE produces a cleaner sample extract similar to LLE, but can be formatted for higher throughput than LLE. SLE has been used for analysis of steroid hormones and methylmalonic acid (following derivitization to increase lipophilicity)20–23. For all of these sample preparation strategies, the chemical properties of the analyte(s), for example lipophilicity and pKa, must be taken into account during selection7.
Liquid chromatography
Liquid chromatography is a technique that separates analytes based on the interaction between a stationary phase (the chromatography column) and a liquid phase (mobile phases)4. These interactions are based on multiple mechanisms including polarity, ionic interactions and size exclusion. Reversed-phase chromatography is most commonly used whereby the stationary phase is less polar than the mobile phase so non-polar molecules adsorb to the stationary phase until a less polar mobile phase passes through. In normal-phase chromatography, the stationary phase is more polar than the mobile phase at sample introduction4. When coupled with mass spectrometry, chromatographic mobile phases also may contain a proton donor species that contributes to ionization of the analytes.
In clinical LC-MS/MS analysis, once the patient sample has undergone sample preparation, the sample extract is injected onto the chromatography column. High-pressure pumps deliver the mobile phases to the column at reproducible flow rates. Gradient elution is most commonly used where the composition of the mobile phase (percentage of polar versus non-polar) is varied over the total run time, for example the time required to elute the analytes of interest, clean and then re-equilibrate the column. A typical analysis time ranges from 2 to 5 min for a routine clinical LC-MS/MS test4. If the conditions are tightly controlled, the time that analyte(s) elute from the column (retention time) should remain constant. Chromatographic separation is particularly important when there are isobaric compounds involved; if these are not sufficiently separated from one another there can be interference when an isobaric species mimics the selected reaction monitoring transition of another analyte in the same analytical window of time. The choice of chromatography column in terms of length, internal diameter and packing material is dependent upon the analyte(s) being measured and the pressure limitations of the liquid chromatography system24.
Ion sources
In order for mass spectrometry analysis to take place, the components of the flow from the liquid chromatography system have to be ionized. There are three main types of atmospheric pressure ionization: ESI, atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI)4,25. ESI (see Supplementary Fig. 1) is the most common type of ionization used in clinical diagnostics, as it is most useful for polar compounds that form ions in solution. APCI (see Supplementary Fig. 2) tends to be used for analysis of more non-polar compounds that do not form ions in solution but are able to be ionized in the gas phase, such as steroids or cannabinoids. APPI can be important for weakly polar or non-polar compounds that are challenging with ESI or APCI. APPI greatly reduces matrix effects and background signal; however, it is rarely used. In ESI, the liquid flow from the liquid chromatography system, containing the analyte and solvent molecules, becomes charged as it flows out of an electrode at high voltage. This charged eluent forms a spray which can be heated by gas flows to evaporate solvent. Molecular ions are derived from small droplets and enter the mass spectrometer in the gas phase4,25. In APCI, the liquid flow from the liquid chromatography system flows through a heated nebulizer tube creating a gaseous mixture of analyte and solvent molecules. Upon exit from the tube, the gaseous mixture passes a charged corona discharge needle creating reactant gas. The reactant gas and analyte interact; the analytes become charged based on gas phase basicity and these ions enter the inlet of the mass spectrometer4,25. In APPI, the liquid flow from the liquid chromatography system is subjected to heated gas creating a vapour. This vapour and, commonly, a dopant (for example, toluene) pass by an ultraviolet lamp emitting photons causing photoionization and the analyte ions enter the front of the mass spectrometer4,25. The charged species are generated as a function of the addition of a proton ([M + H]+, positive ion) or as an anion ([M – H]–, negative ion). Additionally, adducts may be formed of the analyte and solvent/salt species as well as multiply charged species (for example, [M + 2H]2+).
Types of mass analysis
Triple quadrupole mass spectrometers (or tandem mass spectrometers) are most commonly used for clinical diagnostics. Two mass-filtering quadrupoles can transmit ions with a specific m/z value based on the applied radio frequency and direct current voltage. They can also allow all ions to pass through (radio frequency only). Commonly, another quadrupole is employed to act as a collision cell where fragmentation of ions can take place (radio frequency and collision gas applied)4,25 (Fig. 2a). Quantitative clinical LC-MS/MS methods commonly employ selected reaction monitoring. In this type of analysis, quadrupole 1 provides a stable trajectory for ions of a specific m/z value, and only ions of the specific m/z value enter quadrupole 2 where they are fragmented to form a charged product and a neutral loss. These fragment ions enter quadrupole 3, which is set to filter ions of a specific m/z value, and these ions strike the detector4,25 (Fig. 2b). The precursor ion/product ion pair is called a transition; using testosterone as an example, the transitions for testosterone have the precursor ion/product ion pair 289.1/97.1 m/z and 289.1/109.1 m/z.Fig. 2 Overview of mass analysis.
a, A triple quadrupole mass spectrometer and how each quadrupole transmits ions. b, Selected reaction monitoring using testosterone as an example. m/z, mass to charge ratio.
Optimization of transitions for selected reaction monitoring
Optimization of transitions when using ESI is commonly performed by directly infusing a pure standard into the mass spectrometer using a syringe pump and investigating and varying the compound-dependent parameters (for example, precursor ion scan followed by product ion scan, varying collision energy)4. Examples of these optimization experiments are given in Table 1.Table 1 Experiments performed using direct infusion of pure analyte to optimize compound-dependent parameters
Experiment Goal
Quadrupole 1 scan (precursor ion scan) Infuse pure analyte into the mass spectrometer and determine the precursor ion mass
Check negative and positive polarity Determine whether the analyte has higher signal in positive or negative mode
Product ion scan Set quadrupole 1 mass to mass of analyte of interest, fragment this mass in quadrupole 2 and look for range of product ions in quadrupole 3
Collision energy optimization Once precursor ion/product ion transition is chosen, optimize collision energy in quadrupole 2 to produce sufficient fragmentation
Most instruments have automated functions that can perform optimization but it is recommended to also perform this task manually in an iterative manner. Although commonly the transition with the highest signal-to-noise ratio is chosen for quantification, it is possible that this transition is not optimal for use in patient samples owing to interferences. Therefore, during method development, it is common to identify and use more transitions so that they can all be investigated for potential issues. It is recommended that product ions corresponding to a water loss from the precursor ion (–18 atomic mass units (amu)) are avoided owing to lack of specificity and, therefore, higher background noise or interfering signals26. Further, product ions with a mass below 100 amu may also be relatively non-specific, although when analysing small molecules it is not always possible to avoid such transitions. After validation, it is common to use two transitions per analyte (one quantifier transition to determine the amount of analyte present, and one qualifier transition to confirm analyte specificity). Two transitions per internal standard are often used for routine clinical applications.
Liquid flow from the liquid chromatography system can be added to the direct infusion set-up in an experiment known as post-column infusion or T-infusion27. Post-column infusion can be used to optimize mass transitions when using APCI, and it is used in both ESI and APCI to optimize the source parameters (for example, temperature and gas flow)4. Examples of these experiments are provided in Table 2. Once all of these parameters are established, the entire LC-MS/MS method can be run to ensure that adequate sensitivity and specificity are achieved. If not, these experiments can be repeated to further optimize the parameters.Table 2 Experiments performed using T-infusion or post-column infusion to optimize source parameters
Experiment Goal
Optimize capillary voltage (ESI) Optimize the solvent spray from the tip of the ESI probe to optimize ionization efficiency (known as nebulizer/sprayer/ionspray voltage)
Optimize corona current (APCI) Optimize the corona needle discharge current to optimize ionization efficiency
Optimize voltage applied to orifice plate/cone Optimize the voltage that causes ion clusters to break apart before entering the mass spectrometer (cone or capillary voltage/declustering potential)
Optimize source temperature Optimize the temperature to eliminate condensation of aqueous mobile phase components to improve volatilization and reduce matrix components (dependent upon liquid chromatography flow rate and percentage aqueous)
Optimize source gas flows Optimize the gas flow that aids in formation of solvent spray (nebulizer/sheath gas) and optimize gas flow that aids in evaporation of solvents and drives ions into gas phase (desolvation gas)
Optimize probe distance from cone Optimize the distance between the sample probe and/or spray needle and the orifice in the cone
Optimize curtain/cone/orifice plate gas flow Optimize the gas flow that inhibits solvent and non-ionized matrix components from entering the flight tube; use the highest gas flow possible without sacrificing sensitivity
Optimize entrance potential Optimize the voltage used to focus ions on initial ion guide(s) towards quadrupole 1
Optimize collisionally activated dissociation gas Optimize the pressure of the collision gas in quadrupole 2, which helps focus the ions passing through and aids in dissociation to fragment ions
Optimize cell exit potential Optimize the voltage as ions exit quadrupole 2 to focus them towards quadrupole 3
APCI, atmospheric pressure chemical ionization; ESI, electrospray ionization.
Once these mass spectrometer parameters are optimized, the liquid chromatography method should be run to ensure that the method performs adequately. An important consideration is the dwell time or the time that the mass spectrometer spends monitoring each mass transition. An appropriate dwell time is chosen to ensure adequate data points are collected across the chromatographic peak. If the dwell time is too long, the peak will be poorly defined; if the dwell time is too short, the peak will be jagged (Fig. 3). Ideally, the dwell time should be fixed to obtain a minimum of 15–20 data points across the peak4.Fig. 3 Effect of the dwell time being appropriate for the width of the peak versus too long.
The peak acquired with 50 ms dwell time provides a sufficient point across the peak. A dwell time of 150 ms results in a poorly defined peak with only five points.
Internal standardization
The use of an internal standard in clinical mass spectrometry is highly recommended. The internal standard helps normalize for any differences in analyte recovery during sample preparation or ionization efficiency4,24. The internal standard should be added to all samples at a concentration that is within the analytical measurement range of the assay, and that gives a reproducible mass spectrometry response; suggested concentrations are 10–50 times the lower limit of quantitation4.
Stable isotope-labelled internal standards should be used for LC-MS/MS analysis, most commonly labelled with deuterium (D or 2H) or carbon-13 (13C). This enables the internal standard to have theoretically the same chromatographic properties as the analyte (for example, retention time), but the mass spectrometer can distinguish between the analyte and the internal standard by the difference in mass. A minimum mass difference of 3 amu between the analyte and internal standard is recommended for analytes up to 1,000 amu to ensure separation from the isotopic envelope, but in compounds with a large number of chlorines, for example, a larger mass difference may be required4. The response of analyte in an internal standard-only solution should be less than 20% of the analyte’s lower limit of quantitation (caused by inefficient isotopic labelling). The response of the internal standard in high analyte-only concentrations should be below 5% of the typical internal standard response (caused by naturally occurring isotopes)4.
Quality control
Clinical LC-MS/MS assays tend to be run in batch format whereby a calibration curve, quality control samples and patient samples are run and analysed together. It is recommended that quality control samples are matrix-matched to the patient samples (for example, if the patient matrix is serum, then the quality control samples are prepared using serum)4. Conservatively, a minimum of 5% of the total batch size should consist of quality control, and if the batch size is large it is recommended that the quality control samples are spaced throughout the batch. However, the number of quality control samples needed is, ultimately, application-dependent. For quantitative assays, quality control samples should be at concentrations either throughout the analytical measurement range of the assay or at important medical decision limits, with a minimum of two liquid levels. For semi-qualitative assays, as a minimum there should be one quality control around 25% below the cut-off concentration (weak negative) and one around 25% higher than the cut-off concentration (weak positive)4. During method development, acceptance criteria are established for the quality control and once the method is in production, the patient samples can only be reported if the quality control samples pass these criteria.
For methods that will be used over an extended period of time, such as for clinical analysis, it is important to determine the stability of the quality control material and calibrators. In general, large batches of quality control material are prepared or purchased so that the same quality control material is used over an extended period of time (for example, 2 years). Therefore, it is important to know the storage requirements for the quality control material during this time period, at what temperature and whether freeze/thawing cycles are allowed4. Additionally, commutability of the matrix used for calibrators and quality control must be assessed — it can be problematic if the calibrators and quality control behave differently compared with clinical specimens.
Results
Data analysis
LC-MS/MS data are represented as a chromatogram, which is a plot of analyte abundance versus time (Fig. 4a). LC-MS/MS data points making up these individual chromatograms are sequentially scanned for each selected transition (quadrupole 1/quadrupole 3 pair) and averaged across the transition’s assigned dwell time. As the system is not continuously scanning all masses, individual data points are connected to generate a near-Gaussian shape of a chromatographic peak. For a peak, the abundance is proportional to the number of pseudo-molecular ions that survive ionization and subsequent collisional dissociation to reach the detector.Fig. 4 Quantification of testosterone by liquid chromatography–tandem mass spectrometry.
a, Chromatogram of testosterone. b, Signal-to-noise ratio for determination. c, Calculation of testosterone concentration in patient sample based on calibration curve. Peak area ratio = analyte peak area divided by internal standard peak area.
There are typically multiple chromatograms for each assayed analyte in a specimen. At least one or, preferably, two or more distinct transitions are monitored for the analyte of interest. The additional transitions are utilized in an intra-sample determination of specificity described as transition ratios or ion ratios28. These transitions can be distinct fragments if the molecule can provide multiple stable product ions of appropriate abundance, although other mechanisms exist to assess specificity when a single neutral loss is utilized29. The consistency of the relationship between a quantifying transition (used to generate the reported result) and the qualifying transition (used to assess co-eluting interferences) is derived from calibration standards and quality controls for the assay4. Additionally, the internal standard chromatogram will often utilize a second transition for peak purity assessments. Figure 5 shows demonstrative data from LC-MS/MS analysis of leucine isomers in amino acids exhibiting the multiple transitions utilized as well as the co-detection of isomers.Fig. 5 Analysis of leucine isomers.
Example liquid chromatography–tandem mass spectrometry data generated from the analysis of leucine isomers with counts on the y axis (abundance of response) and time on the x axis. a, Dark blue line: transition 132.1 (quadrupole 1) to 44.1 (quadrupole 3) for equimolar concentrations of alloisoleucine (0.16 min), isoleucine (0.25 min) and leucine (0.40 min). Light blue line: transition 132.1 (quadrupole 1) to 43.1 (quadrupole 3), which is used as a qualifying transition for leucine only. The differences in recorded abundance are caused by the ionization and dissociation differences at the applied collision energy for the selected transitions. b, Transition 142.1 (quadrupole 1) to 78.1 (quadrupole 3) for the 10-deuteron labelled (‘D10’) alloisoleucine internal standard (0.14 min), which is used to normalize the recovery of alloisoleucine. c, Transition 142.1 (quadrupole 1) to 96.1 (quadrupole 3) for both D10-alloisoleucine (0.14 min) and D10-leucine (0.37 min); this transition acts as a normalizer for leucine quantification and as a qualifying transition for the alloisoleucine internal standard. The area under the curve for each peak is used for quantification calculations. MRM, multiple reaction monitoring; XIC, extracted ion chromatogram.
Although LC-MS/MS is often described as specific, non-measurand signals can be observed during analysis. These signals can be derived from isomers of the target compound, in-source dissociation of larger molecules, adducts or isotopes of typically lower m/z species or some combination thereof30. Additionally, noise or background signals can be highly variable between different MS/MS transitions and samples (Fig. 4b). Integration of measurand peaks above noise and in the presence of interfering signals remains a highly subjective process, although progress in automated signal interpretation is improving the reliability and reproducibility of data in clinical samples31.
Calibration
Calibration of mass spectrometry assays is performed on an analyte by analyte basis. Note that assay calibration is separate from instrument calibration, in which the latter establishes mass accuracy and resolution of ions with a stable trajectory to the detector. The ionization cross-section and the post-dissociation transmission efficiency for any two compounds are generally non-equivalent. Although relative abundances of signals in a mass spectrometer can be used to indicate certain relationships, such qualitative approaches are less common in clinical LC-MS/MS. According to International Organization for Standardization (ISO) definitions, a quantitative assay requires the use of SI-traceable units32. Moles per volume (for example, picomoles per litre or picomolar) or mass per volume (for example, nanograms per litre) are the most common expressions of quantitative values in clinical LC-MS/MS. Non-liquid matrices such as hair or tissue are generally reported as the mass of analyte per mass of matrix. As with quality controls, best practice is to include matrix-matched calibration standards in order to minimize measurement deviation due to matrix effects.
Calibration curves are generated through the assay of samples of known concentrations. For each analyte in a standard, the area under the curve of the chromatographic peak is assessed, accounting for baseline noise generated in the ionization and detection processes. The peak areas of an analyte’s quantifying transition and its internal standard are divided to generate a normalized response function. These area ratios are then used to derive a linear least squares regression that describes the concentration–area ratio function of the analyte on that instrument (Fig. 4c).
The number of calibration points to generate a standard curve is dependent on the breadth of the intended measurement interval and the assay’s analytical performance. Clinical LC-MS/MS assays can exhibit various measurement intervals, although a 1,000-fold range is an approximate limit of coverage owing to limitations of carry-over in the system33. Calibration points should exist at the extremities of the analytical measurement range with additional points used to provide accuracy of the best-fit line as appropriate; at a minimum, the distribution should include the midpoint of the assay measurement range, and points located halfway between the midpoint and the extremities.
The nature of LC-MS/MS detection leads to heteroscedasticity for calibration curves, or changing variance across the concentration range measured. Thus, weighting of the regression is a standard practice34. The models for the best-fit line are typically either linear or quadratic fits (meaning first-degree and second-degree polynomial equations of the regression); utility of the model is dependent on the desired analytical range and the clinical use of the measurand. Calibration models and weightings are rarely modified from the validated procedure when the assay is put into practice.
Calibration curves can be assessed for back-calculated accuracy of the individual points using established criteria. An allowable accuracy of 85–115% for values greater than the lower limit of quantitation is common. At the lower limit of quantitation, values within 20% of the expected are acceptable35. Points falling outside these criteria may be excluded, dependent on the laboratory’s standard operating procedure. The rate of re-calibration has numerous variables to consider. Changes in response functions of the instrument over time as well as the changes at the sample preparation level (reagent and technical) are the determinants for assay calibration frequency. Calibration per group of co-prepared samples (batch-based calibration) is conventionally practised.
Calibration curves are used to define the analyte’s response function on the instrument of analysis, with sample by sample variations normalized by the internal standard. By itself, a calibration curve is not capable of determining assay bias or imprecision. Thus, quality controls are prepared and measured with specimens to determine whether the assay is performing within expectations. In regulated clinical laboratories, two liquid levels of quality control should be measured per day at a minimum, unless additional internal controls are designed into the instrument36. However, factors which modulate recovery or response of an analyte in LC-MS/MS workflows may be difficult to ascertain under a scheme of two quality controls per day37. The extraction and measurement of quality controls should be coincidental with specimens, with the frequency determined by the nature of the assay (for example, extraction mode) and the risk of error at each step of specimen processing.
Quality controls
Criteria for LC-MS/MS quality control acceptance, and thus batch acceptance, will use one of two approaches. In a model derived from LC-MS/MS-based clinical trials submitted to the FDA, the plurality of quality controls within a batch should be within 15% of the nominal target35. This quality control approach has a long history as being accepted guidance for LC-MS/MS bioanalysis. A different model familiar to clinical laboratories is to assess the mean and the imprecision of each level of quality control via replicate analysis and apply what is commonly known as Westgard rules38. In contrast to the FDA’s quality control analysis, Westgard is largely focused on long-term precision of the analysis. Either approach should be balanced against the expected performance limits for the measurand, with consideration for the nature of LC-MS/MS procedures.
An additional consideration for application of quality control rules is the ability of multiple analytes to be assessed in the same procedure (multiplexed analysis). The application of Westgard rules was derived from statistics based on a single measurand and longitudinal calibration. By contrast, modern LC-MS/MS procedures can measure many chemical species quantitatively in the same analysis; strict application of either Westgard rules or the FDA conditions can lead to unwarranted failures owing to compounding random error39. In these instances, clinical use of the assay and use of results (for example, reference change value from serial monitoring versus acute single measurements) may influence the structure of quality control assessments40.
Data metrics associated with quality assurance are intrinsic in LC-MS/MS. Individual features may indicate degradation of system capabilities, such as a reduced retention time and peak broadening signifying a loss of stationary phase interactions. Comparative elements, such as the internal standard response of a sample measured against the mean internal standard response of quality controls in the same batch, can be evaluated for systematic errors (such as under-pipetting of the internal standard) or random error (sample-specific ion suppression). Limits for each metric can be defined in laboratory standard operating procedures and used to assess data quality prior to result release, which is an important feature of LC-MS/MS41.
Following calibration of an assay, quality control result review and sample quality assurance interrogation, results for samples are posted to a laboratory information management system or other interface for an electronic medical record. Data can be interpreted for critical alert values, compared with reference intervals or evaluated for biomarker level change in the patient over time42.
Applications
The evolution of mass spectrometry from the research setting to the clinical laboratory has continued to grow in the past decade as the advantages of mass spectrometry-based applications have been realized in laboratory medicine. Although not without its challenges, the following sections will highlight some key areas where LC-MS/MS has demonstrated its utility in clinical diagnostics.
Endocrine system
The endocrine system is one area for the laboratory where LC-MS/MS has been emphasized by professional society guidelines such as those of the Endocrine Society and the Urology Society, which provided evidence showing that mass spectrometry-based methods are preferable for the measurement of sex steroid hormones43. Measurement of steroid hormones in the blood often presents a clinical challenge owing to the very low concentrations (for example, picomolar range) and structural similarity of endogenous hormones and metabolites44. For example, the quantification of oestradiol and testosterone is important for the diagnosis, prognosis or treatment monitoring of various disorders such as hypogonadism, amenorrhoea and tumours of the ovary, breast and testes. Although immunoassays are widely available, they suffer from a lack of specificity owing to steroids with similar structures and poor standardization across platforms. In addition, none of the commercially available immunoassays is reliable enough to measure testosterone levels usually found in women and children45. Human heterophilic antibodies and autoantibodies can also lead to false-positive or false-negative results in immunoassays and have been documented (for example, human chorionic gonadotrophin and thyroglobulin)44,46.
Mass spectrometry also enables steroid profiling and the ability to multiplex and analyse a single sample to assess the metabolic signatures of several steroid hormones47. It allows the quantification of individual steroids and metabolites related to the various enzymatic activities. This deeper understanding of the complex metabolic pathways in different diseases can facilitate precision medicine. In addition to multiplexing, mass spectrometry also has a higher throughput especially when coupled with pre-analytical automated liquid handling systems. LC-MS/MS is also better suited over gas chromatography–mass spectrometry as some steroids have poor volatility owing to their higher polarity and lipophilicity47. Lastly, mass spectrometry has been shown to be an effective technique to measure hormones in alternative matrices such as saliva48,49.
In addition to endogenous steroid hormones, biogenic amines, such as catecholamines and metanephrines, are another class of substances where mass spectrometry can excel. Phaeochromocytoma and paraganglioma are neuroendocrine tumours able to secrete catecholamines50. Timely diagnosis is critical and historically relied on measurements of plasma and urinary catecholamines. With LC-MS/MS methods now available to measure free plasma metanephrines or urinary fractionated metanephrines, the Endocrine Society has recommended these as the first-line test in diagnosis51. However, LC-MS/MS is not without its challenges as matrix effects and isobaric interferences need to be properly addressed. In addition, the establishment of new reference intervals for various age-based and sex-based hormones can be difficult.
Therapeutic drug monitoring
TDM is another rapidly expanding area for mass spectrometry. TDM is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. Drugs with a narrow therapeutic index, highly variable pharmacokinetics or toxicity are often measured and include drugs in the following drug classes: antibiotics, antivirals, antifungals, antiepileptics, antipsychotics, antidepressants and anticancer drugs. Immunosuppressive drugs such as tacrolimus, cyclosporine A, everolimus and sirolimus were some of the initial drugs brought into clinical laboratories for LC-MS/MS analysis. Currently, approximately 50% of TDM requests for tacrolimus and cyclosporin A and more than 70% of those for sirolimus and everolimus worldwide are being measured using LC-MS/MS52. However, although immunoassays can offer rapid turnaround times on automated chemistry analysers, they suffer from cross-reactivity to other metabolites or structurally similar compounds.
TDM using LC-MS/MS offers the ability to characterize a patient’s phenotype by measuring the parent and/or active metabolite concentrations with all of the demographic, disease-related and environmental variables that can affect the drug concentrations53. It allows a sensitive, specific and low-cost methodology to be used in precision medicine and patient management. Mass spectrometry has numerous advantages over traditional immunoassays such as superior specificity, expanded linear ranges, ability to multiplex (for example, measure both active parent and metabolites or multiple co-medications) and high throughput relative to existing high performance liquid chromatography methods53. Whereas whole blood or serum represents the most common matrices used, LC-MS/MS assays have also been utilized with dried blood spots54,55 or oral fluid (for example, fluconazole in hospitalized children)56. With the COVID-19 pandemic, these alternative matrices highlight the ability to offer patients an at-home collection method, but still facilitate routine TDM and care at a time when hospitals do not have the resources to collect patient samples. Another promising alternative matrix for TDM using LC-MS/MS is the ability to measure intracellular drug concentrations at the sites of action which more closely correlate to the therapeutic or adverse effects57. LC-MS/MS assays have already been utilized to monitor immunosuppressive drugs in peripheral blood mononuclear cells58. Other applications include intracellular imatinib (tyrosine kinase inhibitor) concentrations in gastrointestinal stromal tumour cells59, intracellular concentrations of ganciclovir60 or 5-fluorouracil nucleotides responsible for the anticancer effects of 5-fluorouracil61.
Toxicology
Clinical toxicology is another challenging area where quick turn-around times, shifting analytical targets and the impact on the clinical decision process all provide an opportunity for mass spectrometry-based techniques. With the opioid epidemic in North America, the use of urine toxicology screening has become standard of care for controlled substance monitoring. It provides unbiased and objective laboratory results to monitor compliance or identify abuse/misuse of medications and illicit substances. Professional and laboratory medicine practice guidelines62 recommend using definitive tests over immunoassays to monitor compliance with over-the-counter, prescribed/non-prescribed medications and illicit substances. Although current immunoassays for urine toxicology screening provide rapid turn-around times for emergency room settings, they primarily detect drug classes and do not identify the specific drugs present. In addition, these immunoassays suffer from poor specificity and sensitivity, so they are susceptible to false-positive and false-negative results. Therefore, definitive testing such as LC-MS/MS or gas chromatography–mass spectrometry is recommended as follow-up testing.
One of the advantages of mass spectrometry for toxicology testing is the ability to multiplex or detect multiple analytes including parent drug and multiple metabolites. With the decriminalization of marijuana and increasing use of cannabinoids in medicine and recreational products, laboratories are required to be able to distinguish between the different patterns of cannabinoid use63. Mass spectrometry methods have been shown to be able to differentiate Δ8-tetrahydrocannabinol (THC) and Δ9-THC in blood and urine64. Δ9-THC is the main psychoactive ingredient in cannabis and is illegal in the United States. Δ8-THC, an isomer of Δ9-THC, has lower potency but has some psychoactive properties and is legal in parts of the United States. Many commercial immunoassays exhibit cross-reactivity between these compounds and their metabolites. Δ8-THC and the Δ8-carboxy-THC metabolite may also cause an interference on some mass spectrometry-based confirmatory tests. However, LC-MS/MS can be used to chromatographically resolve these isomers and allow accurate interpretation of the test results.
Lastly, broad-spectrum toxicology testing using non-targeted mass spectrometry-based methods allows comprehensive screening not only to identify medication usage and trends of illicit drug use but can also identify new and emerging psychoactive substances or designer drugs65. Most mass spectrometry-based methods use targeted analysis, which provides the specificity to identify the drugs that the assay is designed to detect. However, in the ever-changing drug abuse landscape the targets are constantly evolving. As a result, these non-targeted methods allow public health and clinical toxicology laboratories the opportunity to identify new trends. A major challenge for this type of testing is the absence of certified reference materials and standards.
Proteins and newborn screening
LC-MS/MS has also become a leading technology used in newborn screening programmes. Newborn screening programmes are an essential programme to detect, diagnose and mitigate the effect of congenital disorders. In the United States, mandatory screening is performed on around 3.8 million newborns each year66,67. The Recommended Uniform Screening Panel currently suggests screening for a minimum of 60 disorders66. Although other methodologies over the years have been utilized from immunoassays to electrophoresis, mass spectrometry has become the preferred primary testing method because of its high-throughput sampling speed and selectivity. The mass spectrometry-based assays screen for metabolic disorders, amino acid disorders and fatty acid oxidation disorders by measuring the relative abundance of more than 70 amino acids, acylcarnitines and other small molecules. These assays permit rapid measurement directly from filter paper blood spots or biological fluids68, and allow the identification and possible treatment of metabolic disorders even in patients who are asymptomatic. However, expanding panels, isobaric compounds, matrix effects and ion suppression are just a few of the challenges these techniques present, but many can be overcome with chromatography and other separation techniques.
Other areas where mass spectrometry is beginning to gain traction include replacing serum protein electrophoresis to detect and quantify M proteins for multiple myeloma. Multiple myeloma, a cancer of plasma cells, and its precursor condition, monoclonal gammopathy of undetermined significance, lead to dysregulated overproduction of a unique immunoglobulin called the M protein69. Detection of the M protein is crucial for diagnosing multiple myeloma or monoclonal gammopathy of undetermined significance. With increasing demands to distinguish residual disease and new interferences from monoclonal antibody therapies, mass spectrometry methods such as the clonotypic peptide technique70, which may be the most sensitive method to detect M proteins in serum, or the monoclonal immunoglobulin rapid accurate mass measurement (miRAMM)71 method can be utilized. The mass spectrometry techniques offer increased sensitivity and specificity especially for patients under treatment for multiple myeloma69. However, challenges remain for these newer applications, which have only been adopted by a few laboratories to date; therefore, a regulatory approved commercially supported version of the assay along with the support of professional oncology societies may help implementation of these methods.
Reproducibility and data deposition
Reproducibility
Reproducibility of clinical LC-MS/MS results is an important concept that spans intra-laboratory details (both within and between batches) as well as inter-laboratory comparisons. Conceptually, acute LC-MS/MS analysis with normalizing isotopically labelled internal standards is primarily precision-based. The generation of calibration solutions is the predominant step wherein accuracy is of primary importance. In the preparation and analysis of specimens, precision of preparation amongst calibrators, quality controls and patient samples are the only requirements, as the internal standard corrects for subtle inaccuracies that may occur during testing. Longitudinal reproducibility is again reliant on calibration accuracy and stability and should be interrogated in a similar mode to quality control samples. Additionally, proficiency testing is commonly utilized to provide indications of either harmonization or standardization between laboratories testing for the same measurand. Use of certified reference materials or comparison with reference method procedures (when available) is deployed to provide reliable results from distinct vendors, models, platforms or institutions5.
Data deposition
Results for clinical samples are posted to a laboratory information management system or other interface for an electronic medical record. Data can be interpreted for critical alert values, compared with reference intervals or evaluated for biomarker level change in the patient over time42. Long-term storage of reported results is generally mandated by regulatory organizations for all health-care-related details within an electronic medical record. The raw data utilized to produce the result(s) can be retained by a laboratory for interrogations of performance and quality of the assay, instruments and results.
Limitations and optimizations
There are several challenges in implementing LC-MS/MS for clinical diagnostics. These challenges are primarily a result of the manual nature of the assays, lack of integrated automation, relatively low sample throughput, high initial capital expense (several hundred thousand dollars in addition to associated construction and renovation costs), high level of technical proficiency required by technicians, limited assay standardization and lack of widely available commercial standards including quality control material and calibrators72. Given that the majority of clinical LC-MS/MS assays are considered laboratory developed tests, there are limitations related to the significant amount of time, money and technical expertise required to develop, validate and perform the assays. Additionally, data analysis and reporting are time-consuming and are often manual processes.
Clinical LC-MS/MS assays that measure proteins such as apolipoproteins, thyroglobulin, insulin/C-peptide, PTHrP, PTH and angiotensin have many limitations given the multiple steps required for sample preparation73,74, although streamlined sample preparation workflows for some clinical proteomic assays have recently been developed75,76. Consequently, the use of LC-MS/MS for protein-based clinical diagnostics has largely been limited to reference laboratories and large academic centres.
Staffing considerations
Proficient LC-MS/MS technical specialists possess skill sets that are difficult and time-consuming to teach77. Although certified laboratory technicians with a general background in medical or clinical laboratory science can be trained to conduct several of the routine tasks associated with LC-MS/MS assays, specialists are often required to conduct complex troubleshooting and maintenance activities. However, the specialists capable of this complex work often do not have the certification necessary to perform clinical assays and report results. As a significant cost-saving measure, it can be advantageous for clinical laboratories with several LC-MS/MS instrument platforms to have staff who are capable of conducting instrument service as opposed to relying on contracts from the instrument vendors’ service engineers. Smaller laboratories that have a limited number of LC-MS/MS instrument platforms often must rely on external service contracts owing to a lack of advanced in-house expertise. Because they are so few in number, LC-MS/MS technical specialists are often in high demand in various sectors of the clinical laboratory industry. Accordingly, to foster employee retention, it is imperative for employers to carefully consider appropriate compensation and career growth opportunities for LC-MS/MS technical specialists78,79.
Quality management
Careful attention to several parameters when developing clinical LC-MS/MS assays is necessary to mitigate some of the causes of poor assay performance. The lack of optimization of sample preparation, ionization and data processing can significantly compromise data quality and, consequently, patient safety. In this regard, systemic quality management and sustained vigilance are of considerable importance.
The key aspects of quality for clinical LC-MS/MS methods mirror those necessary for all clinical testing methods, and include robust method design and optimization; careful management of all steps of the analytical process to avoid gross handling errors; adequate training of technicians and competency verification; a proactive maintenance plan to limit within-instrument and between-instrument variations; and continuous quality verification based on the periodic analysis of control samples and external quality assessment samples with assigned target concentrations or peer group comparisons80. The quality management plan for LC-MS/MS assays must monitor the entire testing process, including the pre-analytical, analytical and post-analytical phases. The five Clinical Laboratory Improvement Amendments requirements for laboratory accreditation (facility administration, quality systems, proficiency testing, personnel and inspection) apply to all laboratories performing LC-MS/MS testing5.
Proficiency testing and external quality assessment are essential components of the quality management plan for clinical LC-MS/MS assays81. Sources of proficiency testing failures that are unique to LC-MS/MS assays include variable matrix effects, lot-to-lot reagent variation, poor specificity and non-commutability of the testing material82. Different sources and preparation of calibration material can result in distinct concentration assignments and, consequently, disagreement between assigned concentrations83,84.
Assay performance optimization
The process of optimizing an LC-MS/MS assay includes reducing or eliminating interferences, increasing ruggedness and enhancing sample throughput85. Addressing challenges related to interferences is of particular importance for assays that are designed to measure analytes such as steroid hormones, owing to the large number of similar metabolites, some of which are isobars of the analyte(s) of interest86. This is of particular importance for individuals with endocrine disorders owing to altered steroid hormone pathway regulation wherein the presence of analytical interferences can negatively impact assay accuracy, thereby compromising the efficacy of the diagnostic and treatment strategies for the patient87.
Outlook
LC-MS/MS is a highly sensitive and selective technique that can be effectively used for quantitation of many clinically relevant analytes. The appeal of these LC-MS/MS assays is that many can overcome the limitations of other techniques, which include cross-reactivity, low analytical specificity and limited dynamic range88. There are numerous potential advantages for clinical LC-MS/MS assays, which include shorter assay development and optimization time compared with immunoassays; the ability to include multiple analyte analysis in a single method; and wide applicability to various analytes including drugs, hormones, small molecules, carbohydrates, nucleic acids and proteins.
Automated instrumentation
Advances in LC-MS/MS instrumentation and applications are occurring at a rapid pace. Similar to many other methods used in laboratory medicine, the development of front-to-back automation is a goal for clinical LC-MS/MS. Instrument manufacturers are working towards fully automated black box LC-MS/MS systems wherein the entire analytical process from sample preparation to result generation can be accomplished in the absence of manual intervention. The approval of such a device by the FDA as a diagnostic test would greatly facilitate its adoption by clinical laboratories, including those without technical staff who possess specialized LC-MS/MS training.
Recently, the first all-in-one certified clinical mass analyser with regulatory clearance, the Cascadion SM Clinical Analyzer, was developed by Thermo Fisher Scientific. This analyser combines LC and MS/MS in one instrument. The system is compatible with primary specimen collection tubes and operates under full automation with bidirectional communication with the laboratory information system. Currently, the only commercially available application for this analyser is 25-hydroxy vitamin D. The performance of the assay is comparable with that of other FDA-cleared 25-hydroxy vitamin D assays89. Other instrument manufacturers, including Shimadzu, are also developing black box LC-MS/MS solutions that feature end-to-end automation and fully integrated system components so that LC-MS/MS can be performed more similarly to standard automated clinical laboratory assays90.
Automated data processing
The utility of automated LC-MS/MS data processing and analysis will become even greater with the maturation of automated LC-MS/MS instrumentation given the large sizes of the generated data sets. To enable clinical laboratories to fully harness the valuable information contained within these large-scale data sets, novel fit-for-purpose software tools are needed91,92. Some laboratories have developed and implemented dashboard tools to monitor, track, optimize and support specialized laboratory workflows that are not typically well supported by routine laboratory information system functionality.
As an example of one such solution, an open-source software solution to address the LC-MS/MS data review and quality needs of their clinical laboratory was recently developed93. This software solution includes a database and a visualization component to collect LC-MS/MS data and monitor quality assurance parameters. This customizable Web-based dashboard facilitates automated quality control and data analysis for their complex urine opiate and metabolite LC-MS/MS assay. Web-based dashboards such as this are valuable tools that clinical laboratories can utilize when commercial options are not available. When used efficiently, data visualization tools can help maintain high-quality LC-MS/MS instrument and assay performance93.
Novel ionization methods
More recently, novel mass spectrometry ionization methods and direct sampling techniques have been developed that may find use for routine clinical applications in the future. One such technology is rapid evaporative ionization mass spectrometry (REIMS), which enables the direct characterization of biological or environmental samples without a requirement for sample preparation. In this technique, the aerosol generated from the evaporation of the sample by Joule heating or laser irradiation is directly introduced into the inlet of a mass spectrometer. REIMS has promise in the fields of intra-surgical tissue classification, bacterial identification and rapid profiling of cell lines94. For example, the intelligent knife (iKnife) is based on REIMS technology95, and is intended to be used as an alternative to frozen section histology by enhancing near real-time intraoperative decision-making based on surgical margin characterization96. The iKnife combines a tissue dissection tool (handheld electrosurgical device) with a mass spectrometer to analyse the smoke from evaporating tissue during resection. The MasSpec Pen was developed for use as a clinical and intraoperative device for ex vivo and in vivo cancer diagnosis97. Similar to the iKnife, it is based on ambient ionization, but differs in that it is a non-destructive technique, and biomolecules are extracted from tissues using discrete water droplets and delivered to the inlet of the mass spectrometer rather than relying on evaporation of tissue to generate a sample.
There are numerous other ambient ionization techniques that demonstrate potential utility for in vitro analysis or diagnosis. Paper spray mass spectrometry was developed as a direct sampling ionization method for the mass spectrometry analysis of complex mixtures, including dried blood spots for TDM applications and illicit drug detection in urine specimens98,99. This approach performs ESI directly from the tip of the paper used for sample collection, and has potential for rapid point-of-care analysis. Coated blade spray mass spectrometry is a solid phase micro-extraction-based technology that can be directly coupled to mass spectrometry to enable the rapid qualitative and quantitative analysis of complex matrices100. Coated blade spray mass spectrometry is similar to paper spray in that ESI can be performed directly from a sample collection substrate, but it has the advantage of microsample preparation/purification prior to analysis. Laser diode thermal desorption mass spectrometry is another direct sampling technique, but in this case ionization of the sample is achieved using heat to generate gas phase samples rather than electrospray. This technique was developed primarily to increase analytical throughput by eliminating the need for chromatographic separation prior to mass spectrometry detection and has demonstrated numerous potential applications including characterization of illicit drugs and quantification of therapeutic drugs and their metabolites in blood101.
Conclusion
The realization of the full potential of LC-MS/MS in the clinical laboratory requires a thorough understanding of not only the vast opportunities but also the limitations of the technology. Among the barriers to the more widespread implementation of LC-MS/MS in the clinical laboratory is a lack of the ruggedness and robustness of the instrumentation in the context of minimizing downtime and reducing the requisite level of technical expertise for its efficient operation. There is substantial room for improvement of the application of LC-MS/MS in the areas of enhanced automation and the commercial availability of certified reference materials, calibrators and quality control materials. Despite these challenges, LC-MS/MS remains a powerful technology with distinct analytical capabilities that can be applied not only to routine clinical applications but also to unique clinical applications as they present.
Supplementary information
Supplementary Information
Supplementary information
The online version contains supplementary material available at 10.1038/s43586-022-00175-x.
Author contributions
Introduction (W.A.C.); Experimentation (D.F.); Results (B.A.R.); Applications (P.J.J.); Reproducibility and data deposition (B.A.R.); Limitations and optimizations (S.N.T.); Outlook and Conclusion (S.N.T. and W.A.C.); Overview of the Primer (W.A.C.).
Peer review
Peer review information
Nature Reviews Methods Primers thanks Karl Storbeck, Joshua Hayden and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Competing interests
W.A.C. declares consulting for and research support from Thermo Fisher Scientific, consulting for Roche Diagnostics, and research support from Shimadzu Scientific Instruments. The other authors declare no competing interests.
Glossary
Analytic specificity A methodology’s ability to measure only specific analyte(s) of interest, even if they are found alongside several interfering analytes.
Fragmentation An ion dissociation process during which a molecular ion breaks into smaller fragment ions, radicals and/or neutral molecules.
Precursor ions Ions that dissociate into smaller fragment ions; originally termed parent ions.
Product ions Ions formed as the result of a reaction (fragmentation, ion/molecule reaction) involving a precursor ion; originally termed daughter ions.
Quadrupole A mass analyser consisting of four parallel cylindrical conducting rods wherein ions are separated based on the stability of their trajectories in the oscillating radio frequency and direct current electric fields that are applied to the rods.
Sorbent Material used to collect molecules of another substance by the process of sorption.
Time of flight (TOF). A mass analyser within which ions are separated based on their velocity as they travel through a flight tube.
Transition ratios Ratios between precursor and product ion intensities or integrated peak areas that are monitored for analyte identification and quantification; also referred to as ion ratios.
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| 0 | PMC9735147 | NO-CC CODE | 2022-12-14 23:28:32 | no | Nat Rev Methods Primers. 2022 Dec 8; 2(1):96 | utf-8 | Nat Rev Methods Primers | 2,022 | 10.1038/s43586-022-00175-x | oa_other |
==== Front
J Interv Card Electrophysiol
J Interv Card Electrophysiol
Journal of Interventional Cardiac Electrophysiology
1383-875X
1572-8595
Springer US New York
36481832
1442
10.1007/s10840-022-01442-3
Article
Characterization of high-density mapping in catheter ablation for persistent atrial fibrillation: results from the Advisor™ HD Grid Mapping Catheter Observational study
http://orcid.org/0000-0003-2626-3098
Fiedler Lukas [email protected]
123
Roca Ivo 4
Lorgat Faizel 5
Lacotte Jérôme 6
Haqqani Haris 7
Jesser Emily 8
Williams Christopher 9
Roithinger Franz Xaver 12
Steven Daniel 10
1 Department of Internal Medicine, Cardiology and Nephrology, Landesklinikum Wiener Neustadt, Corvinusring 3-5, 2700 Wiener Neustadt, Austria
2 grid.487248.5 0000 0004 9340 1179 Institute of Vascular Medicine and Cardiac Electrophysiology, Karl Landsteiner Society, St. Poelten, Austria
3 grid.21604.31 0000 0004 0523 5263 Department of Cardiology, Clinic of Internal Medicine II, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria
4 grid.410458.c 0000 0000 9635 9413 Hospital Clinic I Provincial de Barcelona, 170, 08036 Barcelona, Catalonia Spain
5 Christiaan Barnard Memorial Hospital, 181 Longmarket Street, Cape Town, 8001 South Africa
6 grid.418134.b Institute Cardio. Paris-Sud - Institut Jacques Cartier, Massy, France
7 grid.415184.d 0000 0004 0614 0266 The Prince Charles Hospital, Rode Road, Queensland 4032 Chermside, Australia
8 grid.417574.4 0000 0004 0366 7505 Abbott, 5050 Nathan Ln N, Plymouth, MN 55441 USA
9 grid.417574.4 0000 0004 0366 7505 Abbott, 5440 Patrick Henry Dr, Santa Clara, CA 95054 USA
10 grid.6190.e 0000 0000 8580 3777 Heart center at the University of Cologne, Kerpener Strasse 62, 50937 Cologne, North Rhine Germany
8 12 2022
111
23 9 2022
27 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Background
We quantified and characterized the outcomes of ablation in persistent atrial fibrillation (PersAF) subjects, and the utility of electroanatomical mapping with a market-released high-density (HD) mapping catheter.
Methods
PersAF subjects received electroanatomical mapping with the Advisor™ HD Grid mapping catheter, Sensor Enabled™ (HD Grid) and radiofrequency (RF) ablation to gather data regarding ablation strategies, mapping efficiency, quality, and outcomes. Subjects were enrolled from January 2019 to April 2020 across 25 international sites and followed for 12 months after the procedure.
Results
Three hundred thirty-four PersAF subjects (average age 64.2 years; 76% male; 25.4% previous AF ablation) were enrolled. Multiple map types were generated in a variety of rhythms using HD Grid. Significant differences in low voltage areas were identified in maps generated with the HD Wave Solution™ electrode configuration when compared to the standard configuration, which in some cases, influenced physicians’ ablation strategies. PV-only ablation strategy was used in 59.0% of subjects and 34.1% of subjects received PV ablation and additional lesions. Of the subjects, 82.0% were free from recurrent atrial arrhythmias at 12 months and new or increased dose of class I/III antiarrhythmic drugs. About 6.0% of subjects experienced a serious adverse event or serious adverse device effect through 12 months including 1 event deemed related to HD Grid and the index procedure by the investigator and 1 death unrelated to study devices.
Conclusions
The results of this study (NCT03733392) support the safety and utility of electroanatomical mapping with HD Grid in subjects with complex arrhythmias, such as PersAF in the real-world setting.
Supplementary Information
The online version contains supplementary material available at 10.1007/s10840-022-01442-3.
Keywords
High-density mapping
Pulmonary vein isolation
Persistent atrial fibrillation
Catheter ablation
http://dx.doi.org/10.13039/100001316 Abbott Laboratories
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pmcIntroduction
Atrial fibrillation (AF) is the most common arrhythmia and is associated with adverse prognosis including increased mortality [1]. Early rhythm control therapy including antiarrhythmic therapy and catheter ablation compared to standard care showed a reduced risk of a composite endpoint of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome in patients with early AF [2]. Catheter ablation reduces morbidity and mortality compared to antiarrhythmic drugs alone [3–5]. Pulmonary vein isolation (PVI) is the cornerstone in patients with paroxysmal AF (PAF) to electrically disconnect pulmonary veins from the left atrium and return patients to sinus rhythm (SR) [6, 7]. In persistent AF (PersAF), catheter ablation success rates are lower and standardized ablation technique is less evident.
While PVI is the cornerstone of catheter ablation for PAF, in PersAF, PVI alone has resulted in higher recurrence rates than those with PAF, indicating the potential for additional ablation targets beyond PVI [8, 9]. However, studies such as the STAR AF II clinical trial have found no significant reduction in the rate of recurrent AF when additional ablations were performed in addition to PVI and indicate that perhaps more selective targets may be needed to better characterize an individual patient’s specific arrhythmic substrate or ablation strategy [7]. Despite the fact that there is currently no consensus on the most successful ablation strategy for patients with PersAF, there is undoubtedly a broad agreement that detailed electroanatomical mapping of atrial substrates holds significant information to plan ablation strategy beyond PVI in PersAF. High-density (HD) mapping has been used to distinguish potential triggers and drivers of PersAF including areas of low voltage, fibrosis, local reentry, dyssynchrony and rotational drivers [10, 11]. Additionally, following AF ablation, complex arrhythmias are not uncommon. The majority of which occur in PersAF subjects and can be related to multiple different mechanisms [12]. This highlights the potential benefit of HD mapping in the identification of substrate, mechanisms, and ablation strategy of PersAF and accompanying atrial flutter (AFL) during redo ablation procedures.
Yeo et al. first identified the concept of “bipolar blindness” as the inability to detect an electrogram (EGM) when propagation of the wavefront is traveling perpendicular to the electrode dipole [12]. To overcome this obstacle, the Advisor™ HD Grid mapping catheter, Sensor Enabled™ (HD Grid) consists of four splines with four 1 mm equidistant electrodes mounted on each spline and attached at the tip to maintain a fixed distance between splines, which allows the HD Wave Solution™ (HDWS) electrode configuration to simultaneous analyze adjacent orthogonal bipolar signals. Therefore, the HDWS configuration preferentially selects EGMs with the greatest amplitude detected by the HD Grid mapping catheter, thus identifying local EGMs and correcting for the directional influence of wavefront propagation on bipolar signal amplitude, which may assist in substrate characterization and ablation strategy decisions.
The aim of this study is to quantify and characterize the outcomes of radiofrequency (RF) ablation in subjects with PersAF in real-world settings, and the utility of electroanatomical mapping with the HD Grid and EnSite Precision™ Cardiac Mapping System (SV 2.2 or higher, hereafter called “EnSite Precision”) with orthogonal bipole (HDWS) configuration.
Methods
Study design
The Advisor™ HD Grid Observational Study (NCT03733392) was a prospective, non-randomized, multicenter observational study designed to quantify and characterize the utility of electroanatomical mapping, and subsequent procedural outcomes of RF ablation after mapping with the Advisor™ HD Grid Mapping Catheter, Sensor Enabled (Abbott, St. Paul, MN) and the EnSite Precision™ Cardiac Mapping System with the HDWS configuration in subjects with PersAF in the real-world environment. Twenty-five international sites within Europe, Canada, Australia, and South Africa participated in this study. The conduct of the clinical study was in accordance with the Declaration of Helsinki and approved by the appropriate Ethics Committee of the respective clinical sites and as specified by local regulation. All patients enrolled in the study provided written informed consent.
Patient selection
This clinical study enrolled subjects over the age of 18 years who were indicated for cardiac RF ablation with electroanatomical mapping for the treatment of PersAF defined as documented continuous AF sustained beyond 7 days but less than 12 months. Patients with a PersAF diagnosis considered secondary to electrolyte imbalance, uncontrollable thyroid disease, or reversible or non-cardiac cause were excluded from the study. Other key exclusion criteria included left atrial diameter > 55 mm, left ventricular ejection fraction < 40%, uncontrolled heart failure or NYHA function class III or IV, or implanted ICD/CRT-D.
Mapping and procedure
Patient demographics, clinical history, and baseline clinical assessments were collected prior to the procedure. PersAF subjects underwent mapping and ablation according to the Instructions for Use (IFU) of the HD Grid, Ensite Precision™ Cardiac Mapping System, and any other medical devices used during the procedure. HD Grid was required to be used with EnSite Precision to generate a baseline electroanatomical map prior to ablation procedure. Complete contact with the cardiac wall was to be achieved before collecting data. Additional maps could be created or retrospectively generated using the Ensite™ TurboMap module (TurboMap). When reported, initial Automap/Turbomap settings used are detailed in Supplement Table S1. Ablation catheters were to be used per IFU to perform ablation per standard of care. Collection of additional maps and performance of additional ablations were allowed if clinically necessary. Ablation to treat other arrhythmias, such as AFL, that occurred during the procedure was allowed per physician discretion and standard of care. Data were collected during procedure regarding mapping activities and characteristics, procedural characteristics, ablation strategies and targets, and physician experience.
HDWS and standard configuration voltage comparisons
Any map generated with the HDWS electrode configuration could also be generated using the standard along-the-spline (hereafter called “standard “) electrode configuration with the same geometry as baseline map. If not performed during the procedure, this was performed after completion of the ablation procedure. A retrospective map was defined as the generation of a map that did not require collection of any new or additional electroanatomical data points. Instead, already collected mapping data was reused with new point collection or acquisition settings or electrode configurations selected (via TurboMap) or manual alteration of a copied open map. To compare overall mean voltage and low voltage surface area, only cases in which pre-ablation SR maps were generated with the HDWS configuration and the standard configuration were analyzed using the Ensite Precision platform.
Follow-up
A pre-discharge visit was performed post-procedure and included a 12-lead ECG, review of medication, and evaluation of any reportable adverse events. A serious adverse event (SAE) was any event that led to death, serious deterioration in health of the subject, or fetal distress, death, congenital abnormality or defect. A serious adverse device effect (SADE) is defined as any SAE that was determined to be a result of a medical device used in the study. A 90-day blanking period was utilized, and follow-up visits were scheduled at 6 months (180 ± 90 days) and 12 months (360 ± 90 days) from the index procedure. Information collected at scheduled follow-up visits included assessment of atrial arrhythmia recurrence (AF, AFL, or atrial tachycardia “AT “ lasting 30 s or longer), antiarrhythmic medication use (including class I/III AAD and dose), completed EQ-5D-5L and AFEQT (Atrial Fibrillation Effect on Quality-of-life) quality of life (QOL) surveys, occurrence of adverse events or protocol deviations. Holter monitors were issued at the 12-month visit and subjects were instructed to obtain a 48-h recording from which a core laboratory reviewed and reported findings to Abbott. Results from the Holter monitors were used for determining the rate of long-term success in PersAF subjects. The proportion of subjects free from repeat ablation procedures to treat PersAF outside the blanking period out of all subjects from which data were available were also documented.
Statistical methods
The objectives of this study were addressed through multiple descriptive endpoints. Categorical variables were reported as proportion and number of subjects. Continuous variables were reported as mean ± standard deviation and number of subjects and, where specified, median (Q1, Q3) (min, max). Comparisons of overall mean voltage and low-voltage surface area were performed using the paired t-test as each initial map served as a patient’s own control. Comparisons of quality-of-life scores at 6 and 12 months relative to baseline were performed using paired t-test. All p values are reported descriptively. Results with p < 0.05 were considered statistically significant. All statistical analyses were performed using SAS 9.4.
Results
Study population
Between January 2019 and April 2020, a total of 334 subjects with PersAF across 25 international sites were enrolled and received an ablation procedure in this study (Supplement Table S2). Seventy-six percent of the population were male with an average age of 64.2 ± 10.4 years, and all underwent electroanatomical mapping with the HD Grid mapping catheter and received RF energy delivery. Baseline characteristics are summarized in Table 1. History of arrhythmia and previous ablation treatment in PersAF subjects is summarized in Table 2. All subjects had a prior history of AF and 25.4% (85/334) were previously ablated to treat AF. Prior AF ablation strategy included PVI only (36.5%) and ablation beyond PVI (40.0%). Subjects also had a history of AFL and AT, some of which had a history of ablation targeting these arrhythmias prior to their enrollment in this study (Table 2).Table 1 Patient baseline characteristics
Variable PersAF subjects (N = 334)
Mean ± SD (n) or % (n/N)
Age (years)
Mean ± SD (n) 64.2 ± 10.4 (334)
Sex (male) 76.0% (254/334)
History of heart failure 28.1% (94/334)
Class I 22.3% (21/94)
Class II 76.6% (72/94)
Class III 1.1% (1/94)
Class IV 0.0% (0/94)
LVEF (%)
Mean ± SD (n) 55.8 ± 7.6 (333)
LAD (mm)
Mean ± SD (n) 44.4 ± 5.6 (331)
LAV (ml)
Mean ± SD (n) 108.3 ± 49.0 (172)
Valvular heart disease 14.1% (47/334)
Cardiomyopathy 15.3% (51/334)
Hypertrophic cardiomyopathy 3.9% (2/51)
Rhythm other than SR on baseline ECG 70.1% (234/334)
Subject is symptomatic 72.2% (169/234)
LVEF left ventricular ejection fraction, LAD left atrial diameter, LAV left atrial volume, SR sinus rhythm, ECG electrocardiogram
Table 2 Arrhythmia and ablation history
PersAF Subjects (N = 334)
% (n/N)
Atrial fibrillation 100.0% (334/334)
Paroxysmal 3.3% (11/334)
Persistent 91.0% (304/334)
Longstanding persistent 5.7% (19/334)
Permanent 0.0% (0/334)
Previous Ablation treatment 25.4% (85/334)
PVI 36.5% (31/85)
Beyond PVI 40.0% (34/85)
Unknown 23.5% (20/85)
Atrial flutter 17.7% (59/334)
Typical 42.4% (25/59)
Atypical 28.8% (17/59)
Unknown 28.8% (17/59)
Previous ablation treatment 37.3% (22/59)
Atrial tachycardia 1.2% (4/334)
Previous ablation treatment 25.0% (1/4)
PVI pulmonary vein isolation
HD Grid mapping characteristics and ablation strategies
After providing consent for study participation, electroanatomical mapping during the ablation procedure was performed with the HD Grid mapping catheter. A total of 496 maps were generated in a variety of cardiac structures (Fig. 1) and rhythms (Table 3) intended for the treatment of PersAF and other arrhythmias (i.e., AFL). These high-density maps were efficiently created with an average of 9799.0 ± 8665.9 and 2064.7 ± 1431.1 total collected and used mapping points, respectively, in an average of 12.5 ± 9.1 min per map (Table 3). Physicians in this study primarily referenced peak-to-peak maps (69.2%; 343/493) to treat PersAF subjects (Table 3). The configuration that compares simultaneous orthogonal bipoles, HDWS configuration, was the primary configuration used to map and identify ablation strategies in the majority of subjects (76.3%; 255/334). Substrates frequently searched for and identified included areas of low voltage, scar/fibrosis, and CFE (Supplement Table S3). PV-only targets were ablated in 59.0% (197/334) of all procedures. 34.1% (114/334) of subjects received PV plus additional lesions and 6.9% (23/334) of subjects’ ablation strategy did not include any PV targets. Non-PV ablation targets included the roof of the left atrium, posterior wall isolation, cavotricuspid isthmus, and mitral isthmus, among others. Ablation targets utilized in this study to treat PersAF subjects are summarized in Fig. 1.Fig. 1 Regions mapped and ablated. The percentage of patients in which a particular region of the left atrium (anterior–posterior view, top left; posterior-anterior view, bottom left) or right atrium (anterior–posterior view, top right; posterior-anterior view, bottom right) was mapped with HD Grid (blue text) or ablated with RF study catheter (green text). LAA = left atrial appendage, RAA = right atrial appendage, LOM = ligament of Marshall, LSPV = left superior pulmonary vein, LIPV = left inferior pulmonary vein, RSPV = right superior pulmonary vein, RIPV = right inferior pulmonary vein, SVC = superior vena cava, IVC = inferior vena cava
Table 3 Summary of HD Grid use and characteristics
All maps generated to treat PersAF subjects (N = 496)
Mean ± SD (n) or % (n/N)
Rhythm during map creation
Sinus rhythm 39.1% (194/496)
Atrial fibrillation 31.7% (157/496)
Atrial flutter 9.9% (49/496)
Typical 16.3% (8/49)
Atypical 83.7% (41/49)
Atrial tachycardia 2.4% (12/496)
A-paced with intrinsic conduction 16.7% (83/496)
Other 0.2% (1/496)
Mapping characteristics
Total mapping points collected 9799.0 ± 8665.9 (494)
Total mapping points used 2064.7 ± 1431.1 (494)
Time to generate map (min) 12.50 ± 9.1 (494)
Map type
Peak-to-peak 69.2% (343/496)
LAT 21.8% (121/496)
CFE mean 6.5% (32/496)
Fractionation 2.0% (10/496)
Peak-negative 0.6% (3/496)
LAT local activation time, CFE complex fractionated electrograms
Identification of substrates with simultaneous orthogonal configuration has an impact on ablation strategy
In order to better understand the role of simultaneous orthogonal bipole configurations with HD Grid in identifying ablation targets beyond traditional mapping methods, maps generated using HDWS configuration were compared to those created with the standard configuration (Supplement Fig. S1). The number of maps reported here was dependent on the data availability of comparative maps, the timing of the map comparisons, and the differences identified in compared maps, therefore resulting in a number of different analysis groups. In cases where comparable maps were generated, physicians reported that mapping with the HDWS configuration showed differences in substrate characteristics in 56.3% (153/272) of maps, including 29 instances where the comparison was performed in real time during the procedure and 124 maps where the comparison was performed after the procedure using retrospective maps generated with the standard configuration. It is important to note that comparisons made in real-time during the procedure actively informed the physicians’ ablation strategy whereas comparisons made after the procedure only indicate potential changes to the ablation strategy. The differences in substrate characteristics identified with the HDWS configuration versus the standard configuration, such as location and/or surface area of low voltage, fractionation, and activation time/activation sequence, have the potential to influence ablation strategy. In comparisons during the procedure, physicians reported the HDWS configuration assisted in identifying the ablation strategy in 69.0% (20/29) of these cases and changed the ablation strategy in 41.4% (12/29). In retrospective comparisons, 32.3% (40/124) of maps generated with the HDWS configuration identified an ablation strategy different than what would have been identified with the standard maps (Fig. 2).Fig. 2 Substrate differences identified and role in ablation strategy of HDWS versus standard configurations. Flow diagram describing the number of maps generated with the HDWS configuration that were compared to maps generated with the standard configuration using the HD Grid mapping catheter, including comparisons made during (boxes outlined in pink) and after (boxes outlined in orange) the procedure in cases which HDWS configuration identified differences in overall substrate characteristics versus standard configuration (boxes outlined and shaded in blue) as well as a further breakdown of the same comparisons in cases which HDWS configuration maps identified differences specifically in surface area and/or location of low voltage substrate versus standard configuration (boxes outlined and shaded in green)
Mapping with HD Grid in the simultaneous orthogonal configuration provides voltage measurements significantly different than standard electrode configuration
Overall, the greatest differences identified in maps generated using the HDWS configuration versus standard were in surface area and/or location of low voltage (79.7%; 122/153). Of the 122 maps in which surface area and/or location of low voltage were reported to differ between HDWS and standard electrode configurations, 15 maps were compared in real-time during the procedure and 107 maps were compared retrospectively after the procedure. Of the real-time comparisons, the HDWS configuration was reported to have assisted in identifying the ablation strategy in 53.3% (8/15) of maps and changed the ablation strategy in 26.7% (4/15) of maps (Fig. 2). Of the retrospective comparisons, the ablation strategy identified by the HDWS configuration was different than what would have been identified with the standard configuration in 30.8% (33/107) of maps. One example of this retrospective comparison in which HDWS configuration identified differences in low voltage that informed the ablation strategy is shown in Fig. 3A. The HDWS configuration map in Fig. 3A clearly shows reduced low voltage areas compared to standard configuration. In this example, the information provided by the HDWS configuration led to less substrate modification especially at the bottom of the left atrium and at the left atrial isthmus.Fig. 3 Low voltage differences between HDWS and standard configurations. A A left atrial high-density voltage map from posterior anterior view (PA) during sinus rhythm (SR) in HD Wave Solution (HDWS; left) and in standard configuration (right). Depicting scar area < 0.2 mV in gray and healthy myocardium > 0.5 mV in purple in both maps. Red circles highlight observable differences in low voltage areas between the two configurations. Six thousand eighty-nine yellow dots depict recorded local atrial signal. LSPV left superior pulmonary vein, LIPV left inferior pulmonary vein, RSPV left posterior pulmonary vein, RIPV left posterior pulmonary vein. B Analysis of pre-ablation maps generated during SR depicting a significant difference in overall mean voltage detected by HDWS configuration versus standard configuration. Paired t-test was used for statistical analysis. C Analysis of pre-ablation maps generated during SR depicting a significant difference in low voltage area (0.2–0.5 mV) detected by HDWS configuration versus standard configuration. Paired t-test was used for statistical analysis
To objectively quantify the change in low voltage identified between electrode configurations, pre-ablation maps of the left atrium generated when subjects were in SR were analyzed (N = 26). As the comparable retrospective maps were generated with the same mapping points and electroanatomical data as the original, each map served as its own control. The mean voltage detected with the HDWS configuration was 1.62 ± 0.80 mV while there was a significant reduction of mean voltage with the standard configuration of 1.38 ± 0.68 mV (average difference in mean voltage of 0.24 (p < 0.0001)) (Fig. 3B). The total surface area of low voltage (LVA) detected in the entire left atrium with the HDWS configuration versus standard configuration was also compared using peak-to-peak bipolar voltage of 0.2–0.5 mV to define LVA. LVA was significantly different with 27.94 ± 12.45 cm2 detected by the HDWS configuration and 31.56 ± 13.34 detected by the standard configuration (p < 0.0001) (Fig. 3C). Therefore, mapping in standard configuration detected a significantly larger total surface area of low voltage in the left atrium.
The Advisor HD Grid Observational Study resulted in safe and effective short- and long-term outcomes for PersAF patients
The procedural characteristics of this study are summarized in Table 4. Acute success defined as the proportion of subjects who received HD Grid mapping and RF energy delivery resulting in termination of clinical arrhythmia or non-inducibility of clinical arrhythmia after ablation with cardioversion allowed prior to inducibility attempt was achieved in 85.9% (287/334) of subjects (Table 4). Utilizing a 90-day blanking period following the index ablation procedure, 82.0% (168/205) of subjects were free from all atrial arrhythmias (AF/AFL/AT) greater than 30 s as documented by 48-h Holter monitor at their 12-month follow-up visit and new or increased dose of class I/III AADs. Additionally, at 12-months follow-up, 97.0% (291/300) of subjects were free from an additional procedure to specifically treat PersAF after the 90-day blanking period. (Table 4).Table 4 Procedural outcomes and effectiveness
PersAF Subjects (N = 334)
Mean ± SD (n) or % (n/N)
Procedural characteristics
Total procedure time (min) 134.3 ± 51.3 (333)
Fluoroscopy used during procedure, %(n/N) 97.9% (327/334)
Total fluoroscopy time (min) 14.5 ± 11.3 (326)
Total RF time (min) 32.0 ± 23.2 (319)
Effectiveness endpoints
Acute termination or non-inducibility of clinical arrhythmia 85.9% (287/334)
Freedom from all atrial arrhythmias (AF/AFL/AT) greater than 30 s (as documented by 48-h Holter at 12-month follow-up) and new or increased dose of class I/III AADs1 82.0% (168/205)
Freedom from all atrial arrhythmias (AF/AFL/AT) greater than 30 s (as documented by 48-h Holter at 12-month follow-up) on or off class I/III AADs1 87.4% (173/198)
Freedom from repeat ablation2 97.0% (291/300)
RF radiofrequency, AAD antiarrhythmic drug
1There were 13 subjects for which a 48-h Holter was reported as administered by the site at 12 months, but not analyzed by the core lab. These subjects were excluded from analysis (unless the subject failed the endpoint due to class I or III AAD where applicable). Two subjects were site-reported as having experienced an arrhythmia greater than 30 s. Eleven subjects were site-reported as not having experienced an arrhythmia greater than 30 s
2Defined as the proportion of subjects free from an additional ablation procedure to treat indicated cardiac arrhythmia (after a blanking period of 90 days) out of the subjects that underwent an initial ablation procedure with RF energy delivered that included the use of an Advisor HD Grid Mapping Catheter SE, and either completed 12 months of follow-up or did not complete 12 months of follow-up but experienced a repeat ablation before withdrawing from the study
Changes in QOL at 6 and 12 months after receiving HD Grid mapping and RF ablation relative to baseline were assessed in validated QOL surveys. Overall AFEQT scores significantly increased from an average of 59.8 ± 22.4 at baseline to 85.0 ± 15.6 at the 12-month visit (p < 0.0001) (Fig. 3). EQ-5D-5L visual analog scales (VAS) scores also significantly increased relative to baseline (p < 0.0001) (Fig. 4).Fig. 4 Quality of life summary. Comparisons of AFEQT and EQ-5D-5L visual analog scores (VAS) scores at 6 and 12 months relative to baseline were performed using paired t-test
Of the PersAF subjects, 6.0% (20/334) experienced an SAE or SADE following the procedure throughout the entire duration of the study. Two SAEs and 12 SADEs occurred periprocedurally and 2 SAEs and 6 SADEs within 30 days postprocedure with 1 event overall deemed related to the HD Grid mapping catheter and index procedure. There was one death in the study from a massive intracranial hemorrhage 226 days postprocedure, the cause of which was unknown and deemed unrelated to the HD Grid mapping catheter or index procedure. Adverse event types are further detailed in Supplement Tables S4 and S5.
Discussion
Main findings of the study
This is the first real world prospective, non-randomized, multicenter observational study investigating the use of the Advisor™ HD Grid mapping catheter and the HDWS configuration in patients undergoing RF ablation for PersAF. HD Grid was efficient and useful for creating detailed electroanatomical maps. In these maps, the use of a the HDWS mapping configuration identified quantifiable differences that changed the ablation strategy of the operator. This study resulted in favorable procedural characteristics and outcomes and demonstrated the utility of mapping with HD Grid.
The age, sex, and concomitant disease in this study population were typical of the PersAF population and comparable to other PersAF trials [7, 13]. Approximately one third of patients had a history of heart failure (28.1%) predominantly with NYHA Class II and the majority of patients were symptomatic from AF. A quarter of patients received at least one previous ablation for AF. Of these patients, 36.5% were treated with PVI only in the previous ablation procedure.
Efficiency of the HD Grid catheter and the HDWS configuration was reflected in 496 maps using a mapping time of 12.5 ± 9.1 min, collecting a mean of 9799 ± 8665.9 points per patient in different rhythms. This is comparable in quantity and time to other mapping systems [14]. The underlying rhythm during mapping was mainly SR or another regular atrial rhythm to allow interpretation of atrial substrate. 31.7% of patients were mapped while in AF.
Comparing the HDWS configuration to the standard configuration revealed clear differences in substrate characteristics. The most prominent differences between the two electrode configurations were seen in location and/or surface area of low voltage (79.7%). Representation of fractionated electrograms or activation time and sequence was less eminent. In SR, total surface area of low voltage areas was significantly smaller (mean difference of 3.63 cm2) and true voltage at these locations was significantly higher (mean difference 0.24 mV) with the HDWS configuration. Furthermore, physicians reported their ablation strategy identified with the HDWS configuration was different than what would have been identified with the standard configuration in 30.8% (33/107) comparisons after the procedure. This particularly important finding demonstrates the potential of the HD Grid catheter to provide a more complete picture and accurate basis for additional ablation strategies beyond PVI.
Primary ablation strategy was PVI (59.0%) followed by 34.1% of patients who received PVI and additional lines. These numbers reflect adhesion to recent international guidelines [6]. Targets of additional ablation were represented by the roof area and posterior wall. Cavo tricuspid isthmus (CTI) and mitral isthmus ablation were performed in approximately 10% of cases each to treat right and left macro-reentry tachycardias.
In a meta-analysis including 956 patients with PersAF, single procedure arrhythmia-free survival for PVI alone showed 66.7% at 12-month follow-up [15]. These data position therapy towards palliation rather than a cure as a realistic future goal. Acute success in this cohort, defined as acute termination or non-inducibility of clinical arrhythmia, was 85.9%, taking into account that cardioversion was allowed prior to final induction. 82.0% of patients were free from atrial recurrence as documented by 48-h Holter monitoring at the 12-month follow-up visit and new or increased dose of class I/III AADs. This finding includes patients with PVI only and patients with PVI and additional lines mainly at the roof and posterior wall. This rather high percentage of patients free of recurrence compared to other studies should be cautiously interpreted [7, 16–18]. It is also important to recall this study enrolled patients with previous ablation procedures rather than only performing de novo ablation. This also applies to the high percentage of patients (97%) who did not receive repeat ablation procedures after the 90-day blanking period to specifically treat AF. Another very promising finding is that catheter ablation significantly improves quality of life measured by AFEQT and EQ-5D-5L VAS Score which goes along with other recent studies [19, 20]. These data emphasize the utility of the Advisor™ HD grid mapping catheter to identify ablation strategies resulting in effective ablation procedures and improved QOL.
A total of 6.0% of PersAF patients experienced a SAE or SADE. However, only one out of 54 total adverse events, a procedure related stroke, was linked to the use of the Advisor™ HD Grid catheter. One patient death occurred due to a severe intracranial hemorrhage 226 days after the index procedure and was considered not related to the procedure. These data underline the safety of the Advisor HD Grid catheter.
Study limitations
Due to the COVID-19 pandemic, early enrollment closures were implemented, thus impacting the study sample size. Additionally, the pandemic prevented many patients from completing required Holter monitoring at their 12-month follow-up visit. This significantly impeded data collection for long-term effectiveness as the analysis of arrhythmia recurrence only considered failures if it was documented by the 48-h Holter monitor. Other forms of arrhythmia documentation were collected at unscheduled visits or 6-month follow-up but were not included in this analysis. As this study was designed to collect data on how the HD Grid catheter was used in the real-world setting, there were no rigid mapping protocols but rather strong recommendations for generating maps with the HDWS configuration versus the standard configuration. Data on mapping comparisons, such as “change in ablation strategy,” were reported by physicians in categorical form. This limits the ability to report details of ablation targets or how ablation strategy differed between HDWS and standard configuration comparisons. Additionally, comparisons of the pre-ablation HDWS configuration maps to the standard electrode configuration maps were largely performed after the procedure was completed and the study was not designed to prospectively compare outcomes related to HDWS guided ablation strategies. Further research is needed to better understand how ablation strategy is impacted by the difference in electroanatomical maps identified in the current study, and how the impacted ablation strategy affects long-term outcomes.
Conclusion
The use of the Advisor™ HD Grid Mapping Catheter, Sensor Enabled™ catheter with the ability to analyze and compare orthogonal signals is feasible and has the potential to influence the ablation strategy in PersAF with high acute and long-term success rates. Overall, this study provides evidence supporting the use of the HD Grid catheter and the HDWS electrode configuration to create detailed, high-quality maps to perceptively search for and identify substrates such as low voltage to treat PersAF subjects. The results of this study support the safety and utility of electroanatomical mapping with HD Grid in subjects with complex arrythmias in the real-world setting.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (PDF 526 kb)
Funding
The Advisor™ HD Grid Observational Study was supported by the manufacturer of the Advisor™ HD Grid Mapping Catheter, Sensor Enabled, Abbott Laboratories.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
Declarations
Ethics approval
The conduct of the clinical study was in accordance with the Declaration of Helsinki and approved by the appropriate Ethics Committee of the respective clinical sites and as specified by local regulation.
Consent to participate
All patients enrolled in the study provided written informed consent.
Conflict of interest
D.S. has received personal fees from Abbott, grants from Abbott and Boston Scientific, and other support from Biotronik. H.H. has received honoraria for lectures and proctoring from Abbott and Boston Scientific. J.L. has received consulting fees and grants or contracts from Abbott and Biosense Webster. All remaining authors have declared no conflicts of interest.
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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6. Hindricks G Potpara T Dagres N 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Eur Heart J 2021 42 5 373 498 10.1093/eurheartj/ehaa612 32860505
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8. Ackerman MJ Priori SG Willems S HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: This document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA) EP Europace 2011 13 8 1077 109 10.1093/europace/eur245 21810866
9. Schade A Costello-Boerrigter L Steinborn F Voltage-guided ablation in persistent atrial fibrillation—favorable 1-year outcome and predictors J Interv Card Electrophysiol 2021 62 2 249 257 10.1007/s10840-020-00882-z 33030630
10. Rolf S, Hindricks G, Sommer P, et al. Electroanatomical mapping of atrial fibrillation: Review of the current techniques and advances. Rolf S, Hindricks G, Sommer P, Richter S, Arya A, Bollmann A, Kosiuk J, Koutalas E.J. Atr Fibrillation. 2014;7(4):1140. 10.4022/jafib.1140
11. Saini A, Huizar JF, Tan A, Koneru JN, Ellenbogen KA, Kaszala K. Scar homogenization in atrial fibrillation ablation: evolution and practice. Journal of Atrial Fibrillation 2017;10(3), 10.4022/jafib.1645 [published Online First: Epub Date]|.
12 Castrejón-Castrejón S Ortega M Pérez-Silva A Organized atrial tachycardias after atrial fibrillation ablation Cardiol Res Pract 2011 2011 1 16 10.4061/2011/957538
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14. Kosiuk J Hilbert S John S Bertagnolli L Hindricks G Bollmann A Preliminary experience with high-density electroanatomical mapping for ablation of atrial fibrillation–Comparison of mini-basket and novel open irrigated magnetic ablation catheter in consecutive patients Int J Cardiol 2017 228 401 405 10.1016/j.ijcard.2016.11.243 27870969
15 Voskoboinik A Moskovitch JT Harel N Sanders P Kistler PM Kalman JM Revisiting pulmonary vein isolation alone for persistent atrial fibrillation: a systematic review and meta-analysis Heart Rhythm 2017 14 5 661 67 10.1016/j.hrthm.2017.01.003 28434446
16. Vogler J Willems S Sultan A Pulmonary vein isolation versus defragmentation: the CHASE-AF clinical trial J Am Coll Cardiol 2015 66 24 2743 2752 10.1016/j.jacc.2015.09.088 26700836
17. Wynn GJ Panikker S Morgan M Biatrial linear ablation in sustained nonpermanent AF: results of the substrate modification with ablation and antiarrhythmic drugs in nonpermanent atrial fibrillation (SMAN-PAF) trial Heart Rhythm 2016 13 2 399 406 10.1016/j.hrthm.2015.10.006 26455343
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| 36481832 | PMC9735148 | NO-CC CODE | 2022-12-14 23:28:32 | no | J Interv Card Electrophysiol. 2022 Dec 8;:1-11 | utf-8 | J Interv Card Electrophysiol | 2,022 | 10.1007/s10840-022-01442-3 | oa_other |
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Nat Rev Genet
Nat Rev Genet
Nature Reviews. Genetics
1471-0056
1471-0064
Nature Publishing Group UK London
36473953
564
10.1038/s41576-022-00564-8
Research Highlight
A deep learning method to map tissue architecture
Koch Linda [email protected]
Nature Reviews Genetics, http://www.nature.com/nrg/
6 12 2022
11
© Springer Nature Limited 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
A new study in Nature Methods describes a computational method named UTAG (unsupervised discovery of tissue architecture with graphs) that aims to identify and quantify higher-level tissue domains from biological images without previous knowledge.
Subject terms
Genetic techniques
Genomic analysis
Machine learning
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pmcChanges in patterns at the tissue and organ level can be a sign of disease development, but combining single-cell data with maps of tissue structure to reveal these patterns relies on time-consuming manual annotation. A new computational method named UTAG (unsupervised discovery of tissue architecture with graphs) promises to identify and quantify organ-specific micro-anatomical domains from biological images without previous knowledge.
The central concept of UTAG is that it leverages multiplexed images to extract and then combine single-cell phenotypical data (such as cell morphology and gene or protein expression) with information on the physical proximity of cells in their native tissue context. Images can be obtained by a range of highly multiplexed single-cell imaging methods, including CODEX (codetection by indexing), CyCIF (cyclic immunofluorescence), IMC (imaging mass cytometry), MIBI (multiplexed ion beam imaging) and multiplexed spatial platforms.Coolstuff/Alamy Stock Photo
UTAG uses unsupervised deep learning to convert cellular phenotypes, such as expression intensities, into a numeric feature matrix, which comprises every marker for each cell. In addition, the model constructs a graph of physical cellular interactions based on the spatial location of cells in the image. This graph is then converted to a binary adjacency matrix (0 for no interaction, 1 for interaction between cells). The two matrices are combined to create a new matrix comprising spatially aggregated phenotypic information, which can be used by clustering methods to group phenotypically and spatially related cells into tissue domains.
The team first tested UTAG on 26 highly multiplexed IMC images of healthy lung tissues, comprising 28 markers. To serve as a reference, micro-anatomical domains, such as airways and vessels, were manually annotated, and UTAG was able to accurately identify corresponding micro-anatomical domains.
Applying their method to diseased lung tissues, using a dataset of 239 IMC images with 37 markers, identified 6 micro-anatomical domains across different disease states, representing airways, vessels and connective tissue, among others. The relative abundance of the domains was dependent on disease state, with, for example, a large proportion of connective tissue in samples of a patient with late-stage COVID-19, which is indicative of fibrosis. The authors were also able to quantify physical interactions between domains, revealing structural differences between healthy and diseased tissues.
“group phenotypically and spatially related cells into tissue domains”
The authors note that the successful application UTAG depends on “the interpretation of the discovered topological domains in terms of their identity and biological relevance”, and thus recommend the involvement of field experts such as pathologists when applying their approach.
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References
Original article
Kim J Unsupervised discovery of tissue architecture in multiplexed imaging Nat. Methods 2022 10.1038/s41592-022-01657-2
| 36473953 | PMC9735151 | NO-CC CODE | 2022-12-14 23:28:32 | no | Nat Rev Genet. 2022 Dec 6;:1 | utf-8 | Nat Rev Genet | 2,022 | 10.1038/s41576-022-00564-8 | oa_other |
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Glob Soc Welf
Glob Soc Welf
Global Social Welfare
2196-8799
Springer International Publishing Cham
259
10.1007/s40609-022-00259-2
Article
Effect of Financial Literacy on Poverty Reduction Across Kenya, Tanzania, and Uganda
http://orcid.org/0000-0002-2929-4992
Koomson Isaac [email protected]
[email protected]
15
http://orcid.org/0000-0002-4624-3337
Ansong David [email protected]
2
http://orcid.org/0000-0003-2555-3077
Okumu Moses [email protected]
3
http://orcid.org/0000-0002-6190-528X
Achulo Solomon [email protected]
4
1 grid.1003.2 0000 0000 9320 7537 Centre for the Business and Economics of Health, The University of Queensland, St Lucia, QLD Australia
2 grid.10698.36 0000000122483208 School of Social Work, University of North Carolina at Chapel Hill, Chapel Hill, NC USA
3 grid.35403.31 0000 0004 1936 9991 School of Social Work, University of Illinois at Urbana-Champaign, Champaign, IL USA
4 grid.4367.6 0000 0001 2355 7002 Brown School, Washington University in St. Louis, St. Louis, MO USA
5 grid.512787.e Network for Socioeconomic Research and Advancement (NESRA), Accra, Ghana
9 12 2022
111
27 11 2022
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Financial literacy can be critical to reducing poverty, but limited evidence exists on the mechanisms of change. Guided by the financial capability framework, this study examines the direct effects of financial literacy on poverty and the indirect effect through financial inclusion and entrepreneurship, using data from wave 5 of the InterMedia Financial Inclusion Insights Program for Kenya, Tanzania, and Uganda. We also examined how the relationships differ by gender and locality. Overall, the endogeneity-corrected results suggest that an increase in financial literacy is associated with a 6.9% decrease in poverty. We found that entrepreneurship and financial inclusion act as mechanisms of change through which financial literacy decreases poverty, with the findings differing by gender and locality. These findings point to the poverty-reducing effect of financial literacy, mainly in Tanzania, followed by Kenya and Uganda. The results contribute to understanding how financial literacy and poverty interact and can inform contextually relevant interventions and policies.
Keywords
Financial literacy
Poverty
Entrepreneurship
Financial inclusion
East Africa
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pmcIntroduction
Before the COVID-19 pandemic, sub-Saharan Africa (SSA) was making positive strides in poverty reduction, shrinking the number of people living in extreme poverty from 56% in 1990 to 34% in 2018 (World Bank, 2020). The prolonged COVID-19 pandemic has eroded these poverty reduction gains (UNCTAD, 2021). Financial literacy (i.e., financial knowledge and skills) is critical to reducing poverty (World Bank, 2018). Two potential pathways by which financial literacy could contribute to poverty reduction are its initial influence on financial inclusion (i.e., access to financial systems and services) and entrepreneurship. However, scant evidence exists on these pathways within the financial literacy-poverty reduction literature (Askar et al., 2020; Engelbrecht, 2008; Faboyede et al., 2015). Even further, persistent gender disparities in financial literacy that may affect these pathways are understudied. This study fills these knowledge gaps by addressing the following research questions: (a) What is the effect of financial literacy on poverty? (b) What pathways transmit the effects of financial literacy on poverty? and (c) To what extent do the effects and pathways depend on gender and locational differences? Empirical insights into these questions could help shed light on how financial literacy could be integrated into poverty reduction strategies and policies to help reduce poverty in SSA.
Financial literacy in SSA is suboptimal. A recent global study found that financial literacy in SSA remains low at 32% compared to 52% in high-income countries (Fanta & Mutsonziwa, 2021). In some SSA regions, such as East Africa, the financial literacy level is even lower. For instance, only 38% of Kenyans, 34% of Ugandans, and 40% of Tanzanians are financially literate (Klapper et al., 2015). East Africa has the highest mobile money penetration rate (i.e., the most popular fintech product in SSA) due to its role as the global hub for mobile money transactions (GSMA, 2019). Mobile money account ownership rates in Kenya (73%), Uganda (51%), and Tanzania (39%) are some of the highest in SSA (Demirgüç-Kunt et al., 2018). In these economies, the mobile money ecosystems have progressed beyond basic payment systems to sophisticated structures that provide savings, credit, insurance, and other services (Koomson, Martey et al., 2022). Although the region boosts of an impressive financial technology (fintech) revolution and start-ups, the low financial literacy is empirically puzzling, especially in contexts with high poverty rates such Kenya (37.1%), Uganda (41.5%), and Tanzanians (49.4%; World Bank, 2020). To address this evidence gap, there is a need to understand how financial literacy can be leveraged as a policy tool to address the rising poverty in East Africa.
Guided by the financial capability framework (Ansong et al., 2020; Sherraden, 2013; Sherraden & Ansong, 2013), this study tests the link between financial literacy and poverty. The financial capability framework posits that when individuals and households are financially literate and have an enabling environment where they can easily access and utilize financial services and products, then they can improve their livelihoods and well-being (Ansong et al., in press; Ansong et al., 2020; Sherraden, 2013). Individuals and families who are financially literate make sound financial management decisions, resulting in more efficient consumption and increased accumulation of both financial and durable assets (Atkinson & Messy, 2013). Evidence points to financial literacy’s direct influence on poverty through increased food and non-food household consumption (Dinkova et al., 2021), an essential indicator of poverty (Askar et al., 2020; Faboyede et al., 2015; Meyer & Sullivan, 2012; World Bank, 2001). This suggests that financial literacy can assist individuals in escaping poverty through increased asset building.
Financial literacy can directly or indirectly influence poverty through financial inclusion and entrepreneurship pathways (see Fig. 1). Evidence shows that financial literacy may affect financial inclusion (access and utilization of beneficial financial services) and shape entrepreneurial practices and choices (Awaworyi, Churchill & Marisetty, 2020; Koomson et al., 2020a; Koomson & Danquah, 2021; Timbile & Kotey, 2022). First, the financial inclusion pathway suggests that financial literacy can reduce vulnerability to poverty through its positive effect on beneficial financial products and services (Koomson et al., 2020a; Timbile & Kotey, 2022). The World Bank (2018) recognizes financial literacy as a key driver to achieving universal financial access. The extant literature also shows that financial literacy significantly enhances financial inclusion (Atkinson & Messy, 2013; Calcagno & Monticone, 2015; Klapper et al., 2013; Koomson et al., 2020b). Second, the entrepreneurship pathway suggests that financial literacy can contribute to poverty reduction through its potential role in enhancing entrepreneurship. For instance, Saptono (2018) found that an increase in financial literacy is associated with a 9.8% increase in entrepreneurship skills among Indonesians. Similarly, Oseifuah (2010) and Burchi et al. (2021) found that financial literacy enhances entrepreneurship intentions and how entrepreneurs grow their businesses. Entrepreneurs play a significant role in poverty reduction in Kenya (Misango & Ongiti, 2013), and China (Si et al., 2015). Financial fragility can impede entrepreneurship because financial constraint is considered one of the most significant barriers to entrepreneurship in emerging economies (Daniels et al., 2016; Peprah & Koomson, 2015). Financial fragility emanating from lower levels of financial literacy can decrease asset accumulation and household consumption. This implies that if financial literacy is misapplied, it might worsen poverty through the above-mentioned pathways. We use data from three East African countries—Kenya, Tanzania, and Uganda—to empirically examine the financial inclusion and entrepreneurship pathways.Fig. 1 Pathways from financial literacy to poverty
The study also explores gender differences in the effect of financial literacy on poverty, which is currently unexplored in emerging economies (Klapper et al., 2015). Gender’s role is particularly amplified through the stack and persistent gender differences in the two mediators—financial inclusion and entrepreneurship—linking financial literacy and poverty. For instance, wide gender gaps exist in entrepreneurship in Kenya (15%), Tanzania (7.05%), and Uganda (11.5%). Similarly, gender differences in financial inclusion persist in Kenya (8%), Tanzania (9%), and Uganda (13%). These gender differences may even be wider for individuals living in rural vs. urban areas. Individuals living in rural areas may be held back by restrictive social norms, especially women who face multiple barriers in navigating financial services and entrepreneurship opportunities. These discriminatory laws, social norms, locality disparities and lack of gender-responsive financial infrastructure affect the financial literacy-poverty relationship (Ansong et al., 2020; Calcagno & Monticone, 2015; Murendo & Mutsonziwa, 2017; Okumu et al., 2021). This study’s pursuit of gender- and location-disaggregated analyses in financial literacy will provide further knowledge on the extent to which gender and locality either strengthen or weaken the financial inclusion and entrepreneurship pathways. This evidence will inform gender- and location-specific interventions and policies, fostering greater consideration of known disparities.
Therefore, guided by the financial capability framework, the current study examines the direct effects of financial literacy on poverty and the indirect effect through financial inclusion and entrepreneurship, using data from three East African countries—Kenya, Tanzania, and Uganda. We also examine how gender and locality may affect the relationships. To achieve these objectives while producing consistent results, we address the endogeneity problem associated with financial literacy (Calcagno & Monticone, 2015; Fernandes et al., 2014; Lusardi & Mitchelli, 2007; Murendo & Mutsonziwa, 2017).
Data, Variables, and Model Specification
The secondary data employed in this paper is from Wave 5 (2017) of the InterMedia Financial Inclusion Insights (FII) Program (InterMedia, 2017). Although the FII program was carried out in different years across 12 emerging economies, we use data for Kenya, Tanzania, and Uganda because these are the only countries in East Africa with wave 5 data. The FII data contains information on respondents aged 15 and above, corresponding to the age cut-off used in the Global Findex database (Demirgüç-Kunt et al., 2018). Apart from data on respondents’ ownership and use of financial productions, the FII data also contains information on financial literacy, financial well-being, entrepreneurship, poverty, demography, and response to shocks. The surveys used a two-stage stratified cluster sampling design (InterMedia, 2017). The dataset included 3129 households in Kenya, 3060 in Tanzania, and 3001 in Uganda. The samples were reduced to 3111 households in Kenya, 3048 in Tanzania, and 2985 in Uganda after accounting for missing observations in the key variables and the covariates.
Financial Literacy
We use a set of seven questions on financial literacy from the InterMedia FII Program’s questionnaire (InterMedia, 2017). The questions sought to determine respondents’ financial knowledge across basic numeracy, risk diversification, inflation, interest rates, and compound interest. For each respondent, a correct response is assigned the value 1, while a wrong response is given the value 0 (Klapper & Lusardi, 2020; Murendo & Mutsonziwa, 2017). From the seven questions, we generate an additive financial literacy score that ranges from 0 to 7. Higher scores represent higher levels of financial literacy.
Poverty
The poverty measure used in the InterMedia FII program is the progress out of poverty index (PPI) (InterMedia, 2017), which uses a standard set of 10 easy-to-answer questions to estimate consumption-based poverty rates for each household included in pro-poor programs (Schreiner, 2017). Examples of the PPI questions which revolve around deprivations in asset ownership, materials for roofs and walls, education, and employment include, “What is the main source of lighting fuel for the household? What is the highest grade that the female head/spouse has completed?” The responses to the ten questions are converted to a probability that the respondent's household is below the national poverty line and other globally recognized poverty lines. The PPI scores range from 0 to 100, with 0 representing the poorest households and 100 representing the wealthiest households. The PPI scores are converted to determine whether a respondent’s household lives below the poverty line of $2.50 per day (Chua et al., 2012; InterMedia, 2017). For the binary poverty variable, 1 denotes living below the poverty line and 0 above the poverty line (i.e., “1 = Poor”; “0 = Non-poor”).
Empirical Model
We employ a Probit model to estimate the association between financial literacy and poverty since poverty is captured as a binary variable. The model for obtaining our preliminary results is specified in Eq. (1).1 PrPovij|Xij=αFLij+βXij+ϑj+εij
where Povij is a binary variable for the poverty status of household i in country j. FLij is a continuous variable representing the financial literacy score for household head i in country j; and X is a vector of control variables considered as other poverty determinants in extant studies (Awaworyi Churchill & Marisetty, 2020; Koomson & Danquah, 2021; Koomson et al., 2020a). These variables include age, gender, education, household size, location, mobile phone ownership, marital status, and religion. ϑj captures country-specific fixed effect while ε is a random error term.
As indicated in previous studies that have analyzed the link between financial literacy and various welfare outcomes, financial literacy is endogenous, and failure to address it will produce biased estimates (Calcagno & Monticone, 2015; Fernandes et al., 2014; Lusardi & Mitchelli, 2007; Murendo & Mutsonziwa, 2017; Van Rooij et al., 2011). In previous studies, the endogeneity problem has been resolved using the average level of financial literacy within one’s region/province (Calcagno & Monticone, 2015; Fernandes et al., 2014; Murendo & Mutsonziwa, 2017), parents’ or siblings’ financial experience (Van Rooij et al., 2011), or background knowledge in economics or business (Lusardi & Mitchelli, 2007) in a two-stage least squares (2SLS) or instrumental variable (IV) regression. Consistent with these studies (see, e.g., Calcagno & Monticone, 2015; Fernandes et al., 2014; Murendo & Mutsonziwa, 2017), we resolve the endogeneity in this study using an IV-Probit model in which the average financial literacy among a respondent’s neighbors (outside their households) is employed as an instrument. Unlike previous studies, we do not generate the overall mean level of financial literacy within respondents’ neighborhoods. However, we apply the leave-out mean approach, which generates the average neighborhood level of financial literacy for each respondent by excluding the household the respondent belongs. This approach helps avoid any potential problem of violating the exclusive restriction condition which can render the instrument invalid.
Apart from the IV-Probit method, we test for consistency in findings by applying the Lewbel (2012) 2SLS method used widely in the literature to address endogeneity (Koomson & Awaworyi Churchill, 2021; Koomson & Danquah, 2021). Table 5 presents the description and summary statistics for all variables included in the analysis.Table 1 Financial literacy and poverty (Probit results)
(1) (2) (3) (4)
Full Kenya Tanzania Uganda
Poverty (0/1) ME ME ME ME
Financial literacy − 0.023*** − 0.023*** − 0.021*** − 0.013*
(0.005) (0.006) (0.005) (0.008)
Age 0.001 − 0.005 0.001 0.003
(0.002) (0.003) (0.002) (0.004)
Female − 0.037*** − 0.082*** − 0.014 − 0.097***
(0.013) (0.017) (0.014) (0.025)
Education (Base = Polygamy)
Primary − 0.167*** − 0.258*** − 0.109*** − 0.110***
(0.023) (0.029) (0.029) (0.035)
Secondary − 0.403*** − 0.472*** − 0.208*** − 0.291***
(0.025) (0.032) (0.031) (0.041)
Tertiary − 0.624*** − 0.626*** − 0.261*** − 0.475***
(0.041) (0.052) (0.046) (0.092)
Household size 0.033*** 0.107*** 0.069*** − 0.149***
(0.003) (0.005) (0.004) (0.008)
Rural 0.287*** 0.144*** 0.133*** 0.306***
(0.014) (0.019) (0.013) (0.027)
Mobile phone − 0.262*** − 0.127*** − 0.071*** − 0.439***
(0.015) (0.020) (0.015) (0.026)
Marital status (Base = Never married)
Polygamy 0.163*** 0.084** 0.037 0.156***
(0.027) (0.034) (0.031) (0.047)
Monogamy 0.062*** − 0.046** − 0.014 0.165***
(0.016) (0.021) (0.016) (0.031)
Divorced/Separated/Divorced 0.054** 0.127*** 0.029 0.269***
(0.023) (0.031) (0.023) (0.040)
Religion (Base = no religion)
Christianity − 0.127 − 0.072 − 0.171* − 0.385**
(0.081) (0.091) (0.100) (0.172)
Islam − 0.127 0.075 − 0.185* − 0.544***
(0.082) (0.096) (0.100) (0.175)
Traditional Africa − 0.354* 0.021 — —
(0.195) (0.137) — —
Hinduism/Buddhism − 0.300** — − 0.422** − 0.497**
(0.125) — (0.174) (0.210)
Country fixed effects Yes No No No
Observations 9149 3111 3048 2985
Robust standard errors in parentheses
* p < 0.1; ** p < 0.05; *** p < 0.01; ME, marginal effects
Mediation Analysis
We also investigated the potential roles of entrepreneurship and financial inclusion as potential pathways via which financial literacy influences poverty. We use a two-step process to confirm whether these variables are significant pathways in line with previous studies (Kofinti et al., 2022; Koomson & Awaworyi Churchill, 2021; Koomson & Danquah, 2021). Entrepreneurship is measured using a binary variable, where 1 refers to self-employment and 0 if otherwise (Nikolaev et al., 2020; Peprah et al., 2015). Financial inclusion is measured using a multidimensional approach that cuts across three dimensions: account ownership, access to credit, and insurance ownership. After obtaining the multidimensional financial inclusion score, we applied a cut of 0.5 to obtain a binary measure of financial inclusion where 1 is assigned to a household head whose financial inclusion score is greater than 0.5 and 0 if otherwise (see, e.g., Koomson & Danquah, 2021; Zhang & Posso, 2019). In the second step, we independently include the potential mediators as additional control variables and note how the coefficient of financial literacy reacts. If any of them is a mediator, its inclusion should result in the shrinking of the magnitude of the coefficient of financial literacy, or it must become statistically insignificant.
Results
Preliminary Results
This section reports preliminary estimates for the relationship between financial literacy and poverty in Table 1. Overall, these results suggest that financial literacy is significantly associated with poverty reduction in East Africa. Results for all countries are displayed in Column 1, while Columns 2 to 4 report estimates for Kenya, Tanzania, and Uganda, respectively. Specifically, we see in Column 1 that a unit increase in financial literacy is associated with a decrease in the probability of being poor by 2.3% points. At the country level, an increase in financial literacy is linked to a decrease in the probability of being poor by 2.3% points in Kenya, 2.1 in Tanzania, and 1.3 in Uganda. Although our analyses depict an inverse relationship between financial literacy and poverty, these Probit estimates can be biased because financial literacy has been identified as inherently endogenous. We resolve the endogeneity problem in the “Financial literacy” section using an IV-Probit model, which employs an external instrument.Table 2 Financial literacy and poverty (IV-Probit results)
(1) (2) (3) (4)
Poverty (0/1) Full Kenya Tanzania Uganda
Pane A: Full sample
Financial literacy − 0.069*** − 0.059*** − 0.067*** − 0.042***
(0.007) (0.011) (0.013) (0.010)
Household head variables Yes Yes Yes Yes
Country fixed effects Yes No No No
First stage
Average FL among neighbors 0.894*** 0.908*** 0.834*** 0.924***
(0.022) (0.039) (0.041) (0.038)
F-statistic of first stage 1613.08 553.48 407.51 595.77
Observations 9149 3111 3048 2985
Pane B: Rural sample
Financial literacy − 0.055*** − 0.066*** − 0.027* − 0.036***
(0.009) (0.015) (0.014) (0.012)
Household head variables Yes Yes Yes Yes
Country fixed effects Yes No No No
First stage
Average FL among neighbors 0.892*** 0.902*** 0.838*** 0.941***
(0.026) (0.049) (0.049) (0.043)
F-statistic of first stage 1134.42 340.32 296.31 482.71
Observations 6128 1912 2059 2155
Pane C: Urban sample
Financial literacy − 0.114*** − 0.056*** − 0.154*** − 0.064***
(0.011) (0.019) (0.018) (0.020)
Household head variables Yes Yes Yes Yes
Country fixed effects Yes No No No
First stage
Average FL among neighbors 0.902*** 0.934*** 0.831*** 0.894***
(0.043) (0.063) (0.080) (0.082)
F-statistic of first stage 452.23 216.06 105.70 116.02
Observations 3003 1197 983 823
Pane D: Male sample
Financial literacy − 0.074*** − 0.063*** − 0.086*** − 0.045***
(0.012) (0.021) (0.022) (0.017)
Household head variables Yes Yes Yes Yes
Country fixed effects Yes No No No
First stage
Average FL among neighbors 0.847*** 0.790*** 0.771*** 0.938***
(0.035) (0.061) (0.067) (0.058)
F-statistic of first stage 579.88 165.86 130.58 257.97
Observations 3450 1165 1162 1120
Pane E: Female sample
Financial literacy − 0.065*** − 0.060*** − 0.056*** − 0.039***
(0.008) (0.013) (0.016) (0.013)
Household head variables Yes Yes Yes Yes
Country fixed effects Yes No No No
First stage
Average FL among neighbors 0.926*** 0.998*** 0.870*** 0.912***
(0.029) (0.049) (0.052) (0.050)
F-statistic of first stage 1036.42 405.20 275.84 334.70
Observations 5699 1946 1885 1865
Note: FL, financial literacy; Standard errors in parentheses
* p < 0.1; ** p < 0.05; *** p < 0.01
The significant results of the control variables in Column 1 indicate a positive relationship between the household head’s age and poverty. Female heads, the educated, those who own mobile phones, and urban residents are less likely to be poor. Also, those married, separated, or divorced are more likely to be poor than those who have never married.
Endogeneity-Corrected Results
This section employs the average financial literacy score among respondents’ neighbors as an instrument in an IV-Probit regression and presents the results in Table 2. Expectedly, the first stage estimates show that the higher the level of financial literacy in a respondent’s neighborhood, the higher the respondent’s own level of financial literacy (Calcagno & Monticone, 2015; Fernandes et al., 2014; Murendo & Mutsonziwa, 2017). The F-statistics are above the threshold of 10, which implies that the instrument is not weakly associated with financial literacy (Stock & Yogo, 2002). Furthermore, the instrumented results are all greater than the preliminary results, signifying that the endogeneity related to financial literacy biased the preliminary estimates downwards. Based on the biasedness of the preliminary results, the endogeneity-corrected estimates are our preferred estimates. Specifically, we observe in Column 1 that an increase in financial literacy reduces poverty by 6.9% points across all countries. When disaggregated by countries, a unit increase in financial literacy is associated with a decrease in the probability of poverty by 5.9% points in Kenya, 6.7 in Tanzania, and 4.2 in Uganda. Our findings suggest that improved financial literacy can be employed as an effective policy strategy for reducing poverty. This finding supports those of Askar et al. (2020) and Faboyede et al. (2015), who have shown that financial literacy is capable of aiding in the reduction of poverty. However, our study focuses on East Africa, which has become home to emerging financial technologies with improved financial literacy as a corollary. Comparatively, respondents in Tanzania are most likely to experience the strongest effect of financial literacy on poverty reduction, followed by Kenya and Uganda, respectively.Table 3 Association between financial literacy and entrepreneurship and financial inclusion
(1) (2)
Poverty (0/1) Entrepreneurship Financial inclusion
Financial literacy 0.013*** 0.019***
(0.004) (0.004)
Household head variables Yes Yes
Household-level variables Yes Yes
Country fixed effects Yes Yes
Observations 9135 5363
Financial literacy; Robust standard errors in parentheses
* p < 0.1; ** p < 0.05; *** p < 0.01
Location and Gender Dimension
In this section, we report location-specific results to explore the differential effects of financial literacy on poverty for rural and urban residents. In Table 3, we report the results for the rural sample in Panel B and see in Column 1 that, overall, a unit increase in financial literacy is associated with a decrease in the probability of being poor in a rural area by 5.5% points. Also, an increase in financial literacy by a unit is related to reductions in the likelihood of poverty by 6.6%, 2.7%, and 3.6% points in the rural areas of Kenya, Tanzania, and Uganda, respectively. In Column 1 of Panel C, we observe that a unit increase in financial literacy generally decreases the probability of being poor in an urban area by 11.4% points. From Columns 2 to 4, we see that a unit increase in financial literacy is associated with a decrease in the probability of poverty by 5.6% points in urban Kenya, 15.4 in urban Tanzania, and 6.4 in urban Uganda. Overall, financial literacy has a bigger poverty-reducing effect in urban than rural areas. The bigger poverty-reducing effect of financial literacy among urban residents is consistently established in Tanzania and Uganda, except in Kenya, where financial literacy reduces poverty more among rural households.
Gender-wise, we report results for the male and female subsamples, respectively, in Panels D and E of Table 3. In Column 1 of Panel D, we find that, across all countries, a unit increase in financial literacy is associated with 7.4% points decrease in the probability of poverty among male-headed households. Our overall results in Column 1 of Panel E show that an increase in financial literacy by a unit is linked to 6.5% points decrease in the probability of poverty among female-headed households. Comparatively, these results show that financial literacy reduces poverty more among male- than female-headed households. The greater effect of financial literacy in reducing poverty among male-headed households is consistent across all the sampled countries.
Robustness Checks
In this section, we check for consistency in our endogeneity-corrected estimates using the Lewbel (2012) 2SLS method and present the results in Table 6. We employ the Lewbel method, combining external and internally generated instruments. The results from the Lewbel regression for all countries in Colum 1 show that, overall, an increase in financial literacy reduces poverty by 5.6% points. For specific countries, a unit increase in financial literacy is associated with a decrease in the probability of poverty by 6.7%, 5.5%, and 3.5% points, respectively, in Kenya, Tanzania, and Uganda. Consistent with existing literature, the Lewbel results, which correct for endogeneity, are greater than the Probit estimates but lower than the IV-Probit results (Awaworyi Churchill & Marisetty, 2020; Koomson & Danquah, 2021). This implied that the poverty-reducing effect of financial literacy is consistent across different endogeneity-correcting models.
Financial Inclusion and Entrepreneurship as Pathways
Per our two-step mediation modeling approach, financial literacy is significantly associated with entrepreneurship and financial inclusion in the first step. The results in Table 3 show that financial literacy is associated with increases in entrepreneurship (Saptono, 2018), and financial inclusion (Koomson et al., 2020b; Koomson, Martey et al., 2022) by 1.3 and 1.9% points, respectively. In Panel A of Table 4, we include entrepreneurship and financial inclusion as covariates and report the results in Columns 1 and 2, respectively. In Column 1, we see that entrepreneurship and financial inclusion are associated with 5.9 and 11.2% points decrease in poverty, respectively. The full model preliminary results for comparison are reported in Panel B. Since the models which included the mediators (see Panel A) have reduced sample sizes, we re-estimate the preliminary models without the mediators (see Panel B) to ensure the coefficients for comparison are obtained from the same sample. This is done to provide adequate grounds on which to compare estimates. After including entrepreneurship and financial inclusion in the models, we see that the coefficients of financial inclusion in Columns 1 and 2 of Panel A have reduced in magnitude compared to those in Panel B, which implies that these variables serve as key pathways through which financial literacy influences poverty. In other words, an increase in financial literacy enhances entrepreneurship and financial inclusion, which provides the financial resources required for poverty reduction.Table 4 Mechanisms of change from financial literacy to poverty
(1) (2)
Mediator:
Entrepreneurship Mediator:
Financial inclusion
Poverty (0/1) Full Full
Panel A: Results for mechanism
Financial literacy − 0.023*** − 0.028***
(0.005) (0.006)
Entrepreneurship − 0.059***
(0.014)
Financial inclusion − 0.112***
(0.020)
Household head variables Yes Yes
Household-level variables Yes Yes
Country fixed effects Yes Yes
Observations 9135 5363
Panel B: Initial results for comparison − 0.025*** − 0.030***
Financial literacy (0.005) (0.006)
All controls Yes Yes
Observations 9135 5363
Robust standard errors in parentheses
* p < 0.1; ** p < 0.05; *** p < 0.01
Implications and Conclusion
Financial literacy can help reduce poverty in SSA, but empirical studies on the causal relationship between financial literacy and poverty remain limited. To fill the knowledge gap, we use data from three East African countries (i.e., Kenya, Tanzania, and Uganda) and apply the IV-Probit model to address the potential endogeneity associated with financial literacy. We explored the potential mediating roles of entrepreneurship and financial inclusion and examined how the results vary by subgroups (i.e., gender and locality). Overall, financial literacy decreased poverty consistently across the three sampled countries, with Tanzania having the largest effect compared to Kenya and Uganda. The findings also show that financial literacy’s ability to enhance entrepreneurship and financial inclusion is a key mechanism through which financial literacy reduces poverty. The poverty-reducing effect of financial literacy is generally greater in rural locations and among male-headed households.
Guided by the financial capability framework, our findings show that financial literacy and financial inclusion are crucial in policies that address poverty. Ansong and et al., (2020) argue that programs aiming at advancing the SDG of ending poverty could leverage existing social and economic structures and networks to better support individuals and families to become financially literate and included (i.e., financially capable). For instance, the existing human services workforce at the forefront of developing and implementing poverty reduction strategies could be trained with financial capability competencies to enhance their ability to infuse financial literacy and inclusion into their programming. Similarly, strategies for incorporating financial literacy training into mainstream education systems may also have lasting effects on the financial literacy levels of emerging youth, thus potentially boosting the effectiveness of poverty reduction tools in the sampled countries and across other emerging economies.
Entrepreneurship is critical in alleviating poverty; however, our findings show that financial literacy is required to further shape entrepreneurial practices, as found in other studies (Bhatti et al., 2021). Based on our findings on the mediating role of entrepreneurship, workforce development programs and policies could benefit from the intentional infusion of financial literacy training to promote sustainable and decent employment (i.e., SDG 1 and 8). In a constantly changing financial sector, new entrepreneurs, in particular, may need support in understanding the prevailing financial system to make sound projections and financial decisions for the businesses (e.g., budgeting, credit management, analysis-based decision-making, and growing and controlling businesses; Jiaton et al., 2021). It is plausible that individuals with high financial literacy will have the necessary financial skills, market knowledge, and finance sources to establish and sustain new businesses and thereby accumulate resources and improve their purchasing power (SDG 6). These improvements could help decrease food insecurity (SDG 2) and boost investments in quality education (SDG 4), good health and well-being (SDG 3), and households’ access to clean water and sanitation.
Thus, based on our study findings, we recommend that policymakers, educational institutions, and other development programs adopt and mainstream the implementation of financial capability (i.e., literacy and inclusion) and entrepreneurship programs to reduce poverty and improve the well-being of people. These financial capability and entrepreneurship programs can be included as foundational courses for university students. Financial capability curricula can also be embedded into academic disciplines as a core subject or unit.
For the informal sector, these combined financial capability and entrepreneurship programs can be infused into localized curricula to benefit local groups and informal traders such as market women associations. Policymakers should take seriously and support initiatives to design and promote national financial capability strategies, such as the financial literacy week observed in many emerging countries.
The formal financial sector could also do more to advance financial literacy. Financial institutions and other key players in the financial industry should consider adopting financial literacy as part of their credit programs. Rather than waiting to foreclose businesses when they fail to pay back the loans, it might be prudent for these institutions to provide continuous and on-demand financial literacy to all individuals who seek loans to start businesses. In the coming years, more empirical studies are expected to shed light on the connection between financial literacy and poverty reduction, encouraging more attention to be given to making financial literacy a priority in Sub-Saharan Africa
Appendix
Table 5 Summary statistics
Variable Description Mean Std. Dev
Poor Dummy variable equals 1 if income lived on is less than $2.50 per day 0.535 0.499
Financial literacy score Continuous variable for financial literacy score obtained from all seven questions 3.691 1.465
Age Continuous variable for age of respondent in years 36.029 15.548
Age squared Continuous variable for the squared age of respondent in years 1539.776 1383.064
Female Binary variable equals 1 if respondent is female 0.623 0.485
Primary Binary variable equals 1 if respondent’s educational level if primary 0.508 0.500
Secondary Binary variable equals 1 if respondent’s educational level if Secondary 0.306 0.461
Tertiary Binary variable equals 1 if respondent’s educational level if Tertiary 0.064 0.245
Household size Continuous variable for number of persons in household 3.607 2.218
Rural Binary variable equals 1 if respondent is located in a rural area 0.670 0.470
Mobile phone Binary variable equals 1 if respondent owns a mobile phone 0.664 0.472
Polygamy Binary variable equals 1 if respondent is in a polygamous marriage 0.077 0.266
Monogamy Binary variable equals 1 if respondent is in a monogamous marriage 0.420 0.494
Divorced/Separated/Divorced Binary variable equals 1 if respondent is Divorced/Separated/Divorced 0.149 0.356
Christian Binary variable equals 1 if respondent is Christian 0.799 0.401
Islamic Variables Binary variable equals 1 if respondent is Islamic 0.187 0.390
Traditional Binary variable equals 1 if respondent is Islamic 0.001 0.035
Hinduism/Buddhism/Other Binary variable equals 1 if respondent is into Hinduism/Buddhism 0.004 0.064
Entrepreneurship Binary variable equals 1 if respondent is self-employed 0.304 0.460
Financial inclusion Binary variable equals 1 if respondent’s multidimensional financial inclusion score is greater than 0.5 0.269 0.444
Average financial literacy neighbors (postcode) Average financial literacy score among neighbors within postcode 3.689 0.635
Table 6 Financial literacy and poverty (Lewbel 2SLS): Internal & internal instruments
(1) (2) (3) (4)
Variables Full Kenya Tanzania Uganda
Financial literacy -0.056*** -0.067*** -0.055*** -0.035***
(0.007) (0.012) (0.013) (0.011)
Household head variables Yes Yes Yes Yes
Household level variables Yes Yes Yes Yes
Country fixed effects Yes No No No
First stage
Average FL among neighbours 0.860*** 0.879*** 0.814*** 0.923***
(0.022) (0.038) (0.041) (0.038)
F-statistic 104.29 43.52 30.79 40.21
Observations 9,149 3,113 3,048 2,988
R-squared 0.361 0.391 0.262 0.428
FL = Financial literacy; Standard errors in parentheses
* p< 0.1; p< 0.05; p< 0.01
Declarations
Ethics Approval
This article relies on publicly available secondary data collected with participant consent for the InterMedia Financial Inclusion Insights (FII) Program.
Competing Interests
The authors declare no competing interests.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735152 | NO-CC CODE | 2022-12-14 23:28:32 | no | Glob Soc Welf. 2022 Dec 9;:1-11 | utf-8 | Glob Soc Welf | 2,022 | 10.1007/s40609-022-00259-2 | oa_other |
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Exp Brain Res
Exp Brain Res
Experimental Brain Research
0014-4819
1432-1106
Springer Berlin Heidelberg Berlin/Heidelberg
36462035
6518
10.1007/s00221-022-06518-0
Research Article
Fatigue and perceived fatigability, not objective fatigability, are prevalent in people with post-COVID-19
Fietsam Alexandra C. 1
Bryant Andrew D. 2
http://orcid.org/0000-0002-2057-7793
Rudroff Thorsten [email protected]
13
1 grid.214572.7 0000 0004 1936 8294 Department of Health and Human Physiology, University of Iowa, Iowa City, IA USA
2 grid.412584.e 0000 0004 0434 9816 Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA USA
3 grid.412584.e 0000 0004 0434 9816 Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA USA
Communicated by Bill J Yates.
3 12 2022
19
12 10 2022
26 11 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Persistent symptoms after acute COVID-19 infection, termed post-COVID-19 fatigue, occur in 44–70% of patients. Characterizing fatigue in this population is vital to determine the etiology of post-COVID-19 fatigue symptoms and to assess the effectiveness of potential interventions. The purpose of this study was to assess differences in perceived and objective fatigability between people with post-COVID-19 symptoms (N = 29, 20 females) and people who had COVID-19 but are not experiencing persistent symptoms (N = 20, 12 females). Perceived fatigability, fatigue, pain, and quality of life were assessed with the Fatigue Severity Scale (FSS), Fatigue Assessment Scale (FAS), Visual Analog Scale for Pain (VAS), and the EQ-5D-5L, respectively. Objective fatigability was evaluated with torque and work fatigue indices (FI-T and FI-W), calculated via an isokinetic fatigue task. The results revealed that, the subjects with post-COVID-19 symptoms had significantly higher FAS (p < 0.01), FSS (p < 0.01), VAS (p < 0.01), and EQ-5D-5L VAS (p < 0.01) scores compared to subjects without post-COVID-19 symptoms, indicating greater fatigue and perceived fatigability, increased pain, and worse quality of life. However, there were no differences between the two groups for the FI-Ts (all p ≥ 0.07) or FI-W (all p ≥ 0.08), indicating no differences in objective fatigability. This study found that people with post-COVID-19 symptoms have increased fatigue and perceived fatigability, but not objective fatigability, compared to subjects without post-COVID-19 symptoms.
Keywords
Post-COVID-19
Fatigue
Perception
Performance fatigability
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pmcIntroduction
As of October 2022, over 96 million cases of coronavirus disease 2019 (COVID-19) have been documented in the United States (Centers for Disease Control and Prevention (CDC)). Despite the high (> 90%) survival rate of the acute illness, a proportion of patients continue to experience persistent symptoms (World Health Organization (WHO)). Importantly, post-COVID-19 condition is characterized as symptoms that last for at least two months after an acute COVID-19 illness (WHO). However, these symptoms have been reported to last over six months in some patients (Huang et al. 2021). Post-COVID-19 symptoms include anosmia, ageusia, myalgia, cognitive issues (e.g., memory or concentration), and, importantly, fatigue (WHO).
Persistent fatigue is one of the most common symptoms, occurring in 44–70% of patients, independent of the severity of the initial infection (i.e., hospitalized vs. non-hospitalized) (Huang et al. 2020; Wang et al. 2020; Xu et al. 2020; Schulze et al. 2022). Wijeratne et al. (Wijeratne and Crewther 2021) reported that, despite complete recovery after infection, 71–87% of people with COVID-19 report fatigue 2–3 months after initial infection. Interestingly, rates of persistent symptoms after COVID-19, particularly fatigue, have been thought to be higher in females than males (Bechmann et al. 2022; Ceban et al. 2022; Fernandez-de-Las-Penas et al. 2022). Although fatigue is a frequent and disabling symptom by people with various neurological disorders (e.g., multiple sclerosis (Krupp 2006) and Parkinson Disease (Friedman et al. 2007)), it remains not well understood, perhaps because there are several potential contributing factors (i.e., central, peripheral, and psychological factors) (Rudroff et al. 2020). In general, fatigue describes the feelings of tiredness, lack of energy, low motivation, and difficulty in concentrating and can only be measured by self-report (Enoka et al. 2021). Fatigability, on the other hand, is a measure of physical or cognitive work capacity. Specifically, perceived fatigability subjectively estimates past or future work capacity whereas objective fatigability determines the magnitude of the change in a performance metric after completing a prescribed task (Enoka et al. 2021).
There are several potential mechanisms underlying the persistent fatigue in people with post-COVID-19. Neurological dysfunctions as a result of viral encephalitis (Hoffman and Vilensky 2017), neuro-inflammation (Rogers et al. 2020; Nalbandian et al. 2021), hypoxia (Ceban et al. 2022), and cerebrovascular disease (Higgins et al. 2021; Komaroff and Lipkin 2021; Nalbandian et al. 2021) have been hypothesized. This is in line with studies on severe acute respiratory syndrome (SARS), another coronavirus, which showed persistent fatigue symptoms in survivors (Caldaria et al. 2020), potentially due to the virus invading tissues in the central and peripheral nervous systems (He et al. 2003; Glass et al. 2004). Therefore, it has been suggested that post-COVID-19 may be a neurological disorder due to the overlap in symptoms and underlying mechanisms. However, studies linking pathophysiological findings with post-COVID-19 symptoms are scarce. Douaud et al. (2022) investigated brain changes pre- and post-COVID-19 and found increased markers of tissue damage and a reduction in gray matter thickness, global brain size, and performance on cognitive tasks in people who became infected with COVID-19 (Douaud et al. 2022). Similarly, Guedj et al. (2021) demonstrated that bilateral hypo-metabolism in various brain regions was significantly associated with post-COVID-19 symptoms, including cognitive impairment, pain, and insomnia (Guedj et al. 2021). On the other hand, other studies found that neurological deficits or significant MRI abnormalities were rarely objectified in people with post-COVID-19 and, if present, could be attributed to other neurological disorders in most cases (Fleischer et al. 2022; Kachaner et al. 2022). In line with this, Dressing et al. (2022) demonstrated no significant changes in cerebral glucose metabolism in post-COVID-19 subjects with self-reported cognitive impairment and fatigue (Dressing et al. 2022).
Most studies that aimed to characterize symptoms in people with post-COVID-19 symptoms used self-report questionnaires to evaluate fatigue and/or perceived fatigability, but no studies have assessed objectively determined performance fatigability. However, comparing these domains of fatigue is vital to determine the etiology of post-COVID-19 fatigue symptoms and to assess the effectiveness of potential interventions. This is important because perceived fatigability is often distinct and independent from objective fatigability. Specifically, it has been suggested that these domains of fatigue are not correlated or only have a moderate association in most conditions (DeLuca et al. 2008; Kluger et al. 2013). For example, in people with multiple sclerosis, several studies have failed to demonstrate a consistent association between perceived fatigability and behavioral performance (Jennekens-Schinkel et al. 1988; Johnson et al. 1997; Beatty et al. 2003; Genova et al. 2013). Moreover, it is theorized that some clinical population may be able to perform a task as well as healthy controls (i.e., same objective fatigability), but they perceive the task as more difficult (i.e., increased perceived fatigability) (DeLuca et al. 2008; Kohl et al. 2009).
The primary aim of this study was to characterize fatigue in people with post-COVID-19 symptoms. Specifically, we assessed differences in fatigue as well as perceived and objective fatigability between people with post-COVID-19 symptoms and people who had COVID-19, but are not experiencing persistent symptoms (i.e., people without post-COVID-19 symptoms). We hypothesized that people with post-COVID-19 symptoms would have greater fatigue and perceived fatigability, according to self-report questionnaires, but not objective, performance fatigability, as assessed by fatigue tests, compared to subjects without post-COVID-19 symptoms.
Methods
Subjects
29 subjects (20 females) with post-COVID-19 and 20 (12 females) subjects without post-COVID-19 symptoms (people who had a confirmed diagnosis of COVID-19 but are not experiencing persistent symptoms) were recruited from the University of Iowa Hospitals and Clinics via mass email to university students, staff, faculty, and alumni between January 2021 and June 2022. Only patients who meet CDC guidelines for discontinuation of home isolation were recruited. Subject characteristics are displayed in Table 1. Inclusion criteria were: (1) between the ages of 18–80 years old, (2) previous positive COVID-19 test (confirmed via medical record), (3) at least 6 weeks post quarantine, (3) experiencing or not experiencing post-COVID-19 symptoms (depending on group assignment), based on the Chalder Fatigue Scale CFQ-11 score (post-COVID-19 fatigue ≥ 5 (Chalder et al. 1993)) and the COVID-19 Yorkshire Rehab Screen (C19-YRS) (O'Connor et al. 2022), (4) have no current or past medical conditions that would make the completing the protocol dangerous for the subject, (5) demonstrated an understanding of the study protocol during screening phone call, and (6) fluent in English. Exclusion criteria included: (1) the presence of any medical conditions that are contraindications to exercising training (e.g., major renal, pulmonary, hepatic, or cardiovascular disorders), (2) being diagnosed with any condition that may exacerbate fatigue (e.g., anemia, hypothyroidism, B12 deficiency, major sleep disorder, major depressive disorder, stress, anxiety), (3) history of significant traumatic brain injury or hydrocephalus, or 4) pregnancy. This study was approved by the Institutional Review Board at the University of Iowa (IRB #202,009,381) and was performed in accordance with the Declaration of Helsinki.Table 1 Subject Characteristics
Without post-COVID-19 symptoms With post-COVID-19 symptoms
N (females) 20 (12) 29 (20)
Chalder fatigue scale 1.20 ± 1.47 7.64 ± 2.11*
Time since COVID-19 diagnosis (months) 6.89 ± 4.76 6.45 ± 4.04
Age (years) 32.10 ± 12.68 37.07 ± 14.81
Weight (kg) 77.17 ± 13.42 76.89 ± 13.47
Height (cm) 171.98 ± 11.38 168.07 ± 10.90
BMI 26.20 ± 4.91 27.37 ± 5.14
Data are mean ± SD. *Indicates significant difference between the groups (p < 0.01).
Experimental protocol
Subjects completed one experimental session to assess fatigue as well as perceived and objectively determined fatigability. During this session, subjects were consented, then completed questionnaires to assess their fatigue and perceived fatigability, followed by an isokinetic fatigue test.
Measurements
Fatigue, perceived fatigability, pain, and quality of life assessments
The Fatigue Assessment Scale (FAS) contains 10 statements to evaluate fatigue (Michielsen et al. 2003). Subjects rated each statement on a 5-point scale (1 = “never”–5 = “always”), depending on how appropriate they felt the statement applied to them. A low value indicates that the statement does not apply to them, whereas a high value indicates high agreement with the statement. The scores from the statements are summed, with statements 4 and 10 “reverse-scored.” Total scores range from 10 (lowest level of fatigue) to 50 (highest level of fatigue).
The Fatigue Severity Scale (FSS) contains nine statements to assess perceived fatigability (Krupp et al. 1989; Enoka et al. 2021). Subjects rated each statement on a 7-point scale, depending on how appropriate they felt the statement applied to them over the preceding week. A low value indicates that the statement does not apply to them, whereas a high value indicates high agreement with the statement. This questionnaire is scored by calculating the average response to the statements. A score ≥ 4 indicates a clinically significant level of fatigue severity and a change of 0.5–0.89 points is considered the minimally clinically important difference (Rooney et al. 2019).
The Visual Analog Scale for Pain (VAS) asks subjects to indicate on a scale from 0 (no pain) to 100 (pain as bad as it could be) how much pain, on average, they experienced over the past 24 h.
EQ-5D-5L questionnaire assesses quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (Janssen et al. 2013). Subjects rated each component by indicating which statement best describes the degree of problems that they are experiencing in that area (e.g., “I have no problems walking” to “I am unable to walk”). Subjects are then asked to rate their current overall health on a scale from 0 (worst health imaginable) to 100 (best health imaginable).
Objective fatigability assessments
The isokinetic fatigue test consisted of 40 consecutive maximal effort contractions of the knee extensors and flexors (120°/s, concentric/concentric) performed on an isokinetic dynamometer (HUMAC NORM, CSMi, Stoughton, MA). Prior to the fatigue test, subjects completed a 10-repetition warm-up (60°/s, concentric/concentric). The right leg fatigue test was performed first, followed by the left leg. Visual (i.e., per rep work bars) and verbal encouragement was provided to ensure a maximal effort performance from the subjects. Peak torque and total work for each repetition were retained for analysis. The first two repetitions of the fatigue task were considered adaptions and removed from subsequent analyses. Two fatigue indices were calculated: a torque-derived fatigue index (FI-T) and a work-derived fatigue index (FI-W). The peak torque from each repetition was used to calculate the FI-T as follows: ([mean of first five repetitions–mean of last five repetitions]/mean of first five repetitions) × 100 (Lambert et al. 2001; Workman et al. 2020b). A high FI-T indicates increased fatigability, as the subject was not able to produce a similar torque during the first and last five repetitions. The total work from each repetition was used to calculate the FI-W as follows: (total work performed in last half of the fatigue task/total work performed in the first half of the fatigue task) × 100 (Janssen et al. 2013; Rooney et al. 2019). A low FI-W indicates increased fatigability, as the subject was unable to produce a similar amount of work in the second half of the fatigue test as compared to the first half.
Statistical analysis
Unpaired t tests were used to evaluate differences between the people with and without post-COVID-19 symptoms on each outcome variable. Normality and linearity assumptions for the t tests were investigated via histograms, skewness and kurtosis statistics, and Q–Q plots of the residuals of the outcome variables. One-way ANOVAs were used to assess sex differences between the subgroups, stratified by sex and fatigue status (females with post-COVID-19 symptoms, females without post-COVID-19 symptoms, males with post-COVID-19 symptoms, and males without post-COVID-19 symptoms). Normality and homogeneity assumptions for the ANOVA were assessed with Q–Q plots and Levene’s test for Homogeneity of Variances, respectively. Cohen’s d was calculated to clarify any significant differences. Significance was accepted at p ≤ 0.05, after a Tukey correction, and analyses were performed using GraphPad Prism 9 (GraphPad Software, San Diego, CA, USA).
Results
All subjects completed all experimental tasks. Table 1 shows the subject characteristics. Data are reported as mean ± SD in the text and mean ± SEM in the figures.
The results of the unpaired t tests revealed that, the subjects with post-COVID-19 symptoms had significantly higher FAS (Without Post-COVID-19 symptoms: 15.10 ± 4.02, with post-COVID-19 symptoms: 28.35 ± 7.70, p < 0.01, d = 2.16, Fig. 1A) and FSS scores compared to subjects without post-COVID-19 symptoms (Without Post-COVID-19 symptoms: 2.06 ± 0.57, with post-COVID-19 symptoms: 4.71 ± 1.41, p < 0.01, d = 2.46, Fig. 1B), indicating increased fatigue and perceived fatigability.Fig. 1 A Fatigue Assessment Scale (FAS) scores stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. *Indicates significantly increased fatigue in the post-COVID-19 group (p < 0.01). B Fatigue Severity Scale (FSS) scores stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. *Indicates significantly increased fatigue in the subjects with post-COVID-19 symptoms (p < 0.01)
The subjects with post-COVID-19 symptoms also reported higher pain compared to the people without post-COVID-19 symptoms, according to their VAS scores (Without Post-COVID-19 symptoms: 4.30 ± 11.46, with post-COVID-19 symptoms: 25.34 ± 21.42, p < 0.01, d = 1.22), and lower quality of life, as indicated by their EQ-5D-5L VAS scores (Without Post-COVID-19 symptoms: 86.08 ± 8.39, with post-COVID-19 symptoms: 68.90 ± 18.43, p < 0.01, d = 1.20, Fig. 2).Fig. 2 The Visual Analog Scale for quality of life (EQ-5D-5L VAS) scores stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. *Indicates significantly lower quality of life in the subjects with post-COVID-19 symptoms (p < 0.01)
The results of the unpaired t tests for the FI-T of the right knee extensors (Without Post-COVID-19 symptoms: 59.71 ± 10.98, with post-COVID-19 symptoms: 59.51 ± 12.23, p = 0.95, d = 0.02, Fig. 3A) left knee extensors (Without Post-COVID-19 symptoms: 58.69 ± 10.50, with post-COVID-19 symptoms: 59.48 ± 12.10, p = 0.81, d = 0.07), right knee flexors (Without Post-COVID-19 symptoms: 40.89 ± 11.09, with post-COVID-19 symptoms: 44.59 ± 12.63, p = 0.30, d = 0.31), and left knee flexors (Without Post-COVID-19 symptoms: 42.93 ± 10.39, with post-COVID-19 symptoms: 35.95 ± 13.67, p = 0.07, d = 0.57) showed no significant differences in fatigability between subjects with and without post-COVID-19 symptoms. Similarly, the FI-W of the right knee extensors (Without Post-COVID-19 symptoms: 53.78 ± 9.30, with post-COVID-19 symptoms: 52.39 ± 10.88, p = 0.65, d = 0.14, Fig. 3B), left knee extensors (Without Post-COVID-19 symptoms: 57.88 ± 9.44, with post-COVID-19 symptoms: 55.99 ± 10.41, p = 0.52, d = 0.19), right knee flexors (Without Post-COVID-19 symptoms: 65.63 ± 8.61, with post-COVID-19 symptoms: 63.66 ± 10.41, p = 0.49, d = 0.21), and left knee flexors (Without Post-COVID-19 symptoms: 70.37 ± 9.68, with post-COVID-19 symptoms: 65.63 ± 7.96, p = 0.08, d = 0.53) revealed no significant differences between people with and without post-COVID-19 symptoms.Fig. 3 A Fatigue index derived from the torque data for the right knee extensors stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. There were no significant differences between the groups (p = 0.95). B Fatigue index derived from the work data for the right knee extensors stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. There were no significant differences between the groups (p = 0.65)
The results of the one-way ANOVAs for the FAS, FSS, VAS, and EQ-5D-5L revealed significant differences between subgroups (all F (3, 45) ≤ 22.01, p < 0.01). However, post hoc testing revealed no significant differences between females with post-COVID-19 symptoms and males with post-COVID-19 symptoms (all p ≥ 0.34) or females without post-COVID-19 symptoms and males without post-COVID-19 symptoms (all p = 0.93) for all of the questionnaires.
Discussion
To our knowledge, this is the first study to assess differences in fatigue as well as perceived and objectively fatigability in people with post-COVID-19 symptoms and people who had COVID-19 but are not experiencing post-COVID-19 persistent symptoms. The main findings were that subjects with post-COVID-19 symptoms reported higher levels of fatigue and perceived fatigability than subjects without post-COVID-19 symptoms, but there were no differences in objective fatigability between the groups. Furthermore, people with post-COVID-19 symptoms reported worse fatigue-related factors, such as increased pain and decreased quality of life, which has been demonstrated in other studies in people with post-COVID-19 symptoms (Haider et al. 2022; Peterson et al. 2022) and is common in other neurological disorders (e.g., multiple sclerosis and chronic fatigue syndrome) (Harrison et al. 2015; Heitmann et al. 2016; Workman et al. 2020a, 2020c). These findings support our hypothesis regarding perceived and objectively determined fatigability.
Discrepancies between fatigue as well as perceived and objective fatigability have been demonstrated in other patient populations, such as people with multiple sclerosis (PwMS). For example, DeLuca and colleagues indicated that these domains of fatigue are often not correlated or have no more than a moderate association in PwMS (DeLuca et al. 2008). Studies in PwMS and people with traumatic brain injuries (TBI) suggest that, although these clinical populations may be able to perform a task at comparable levels to healthy controls (i.e., same objective fatigability), their increased perception of fatigability may reflect an increase in the amount of cerebral resources needed to do so (DeLuca et al. 2008; Kohl et al. 2009). However, the pathophysiology of fatigue and perceived fatigability in people with post-COVID-19 remains vague. Previous studies have assessed structural damage to the central nervous system (CNS) using advanced MRI techniques, such as diffusion tensor imaging (DTI) in PwMS and failed to find a significant association between perceived fatigability and structural alterations (Codella et al. 2002a, 2002b). Similarly, recent studies in people with post-COVID-19 symptoms found no significant differences in MRI findings between subjects with and without cognitive impairments and fatigue after acute infection (Hellgren et al. 2021; Huang et al. 2022). Moreover, despite several studies detecting changes in brain microstructure of people with post-COVID-19 with structural MRI (Colonna et al. 2020; Freeman et al. 2021; Hixon et al. 2021; Nuzzo et al. 2021; Cecchini et al. 2022) and DTI (Liu et al. 2019; Tian et al. 2020; Qin et al. 2021), no correlations with fatigue symptoms have been reported. Other recent studies found that post-COVID-19 symptoms were rarely associated with damage of the central or peripheral nervous system (Fleischer et al. 2022) or alterations in regional cerebral glucose metabolism (Dressing et al. 2022). Moreover, the Fleischer and colleagues concluded that psychosomatic mechanisms, such as somato-sensoric amplification may play a role in the pathogenesis of post-COVID-19 symptoms (Fleischer et al. 2022).
As mentioned previously (Rudroff et al. 2020), fatigue and perceived fatigability also depend on other factors, such as mood, stress, pain, depression and anxiety. Specifically in people with post-COVID-19 symptoms, Calabria et al. (2022) found that increased levels of neuropsychiatric symptoms were important predictors of fatigue (Calabria et al. 2022), and a systematic review found that depression and anxiety was reported in 32% and 34% of subjects with post-COVID-19 symptoms, respectively (Jennings et al. 2021). However, Schulze and colleagues demonstrated that fatigue was not associated with symptoms of anxiety or depression in males and females with post-COVID-19 symptoms (Schulze et al. 2022). Moreover, Peterson et al. demonstrated that conditioned pain modulation was impaired in people who had symptomatic acute COVID-19 (Peterson et al. 2022) and Haider et al. found that pain levels in people with post-COVID-19 symptoms are comparable to people with fibromyalgia and chronic fatigue syndrome (Haider et al. 2022), which is line with the results of the current study. Additionally, it has been suggested that self-reporting post-COVID-19 symptoms may be influenced by one’s perception of the COVID-19 pandemic and apprehension about developing post-COVID-19 symptoms (Engelmann et al. 2022; Matta et al. 2022). Therefore, it is warranted that future research characterizes how psychosomatic factors contribute to the pathophysiology of post-COVID-19 fatigue.
Functional neuroimaging techniques to study fatigue, such as positron emission tomography with the glucose analog 18F-fluorodeoxyglucose (FDG-PET), may provide more information about the underlying mechanisms of post-COVID-19 fatigue symptoms. A review by Rudroff et al. (Rudroff et al. 2021) summarized studies in people with post-COVID-19 that showed FDG-PET hypo-metabolism in a variety of brain regions and associations with symptoms (Fleischer et al. 2022). For example, Guedj et al. (Guedj et al. 2021) found hypo-metabolism in the bilateral rectal/orbital gyrus (including the olfactory gyrus), hippocampus, temporal lobe (including the amygdala), bilateral pons/medulla brainstem, thalamus, and the bilateral cerebellum using FDG-PET in people with post-COVID-19 symptoms (Guedj et al. 2021). Importantly, this hypo-metabolism was associated with the patients’ symptoms (e.g., hyposmia/anosmia, cognitive impairment, pain and insomnia) (Guedj et al. 2021). Similarly, Sollini et al. (Sollini et al. 2021) demonstrated an association between brain hypo-metabolism in the thalamus as well as the right para-hippocampal gyrus and persistent symptoms (e.g., fatigue and anosmia/ageusia) in people with post-COVID-19 (Sollini et al. 2021). These findings are in line with the model fatigue suggested by Chaudhuri & Behan (Chaudhuri and Behan 2000), which hypothesized that perceived fatigue is associated with impairment of the non-motor functions within the basal ganglia, which in turn negatively impacts the striatal-thalamic-frontal cortical system (Chaudhuri and Behan 2000). Similarly, in PwMS, pathology of the striatum, thalamus, superior frontal gyrus and inferior parietal gyrus has been associated with increased levels of perceived fatigue (Roelcke et al. 1997; Tellez et al. 2008; Calabrese et al. 2010; Pardini et al. 2010). However, more work is needed to establish a fatigue network specific to people with post-COVID-19.
Interestingly, the results of the current study demonstrated no sex differences between women and men with post-COVID-19 symptoms, which contradicts previous studies. There are several contributing factors to potential sex differences in fatigue, pain, and quality of life including biological (e.g., levels of fluctuating hormones) and social (e.g., gender norms) (Bensing et al. 1999; Rudroff et al. 2022). These factors were not addressed by the questionnaires used to assess fatigue and perceived fatigability and, therefore, may not be sensitive enough to examine sex differences. Moreover, the sample size in current study may not be large enough to determine sex differences, although they may have affected the results.
Limitations and future studies
There are several limitations in this study. First, although there were no significant differences between the groups. There is a large variation in the time since COVID-19 diagnosis within each group. This is important because symptom severity may decrease as more time passes after acute illness (Sandler et al. 2021). Similarly, although there were no differences between the groups, there is a large age range of the subjects in each group, which may influence both perceived and objective fatigability. Additionally, the cohort of subjects in this study is young and the results may not generalize to older people with post-COVID-19 symptoms. Moreover, although potential subjects were excluded if they had a condition known to exacerbate fatigue, we did not assess additional factors that may influence fatigue, such as psychological stress or levels of anxiety and depression. Lastly, a larger sample size may be needed to thoroughly evaluate sex differences in people with post-COVID-19 symptoms. No power calculation was performed and the study should be seen as a preliminary investigation, conducted with the aim of informing further research, not providing any definitive conclusions.
Future studies should further characterize and establish a clinical definition of fatigue and perceived fatigability in people with post-COVID-19 symptoms, which will allow for the development of reliable and valid approaches to diagnose these domains of fatigue in this patient population. These studies should assess other factors that may influence fatigue, such as levels of depression, stress, sleep quality, physical activity levels, pain, and anxiety as well as various factors that may contribute to the development of post-COVID-19 symptoms, including time since acute illness, the variant in which subjects were infected with, and vaccination status. Moreover, future studies should compare people who have not had COVID-19 in addition to people with and without post-COVID-19 symptoms. Importantly, future research should evaluate underlying physiological and psychological mechanisms of fatigue and perceived fatigability to determine risk factors for post-COVID-19 fatigue and evaluate the effectiveness of potential interventions. For example, determining alterations in glucose metabolism in the brain via FDG-PET may lead to the establishment of a “Post-COVID-19 Fatigue Network,” which may establish target structures for neurophysiological treatments.
Summary
This study found that people with post-COVID-19 symptoms have significantly increased fatigue and perceived fatigability, but not objective fatigability compared to people who had COVID-19, but are not experiencing post-COVID-19 persistent symptoms. However, more research with larger sample sizes is needed before any conclusions can be made. Furthermore, it is suggested that future research should take into account psychosomatic factors as possible triggers for post-COVID-19 fatigue. Moreover, there were no differences in perceived fatigability between males and females, which also requires further investigation. This research is highly significant, especially regarding treatment of symptoms and the development of assessments to distinguish between perceived and objective fatigability in people with post-COVID-19 fatigue.
Acknowledgements
The authors would like to thank the study participants for their time and effort.
Author contributions
Conceptualization, A.C.F. and T.R.; methodology, A.C.F. and T.R.; formal analysis, A.C.F.; writing—original draft preparation, A.C.F. and T.R., writing—review and editing A.C.F., A.D. B., and T.R. All authors have read and agreed to the published version of the manuscript.
Funding
No funding was received for conducting this study.
Data availability
The data that support the findings of this study are available on request to the corresponding author.
Declarations
Conflict of interest
The authors declare no conflict of interest.
Institutional review board statement
This study was performed per the Declaration of Helsinki, approved by the University of Iowa Institutional Review Board (IRB #202009381).
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36462035 | PMC9735153 | NO-CC CODE | 2022-12-14 23:29:52 | no | Exp Brain Res. 2022 Dec 3;:1-9 | utf-8 | Exp Brain Res | 2,022 | 10.1007/s00221-022-06518-0 | oa_other |
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Exp Brain Res
Exp Brain Res
Experimental Brain Research
0014-4819
1432-1106
Springer Berlin Heidelberg Berlin/Heidelberg
36462035
6518
10.1007/s00221-022-06518-0
Research Article
Fatigue and perceived fatigability, not objective fatigability, are prevalent in people with post-COVID-19
Fietsam Alexandra C. 1
Bryant Andrew D. 2
http://orcid.org/0000-0002-2057-7793
Rudroff Thorsten [email protected]
13
1 grid.214572.7 0000 0004 1936 8294 Department of Health and Human Physiology, University of Iowa, Iowa City, IA USA
2 grid.412584.e 0000 0004 0434 9816 Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA USA
3 grid.412584.e 0000 0004 0434 9816 Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA USA
Communicated by Bill J Yates.
3 12 2022
19
12 10 2022
26 11 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Persistent symptoms after acute COVID-19 infection, termed post-COVID-19 fatigue, occur in 44–70% of patients. Characterizing fatigue in this population is vital to determine the etiology of post-COVID-19 fatigue symptoms and to assess the effectiveness of potential interventions. The purpose of this study was to assess differences in perceived and objective fatigability between people with post-COVID-19 symptoms (N = 29, 20 females) and people who had COVID-19 but are not experiencing persistent symptoms (N = 20, 12 females). Perceived fatigability, fatigue, pain, and quality of life were assessed with the Fatigue Severity Scale (FSS), Fatigue Assessment Scale (FAS), Visual Analog Scale for Pain (VAS), and the EQ-5D-5L, respectively. Objective fatigability was evaluated with torque and work fatigue indices (FI-T and FI-W), calculated via an isokinetic fatigue task. The results revealed that, the subjects with post-COVID-19 symptoms had significantly higher FAS (p < 0.01), FSS (p < 0.01), VAS (p < 0.01), and EQ-5D-5L VAS (p < 0.01) scores compared to subjects without post-COVID-19 symptoms, indicating greater fatigue and perceived fatigability, increased pain, and worse quality of life. However, there were no differences between the two groups for the FI-Ts (all p ≥ 0.07) or FI-W (all p ≥ 0.08), indicating no differences in objective fatigability. This study found that people with post-COVID-19 symptoms have increased fatigue and perceived fatigability, but not objective fatigability, compared to subjects without post-COVID-19 symptoms.
Keywords
Post-COVID-19
Fatigue
Perception
Performance fatigability
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pmcIntroduction
As of October 2022, over 96 million cases of coronavirus disease 2019 (COVID-19) have been documented in the United States (Centers for Disease Control and Prevention (CDC)). Despite the high (> 90%) survival rate of the acute illness, a proportion of patients continue to experience persistent symptoms (World Health Organization (WHO)). Importantly, post-COVID-19 condition is characterized as symptoms that last for at least two months after an acute COVID-19 illness (WHO). However, these symptoms have been reported to last over six months in some patients (Huang et al. 2021). Post-COVID-19 symptoms include anosmia, ageusia, myalgia, cognitive issues (e.g., memory or concentration), and, importantly, fatigue (WHO).
Persistent fatigue is one of the most common symptoms, occurring in 44–70% of patients, independent of the severity of the initial infection (i.e., hospitalized vs. non-hospitalized) (Huang et al. 2020; Wang et al. 2020; Xu et al. 2020; Schulze et al. 2022). Wijeratne et al. (Wijeratne and Crewther 2021) reported that, despite complete recovery after infection, 71–87% of people with COVID-19 report fatigue 2–3 months after initial infection. Interestingly, rates of persistent symptoms after COVID-19, particularly fatigue, have been thought to be higher in females than males (Bechmann et al. 2022; Ceban et al. 2022; Fernandez-de-Las-Penas et al. 2022). Although fatigue is a frequent and disabling symptom by people with various neurological disorders (e.g., multiple sclerosis (Krupp 2006) and Parkinson Disease (Friedman et al. 2007)), it remains not well understood, perhaps because there are several potential contributing factors (i.e., central, peripheral, and psychological factors) (Rudroff et al. 2020). In general, fatigue describes the feelings of tiredness, lack of energy, low motivation, and difficulty in concentrating and can only be measured by self-report (Enoka et al. 2021). Fatigability, on the other hand, is a measure of physical or cognitive work capacity. Specifically, perceived fatigability subjectively estimates past or future work capacity whereas objective fatigability determines the magnitude of the change in a performance metric after completing a prescribed task (Enoka et al. 2021).
There are several potential mechanisms underlying the persistent fatigue in people with post-COVID-19. Neurological dysfunctions as a result of viral encephalitis (Hoffman and Vilensky 2017), neuro-inflammation (Rogers et al. 2020; Nalbandian et al. 2021), hypoxia (Ceban et al. 2022), and cerebrovascular disease (Higgins et al. 2021; Komaroff and Lipkin 2021; Nalbandian et al. 2021) have been hypothesized. This is in line with studies on severe acute respiratory syndrome (SARS), another coronavirus, which showed persistent fatigue symptoms in survivors (Caldaria et al. 2020), potentially due to the virus invading tissues in the central and peripheral nervous systems (He et al. 2003; Glass et al. 2004). Therefore, it has been suggested that post-COVID-19 may be a neurological disorder due to the overlap in symptoms and underlying mechanisms. However, studies linking pathophysiological findings with post-COVID-19 symptoms are scarce. Douaud et al. (2022) investigated brain changes pre- and post-COVID-19 and found increased markers of tissue damage and a reduction in gray matter thickness, global brain size, and performance on cognitive tasks in people who became infected with COVID-19 (Douaud et al. 2022). Similarly, Guedj et al. (2021) demonstrated that bilateral hypo-metabolism in various brain regions was significantly associated with post-COVID-19 symptoms, including cognitive impairment, pain, and insomnia (Guedj et al. 2021). On the other hand, other studies found that neurological deficits or significant MRI abnormalities were rarely objectified in people with post-COVID-19 and, if present, could be attributed to other neurological disorders in most cases (Fleischer et al. 2022; Kachaner et al. 2022). In line with this, Dressing et al. (2022) demonstrated no significant changes in cerebral glucose metabolism in post-COVID-19 subjects with self-reported cognitive impairment and fatigue (Dressing et al. 2022).
Most studies that aimed to characterize symptoms in people with post-COVID-19 symptoms used self-report questionnaires to evaluate fatigue and/or perceived fatigability, but no studies have assessed objectively determined performance fatigability. However, comparing these domains of fatigue is vital to determine the etiology of post-COVID-19 fatigue symptoms and to assess the effectiveness of potential interventions. This is important because perceived fatigability is often distinct and independent from objective fatigability. Specifically, it has been suggested that these domains of fatigue are not correlated or only have a moderate association in most conditions (DeLuca et al. 2008; Kluger et al. 2013). For example, in people with multiple sclerosis, several studies have failed to demonstrate a consistent association between perceived fatigability and behavioral performance (Jennekens-Schinkel et al. 1988; Johnson et al. 1997; Beatty et al. 2003; Genova et al. 2013). Moreover, it is theorized that some clinical population may be able to perform a task as well as healthy controls (i.e., same objective fatigability), but they perceive the task as more difficult (i.e., increased perceived fatigability) (DeLuca et al. 2008; Kohl et al. 2009).
The primary aim of this study was to characterize fatigue in people with post-COVID-19 symptoms. Specifically, we assessed differences in fatigue as well as perceived and objective fatigability between people with post-COVID-19 symptoms and people who had COVID-19, but are not experiencing persistent symptoms (i.e., people without post-COVID-19 symptoms). We hypothesized that people with post-COVID-19 symptoms would have greater fatigue and perceived fatigability, according to self-report questionnaires, but not objective, performance fatigability, as assessed by fatigue tests, compared to subjects without post-COVID-19 symptoms.
Methods
Subjects
29 subjects (20 females) with post-COVID-19 and 20 (12 females) subjects without post-COVID-19 symptoms (people who had a confirmed diagnosis of COVID-19 but are not experiencing persistent symptoms) were recruited from the University of Iowa Hospitals and Clinics via mass email to university students, staff, faculty, and alumni between January 2021 and June 2022. Only patients who meet CDC guidelines for discontinuation of home isolation were recruited. Subject characteristics are displayed in Table 1. Inclusion criteria were: (1) between the ages of 18–80 years old, (2) previous positive COVID-19 test (confirmed via medical record), (3) at least 6 weeks post quarantine, (3) experiencing or not experiencing post-COVID-19 symptoms (depending on group assignment), based on the Chalder Fatigue Scale CFQ-11 score (post-COVID-19 fatigue ≥ 5 (Chalder et al. 1993)) and the COVID-19 Yorkshire Rehab Screen (C19-YRS) (O'Connor et al. 2022), (4) have no current or past medical conditions that would make the completing the protocol dangerous for the subject, (5) demonstrated an understanding of the study protocol during screening phone call, and (6) fluent in English. Exclusion criteria included: (1) the presence of any medical conditions that are contraindications to exercising training (e.g., major renal, pulmonary, hepatic, or cardiovascular disorders), (2) being diagnosed with any condition that may exacerbate fatigue (e.g., anemia, hypothyroidism, B12 deficiency, major sleep disorder, major depressive disorder, stress, anxiety), (3) history of significant traumatic brain injury or hydrocephalus, or 4) pregnancy. This study was approved by the Institutional Review Board at the University of Iowa (IRB #202,009,381) and was performed in accordance with the Declaration of Helsinki.Table 1 Subject Characteristics
Without post-COVID-19 symptoms With post-COVID-19 symptoms
N (females) 20 (12) 29 (20)
Chalder fatigue scale 1.20 ± 1.47 7.64 ± 2.11*
Time since COVID-19 diagnosis (months) 6.89 ± 4.76 6.45 ± 4.04
Age (years) 32.10 ± 12.68 37.07 ± 14.81
Weight (kg) 77.17 ± 13.42 76.89 ± 13.47
Height (cm) 171.98 ± 11.38 168.07 ± 10.90
BMI 26.20 ± 4.91 27.37 ± 5.14
Data are mean ± SD. *Indicates significant difference between the groups (p < 0.01).
Experimental protocol
Subjects completed one experimental session to assess fatigue as well as perceived and objectively determined fatigability. During this session, subjects were consented, then completed questionnaires to assess their fatigue and perceived fatigability, followed by an isokinetic fatigue test.
Measurements
Fatigue, perceived fatigability, pain, and quality of life assessments
The Fatigue Assessment Scale (FAS) contains 10 statements to evaluate fatigue (Michielsen et al. 2003). Subjects rated each statement on a 5-point scale (1 = “never”–5 = “always”), depending on how appropriate they felt the statement applied to them. A low value indicates that the statement does not apply to them, whereas a high value indicates high agreement with the statement. The scores from the statements are summed, with statements 4 and 10 “reverse-scored.” Total scores range from 10 (lowest level of fatigue) to 50 (highest level of fatigue).
The Fatigue Severity Scale (FSS) contains nine statements to assess perceived fatigability (Krupp et al. 1989; Enoka et al. 2021). Subjects rated each statement on a 7-point scale, depending on how appropriate they felt the statement applied to them over the preceding week. A low value indicates that the statement does not apply to them, whereas a high value indicates high agreement with the statement. This questionnaire is scored by calculating the average response to the statements. A score ≥ 4 indicates a clinically significant level of fatigue severity and a change of 0.5–0.89 points is considered the minimally clinically important difference (Rooney et al. 2019).
The Visual Analog Scale for Pain (VAS) asks subjects to indicate on a scale from 0 (no pain) to 100 (pain as bad as it could be) how much pain, on average, they experienced over the past 24 h.
EQ-5D-5L questionnaire assesses quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (Janssen et al. 2013). Subjects rated each component by indicating which statement best describes the degree of problems that they are experiencing in that area (e.g., “I have no problems walking” to “I am unable to walk”). Subjects are then asked to rate their current overall health on a scale from 0 (worst health imaginable) to 100 (best health imaginable).
Objective fatigability assessments
The isokinetic fatigue test consisted of 40 consecutive maximal effort contractions of the knee extensors and flexors (120°/s, concentric/concentric) performed on an isokinetic dynamometer (HUMAC NORM, CSMi, Stoughton, MA). Prior to the fatigue test, subjects completed a 10-repetition warm-up (60°/s, concentric/concentric). The right leg fatigue test was performed first, followed by the left leg. Visual (i.e., per rep work bars) and verbal encouragement was provided to ensure a maximal effort performance from the subjects. Peak torque and total work for each repetition were retained for analysis. The first two repetitions of the fatigue task were considered adaptions and removed from subsequent analyses. Two fatigue indices were calculated: a torque-derived fatigue index (FI-T) and a work-derived fatigue index (FI-W). The peak torque from each repetition was used to calculate the FI-T as follows: ([mean of first five repetitions–mean of last five repetitions]/mean of first five repetitions) × 100 (Lambert et al. 2001; Workman et al. 2020b). A high FI-T indicates increased fatigability, as the subject was not able to produce a similar torque during the first and last five repetitions. The total work from each repetition was used to calculate the FI-W as follows: (total work performed in last half of the fatigue task/total work performed in the first half of the fatigue task) × 100 (Janssen et al. 2013; Rooney et al. 2019). A low FI-W indicates increased fatigability, as the subject was unable to produce a similar amount of work in the second half of the fatigue test as compared to the first half.
Statistical analysis
Unpaired t tests were used to evaluate differences between the people with and without post-COVID-19 symptoms on each outcome variable. Normality and linearity assumptions for the t tests were investigated via histograms, skewness and kurtosis statistics, and Q–Q plots of the residuals of the outcome variables. One-way ANOVAs were used to assess sex differences between the subgroups, stratified by sex and fatigue status (females with post-COVID-19 symptoms, females without post-COVID-19 symptoms, males with post-COVID-19 symptoms, and males without post-COVID-19 symptoms). Normality and homogeneity assumptions for the ANOVA were assessed with Q–Q plots and Levene’s test for Homogeneity of Variances, respectively. Cohen’s d was calculated to clarify any significant differences. Significance was accepted at p ≤ 0.05, after a Tukey correction, and analyses were performed using GraphPad Prism 9 (GraphPad Software, San Diego, CA, USA).
Results
All subjects completed all experimental tasks. Table 1 shows the subject characteristics. Data are reported as mean ± SD in the text and mean ± SEM in the figures.
The results of the unpaired t tests revealed that, the subjects with post-COVID-19 symptoms had significantly higher FAS (Without Post-COVID-19 symptoms: 15.10 ± 4.02, with post-COVID-19 symptoms: 28.35 ± 7.70, p < 0.01, d = 2.16, Fig. 1A) and FSS scores compared to subjects without post-COVID-19 symptoms (Without Post-COVID-19 symptoms: 2.06 ± 0.57, with post-COVID-19 symptoms: 4.71 ± 1.41, p < 0.01, d = 2.46, Fig. 1B), indicating increased fatigue and perceived fatigability.Fig. 1 A Fatigue Assessment Scale (FAS) scores stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. *Indicates significantly increased fatigue in the post-COVID-19 group (p < 0.01). B Fatigue Severity Scale (FSS) scores stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. *Indicates significantly increased fatigue in the subjects with post-COVID-19 symptoms (p < 0.01)
The subjects with post-COVID-19 symptoms also reported higher pain compared to the people without post-COVID-19 symptoms, according to their VAS scores (Without Post-COVID-19 symptoms: 4.30 ± 11.46, with post-COVID-19 symptoms: 25.34 ± 21.42, p < 0.01, d = 1.22), and lower quality of life, as indicated by their EQ-5D-5L VAS scores (Without Post-COVID-19 symptoms: 86.08 ± 8.39, with post-COVID-19 symptoms: 68.90 ± 18.43, p < 0.01, d = 1.20, Fig. 2).Fig. 2 The Visual Analog Scale for quality of life (EQ-5D-5L VAS) scores stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. *Indicates significantly lower quality of life in the subjects with post-COVID-19 symptoms (p < 0.01)
The results of the unpaired t tests for the FI-T of the right knee extensors (Without Post-COVID-19 symptoms: 59.71 ± 10.98, with post-COVID-19 symptoms: 59.51 ± 12.23, p = 0.95, d = 0.02, Fig. 3A) left knee extensors (Without Post-COVID-19 symptoms: 58.69 ± 10.50, with post-COVID-19 symptoms: 59.48 ± 12.10, p = 0.81, d = 0.07), right knee flexors (Without Post-COVID-19 symptoms: 40.89 ± 11.09, with post-COVID-19 symptoms: 44.59 ± 12.63, p = 0.30, d = 0.31), and left knee flexors (Without Post-COVID-19 symptoms: 42.93 ± 10.39, with post-COVID-19 symptoms: 35.95 ± 13.67, p = 0.07, d = 0.57) showed no significant differences in fatigability between subjects with and without post-COVID-19 symptoms. Similarly, the FI-W of the right knee extensors (Without Post-COVID-19 symptoms: 53.78 ± 9.30, with post-COVID-19 symptoms: 52.39 ± 10.88, p = 0.65, d = 0.14, Fig. 3B), left knee extensors (Without Post-COVID-19 symptoms: 57.88 ± 9.44, with post-COVID-19 symptoms: 55.99 ± 10.41, p = 0.52, d = 0.19), right knee flexors (Without Post-COVID-19 symptoms: 65.63 ± 8.61, with post-COVID-19 symptoms: 63.66 ± 10.41, p = 0.49, d = 0.21), and left knee flexors (Without Post-COVID-19 symptoms: 70.37 ± 9.68, with post-COVID-19 symptoms: 65.63 ± 7.96, p = 0.08, d = 0.53) revealed no significant differences between people with and without post-COVID-19 symptoms.Fig. 3 A Fatigue index derived from the torque data for the right knee extensors stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. There were no significant differences between the groups (p = 0.95). B Fatigue index derived from the work data for the right knee extensors stratified by group (With post-COVID-19 symptoms vs. without Post-COVID-19 symptoms). Females are shown in red while males are shown in blue. There were no significant differences between the groups (p = 0.65)
The results of the one-way ANOVAs for the FAS, FSS, VAS, and EQ-5D-5L revealed significant differences between subgroups (all F (3, 45) ≤ 22.01, p < 0.01). However, post hoc testing revealed no significant differences between females with post-COVID-19 symptoms and males with post-COVID-19 symptoms (all p ≥ 0.34) or females without post-COVID-19 symptoms and males without post-COVID-19 symptoms (all p = 0.93) for all of the questionnaires.
Discussion
To our knowledge, this is the first study to assess differences in fatigue as well as perceived and objectively fatigability in people with post-COVID-19 symptoms and people who had COVID-19 but are not experiencing post-COVID-19 persistent symptoms. The main findings were that subjects with post-COVID-19 symptoms reported higher levels of fatigue and perceived fatigability than subjects without post-COVID-19 symptoms, but there were no differences in objective fatigability between the groups. Furthermore, people with post-COVID-19 symptoms reported worse fatigue-related factors, such as increased pain and decreased quality of life, which has been demonstrated in other studies in people with post-COVID-19 symptoms (Haider et al. 2022; Peterson et al. 2022) and is common in other neurological disorders (e.g., multiple sclerosis and chronic fatigue syndrome) (Harrison et al. 2015; Heitmann et al. 2016; Workman et al. 2020a, 2020c). These findings support our hypothesis regarding perceived and objectively determined fatigability.
Discrepancies between fatigue as well as perceived and objective fatigability have been demonstrated in other patient populations, such as people with multiple sclerosis (PwMS). For example, DeLuca and colleagues indicated that these domains of fatigue are often not correlated or have no more than a moderate association in PwMS (DeLuca et al. 2008). Studies in PwMS and people with traumatic brain injuries (TBI) suggest that, although these clinical populations may be able to perform a task at comparable levels to healthy controls (i.e., same objective fatigability), their increased perception of fatigability may reflect an increase in the amount of cerebral resources needed to do so (DeLuca et al. 2008; Kohl et al. 2009). However, the pathophysiology of fatigue and perceived fatigability in people with post-COVID-19 remains vague. Previous studies have assessed structural damage to the central nervous system (CNS) using advanced MRI techniques, such as diffusion tensor imaging (DTI) in PwMS and failed to find a significant association between perceived fatigability and structural alterations (Codella et al. 2002a, 2002b). Similarly, recent studies in people with post-COVID-19 symptoms found no significant differences in MRI findings between subjects with and without cognitive impairments and fatigue after acute infection (Hellgren et al. 2021; Huang et al. 2022). Moreover, despite several studies detecting changes in brain microstructure of people with post-COVID-19 with structural MRI (Colonna et al. 2020; Freeman et al. 2021; Hixon et al. 2021; Nuzzo et al. 2021; Cecchini et al. 2022) and DTI (Liu et al. 2019; Tian et al. 2020; Qin et al. 2021), no correlations with fatigue symptoms have been reported. Other recent studies found that post-COVID-19 symptoms were rarely associated with damage of the central or peripheral nervous system (Fleischer et al. 2022) or alterations in regional cerebral glucose metabolism (Dressing et al. 2022). Moreover, the Fleischer and colleagues concluded that psychosomatic mechanisms, such as somato-sensoric amplification may play a role in the pathogenesis of post-COVID-19 symptoms (Fleischer et al. 2022).
As mentioned previously (Rudroff et al. 2020), fatigue and perceived fatigability also depend on other factors, such as mood, stress, pain, depression and anxiety. Specifically in people with post-COVID-19 symptoms, Calabria et al. (2022) found that increased levels of neuropsychiatric symptoms were important predictors of fatigue (Calabria et al. 2022), and a systematic review found that depression and anxiety was reported in 32% and 34% of subjects with post-COVID-19 symptoms, respectively (Jennings et al. 2021). However, Schulze and colleagues demonstrated that fatigue was not associated with symptoms of anxiety or depression in males and females with post-COVID-19 symptoms (Schulze et al. 2022). Moreover, Peterson et al. demonstrated that conditioned pain modulation was impaired in people who had symptomatic acute COVID-19 (Peterson et al. 2022) and Haider et al. found that pain levels in people with post-COVID-19 symptoms are comparable to people with fibromyalgia and chronic fatigue syndrome (Haider et al. 2022), which is line with the results of the current study. Additionally, it has been suggested that self-reporting post-COVID-19 symptoms may be influenced by one’s perception of the COVID-19 pandemic and apprehension about developing post-COVID-19 symptoms (Engelmann et al. 2022; Matta et al. 2022). Therefore, it is warranted that future research characterizes how psychosomatic factors contribute to the pathophysiology of post-COVID-19 fatigue.
Functional neuroimaging techniques to study fatigue, such as positron emission tomography with the glucose analog 18F-fluorodeoxyglucose (FDG-PET), may provide more information about the underlying mechanisms of post-COVID-19 fatigue symptoms. A review by Rudroff et al. (Rudroff et al. 2021) summarized studies in people with post-COVID-19 that showed FDG-PET hypo-metabolism in a variety of brain regions and associations with symptoms (Fleischer et al. 2022). For example, Guedj et al. (Guedj et al. 2021) found hypo-metabolism in the bilateral rectal/orbital gyrus (including the olfactory gyrus), hippocampus, temporal lobe (including the amygdala), bilateral pons/medulla brainstem, thalamus, and the bilateral cerebellum using FDG-PET in people with post-COVID-19 symptoms (Guedj et al. 2021). Importantly, this hypo-metabolism was associated with the patients’ symptoms (e.g., hyposmia/anosmia, cognitive impairment, pain and insomnia) (Guedj et al. 2021). Similarly, Sollini et al. (Sollini et al. 2021) demonstrated an association between brain hypo-metabolism in the thalamus as well as the right para-hippocampal gyrus and persistent symptoms (e.g., fatigue and anosmia/ageusia) in people with post-COVID-19 (Sollini et al. 2021). These findings are in line with the model fatigue suggested by Chaudhuri & Behan (Chaudhuri and Behan 2000), which hypothesized that perceived fatigue is associated with impairment of the non-motor functions within the basal ganglia, which in turn negatively impacts the striatal-thalamic-frontal cortical system (Chaudhuri and Behan 2000). Similarly, in PwMS, pathology of the striatum, thalamus, superior frontal gyrus and inferior parietal gyrus has been associated with increased levels of perceived fatigue (Roelcke et al. 1997; Tellez et al. 2008; Calabrese et al. 2010; Pardini et al. 2010). However, more work is needed to establish a fatigue network specific to people with post-COVID-19.
Interestingly, the results of the current study demonstrated no sex differences between women and men with post-COVID-19 symptoms, which contradicts previous studies. There are several contributing factors to potential sex differences in fatigue, pain, and quality of life including biological (e.g., levels of fluctuating hormones) and social (e.g., gender norms) (Bensing et al. 1999; Rudroff et al. 2022). These factors were not addressed by the questionnaires used to assess fatigue and perceived fatigability and, therefore, may not be sensitive enough to examine sex differences. Moreover, the sample size in current study may not be large enough to determine sex differences, although they may have affected the results.
Limitations and future studies
There are several limitations in this study. First, although there were no significant differences between the groups. There is a large variation in the time since COVID-19 diagnosis within each group. This is important because symptom severity may decrease as more time passes after acute illness (Sandler et al. 2021). Similarly, although there were no differences between the groups, there is a large age range of the subjects in each group, which may influence both perceived and objective fatigability. Additionally, the cohort of subjects in this study is young and the results may not generalize to older people with post-COVID-19 symptoms. Moreover, although potential subjects were excluded if they had a condition known to exacerbate fatigue, we did not assess additional factors that may influence fatigue, such as psychological stress or levels of anxiety and depression. Lastly, a larger sample size may be needed to thoroughly evaluate sex differences in people with post-COVID-19 symptoms. No power calculation was performed and the study should be seen as a preliminary investigation, conducted with the aim of informing further research, not providing any definitive conclusions.
Future studies should further characterize and establish a clinical definition of fatigue and perceived fatigability in people with post-COVID-19 symptoms, which will allow for the development of reliable and valid approaches to diagnose these domains of fatigue in this patient population. These studies should assess other factors that may influence fatigue, such as levels of depression, stress, sleep quality, physical activity levels, pain, and anxiety as well as various factors that may contribute to the development of post-COVID-19 symptoms, including time since acute illness, the variant in which subjects were infected with, and vaccination status. Moreover, future studies should compare people who have not had COVID-19 in addition to people with and without post-COVID-19 symptoms. Importantly, future research should evaluate underlying physiological and psychological mechanisms of fatigue and perceived fatigability to determine risk factors for post-COVID-19 fatigue and evaluate the effectiveness of potential interventions. For example, determining alterations in glucose metabolism in the brain via FDG-PET may lead to the establishment of a “Post-COVID-19 Fatigue Network,” which may establish target structures for neurophysiological treatments.
Summary
This study found that people with post-COVID-19 symptoms have significantly increased fatigue and perceived fatigability, but not objective fatigability compared to people who had COVID-19, but are not experiencing post-COVID-19 persistent symptoms. However, more research with larger sample sizes is needed before any conclusions can be made. Furthermore, it is suggested that future research should take into account psychosomatic factors as possible triggers for post-COVID-19 fatigue. Moreover, there were no differences in perceived fatigability between males and females, which also requires further investigation. This research is highly significant, especially regarding treatment of symptoms and the development of assessments to distinguish between perceived and objective fatigability in people with post-COVID-19 fatigue.
Acknowledgements
The authors would like to thank the study participants for their time and effort.
Author contributions
Conceptualization, A.C.F. and T.R.; methodology, A.C.F. and T.R.; formal analysis, A.C.F.; writing—original draft preparation, A.C.F. and T.R., writing—review and editing A.C.F., A.D. B., and T.R. All authors have read and agreed to the published version of the manuscript.
Funding
No funding was received for conducting this study.
Data availability
The data that support the findings of this study are available on request to the corresponding author.
Declarations
Conflict of interest
The authors declare no conflict of interest.
Institutional review board statement
This study was performed per the Declaration of Helsinki, approved by the University of Iowa Institutional Review Board (IRB #202009381).
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Rogers JP Chesney E Oliver D Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic Lancet Psychiatry 2020 7 611 627 10.1016/S2215-0366(20)30203-0 32437679
Rooney S McFadyen DA Wood DL Moffat DF Paul PL Minimally important difference of the fatigue severity scale and modified fatigue impact scale in people with multiple sclerosis Mult Scler Relat Disord 2019 35 158 163 10.1016/j.msard.2019.07.028 31400557
Rudroff T Fietsam AC Deters JR Bryant AD Kamholz J Post-COVID-19 Fatigue: Potential Contributing Factors Brain Sci 2020 10.3390/brainsci10121012 33352638
Rudroff T Workman CD Ponto LLB (18)F-FDG-PET Imaging for Post-COVID-19 Brain and Skeletal Muscle Alterations Viruses 2021 10.3390/v13112283 34835088
Rudroff T Workman CD Bryant AD potential factors that contribute to post-COVID-19 fatigue in women Brain Sci 2022 10.3390/brainsci12050556 35884627
Sandler CX Wyller VBB Moss-Morris R Long COVID and post-infective fatigue syndrome: a review Open Forum Infect 2021 10.1093/ofid/ofab440
Schulze H Charles James J Trampe N Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome Front Neurol 2022 13 979152 10.3389/fneur.2022.979152 36313487
Sollini M Morbelli S Ciccarelli M Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study Eur J Nucl Med Mol Imaging 2021 48 3187 3197 10.1007/s00259-021-05294-3 33677642
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| 0 | PMC9735156 | NO-CC CODE | 2022-12-14 23:29:52 | no | gynäkologie + geburtshilfe. 2022 Dec 7; 27(6):14 | latin-1 | null | null | null | oa_other |
==== Front
Memo
Memo
Memo
1865-5041
1865-5076
Springer Vienna Vienna
851
10.1007/s12254-022-00851-4
Editorial
ASCO update—best of the best
Petzer Andreas [email protected]
Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz GmbH Barmherzige Schwestern, Elisabethinen, Seilerstätte 4, 4010 Linz, Austria
5 12 2022
2022
15 4 255256
6 10 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
issue-copyright-statement© Springer-Verlag GmbH Austria, part of Springer Nature 2022
==== Body
pmcDear colleagues,
For many of us, the “face to face” attendance at the most important meeting for medical oncologists and colleagues from several other disciplines related to clinical oncology, namely the ASCO annual meeting, was already a highlight by itself after numerous—in general also excellent—virtual meetings over the past 2 years during the coronavirus disease 2019 (COVID-19) pandemic. In spite of numerous challenges caused by the pandemic, it is noteworthy that several clinically important studies were performed and successfully finished during the pandemic. ASCO 2022 was characterized by three main topics: First, the success with the new generation of antibody drug conjugates (ADCs). Second, the transfer of the success of immune checkpoint inhibitor (ICI) therapy from the palliative setting into the adjuvant and neoadjuvant setting and third, de-escalation of therapy by using circulating tumor DNA (ct-DNA) measurements or replacing classical chemotherapy and radiotherapy with immunotherapy.
Trastuzumab deruxtecan (TDX-d) had already shown its superiority in “classical HER2-positive” breast cancer (BC) compared to trastuzumab emtansine (T-DM1) in patients who were previously treated with trastuzumab and taxane in the phase III DESTINY-Breast03 trial [1]. In the phase III DESTINY-Breast04 trial TDX‑d now demonstrated a significantly superior progression-free (PFS) and overall survival (OS) compared to physician’s choice in patients with previously treated “HER2 low” metastatic BC [2]. HER2 low was defined as immunohistochemical (IHC)1+, or IHC2+ and in situ hybridization (ISH) negative. These data will broaden the population of patients with metastatic BC who are candidates for a HER-directed therapy dramatically by about 50%! Other ADCs, like sacituzumab govitecan (SG) also showed superior OS in pretreated triple-negative BC compared to physician’s choice [3] and disitamab vedotin showed excellent response rates again not only in HER2/IHC3+ and HER2/IHC2+ positive patients but also in HER2 low (i.e., HER2/IHC2+ FISH negative) patients with locally advanced or metastatic urothelial carcinoma [4].
Immunotherapy, especially with ICIs is very strongly on the rise, not only in the palliative but also in the adjuvant and neoadjuvant setting. The presence of the tumor in the neoadjuvant situation may lead to higher numbers of tumor-resident T cell clones in the periphery after neoadjuvant therapy and subsequently to better outcome. This hypothesis is supported among others by the PRADO trial in stage IIIB/C de novo or recurrent melanoma patients who achieved pathologically complete or near-complete remission rates of 61% with ipilimumab and nivolumab [5]. A highlight of ICI therapy was a small but nevertheless groundbreaking study on 14 patients with mismatch repair (MR) deficient locally advanced rectal cancer that were treated with a single programmed death 1 (PD-1) blocking agent, namely dostarlimab, over 6 months [6]. All 14 patients (100%) achieved a clinically complete response and remained progression free for up to 14 months so far. This means that in this small population of MR-deficient patients with locally advanced rectal cancer chemotherapy, radiotherapy and surgery could be possibly omitted in the future. The effectiveness of ICI therapy in microsatellite-high (MSI-H) tumors or tumors with MR-deficiency with the PD1-inhibitor dostarlimab was also documented in the phase III GARNET study in advanced/metastatic endometrial cancer [7]. Patients with MSI‑H tumors or tumors with MR-deficiency showed a superior PFS and OS compared to patients with mismatch repair-proficiency or those with microsatellite-stable tumors.
Another important finding reported at the recent ASCO meeting was the de-escalation of chemotherapy by using circulating tumor DNA (ct-DNA) in order to avoid adjuvant chemotherapy in stage II colon cancer in the DYNAMIC trial [8]. This ct-DNA-guided strategy was able to halve the number of patients that received chemotherapy post surgery, while the chance of remaining alive and free of cancer at 3 years remained comparable.
Some of these data with more details as well as data on other entities such as hepatocellular carcinoma, cholangiocellular carcinoma, bladder cancer and central nervous system tumors will be presented in the following articles.
Conflict of interest
A. Petzer: Honoraria/advisory role: Novartis, Amgen, Celgene-BMS, Sandoz, Janssen, Astra Zeneca, AbbVie, Takeda, Sanofi, Kite-Gilead, Roche, Pfizer, Seagen, Daiichi Sankyo. Travel support: Janssen, Astra Zeneca, Kite-Gilead, Roche, Pfizer, Daiichi Sankyo.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References
1. Cortes J N Engl J Med 2022 386 1143 1115 10.1056/NEJMoa2115022 35320644
2. Modi S J Clin Oncol 2022 40 suppl 16 abstr LBA 3 10.1200/JCO.2022.40.17_suppl.LBA3
3. Rugo HS J Clin Oncol 2022 40 suppl 16 abstr LBA 1001 10.1200/JCO.2022.40.17_suppl.LBA1001
4. Sheng X J Clin Oncol 2022 40 suppl 16 abstr 4518 10.1200/JCO.2022.40.16_suppl.4518
5. Blank CU J Clin Oncol 2022 40 suppl 16 abstr 9501 10.1200/JCO.2022.40.16_suppl.9501
6. Cercek A J Clin Oncol 2022 40 suppl 16 LBA No. 5 10.1200/JCO.2022.40.17_suppl.LBA5
7. Oaknin A J Clin Oncol 2022 40 suppl 16 abstr 5509 10.1200/JCO.2022.40.16_suppl.5509
8. Thie J J Clin Oncol 2022 40 suppl 16 abstr LBA 100 10.1200/JCO.2022.40.17_suppl.LBA100
| 0 | PMC9735157 | NO-CC CODE | 2022-12-14 23:29:52 | no | Memo. 2022 Dec 5; 15(4):255-256 | utf-8 | Memo | 2,022 | 10.1007/s12254-022-00851-4 | oa_other |
==== Front
J Fam Violence
J Fam Violence
Journal of Family Violence
0885-7482
1573-2851
Springer US New York
478
10.1007/s10896-022-00478-3
Original Article
The Mental Health of Emerging Adults: Hostile Home Environments and COVID-19
Maly Ellie G.
Grower Petal L.
Robertson Katherine E.
Haran Neil J.
Graham-Bermann Sandra A. [email protected]
grid.214458.e 0000000086837370 Department of Psychology, University of Michigan, 530 Church St., Ann Arbor, MI 48109 USA
6 12 2022
113
28 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Purpose
Due to shifts in societal and educational expectations alongside the COVID-19 pandemic, many emerging adults live with their family of origin for extended periods of time. Little is known about patterns of parent-perpetrated maltreatment in emerging adulthood. Therefore, this study evaluates the relation between forms of parent-perpetrated maltreatment, including economic abuse, and COVID stress, on symptoms of depression, anxiety, and traumatic stress.
Method
423 emerging adults who were enrolled in college in the United States in March of 2020 were recruited via MTurk to complete an online survey. An age-related COVID questionnaire and six empirically validated measures assess levels of COVID-19 exposure, lifetime maltreatment, economic abuse, and mental health status.
Results
13.0% of participants reported maltreatment that most recently occurred over the age of 18 in their household of origin. Mean COVID stress level was found to be significantly higher in the Maltreated Over 18 group compared to the Never Maltreated group (t(345) = -3.03, p = 0.003), and in the Maltreated Under 18 group compared to the Never Maltreated group (t(346) = -3.20, p = 0.002). In accounting for the contribution of demographic variables, maltreatment chronicity, economic abuse, and COVID stress, our model predicted 38.6% of variance in depression symptoms, 37.2% of variance in anxiety symptoms, and 42.9% of variance in traumatic stress.
Conclusions
Findings indicate need for increased maltreatment screenings within the emerging adult population and calls for age-specific interventions to address the mental health disparities experienced by emerging adults with maltreatment histories.
Keywords
Maltreatment chronicity
COVID-19
Mental health
Emerging adult
==== Body
pmcIn the United States, individuals are legally recognized as adults at age 18. However, many psychologists differentiate legal adulthood from social and psychological adulthood. Arnett’s emerging adulthood theory describes a period in which 18 to 29-year-olds gradually achieve different markers of self-sufficiency (Arnett et al., 2014). For many in the US, this means finding stable employment, housing, and insurance immediately after high school. For others, this means paying tuition and housing costs while attending college away from their household of origin. However, 59% of emerging adults in the US reported insufficient financial support to complete their education (Clark University, 2015), requiring many to maintain some level of financial dependence upon their parents during college, thus leaving them more vulnerable to parental control and parent-perpetrated maltreatment. Further, due to the COVID-19 pandemic, many college students returned to their households of origin, whether voluntarily or because of a lack of other housing options due to university closures. This increased proximity to households of origin creates the potential for patterns of abuse to persist. The present study evaluates the relation between these adverse experiences and emerging adults’ mental health.
Parent–Child Relationships in Emerging Adulthood
Yet another area of potential risk is parental control of emerging adults’ finances. One shift brought about by the transitions of emerging adulthood is that of the parent–child relationship: A tension arises between dependence upon parental guidance and resources and acquiring features of independence. For relationships that have been historically tumultuous, this strain can risky. Autonomy development may be supported or hindered depending on levels of parent psychological control. Gong and Wang (2021) found autonomy-supportive parenting to be related to greater capacity for emotional regulation and better self-esteem; however, increased levels of parent psychological control reduce capacity for emotion regulation and comparatively, levels of self-esteem. Recent studies have also found higher levels of parent psychological control to be positively associated with risk-behaviors during emerging adulthood (Faherty et al., 2020).
Financial independence is often seen as a marker of adulthood; however, finances frequently cause conflict between emerging adults and their parents. Parents may view a lack of financial independence beyond legal adulthood as a burden or as related to long-term failure to attain independence (Lowe & Arnett, 2020). However, emerging adults use familial financial support to ease their age-related stressors, including balancing work and academic commitments; Lindell and colleagues (2021) found increased financial support was associated with improved emotional adjustment at this time. Their findings also suggested that when financial support is unavailable, quality of parental-child relationship is related to improved emotional health among emerging adult women (Lindell et al., 2021). This study underscores the importance of financial communication to parent–child relationships and to the emerging adults’ mental health.
Maltreatment of Children and Emerging Adults
Previous research by the U.S. Department of Health & Human Services (DHHS, 2021) established that rates of child maltreatment decrease as children age. Despite this trend and the legal implications of turning 18, there is no age or developmental milestone that immediately ends parental control and parent-perpetrated abuse. Notably, McKinney and colleagues (2020) found that in their sample of college students, 30% of men and 17.3% of women reported that one or both parents perpetrated a severe physical assault in the past year, and that 78.7% of men and 74.4% of women experienced at least one psychological aggression in the past year. However, few studies of this population assess parent-perpetrated maltreatment, and those that do measure the frequency of abuse in the previous year rather than the cumulative effects of abuse that persists from childhood into adulthood (McKinney et al., 2020; Rogers et al., 2018). Furthermore, a majority of family violence research essentially ignores the parent-perpetrated abuse endured by adolescents and emerging adults. Yet, the Child Maltreatment 2019 report indicates that 3.7 per 100,000 17-year-olds were confirmed maltreatment victims (DHHS, 2021). While the report includes a category for “unborn, unknown, and 18–21” (DHHS, 2021, p. 34), this categorization obfuscates accurate examination of maltreatment patterns among 18 to 21-year-olds. Additionally, abuse of older teens and 18 to 21-year-olds is rarely reported to Protective Services, with the blended category making up only 0.4% of victims (DHHS, 2021). These referrals are rarely screened-in, and reports are handled variably by state. Thus, the rate of parent-perpetrated maltreatment in emerging adults may be higher than reported, necessitating more research and specific intervention mechanisms to mitigate hardship and victimization of emerging adults transitioning out of hostile homes (Gochez-Kerr & Helton, 2017).
Maltreatment comes in many forms, irrespective of age. Physical abuse, sexual abuse, and emotional abuse are known to occur under dynamics of power and control; this can describe scenarios of intimate partner violence, but also of parent-perpetrated abuse (Duron et al., 2021; Linell, 2017). Despite the awareness brought to this issue by Straka & Montminy in 2008, systems designed to detect and intervene in cases of family violence still vary greatly in modality by type (child abuse, intimate partner violence, elder abuse) and so struggle to meet the needs of individuals whose circumstances seem atypical (i.e., parent-perpetrated maltreatment in the emerging adult population). Further, parent-perpetrated maltreatment that has persisted into adulthood proves especially challenging to detect as systems meant to detect abuse in childhood have already failed; often, in emerging adulthood, maltreatment is often only detected by self-report. Lastly, there are few forms of support for parent-perpetrated maltreatment accessible to emerging adults without access to parent resources (for example, needing parent health insurance to access therapeutic services that can identify and intervene in patterns of enduring maltreatment).
Further, after adolescents turn 18, they may be susceptible to a new type of maltreatment: economic abuse. As defined by Adams and colleagues, economic abuse involves “behaviors that control a [person]’s ability to acquire, use, or maintain economic resources, thus threatening [their] economic security and potential for self-sufficiency” (2008, p. 565). Economic abuse has been established as a tool of coercive control among intimate partners, perpetuating cycles of abuse and producing adverse psychological and financial consequences (Adams et al., 2020; Crossman & Hardesty, 2018). Yet, little is known about the prevalence and outcomes of economic abuse between parents and their adult children. Of further complication, while covert mechanisms of economic abuse may be more difficult to detect than other forms of maltreatment (Postmus et al., 2020), they may significantly limit the victim’s autonomy (Adams et al., 2020).
Central to this investigation is the cumulative effect of chronic maltreatment on mental health. While isolated events can contribute to traumatic stress reactions, studies have found that single and combined types of chronic, repetitive maltreatment can result in devastating mental health consequences and increased vulnerability to later revictimization (Jonson-Reid et al., 2012; Schaaf & McCanne, 1998). Further, due to state-differentiated counting and reporting laws, national rates of chronic maltreatment are underestimated (Wildeman, 2019).
Mental Health in Emerging Adulthood
The World Health Organization World Mental Health Survey Initiative found emerging adults aged 18–22 to have a 12-month prevalence of any mental disorder of between 20.3% to 25.0%, with 11.7% to 14.7% expressing anxiety disorders (e.g., Generalized Anxiety Disorder; Post-Traumatic Stress Disorder), and 6.0% to 9.9% experiencing mood disorders (e.g., Major Depressive Disorder; Auerbach et al., 2016). Although emerging adults exhibit elevated prevalence of mental disorders compared to other age groups, little support is available to them. Specifically, few psychotherapy interventions have been adapted for the distinct conditions faced by emerging adult populations (e.g., role transition stress, identity formation, and sudden freedom from previously surveilled environments). Notably, when they do seek help, adolescents and emerging adults have high attrition rates in mental health services, with studies estimating that 20% to more than 60% of adolescents accessing mental health services discontinue care after turning 18 (Cohen et al., 2020; Copeland et al., 2015). Thus, further empirical attention is imperative for developing appropriate and supportive resources for emerging adults.
Stress Related to COVID-19 Pandemic
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), commonly known as COVID-19, originated in late 2019 in China. The international spread was rapid, and by March of 2020, COVID-19 was declared a pandemic by the World Health Organization and had reached much of the United States (Cucinotta & Vanelli, 2020). Millions of people were quarantined at home, with some facing acute financial and psychological distress. The global impact has been tremendous, causing uncertainty about the future, changes to existing plans, and concerns about personal and family health (Paredes et al., 2021; Reizer et al., 2021). This has been a particular stress for emerging adults who are in a stage of exploration, uncertainty, and transition (Arnett et al., 2014). Studies have shown that psychosocial stressors in the wake of the pandemic are associated with negative mental health outcomes, such as anxiety and depression (Kujawa et al., 2020). Further, studies have found that emerging adults with preexisting mental and physical health conditions, along with demographic risk factors, experience comparatively higher levels of distress within the context of COVID-19 (Alonzi et al., 2020). Therefore, the lack of sufficient mental health resources for this age group combined with maltreatment status may exacerbate the situational factors of the pandemic and lead to poor mental health.
Family Violence and the COVID-19 Pandemic
While stay-at-home orders were implemented nationally, slogans such as “Stay Home, Stay Safe” offered a false narrative to victims of family violence (State of Michigan, 2020). In the COVID-19 Special Report on the first 60 days of the pandemic released by The National Domestic Violence Hotline (NDVH), between March 16th and May 16th of 2020 there was a 9% increase in total contacts received (NDVH, 2020). 17% of these contacts were between 19 and 24-years-of-age, and 8% of these were contacts from non-IPV victims—those who have “experienced abuse from anyone other than an intimate partner (i.e., parent, sibling, caretaker)” (NDVH, 2020, p. 1). Notably, there was a 219% increase in reports of housing instability amongst contacts during 2020 (NDVH, 2021b), and within one year of the pandemic, 23,056 contacts to the NDVH cited COVID-19 as a contributor to their experience. Increased proximity to perpetrators due to quarantine and conditions of the pandemic including job loss and housing instability also contributed to domestic violence experiences (NDVAH, 2021a).
Stay-at-home orders not only failed to support those who lack safe living circumstances, but actively limited the potential for detection of and intervention in maltreatment. In a study comparing police reports of domestic violence in Chicago during March 2019 and March 2020, McLay (2021) identified a 67% drop in cases with child victims, stressing that further research is needed to distinguish between a true decrease in child victims or in reporting. Many mental health professionals have expressed concern about the impact of school closures on maltreatment reporting (Baron et al., 2020), with Rodriguez and colleagues highlighting the inadequacies of “a reactive welfare system rather than a proactive public-health oriented approach to child maltreatment” (2021, pg. 139). Further, studies have indicated that the pandemic has increased family violence risk factors, including isolation and resultant reduced detection, parental burnout, and parental job loss (Griffith, 2020; Lawson et al., 2020; Lee et al., 2021). Therefore, assessing prevalence of maltreatment in this population is both essential and firmly reliant on self-report.
Research Hypotheses
The cost to individuals, to families and to society of maltreatment is enormous. The existing lack of resources for emerging adults presents prevents emerging adults from reaching their full potential. Accordingly, the present study seeks to evaluate the cumulative impact of parent-perpetrated maltreatment on mental health and to assess the extent to which the COVID-19 pandemic is associated with those effects within a sample of emerging adults. This study addresses the following hypotheses: (1) Emerging adults with a history of maltreatment will continue to experience parent-perpetrated maltreatment beyond age 18 when living in their households of origin; (2) Emerging adults who have experienced recent emotional, physical, or sexual abuse, emotional or physical neglect, or economic abuse will have higher levels of COVID stress compared to those who have not; (3) Emerging adults experiencing parent-perpetrated maltreatment while living at home during the COVID-19 pandemic will have higher levels of COVID stress than those who experienced parent-perpetrated maltreatment in childhood; and (4) The chronicity of parent-perpetrated abuse and neglect, degree of economic abuse, and level of COVID stress will significantly contribute to variance in mental health (here depression, anxiety, and traumatic stress).
Method
Procedures
Prior to the study, ethical clearance was obtained from the Institutional Review Board at the University of Michigan. The study included 423 participants recruited via Amazon Mechanical Turk (MTurk), a virtual Human Intelligence Task (HIT) marketplace, who completed a self-report survey administered via Qualtrics. This format adhered to contemporaneous COVID-mandated health and safety restrictions requiring physical distancing. This approach also meant that participants were randomly sampled across the United States.
Inclusion criteria restricted participants to emerging adults between 18 years 0 months and 25 years 11 months of age, who had been students at a higher education institution in the United States in March 2020. Additionally, MTurk workers must have (1) been located within the United States at the time of participation, as verified by IP address via MTurk, (2) had a HIT approval rate of over 97%, meaning their completed assignments had been approved by MTurk requesters at least 97% of the time, (3) had at least 50 HITs approved prior to participation, (4) not previously completed the survey, and (5) completed the informed consent page. As data was collected online without direct participant contact, these qualifiers were established to ensure that the survey was completed with honest intent. Once posted to MTurk, the first 423 participants to complete the survey and have their response validated received a payment of one USD.
After electing to complete the study's HIT in MTurk, participants were directed to a Qualtrics survey where they entered a passcode given via MTurk. Participants read a description of the study and eligibility requirements, and began the questionnaire once they consented. If participants indicated within the survey that they did not meet inclusion criteria, they were directed to the end of the survey and their data was not included in our analyses. Participants took an average of 27.78 min to complete the survey (SD = 80.409). Upon completing the survey, participants were given instructions for MTurk submission along with a passcode used by researchers to confirm completion. Data was manually reviewed by the researchers, who identified and rejected participants who (1) clicked survey options in a rapid, patterned response, (2) provided answers that did not respond to the question, (3) provided multiple survey submissions, or (4) did not pass attention checks. For the purposes of this study, only complete cases were included. If the participant successfully completed the survey, they received payment via MTurk within 72 h. Below the consent, during the survey, and with the end-of-survey statement, national resources for maltreatment, suicidality, and COVID-19 were provided.
Participants
Initially, 2,094 MTurk workers clicked on the survey link. Of those, 1,508 did not complete the survey or did not submit it to MTurk. Of the 586 submissions, 163 did not pass validation checks and were rejected, leaving 423 validated responses. The average age was 23.25 years (SD = 1.84). Half of the sample identified as cisgender men (50.4%), while 47.0% identified as cisgender women and 2.6% identified as transgender or non-binary. Participant characteristics by maltreatment group are found in Table 1.Table 1 Participant characteristics
Characteristic Total (%) NM MU18 MHO18
N in group 423 292 (69.0%) 56 (13.2%) 55 (13.0%)
Gender
Man 213 (50.4%) 176 (60.3%) 24 (42.9%) 8 (14.5%)
Woman 199 (47.0%) 115 (39.4%) 30 (53.6%) 42 (76.4%)
Trans Man 3 (0.7%) 0 (0.0%) 1 (1.8%) 1 (1.8%)
Trans Woman 1 (0.2%) 1 (0.3%) 0 (0.0%) 0 (0.0%)
Nonbinary 7 (1.7%) 0 (0.0%) 1 (1.8%) 4 (7.3%)
Ethnoracial Identity
Asian 37 (8.7%) 25 (9.0%) 3 (5.8%) 7 (14.3%)
Black or African American 39 (9.2%) 26 (9.4%) 6 (11.5%) 5 (10.2%)
Hispanic, Latinx, or Spanish 18 (4.3%) 10 (3.6%) 3 (5.8%) 5 (10.2%)
Middle Eastern or North African 1 (0.2%) 1 (0.4%) 0 (0.0%) 0 (0.0%)
Native Hawaiian or Other Pacific Islander 1 (0.2%) 1 (0.4%) 0 (0.0%) 0 (0.0%)
Native or Indigenous American 2 (0.5%) 1 (0.4%) 1 (1.9%) 0 (0.0%)
White 294 (69.5%) 210 (75.5%) 39 (75.0%) 31 (63.3%)
Mixed 27 (6.4%) 15 (5.1%) 4 (7.1%) 6 (10.9%)
Participant Educational Background
Some College, No Degree 176 (41.6%) 121 (41.4%) 15 (26.8%) 32 (58.2%)
Associate Degree 61 (14.4%) 39 (13.4%) 8 (14.3%) 11 (20.0%)
Bachelor’s Degree 153 (36.2%) 110 (37.7%) 27 (48.2%) 8 (14.5%)
Master’s Degree 32 (7.6%) 22 (7.5%) 5 (8.9%) 4 (7.3%)
Doctoral Degree 1 (0.2%) 0 (0.0%) 1 (1.9%) 0 (0.0%)
Parental Educational Background
High School Degree/Equivalent 84 (19.9%) 53 (18.2%) 12 (21.4%) 18 (32.7%)
Some College, No Degree 48 (11.3%) 32 (11.0%) 8 (14.3%) 6 (10.9%)
Associate Degree 42 (9.9%) 29 (9.9%) 6 (10.7%) 4 (7.3%)
Bachelor’s Degree 136 (32.2%) 98 (33.6%) 21 (37.5%) 10 (18.2%)
Master’s Degree 75 (17.7%) 53(18.2%) 7 (12.5%) 10 (18.2%)
Doctoral Degree 27 (6.4%) 20 (6.8%) 2 (3.6%) 4 (7.3%)
Personal Finances
Much Worse 25 (5.9%) 9 (3.1%) 6 (10.7%) 8 (14.5%)
Worse 93 (22.0%) 50 (17.1%) 21 (37.5%) 17 (30.9%)
About Average 231 (54.6%) 180 (61.6%) 20 (35.7%) 23 (41.8%)
Better 59 (13.9%) 41 (14.0%) 8 (14.3%) 5 (9.1%)
Much Better 15 (3.6%) 12 (4.1%) 1 (1.8%) 2 (3.6%)
Family Finances
Much Worse 17 (4.0%) 7 (2.4%) 2 (3.6%) 7 (12.7%)
Worse 72 (17.0%) 40 (13.7%) 18 (32.1%) 14 (3.3%)
About Average 236 (55.8%) 174 (59.6%) 29 (6.9%) 23 (41.8%)
Better 80 (18.9%) 57 (19.5%) 6 (10.7%) 8 (14.5%)
Much Better 18 (4.3%) 14 (4.8%) 1 (1.8%) 3 (5.5%)
*Not all percentages total to 100% due to rounding or participant choice not to report
In all, participants reported seven living arrangements at three time points: dorm or community setting, alone, with one or more roommates, with significant other, household of origin/family home, with other/extended family, and with child. Notably, prior to the pandemic, participants most frequently reported living with one or more roommates (35.3%); only 18.2% of participants reported living in their household of origin or family home. However, in March 2020 at the beginning of the pandemic in the United States, participants most frequently reported living in their household of origin or family home (41.8%). At the time of the survey in January and February 2021, participants still most frequently reported living in their household of origin or family home (35.9%). Further, a moderate degree of financial assistance from parents was most frequently reported (M = 2.58, min = 1, max = 5, SD = 1.23).
Measures
First, participant demographics and information concerning the participant’s family was collected, including age, gender, years of education, (non)student status, ethnoracial status, annual family income, and the parent’s highest level of education. For the purposes of this study, gender refers to either cisgender man or cisgender woman identity; trans and nonbinary genders were underrepresented in this sample (2.6%) and therefore not included in further gender-related analyses. Additionally, analyses based on ethnoracial identities underrepresented in the sample (here, Middle Eastern or North African, Native Hawaiian or Other Pacific Islander, and Native or Indigenous) were not completed. Finally, seven empirically validated measures were administered in a randomized order to assess levels of COVID-19 exposure, lifetime maltreatment, economic abuse, and mental health status. Two attention-check questions were included to ensure careful completion.
Assessment of COVID-19 exposure
The COVID-19 Adolescent Symptom & Psychological Experience Questionnaire (CASPE; Ladouceur, 2020) is a 42-item survey assessing participants’ general, emotional, cognitive, and social experiences at home and in their academic life within the COVID-19 pandemic context. While some items were modified for use with college students, none of the items included in this study required modification to be age appropriate. A sample item asks “COVID-19 presents a lot of uncertainty about the future. In the past 7 days, including today, how stressful have you found this uncertainty to be?”. For the present study, a Likert scale anchored at 1 (very slightly or not at all) and 5 (extremely) was applied to three questions of the emotional experience section of the measure to describe COVID stress. These questions were treated as continuous variables in analyses, reflecting uncertainty, disruptions, and worry about family becoming sick. Here, reliability (α) was found to be 0.79.
Assessments of lifetime maltreatment
The Adverse Childhood Experiences (ACEs) Questionnaire (Felitti et al., 1998) asks participants to report whether (yes/no) each of ten adverse experiences occurred before they were 18 years old. The measure was modified here to determine the most recent age the participant lived in their household of origin. It was also modified to include the chronicity of experiences that occurred while participants were living in their household of origin (including beyond age 18 if applicable). The chronicity modifier asked: 1) how frequently did this happen? and 2) when was the last time this happened? A subscale was developed to measure maltreatment from items one to five: emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. In subsequent analyses, participants were categorized as “Maltreated at Home Over the age of 18” (MHO18) if they reported at least one maltreatment item had most recently occurred after their eighteenth birthday while also reporting living in their household of origin at that age, “Maltreated Under 18” (MU18) if maltreatment in their household of origin most recently occurred under the age of 18, and “No Maltreatment” (NM) if no lifetime treatment was reported. Frequency of maltreatment was not included in analyses (see limitations). Studies have consistently shown the ACEs measure to have high reliability and validity (Felitti, 2017; Felitti et al., 1998). Here, reliability (α) was 0.71 for the maltreatment subscale and 0.70 for the total scale, which included all ten ACEs.
The Revised Scale of Economic Abuse (SEA-2; Adams et al., 2020) is a 14-item self-report scale in which participants indicate whether specific aspects of financial control have been used against them by their parents, beginning at age 16. Two 5-point Likert subscales measure economic restriction, or withholding access to economic resources (e.g., “keeping you from having the money you needed to buy food, clothes, and necessities”), and economic exploitation, or coercively taking advantage of someone’s economic resources (e.g., “make you use your money to buy [them] things or pay [their] bills when you didn’t want to”; Adams et al., 2020). In the present study, variables “economic restriction” and “economic exploitation” were conceptualized as continuous variables based on total score. While this measure was designed for use in situations of intimate partner violence, it has been adapted to detect economic abuse within the context of a parent–child relationship (e.g., changing “keep financial information from you” to “keep relevant/important financial information from you”, as parental financial information is not expected to be shared within a parent–child relationship. The SEA-2 shows strong internal consistency and construct validity (Adams et al., 2020). Here, reliability (α) was 0.94 for the total scale, and 0.89 and 0.93 for the restriction and exploitation subscales respectively.
Assessments of mental health status
The Patient Health Questionnaire-9 (PHQ-9; Kroenke et al., 2001) is a 9-item self-report measure assessing frequency and severity of depressive symptoms through ratings on a 4-point Likert scale, anchored by “not at all” and “nearly every day” (Kroenke et al., 2001). Studies have shown consistent reliability and validity (Kroenke et al., 2001); current study reliability (α) was 0.92. In analyses, this data was conceptualized as a continuous variable for depressive symptoms based on total score.
The Generalized Anxiety Disorder Scale-7 (GAD-7; Spitzer et al., 2006) is a seven-item self-report measure assessing anxiety symptoms and associated severity. Ratings fall on a 4-point Likert scale, ranging from “not at all” to “nearly every day”. The measure has been shown to be both reliable and valid with college student populations (Lee & Kim, 2019); in the present study, reliability (α) was 0.94. In analyses, this data was treated as a continuous variable for anxiety symptoms based on total score.
The PTSD Checklist for DSM-5 (PCL-5; Weathers et al., 2013) uses 20 items to assess the 20 DSM-5 symptoms of PTSD. This measure was administered if adverse life experiences were reported. It has been shown to be internally reliable and valid across diverse populations (Carvalho et al., 2020; Ghazali & Chen, 2018); current study reliability (α) was 0.97. In analyses, this data was treated as a continuous variable for traumatic stress symptoms based on total score.
Statistical Analyses
All analyses were performed using SPSS 27.0 (2021). For the purposes of this study, gender refers to either cisgender men or cisgender women. Descriptive analyses were used to characterize maltreatment chronicity within the sample, including considerations of demographic differences. Correlations were used to assess statistically significant correlations between continuous variables. Demographic differences and associations with COVID stress and the three mental health outcomes (anxiety, depression, and traumatic stress) were similarly evaluated. Linear regression was used to assess the relation between significant demographics, maltreatment chronicity status, economic abuse, COVID stress, and mental health. Separate analyses were conducted for depression, anxiety, and traumatic stress symptoms.
Results
Demographic Effects and Maltreatment
Results of the ACEs measure indicate that of the 423 participants, 292 (69.0%) reported no lifetime maltreatment (NM), 56 (13.2%) reported maltreatment that last occurred under the age of 18 in their household of origin (MU18), and 55 (13.0%) reported maltreatment that last occurred over the age of 18 in their household of origin (MHO18). The 20 (4.7%) participants who reported maltreatment that occurred over the age of 18 while living outside their household of origin were not included in subsequent analyses, as parent-perpetrated maltreatment could not be distinguished from other perpetrators, such as intimate partners. Of the 423 participants, 294 (69.5%) reported at least one form of economic restriction, and 144 (34.0%) reported at least one form of economic restriction happened often or very often. Additionally, 153 (36.2%) participants reported at least one form of economic exploitation and 59 (13.9%) reported at least one form of economic exploitation happened often or very often. Of all 423 participants, only 4 (0.9%) reported economic exploitation but not economic restriction. These findings support our first hypothesis and indicate that a many emerging adults continue to experience parent-perpetrated maltreatment beyond age 18 while living in their households of origin.
A one-way analysis of variance (ANOVA) was conducted to test for demographic differences among the three maltreatment groups (NM, MU18, MHO18). No age differences were found for any of the three maltreatment groups (F(2, 402) = 1.64, p = 0.20). However, personal financial situation (F(2, 402) = 10.00, p = 0.001), family financial situation (F(2, 402) = 7.69, p = 0.001), and level of education (F(2, 402) = 7.11, p = 0.001) differed significantly between maltreatment groups; parent education did not (F(2, 402) = 0.83, p = 0.44). Here, the No Maltreatment (NM) group reported significantly higher SES (personal and family) compared to both maltreatment groups, but the maltreated at home over the age of 18 (MHO18) group reported having completed significantly less education compared to the other groups. Chi-Square tests revealed significant gender differences in maltreatment group (χ2(2, 395) = 35.56, p < 0.001), such that men were more likely to report no lifetime maltreatment, while women were more likely to report maltreatment happening while living in their households of origin over the age of 18. There were no statistically significant differences in maltreatment status between ethnoracial groups (χ2(16, 403) = 13.54, p = 0.63).
Results of the strength of the relationship between economic abuse and continuous demographic variables is shown in Table 2.Table 2 Correlation matrix showing Pearson’s r for mental health outcomes, economic abuse, and demographic data
1 2 3 4 5 6 7 8 9 10 11
1. Depression –
2. Anxiety .85** –
3. Traumatic Stress .79** .76** –
4. Economic Restriction .42** .39** .52** –
5. Economic Exploitation .36** .33** .46** .78** –
6. Age -.04 -.001 -.04 .04 .08 –
7. Personal Finances -.20** -.22** -.18** -.17** -.07 -.12* –
8. Family Finances -.11* -.13** -.11* -.12* -.10* -.13** .54** –
9. Financial Dependence .05 -.02 .08 .005 .02 -.19** .12* .30** –
10. Participant Education -.01 -.03 -.02 .14** .20** .37** .11* .08 -.05 –
11. Parental Education -.03 -.003 .002 .03 -.05 -.09 .05 .22** .19** .10** –
*p < .05, **p < .01
T-tests result revealed no significant difference between men and women for economic restriction (t(410) = -0.90, p = 0.37) and economic exploitation (t(410) = 0.56, p = 0.58). A one-way ANOVA detected no differences in economic restriction (F(8, 422) = 0.86, p = 0.55) or economic exploitation (F(8, 422) = 1.05, p = 0.34) between ethnoracial identities.
Demographic Effects and Mental Health
Participants reported a mean score of 7.14 (SD = 6.55) on the measure of depression (PHQ-9), a mean score of 6.27 (SD = 5.80) on the measure of anxiety (GAD-7), and a mean score of 19.02 (SD = 19.180) on the traumatic stress symptom measure (PCL-5). The PCL-5 indicates that scores of 31 and over are considered clinically significant; thus, 21% of the sample reported clinically significant symptoms. As seen in Table 2, while personal and family finances were significantly negatively correlated with depression, anxiety, and trauma, there was no significant association found between depression, anxiety, or trauma and age, financial dependence on family, participant level of education, or parent level of education. Women displayed significantly higher levels of depression (t(409) = -2.51, p = 0.01), anxiety (t(410) = -3.02, p = 0.003), and traumatic stress symptoms (t(366) = -2.15, p = 0.03) compared to men. A one-way ANOVA indicated no statistically significant associations between any ethnoracial identity and depression (F(8, 421) = 1.00, p = 0.44), anxiety (F(8, 422) = 1.46, p = 0.17), or trauma symptoms (F(7, 378) = 0.47, p = 0.86).
Demographic Effects and COVID Stress
COVID stress levels incorporated uncertainty about the future, disruptions to plans, and worry about family becoming sick. Mean level stress level regarding uncertainty about the future was slight to moderate (M = 2.72, min = 1, max = 5, SD = 1.09). Their stress level regarding disruptions to plans had a mean of 2.68 (min = 1, max = 5, SD = 1.12). Participants' mean stress level regarding a family member becoming sick was 2.68 (min = 1, max = 5, SD = 1.22).
Women reported significantly higher levels of COVID uncertainty (t(410) = -3.26, p < 0.001), disruptions (t(410) = -2.74, p = 0.003), and worry about family becoming sick (t(410) = -2.99, p = 0.002) compared to men. A one-way ANOVA showed no statistically significant associations between any ethnoracial identity and uncertainty (F(8, 414) = 1.31, p = 0.24), disruptions (F(8, 414) = 0.77, p = 0.63), or worry about becoming sick (F(8, 414) = 1.79, p = 0.08). While personal and family finances were significantly negatively correlated with uncertainty (r(423) = -0.20, p < 0.001; r(423) = 0.16, p = 0.001) and disruptions (r(423) = -0.16, p = 0.001; r(423) = -0.12, p = 0.02), there was no significant association between uncertainty and disruptions and age, financial dependence on family, or participant or parent level of education. There were no significant associations between worry about family becoming sick and any continuous demographic variable.
Maltreatment and COVID Stress
Regarding our second hypothesis, mean COVID stress level scores were found to be significantly higher in the MU18 group compared to the NM group (t(346) = -3.20, p = 0.002). Similarly, mean COVID stress level was significantly higher in the MHO18 group compared to the NM group (t(345) = -3.03, p = 0.003). It was hypothesized that emerging adults experiencing parent-perpetrated maltreatment while living at home during the pandemic would have higher levels of COVID stress than those who experienced parent-perpetrated maltreatment only during childhood; however, this hypothesis was not supported (t(109) = 0.17, p = 0.87). As hypothesized, we found both types of economic abuse to be significantly positively associated with all three types of COVID stress (r(421) = 0.27, p < 0.001). Economic restriction and COVID stress regarding uncertainty (r(421) = 0.25, p < 0.001), disruptions (r(421) = 0.33, p < 0.001), and worry about family becoming sick (r(421) = 0.20, p < 0.001) were all significantly correlated. Similarly, economic exploitation was positively correlated with COVID stress regarding uncertainty (r(421) = 0.15, p = 0.002), disruptions (r(421) = 0.21, p < 0.001), and worry about family becoming sick (r(421) = 0.13, p = 0.01).
Predicting Variance in Mental Health
Results of regression analyses are shown in Table 3. In the first block of the model, significant demographics of gender, personal finances and parental finances were entered. The second block added the three forms of COVID stress, and the third block considered two forms of economic abuse. The fourth block tested the added contribution of maltreatment chronicity. Here, the maltreatment chronicity variable was created through a series of dummy variables comparing a) the no maltreatment (NM) group (0) to the maltreatment under the age of 18 (MU18) group (1); b) the NM group (0) to the maltreatment that last occurred over the age of 18 (MHO18) group (1); c) the MU18 group (0) to the NM group (1), and d) the MU18 group (0) to MHO18 group (1). Block 4a weighs the NM/MU18 and NM/MHO18 contributions, while block 4b weighs the MU18/NM and MU18/MHO18 contributions. The same model was repeated for each mental health variable.Table 3 Multiple regression results predicting depression, anxiety, and traumatic stress by demographics, maltreatment chronicity, economic abuse, and COVID stress
Depression Anxiety Traumatic Stress
B ß B ß B ß
Block 1
Demographics
Gender 1.47 .12* 1.50 .13** 4.08 .11*
Personal Finances -1.002 -.13* -1.07 -.16** -1.31 -.06
Family Finances -0.38 -.05 -0.46 -.07 -2.17 -.10
Block 2
Demographics
Gender 0.63 .05 0.68 .06 1.75 .05
Personal Finances -0.54 -.07 -0.70 -.10* -0.23 -.01
Family Finances 0.09 .01 -0.04 -.01 -0.93 -.04
COVID Stress
Uncertainty 1.55 .26*** 1.46 .28*** 3.56 .21**
Disruptions 1.72 .30*** 1.19 .23*** 4.18 .25***
Becoming Sick -0.004 -.001 0.35 .07 1.73 .11*
Block 3
Demographics
Gender 0.72 .06 0.76 .07 2.19 .06
Personal Finances -0.50 -.07 -0.68 -.10* -0.06 -.003
Family Finances 0.29 .04 0.13 .019 0.08 .004
COVID Stress
Uncertainty 1.68 .28*** 1.57 .29*** 4.04 .24**
Disruptions 1.31 .23*** 0.88 .17** 2.69 .16*
Becoming Sick -0.18 -.03 0.22 0.05 0.94 .06
Economic Abuse
Restriction 0.16 .15* 0.12 .12 0.67 .22**
Exploitation 0.19 .14* 0.16 .13* 0.77 .20**
Block 4a
Demographics
Gender 0.10 .01 0.30 .03 0.49 .01
Personal Finances -0.41 -.05 -0.60 -.09 0.25 .01
Family Finances 0.40 .05 0.22 .03 0.38 .02
COVID Stress
Uncertainty 1.49 .25*** 1.43 .27*** 3.52 .21***
Disruptions 1.36 .24*** 0.90 .18** 2.81 .17**
Becoming Sick -0.08 -.02 0.29 .06 1.20 .08
Economic Abuse
Restriction 0.10 .09 0.07 .07 0.48 .16*
Exploitation 0.20 .15* 0.16 .13* 0.78 .21**
Maltreatment Chronicity
NM v MU18 1.98 .11* 1.85 .11* 7.65 .15***
NM v MHO18 3.28 .17*** 2.38 .14** 8.44 .16***
Block 4b
Demographics
Gender 0.10 .01 0.30 .03 0.49 .01
Personal Finances -0.41 -.05 -0.60 -.09 0.25 .01
Family Finances 0.40 .05 0.22 .03 0.38 .02
COVID Stress
Uncertainty 1.49 .25*** 1.43 .27*** 3.52 .21***
Disruptions 1.36 .24*** 0.90 .18** 2.81 .17**
Becoming Sick -.08 -.02 0.29 .06 1.20 .08
Economic Abuse
Restriction 0.10 .10 0.07 .07 0.480 .16*
Exploitation 0.20 .15* 0.16 .13* 0.79 .21**
Maltreatment Chronicity
MU18 v NM -1.98 -.14* -1.85 -.14* -7.65 -.19**
MU18 v MHO18 1.31 .07 0.55 .03 .79 .02
Block 1: Depression: R2 = 0.045, Adj R2 = 0.037, F = 6.06***, Anxiety: R2 = 0.064, Adj R2 = 0.057, F = 8.92***, Traumatic Stress: R2 = 0.034, Adj R2 = 0.026, F = 4.10***
Block 2: Depression: R2 = 0.305, Adj R2 = 0.294, F = 28.32***, Anxiety: R2 = 0.316, Adj R2 = 0.305, F = 29.88***, Traumatic Stress: R2 = 0.270, Adj R2 = 0.257, F = 21.16***
Block 3: Depression: R2 = 0.373, Adj R2 = 0.360, F = 28.68***, Anxiety: R2 = 0.367, Adj R2 = 0.353, F = 27.93***, Traumatic Stress: R2 = 0.414, Adj R2 = 0.401, F = 30.24***
Block 4a: Depression: R2 = 0.401, Adj R2 = 0.386, F = 25.67***, Anxiety: R2 = 0.388, Adj R2 = 0.372, F = 24.32***, Traumatic Stress: R2 = 0.445, Adj R2 = 0.429, F = 27.26***
Block 4b: Depression: R2 = 0.401, Adj R2 = 0.386, F = 25.6***, Anxiety: R2 = 0.388, Adj R2 = 0.372, F = 24.32***, Traumatic Stress: R2 = 0.445, Adj R2 = 0.429, F = 27.26***
When predicting depression symptoms, gender (ß = 0.12) and personal finances (ß = -0.13) were significant in the first block. However, after COVID stress variables were entered into the next block, gender and finances were no longer significant. In the second block, uncertainty about the future (ß = 0.26) and disruptions (ß = 0.30) added to the prediction of depression. Both economic restriction (ß = 0.15) and economic exploitation (ß = 0.14) were significant predictors of depression when entered in the third block. Here, uncertainty (ß = 0.25) and disruptions (ß = 0.24) remained significant. In the final blocks, individuals who had experienced enduring maltreatment (MHO18 ß = 0.17) or childhood maltreatment (MU18 ß = 0.14) also reported greater depression compared to the NM group. However, there was no significant difference between the enduring maltreatment (MHO18) and childhood maltreatment (MU18) groups (ß = 0.07) in depression symptoms. In all, this model accounted for 38.6% of the variance in depression symptoms, with COVID stress and enduring maltreatment accounting for more variance than childhood maltreatment or economic exploitation.
A similar pattern arose for anxiety. As before, gender (ß = 0.13) and personal finances (ß = -0.16) predicted anxiety in the first block. However, the contribution of gender was no longer significant when COVID uncertainty (ß = 0.28) and COVID disruptions (ß = 0.23) were added. Here, personal finances (ß = -0.10), COVID stress around uncertainty (ß = 0.29) and disruptions (ß = 0.17), and economic exploitation (ß = 0.13) were significant contributors in the third block. In the final blocks, individuals who experienced childhood maltreatment (MU18 ß = 0.112) or enduring maltreatment (MHO18 ß = 0.14) reported significantly more depression compared to the NM group. However, individuals experiencing enduring maltreatment did not report more symptoms of anxiety than those who reported childhood maltreatment, ß = 0.031. Here, COVID stress variables (ß = 0.27; ß = 0.18) and economic exploitation (ß = 0.13) remained significant contributors to anxiety. This model contributed to 37.2% of the variance in anxiety, with the largest beta values for COVID uncertainty and COVID disruptions.
The final model predicted 42.9% of the variance in traumatic stress. Participant gender (ß = 0.11) was a significant predictor of traumatic stress in the first block, while all three forms of COVID stress (uncertainty ß = 0.21; disruptions = 0.25; family becoming sick ß = 0.11) were significant in the second block. Both forms of economic abuse were found to be significant in the third block (restriction ß = 0.22; exploitation ß = 0.20). COVID uncertainty (ß = 0.24) and disruptions (ß = 0.16) also remained significant in the third block. Both COVID stress variables and economic abuse variables remained significant in the fourth blocks when enduring and childhood maltreatment were considered in comparison to non-maltreated groups (MHO18/NM ß = 0.16; MU18/NM ß = 0.15). Economic exploitation and COVID uncertainty accounted for the most variance.
Discussion
The findings of this study provide empirical support that parent-perpetrated maltreatment occurs beyond the age of 18 and is associated with poor mental health outcomes, including depression, anxiety, and traumatic stress. Whereas previous literature has not addressed cumulative, parent-perpetrated maltreatment, our sample’s high rate of reported maltreatment occurring in the household of origin indicates the persistence of parent-perpetrated maltreatment. In our study, 13% of participants reported any type of maltreatment happening in emerging adulthood, somewhat similar to other studies investigating parent-perpetrated maltreatment among college students (McKinney et al., 2020). To interrupt enduring patterns of maltreatment, large changes such as the victim moving out of the home or focused therapeutic interventions are often needed; especially given pandemic’s influence on housing accessibility, which has allowed parent-perpetrated maltreatment to continue well beyond the age of 18 for many.
Our results also support the hypothesis that emerging adults who have experienced emotional, physical, or sexual abuse, emotional or physical neglect, or economic abuse will have higher levels of COVID stress compared to those who did not experience abuse or neglect. Still, the data did not show that one group of emerging adults, those who experienced parent-perpetrated maltreatment while living in their household of origin over the age of 18, had significantly higher levels of COVID stress compared to those who experienced abuse or neglect in childhood alone. This may be due to the enduring health effects of traumatic stress, even in the absence of abuse or neglect during the college years (Springer et al., 2003). Individuals who had experienced parent-perpetrated maltreatment over the age of 18 may be experiencing similar traumatic stress symptoms; research by Seery and colleagues (2013) would suggest that this group was more resilient to COVID stress due to steeling effects of the high levels of home environment stress, thus producing similar levels of COVID stress between groups.
Finally, the findings supported that chronicity of parent-perpetrated abuse and neglect, level of economic abuse, and level of COVID stress account for significant variance in mental health (depression, anxiety, and traumatic stress). Maltreatment chronicity, economic exploitation, and COVID stress around uncertainty about the future and disruptions due to COVID each contributed to depression. This is consistent with the findings of other studies regarding the relation between COVID stress and mental health outcomes (Alonzi et al., 2020; Kujawa et al., 2020). Given our similar results for anxiety and traumatic stress, it appears that not only do abusive elements of the home environment add significant challenge to mental health, but chronic maltreatment extending into emerging adulthood exacerbates these challenges.
Strengths and Limitations
Important strengths of our study include the consideration of developmentally relevant stressors for emerging adults. Our study assessed for three mental health outcomes (depression, anxiety, and traumatic stress), which, consistent with previous research on child maltreatment, were strongly associated with parent-perpetrated maltreatment in emerging adults. Finally, our study was able to account for associations between both COVID stress and maltreatment within each mental health outcome, contributing to previous literature on mental health during COVID-19. However, despite these strengths, our study also has limitations. Our findings may not be generalizable to populations outside of the cultural norms and higher education system of the United States. Studies of more ethnoracially diverse populations of emerging adults should be conducted to establish their prevalence of varying types of parent-perpetrated maltreatment and related mental health outcomes. Additionally, the use of MTurk to conduct this study assumes a certain financial privilege (access to computer, internet), so other inclusive methodologies should be considered. Furthermore, the methodology selected by the researchers utilized a digital, self-report questionnaire, wherein participants may have been reluctant to report the true severity of their symptoms; although literature has shown that self-report is a valid methodology within the emerging adult population (An & Zhang, 2018), and especially due to the difficulty of detection with pandemic isolation, maltreatment identification is increasingly reliant on self-report.
Additionally, omission of some items from our measure of chronicity, (e.g., “frequency of maltreatment”) is a limitation. Researchers felt that considering frequency without severity gives incomplete insight into the degree of maltreatment; yet our online methodology limited safe and ethical evaluation of the maltreatment endured. Further, reports of maltreatment were counted without type distinction, due to the overall desire to understand prevalence of any type of maltreatment in this age group. However, future studies should consider that specific types of chronic maltreatment (e.g., combined physical and sexual abuse, physical neglect only) have been differentially associated with mental health outcomes and later life revictimization.
Finally, our study is limited within the context of COVID-19: while some maltreatment measured here is a function of living at home due to COVID-19, we are unable to distinguish between ongoing maltreatment participants may have experienced had the pandemic not occurred. Future studies should aim to measure this outside the context of COVID-19.
Clinical Implications and Further Research
The findings of this study indicate that parent-perpetrated maltreatment of emerging adults is more prevalent than previously shown. Therefore, we recommend increased screening for this concern through healthcare providers and higher education institutions. Results of this study reveal that many participants have experienced multiple forms of chronic, traumatic, and stressful events, thus indicating the need to address both their safety and their mental health. Further research could use qualitative data to inform both preventative and reactive measures for maltreatment in this age group, allowing for broader description of maltreatment issues and their effects. A natural progression of this work is to ethically and robustly assess both the chronicity and severity of maltreatment endured by the participant in relation to mental health outcomes. Furthermore, studies could assess emerging adult access to, use of, and efficacy of established mental health resources currently available to the population of emerging adults transitioning out of hostile homes. Future investigations could explore how to design interventions tailored to the unique needs of emerging adults. As the results of this study show, at least for this sample of participants, chronic maltreatment is a serious and deleterious part of the lives of many emerging adults whose plight is often left unrecognized and untreated.
Funding
This work was supported by the University of Michigan Psychology Department Thesis Grant (EM) and the Fine Family through the University of Michigan Honors Department Grant (EM).
Data Availability
Data used in this study are available from the corresponding author (SGB) upon reasonable request.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735161 | NO-CC CODE | 2022-12-14 23:29:52 | no | J Fam Violence. 2022 Dec 6;:1-13 | utf-8 | J Fam Violence | 2,022 | 10.1007/s10896-022-00478-3 | oa_other |
==== Front
Child Psychiatry Hum Dev
Child Psychiatry Hum Dev
Child Psychiatry and Human Development
0009-398X
1573-3327
Springer US New York
36484884
1476
10.1007/s10578-022-01476-8
Original Article
Daily COVID-19 Stressor Effects on Children’s Mental Health Depend on Pre-pandemic Peer Victimization and Resting Respiratory Sinus Arrhythmia
http://orcid.org/0000-0002-0698-7817
Wong Tracy K. Y. [email protected]
Colasante Tyler
Malti Tina
grid.17063.33 0000 0001 2157 2938 Department of Psychology and Centre for Child Development, Mental Health, and Policy, University of Toronto, Deerfield Hall, 3359 Mississauga Rd., Mississauga, ON L5L 1C6 Canada
9 12 2022
112
24 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Children’s risk of poorer mental health due to the COVID-19 pandemic may depend on risk and protective factors heading into the pandemic. This study examined same-day associations between COVID-19 stressors and children’s mental health using a daily diary design across 14 days, and considered the moderating roles of pre-pandemic peer victimization experiences and resting respiratory sinus arrhythmia (RSA; an indicator of cardiac regulatory capacity). Forty-nine Canadian children aged 8–13 years (Mage = 10.69, 29 girls) participated in the final wave of a longitudinal study just prior to the pandemic and a daily diary extension during the pandemic (N = 686 pandemic measurement occasions). Multilevel modeling indicated that children had poorer mental health on days when they experienced a COVID-19 stressor (e.g., virtual academic difficulties, social isolation). A three-way interaction indicated that this association was stronger for those with higher pre-pandemic peer victimization experiences and lower pre-pandemic resting RSA; however, highly victimized children with higher resting RSA did not experience poorer mental health on days with COVID-19 stressors. Findings offer preliminary insights into the preceding risk and protective factors for children’s mental health amidst major subsequent stress.
Keywords
COVID-19
Childhood
Mental health
Peer victimization
Respiratory sinus arrhythmia
Canadian Institutes of Health Research Foundation SchemeFDN-148389 Malti Tina
==== Body
pmcThe COVID-19 pandemic has heightened psychosocial stress and threatened mental health on a global scale. Accumulating evidence suggests that children and adolescents may be particularly vulnerable due to greater difficulties in understanding and adapting to sudden pandemic changes [1–3]. The majority of extant developmental studies on this topic are cross-sectional [3]; however, given the uncertain and fluctuating nature of the pandemic, effects on child mental health should ideally be examined as a dynamic process [4, 5]. Moreover, relatively novel and poorly understood pandemic effects may be best assessed in an ecologically valid manner as they naturally unfold in daily life [6, 7]. Hence, we adopted a daily diary approach in the present study to explore COVID-19 stressor effects on children’s mental health over a 14-day snapshot of pandemic life. While the pandemic’s effects on mental health have been unprecedented in scale, not everyone has been affected to the same degree [3]. Factors denoting pre-pandemic risk and readiness may explain these differential effects [2–4]. We thus accounted for between-child differences in well-known risk and protective factors that were present before the pandemic to further understand which children were more or less likely to experience subsequent pandemic-related mental health challenges.
COVID-19 Stress and Child Mental Health
The enduring COVID-19 pandemic has put children and adolescents of various backgrounds at risk of poor mental health [8]. A meta-analysis of 29 studies indicated that global rates of anxiety and depression in children and adolescents doubled during the pandemic relative to pre-pandemic estimates [9]. Suggested causes include limited peer contact and the transition to online learning due to school closures and lockdowns [10]. Nonetheless, the majority of evidence concerning the impacts of COVID-19 on child mental health is based on cross-sectional studies that utilized one-time, retrospective reports [3]. This methodological approach offers preliminary support for a link between COVID-19 and mental health challenges but falls short of explaining the dynamics of when and whether these factors actually co-occur for children on a daily basis. Even during typical times, indicators of mental health can vary considerably day-to-day within children and these within-child processes can further differ from one child to another [11–13]. Considering stress and mental health as dynamic processes may be especially worthwhile during COVID-19 because pandemic-related stressors are likely to introduce even more volatility [4, 14].
Capturing within- and between-child variations in mental health and isolating the contributions of ongoing COVID-19 stressors requires intensive longitudinal assessments of children’s daily lives. A common intensive longitudinal method is the daily diary approach, which taps into the micro-level processes that unfold in real life by requiring respondents to report on the same set of variables once per day for a given period of time—usually about 2 weeks [15]. Yet, only a handful of studies examining pandemic impacts on child mental health have leveraged the daily diary approach [4, 7, 14, 16]. Moreover, although some of these studies have considered moderators immediate to the pandemic, such as child age [16], daily coping strategies and parental support [14], and COVID-related worries and isolation [4], none have considered pre-pandemic moderators. Addressing this gap is important because discerning how children’s existing or pre-pandemic capacities support or hinder their adjustment during the pandemic can inform proactive efforts to foster resilience to future challenges [2, 5].
Pre-Pandemic Risk and Protective Factors
Well-studied pre-pandemic factors may represent a promising starting point for explaining which children fare worse or better throughout the pandemic [2, 5]. In this study, we considered children’s peer victimization experiences as a well-established risk factor [17, 18] and their resting respiratory sinus arrhythmia (RSA) as a biological regulatory capacity with links to various aspects of well-being and adjustment [19, 20].
Peer Victimization Experiences
Some children may enter the pandemic with pre-existing stressors, which may put them at increased risk of developing mental health problems during the pandemic [2, 5]. One stressor that is common to children is bullying victimization, which is regarded as a global public health issue due to its high prevalence and negative developmental impacts [18]. Previous research indicates that highly victimized children are at heightened risk of mental health problems, particularly depression and anxiety [17, 21], as well as aggressive and externalizing behaviours [22]. Rudolph et al. [23] found that child-reported victimization experiences interacted with cortisol stress measured in anticipation of an impending interaction with an unfamiliar peer to predict depression 1 year later, suggesting that prior victimization heightened children’s vulnerability to the negative implications of additional stress. Such findings align with the cumulative risk model, which posits that children who are exposed to multiple stressors in different life domains are at accumulated risk of mental health problems (for more empirical evidence of cumulative risk, see [24, 25]). Based on this cumulative risk perspective, children who were victimized heading into the pandemic may be particularly vulnerable to poorer mental health because they would be exposed to dual stressors and their compounding negative implications. Thus, the stress associated with pre-pandemic peer victimization and COVID-19 may accumulate and surpass children’s stress tolerance threshold, heightening their risks of mental health challenges.
Respiratory Sinus Arrhythmia (RSA)
One potential protective factor that is relevant to the examination of mental health amidst the pandemic is children’s capacity to regulate their negative emotions and stress [26, 27]. Previous research from across the developmental spectrum suggests that regulatory capacities reduce the negative implications of stress [28]. For example, children with better emotion regulation tend to be less susceptible to the transgenerational effects of chronic physiological stress [29] and adolescents with more effective regulatory capacities tend to have better physical health in the face of increased family stress [30]. RSA is a biological indicator that allows researchers to assess regulatory capacities without the potential biases of traditional questionnaire reports [31]. It indicates vagus nerve activity in the parasympathetic division of the autonomic nervous system. The vagus nerve acts like a brake that slows the heart when engaged [32]. Higher RSA thus reflects greater autonomic regulatory capacity. When RSA is measured in a resting state (i.e., resting RSA), it is thought to reflect an individual’s dispositional autonomic regulatory capacity [32]. Indeed, children with higher resting RSA tend to show better stress regulation and social competence [20, 33], whereas lower resting RSA has been characterized as a general marker of stress vulnerability [34]. Hence, higher resting RSA may buffer the association between pandemic stress and mental health.
Peer Victimization Experiences and RSA
Pre-pandemic risk and protective factors may also have interactive effects on mental health amidst COVID-19. Specifically, the negative implications of victimization experiences may be weakened by stronger regulatory capacities. Cooley et al. [35] found that children who could effectively regulate their sadness and worry when exposed to bullying victimization were less likely to experience depressive and anxiety symptoms. McLaughlin et al. [36] found that psychosocial stressors across different domains, including peer victimization, were associated with greater anxiety and depression for adolescents with lower resting RSA but not for those with higher resting RSA. In a similar vein, adolescents with a bullying victimization history reported more depressive symptoms when they also demonstrated blunted RSA reactivity in response to a stressful social exclusion paradigm [37]. These findings suggest that higher resting RSA in the current study may attenuate the exacerbating role of victimization experiences on pandemic stress and mental health. This assumption aligns with the risk-protective model of resiliency whereby protective factors mitigate the association between risk factors and negative outcomes [38].
Developmental Context
We situated our examination within the context of middle childhood because it marks a period when children not only become increasingly sensitive to their environment, but also undergo substantial changes across social and emotional domains of development [39]. For example, children’s social networks expand significantly and peer relationships become salient as implied by increases in peer conflicts and friendship formations [40]. These changes can be accompanied by greater social-emotional challenges (e.g., unfamiliar peer and academic problems) and distressed feelings (e.g., anxiety, sadness), which may evolve into early-onset mental health challenges [41, 42]. In contrast, the developmental trajectory of resting RSA begins to level off from middle childhood to adolescence, implying that its regulatory role in middle childhood may continue into adolescence [43, 44]. Due to these developmental patterns, middle childhood presents a relevant context to examine effects of pre-pandemic resting RSA and peer-related challenges on unpredictable COVID-19 stressors and mental health.
The Present Study
Although the pandemic has generally been associated with poorer mental health for children [3], our understanding of this association remains cursory because of limited research on the daily effects of specific pandemic stressors on same-day mental health. Additionally, little is known about how pre-pandemic risk and protective factors moderate these dynamic pandemic processes. To address these questions, the current study leveraged a longitudinal project that began prior to and continued into the pandemic. Specifically, we examined the association between pandemic stressors and child mental health across 14 days and hypothesized that children would have poorer mental health on days with a pandemic stressor. We then leveraged point-in-time data collected prior to the pandemic to examine the extent to which between-child differences in peer victimization experiences and resting RSA exacerbated or weakened this day-to-day association. We hypothesized that higher pre-pandemic peer victimization experiences would exacerbate the association between pandemic stress and child mental health. In contrast, we hypothesized that higher resting RSA would buffer the daily effects of pandemic stress. In line with previous empirical findings [36, 37] and the risk-protective model of resiliency [38], we remained open to the possibility that the aggravating effects of pre-pandemic peer victimization on pandemic-induced mental health challenges would be lessened for children with higher resting RSA (i.e., a three-way interaction). Finally, we accounted for child age and gender as covariates based on previous studies linking them to stress tolerance and common mental health outcomes, such as anxiety and depression [9, 45].
Methods
Participants
Participants were children and their caregivers in Canada who participated in a 4-wave annual longitudinal study in the years leading up to the pandemic (2015–2020; N = 197 at wave 4). During the pandemic in January–February 2021 (post provincial COVID-19 lockdown), caregivers were contacted to see if they were willing to participate in a 14-day daily diary extension study. Forty-nine caregivers of children aged 8–13 years (Mage = 10.69; 59% girls) agreed to participate (84% biological mothers; 84% married; 75% bachelor’s degree or above; 76% had multiple children; 63% household income above $60,000 CAD). Their ethnic composition included 47% Western European, 18% multi-ethnic, 6% Eastern European, 6% South/South-East Asian, 2% Middle Eastern, 2% East Asian, 2% African, 2% Central/South American and Caribbean, and 8% other (6% chose not to report). The present study utilized data from the pandemic diary study and the fourth wave of the prior longitudinal study (collected between February 2018 and February 2020). Independent-samples t-tests revealed that families who agreed vs. disagreed to participate in the COVID daily diary extension did not significantly differ along the relevant demographic characteristics we collected (i.e., caregiver’s level of education and household income; ps = 0.83 and 0.74, respectively).
Procedures
Ethics approval was obtained from the University’s Research Ethics Board. Oral assent was obtained from children and written informed consent was obtained from caregivers. Prior to the pandemic, children and their caregivers attended a 60- to 90-min laboratory session that was led by trained research assistants. Children were outfitted with physiological equipment and completed a battery of assessments in a designated room. Caregivers completed a questionnaire on their child’s social-emotional development in a waiting area. At the end of the session, caregivers were debriefed and children were offered an age-appropriate book. For the pandemic daily dairy study, caregivers received an email link to a questionnaire asking about their child’s negative emotions and related experiences each night at 7 pm for 14 days. They were compensated with an age-appropriate book for their child.
Daily Mental Health
In line with previous daily diary studies conceptualizing negative emotional experiences as indicators of children’s state mental health [4, 7], daily mental health was measured by the intensity of children’s sadness and anxiety experiences. This approach was also taken because the repetitive nature of diary studies necessitates brief and specific daily measures [14, 16]. Caregivers responded to the item “To the best of your knowledge, how intensely did your child experience the following emotions today?” for sadness and anxiety on a 10-point scale ranging from 0 = not at all intense to 9 = very intense. These scores were averaged and higher levels indicated poorer daily mental health.
Daily COVID-19 Stress
Caregivers indicated whether or not their child experienced a COVID-19 stressor that day (0 = no, 1 = yes). For descriptive purposes, when caregivers stated yes, they were prompted to select the specific stressor from a list including the following: concerns about own health, concerns about the health of a loved one, interpersonal or social issues (e.g., couldn’t see a family member or friend in person), school issues (e.g., difficulty adapting to a new schooling situation), family issues, restrictions on behaviour, others’ pandemic-related behaviour, and other. This list was based on previous studies examining children’s and adolescents’ most prominent concerns about the pandemic [46, 47].
Pre-pandemic Peer Victimization Experiences
Pre-pandemic peer victimization experiences were measured by three items adapted from a widely used peer victimization scale [48]. Items were “is picked on by other children”, “is teased or made fun of by other children”, and “is called names by other children.” Caregivers reported these items on a scale ranging from 1 = never true to 4 = often true. Items were averaged, with higher levels representing more frequent victimization experiences (α = 0.90).
Pre-Pandemic Resting RSA
Monitoring electrodes were secured slightly below the right clavicle and below the ribs on both sides. Three‐lead electrocardiogram data were recorded with a Biopac MP150 data acquisition system and a BioNomadix module at a sampling rate of 2 kHz (Biopac Systems, Goleta, CA, USA). Leads from each electrode were connected to a module fastened around the midsection that communicated wirelessly via the MP150 with a computer in an adjacent room running the AcqKnowledge 4.2 data acquisition software (AcqKnowledge Software, RRID:SCR_014279). After a 5-min rest period, children were asked to remain still while watching a 120-s video depicting a sea turtle swimming slowly in the ocean (see [49]). The research assistant left the room for the duration of the video. Physiological data collected during the video were imported to Mindware HRV 3.0.21 (Mindware Technologies, Gahanna, OH, USA) for visual inspection, cleaning, and RSA calculation. They were cleaned in two 60‐second intervals to ease processing. An interval that required more than 20% of editing was excluded from further analysis. Resting RSA was computed as the mean level of RSA across the video.
Analytic Strategy
First, missing data and preliminary analyses (i.e., tests of normality, descriptive statistics, correlations) were conducted. Given the nested structure of the data (i.e., daily measures of COVID-19 stress and mental health nested within children), multilevel modeling (MLM) was conducted in Mplus 8.5 [50]. An intercept-only model was examined to determine if there was variability in mental health to warrant an investigation of within- and between-child factors. Following this, a random slope model with COVID-19 stressors as a random effect at level 1 and the sole predictor was tested to determine if there was significant between-child variability in the within-child association between daily COVID-19 stress and mental health. Significant variability in the slope would allow an examination of the moderating roles of pre-pandemic peer victimization experiences and resting RSA.
In the model with predictors, COVID-19 stress was specified as a time-varying predictor at level 1 to determine its daily association with mental health and this slope was allowed to randomly vary between children at level 2. At level 2, pre-pandemic peer victimization experiences and resting RSA were specified as time-invariant predictors of the aforementioned slope to determine their respective roles in the association between daily COVID-19 stress and mental health. Additionally, the interaction term Peer Victimization Experiences × Resting RSA was created and added at level 2 to test whether resting RSA moderated a potential aggravating effect of peer victimization experiences on the level-1 stress–mental health slope. To account for potential confounds of age and gender differences, these two variables were added as covariates at level 2 predicting mental health and the level-1 stress–mental health slope. However, only significant covariates were retained in the final model to maintain model parsimony and as much power as possible [51]. Simple slopes analyses were conducted to probe significant interactions [51].
Results
Missing Data
Missing data rates for victimization experiences and resting RSA were 8.16% and 18.37%, respectively. Caregivers completed an average of 10.96 (SD = 3.61) records for the 14-day diary study. In other words, the compliance rate for the daily diary variables was approximately 78%. Little’s MCAR test was not significant, χ2(819) = 772.29, p = 0.88, indicating that the data might be missing completely at random (MCAR). Accordingly, full information maximum likelihood (FIML) estimation was used to retain all participants at level 2 and bolster the level-1 sample size to 686. This estimation method has been found to provide more reliable estimates than listwise deletion, pairwise deletion, and multiple imputation under the assumption of ignorable missing data patterns [52].
Preliminary Analyses
Within-child variables (i.e., COVID-19 stress and mental health) were averaged up to create between-child scores for descriptive analyses. No issues concerning normality (skewness = 0.08 to 1.54, kurtosis = − 0.73 to 2.99) were evident based on recommended guidelines (skewness < 3, kurtosis < 8; [53]). Descriptive statistics and zero-order correlations between the examined variables and covariates are presented in Table 1. COVID-19 stress was at moderate levels. Frequencies of underlying reasons for stress are outlined in Table 2 to aid interpretation of results. The most frequently cited COVID-19 stressor for children was school issues, such as difficulty adapting to a new schooling situation (e.g., online learning). COVID-19 stress was correlated with poorer mental health at the within and between level. In other words, the presence of COVID-19 stress was correlated with same-day poorer mental health (as compared to typical days with stress unrelated to COVID-19). In addition, children who were exposed to more COVID-19 stress across the entire study tended to have poorer overall mental health relative to other children with less stress. Pre-pandemic victimization experiences were associated with poorer overall mental health during the pandemic. On average, girls were more likely to experience COVID-19 stress across the 14 days.Table 1 Descriptive statistics and zero-order correlations
Variable 1 2 3 4 5 6 M SD Range (min–max)
1. Mental health 1 0.19*** 1.57 1.76 0.00–9.00
2. COVID-19 stress 0.51*** 1 0.31 0.31 0.00–1.00
3. Victimization experiences 0.30* 0.24 1 1.70 0.65 1.00–3.33
4. Resting RSA 0.02 0.02 − 0.04 1 6.96 1.08 4.71–9.87
5. Age − 0.06 − 0.16 − 0.01 0.01 1 10.69 2.21 8.23–13.99
6. Gender − 0.11 − 0.29* 0.20 0.20 − 0.18 1 – – –
Above the diagonal line = within-level correlations. Below the diagonal line = between-level correlations. For between level, COVID-19 stress and mental health = average across 14 days. COVID-19 stress: unrelated to COVID-19 = 0 and related to COVID-19 = 1. Gender: girls = 0 and boys = 1. Descriptive statistics are averaged up to the between level as applicable
*p < 0.005; ***p < 0.001
Table 2 Reasons for children’s daily COVID-19 stress
Reason %
Concerns about own health 6.62
Concerns about the health of a loved one 10.29
Interpersonal or social issues (e.g., couldn’t see a family member or friend in person) 12.50
School issues (e.g., difficulty adapting to a new schooling situation) 34.56
Family issues (e.g., conflict with siblings) 11.03
Restrictions on behaviour (e.g., having to wear a mask or follow social guidelines) 12.50
Others’ pandemic-related behaviour (e.g., others not following public health guidelines) 7.35
Other 5.15
Percentage frequency of overall occurrence reported
Predicting Mental Health and the Daily Association Between COVID-19 Stress and Mental Health
A preliminary null (intercept-only) model revealed an intraclass correlation (ICC) of 0.48, indicating that 48% of the variance in mental health could be explained by between-child factors and thus confirming the use of multilevel modeling to disaggregate variance into within variance = 1.63, SE = 0.26, p < 0.001, 95% CI [1.28, 2.14], and between variance = 1.48, SE = 0.53, p = 0.005, 95% CI [0.44, 2.52]. The random slope model, within R2 = 0.17, p < 0.001, indicated a significant overall effect of COVID-19 stress on mental health, b = 0.51, SE = 0.21, p = 0.01, 95% CI [0.10, 0.92], suggesting that, on average across participants, mental health was worse on days with vs. without the presence of COVID-19 stress (residual variance at within level = 1.45, SE = 0.25, p < 0.001, 95% CI [0.96, 1.93]). As presented in Fig. 1, significant variance was found for this level-1 daily association from child to child at the between level, variance = 1.03, SE = 0.26, p < 0.001, 95% CI [0.51, 1.54], with some children showing poorer daily mental health in lockstep with COVID-19 stress but others showing little to no link between these factors. Children also differed in their average level of mental health at between level, variance = 0.88, SE = 0.28, p < 0.001, 95% CI [0.35, 1.42]). Hence, our planned moderation analyses were conducted to potentially explain this variability.Fig. 1 Graphical depiction of the dispersion in the association between daily COVID-19 stress and mental health
Two models (i.e., with vs. without covariates) were compared to determine the most parsimonious model. For the model with covariates, neither age (b = 0.07, SE = 0.09, p = 0.43, 95% CI [− 0.10, 0.24]) nor gender (b = − 0.55, SE = 0.48, p = 0.25, 95% [− 1.49, 0.39]) emerged as a significant covariate of the slope. Similarly, no significant main effects were evident on mental health for age (b = − 0.06, SE = 0.08, p = 0.43, 95% CI [− 0.23, 0.10]) and gender (b = − 0.24, SE = 0.29, p = 0.41, 95% CI [− 0.81, 0.33]). To identify the best-fitting model, their Akaike’s Information Criterion (AIC) and Bayesian Information Criterion (BIC) values were compared. A difference larger than 10 is considered sufficient and the model with lower AIC and BIC values is deemed a better fit to the data [53, 54]. Results indicated that the model without covariates (AIC = 2706.38, BIC = 2792.47) fit the data better than the model with covariates (AIC = 3004.26, BIC = 3126.59). Moreover, the findings for the core variables were consistent across both models. Hence, the model without covariates was retained (see Table 3).Table 3 Two-level MLM predicting mental health and daily association between COVID-19 stress and mental health
Within-level outcome Predictor Coefficient SE p 95% CI
Mental health COVID-19 stress 0.48 0.24 0.04 [0.02, 0.95]
Residual variance
Mental health 1.42***
R2
Mental health 0.17***
Between-level outcome Predictor Coefficient SE p 95% CI
COVID-19 stress → Mental health slope Victimization experiences 0.68 0.29 0.02 [0.12,1.24]
Resting RSA 0.16 0.19 0.41 [− 0.21, 0.52]
Victimization Experiences × Resting RSA − 0.52 0.23 0.02 [− 0.96, − 0.07]
Mental health Victimization experiences 0.27 0.20 0.19 [− 0.13, 0.67]
Resting RSA 0.05 0.10 0.62 [− 0.15, 0.25]
Victimization Experiences × Resting RSA − 0.01 0.13 0.94 [− 0.27, 0.25]
Residual variance
COVID-19 stress → Mental health slope 0.71, p = 0.059
Mental health 0.93**
R2
COVID-19 stress → Mental health slope 0.30***
Mental health 0.11***
Same-day effect of COVID-19 stress → Mental health was also significant in a random-slope model without level-2 predictors/covariates, b = 0.51, SE = 0.21, p = 0.01, 95% CI [0.10, 0.92]
**p < 0.01; ***p < 0.001
As presented in Table 3, the between-level residual variance in the slope of COVID-19 stressors on daily mental health became marginally significant with the addition of level-2 predictors (compared to the significant variance found in the slope-only model), indicating that the variance in the slope was meaningfully explained by the predictors. With respect to the core analyses, no significant main effects on mental health were evident at level 2 for victimization experiences, resting RSA, and their interaction. However, peer victimization experiences significantly predicted the level-1 stress–mental health slope, such that the daily association between COVID-19 stress and mental health was stronger for those with higher pre-pandemic peer victimization experiences. No significant moderation effect was evident for resting RSA on the slope but its interaction with peer victimization experiences on the slope was significant. Specifically, the positive, aggravating effect of peer victimization experiences on the stress-mental health slope was significant for children with lower (− 1 SD) levels of resting RSA, b = 1.25, SE = 0.37, p < 0.001, 95% CI [0.54, 1.97], but not for those with higher (+ 1 SD) levels of resting RSA, b = 0.15, SE = 0.36, p = 0.67, 95% CI [− 0.55, 0.86] (see Fig. 2).Fig. 2 Moderating role of peer victimization experiences on the association between daily COVID-19 stress and mental health at different levels of resting RSA
Discussion
The aim of the present study was to examine the dynamic association between pandemic stressors and child mental health while considering the moderating roles of pre-pandemic risk and protective factors. To address this aim, we employed a daily diary approach during the pandemic and leveraged information collected in a longitudinal study prior to the pandemic. Current findings suggest that COVID-19 stressors have negative implications for children’s mental health on a daily basis, but also shed light on pre-pandemic factors that may heighten or lower children’s susceptibility to these implications.
Consistent with our primary hypothesis, children experienced poorer mental health on days when there was a COVID-19 stressor. These findings align with pre-pandemic developmental patterns indicating increased mental health challenges in response to unpredictable stressors in middle childhood [39]. Moreover, they corroborate extant cross-sectional literature concerning the negative impacts of COVID-19 stress on children’s mental health [8, 9]. Importantly, the findings add to the limited body of work demonstrating the daily dynamics of this association [14, 16]. Given that cumulative effects of daily stress can increase vulnerability to depressive symptoms and anxiety [55, 56], and that internalizing emotions such as sadness and anxiety underpin depression and anxiety disorders [57, 58], these findings suggest that children who are exposed to COVID-19 stressors on a daily basis may be at risk of developing pathological symptoms over time.
However, there is also a possibility that children learn to adapt to COVID stress over time by using relevant coping strategies. In line with this assumption, the stress inoculation model posits that mild to moderate (i.e., manageable) levels of stress may help children develop adaptive stress responses to subsequent stressors [59, 60]. Some empirical studies suggest that exposure to moderate levels of stress activates coping mechanisms and promotes affective regulation in childhood [61, 62]. Longer-term studies conducted later into the pandemic are needed to clarify the potential inoculating effects of chronic pandemic stress.
Although not the primary focus of the present study, results from descriptive analyses pinpointed school-related issues (e.g., sudden transition to online learning) as the most salient source of COVID-19 stress for children on a daily basis. A potential reason is that parents became heavily involved in school-related matters as a result of school closures—a novel challenge that may have increased the likelihood of negative parent–child interactions (stemming from shared stress) and corresponding negative affect for children (see [7, 63]). Researchers could extend the current findings by considering the effects of specific school-related concerns on child mental health to better understand this association and inform approaches to improve distance learning or hybrid models. Another significant source of children’s daily COVID-19 stress was social issues (e.g., not being able to see friends). These findings align with developmental work on the increased significance of peer relationships in middle childhood [40], which may explain why social issues factored prominently into children’s stress levels over our 14-day study.
Partly in line with our secondary hypothesis, children who were victimized prior to the pandemic were at increased risk of poorer mental health during the pandemic. These findings substantiate the developmental significance of peer relationships in middle childhood by implicating pre-pandemic peer victimization in the negative mental health impacts of COVID-19 stress for children of this age. They also align with previous studies demonstrating the additive contributions of peer victimization and other sources of stress (e.g., family conflict and adverse childhood experiences) to poor mental health [64, 65]. These findings suggest that pre-pandemic victimization may have long-term compounding impacts with non-victimization-related stressors, including COVID-19. This parallels Guo et al.’s [66] study, which indicated that pre-pandemic adverse childhood experiences (e.g., maltreatment) exacerbated the negative impacts of COVID-19 exposure on post-traumatic stress symptoms and anxiety among a group of adolescents in rural China. Thus, children with cumulative risk experiences may be particularly vulnerable to mental health challenges in the context of COVID-19 [24].
Regarding our final, more exploratory hypothesis, pre-pandemic resting RSA interacted with pre-pandemic peer victimization experiences when predicting the effects of daily pandemic stressors. Specifically, children who had been victimized but had higher resting RSA were less likely to be emotionally impacted by COVID-19 stressors. Higher resting RSA capacities might have helped children modulate pre-pandemic victimization experiences, thereby mitigating their exacerbating role in later COVID-19 stress. These findings align with previous studies indicating that children with lower resting RSA tend to have worse mental health when exposed to stressors (e.g., violence exposure), whereas children with higher resting RSA experience lesser or null effects of stress [6, 36, 67]. However, contrary to our hypothesis that pre-pandemic resting RSA would directly mitigate the role of pandemic stress on mental health, no significant moderation effects were evident on the daily stress–mental health slope after controlling for effects of pre-pandemic peer victimization and the aforementioned significant interaction of pre-pandemic peer victimization and resting RSA. As resting RSA is subject to changes as a function of environmental stress [44, 68], future studies may wish to investigate pre-pandemic and concurrent (i.e., pandemic) resting RSA to gain a more comprehensive understanding of its protective potential. For example, in the present case, the buffering role of resting RSA might have been stronger on pre-pandemic victimization relative to pandemic stress because it was also measured before the pandemic.
Limitations, Contextual Considerations, and Future Directions
The current findings need to be interpreted in light of some limitations. First, pre-pandemic peer victimization experiences were parent reported. Although child–parent agreement on peer victimization can be quite high (e.g., interrater reliability = 0.81 to 0.92) in middle to late childhood; [71]), future research should include child reports because children might not disclose all victimization experiences to their parents. Relatedly, daily diary data were parent reported. Although the pandemic might present a context for parents to be more aware of children’s mental health (e.g., parents may have more opportunities to interact with children due to less commuting/more home time) and child–parent agreement on children’s feelings and emotions is significant and moderate (albeit weaker compared with external symptoms/behaviors; [69, 70]), future research should include child reports to fully capture the dynamics of their daily mental health. These limitations should also be considered within the mitigating context of our design, as repeated measures gave parents more opportunities to observe and capture their children’s experiences in the realm of mental health and the time lapse between pre-pandemic reports of peer victimization experiences and pandemic daily diary reports may have offset potential shared-informant/shared-method effects. Second, mental health was evaluated by the intensity of internalizing emotions (i.e., sadness and anxiety). To better account for the spectrum of child mental health, future studies should incorporate behavioral mental health symptoms in children that are pertinent to the pandemic (e.g., disruptive and aggressive behaviors). Lastly, our relatively small sample size limited our power at level 2. Although our main effect of pre-pandemic victimization and our interaction effect held across models with and without covariates and align with previous findings and theory, they should be interpreted with proportionate caution relative to our level-1 findings. Nonetheless, these sample limitations should be considered in light of the diary portion being mobilized in the middle of a global pandemic. The level-2 findings also add to very limited literature on potential pandemic moderators and can be used as a starting point to further consider the buffering and hindering roles of pre-existing factors in major subsequent stress.
Conclusions
The American Academy of Pediatrics, American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association have declared a national emergency for child and adolescent mental health due to the COVID-19 pandemic [72]. Our findings concur with these cautionary calls by underscoring the effects of COVID-19 stressors on children. Daily pandemic stressors had a greater mental health impact than other sources of daily stress. Children who experienced peer victimization heading into the pandemic were seemingly less equipped to deal with pandemic challenges. Autonomic regulatory capacities may act as a potential buffer for such children. From a practical perspective, our findings tentatively suggest that preventative initiatives and/or interventions to support vulnerable or victimized children’s capacity to cope with concurrent stressors (see [26, 73]) may have knock-on benefits, as well-regulated victimized children may be better equipped to deal with major subsequent stress in novel realms.
Summary
Not all children are affected by COVID-19 to the same degree, suggesting that pre-pandemic risk and protective factors may be at play. We adopted a daily diary approach to examine dynamic associations between daily COVID-19 stressors and mental health while leveraging longitudinal data to account for pre-pandemic risk and protective factors, namely peer victimization and resting respiratory sinus arrhythmia (RSA). Children had poorer mental health on days when they experienced a COVID-19 stressor, and this association was stronger for those with higher pre-pandemic peer victimization experiences and lower pre-pandemic resting RSA. Current findings suggest that preventative initiatives and/or interventions may benefit from focusing resources on vulnerable or victimized children’s coping .
Acknowledgements
The authors thank the children and caregivers who participated, and the members of the Centre for Child Development, Mental Health, and Policy who helped with data collection and cleaning.
Funding
This research was supported by a Canadian Institutes of Health Research Foundation Scheme Grant (FDN-148389) awarded to Tina Malti.
Data Availability
The data underlying this manuscript cannot be shared publicly because we did not receive permission from our Research Ethics Board.
Declarations
Conflict of interest
The authors have declared that they have no competing or potential conflicts of interest.
Ethical Approval
This study was approved by the University’s Research Ethics Board.
Informed Consent
Children provided informed oral assents and caregivers provided informed consents.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36484884 | PMC9735162 | NO-CC CODE | 2022-12-14 23:29:52 | no | Child Psychiatry Hum Dev. 2022 Dec 9;:1-12 | utf-8 | Child Psychiatry Hum Dev | 2,022 | 10.1007/s10578-022-01476-8 | oa_other |
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Indian J Otolaryngol Head Neck Surg
Indian J Otolaryngol Head Neck Surg
Indian Journal of Otolaryngology and Head & Neck Surgery
2231-3796
0973-7707
Springer India New Delhi
3293
10.1007/s12070-022-03293-w
Original Article
The Retrospective Pilot Study of the Prevalence of Olfactory Dysfunction or Loss of Smell, Loss of Taste and Oral Manifestations Among COVID-19 Positive Health Workers in Muscat, Oman
http://orcid.org/0000-0002-5190-1883
Saraf Sanjay [email protected]
1
Nalawade Triveni 1
Mallikarjuna Rachappa 1
Al Kashmiri Ammar 12
1 Oman Dental College, Wattayah, PO BOX 835, 116 Muscat, Oman
2 grid.415206.4 0000 0004 0621 7948 Department of Emergency, Khoula Hospital, Muscat, Oman
3 12 2022
15
18 10 2022
21 11 2022
© Association of Otolaryngologists of India 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
A retrospective study evaluating the prevalence of loss of smell, loss of taste and oral manifestations was carried out by framing an online questionnaire and disseminated among the health care workers including medical and dental students, who were afflicted with COVID-19. The objective of this study was to find out the prevalence of the loss of smell, loss of taste (LOST) and oral manifestations and whether these (LOST & oral manifestations) can be the premonitory manifestations and also whether these can predict the prognosis of COVID-19 disease. Our study showed that the loss of smell, loss of taste and dry mouth did occur before the other symptoms considerably in the COVID-19 infected health workers. All the infected health workers were in home quarantine phase and not hospitalized during the occurrence of COVID-19. The loss of smell, loss of taste and oral manifestations can be the prodromal signs of COVID-19 and may be used as a screening tool to predict the severity of the disease.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12070-022-03293-w.
Keywords
Olfactory dysfunction
COVID-19
Prognosis
Health care workers
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pmcIntroduction
The closing of the year 2019 heralded with the rapid spread of the COVID-19(SARS-COV-2) disease across the globe mapping almost all the countries and posing threat to the whole mankind [1, 2].
The first-time occurrence of COVID-19 was reported by WHO among the patients exposed to seafood market in Wuhan city of China on 31st December 2019. The causative microorganism of this disease was first identified and reported by Chinese Centre for Disease Control and Prevention (CCDC) on 7th January, 2020 followed by its notification to WHO [3, 4]. As of July 2021, the disease did affect more than 195 million individuals causing over four million deaths worldwide [1]. In Oman the COVID-19 positive patients were first reported on 24 February 2020 and these COVID-19 affected patients had returned after travelling to Iran [5]. The main mode of human to human spread of COVID-19 virus has been found to be varied ranging from direct contact and airborne transmission. The dissemination of this virus is facilitated by sneezing, coughing, droplet inhalation and direct contact with the oral, nasal and eye mucous membrane of the asymptomatic or symptomatic carrier [6]. The time elapsed between the onset of infection till the appearance of signs and symptoms ranges from 0–24 days with an average of 5–7 days. The signs and symptoms of this disease have a diverse range of severity [2]. According to the report from WHO-China Joint Mission, most of the COVID-19 disease is of mild-moderate nature with only few cases (6.1%) tapering to serious condition and requiring hospital admission [3]. The disease is characterized by the common symptoms of fever, dry cough, fatigue and myalgia with few cases showing Gastro Intestinal Tract (GIT) disorder that includes abdominal pain and diarrhea. [2, 3]
The COVID-19 infection has also shown the signs and symptoms featuring dysfunction of smell and taste as seen in other common upper respiratory viral infections and this has been supported by plenty of studies [7–9]. In fact, one of the recent studies have shown that smell and taste alterations occurs in about 75% of COVID-19 individuals [10]. These localised alterations have been seen as the only manifestations in mild infections or heralding symptoms of the severe COVID-19 disease progressing eventually to pneumonia. There is not much evidence of a direct link of other reported oral manifestations, like ulcerative, erosive, vesiculobullous and plaque like lesions, besides taste loss in COVID-19 [10, 11]. However there have been reports that among the oral manifestations, the localized condition like xerostomia or dry mouth may be the common, initial manifestations or the sole presentation in COVID-19 patients besides gustatory and olfactory alterations [12, 13]. The COVID-19 virus does show an initial manifestation of smell and taste alterations because presumably during the initial transmission, the virus comes in contact with the oral, nasal and eye mucosa. A study also reports, that the COVID 19 positive patients are more prone for these manifestations as compared to the COVID-19 negative individuals [14]. It becomes therefore imperative to study the initial nature and course of the disease or the prodromal signs and symptoms because an early recognition of the disease can facilitate the diagnosis and a quick management. Therefore, keeping this aim and objective in view, we conducted a web or online based questionnaire survey to find out the prevalence of dysfunction/loss of smell and taste (LOST) and oral manifestations related to COVID-19 disease among the health care workers (HCW) and dental/medical students of Oman. The aim and objectives of this study was also to relate the symptoms of taste and smell dysfunction and oral manifestations with the prognosis of the disease.
Methods
After the approval of the present study by Ministry of Health, Oman. we formulated a questionnaire especially for the HCW and dental/medical students (studying in Muscat). The health care workers that were targeted included the residents, post graduates, doctors, nurses, medical assistants and other allied health workers working in Muscat, Oman. A web based SurveyMonkey questionnaire link was created, uploaded and circulated/posted (via WhatsApp) in September 2021 among the health workers and dental/medical students in Muscat. The online questionnaire ensured anonymity and confidentiality of the respondents. The participants were queried for their profession, work place, age, gender, smoking history, medical history and whether they experienced any signs and symptoms akin to upper respiratory infection (including loss of smell, loss of taste, oral manifestations) past 6–7 months retrospectively.
The online responses with incomplete history and the participants who did not go for COVID-19 testing were not included in the study. The patients with a history of any nasal or sinus disease, Bell’s palsy or medications known to cause taste disturbances were also disregarded. Furthermore the patients with psychological disturbances and recent surgeries of head and neck region were also removed from the list of study group.
Results
A total of 83 HCW’s and medical/dental students retorted to the questionnaire, that was earlier uploaded and circulated via the link interface-Survey Monkey. All had a history of upper respiratory infection (URI) past 6 months, retrograde from September 2021. Out of the total responses, only 69 subjects admitted, that they tested for COVID-19 infection. Therefore, the remaining 14 were left out from the study group. The answered questionnaire forms for the study group of 69 individuals were further segregated into 2 groups on the basis of the declaration of the respondents, about their COVID status. About 58 respondents were identified and labelled as COVID-19 positive (GRP-I) while 11 were labelled as COVID negative (GRP-II).
The GRP-I comprised of 22 Doctors/Dentists (37.93%), 15 Medical Nurses (25.86%), 9 Residents/Interns (15.51%), 9 Auxiliary staff (15.51%) & 3 Medical assistants (5.17%). About 38(65.51%) individuals in GRP-I worked mainly in hospital under Ministry of Health, Muscat, and 20(34.48%) in private hospitals/polyclinic, Oman. The group GRP-II comprised of 9(81.81%) Medical/Dental students (81.81%) and 2 Interns studying/working (18.18%) in Medical/Dental College in Muscat, Oman. All the individuals in GRP-I (58) were in an age range of 25–45 years (mean 35 years), while the GRP-II had all the young adults (11) in an age range of 18–24 years. The GRP-I presented with 51 males (87.93%) and 7 females (12.06%) while the GRP-II, that comprised of 11 individuals, had a balanced gender ratio with 6 males and 5 females with a ratio of 1:1.2.
Mostly the subjects of about 50(88.40%) in GRP-I were non-smokers, however about 8(13.79%) had smoking history, while in GRP-II, there was none with smoking history. Interestingly, about 42(60.86%) subjects out of the total of 69 in GRP-I & GRP-II, who answered the questionnaire, had no evidence of significant medical history, however few respondents in GRP-I & GRP-II declared their medical history, for example; 14(20.28%) of them had a history of diabetes, 10(14.49%) had a history of hypertension, 1 (1.44%) had the history of allergic rhinitis/ sinusitis, 1(1.44%) respondent reported having undergone dental treatment/radiation while 1(1.44%) had a history of asthma.
All the participants in GRP-I & GRP-II encountered the clinical signs and symptoms of a typical upper respiratory infection (URI) past 6–7 months retrograde. The manifestations in the GRP-I, individuals predominantly were the occurrence of fever in 43(74.13%) respondents, followed by sore throat/dry cough in 38(65.51%), runny nose in 35(60.34%), myalgia in 31(53.44%), and GI symptoms in 2(3.44%) individuals respectively. There were 15(25.86%) subjects, who did not have any medical symptoms. In GRP-II, out of the total of 11 respondents, all observed and wrote about the constitutional signs and symptoms of fever. There was dry cough /sore throat in 9(81.81%) subjects, followed by myalgia/fatigue in 2(3.44%). The questionnaire forms were analysed for their answers to the queries relating to LOST and oral manifestations respectively. Most (about77.58%) of the COVID-19 positive individuals could not identify the source of infection. The remaining members reported to have come in contact with the infected patients, while rendering the medical care in the hospital. The queries relating to the occurrence of loss of smell and loss of taste and oral manifestations were answered by the study group. It was revealed, that none of the subjects in GRP-II did experience any loss of taste and smell sensation or any oral manifestations. However, in GRP-I, the LOST was reported to have occurred together in 16(44.82%) participants. There were 30(34.48%) individuals, who reported the loss of smell sensation, while the loss of taste was reported in 10 (17.24%) individuals separately. Only 2(3.44%) individuals had none of these signs and symptoms. The onset of the loss of smell was reported to have occurred mostly before the other symptoms in 38(65.51%) individuals or with the other symptoms in 10(17.24%) individuals and 2(3.44%) individuals did not remember the onset. The onset of the loss of taste was also reported to have occurred before the other systemic manifestations in 31(53.44%) individuals and in 10(17.24%) with the other symptoms and in 7(12.06%) after the other symptoms subsided. The remaining 10(17.24%) subjects did not remember any loss of taste. During the LOST manifestations, more than half 47(81.03%) individuals were home quarantined, while none were in the hospital and 11(18.96%) respondents attended the Out Patient Department (OPD). The recovery of the loss of smell and or loss of taste varied from a period of 5 days–10 days and up to 30 days. Out of 58 COVID-19 positive subjects, about 45(77.58%) people recovered from the loss of smell &/ or taste within a period of 30 days and 11 did recover from 5 to 10 days and 2(3.46%) did not remember the recovery period. The overall COVID-19 disease after the observance of the loss of smell and taste worsened mostly in about 7(12.06%) COVID-19 infected respondents and improved in 9(15.51%), was stable in 30(51.72%), while about 12(20.68%) individuals did not remember. The loss of smell and loss of taste did resolve eventually in 55(94.82%) and the same number did not receive any treatment for the disorders. More than half of the individuals 33(53.44%) out of the total 58 respondents did not have any oral manifestations, however 18(31.03%) wrote about dry mouth as the oral manifestations during COVID-19 infection. About 3(5.17%) individuals had swollen red tongue or sore tongue followed by two (3.44%) subjects each with a history of bleeding in gingiva and swelling/painless or painful ulcerations. The onset of the oral manifestations was seen in 25(43.10%) individuals before the other symptoms and after the other symptoms in 26(44.82%) subjects. The oral manifestations during post recovery period was seen in about seven (12.06%) individuals. The oral lesions resolved in more than 10 days as reported by most 38(65.51%) affected COVID-19 positive patients. Other 20 (34.48%) individuals reported the oral lesion recovery in between 5 and 10 days respectively.
Discussion
Plenty of studies have emerged during COVID-19 pandemic, evaluating (LOST) among the COVID-19 infected patients [4, 7–9, 12, 14, 15]. We conducted an online questionnaire-based study evaluating the prevalence of dysfunction or loss of smell, taste and oral manifestations among the COVID-19 positive HCW, working in Muscat, Oman. We chose HCW as the study group, because they could, perhaps interpret and answer the queries related to the signs or symptoms related to LOST & oral manifestations with accuracy. This study according to best of our knowledge is one of the few studies carried out in Muscat, Oman.
We, in our survey-questionnaire, identified 58 COVID-19 positive & 11 COVID-19 negative responses respectively. The COVID-19 positive individuals comprised of more of doctors/dentists (37.93%) and medical/dental nurses (25.86%), followed by residents (15.51%) and medical auxiliaries (15.51%). This goes in agreement with the study that reported a high COVID-19 infection rate among doctors (53/100) and in nurses (50/1000) respectively in Milan during peak of COVID-19 disease [15]. The increased infection rate among doctors and nurses can be explained based on the fact that, these are the vulnerable groups of HCW, who came in contact with the COVID-19 patients, while rendering the health care. The 11 COVID-19 negative responses in the questionnaire received by us, included solely the medical/dental students. This COVID-19 negative status among medical and dental students, presumably could be due to the closure of onsite classes, confinement at home and resumption of online classes, thereby leading to less exposure to the virus. There was more prevalence of COVID-19 infection among young adults & elderly and in males (87.93%) in age range of 25–55 years. A study evaluating the epidemiological characteristics of COVID-19 patients in Oman also showed (75%) prevalence in males between the age range of 20–49 years [16]. The predilection of male gender among COVID-19 positive infected individuals also has been reported from the studies carried out in Oman, Italy and USA [5]. The reason of more COVID-19 positivity in males is suggested to occur because they indulge more in outdoor activities, but our study, had both male and female health workers equally working in the hospitals and therefore this assumption does not apply to our study. The various pre-existing medical conditions and co-morbidities seem to be the predisposing factors for the symptomatic and severe COVID-19 infection according to the recent systematic review and meta-analysis of the prevalence of underlying diseases among COVID-19 infected patients [17]. The COVID-19 positive respondents, who answered our study questionnaire, were mostly non-smokers (88.40%). Out of the total respondents in GRP-I & GRP-II, considerable number of them (77.58%) had no pre-existing medical localised or generalised conditions. The minimal co-morbidities and the non-smoking status in most of the respondents could be the reason for the less severity of COVID-19 disease among the GRP-I. The disease was less severe and same can be seen in their answered questionnaire in which most of the health HCW reported that they were home quarantined and none was admitted to the hospital during their stint with COVID-19 infection. The COVID-19 positive individuals answered to the queries and it was identified that most of them had the clinical manifestations of fever (74.13%), sore throat/dry cough (65.51%), nasal stuffiness or rhinorrhoea (60.34%) and myalgia/fatigue (53.44%) and GI symptoms (34.38%). The various systematic reviews and meta-analysis and other studies have also reported the common occurrence of fever, cough, fatigue & rhinorrhoea/nasal stuffiness as the common symptoms in COVID-19 infected patients. [17–20]. On the other hand, all the COVID-19 negative individuals also had a history of fever and a considerable group had dry cough/sore throat and few had a history of myalgia only.
After the analysis of the answers to the queries in the questionnaire, it was found that both the loss of smell and taste was reported by 16(27.58%) and the loss of smell was separately observed by 30(51.72%) respondents and the loss of taste was seen in ten (17.24%) individuals. The reason of the increased prevalence of loss of smell or olfactory dysfunction (OD) in our study is agreeable, because it is an established fact, that the smell impairment is one of the frequent symptoms of COVID-19 infection [21]. Although the pathogenesis of the OD is not still clear but it is suggested that the COVID-19 virus prefers the ACE2 receptors that are expressed in epithelial cells of oral mucosa and nasal mucosa [22]. A multicentric study in patients from China, France and Germany reported the loss of smell or the loss or taste in 19% before the other symptoms [14]. Our study showed the loss of smell and the loss of taste before the other systemic manifestations in (65. 51%) and (53. 44%%) respectively. This strongly suggests that OD and loss of taste could act as a prodromal sign and strong indicator of COVID-19 disease. Most of the individuals recovered their loss of smell and taste by about two months’ time according to the study reported from Greece [21]. A systematic review also reveals the recovery of OD within 30 days that was similar to our study [23]. Furthermore, a multicentric European study reports the recovery of smell and taste within two weeks after the resolution of general symptoms, which is earlier than the recovery observed by most of the individuals in our study [24]. Our study showed more of OD and recovery of the same within 30 days and the condition of the patients was stable and in fact all the patients were home quarantined. A study in Brazil reports that OD is more prevalent in patients with mild flu-like symptoms [25]. Our study also showed the respondents having more of OD and this feature may reflect or predict good prognosis of COVID disease.
Besides the loss of taste, the other oral manifestations reported from the studies on COVID-19, are the manifestations of painful ulcers, macular-papular & vesiculobullous lesions [26]. The other cross-sectional study reports the difficulty in swallowing, burning mouth and bleeding through gingiva as the oral manifestations however, xerostomia was common and was seen in 44% individuals. [27]
Our study also showed most of the individuals manifesting dry mouth in 18 individuals (31.03%) besides taste loss and this also goes in agreement with the above-mentioned cross-sectional study and other study from India that showed xerostomia in about 28% of individuals. There have been other studies also that show xerostomia as one of the oral manifestations of COVID 19 [28–30]. The xerostomia could have occurred due to the fever and dehydration.
Conclusion
Our study showed OD inclusive of gustatory dysfunctions and xerostomia that occurred before the disease occurrence. Therefore, these prodromal signs and symptoms of COVID can help to predict the disease occurrence and even the severity of the disease. This study had a limitation of small sample size and moreover, we had to depend on the answers to the queries, that was based solely on recall. Large scale study needs to be done to evaluate the prodromal signs and symptoms of the COVID-19 by accessing the hospital records.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (XLSX 131 KB)
Declarations
Conflict of interest
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| 0 | PMC9735163 | NO-CC CODE | 2022-12-14 23:29:52 | no | Indian J Otolaryngol Head Neck Surg. 2022 Dec 3;:1-5 | utf-8 | Indian J Otolaryngol Head Neck Surg | 2,022 | 10.1007/s12070-022-03293-w | oa_other |
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Biometals
Biometals
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10.1007/s10534-022-00473-7
Article
Efficacy of copper blend coatings in reducing SARS-CoV-2 contamination
Glass Arielle 1
Klinkhammer Katharina E. 1
Christofferson Rebecca C. 2
Mores Christopher N. [email protected]
1
1 grid.253615.6 0000 0004 1936 9510 Milken Institute School of Public Health, The George Washington University, Washington, DC USA
2 grid.64337.35 0000 0001 0662 7451 School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA USA
7 12 2022
19
20 7 2022
19 11 2022
© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
SARS-CoV-2 is a highly infectious virus and etiologic agent of COVID-19, which is spread by respiratory droplets, aerosols, and contaminated surfaces. Copper is a known antiviral agent, and has resulted in successful reduction of pathogens and infections by 83–99.9% when coated on surfaces in intensive care units. Additionally, copper has been shown to inactivate pathogens such as Coronavirus 226E, a close relative of SARS-CoV-2. Here, we examine the ability of two copper blends with differing compositions to inactivate SARS-CoV-2 virus at different time points. Copper Blend 2 (75.07% pure copper) was found to significantly reduce (over 50%) the viability of SARS-CoV-2 at 5 min of contact, with at least 98% reduction in recovered virus at 20 min (vs. plastic control). However, Copper Blend 1 (48.26% pure copper), was not found to significantly reduce viability of SARS-CoV-2 at any time point when compared to plastic. This may indicate that there is an important percentage of copper content in materials that is needed to effectively inactivate SARS-CoV-2. Overall, this study shows that over the course of 20 min, coatings made of copper materials can significantly reduce the recovery of infectious SARS-CoV-2 compared to uncoated controls, indicating the effective use of copper for viral inactivation on surfaces. Furthermore, it may suggest higher copper content has stronger antiviral properties. This could have important implications when short turnaround times are needed for cleaning and disinfecting rooms or equipment, especially in strained healthcare settings which are struggling to keep up with demand.
Keywords
SARS-CoV-2
COVID-19
Copper
Copper blend
Viral inactivation
Antiviral agent
Teck Resources Limited
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pmcIntroduction
SARS-Coronavirus-2 (SARS-CoV-2), the etiologic agent of COVID-19, is primarily spread by respiratory droplets, but also through contaminated surfaces and aerosols (Govind et al. 2021; Jin et al. 2020; Kraay et al. 2020; Marquès and Domingo 2021; Ren et al. 2020; van Doremalen et al. 2020; Ye et al. 2020; Zuo et al. 2020). To prevent spread of the virus, emphasis was initially put on basic public health practices, including isolating, hand washing, and mask wearing (CDC, 2021, 2020; Gostin et al. 2020; Johns Hopkins University, 2021). These mitigation efforts were largely aimed at stopping the spread of droplet-associated SARS-CoV-2 viral particles both in the context of human-to-human transmission, as well as surface contamination. Even with these efforts, SARS-CoV-2 spread across the globe, indicating a need for additional research on transmission prevention.
Recent research suggests that respiratory droplets from breathing, speaking, coughing, and sneezing can be carried distances greater than 2 m (Bahl et al. 2020). These droplets often land on high-touch surfaces (e.g., doorknobs, elevator buttons, cell phones), which allows infectious virus to be mechanically transmitted to the mouth, nasal mucosa, or conjunctiva of others. Droplet spread and pathogen survival depend on factors including surface porosity, temperature, ventilation, and relative humidity, but some droplet-associated viruses remain infectious on common surfaces for days or weeks (Aboubakr et al. 2021; Bueckert et al. 2020). Infectious pathogens have been found to survive and remain infectious for extended periods of time on high-touch surfaces, including those in healthcare settings (e.g., bed rails, IV poles) (CDC, 2021; Mantlo et al. 2020; Otter et al. 2013; Zerbib et al. 2020). Specifically, SARS-CoV-2 has been found to be viable on non-porous surfaces for days to weeks (Biryukov et al. 2020; Chin et al. 2020; Liu et al. 2021; Riddell et al. 2020; van Doremalen et al. 2020). Additionally, SARS-CoV-2 was found to have substantial transfer from non-porous solids to artificial skin through light touch when the droplet was wet (13–16% virus transfer) as well as after it had evaporated (3–9% virus transfer) (Behzadinasab et al. 2021a). Consequently, disinfection of high-touch surfaces, particularly during a pandemic and in healthcare settings, provides an opportunity to decrease the spread of deadly pathogens (Bahl et al. 2020; Otter et al. 2016).
Numerous studies have demonstrated the antibacterial and antiviral activity of copper against a wide range of pathogens including E. coli, Influenza A, Norovirus, SARS-CoV-1, herpes simplex, Junin, HIV-1, poliovirus, monkeypox, and Marburg and Ebola viruses (Champagne et al. 2019; Cortes and Zuñiga 2020; Govind et al. 2021; Grass et al. 2011; Han et al. 2005; Imai et al. 2012; Mantlo et al. 2020; Manuel et al. 2015; Michels et al. 2015; Montero et al. 2019; Noyce et al. 2007; Rakowska et al. 2021; Rosenberg et al. 2018; Różańska et al. 2017; Warnes et al. 2012; Wilks et al. 2005). In addition, laboratory results have led to the use of copper materials in clinical trials in healthcare facilities and community centers (Casey et al. 2010; Colin et al. 2018; Hinsa-Leasure et al. 2016; Ibrahim et al. 2018; Poggio et al. 2020; Zerbib et al. 2020; Schmidt et al. 2012), with hospital intensive care units containing copper-coated appliances reporting 83–99.9% reduction in the burden of pathogens and infections (Montero et al. 2019; Salgado et al. 2013). The exact mechanism behind the ability of copper to inactivate or kill pathogens is believed to differ between pathogen types (Festa and Thiele 2011; Manuel et al. 2015; Rosenberg et al. 2018; Warnes et al. 2012, 2015). For viruses, the proposed mechanism is that copper ions disrupt viral envelopes, prevent cellular respiration, produce free radicals, and destroy the DNA/RNA of microbes when in contact with copper surfaces (Rakowska et al. 2021).
Copper inactivation of Coronavirus 226E, another common respiratory virus and close relative of SARS-CoV-2, has been successful, with inactivation observed in 40 min or less (Warnes et al. 2015). Recent studies by Behzadinasab et al. (2020), Hutasoit et al. (2020), and Mantlo et al. (2020) examined Cu2O/PU film, 3D-printed copper-coated surfaces, and cold-spray copper coating, respectively, for SARS-CoV-2 inactivation capabilities. Behzadinasab et al. (2020) reported 99.99% inactivation after 1-h incubation while Hutasoit et al. (2020) and Mantlo et al. (2020) found 96% and 99% inactivation after 2 h. Another study by Behzadinasab et al. (2021b) studied two transparent surface coatings, PDA/Cu and PDA/Cu2O, which also found 99.98% and 99.88% inactivation of SARS-CoV-2 after 1-h incubation, respectively. However, viability of the novel SARS-CoV-2 virus immediately after contact with copper materials has not been adequately tested. It may be that, coating surfaces with copper infused materials can more rapidly inactivate SARS-CoV-2 than we currently understand. Accordingly, in this study, we evaluated the inactivation of SARS-CoV-2 virus upon contact with two copper blend coatings from 1 to 20 min.
Materials and methods
Viral strains and cell lines
Vero E6 (ATCC® CRL-1586™) cells were cultured in 1× Dulbecco’s Modification of Eagle’s Medium with 4.5 g/l glucose supplemented with 1% l-glutamine (DMEM; Corning, Corning, NY) and 10% (v/v) fetal bovine serum (FBS; Corning, Corning, NY). Vero E6 cells were grown in T175 flasks and passaged when the cells were 90% confluent. 1.2 × 106 cells were plated in 6- well plates overnight before use.
The SARS-CoV-2 Chile strain was obtained from BEI (NR-52439). One hundred μl was added to a confluent T75 flask of Vero E6 cells in serum-free media (SFM) with antibiotics. Forty-eight hours later, 100 μl of supernatant was added to a second flask with uninfected cells. If cytopathic effects were observed after 48 h, the supernatant was removed and the flask containing the remainder of the cells were placed in a freezer for 5 min. The flask was then thawed, and the cells were collected using 5 ml of new media. The cell lysate was mixed with supernatant and centrifuged at 500×g for 5 min before aliquoting.
Surfaces tested
Two distinct copper blends were formulated by Alloi, with Copper Blend 1 containing 48.26% pure copper and Copper Blend 2 containing 75.07% pure copper. The composition of each blend’s inputs is characterized in Table 1. To create these materials, copper and zinc were ordered from a third-party and then mixed with a non-metal binder (styrene resin sold under COR75-AQ-010L [INTERPLASTICS Unsaturated Polyester Resin product code: SIL94BA-990]) and catalyst (Methyl ethyl ketone peroxide [MEKP]). Both blends consist of metallic components as well as the binder, to make the material as a whole not conductive, and the catalyst, to harden the binder. All materials were measured using a scale with an uncertainty of ± 0.01 g. The two copper blends were then used to completely cover pieces of 2 cm × 2 cm polycarbonate plastic sheets with 0.1 mm thickness using cold-spray technology. These materials were then brought to the George Washington University Nanofabrication and Imaging Center and imaged using the GEI Teneo LV scanning electron microscope (SEM) with an EDAX Octane Pro detector for elemental analysis. SEM was done at 5000 × and energy-dispersive x-ray spectroscopy (EDS) was performed at 30 kV for 100 s showing Copper Blend 1 to be mainly copper (Cu) 41.61% and zinc (Zn) 14.59%, and Copper Blend 2 to be predominately Cu 100%. Further analysis of these coated materials by SEM and energy-dispersive X-ray spectroscopy (EDS) is shown in Fig. 1 and Table 2. The copper blend-coated samples arrived in sealed bags and were tested as is. The uncoated plastic samples arrived with a thin sheet of plastic adhesive covering one side. The plastic adhesive was removed with 70% ethanol and allowed to dry before experimentation. The components of the copper blends were unknown to the researchers at the time of experimentation; however, composition was revealed to the researchers after analysis of results.Table 1 Composition of the inputs for Copper Blend 1 and 2 by weight and percent of total weight
Material Copper Blend 1 Copper Blend 2
Weight (g) Percent of total weight Weight (g) Percent of total weight
Binder (styrene resin [COR75-AQ-010L]) 45.0 24.13% 45.0 24.13%
Catalyst (methyl ethyl ketone peroxide [MEKP]) 1.5 0.80% 1.5 0.80%
Pure copper (without brass) 90.0 48.26% 140.0 75.07%
Brass (70% copper/30% zinc) 50.0 26.81% 0.0 0.00%
Total weight 186.5 – 186.5 –
Zinca 15.0 8.04% 0.0 0.00%
Total copper (pure copper + brass)a 125.0 67.02% 140.0 75.07%
aZinc weight and percent of total weight were calculated based on brass content. Total copper weight and percent of total weight were calculated based on brass and pure copper content
Fig. 1 Photographs of the appearance of: A) Copper Blend 1 from left to right: tested material in a 2 × 2 cm square, scanning electron microscopy (SEM) done at 5000x, energy-dispersive X-ray spectroscopy (EDS) at 30 kV for 100 s showing composition of Copper Blend 1 Spot 2 to be predominately copper (Cu) 41.61% and zinc (Zn) 14.59%; B) Copper Blend 2 from left to right: tested material in a 2 × 2 cm square, SEM done at 5000x, EDS at 30 kV for 100 s showing composition of Copper Blend 2 Spot 1 to be predominately Cu 100% (background analysis of Copper Blend 2 Spot 2 and Spot 3 were predominantly carbon, 57.64% and 43.18%, respectively)
Table 2 Composition of Copper Blend 1 and 2 products by percent weight using energy-dispersive x-ray spectroscopy (EDS)
Copper Blend 1 (spot 2)a Copper Blend 2 (spot 1)a
Element Weight % Error % Weight % Error %
Copper 41.61 1.34 100 0.99
Zinc 14.59 1.45 – –
Carbon 33.98 8.96 – –
Oxygen 9.82 9.90 – –
aEDS spot locations are displayed in Fig. 1 above
Infectivity assay for SARS-CoV-2
Viral stock solution was thawed and placed in ten 1 μl droplets on two different copper blend-coated surfaces to simulate respiratory droplet contact (Lindsley et al. 2013; Warnes et al. 2015). The distinct 1 μl droplets were used instead of one 10 μl droplet to allow for more direct contact with the copper blend surfaces due to the surface tension of the solution (Mantlo et al. 2020). The virus was removed from the test surfaces by washing with 490 μl EMEM supplemented with 1% penicillin, streptomycin, amphotericin B and non-essential nucleic acids after incubation at room temperature for various time points: 1 min, 5 min, 10 min, and 20 min. The virus and media mixture was assayed for infectious virus survival using a plaque assay, quantified as plaque forming units (PFU). Serial dilutions of the virus mixture were prepared in infection medium before 200 μl aliquots were plated onto confluent monolayers of Vero E6 cells in Corning® 6-well plates. After 1 h, a 1:1 agar and EMEM overlay was added and plates were incubated at 37 °C and 5% CO2 for 72 h. Following incubation, the plates were fixed with 10% (w/v) formaldehyde, stained with 0.5% Crystal Violet and allowed to dry before plaques were counted.
Statistical analyses
All statistical analyses were performed in R Studio (version 1.3.1093) with base R (version 3.6.3) and significance was assessed at the α = 0.05 level. We first wanted to compare whether the recovery of viable SARS-CoV-2 was differentially affected by incubation on three different materials (Copper Blend 1, Copper Blend 2, and plastic) at four different time points. Median rank titers (Log PFU/ml) across the three materials were compared using the Kruskal–Wallis non-parametric analysis of variance (kruskal.test) after determination that data were not distributed normally (shapiro.test, p < 0.05). When warranted, post-hoc tests for pairwise differences were performed using the Dunn Test (dunnTest, package FSA). We next wanted to compare the performance of each blend compared to the baseline material of plastic. We took the difference of recovered viral titer (log PFU/mL) for each trial-blend combination and calculated the percent reduction from the corresponding trial’s plastic control at each time point. We then used a t-test to determine whether these calculated differences were significantly greater from select null values; namely, 50%, 75%, and 98%. A rejection of the null in this case would indicate that an blend had at least or greater reduction than the null value tested.
Results
Comparison of recovered titer from each type of material
At 1-min exposure time, there was no significant difference in the recovered viral titer (PFUs/mL) among the three materials. At 5, 10, and 20 min contact with Copper Blend 2, there were significantly lower recovered titers of SARS-CoV-2 than both Copper Blend 1 and plastic. The viral titer recovered from Copper Blend 1 was not significantly different from the plastic control at any time point measured (Fig. 2).Fig. 2 At 5, 10, and 20 min, contact with Copper Blend 2 produced significantly (*) lower titers (Log PFU/ml) than exposure to either Copper Blend 1 or plastic (p < 0.05). Presented are data points and boxplot data summaries
Percent reduction of recovered titer of Copper Blend 1 or Copper Blend 2 compared to the plastic control
When the recovered viral titer of each copper blend was compared to that of the plastic control, Copper Blend 1 did not result in a SARS-CoV-2 titer reduction that was significantly greater than 50% at any timepoint. However, for Copper Blend 2, the percent reduction in titer compared to the plastic control was significantly higher. Reduction was significantly greater than a maximum of 50% at time point 5 min, 75% at 10 min, and 98% at 20 min (Fig. 3).Fig. 3 For each copper blend material, points represent percent reduction from matching plastic control. Lines represent the mean percent reduction with ± standard error. *Indicates significantly greater reduction than 50%, **Indicates significantly greater reduction than 75%, ***Indicates significantly greater reduction than 98%
Discussion
Basic infection prevention and control practices are important to prevent the rapid spread of novel viruses, such as SARS-CoV-2. Part of this strategy includes timely and consistent disinfection of surfaces, especially in high-trafficked spaces where respiratory droplets may contain viruses capable of surviving for extended periods of time on commonly used surfaces. Reducing environmental contamination is particularly important during pandemics and in health care settings. Previous studies found copper is an effective option to combat fomite transmission both in laboratory and in clinical settings (Behzadinasab et al. 2020; Hutasoit et al. 2020; Mantlo et al. 2020; Warnes et al. 2015). This current study sought to build on the growing body of knowledge regarding the uses of copper and copper materials as deterrents of surface-mediated transmission of viruses.
Our results indicate that contact with a high copper-content material inactivated SARS-CoV-2 as compared to a plastic control in a time-dependent manner. There was no significant difference in recovered titer between Copper Blend 1, Copper Blend 2, and the plastic control after 1 min of contact, suggesting a minimum time of contact is needed for efficacy. Copper Blend 2 begins to significantly reduce the viability of SARS-CoV-2 at 5 min of contact with at least 98% reduction in recovered virus at 20 min of contact.
Copper Blend 2 is 75.07% pure copper composition by weight compared to Copper Blend 1, which has a pure copper composition of 48.26%. The difference in recovered virus between the two suggests that higher copper content may have stronger antiviral properties. It is important to note that Copper Blend 1 also contained brass, which is a copper alloy with 70% copper/30% zinc, meaning Copper Blend 1 has a total copper content of 67.02%. Our results are similar to a study that demonstrated copper was efficacious at inactivating a human Alphacoronavirus, HuCoV-229E (Warnes et al. 2015). Pure copper and 90% copper materials were able to inactivate HuCoV-229E in 20 min (Warnes et al. 2015). Interestingly, inactivation efficiency began to decrease when the pure copper content was reduced to 85%. As SARS-CoV-2 is more stable on surfaces than HuCoV-229E, determining the efficacy of a specific material’s copper content is critical to evaluate further (Rabenau et al. 2005; van Doremalen et al. 2020).
Other studies have reported greater than 96% inactivation of SARS-CoV-2 after an hour of contact with different copper formulations (Behzadinasab et al. 2020; Hutasoit et al. 2020; Mantlo et al. 2020). Accordingly, our experimental limit of 20 min of contact between the viral inoculum and copper blends may offer a conservative estimate of the ultimate effectiveness of such materials. We cannot rule out the possibility that Copper Blend 1 may have more effectively inactivated SARS-CoV-2 or that Copper Blend 2 may have achieved even greater reduction at contact times exceeding 20 min. However, the effectiveness of Copper Blend 2 at such a short interval may prove beneficial during periods of high community transmission and healthcare stress, when shorter turnaround times for cleaning and disinfecting rooms or equipment is needed to keep pace with demand.
In conclusion, this study has found that over the course of 20 min, copper blend coatings can significantly reduce the recovery of infectious SARS-CoV-2 compared to uncoated controls. Our results indicate the continued use of copper as a viral inactivator for surfaces at-risk for contamination. Furthermore, it may be that there is an important percentage of copper content in materials that is needed for effectiveness against SARS-CoV-2.
Author contributions
AG performed the laboratory work and wrote the main manuscript text, KEK co-led the writing of the manuscript, RCC led the data analysis, CNM conceptualized the study and secured funding. All authors read and approved the final manuscript.
Funding
The research was funded by Teck Resources Limited. Copper blend materials provided by Isaac Lichter, Nick O'brien, and Andrew Medland at Alloi. Neither organization had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Declarations
Conflict of interest
The authors have declared that no competing interests exist.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36474101 | PMC9735165 | NO-CC CODE | 2022-12-14 23:29:52 | no | Biometals. 2022 Dec 7;:1-9 | utf-8 | Biometals | 2,022 | 10.1007/s10534-022-00473-7 | oa_other |
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Biometals
Biometals
Biometals
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Springer Netherlands Dordrecht
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10.1007/s10534-022-00473-7
Article
Efficacy of copper blend coatings in reducing SARS-CoV-2 contamination
Glass Arielle 1
Klinkhammer Katharina E. 1
Christofferson Rebecca C. 2
Mores Christopher N. [email protected]
1
1 grid.253615.6 0000 0004 1936 9510 Milken Institute School of Public Health, The George Washington University, Washington, DC USA
2 grid.64337.35 0000 0001 0662 7451 School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA USA
7 12 2022
19
20 7 2022
19 11 2022
© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
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SARS-CoV-2 is a highly infectious virus and etiologic agent of COVID-19, which is spread by respiratory droplets, aerosols, and contaminated surfaces. Copper is a known antiviral agent, and has resulted in successful reduction of pathogens and infections by 83–99.9% when coated on surfaces in intensive care units. Additionally, copper has been shown to inactivate pathogens such as Coronavirus 226E, a close relative of SARS-CoV-2. Here, we examine the ability of two copper blends with differing compositions to inactivate SARS-CoV-2 virus at different time points. Copper Blend 2 (75.07% pure copper) was found to significantly reduce (over 50%) the viability of SARS-CoV-2 at 5 min of contact, with at least 98% reduction in recovered virus at 20 min (vs. plastic control). However, Copper Blend 1 (48.26% pure copper), was not found to significantly reduce viability of SARS-CoV-2 at any time point when compared to plastic. This may indicate that there is an important percentage of copper content in materials that is needed to effectively inactivate SARS-CoV-2. Overall, this study shows that over the course of 20 min, coatings made of copper materials can significantly reduce the recovery of infectious SARS-CoV-2 compared to uncoated controls, indicating the effective use of copper for viral inactivation on surfaces. Furthermore, it may suggest higher copper content has stronger antiviral properties. This could have important implications when short turnaround times are needed for cleaning and disinfecting rooms or equipment, especially in strained healthcare settings which are struggling to keep up with demand.
Keywords
SARS-CoV-2
COVID-19
Copper
Copper blend
Viral inactivation
Antiviral agent
Teck Resources Limited
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pmcIntroduction
SARS-Coronavirus-2 (SARS-CoV-2), the etiologic agent of COVID-19, is primarily spread by respiratory droplets, but also through contaminated surfaces and aerosols (Govind et al. 2021; Jin et al. 2020; Kraay et al. 2020; Marquès and Domingo 2021; Ren et al. 2020; van Doremalen et al. 2020; Ye et al. 2020; Zuo et al. 2020). To prevent spread of the virus, emphasis was initially put on basic public health practices, including isolating, hand washing, and mask wearing (CDC, 2021, 2020; Gostin et al. 2020; Johns Hopkins University, 2021). These mitigation efforts were largely aimed at stopping the spread of droplet-associated SARS-CoV-2 viral particles both in the context of human-to-human transmission, as well as surface contamination. Even with these efforts, SARS-CoV-2 spread across the globe, indicating a need for additional research on transmission prevention.
Recent research suggests that respiratory droplets from breathing, speaking, coughing, and sneezing can be carried distances greater than 2 m (Bahl et al. 2020). These droplets often land on high-touch surfaces (e.g., doorknobs, elevator buttons, cell phones), which allows infectious virus to be mechanically transmitted to the mouth, nasal mucosa, or conjunctiva of others. Droplet spread and pathogen survival depend on factors including surface porosity, temperature, ventilation, and relative humidity, but some droplet-associated viruses remain infectious on common surfaces for days or weeks (Aboubakr et al. 2021; Bueckert et al. 2020). Infectious pathogens have been found to survive and remain infectious for extended periods of time on high-touch surfaces, including those in healthcare settings (e.g., bed rails, IV poles) (CDC, 2021; Mantlo et al. 2020; Otter et al. 2013; Zerbib et al. 2020). Specifically, SARS-CoV-2 has been found to be viable on non-porous surfaces for days to weeks (Biryukov et al. 2020; Chin et al. 2020; Liu et al. 2021; Riddell et al. 2020; van Doremalen et al. 2020). Additionally, SARS-CoV-2 was found to have substantial transfer from non-porous solids to artificial skin through light touch when the droplet was wet (13–16% virus transfer) as well as after it had evaporated (3–9% virus transfer) (Behzadinasab et al. 2021a). Consequently, disinfection of high-touch surfaces, particularly during a pandemic and in healthcare settings, provides an opportunity to decrease the spread of deadly pathogens (Bahl et al. 2020; Otter et al. 2016).
Numerous studies have demonstrated the antibacterial and antiviral activity of copper against a wide range of pathogens including E. coli, Influenza A, Norovirus, SARS-CoV-1, herpes simplex, Junin, HIV-1, poliovirus, monkeypox, and Marburg and Ebola viruses (Champagne et al. 2019; Cortes and Zuñiga 2020; Govind et al. 2021; Grass et al. 2011; Han et al. 2005; Imai et al. 2012; Mantlo et al. 2020; Manuel et al. 2015; Michels et al. 2015; Montero et al. 2019; Noyce et al. 2007; Rakowska et al. 2021; Rosenberg et al. 2018; Różańska et al. 2017; Warnes et al. 2012; Wilks et al. 2005). In addition, laboratory results have led to the use of copper materials in clinical trials in healthcare facilities and community centers (Casey et al. 2010; Colin et al. 2018; Hinsa-Leasure et al. 2016; Ibrahim et al. 2018; Poggio et al. 2020; Zerbib et al. 2020; Schmidt et al. 2012), with hospital intensive care units containing copper-coated appliances reporting 83–99.9% reduction in the burden of pathogens and infections (Montero et al. 2019; Salgado et al. 2013). The exact mechanism behind the ability of copper to inactivate or kill pathogens is believed to differ between pathogen types (Festa and Thiele 2011; Manuel et al. 2015; Rosenberg et al. 2018; Warnes et al. 2012, 2015). For viruses, the proposed mechanism is that copper ions disrupt viral envelopes, prevent cellular respiration, produce free radicals, and destroy the DNA/RNA of microbes when in contact with copper surfaces (Rakowska et al. 2021).
Copper inactivation of Coronavirus 226E, another common respiratory virus and close relative of SARS-CoV-2, has been successful, with inactivation observed in 40 min or less (Warnes et al. 2015). Recent studies by Behzadinasab et al. (2020), Hutasoit et al. (2020), and Mantlo et al. (2020) examined Cu2O/PU film, 3D-printed copper-coated surfaces, and cold-spray copper coating, respectively, for SARS-CoV-2 inactivation capabilities. Behzadinasab et al. (2020) reported 99.99% inactivation after 1-h incubation while Hutasoit et al. (2020) and Mantlo et al. (2020) found 96% and 99% inactivation after 2 h. Another study by Behzadinasab et al. (2021b) studied two transparent surface coatings, PDA/Cu and PDA/Cu2O, which also found 99.98% and 99.88% inactivation of SARS-CoV-2 after 1-h incubation, respectively. However, viability of the novel SARS-CoV-2 virus immediately after contact with copper materials has not been adequately tested. It may be that, coating surfaces with copper infused materials can more rapidly inactivate SARS-CoV-2 than we currently understand. Accordingly, in this study, we evaluated the inactivation of SARS-CoV-2 virus upon contact with two copper blend coatings from 1 to 20 min.
Materials and methods
Viral strains and cell lines
Vero E6 (ATCC® CRL-1586™) cells were cultured in 1× Dulbecco’s Modification of Eagle’s Medium with 4.5 g/l glucose supplemented with 1% l-glutamine (DMEM; Corning, Corning, NY) and 10% (v/v) fetal bovine serum (FBS; Corning, Corning, NY). Vero E6 cells were grown in T175 flasks and passaged when the cells were 90% confluent. 1.2 × 106 cells were plated in 6- well plates overnight before use.
The SARS-CoV-2 Chile strain was obtained from BEI (NR-52439). One hundred μl was added to a confluent T75 flask of Vero E6 cells in serum-free media (SFM) with antibiotics. Forty-eight hours later, 100 μl of supernatant was added to a second flask with uninfected cells. If cytopathic effects were observed after 48 h, the supernatant was removed and the flask containing the remainder of the cells were placed in a freezer for 5 min. The flask was then thawed, and the cells were collected using 5 ml of new media. The cell lysate was mixed with supernatant and centrifuged at 500×g for 5 min before aliquoting.
Surfaces tested
Two distinct copper blends were formulated by Alloi, with Copper Blend 1 containing 48.26% pure copper and Copper Blend 2 containing 75.07% pure copper. The composition of each blend’s inputs is characterized in Table 1. To create these materials, copper and zinc were ordered from a third-party and then mixed with a non-metal binder (styrene resin sold under COR75-AQ-010L [INTERPLASTICS Unsaturated Polyester Resin product code: SIL94BA-990]) and catalyst (Methyl ethyl ketone peroxide [MEKP]). Both blends consist of metallic components as well as the binder, to make the material as a whole not conductive, and the catalyst, to harden the binder. All materials were measured using a scale with an uncertainty of ± 0.01 g. The two copper blends were then used to completely cover pieces of 2 cm × 2 cm polycarbonate plastic sheets with 0.1 mm thickness using cold-spray technology. These materials were then brought to the George Washington University Nanofabrication and Imaging Center and imaged using the GEI Teneo LV scanning electron microscope (SEM) with an EDAX Octane Pro detector for elemental analysis. SEM was done at 5000 × and energy-dispersive x-ray spectroscopy (EDS) was performed at 30 kV for 100 s showing Copper Blend 1 to be mainly copper (Cu) 41.61% and zinc (Zn) 14.59%, and Copper Blend 2 to be predominately Cu 100%. Further analysis of these coated materials by SEM and energy-dispersive X-ray spectroscopy (EDS) is shown in Fig. 1 and Table 2. The copper blend-coated samples arrived in sealed bags and were tested as is. The uncoated plastic samples arrived with a thin sheet of plastic adhesive covering one side. The plastic adhesive was removed with 70% ethanol and allowed to dry before experimentation. The components of the copper blends were unknown to the researchers at the time of experimentation; however, composition was revealed to the researchers after analysis of results.Table 1 Composition of the inputs for Copper Blend 1 and 2 by weight and percent of total weight
Material Copper Blend 1 Copper Blend 2
Weight (g) Percent of total weight Weight (g) Percent of total weight
Binder (styrene resin [COR75-AQ-010L]) 45.0 24.13% 45.0 24.13%
Catalyst (methyl ethyl ketone peroxide [MEKP]) 1.5 0.80% 1.5 0.80%
Pure copper (without brass) 90.0 48.26% 140.0 75.07%
Brass (70% copper/30% zinc) 50.0 26.81% 0.0 0.00%
Total weight 186.5 – 186.5 –
Zinca 15.0 8.04% 0.0 0.00%
Total copper (pure copper + brass)a 125.0 67.02% 140.0 75.07%
aZinc weight and percent of total weight were calculated based on brass content. Total copper weight and percent of total weight were calculated based on brass and pure copper content
Fig. 1 Photographs of the appearance of: A) Copper Blend 1 from left to right: tested material in a 2 × 2 cm square, scanning electron microscopy (SEM) done at 5000x, energy-dispersive X-ray spectroscopy (EDS) at 30 kV for 100 s showing composition of Copper Blend 1 Spot 2 to be predominately copper (Cu) 41.61% and zinc (Zn) 14.59%; B) Copper Blend 2 from left to right: tested material in a 2 × 2 cm square, SEM done at 5000x, EDS at 30 kV for 100 s showing composition of Copper Blend 2 Spot 1 to be predominately Cu 100% (background analysis of Copper Blend 2 Spot 2 and Spot 3 were predominantly carbon, 57.64% and 43.18%, respectively)
Table 2 Composition of Copper Blend 1 and 2 products by percent weight using energy-dispersive x-ray spectroscopy (EDS)
Copper Blend 1 (spot 2)a Copper Blend 2 (spot 1)a
Element Weight % Error % Weight % Error %
Copper 41.61 1.34 100 0.99
Zinc 14.59 1.45 – –
Carbon 33.98 8.96 – –
Oxygen 9.82 9.90 – –
aEDS spot locations are displayed in Fig. 1 above
Infectivity assay for SARS-CoV-2
Viral stock solution was thawed and placed in ten 1 μl droplets on two different copper blend-coated surfaces to simulate respiratory droplet contact (Lindsley et al. 2013; Warnes et al. 2015). The distinct 1 μl droplets were used instead of one 10 μl droplet to allow for more direct contact with the copper blend surfaces due to the surface tension of the solution (Mantlo et al. 2020). The virus was removed from the test surfaces by washing with 490 μl EMEM supplemented with 1% penicillin, streptomycin, amphotericin B and non-essential nucleic acids after incubation at room temperature for various time points: 1 min, 5 min, 10 min, and 20 min. The virus and media mixture was assayed for infectious virus survival using a plaque assay, quantified as plaque forming units (PFU). Serial dilutions of the virus mixture were prepared in infection medium before 200 μl aliquots were plated onto confluent monolayers of Vero E6 cells in Corning® 6-well plates. After 1 h, a 1:1 agar and EMEM overlay was added and plates were incubated at 37 °C and 5% CO2 for 72 h. Following incubation, the plates were fixed with 10% (w/v) formaldehyde, stained with 0.5% Crystal Violet and allowed to dry before plaques were counted.
Statistical analyses
All statistical analyses were performed in R Studio (version 1.3.1093) with base R (version 3.6.3) and significance was assessed at the α = 0.05 level. We first wanted to compare whether the recovery of viable SARS-CoV-2 was differentially affected by incubation on three different materials (Copper Blend 1, Copper Blend 2, and plastic) at four different time points. Median rank titers (Log PFU/ml) across the three materials were compared using the Kruskal–Wallis non-parametric analysis of variance (kruskal.test) after determination that data were not distributed normally (shapiro.test, p < 0.05). When warranted, post-hoc tests for pairwise differences were performed using the Dunn Test (dunnTest, package FSA). We next wanted to compare the performance of each blend compared to the baseline material of plastic. We took the difference of recovered viral titer (log PFU/mL) for each trial-blend combination and calculated the percent reduction from the corresponding trial’s plastic control at each time point. We then used a t-test to determine whether these calculated differences were significantly greater from select null values; namely, 50%, 75%, and 98%. A rejection of the null in this case would indicate that an blend had at least or greater reduction than the null value tested.
Results
Comparison of recovered titer from each type of material
At 1-min exposure time, there was no significant difference in the recovered viral titer (PFUs/mL) among the three materials. At 5, 10, and 20 min contact with Copper Blend 2, there were significantly lower recovered titers of SARS-CoV-2 than both Copper Blend 1 and plastic. The viral titer recovered from Copper Blend 1 was not significantly different from the plastic control at any time point measured (Fig. 2).Fig. 2 At 5, 10, and 20 min, contact with Copper Blend 2 produced significantly (*) lower titers (Log PFU/ml) than exposure to either Copper Blend 1 or plastic (p < 0.05). Presented are data points and boxplot data summaries
Percent reduction of recovered titer of Copper Blend 1 or Copper Blend 2 compared to the plastic control
When the recovered viral titer of each copper blend was compared to that of the plastic control, Copper Blend 1 did not result in a SARS-CoV-2 titer reduction that was significantly greater than 50% at any timepoint. However, for Copper Blend 2, the percent reduction in titer compared to the plastic control was significantly higher. Reduction was significantly greater than a maximum of 50% at time point 5 min, 75% at 10 min, and 98% at 20 min (Fig. 3).Fig. 3 For each copper blend material, points represent percent reduction from matching plastic control. Lines represent the mean percent reduction with ± standard error. *Indicates significantly greater reduction than 50%, **Indicates significantly greater reduction than 75%, ***Indicates significantly greater reduction than 98%
Discussion
Basic infection prevention and control practices are important to prevent the rapid spread of novel viruses, such as SARS-CoV-2. Part of this strategy includes timely and consistent disinfection of surfaces, especially in high-trafficked spaces where respiratory droplets may contain viruses capable of surviving for extended periods of time on commonly used surfaces. Reducing environmental contamination is particularly important during pandemics and in health care settings. Previous studies found copper is an effective option to combat fomite transmission both in laboratory and in clinical settings (Behzadinasab et al. 2020; Hutasoit et al. 2020; Mantlo et al. 2020; Warnes et al. 2015). This current study sought to build on the growing body of knowledge regarding the uses of copper and copper materials as deterrents of surface-mediated transmission of viruses.
Our results indicate that contact with a high copper-content material inactivated SARS-CoV-2 as compared to a plastic control in a time-dependent manner. There was no significant difference in recovered titer between Copper Blend 1, Copper Blend 2, and the plastic control after 1 min of contact, suggesting a minimum time of contact is needed for efficacy. Copper Blend 2 begins to significantly reduce the viability of SARS-CoV-2 at 5 min of contact with at least 98% reduction in recovered virus at 20 min of contact.
Copper Blend 2 is 75.07% pure copper composition by weight compared to Copper Blend 1, which has a pure copper composition of 48.26%. The difference in recovered virus between the two suggests that higher copper content may have stronger antiviral properties. It is important to note that Copper Blend 1 also contained brass, which is a copper alloy with 70% copper/30% zinc, meaning Copper Blend 1 has a total copper content of 67.02%. Our results are similar to a study that demonstrated copper was efficacious at inactivating a human Alphacoronavirus, HuCoV-229E (Warnes et al. 2015). Pure copper and 90% copper materials were able to inactivate HuCoV-229E in 20 min (Warnes et al. 2015). Interestingly, inactivation efficiency began to decrease when the pure copper content was reduced to 85%. As SARS-CoV-2 is more stable on surfaces than HuCoV-229E, determining the efficacy of a specific material’s copper content is critical to evaluate further (Rabenau et al. 2005; van Doremalen et al. 2020).
Other studies have reported greater than 96% inactivation of SARS-CoV-2 after an hour of contact with different copper formulations (Behzadinasab et al. 2020; Hutasoit et al. 2020; Mantlo et al. 2020). Accordingly, our experimental limit of 20 min of contact between the viral inoculum and copper blends may offer a conservative estimate of the ultimate effectiveness of such materials. We cannot rule out the possibility that Copper Blend 1 may have more effectively inactivated SARS-CoV-2 or that Copper Blend 2 may have achieved even greater reduction at contact times exceeding 20 min. However, the effectiveness of Copper Blend 2 at such a short interval may prove beneficial during periods of high community transmission and healthcare stress, when shorter turnaround times for cleaning and disinfecting rooms or equipment is needed to keep pace with demand.
In conclusion, this study has found that over the course of 20 min, copper blend coatings can significantly reduce the recovery of infectious SARS-CoV-2 compared to uncoated controls. Our results indicate the continued use of copper as a viral inactivator for surfaces at-risk for contamination. Furthermore, it may be that there is an important percentage of copper content in materials that is needed for effectiveness against SARS-CoV-2.
Author contributions
AG performed the laboratory work and wrote the main manuscript text, KEK co-led the writing of the manuscript, RCC led the data analysis, CNM conceptualized the study and secured funding. All authors read and approved the final manuscript.
Funding
The research was funded by Teck Resources Limited. Copper blend materials provided by Isaac Lichter, Nick O'brien, and Andrew Medland at Alloi. Neither organization had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Declarations
Conflict of interest
The authors have declared that no competing interests exist.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735169 | NO-CC CODE | 2022-12-16 23:17:46 | no | ZVersWiss. 2022 Dec 9; 111(4):535-537 | latin-1 | null | null | null | oa_other |
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NeuroTransmitter
NeuroTransmitter
1436-123X
2196-6397
Springer Medizin Heidelberg
2989
10.1007/s15016-022-2989-2
Aus den Verbänden
Gesundheitssystem vor dem Abgrund?
Meier Uwe
Neurologe, Am Ziegelkamp 1 F, 41515 Grevenbroich, Germany
9 12 2022
2022
33 12 1015
© Berufsverband Deutscher Nervenärzte e.V. (BVDN) 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
issue-copyright-statement© Berufsverband Deutscher Nervenärzte e.V. (BVDN) 2022
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pmcReformen im Gesundheitswesen sind dringend erforderlich, um auch zukünftig eine adäquate Versorgung der Patientinnen und Patienten zu gewährleisten. Die politisch Verantwortlichen sind aufgerufen, Veränderungen in die Wege zu leiten, die sich an klaren Zielen orientieren und langfristig tragfähig sind. Ärztinnen und Ärzte sollten sich mit ihrem fachlichen Knowhow und Erfahrungswissen aktiv in den Diskurs einbringen.
Es muss sich etwas ändern im Gesundheitssystem. Da sind sich alle einig. Ohne tiefgreifende Reformen fahren wir mit mathematischer Gewissheit auf einen Abgrund zu - oder, wie unlängst die ÄrzteZeitung den G-BA-Chef Prof. Josef Hecken zitierte: "Wir planen gerade, wie wir gemeinschaftlich Suizid begehen wollen." Die Probleme seien in den vergangenen zehn Jahren ignoriert worden, trotz seit Langem bekannter Fakten wie sinkender GKV-Einnahmen aufgrund der demografischen Entwicklung und steigender Behandlungskosten wegen des medizinisch-technischen Fortschritts.
Auf diese unheilvolle Dynamik haben auch wir im NeuroTransmitter und im politischen Raum immer wieder hingewiesen, zuletzt im BDN-Forum 2 auf der Neurowoche 2022. Gerade in der Neurologie haben wir es mit wachsenden Versorgungsbedarfen zu tun, da vor dem demografischen Hintergrund hier die Erkrankungen zunehmen. Außerdem fordern die medizinischen Fortschritte immer mehr Ressourcen, nicht nur ärztlich und im Bezug auf die Mitarbeitenden, sondern auch finanziell, wenn wir etwa an die Kosten für heutzutage unverzichtbare Biologika denken. Das stößt insofern auf taube Ohren, da Politiker und Politikerinnen wiedergewählt werden wollen, jedoch sind Veränderungen ohne Zumutungen für die Wählerinnen und Wähler undenkbar. Ohne diese wirklich substantiellen Veränderungen werden wir alle ein im Prinzip gutes Gesundheitssystem verlieren, da es absehbar so nicht mehr finanzierbar sein wird.
Wir sind also gut beraten, wenn wir uns die Daten vor Augen führen und uns aktiv an Lösungen beteiligen. Proteste, die das Bewahren des Status quo einfordern, werden kaum hilfreich sein, zumal sich die Dynamik durch drohende Rezession, Energiekrise und hohe Inflationsraten noch verstärkt. So wurde im September 2022 auf Grundlage des Krankenhausentgeltgesetzes vom Statistischen Bundesamt (Destatis) der aktuelle Orientierungswert für Krankenhäuser publiziert, der eine wichtige Kennzahl für die durchschnittliche jährliche prozentuale Veränderung der Krankenhauskosten darstellt, die auf Preis- oder Verdienständerungen zurückzuführen ist.
Der Orientierungswert stellt eine wichtige Basis für Budgetverhandlungen im stationären Bereich für Krankenhäuser und Krankenkassen dar. Dieser liegt bei 6,07 % für den Zeitraum des zweiten Halbjahres 2021 und ersten Halbjahres 2022 im Vergleich zum entsprechenden Vorjahreszeitraum. Die dramatischen Steigerungen durch die aktuellen Preisentwicklungen sind hier also noch nicht einmal berücksichtigt.
Bessere Versorgung, steigende Kosten
Wenn wir uns ein paar Eckdaten zur Versorgung anschauen, so zeigt sich, dass die Ausgaben für die Gesundheit von 1997 bis 2020 von 197 auf 441 Milliarden € gestiegen sind. Das ist nicht nur ein absoluter Anstieg. Bezogen auf das Bruttoinlandsprodukt entspricht das einer Erhöhung von 10 % auf 13 %. Damit steigen die Gesundheitskosten schneller als die Wirtschaftsleistung. Deutschland gehört so zu den Ländern mit den höchsten Ausgaben für die Gesundheit. Auch was die Gesundheitsausgaben pro Kopf anbetrifft, ist Deutschland, von wenigen Ausnahmen wie den USA abgesehen, ganz weit vorn. Im Jahr 2021 hat Deutschland pro Kopf 7.382 $ ausgegeben. Die anderen europäischen Staaten blieben deutlich darunter. Und selbst Länder wie Australien, dem Quell-Land der "diagnosis related groups" (DRGs), gaben nur 5.627 $ pro Kopf aus.
Schauen wir uns die Versorgungslandschaft und -daten genauer an: Im Jahr 2021 gab es in Deutschland laut statistischem Bundesamt 1.887 Krankenhäuser mit 483.606 Betten. In den Krankenhäusern gab es 16.742.344 Behandlungsfälle. Rein statistisch gesehen befand sich damit jede fünfte Person einmal in diesem Jahr für durchschnittlich 7,2 Tage im Krankenhaus. Anders ausgedrückt: 20 % der Bürgerinnen und Bürger Deutschlands haben zusammen an 120 Millionen Tagen 2021 im Krankenhaus gelegen. Dass es sich demnach bei den Deutschen um eine sehr kranke Bevölkerung handeln muss, zeigt auch die Anzahl der ambulanten Behandlungsfälle. Nach Angaben des statistischen Bundesamtes betrug die Zahl der Behandlungsfälle ambulant in den letzten Jahren relativ stabil circa 700 Millionen. Der Behandlungsfall wird in Deutschland definiert als die Behandlung desselben Versicherten durch dieselbe Arzt- oder Psychotherapiepraxis in einem Quartal zulasten derselben Krankenkasse.
Um diese Zahlen anschaulich zu machen, hilft auch hier eine rein statistische Betrachtung: Folglich verursacht jede hierzulande gemeldete Person theoretisch 8,5 Behandlungsfälle pro Jahr in einer Arzt- oder Psychotherapeutenpraxis. Darunter befinden sich natürlich viele chronisch Kranke, die an mehreren Quartalen zu einer Ärztin oder einem Arzt gehen. Nimmt man mal nur rein rechnerisch an, dass jede Person chronisch krank ist und jedes Quartal dieselbe Arztpraxis konsultiert, was natürlich nicht der Fall ist, bleiben immer noch durchschnittlich 2,1 Praxen übrig, die von jeder Person von Quartal zu Quartal aufgesucht werden.
Das kostet alles Unmengen an Geld, das nicht vorhanden ist. Und ob alle stationären und ambulanten Maßnahmen nachhaltig zur Gesundheit der Bevölkerung beitragen, ist doch mehr als fraglich. Diese Zahlen machen deutlich, dass es so nicht weiter gehen kann. Konnten wir uns diesen Luxus bisher leisten, droht diese Blase in absehbarer Zeit zu platzen. Gleichwohl die Herausforderungen der Zukunft hier noch gar nicht eingepreist sind.
Herausforderungen in der Neurologie und Psychiatrie
Betrachten wir die Entwicklungen in der Neurologie einmal am Beispiel der Demenz: Das statistische Bundesamt hat in einer Pressemeldung vom 22. September 2022 zum Welt-Alzheimer-Tag 2022 darauf hingewiesen, dass im Jahr 2020 fast 20.000 Menschen wegen einer Alzheimer-Erkrankung im Krankenhaus behandelt werden mussten. Damit hat die Zahl der stationären Behandlungen in 20 Jahren um 138 % zugenommen und sich weit mehr als verdoppelt. Dieser Trend wird sich ungebremst fortsetzen - nicht nur bei Alzheimer-Patientinnen und -Patienten, sondern bei allen stark altersassoziierten Krankheiten; in der Neurologie speziell bei neurodegenerativen und vaskulären Erkrankungen.
Ein anderer Punkt ist aber in diesem Zusammenhang noch viel bedeutender: Wenn wirksame Biologika gegen Alzheimer zugelassen werden, was in den kommenden Jahren realistisch ist, werden die Arzneimittelkosten allein in der Neurologie/Psychiatrie explodieren. Nehmen wir in einem Szenario an, dass eine Millionen Menschen mit einer Alzheimer-Demenz mit leichter kognitiver Beeinträchtigung (MCI-AD) einen Antikörper gegen β-Amyloid erhalten. Dann wären das bei geschätzten Jahreskosten von 20.000 € pro Person und Medikament 20 Milliarden € zusätzliche Kosten allein für die neuen antidementiven Therapien. Wenn wir von drei Millionen MCI-AD-Betroffenen ausgehen, wären es schon 60 Milliarden €.
Und das sind nur die reinen Arzneimittelkosten. Wenn wir beim Aufwand für die Diagnostik mit einer Minimalschätzung von einer Millionen MCI-AD-Betroffenen ausgehen, dann müssen diese differenzialdiagnostisch abgegrenzt werden, von kognitiv Gesunden mit positivem Amyloid (geschätzt sechs Millionen Menschen), Betroffenen mit subjektiven kognitiven Defiziten (SCD), mit schweren Bedenken (2,5 Millionen) sowie von Pseudodemenz- und Angstpatienten (2,5 Millionen). Somit kommen wir auf eine Zahl von zwölf Millionen Erkrankten mit entsprechenden Liquorentnahmen, pschologischen Testungen und bildgebenden Verfahren. Gehen wir von einem ärztlichen Zeitaufwand von 30 Minuten pro Liquorpunktion aus, was eher eine geringe Annahme darstellt, weil es auch einer entsprechenden Aufklärung und Vorbereitung bedarf, würde dies schon einen zeitlichen Aufwand von sechs Millionen Stunden bedeuten.
Bei einem Aufwand von 60 Minuten pro psychologischer Testung, was ebenfalls niedrig angesetzt ist, haben wir einen zusätzlichen Aufwand von zwölf Millionen Stunden. Das würde bedeuten, dass alleine für diese Diagnostik 2.000 Fachkräfte ein Jahr lang durchgehend jeden Tag acht Stunden nur Liquorentnahmen tätigen dürften - ohne Pausen und Urlaub. Weitere 4.000 Fachkräfte wären ein Jahr lang ausschließlich jeden Tag für acht Stunden mit neuropsychologischer Testung beschäftigt. Dies würde nur einen Teil des tatsächlichen Aufwands abbilden.
Nun ist dies nur ein Szenario. Wir können die Patientenzahlen jeweils nach oben oder nach unten korrigieren, ebenso die Arzneimittelkosten. Wir werden vielleicht Serum-Biomarker bekommen und die Liquorentnahme fiele dann weg. Wie immer man es dreht und wendet, der Aufwand wäre immens hoch. Über eines bräuchten sich Neurologinnen und Neurologen sicher keine Gedanken machen: arbeitslos werden sie nicht.
Wir sprechen hier nur von einer Erkrankung aus unserem Fachgebiet. Wenn wir andere psychiatrische Krankheiten wie Depressionen und Angsterkrankungen dazunehmen, haben wir es seit vielen Jahren mit einer dramatischen Zunahme der Inanspruchnahme medizinischer Leistungen zu tun. Dies ist nur ein kleiner Ausblick in unseren Fächern. Andere Fachgebiete, die ebenfalls eine steigende Beanspruchung und medizinische Fortschritte verzeichnen, sind hier noch gar nicht berücksichtigt.
Gesundheitsversorgung - alles für jeden und jederzeit?
Eine Besonderheit in Deutschland liegt darin, dass die Politik ihren Bürgerinnen und Bürgern ein unbegrenztes Leistungsversprechen gegeben hat. Die Versorgungsstrukturen sind historisch gewachsen, das System, so wie wir es jetzt erleben, folgte keinem Masterplan. Wenn man für das bestehende System rein hypothetisch ein Versorgungsziel formulieren wollte, was das real existierende System im Nachhinein plausibilisieren könnte, dann wäre das Folgendes: Wir können beliebig oft, auch wegen Bagatellen zum Arzt gehen, ohne Zuzahlungen, immer sofort, am besten gestern. Das mag im letzten Millennium nach Gründung der Bundesrepublik angemessen gewesen sein, kann auf Dauer aber nicht funktionieren.
Menschen ihre Privilegien zu nehmen, ist immer ein schwieriger Akt. So wie wir derzeit von der Politik auf einen kalten Winter mit Waschlappen statt Duschen vorbereitet werden, wird es irgendwann auch mit der Gesundheitsversorgung sein, wenn wir jetzt nicht handeln. Ich sage voraus, dass dies in absehbarer Zeit neben Klimawandel, Energiekrise und Frieden eines der vorherrschenden Themen sein wird. In Talkshows wird diskutiert werden, dass das - wie die Klimaentwicklung auch - alles vorhersehbar gewesen sei, aber politisch ignoriert wurde. Politikerinnen und Politiker wollen Wählerinnen und Wähler nicht verprellen und sie wollen ein sozial gerechtes System. Keiner möchte hier eine Zweiklassenmedizin oder US-amerikanische Verhältnisse. Aber genau das wird unvermeidbar sein, wenn wir jetzt nicht gegensteuern.
Das Problem der Finanzierbarkeit des Gesundheitssystems ist natürlich bekannt. Um auch künftig alle zumindest Schwerkranken zu behandeln und am medizinischen Fortschritt teilhaben zu lassen, braucht es einen ganzen Strauß an Maßnahmen. Hecken hat in diesem Zusammenhang einige Stichworte geliefert. So sprach er sich für eine stringente Nutzen- und Methodenbewertung aus und er fordert ein stärkeres Augenmerk auf Diagnose- und Indikationsqualität. Dies ist verständlich.
Wir werden es uns künftig weder leisten können, fragwürdige Behandlungen solidarisch zu finanzieren, noch jeden mit einem Ziehen in der Brust einer Herzkatheteruntersuchung zu unterziehen, noch jeden Älteren mit Verschleiß im Hüftgelenk einer Endoprothetik zuzuführen. Weiterhin sprach sich Hecken für eine gemeinsame Betrachtung ambulanter und stationärer Bedarfsplanung aus. Es gibt inzwischen auch zahlreiche Gutachten zu dem Thema, über die wir auszugsweise schon berichtet haben (Bertelsmann-Gutachten, Leopoldina). Ein Schlagwort kommt von allen Gutachtern und Experten regelmäßig an dieser Stelle zum Tragen: die Ambulantisierung. Auch im Koalitionsvertrag der aktuellen Ampelkoalition ist es Thema. Hier wird konkret die Bildung von sogenannten Hybrid-DRGs erwähnt.
Wie reagiert die Politik?
Gesundheitspolitik ist eigentlich ein unmögliches Unterfangen, weil es mit begrenzten Ressourcen und wachsenden Anforderungen die unterschiedlichen Interessenlagen von Krankenkassen, Krankenhäusern sowie Vertragsärztinnen und -ärzten berücksichtigen und vor allem für die Wählerinnen und Wähler wirksame politische Entscheidungen treffen muss. Ein paar Beispiele der Vergangenheit sollen dies beleuchten.
Unser heutiger Gesundheitsminister war im Jahr 2004 bei der Einführung der DRGs in Deutschland maßgeblich beteiligt. Es war aber bereits damals absehbar, dass die Versorgung kranker Menschen nicht einer kapitalistischen Wettbewerbsdynamik ausgesetzt werden kann. Die Folgen waren vorhersehbar: Auf der Kostenseite wird gespart, vor allem am Personal. Auf der Einnahmeseite besteht ein Anreiz zur Ausweitung gut bezahlter Leistungen, eine Patienten- und Bedarfsorientierung hat hier keinen Platz. Das kann Krankenhausträgern nicht zum Vorwurf gemacht werden, wohl aber der Politik, die diese Rahmenbedingungen gesetzt hat. Ausgerechnet der derzeitige Gesundheitsminister möchte nun diese Dynamik zurückdrehen und neue Vergütungsmuster vorschlagen. Der Brandstifter wechselt zur Feuerwehr. Das ist überhaupt ein Merkmal politischen Handelns: Reduziert auf einzelne Faktoren scheinen einzelne Maßnahmen politisch sinnvoll, die Auswirkungen auf das gesamte System werden aber nicht wahrgenommen. Dabei sind die Folgen vorhersehbar. Und dies ist der eigentliche Vorwurf an die Politik: Auch politisch Verantwortliche sind nicht allwissend und allmächtig. Das sind Ärztinnen und Ärzte auch nicht. Deshalb evaluieren wir medizinisches Handeln, werten Daten aus, konsentieren Handlungsempfehlungen auf der Grundlage von Evidenzen und aktualisieren sie, wenn neue Evidenzen vorliegen, dem Regelwerk nach unter weitgehender Elimination von Partialinteressen oder Offenlegung von möglichen Interessenkonflikten wie etwa bei der Leitlinienentwicklung. Warum ist dies kein Vorbild für politisches Handeln?
Immer wieder müssen wir sehen, dass schnell ein neues Gesetz verabschiedet wird, meistens mit euphemistisch klingenden Namen, mit dem sich die Ministeriumsleitung brüstet. Dabei sind nicht nur unerwünschte Folgen und Effekte vorhersehbar, was man in der Gesetzgebung hätte berücksichtigen und damit verhindern können, es erfolgt auch keine Evaluation, die eine Korrektur ermöglichen würde.
Politische Maßnahmen brauchen klare Ziele
Politik gibt sich an dieser Stelle unfehlbar; zum Nachteil der Bürgerinnen und Bürger. Eine Evaluation wäre ein Leichtes. Es dürfte aber kaum ein Interesse der Politik daran bestehen, weil es Irrtümer transparent machen würde. Es sei der Politik nachzusehen, dass es keine Kultur des Umgangs mit politischen Fehlern gibt, weil sich die politische Gegenseite und die Medien mit Genuss darauf stürzen würden. Das muss sich ändern. Auch politische Maßnahmen sollten klare Ziele verfolgen. Die Ziele sollten eindeutig formuliert sein und der Erfolg einer Maßnahme muss sich an Daten messen lassen, damit Korrekturen möglich sind, ohne dass es das politische Aus der Protagonistinnen und Protagonisten bedeutet. Wir können es uns einfach nicht mehr leisten, unausgereifte Gesetze zu verfassen, die ungeprüft ihre auch negative Wirkung entfalten, damit eine Politikerin, ein Politiker oder eine Partei nicht das Gesicht verlieren. Hier muss das kollektive Interesse vor den jeweiligen Interessen, auch der Partei, stehen.
Terminvergabe: Neues Gesetz - gerechtere Versorgung?
Nehmen wir das Beispiel Terminservice- und Versorgungsgesetz (TSVG): Im Jahr 2019 wurde ein Gesetz verabschiedet, das eine Gleichbehandlung gesetzlich und privat versicherter Personen bei der Terminvergabe herstellen sollte. Hier war immerhin ein Ziel formuliert. Die Idee war, dass Termine in dringlichen Fällen schneller vergeben werden, Anreize für die Aufnahme von Neupatientinnen und -patienten geschaffen werden und anderes. Diesen Überlegungen liegen explizit oder implizit die Annahmen zugrunde, dass es ein Problem bei der Vergabe von Terminen bei Fachärztinnen und -ärzten gibt, und dass privat Versicherte bei der Terminvergabe bevorzugt werden. Letzteres kann durchaus sein. Ob das zu einem Problem in der Versorgung gesetzlich Versicherter führt, ist dabei nicht formuliert und welcher Art dieses Problem ist, beziehungsweise ob es durch das Gesetz behoben werden soll, blieb im Dunkeln.
Wie hat sich das Gesetz ausgewirkt?
Das Fazit ist gespalten, einerseits in der Tat positiv, andererseits fraglich. Fangen wir mit dem Fraglichen an: Aus meiner Praxis kann ich berichten, dass die Patientinnen und Patienten, die mit einer Notfallüberweisung über die Termin-Servicestelle (TSS) vermittelt werden, meistens Bagatellbeschwerden haben, die schon länger bestehen. Nur selten sind Erkrankte mit einer gewissen Dringlichkeit dabei. Die "echten" Notfallpatientinnen und -patienten kommen ohnehin direkt zu uns und die behandeln wir natürlich auch. Die TSS-vermittelten Personen waren nur so "clever", sich einen rascheren Termin zu verschaffen. Der Nebeneffekt ist aber, dass die Wartezeit für die anderen Patientinnen und Patienten sich nach hinten verschiebt. Der Vorteil des Einen ist der Nachteil des Anderen, ohne dass wir das nach medizinischen Gesichtspunkten gewichten könnten. Der jetzige Minister hat das als großen Erfolg zur Gleichbehandlung verkauft.
Ist das System damit besser geworden?
Wohl kaum. Dafür ist der bürokratische Aufwand und die Regelungstiefe größer geworden. Anders verhält es ich mit Neupatientinnen und -patienten und Patientinnen und Patienten für die offene Sprechstunde. Diese sind tatsächlich sehr viel aufwändiger in der Behandlung. Wir müssen deutlich mehr personelle, diagnostische, zeitliche und organisatorische Ressourcen vorhalten. Nicht wenige Praxen entscheiden daher, keine Neupatientinnen und -patienten mehr zu nehmen. Aus Sicht der Sicherstellung ist das kein zulässiges Verhalten, aus betriebswirtschaftlicher Sicht allerdings vernünftig. Es ist daher richtig und notwendig, Anreize für die Aufnahme von Neupatientinnen und -patienten zu schaffen. Genau dieser Teil des TSVG wurde nun von Gesundheitsminister Karl Lauterbach mit dem GKV-Finanzstabilisierungs-Gesetz zurückgenommen mit dem Argument, dass es sich nicht bewährt habe. Doch gerade dieser Teil des TSVG hat sich aber bewährt, wie die Daten der KBV zeigen. Evidenzen liefert Lauterbach nicht. Dies enthält eine Tragik und bietet Anlass zu großer Sorge.
Terminproblem bleibt weiterhin bestehen
Karl Lauterbach war nicht unbedingt immer der beliebteste Politiker der Republik, auch oder insbesondere nicht bei Ärztinnen und Ärzten. Dies hat sich in der COVID-19-Pandemie jedoch deutlich geändert. Vor allem durch sein Fachwissen und durch einen fast unermüdlichen Eifer, sich in die Datenlage einzudenken und diese fast täglich in Talk-Shows den Mitmenschen zu erklären, hat er einen enormen Imagegewinn verzeichnen können. Nicht nur Kompetenz und Arbeitseifer, sondern auch die Orientierung an den Evidenzen und nicht an Parteiinteressen, haben dazu maßgeblich beigetragen.
Pandemien eignen sich nicht für eine parteipolitische Positionierung. Wenn Lauterbach also jetzt an Fakten vorbei einfach Behauptungen in den Raum stellt, die durch nichts zu beweisen sind, wird einem einmal mehr bewusst, dass man Teil einer postfaktischen Gesellschaft geworden ist. Weil aber an der Realität nicht vorbeizukommen ist und das Terminproblem bei Fachärztinnen und -ärzten sowie das Problem der Neupatientinnen und -patienten weiter besteht, wird an einer neuen Lösung gearbeitet. Demnach bekommt der Hausarzt 15 €, wenn er es schafft, eine Patientin oder einen Patienten notfallmäßig zu vermitteln. Mit anderen Worten: Die Züge sind maximal voll, was für Zugpersonal und Beförderungsbedürftige eine kaum zumutbare Situation darstellt. Statt Züge aufzustocken liegt die Problemlösung darin, Mitarbeiterinnen und Mitarbeitern auf dem Bahnsteig ein Kopfgeld zu zahlen, wenn es ihnen gelingt, noch einen Fahrgast in den Zug zu stopfen.
Strukturreform statt Flickwerk
In Anbetracht der gewaltigen Herausforderungen sind das aber alles eher Nebenkriegsschauplätze und es wird an eher kleinen Symptomen herumgedoktert. Treffend auch die Worte von Jens Baas, Chef der Techniker Krankenkasse und selbst Arzt: "Das Gesetz ist wie ein Pflaster auf einem Tumor." Wir brauchen eine umfassende, kausal wirksame Reform des Gesundheitssystems insgesamt - der Gesundheitsminister ist unter Zugzwang. Im Koalitionsvertrag ist die Einführung von Hybrid-DRGs vorgesehen. Dem vorgeschaltet hat er bereits eine andere Maßnahme angekündigt, quasi als Vorstufe: die Tagesbehandlungen in den Kliniken. Demnach sollen Kliniken die Möglichkeit bekommen, Erkrankte auch ambulant in Form von Tagesbehandlungen versorgen zu können. Die Übernachtung fiele dann weg. Der Minister stellt das nach außen insofern euphemistisch dar, als dass er dies als Vorteil der Kliniken darstellt. Immerhin erweitern die Kliniken ihre Behandlungsmöglichkeiten und können Personal für die Nacht einsparen, die dann für eine bessere Versorgung der Patientinnen und Patienten zur Verfügung stünden.
Das Ziel dieses Vorgehens ist aber natürlich ein anderes, nämlich Krankenhausbetten beziehungsweise stationäre Behandlungen zu reduzieren. Zweifelsohne wird dann die um die Übernachtung reduzierte Behandlung nicht voll vergütet, sondern mit Abschlägen versehen werden. Und die Tagesbehandlungen dürfen lediglich als Ersatz für ansonsten stationär erbrachte Leistungen fungieren, keinesfalls als zusätzliche Behandlung. Letzteres wäre natürlich Öl ins Feuer der Kostenentwicklungen. Das wird man zu unterbinden wissen. Am Ende wird also ein gewisser Druck auf die Kliniken ausgeübt, beziehungsweise ein Wettbewerb um neue Versorgungsformen angefacht. Das wird sich durch die Einführung der Hybrid-DRGs nochmal verschärfen. An einem Bettenabbau in Deutschland wird also keine Strukturreform vorbeikommen. Auch die Sektorengrenzen werden bei künftigen Reformen so kaum aufrechterhalten werden können.
Was bedeutet das für die Neurologie?
In den Diskussionen rund um dieses Thema wechseln sich Hoffnungen auf neue Versorgungsmöglichkeiten und die Angst vor mehr Konkurrenz der Sektoren ab. Niedergelassene haben die Sorge, dass die Kliniken jetzt die ambulante Versorgung mit übernehmen, Kliniker haben die Sorge, dass Niedergelassene jetzt vermehrt stationsersetzende Leistungen erbringen könnten. Diese Sorgen sind verständlich in unsicheren Zeiten. Es gibt jedoch viel Anlass zu der Einschätzung, dass diese Suppe für die Neurologie keinesfalls so heiß gegessen wird, wie sie vielleicht demnächst gekocht wird.
Was die Hoffnungen anbetrifft: Wir sollten uns nicht der Illusion hingeben, dass mit dem Aufbrechen der Sektorengrenzen zusätzliche Ressourcen bereit gestellt werden. Das wird die Politik schon zu verhindern wissen. Was die Sorgen anbelangt, so bleibt festzustellen, was wir alle schon wissen: Der Bedarf an neurologischen Behandlungen wird unsere Möglichkeiten auch in der Zukunft übersteigen. Wir sollten uns daher gemeinsam, in Klinik und Niederlassung, für eine patientenorientierte Versorgung einsetzen, die diesen Namen auch verdient. Denn dafür sind wir angetreten, deshalb sind wir Ärztinnen und Ärzte. Wir sind primär einer guten Patientenversorgung verpflichtet und nicht primär der Rendite von Klinikkonzernen. Gleichwohl müssen auch die wirtschaftlichen Rahmenbedingungen stimmen, sonst konterkariert dies eine gute Versorgung und schafft Fehlanreize. Es braucht eine echte Allianz zwischen medizinischem und betriebswirtschaftlichem Sachverstand. In diesem Sinne gibt es viel zu tun und es lohnt sich, dafür gemeinsam zu kämpfen.
Mit ideologischen Grabenkämpfen ist weder uns geholfen, noch den Patientinnen und Patienten. Wir sollten uns daher bei der Suche nach guten Lösungen unser medizinisches Knowhow und unser Erfahrungswissen einbringen und uns einer Diskursethik verbunden fühlen. Dafür setzen wir uns berufspolitisch ein und laden Vertreterinnen und Vertreter aller Versorgungsbereiche ein. Der BDN hat sich von je her einer konsensgetragenen Arbeitsweise verpflichtet und gemeinsame Arbeitsgruppen für neue Versorgungsformen, aktuell für die "Ambulante spezialfachärztliche Versorgung" (ASV) für Multiple Sklerose oder für die Entwicklung von Hybrid-DRGs gebildet.
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| 0 | PMC9735172 | NO-CC CODE | 2022-12-14 23:29:52 | no | NeuroTransmitter. 2022 Dec 9; 33(12):10-15 | utf-8 | null | null | null | oa_other |
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Air Qual Atmos Health
Air Qual Atmos Health
Air Quality, Atmosphere, & Health
1873-9318
1873-9326
Springer Netherlands Dordrecht
1284
10.1007/s11869-022-01284-y
Article
Spatial distribution and temporal variation of biomass burning and surface black carbon concentrations during summer (2015‒2021) in India
http://orcid.org/0000-0001-8063-7623
Majumdar Deepanjan [email protected]
Kolkata Zonal Centre, CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), i-8, Sector C, EKADP, EM Bypass, Kolkata, India
7 12 2022
118
15 2 2022
13 11 2022
© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Historical biomass burning in summer season (April‒June, during 2015‒2021) was assessed by studying active fire spot data recorded by the Visible Infrared Imaging Radiometer Suite (VIIRS) aboard NASA/NOAA Suomi NPP satellite and mapping the same over Indian landmass. The fire spots often formed regional clusters and most profusely covered the states of Odisha, Chhattisgarh, Andhra Pradesh, Telengana, Madhya Pradesh, Maharashtra, Jharkhand, Karnataka, Punjab, Uttar Pradesh, Haryana, Gujarat, Tamil Nadu, Manipur, Nagaland, and Mizoram during April but their number decreased conspicuously in May and further in June. Forward movements of air masses potentially carrying fire-induced air pollutants from five principal fire cluster regions (northern, south eastern, western, north-eastern, and central) of India during April and May in 2021 were traced by 6-day forward airtrajectory modelling. It was observed that many parts of India were the recipients of air coming from the above principal fire clusters. In each year, the surface mass concentration of black carbon (BC), one of the most prominent markers of biomass burning, was higher in April over May and June in the affected regions, commensurate with the most active period of fire. The BC surface mass concentrations progressively declined thereafter in May and June with decreasing number of active fire spots along with declining average monthly height of the planetary boundary layer (PBL), indicating integral connection of surface BC levels with biomass burning. The study suggests that in spite of more favourable meteorological conditions in summer, extensive biomass burning may have had a crucial role to play in perturbing local and regional air quality over India by generating BC and other air pollutants.
Keywords
Atmospheric reanalysis
Hysplit
Planetary boundary layer
Satellite remote sensing
Trajectory modelling
VIIRS
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pmcIntroduction
Biomass burning is known to be prevalent in many parts over the globe since the late twentieth century (Crutzen and Andreae 1990; Kaufman et al. 1990; Andreae 1991; Hao and Liu 1994). Biomass burning is a form of vegetation fire triggered by arson for clearing land for agriculture, fire induced by friction in dry biomass and natural lightning-induced burning. World’s most biomass burning incidences occur in the tropical forests, reportedly about 90% of which could be arson for land clearing and initiating land-use changes (Levine 2003). As per one estimate, Savannah fires, forest fires, shifting cultivation (or slash and burn agriculture), wood fuel burning, and crop residue burning (CRB) had shares of 50, 24, 10, 11, and 5%, respectively, in total tropical biomass burnt during the late 1970s (Hao and Liu 1994). Worldwide, stubble burning accounts for about 25% of biomass burnt that included forest fires (Zhang et al. 2016; Yadav and Devi 2018). It is reported that about 730 Tg biomass was burnt annually in Asia that included forest and grassland fires and CRB wherein India contributed about 18% (Streets et al. 2003). As per Venkataraman et al. (2006), around 18–30% of crop residue was burnt in India while the same in the western Indo-Gangetic plain was 30–40% and much lower in other parts (12–18%) during 1995–2000. In more recent times, about 15.9% of crop residue was reportedly burnt on crop fields in India (Jain et al. 2014). In central and lower Northern Thailand, paddy residue burning has become a common practise due to very short period in between harvesting of standing crops and sowing of the next paddy (Junpen et al. 2018). The mean interval between paddy harvest and wheat sowing is about 15 days, prompting farmers to put paddy residues on fire during October–November in India while on the contrary, the interval between wheat harvest and paddy sowing during April–May is about 46–48 days (Vadrevu et al. 2011). The short period in between harvesting of paddy and sowing of wheat is one of the primary reasons behind burning of paddy stubble in India (Ravindra et al. 2018). The ministry of agriculture in India attributed the escalation in CRB to paucity of agricultural labour (NPMCR, http://agricoop.nic.in/sites/default/files/NPMCR_1.pdf). A detailed account of policy interventions to minimise CRB India is documented (Bhubaneshwari et al. 2019).
Information on biomass burning can be quickly and effectively provided by satellite remote sensing of active fires by detecting infrared (electromagnetic) radiation emitted from fires. Remote detection of biomass fires was initiated in the early 1980s by using low earth orbit (LEO) satellites that mapped the location and timing of landscape fire occurrences while from the early 2000s, global-scale fire information started to get updated multiple times in a day (Wooster et al. 2021). Active fire spots captured by radiometric sensors installed on satellites are now used to track and study regional and global biomass fire activities (Schroeder et al. 2010; Csiszar et al. 2014; Schroeder et al. 2014a, b). Fire radiative power (FRP), representing instantaneous radiative energy released by active fires, is used as a surrogate of the intensity of fire for identification of fire spots (Freeborn et al. 2016; Roy and Kumar 2017).
Biomass burning is known to contribute significantly to local and regional air pollution (Gurjar et al. 2016). In China, CRB contributed about 60% in total emissions coming from biomass burning (Zhang et al. 2015). In the early nineties, biomass burning reportedly contributed around 20–30% of CO2, hydrocarbons, CO, and NOx emitted globally (Andreae 1991). The PM10 and PM2.5 are known to be emitted by paddy straw burning (Chang et al. 2013) while its incomplete combustion produces black carbon (BC) that contributes significantly to global warming by absorbing solar radiation, estimated as the second largest contributor after CO2 (Bond et al. 2013). Studies indicate that when combined with other aerosol components, BC absorbs more strongly than pure, uncoated BC (Fierce et al. 2020). Bond et al. (2004) estimated that biomass burning contributed about 42% of BC and 74% of primary organic carbon (OC) in the atmosphere. In India, paddy stubble burning after rice harvest during October–November at the onset of winter had devastating short-term effects on regional air quality. The deleterious effect of CRB on air quality is higher during October–November, as ushering winter conditions start to produce increasingly stable atmospheric conditions (Chawala and Sandhu 2020). Stubble burning in summer has not garnered as much attention as winter stubble burning did in India, possibly due to more favourable meteorological conditions in the former that aided in the dissipation of air pollutants far more easily, leading to less aggravated local and regional air quality. But, biomass burning can also have significant impacts on sustainable living in urban centres and their peripheries by negatively affecting climatic comfort via altering vegetative cover, water resources and surface temperature (Cetin et al. 2019; Cetin 2020a). It has been reported that the majority of bioclimatic comfort zones in Trabzon Province in Turkey consisted of agricultural, followed by natural and semi-natural areas, forest areas, and settlements (Cetin and Sevik 2020), implying that forest and crop fires can have negative impacts on zones of climatic comfort. Increase in heat island effect due to deforestation and escalated urbanisation causes reduced bioclimatic comfort that potentially affects tourism also, apart from impacting sustainable human settlements (Cetin 2019; Adiguzel et al. 2019, 2022). Also, emissions from biomass burning can have disastrous impacts on global climate change, landscape management, and settlement planning efforts (Cetin et al. 2020; Cetin 2020b). Escalation in summer heat waves as a direct result of aggravation in urban heat island effect caused by reduction in green cover, urbanisation and climate change is posing substantial roadblocks on urban planning and management (Cetin 2020b).
The spatial distribution and temporal variations in biomass burning were studied during 2015–2021 in India. The potential distribution of air pollutants generated from biomass burning over Indian landmass with moving air masses was assessed by 6-day air trajectory modelling in April and May in 2021. Simultaneous surface concentrations of BC, a strong marker of biomass combustion, were estimated over the entire Indian landmass during April–June (2015–2021) and linked with biomass burning as a source, with the help of air mass trajectories and resultant monthly wind vectors over India. The monthly average planetary boundary layer height (PBLH) over Indian landmass during April–June in 2020 and 2021 was also studied to understand its potential influence on temporal variation of BC surface mass concentrations. The majority of earlier papers originating from all over the globe, including India, have reported short-term crop and biomass burning in winter and their potential impacts on regional air quality over limited geographical expanse. This paper analyses summer fires for a 7-year long period over the entire landmass of a large country like India and its potential impacts on countrywide BC surface mass concentrations in summer. Apart from highlighting the seemingly un-scrutinised case of summer biomass burning in India, this study showcases the application of methodologies like geospatial mapping of biomass fire spots, simulation of monthly resultant wind vectors over landmass, wind trajectories originating from various fire cluster regions and atmospheric reanalysis to simulating BC surface mass concentrations and PBLH, as a package of tools to interpret the potential role of biomass fires on BC surface mass concentrations over India. The information is likely to help researchers and policymakers alike to evaluate the impacts of biomass burning on BC surface mass concentrations and its potential role on radiative forcing and regional climate change. Also, the combination of tools used in this study can be replicated by others for similar regional-scale studies. This would eventually lead to the development of wider information on vulnerable regions to biomass fire incidences and scale of fires that would go on to assist in improved forest and biodiversity conservation, sustainable urban planning and delineation of bioclimatic comfort zones.
Materials and methods
Background of study area
The study was conducted for the entire Indian landmass consisting of 28 states and 8 union territories, covering an area of 32, 87, and 263 sq. km (Govt. of India, https://www.india.gov.in/india-glance/profile). Indian landmass is restricted by 8°4′ and 37°6′ North latitudes, 68°7′ and 97°25′ East longitudes. The north-to-south distance is 3214 km while east to west distance is 2933 km. India’s land frontier is of about 15,200 km and the coastline length of the mainland, Andaman & Nicobar and Lakshadweep Islands together is 7516.6 km (Govt. of India, https://www.india.gov.in/india-glance/profile).
In the total amount of paddy stubble generated each year in India, about 14 million tons accounting for about 63.6%, is put on fire (IARI 2012) with the states of Haryana and Punjab contributing about 48% (Gadde et al. 2009). Paddy is customarily transplanted around June/July and harvested in and around October/November while wheat is normally sown mostly during December and harvested in summer in the next year. In recent years, CRB in summer coinciding with winter wheat harvest season in India has been reported but has not garnered much scientific attention (Jitendra et al. 2017, https://www.downtoearth.org.in/coverage/agriculture/river-of-fire-57924). The authors reported that about 80% of CRB was observed during April–May and November–December (post-harvest periods) and attributed it to the required adjustment in crop calendar, implying that only limited time remained in between two consecutive crops to effectively clear the fields. The rationale behind wheat crop residue burning in summer is reported to be costly labour, mechanised harvesting of crop leading to non-viability of animal grazing of short stubbles and increasingly lower importance given to wheat straw as an animal fodder (Jitendra et al. 2017, https://www.downtoearth.org.in/coverage/agriculture/river-of-fire-57924). Apart from CRB, summer forest fires are also prevalent in many regions of India that are reportedly rising in recent times (Roy 2022).
Retrieval of biomass fire data
Data on active biomass fire spots detected on April 25th, May 25th, and June 25th and reported by active fires air reanalysis product (ARP) were extracted through the Fire Resource Management System of NASA. The active fire data captured by VIIRS (I-band 375 m) on board Suomi NPP and processed by NASA LANCE FIRMS, were extracted and fire spot maps of India were developed by integrating the data with shape files of India that included country boundary and first level administrative division (i.e. state), on a GIS platform. The generated fire maps demonstrated biomass fires as spots over Indian landmass marked with state borders. Gas flares are not picked up by VIIRS fire products as they are primarily designed to detect wildfires having larger surface area and those burning at lower temperature than small and bright hot sources like the former (Sharma et al. 2017). Fire spots detected by VIIRS are small, intense or burning over a broader area within the pixel, implying that the entire pixel is on fire. The VIIRS swath of 3040 km ensures a ≈15% image overlap between successive orbits over the equator, thus having a 12-hourly worldwide coverage.
Air trajectory and wind vector simulation
The Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model was used to compute air parcel trajectories to assess the distance and direction of moving air parcels carrying air pollutants (Air Resources Laboratory, NOAA, https://www.arl.noaa.gov/hysplit/). In this study, HYSPLIT was run in forward trajectory mode for 144 h (6 days on 4th week of each month, overlapping the period of observed fire spots), separately from five locations situated in five different parts of India (North, West, Central, South-East and North-East) that were found have either hosted the majority of biomass burning clusters or located adjacent to the clusters. The selected source locations were Ludhiana in state of Punjab in North India (30.9010°N, 75.8573°E), Vizag in state of Andhra Pradesh in South-Eastern India (17.6868°N, 83.2185°E), Mumbai in state of Maharashtra in Western India (19.0760°N, 72.8777°E), Agartala in state of Tripura in North-Eastern India (23.9408°N, 91.9882°E), and Bhopal in state of Madhya Pradesh in Central India (23.2599°N, 77.4126°E). HYSPLIT was run on the 25th day onwards in April and May in 2021 with archival meteorological database (3-hourly) of global data assimilation system (GDAS1; National Weather Service’s National Centres for Environmental Prediction, NCEP). Forward air movements originating from these source locations, potentially carrying smoke and air pollutants generated by biomass fires could be fundamental in influencing local and regional air quality vis a vis surface BC over India. The HYSPLIT model has been used earlier for tracking the movements of air masses and interpreting their role in governing atmospheric chemistry in a mega city in India (Majumdar and Adhikary 2022).
Furthermore, monthly resultant wind vectors at 1000 mb (near surface) were simulated by using the atmospheric reanalysis tool of the National Centres for Environmental Prediction/National Centre for Atmospheric Research to visualise and understand resultant airflow over Indian landmass that would also have immense bearing on transfer of smoke and air pollutants generated by biomass fires. The wind direction and wind speed contours were plotted and presented through the reanalysis tool.
Assessment of BC surface mass concentrations
Black carbon is one of the best aerosol markers of wildfires and biomass burning (Cheng 2014; Duc et al. 2020). The BC surface mass concentrations over India were extracted from version 2 of Modern-Era Retrospective Analysis for Research and Applications (MERRA-2), an atmospheric reanalysis product of the Global Modelling and Assimilation Office (GMAO) of National Aeronautics and Space Administration (NASA) that uses Goddard Earth Observing System Model (GEOS-5). The GEOS-5 is radiatively coupled to the Goddard Chemistry Aerosol Radiation and Transport (GOCART) aerosol module to simulate dust, sea salt, sulphate, BC, and organic carbon and is used to generate aerosol products (Gelaro et al. 2017; Randles et al. 2017). In reanalysis, a data assimilation system consistently reprocesses meteorological observations, typically historical, by using an inbuilt forecast model to combine different observations to produce gridded data sets even for variables that may not be directly observed (Gelaro et al. 2017). Upgradation from MERRA to MERRA-2 has empowered the latter with the ability to perform aerosol reanalysis including BC (Gelaro et al. 2017). MERRA-2 utilises data assimilation techniques to analyse aerosol optical depth (AOD) data received from Moderate Resolution Imaging Spectroradiometer (MODIS), Advanced Very High-Resolution Radiometer (AVHRR), Multiangle Imaging Spectro-Radiometer (MISR) and Aerosol Robotics Network (AERONET) stations (Level-2 AOD) (Buchard et al. 2017; Gelaro et al. 2017). MERRA-2 has been successfully used to model aerosol optical properties during the Californian wildfires of 2013 that agreed well with aircraft observations (Buchard et al. 2017). The conformity of actual observations with reanalysis exhibited the prospects for successful implementation of MERRA-2 in the optimal representation of surface BC during bushfire events (Duc et al. 2020). For this study, monthly average BC surface mass concentrations from MERRA-2 aerosol diagnostics were obtained at 0.5° × 0.625° resolution over India during April, May and June of 2015 to 2021 and their maps were generated by the MERRA-2 reanalysis tool, that were used to assess temporal and spatial variations in surface BC during biomass-burning periods in summer (April–June).
Variation in planetary boundary layer height (PBLH)
Eventual manifestation of local and regional air pollution on the regional air quality is largely controlled by the structure (height) and processes involved with the planetary boundary layer (PBL) (Miao et al. 2015). Temporal and spatial variation in the height of the planetary boundary layer (PBL) is crucial in controlling concentrations of air pollutants including BC. The PBLH over India as monthly averages were extracted into overlay maps and histograms with statistical summary, generated by Merra-2 reanalysis tool, for the months of April, May and June of 2020 and 2021 via MERRA-2. Sathyanadh et al. (2017) has earlier validated PBLHs reanalysed by MERRA-2 against PBLHs derived from radiosonde flight observations over India and found that MERRA-2 and radiosonde-derived PBLHs had correlation coefficients in the range of 0.74‒0.83 for selected stations over Indian landmass, confirming the reliability of PBLH data reanalysed by MERRA-2.
Results
Spatial distribution of biomass fires
Biomass burning spots in summers of 2015–2021 were found to be primarily concentrated in parts of Northern India, South-Eastern India, Central India, Western India, and parts of North-Eastern India. However, the month-wise spatial distribution patterns of fire spots were variable over 2015–2021. The fire spots are often observed to have formed clusters, indicating firing over adjacent stretches of land (Fig. 1p–u), as VIIRS 375 m active fire product is known to provide higher response for fires burning over smaller areas due to better spatial resolution and night-time performance (Schroeder and Giglio 2016). But, the closely located fire spots in clusters on the maps may be further apart on land, considering the given scale of maps against the huge expanse of the Indian landmass. The fire clusters largely covered states of Odisha, Chhattisgarh, Andhra Pradesh, Telengana, Madhya Pradesh, Maharashtra, Jharkhand, Karnataka, Punjab, Uttar Pradesh, Haryana, Gujarat, and Tamil Nadu that are known to be major wheat-growing states of India. Also, Manipur, Nagaland, and Mizroram in mountainous North-East India hosted substantial number of fire spots. Fire clusters were comparatively less pervasive in parts of Eastern (West Bengal, Bihar), Western (Rajasthan), Northern (Jammu and Kashmir, Ladakh, Himachal Pradesh), Southern (Kerala), and North Eastern India (Upper Assam). The fire clusters were heavily loaded with fire spots in April while diminished coverage of clusters by fire spots and increased isolation of fire spots from each other were starkly evident in May and further in June, implying much lesser fire incidences.Fig. 1 a–u Active fire spots (denoted by dots) detected by the 375-m VIIRS in April, May and June during 2015‒2021 on Indian landmass
Movement of air masses
Air trajectories emanating from the selected location in Northern India (Ludhiana) during April and May in 2021 showed movement of air masses primarily towards eastern and south-eastern directions, covering over 900 km in 6 days’ time, potentially affecting air quality in several regions on the way, expectedly more so in the first 2–3 days when moving air masses are more heavily loaded with air pollutants generated by biomass burning. A few specific air trajectories travelled over 2700 km in the eastern direction, reaching beyond Indian landmass on that direction. In May 2021, some air masses travelled beyond 2000 km in South-Eastern direction to cover parts of Madhya Pradesh, Telengana, and Andhra Pradesh primarily. Air trajectories from South-Eastern location (Vizag) mostly moved into specific eastern and southern parts of India in two opposite directions in April 2021 covering > 600 km in each direction and Eastern and North-Eastern Region (NER) in May 2021. In the latter case, trajectories moved over Bay of Bengal to re-enter Indian landmass in east. Several trajectories in May 2021 travelled beyond 2500 km on eastern direction in 6 days, transcending Indian boundary. Air trajectories from the Western cluster (Mumbai) encompassed coastal (west) southern India in April 2021 but changed direction in May 2021 to enter parts of south-eastern and eastern India in states of Andhra Pradesh, Telengana, Odisha and West Bengal, partly moving over Bay of Bengal in a path covering > 1600 km in 6 days. On the other hand, trajectories from the north-eastern location (Agartala) travelled further into other north-eastern parts of India, except upper Assam, Meghalaya and Arunachal Pradesh in April 2021. Many trajectories travelled to Bay of Bengal and some other beyond Indian boundary in eastern direction. In May 2021, entire eastern (West Bengal, Bihar, Jharkhand) and parts of North-East India was covered by the trajectories, some transcending Indian landmass in north-east direction. In April 2021, the air trajectories covered the entire Indian peninsula from the Central location (Bhopal), covering states of Maharashtra, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, and Telengana. On the other hand, the trajectories covered a part of South-Eastern India before moving to the Bay of Bengal and then entering Indian landmass in May 2021 (Fig. 2a, b).Fig. 2 a and b The 6-day forward trajectories of air masses from selected regions (Ludhiana, Vizag, Mumbai, Agartala and Bhopal) in a April 2021 and b May 2021
The simulated monthly resultant wind vectors over Indian landmass in April and May 2021 (Fig. 3a, b) showed that majority of winds flowing within Indian landmass moved from Northern India towards Central India and from Western India towards Eastern India. Furthermore, maritime winds from the Bay of Bengal moved inside Indian landmass through the South-Eastern, Eastern and also from Southern and South-Western directions and penetrated further into Indian landmass in April and May. The observed wind vectors underlined the scope of inland transfer of biomass smoke to various parts of India from prominent fire clusters. Over April to May, spatial shifts in wind speed contours were observed that would have influenced airflow movements and smoke dispersal over these two months.Fig. 3 a and b Wind vectors at 1000 mb showing resultant monthly wind direction and wind speed (m s.−1) contours over India in a April 2021 and b May 2021
BC surface mass concentration and corresponding PBLH
The regions with highest surface BC levels during 2015‒2021 covered parts of states like Uttar Pradesh (part of Indo-Gangetic Plain), Punjab and Haryana and also, Delhi National Capital Region (NCR) in Northern India; Bihar and West Bengal in Eastern India representing the Indo-Gangetic Plain; Tripura, Mizoram, Manipur, Meghalaya, and parts of Assam in north-eastern India. During the entire period of study, the concentration of surface BC was highest in April when fire spots were also most expansive whereas, in May and June, BC concentrations progressively declined along with declining fire incidents (Fig. 4a–u). Parts of a few states like Madhya Pradesh, Chhattisgarh, Odisha, and Andhra Pradesh in Central and South-Eastern India had lower levels of BC while parts of Rajasthan, Ladakh, Jammu and Kashmir, and Gujarat witnessed lowest BC levels. The states involved in hosting prominent fire clusters during the study period or that became the primary recipients of air masses coming from major fire clusters, had high levels of surface BC.Fig. 4 a–u BC surface mass concentrations (kg m.−3, monthly time-averaged) at a resolution of 0.5 × 0.625 degrees over Indian landmass in April, May and June during 2015‒2021
The temporal variation in PBLH was studied in 2020 and 2021. Over April to June during this period, the average monthly PBLH decreased with time (Fig. 5a–f) along with decreasing monthly median and maximum but increasing monthly minimum, except in June 2021 (Fig. 6a, b). In 2020, the mean PBLH declined from 1628.84 m in April to 1035.25 m in June while in 2021, the decline was from 1865.34 to 1030.58 m. The maximum PBLH also had conspicuous decrease in 2020 and 2021 over April to June (2792.53 to 2045.39 m and 3218.27 to 2143.45 m, respectively). The zones of maximum PBLH shifted from Central Indian regions in April towards north-western parts over May to June as summer conditions progressed in India.Fig. 5 Overlay maps of planetary boundary layer height (m, monthly time-averaged) at a resolution of 0.5 × 0.625 degrees over Indian landmass in April, May and June of 2020 and 2021
Fig. 6 a and b Histogram with descriptive statistical summary of planetary boundary layer height (m, monthly time-averaged) at a resolution of 0.5 × 0.625 degrees over Indian landmass in April, May and June during a 2020 and b 2021
Discussion
A substantial share in the summer fires can be attributed to wheat stubble burning after analysing available information on concurrent agricultural practises. Some of the states hosting major fire clusters are also major paddy-producing ones viz. Punjab, Chhattisgarh, Bihar, Odisha, Andhra Pradesh, Uttar Pradesh, Tamil Nadu, and West Bengal, where wheat fields need to be cleared in summer starting from April, for Kharif (June-September) paddy cultivation. Maize, the third most important crop in India after rice and wheat, is also cultivated during Kharif season in states like Andhra Pradesh, Karnataka, Rajasthan, Maharashtra, Bihar, Uttar Pradesh, Madhya Pradesh, and Himachal Pradesh, most of which are also wheat growing states (https://farmer.gov.in/m_cropstaticsmaize.aspx). Also, the states of Gujarat, Haryana, Maharashtra, Andhra Pradesh, and Rajasthan, jointly accounted for 83.7% of the national acreage of Kharif groundnut in 2018 (Agricultural and Processed Food Products Export Development Authority, https://www.apeda.gov.in/apedawebsite/HACCP/2018_Groundnut_Survey_Report.pdf). All the above states that need to clear their fields for either Kharif paddy or maize or groundnut after wheat harvest by March, hosted most of the fire clusters during April–June. The heavy fires witnessed in April in these states that diminished by May and June vindicates wheat stubble burning theory. Ravindra et al. (2022) have reported about 60% increase in paddy residue burning in Indo-Gangetic Plain in India during COVID-19 pandemic and linked this to declining income of famers during the pandemic. In recent years (2020 and 2021), fire spots are observed to have substantially grown in expanse in parts of the North-Eastern Region (NER) of India, covering the states of Tripura, Meghalaya, Manipur, and Nagaland.
It is also important to note that many of the fire clusters are co-located with forested regions in the states of Odisha, Madhya Pradesh, Chhattisgarh and Maharashtra and North-Eastern states of Tripura, Meghalaya, Manipur, Mizoram, and Nagaland (https://www.isro.gov.in/earth-observation/forest-environment). These regions in NER are notable areas of shifting (Jhum) cultivation (Seitinthang 2014) and are conveniently co-located with the fire clusters. Therefore, fire clusters appearing during April–June in NER could be dominated by forest fires resulting from shifting cultivation and other forms of forest fires. In past, about 50% of forest fires took place in NER of India (Bahuguna and Upadhyay 2002) and about 95% of that were caused by shifting cultivation. During January 2001 to April 2014, around 143,761 forest fire incidences occurred in NER (North Eastern Space Applications Centre 2014). In 2009, Mizoram and Meghalaya were amongst the prominent states in India in terms of the number of detected fire spots (Sahu et al. 2015). The authors reported fire counts detected by the Along-Track Scanning Radiometer (ATSR) satellite sensors during 1998–2009 and the highest and lowest monthly fire counts were observed during March–May and July–September, respectively. Biomass fires were highest in Madhya Pradesh and Maharashtra, two central states of India which together had a share of about 25–45% of total annual fire counts in India. As per North Eastern Space Applications Centre (2014), month-wise fire incidences in NER were maximum in April in Arunachal Pradesh, Assam and Tripura and the minimum in February in all other states except Tripura, where no fire was observed. On the other hand, maximum fire incidences occurred in March in Nagaland, Manipur, Meghalaya, and Mizoram. It was concluded that man-made forest fires perpetrated for shifting cultivation was the primary cause of fire incidences in NER. The evergreen/semi-evergreen forests had highest susceptibility to fire, followed by deciduous forests while alpine forests had least vulnerability. On the other hand, open forests had the highest vulnerability to fire.
The observed trajectories of air masses moving out from five principal regions of India during April and May in 2021 suggest that a major part of Indian landmass can be potentially affected by particulates and gases emanating from the fires. It is known that during smouldering of biomass in wildfire incidents, larger combustion products like pyrometeors are suspended in fire front and smoke plume, subsequently depositing to ground within minutes to hours (McCarthy et al. 2019), whereas particulate matter (PM) and gases disperse much longer to local, regional, or continental scales and remain in atmosphere for days, months, and sometimes, even years (Guyot et al. 2021). Therefore, air movements over fire clusters are expected to affect local and regional air quality over India in terms of principal combustion products like particulates, BC, SO2, NOx, CO, and others. Earlier, Badrinath et al. (2009) used 5-day trajectory modelling to find that winds from North-Indian stubble fire clusters in October actually reached Hyderabad, a city in south-eastern India about 1500 km away.
In spite of the potential role of biomass fires on air quality, summer fires have received inadequate attention thus far, possibly due to the arrival of summer by March, trigerring easy dispersion of air pollutants and sparing prominent urban centres of winter-like air quality. But, the scale of spatial expanse of summer fires definitely indicates likely perturbation in regional air quality in terms of BC, one of the major pollutants generated during biomass combustion. The Northern Indo-Gangetic Plain (IGP) hosted highest BC surface mass concentrations in summer, as this zone is within the zone of influence of wind movements from several biomass fire clusters (viz. northern in April and May, south-eastern in April and May and western in May) as explained earlier. The Indo-Gangetic Plain (IGP) is known to have near stagnant wind conditions combined with shallow PBLH in winter and post-monsoon seasons so that air masses travelling to IGP are confined to a small volume (Vaishya et al. 2017), thereby having a possible build-up of air pollutants. In summer, however, IGP may witness better ventilation. As per a recent study, Sonbawne et al. (2021) found strong association of BC measured at ground level with fossil-fuel emissions, biomass smoke, and wood-burning activities at a rural station in Haryana in India. In Ontario (Canada), a significant contribution (35%) of seasonal biomass burning to ambient BC was observed in winter at a control site with low traffic contribution (Healy et al. 2017). BC being an important agent involved in triggering radiative forcing and climate change (Walsh 2014), biomass burning at such scale over India would surely accelerate radiative forcing over Indian landmass in summer. Furthermore, BC being an important component of PM2.5, would play a key role in aggravating ambient PM2.5 levels. Stubble burning is known to have led to serious deterioration of air quality in terms of suspended particulate matter (SPM), SO2 and NO2 in selected areas in Haryana and Punjab in India (Singh et al. 2010; Grover and Chaudhry 2019).
Urban air pollution is influenced by the depth and structure of the planetary boundary layer (PBL) (Garratt 1994; Xu et al. 2018). The upward dispersion, mixing, transport, transformation, deposition of air pollutants, and exchange of cleaner air from above are strongly dependent on the PBL height (PBLH) and characteristics (Baklanov et al. 2011; Xu et al. 2018; Miao and Liu 2019). As BLH increases, vertical mixing height in the atmosphere also increases, helping dissipation and dilution of ground-level air pollutants and vice versa (Xiang et al. 2018). The PBLH undergoes large spatiotemporal variations vis a vis geographical location, land cover, soil characteristics, topography, season, and weather conditions (Sathyanadh et al. 2017). PBLH can have substantial diurnal variation also. In a year-long ground-based lidar measurement study on PBL over New Delhi in India, it was found that in the pre-monsoon season, PBLH grew by 100–300 m h−1 (mean: 206 ± 134 m h−1) (Nakoudi et al. 2019). In the study period, PBLH remained lower in many parts of IGP than central and many other parts of India, potentially supporting a build-up of BC in the former. Decreasing monthly average height of PBL over April to June ensured progressively declining vertical mixing and lower dilution of air but, in spite of that, the concurrent decline in BC surface mass concentrations along with declining fire counts over April to June was clearly witnessed, implying the influence of biomass burning on BC surface mass concentrations.
Conclusions
Fire spots detected by VIIRS over India in the summer months (April to June) during 2015–2021 suggest the prevalence of wheat stubble burning in some regions, corroborated by co-locating fire clusters with wheat growing areas, coinciding with harvesting season and confirming the significant decrease in number of fires after April when majority of wheat is harvested. In forested regions, the majority of fire incidents are expected to have been caused by shifting cultivation (in NE hilly region) and other types of forest fires. The potential distribution of polluted air moving from five principal fire cluster locations in northern, south-eastern, western, north-eastern, and central locations via wind movements during April–June may be a key contributor to air pollution in summer over India. The strongest connection of surface BC with biomass burning is the reduction in BC surface mass concentrations simultaneously with decreasing number of forest fires even as PBLH decreased, which must have helped increase stagnation of regional atmosphere in several areas. The IGP had higher levels of BC than other regions at any given time within the study period, possibly prompted by lower PBLH and influx of BC through air masses entering IGP from fire clusters in northern, central, and south-eastern regions.
Summer stubble burning and ensuing air pollution in India have rarely been discussed, possibly due to easy dissipation of air pollutants under favourable meteorological conditions with the advent of summer, but nevertheless, stubble burning potentially has a key role to play in perturbing air quality during summer over India. Furthermore, prominent regional fire clusters in forested regions were also observed during this study which has a confirmation from Roy (2022), who reported the appearance of big summer fire hotspots in the forested regions hosting national parks and wildlife sanctuaries in Chhattisgarh, Andhra Pradesh, Odisha, and parts of Telengana states in India. The significant escalation in fire spots in recent years is a cause of grave concern in terms of air pollution, radiative forcing and global warming, climate change, reduction in bioclimatic comfort in and around fire-affected areas, loss of forest cover, animal habitats and biodiversity and therefore, CRB and wildfires in India need urgent attention. The priorities in socially relevant environmental sustainability are long-term sustainable landscape management, sustainable human settlements based on bioclimatic comfort, clean agriculture and food production, all of which will be severely impacted by continual occurrence of crop and biomass fires. Therefore, policy intervention to ensure socially and economically acceptable means of clean agriculture vis a vis stubble management, shifting cultivation and sustainable biomass and forest management are necessary in de-escalation of biomass fire incidents in India.
This study underlines the fact that summer biomass burning incidences in India are too large in number and widespread spatially to be either downplayed or disregarded. But, unfortunately, such incidences and their potential implications on summer air quality are under-reported and less discussed in the scientific community so far. Akin to paddy residue burning, wheat residue burning also needs to be recognised as an evolving problem in crop management and ambient air quality. This along with forest fires needs to be fixed urgently and early, considering them as means of resource destruction and deteriorating local and regional air quality in summer. The future course of scientific research and deliberation on this subject area can be the following: (i) To assess the impacts of biomass fires on likely perturbations in regional meteorology and wind movements in summer, (ii) to estimate regional emission loads of principal air pollutants from summer fires, (ii) to decode the causes of increasing forest fires in summer in India and streamline management of the same to improve regional air quality, and (iii) to find suitable ways to minimise wheat residue burning and prioritise alternate ways of residue utilisation.
Acknowledgements
The Global Modelling and Assimilation Office (GMAO) and GES DISC are acknowledged for the dissemination of MERRA-2 data. The MERRA-2 is an official product of the GMAO at NASA GSFC, supported by NASA’s Modelling, Analysis, and Prediction (MAP) programme. The author acknowledges the support and encouragement received from Director, NEERI from time to time for carrying out various scientific assessments. No funding was received for this study. The manuscript number assigned by the Knowledge Resource Centre (KRC) of CSIR-NEERI is CSIR-NEERI/KRC/2022/SEP/KZC/1.
Author contribution
The author contributed to the study conception and design, material preparation, data collection and analysis, modelling, first draft preparation, and all revisions. The author read and approved the final manuscript [Deepanjan Majumdar].
Data availability
The datasets generated during and/or analysed during the current study are available with the corresponding author on reasonable request.
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Informed consent
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Competing interests
The authors declare no competing interests.
Research involving human participants and/or animals
This research did not involve any human participants and/or animals.
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We report a rare case of new-onset MDA-5-positive amyopathic dermatomyositis with rapidly progressive interstitial lung disease (RP-ILD) following the second dose of the COVID-19 mRNA vaccine. Our patient was a previously healthy Asian female in her 60 s who presented with fatigue, dyspnea on exertion, and typical dermatomyositis (DM) rashes without muscle involvement two weeks after receiving the second dose of the COVID-19 mRNA BNT162b2 vaccine. Workup revealed high titer MDA-5 antibodies, abnormal pulmonary function tests, and ground-glass opacities on chest imaging. She had good response to early aggressive therapy with high-dose steroids, intravenous (IV) rituximab, mycophenolate mofetil, and intravenous immunoglobulin (IVIG). This case highlights the potential immunogenicity of COVID-19 mRNA vaccines and the possibility of new-onset systemic rheumatic syndromes after vaccination. More studies are needed to understand a definitive causal relationship and improve surveillance of adverse immunological events following COVID-19 vaccinations.
Keywords
Case report
Dermatomyositis
Interstitial lung disease
Anti-MDA-5 syndrome
COVID-19 mRNA vaccines
issue-copyright-statement© Springer Nature Switzerland AG 2023
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pmcIntroduction
Rapid and successful development of vaccines to prevent SARS-CoV-2 infection is considered the most promising approach for curbing the global COVID-19 pandemic. The mRNA vaccine is delivered in a lipid nanoparticle to express a full-length SARS-CoV-2 spike protein which is the main antigenic target for vaccination. Currently in the USA, the COVID-19 mRNA vaccines BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) are fully approved by the Food and Drug Administration (FDA) for persons aged 16 years and older and persons aged 18 years and older, respectively. The mRNA COVID-19 vaccines are highly effective in reducing infection, severity, hospitalization, and mortality [1]. Advantages of the mRNA vaccines include fast to produce, low manufacture cost, high efficacy, and exceedingly safe profile [2]. The most common reported side effects are injection site reactions and systemic events including fatigue, headache, myalgias, arthralgia, fever, and chills [3].
Vaccination against SARS-CoV-2 is crucial for patients with systemic rheumatic diseases (SRDs) who may be at increased risk of severe outcomes from COVID-19 infections. Although the mRNA vaccines have an excellent safety profile in the general population, the trials excluded patients with SRDs [4]. There are rare reports of de novo systemic rheumatologic diseases as well as flare ups of established systemic rheumatic diseases after vaccination. In a web-based survey conducted in New York City, 14.9% respondents reported systemic rheumatic disease (SRD) flare following COVID-19 vaccine [5]. Rare reports of myocarditis and pericarditis, mainly in male adolescents and young adults, have also been reported following receipt of the mRNA vaccines [6]. There are hypotheses that mRNA vaccines may trigger SRD flares or de novo SRDs through molecular mimicry activating the immune system or nonspecific adjunct effects in rare cases.
In our case report, we present a unique case of new-onset MDA-5-positive amyopathic dermatomyositis with rapidly progressive interstitial lung disease following the second dose of COVID-19 mRNA BNT162b2 vaccination.
Case Presentation
History and Physical
The patient is a previously healthy Asian woman in her early 60s who developed diffuse rash two weeks after receiving the second dose of COVID-19 mRNA vaccine. The rash was non-pruritic, painless, and covered her upper extremities, torso, palmar and dorsum of hands, chest wall, neck, bilateral eyelids, and edge of her mouth. She was initially diagnosed with Coxsackie A infection based on positive Coxsackie A IgG antibodies. Her rash continued to worsen and within two weeks, she started to have significant dyspnea on exertion with frequent coughing spells. She also reported profound fatigue but denied fevers, chills, sputum production, and history of Raynaud’s or sicca symptoms. She denied recent travels, sick contacts, or prior history of COVID infection. She has no relevant family history.
Her physical exam was notable for normal cardiovascular and neurologic exam, lungs with mild bibasilar crackles, and skin rash suspicious for dermatomyositis including Gottron’s papules (erythematous papules overlying metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints), Shawl sign on her chest wall and neck, and heliotrope rash with associated eyelid and facial swelling. She also had small ulcers on her lower lip and erythematous papules on the palmar surface of her hands (Fig. 1a–c). Interestingly, she had symmetric joint swelling in her wrists, elbows, and MCP and PIP joints without complaint of joint pain. She had a normal nailfold capillaroscopy exam. Her strength testing in all muscle groups was within normal limits.Fig. 1 a Violaceous papules around eyes and on chest wall with mild facial swelling and small ulceration on the lower lip. b Erythematous papules on hands (Gottron’s papules) with associated MCP and PIP synovitis. c Erythematous papules on palmar surface of hands
Initial laboratory testing was notable for normal blood counts, elevated liver function tests, normal creatine kinase and aldolase, and elevated segmentation rate (76 mm/h). Antinuclear antibody (ANA), ANA comprehensive panel, and rheumatoid factor were negative, and cyclic citrullinated peptide (CCP) antibody was mildly elevated. Fungal infections ruled out with negative urine Histoplasma antigen enzyme immunoassay, Blastomyces antibodies, and serum Cryptococcus antigen. Her COVID-19 rapid antigen tests and COVID-19 IgM antibody were negative. Rocky Mountain spotted fever and syphilis screening tests were non-reactive (Table 1).Table 1 Laboratory testing
Range Initial labs 3 months 6 months
CBC/differential
WBC 3.4–10.8 (× 10E3/µL), 4–10 5.3 10.3 7.3
Hemoglobin 11.1–15.9 (g/dL), 11.2–15.7 11.1 12.8 12.3
Hematocrit 34.0–46.6 (%), 34–45 32.5 38 35.9
MCV 79–97 (fL), 79–95 90 97 95
Platelets 150–450 (× 10E3/µL), 150–400 298 225 251
Neutrophils Not estab (%), 34–71 60 86 86
Lymphocytes Not estab (%) 19–52 22 5 11
Monocytes Not estab (%), 5–13 15 7 3
Eos Not estab (%), 1–6 1 0 0
Basos Not estab (%), 0–1 0 0 0
Comp. metabolic panel
Glucose 65–99 (mg/dL), 70–100 94 N/A 91
BUN 8–27 (mg/dL) 12 21 19
Creatinine 0.57–1.00 (mg/dL), 0.6–1.1 0.62 0.58 0.73
eGFR if non-African Am > 59 (mL/min/1.73), > 60 96 98 87
Sodium 134–144 (mmol/L), 136–145 134 127 137
Potassium 3.5–5.2 (mmol/L), 3.5–4.8 4.6 N/A 4.2
Chloride 96–106 (mmol/L), 98–107 100 91 103
Carbon dioxide, total 20–29 (mmol/L) 23 20 22
Calcium 8.7–10.3 (mg/dL), 8.4–10.4 8.8 8.4 9.1
Protein, total 6.0–8.5 (g/dL), 6.7–8.6 6.5 5.8 8.0
Albumin 3.8–4.8 (g/dL), 3.5–5.2 3.6 3.1 3.4
Globulin, total 1.5–4.5 (g/dL) 2.9 2.7 4.6
A/G ratio 1.2–2.2 1.2 1.1 0.7
Bilirubin, total 0.0–1.2 (mg/dL), 0.2–1.2 0.4 0.4 0.6
Alkaline phosphatase 48–121 (IU/L), 40–150 79 69 44
AST (SGOT) 0–40 (IU/L), 5–34 164 59 36
ALT (SGPT) 0–32 (IU/L), 0–37 123 67 26
C-reactive protein, Quant 0–10 (mg/L), 0–5 < 1 < 1
Sedimentation rate-Westergren 0–40 (mm/h) 76 66
Ferritin 15–150 ng/mL 1183
Creatine kinase, total 32–182 (U/L), 29–168 163 44
Aldolase test 3.3–10.3 (U/L), 1.5–8.1 8.5 9.0
Vitamin D, 25-hydroxy 30.0–100.0 (ng/mL) 32.6
TSH reflex to T4F, TSH 0.450–4.500 (uIU/mL) 1.8
Thyroid peroxidase (TPO) Ab 0–34 (IU/mL) 12
Thyroglobulin antibody 02 0.0–0.9 (IU/mL) < 1.0
Rheumatologic markers
Antimyeloperoxidase (MPO) Abs 0 0.0–9.0 (U/mL) < 9.0
Antiproteinase 3 (PR-3) Abs 01 0.0–3.5 (U/mL) < 3.5
Cytoplasmic (C-ANCA) 01 Neg < 1.2 titer < 1.20
Perinuclear (P-ANCA) 01 Neg < 1.2 titer < 1.20
ANA IFA Neg Neg
ANA comprehensive panel Neg Neg
Anticentromere B antibody Neg Neg
Anti-dsDNA antibody Neg Neg
Antichromatin antibody Neg Neg
Anti-Jo1 antibody Neg Neg
RNP antibodies Neg Neg
Antiscleroderma 70 antibodies Neg Neg
Smith antibodies Neg Neg
Sjogren anti-SS-A Neg Neg
Sjogren anti-SS-B Neg Neg
Rheumatoid factor (RF) 0.0–13.9 (IU/mL) < 10.0
CCP antibodies IgG/IgA Neg < 20, strong pos > 59 26
Complement C4, serum 12–38 (mg/dL) 42
Complement C3, serum 82–167 (mg/dL) 97
MyoMarker 3 Plus Profile (RDL)
Anti-MDA-5 Ab < 20 (AU/mL) 113 27 < 20 Neg
Anti-SS-A 52kD Ab, IgG < 20, < 29 Neg, range 0–40 120 49 29
Anti-U1 RNP Ab (RDL) < 20 < 20 23 Neg
Anti-U2 RNP Ab (RDL) < 20 Neg Neg Neg
Anti-U3 RNP Ab (RDL) < 20 Neg Neg Neg
Infectious workup
Coxsackie A IgM < 1:10 Neg
Coxsackie A IgG < 1:100 1:1600
Hep A Ab, IgM Neg Neg
HBsAg screen Neg Neg
Hep B Core Ab, IgM Neg Neg
Hep C virus Ab 0.0–0.9 (s/co ratio) < 0.1
QuantiFERON-TB Gold Plus Neg Neg
RPR Non-reactive Non-reactive
Lyme IgG/IgM Ab 0.00–0.90 (ISR) < 0.91
Rocky Mountain spotted fever, IgM and IgG Neg Neg
Histoplasma Gal’mannan Ag Ur < 0.5 ng/mL Negative
Blastomyces Abs, Qn, DID Neg: < 1:1 Neg
Cryptococcus antigen, serum Neg Neg
SARS-CoV-2 rapid antigen test Neg Neg
SARS-CoV-2 antibody, IgM Neg Neg
SARS-CoV-2 Ab, nucleocapsid Neg Neg
Skin biopsy revealed interface dermatitis. Pulmonary function tests (PFTs) showed forced vital capacity (FVC) 71% (normal range: 80 to 120%), forced expiratory volume during first second (FEV1) 70%, and diffuse capacity for carbon monoxide (DLCO) 31% and computed tomography (CT) of the chest had ground-glass opacities (GGOs) in the subpleural distribution (Table 2, Fig. 2a). Malignancy was ruled out with normal abdominal ultrasound, pelvis ultrasound, and CT of the abdomen and pelvis. MRI of the thighs and electromyography (EMG) were deferred given normal strength testing and muscle enzyme levels.Table 2 Treatment and pulmonary response measured by PFTs and CT of the chest
Month Treatment Pulmonary function tests CT of the chest
Steroid DMARDs Infusions FVC FEV1 TLC DLCO 6MWT
1 MPred 48 mg 71% 70% 102% 31% Multifocal scattered GGOs and sub-solid opacities in peripheral
2 MPred 48 mg MMF 1 g Rituximab 1 g 64% 64% 83% Moderately increased GGOs and sub-solid opacities
3 MPred 40 mg MMF 2 g 55% 60% 81% 89
4 MPred 32 mg MMF 2 g IVIG 1 mg/kg 60% 66% 70% 57% No O2 Less GGOs, more dense fibrotic changes
5 MPred 24 mg MMF 2 g IVIG 1 mg/kg, ZA 5 mg 65% 70% 87% 64% No O2
6 MPred 20 mg MMF 2.5 g IVIG 1 mg/kg 78% 83% 87% 67%
7 MPred 20 mg MMF 3 g IVIG 1 mg/kg 83% 88% 102% 81% Significant improvement GGOs
8 MPred 16 mg MMF 3 g Rituximab 1 g, IVIG 1 mg/kg
DMARDs disease-modifying antirheumatic drugs, FVC forced vital capacity, FEV1 forced expiratory volume in first second, TLC total lung capacity, DLCO diffuse capacity for carbon monoxide, 6MWT 6-min walk test, MPred methylprednisolone, GGOs ground-glass opacities, MMF mycophenolate mofetil, IVIG intravenous immunoglobulins, ZA zolendronic acid
Fig. 2 CT of the chest without contrast on a initial visit showing multifocal scattered GGOs and sub-solid opacities in peripheral, b 3 months visit showing less GGOs and denser fibrotic changes, c 6 months visit with significant improvement in GGOs
One week after presentation, her Myomarker® panel came back with positive anti-MDA-5 antibody 113 (normal value < 20 units) and anti-SSA 52KD antibody IgG 120 (normal value < 20 units) (Table 1).
Differential Diagnosis
The patient’s primary care physician initially diagnosed her with Coxsackie A infection given her palmar rash and positive Coxsackie A IgG antibody. She was expected to improve with time, but her rash worsened, and she developed abnormal lung findings. Sarcoidosis was considered but her skin rash was atypical for sarcoidosis, and she did not have mediastinal or hilar lymphadenopathy. Differential diagnosis also included serum sickness–like syndrome following vaccination given skin rashes and symmetric polyarthritis. However, the patient did not have fevers and her rash was more consistent with dermatomyositis than typical urticarial rash in serum sickness–like reactions. Given the diffuse GGO on CT of the chest, interstitial lung disease (ILD) with nonspecific interstitial pneumonia (NSIP) or organizing pneumonia pattern was high on the differential but infections had to be ruled out before initiation of immunosuppression.
Disseminated fungal infections can also present with acute and chronic lung diseases. Acute pneumonia from blastomycosis often presents with fever and nonproductive cough and CT of the chest may show nodules, consolidations with or without cavitation, and/or tree in bud opacities [7]. Pulmonary histoplasmosis can mimic sarcoidosis with diffuse pulmonary infiltrates and mediastinal or hilar lymphadenopathy, and cavitary lung disease in chronic cases [8]. Pulmonary cryptococcosis can be asymptomatic in immunocompetent adults and radiographic findings include noncalcified nodules, lobar infiltrates, hilar and mediastinal adenopathy, and pleural effusions [9]. Our patient did not live in an endemic area for fungal infections, and active fungal infections were ruled out with blood and urine testing (Table 1).
Given the diffuse GGOs and abnormal PFTs, COVID-19 pneumonia was also on the differential. She had multiple negative rapid antigen testing for COVID-19 and negative COVID-19 IgM antibody and nucleocapsid IgG antibody.
We diagnosed the patient with MDA-5-positive amyopathic DM with rapidly progressive interstitial lung disease (RP-ILD) based on her characteristic DM rashes with skin biopsy showing interface dermatitis, abnormal CT of the chest/PFT findings, and high titer MDA-5 antibodies.
Treatment Course
After fungal infections were ruled out, she was promptly started on methylprednisolone 1 mg/kg with slight improvement in her dyspnea on exertion and energy level. Given her extensive lung disease, she was started on combination therapy that consisted of rituximab infusions 1000 mg every 2 weeks spaced 6 months apart and mycophenolate mofetil (MMF) titrated to 1500 mg BID (Table 2). Combination therapy rituximab plus MMF was chosen over cyclophosphamide due to a more favorable side effect profile and a reported good outcome achieved in a similar case of antisynthetase syndrome with RP-ILD [10]. For her extensive skin involvement, she also received intravenous immunoglobulin (IVIG) 2 g/kg divided over 3 days every 4 weeks. Methylprednisolone was tapered slowly based on treatment response by approximately 8 mg every month.
The patient was concomitantly treated with trimethoprim/sulfamethoxazole for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, calcium/vitamin D, and received one dose of IV zolendronic acid 5 mg.
Despite initial aggressive treatment, the patient had worsening of GGO on CT of the chest and slightly worse PFTs with oxygen requirement on the six-minute walk test during the first 2 months (Table 2). However, on her third month follow-up, she demonstrated mild clinical improvement with slightly less GGO on CT of the chest and stabilization of PFTs. Approximately 6 months after diagnosis, she had normalization of PFTs and significant improvement of pulmonary infiltrates on CT of the chest (Fig. 2b, c). Her dermatomyositis rash improved drastically as well with near complete resolution. Interestingly, her MDA-5 antibody titers decreased to 27 (< 20 units) at 3 months and to undetectable level by 6 months.
Discussion
We described a rare case of new-onset MDA-5-positive dermatomyositis with rapidly progressive interstitial lung disease two weeks after receiving the second dose of COVID-19 mRNA vaccination. The patient had classic dermatomyositis rashes (Gottron’s papules, shawl sign, and heliotrope rash), no evidence of muscle involvement, and RP-ILD associated with high titer MDA-5 antibodies. Her ILD and rash improved with aggressive combination therapy including high-dose steroids, rituximab, mycophenolate mofetil, and IVIG.
Interstitial lung disease (ILD) is a major cause of morbidity and mortality among patients with dermatomyositis or polymyositis. Anti-MDA-5 syndrome is a rare presentation of idiopathic inflammatory myositis associated with rapidly progressive course of ILD and poor prognosis [11]. The target antigen is the ribonucleic acid (RNA) helicase encoded by the melanoma differentiation–associated gene 5, which is an intracellular sensor of viral RNA (including coronavirus) that triggers the innate immune and subsequent production of cytokines including type I interferon, tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1), IL-6, and IL-18 [11, 12]. The proposed pathogenesis involves a role of infectious and environmental factors superimposed on a genetic susceptibility [13]. RNA viruses such as Coxsackie virus and parvovirus B19 have been implicated in causation of DM in the past [13, 14].
Clinically, anti-MDA-5 DM has unique features of cutaneous vasculopathy and RP-ILD. In addition to classic rashes of DM, patients often have oral ulcers, palmar papules, and eyelid edema which were seen in our patient [15]. Arthritis typically presents in symmetric distribution similar to rheumatoid arthritis in 50–80% patients with anti-MDA-5 DM. Early and aggressive treatment with a combination of immunosuppressant is critical for survival [16, 17]. Retrospective series suggest benefit from initial combination therapy including the use of steroids, tacrolimus, cyclophosphamide, mycophenolate mofetil, and rituximab [18–22]. A recent retrospective study demonstrated adjunct IVIG therapy as a very effective first-line therapy for patients with MDA-5–RP-ILD, increasing survival and remission by lowering ferritin concentration, anti-MDA-5 titer, and GGO score on CT [23]. Interestingly, anti-MDA-5 concentrations correlated with RP-ILD activity as well as relapse [24]. Our patient’s anti-MDA-5 levels became undetectable after 6 months of treatment which correlated with improvement in her PFTs and radiographic imaging and resolution of her rash.
Megremis et al. identified three immunogenic linear epitopes with high sequence identity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in patients with dermatomyositis [25]. This may suggest that exposure to Coronaviridae family might contribute to development of dermatomyositis or musculoskeletal autoimmune disease. There are reports of new-onset inflammatory myositis in COVID-19 survivors [26, 27] as well as other autoimmune and rheumatic diseases occurring after COVID-19 infection including reactive arthritis, lupus, inflammatory arthritis, cutaneous vasculitis, hemolytic anemia, and among others [27].
Development of systemic rheumatic disease after COVID-19 vaccination is rare and not well described in literature. We only found one other case of a 58-year-old man who developed probable amyopathic dermatomyositis with RP-ILD 4 days after receiving the mRNA COVID-19 vaccine. He was admitted to the intensive care unit in respiratory failure with diffuse GGO, oral sores, digital tip ischemia, and ulceration with skin biopsy consistent with dermatomyositis; his lab work showed positive ANA and elevated inflammatory markers, but MDA-5 antibodies were not reported [28]. He expired despite aggressive therapy.
Vaccine-induced inflammation may trigger or precipitate underlying autoimmunity. One proposed mechanism in development of autoimmunity to vaccines is molecular mimicry. Significant similarities between pathogenic elements contained in the vaccine and specific human proteins can potentially cause immune cross-reactivity and development of autoimmunity in predisposed individuals [29]. For instance, antibodies to SARS-COV-2 spike protein can potentially bind to human antigens such as MDA-5, extractable nuclear antigens, and nuclear antigens. Studies have also shown that SARS-COV-2 spike protein can also act as a pathogen-associated molecular pattern (PAMP) which may activate the inflammasome and TLR-mediated pathways leading to overproduction of cytokines [30, 31]. Our patient developed symptom one week after mRNA vaccination and persisted for more than four weeks. This temporal relationship suggests a distinct immunological hyperactivation rather than immediate post-vaccination immunological phenomena.
Overall, the occurrence of interstitial lung disease associated with amyopathic dermatomyositis following COVID-19 vaccination is exceedingly rare and the benefits of COVID-19 vaccination far outweigh the risks. Strength of this case report includes comprehensive patient information and good patient adherence to treatment and follow-up. The major limitation is the case report design which cannot prove direct causation and we can only postulate COVID-19 vaccination as a probable inciting trigger for ILD. Our patient also tested positive for Coxsackie A which has been associated for DM as well. However, it is important to describe this interesting case to alert clinicians the possibility of ILD associated with amyopathic dermatomyositis following COVID-19 vaccination because early aggressive therapy is critical for survival and good outcomes.
Conclusions
We described a unique case of MDA-5 syndrome with RP-ILD shortly after COVID-19 vaccination. The patient responded well to early identification and prompt aggressive immunosuppressive therapy. Larger epidemiology studies are needed to prove a causal relationship and establish surveillance for vaccine-induced immunological adverse events.
Author Contribution
Shuwei Wang: (1) substantial contributions to conception and interpretation of data; (2) drafting the article and revising it critically for important intellectual content; and (3) final approval of the version to be published.
Bassel Noumi: (1) substantial contributions to conception and interpretation of data; (2) revising it critically for important intellectual content; and (3) final approval of the version to be published.
Fardina Malik: (1) substantial contributions to conception and interpretation of data; (2) revising it critically for important intellectual content; and (3) final approval of the version to be published.
Shudan Wang: (1) substantial contributions to conception and interpretation of data; (2) revising it critically for important intellectual content; and (3) final approval of the version to be published.
Data Availability
Not applicable.
Code Availability
Not applicable.
Declarations
Ethics Approval
This manuscript is compliant with ethical standards.
Consent to Participate
The patient provided informed consent to participate for the purpose of publication of this case study.
Written Consent for Publication
The patient has provided written consent for publication of this case report.
Conflict of Interest
The authors declare no competing interests.
This article is part of the Topical Collection on Covid-19
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| 0 | PMC9735185 | NO-CC CODE | 2022-12-14 23:29:52 | no | SN Compr Clin Med. 2023 Dec 7; 5(1):18 | utf-8 | SN Compr Clin Med | 2,022 | 10.1007/s42399-022-01357-0 | oa_other |
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16 11 2022
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Purpose
Laparoscopic surgery has demonstrated various advantages for the patients’ care, but also presents some difficulties for the surgeons, such as kinematic restrictions. Robotic comanipulation, in which control of instruments is shared between the robot and the surgeon, can provide adaptative damping assistance which allows stabilisation of movements. The objective of the present study was to determine the contribution of this assistance on a bimanual laparoscopic task.
Methods
Adaptative damping was studied on Peg Transfer task, performed by eighteen surgery-naive subjects. This exercise was repeated seven times without (Classic repetitions) and seven times with comanipulated robots (Robot repetitions), in a randomised order. We measured task performance, using Peg Transfer score; gesture performance, using hand oscillations and travelled distance; eye-tracking movements as an indicator of emergence of expertise. Participants’ perceived workload was assessed by NASA TLX questionnaire, and difference in impression between the two conditions by UEQ questionnaire.
Results
Adaptative damping improved gesture performance (oscillations F(1,17) = 23.473, p < 0.001, η2 = 0.580), with a statistically significant simple effect on the tool oscillation for both non-dominant (p < 0.001) and dominant hands (p = 0.005), without influencing task performance (mean Peg Transfer score t(17) = 0.920, p = 0.382, d = 0.29), but deteriorating eye-tracking movements associated with emergence of expertise (mean fixation rate per second F(1,17) = 6.318, p = 0.022, η2 = 0.271), at the cost of a high perceived workload (NASA TLX score 59.78/100).
Conclusion
Assistance by adaptative damping applied by comanipulated robots improved gesture performance during a laparoscopic bimanual task, without impacting task’s performance without allowing the emergence of comportments associated with an expertise, and at the cost of a high perceived workload. Further research should investigate this assistance on more precise and clinical tasks performed by professionals.
Keywords
Comanipulation
Laparoscopic surgery
Bimanual task
Adaptative damping
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pmcIntroduction
Laparoscopic surgery consists of millimetre incisions in order to operate the patient, with surgical instruments and camera inserted into the abdomen through trocars, while watching the abdominal cavity on a 2D screen. This type of surgery presents various advantages compared to open surgery, such as decreased postoperative complications and shorter hospital stay [1, 2], and became during the past decades the gold standard in various abdominal interventions.
However, laparoscopic surgery also presents some difficulties, such as kinematic restrictions and lever-effect due to the trocars [3], compromised visuo-motor coordination [4], as well as ergonomic issues for the surgeon. 3D laparoscopy is nowadays available to improve depth perception, but is not yet the standard in operating room in many countries. [5]
Robot-assisted surgery is today well developed, with over than a million interventions performed in 2018 with the telemanipulated Da Vinci robot. However, telemanipulation introduces a new expertise, without a transfer of skill to the classic laparoscopic surgery [6], and as well limits the communication between the surgeon and the operating room team [7].
Apart from telemanipulated robots, another type of robotic-assisted surgery is developed: comanipulation, in which control of instruments is shared between the robot and the surgeon, keeping the surgeon close to the patient. With comanipulation, the surgeon does the same movement as usual, but the robot can bring some help and amelioration of the movement by holding the same instrument. Comanipulation can be applied to tasks requiring human judgement and precise gesture [8], with an easiest installation and a lower expense than telemanipulated robots. Applied to laparoscopic surgery, comanipulated robots do not change the installation of the patients or the trocars, and allow skill transferability [9].
One of the applications of comanipulated robots is the application of a viscous force, which slow the movement but maintain motions stable and precise, mostly used in ophthalmology [10, 11]. Indeed, hand tremor can be an obstacle in performing delicate surgical procedure, such as microsurgery, and applying a viscous force is one way to tremor filtering [8]. In laparoscopic surgery, viscous force could ensure safety and accuracy in precise procedures, but unlike in microsurgery, distance to cover is relatively long and slowing down larger movements can lead to fatigue and increased operative time.
Previous work proposed to utilise variable viscosity according to velocity [12]. This adaptative damping algorithm allows realising fast movements without applying viscous field, but when the motion is slower the robot generate a large viscous force to stabilise the hand movement. Similar damping has shown its benefits with comanipulation robots in other tasks than surgical ones [13, 14].
Results of this previous work [12] suggest that adaptative damping decrease hand tremor and realisation time of point-by-point trajectories in direct manipulation, with an improvement of trajectories, especially long trajectories, as well as in laparoscopy. In laparoscopy, viscous field seems to be more comfortable when applied in the tip of the laparoscopic instrument for small depth, and on the handle of the instrument for deeper movements.
However, those first results were made on simple tasks, far from clinical context, and on only one hand.
To get closer to a clinical context, the first step is to propose a bimanual task, as surgeons always use both hands to operate. Some exercises are specially made to train and evaluate ambidexterity, such as Peg Transfer [15]. To analyse a bimanual task, motion analysis has demonstrated to be a useful assessment of laparoscopic dexterity [16], and use of eye tracking is well known to evaluate expertise in laparoscopy [17] as experts tend to maintain their eye gaze on a target while novices will look back and forth from the target to their instrument to guide their motion. Robotic assistance in laparoscopic surgery has shown in previous work its impact on acquisition of expertise and amelioration of hand–eye coordination, studied by eye tracking [18].
Therefore, the present study aimed to assess the impact of variable viscosity field on a bimanual task in laparoscopic surgery, by analysing the effect of variable viscosity on task performance, gesture performance, and comportments associated to the emergence of an expertise, during a task that is made to evaluate bimanuality.
Methods
Participants
Eighteen participants, four women and fourteen men, without any experience in laparoscopic surgery were recruited. Three are left-handed. Participants were aged from 20 to 64 years at the time of the experiment, with a median age of 25 years. Among them, eight (44.4%) were daily users of computer video games, and five others (27.8%) had a manual job. All participants realised the same task (Fig. 1). All participants had an information letter and signed a written consent. All procedures are in accordance with ethical standard of the institutional board and with Helsinki declaration.Fig. 1 Summary of protocol, apparatus and methods
Material
Two set ups were used for this protocol: one without and one with comanipulated robots. These set-ups are illustrated in Fig. 2: Classic repetition set-up: it includes a laparoscopy training set-up (LaparoAnalytic) with one grasper for the left hand and one dissector for the right hand, and with a 2D screen above it displaying the working space. The set-up camera did not move during the task. The graspers and trocars are provided with movement’s sensors.
Robot repetition set-up: the same pelvi-trainer set-up is used, with a 2D screen, and with two robotic arms in addition, each holding the grasper and dissector for left and right arm, respectively, and placed on each side of the pelvi-trainer.
Fig. 2 Protocol set-up. a Represent the Classic set-up, and b the Robot set-up
The comanipulator used is a robotic arm designed on a technological basis from Haption 3D robots (https://www.haption.com/fr/products-fr/virtuose-3d-fr.html). It is composed of six articulated joints: the first three are actively controlled, composing the “shoulder” and “elbow”, and three distal constitute a free spherical wrist, rotation of which follows the rotation of the instrument. Instruments are attached to the robot by a magnet. All joints are equipped with position sensors.
In addition to providing artificial forces, the measures provided in real time by the robot are as follows:• Orientation of the instrument axis and positions of any point belonging to the instrument with respect to the frame attached to the fixed robot base
• The output of the robot is a force exerted at point P in real time (see Fig. 3).
Fig. 3 Representation of the robotic arm and its kinematics. Point H represents the handle, Point T the tip of the instrument, Point P is the point where the robot holds the instrument
Algorithms implemented in these robotic arms are:Gravity compensation and the associated trocar detection needed to its implementation, described before by our team in [19].
Adaptative damping algorithm, proportional to velocity [12]: as described above, the robot sensors can measure position and velocity of point P, and a force f can be exerted at point P. The following controller achieves programming a viscosity:f=-b.y
We propose in addition to make the viscosity b depending on the norm of the velocity:b=bmax.λ‖v‖
where bmax is the maximal value of the viscosity and 0 ≤ λ ≤ 1.
More precisely, two thresholds, vmin and vmax, are defined, with 0 < vmin < vmax, and λ is computed by linear interpolation between its maximal value 1 and its minimal value bmin/bmax:λ={1,ifv<vminbminbmax,ifv>vmax1-v-vminvmax-vmin1-bminbmax,otherwise
In order to avoid stick–slip motions (see Lin Dong thesis), a first-order low-pass filter is applied to the viscosity coefficient.
The viscosity parameters bmin, bmax, vmin and vmax were determined empirically in advance in order to be assistive but felt comfortable.
Procedure
Participants performed one exercise, with fourteen repetitions. Before the beginning of the session, a randomisation determined whether the task was performed with or without robotic help for each repetition (for example: with robot-without robot-without robot-with robot etc.), so that seven repetitions were performed without robotic help (Classic repetitions) and seven with robotic help (Robot repetitions) (Fig. 1).
Participants had to realise the same exercise with seven Classic repetitions and seven Robot repetitions, as the whole session was composed of 14 exercises, with a total duration of two hours. The chosen exercise was the Peg Transfer, defined by the Fundamentals of Laparoscopic Surgery protocol [20]. Before the beginning of the repetitions, participants had two minutes to familiarise with the set-up and instruments on another exercise (Marbles). Between repetitions, a pause was proposed to the participants, and a pause was imposed at mid-session.
Peg Transfer protocol: six pegs are disposed on the left side of a pegboard. The participant had to take a peg with his left hand, transfer it mid-air from the left to the right hand, and put the peg on the right side of the pegboard with his right hand. Once the six pegs were placed on the right side, the participant had to do the same manoeuvre from right to left, by taking a peg with the right hand, transferred it from the right to the left hand and put the peg on the left side of the board. No order was defined to take the pegs. All transfers had to be done on a good height, without the help of the board. This procedure is illustrated in Fig. 4.Fig. 4 Peg Transfer Procedure. The present figure shows one example of a left—to—right movement. The first image is the set-up at the beginning of the exercise. The participant grabs a peg with his left hand on the second and third image. On the fourth image, the participant transfers the peg from his left to his right hand. The fifth image shows the drop of the peg with his right hand. This movement is repeated for all the pegs from left to right, and then from right to left
A penalty was counted each time a peg dropped outside of the pegboard, or if it dropped into the pegboard but the participant could not reach it. One penalty corresponds to 10 points. The penalty was counted into the Peg Transfer score, as described below.
Maximal time to realise the exercise was 300 s. The time count begun at the moment the first peg is touched, and ended when the last peg is released. Participants were told to realise the exercise as fast as possible, without penalty.
The Peg Transfer is an exercise use in laparoscopic training to evaluate hand–eye coordination, depth perception, and ambidexterity [15]. Peg Transfer repetition is also used to evaluate novices, because it does not require technical surgical skills but is adequate to differentiate novices from experts [21].
Measures
To investigate the impact of damping on this bimanual task, we analysed task performance, gesture performance, acquisition of expertise, workload and the difference of impression between Classic and Robot repetitions.Task performance: to measure task performance, we used Peg Transfer scores:
Time to realise the exercise and penalty score (= 10 × number of dropped peg)
Overall score = maximal time accorded (300 s) – time to realise the exercise – penalty score
Corrected time, calculated according to the number of successful transfers, to determine the time that the participant would have taken to finish the exercise when he could not; calculated as followed:
Corrected time = time to realise the exercise x (12/number of successful transfers).Gesture performance: to measure gesture performance, we used the laparoscopy simulator LAPARO Analytic© (https://laparosimulators.com/analytic/), which is using the movement’s sensors on instruments and trocars to calculate different parameters, for each hand individually:Travelled distance by the tip of the instrument, in meters
Hand oscillations (score with no specific units)
Percentage of visibility of the instrument, calculated by a monitoring algorithm of the camera’s image
Emergence of an Expertise: we used an eye-tracking device to analyse the emergence of expert movement during the session, as experts tend to maintain eye gaze in the target while manipulating the instruments [22]. Two moments were chosen to define targets: the Grab phase, where the instrument is reaching the target which is the peg that it will catch, and the Transfer/Drop phase, were the peg is transferred between the two hands before being dropped on the target. Examples of targets for the first peg taken are represented in Fig. 5. Measures used were the number of fixations on the target before reaching it (a low number of fixations shows the maintenance of the gaze on the target), duration of fixations (which tend to lengthen when there is less back and forth from the tip of the instrument to the target), and fixation rate per second [17, 23]. Gaze data were recorded with a Tobii© screen-based eye tracker, with a sampling rate of 120 Hz. Data analysis was performed with Tobii Pro Lab©.
Workload: results obtained at the NASA TLX questionnaire allowed analysing self-perception of comfort during the exercise. It is a subjective multidimensional tool measuring workload during a task realised with a human-machine system [24]. It is based on six subscales: mental demand, physical demand, temporal demand, performance, effort and frustration. The questionnaire was given to the participants at the end of the whole session, and was filled only to assess Robot repetitions.
Difference of impressions between Classic and Robot repetitions: UEQ questionnaire was used to compare feelings of the participants when they did the exercise with or without the robotic arms. This questionnaire is validated to compare two products or experiences according to their utilisation (efficiency, perspicuity, dependability) and the impression of the user (originality, stimulation, attractiveness) [25, 26]. Two identical questionnaires were sent to the participant after their session, one to determine their feeling during Classic and one for Robot repetitions, and results were compared between the two questionnaires.
Fig. 5 Eye-tracking targets during the Peg Transfer exercise. The yellow circles represent targets where fixations are counted during the interest phases. The purple area represents the areas where the gaze can move back and forth during the interest phases, without fixations being counted. During the Grab phase, where the hand will grab the peg before it touches it, the target is the peg before it is grabbed. In the Transfer/Drop phase, in which the participant transfers the peg between his two hands and then places it down, the target is the peg on which the peg will be placed before it is dropped down
COVID-19 related procedures
Wearing a mask covering nose and mouth was mandatory during the whole session for participant and examiner. A minimal distancing of two meters was respected at all times. Each participant had to wash his hands with hydro-alcoholic gel before beginning the session. Between two participants, instruments and the whole set-up were disinfected and the room was ventilated.
Statistical analysis
The data recorded to appreciate the task performance were used to conducted inferential statistical analysis. For each metric, we analysed the effect of the robot use presenting two levels (Classic, Robot) using paired t tests.
For each metric of gesture performance, data were compared using a two-way repeated measures ANOVA to analyse the effects of robot assistance with two levels (Classic, Robot), and the hand characteristics also including two levels (dominant, non-dominant).
For each metric of the emergence of expertise, data were compared using a two-way repeated measures ANOVA to analyse the effects of robot assistance with two levels (Classic, Robot) and grab/drop phase also with two levels (grab, drop).
For all metrics, we checked the normality of the data before the statistical analyses if it was not respected, we used a logarithmic transformation to ensure the normality of the data. Statistical significance was set to 0.05. Data were analysed with SPSS software.
For the UEQ questionnaire’s measures, data were compared between the seven Classic repetitions and seven Robot repetitions, using Welch’s T test. All results are presented in mean ± SD. A p value of less than 0.05 was considered as statistically significant.
Results
Task performance
A paired-samples t test was conducted to compare mean Peg Transfer score, mean time of realisation and mean corrected time in Classic and Robot conditions. A logarithmic transformation has been applied to meet the normality hypothesis for Peg Transfer score and time of realisation.
There was no significant difference in the Peg Transfer scores for Classic (M = 32.1, SD = 54.1) and Robot (M = 26.6, SD = 48.2) conditions (t(17) = 0.920, p = 0.382, d = 0.29). There was also no significant difference in the scores for Classic (M = 263, SD = 52.5 s) and Robot (M = 263, SD = 1.14 s) conditions (t(17) = – 1.175, p = 0.256, d = – 0.28). There was no significant difference regarding mean corrected time for Classic (M = 434, SD = 351 s) and Robot (M = 463, SD = 503 s) conditions (t(17) = – 0.231, p = 0.820, d =−0.05).
Gesture performance
Gesture performance results are represented in Fig. 6.Fig. 6 Results of two-way ANOVA for gesture performance. a For mean travelled distance (mm), b For mean oscillations, c for visibility of instruments (%)
A repeated measures two-way ANOVA was performed to analyse the effect of adding robot assistance and using dominant/non-dominant hand on the total distance travelled by the tool tip. It revealed that there was a statistically significant interaction between the effects of adding the robot assistance and the studied hand (F(1,17) = 9.069, p = 0.008, η2 = 0.348). The main effects were not significant, with F(1,17) = 0.426, p = 0.522, η2 = 0.024 for the robot and F(1,17) = 0.082, p = 0.777, η2 = 0.005 for the hand. Simple effects analysis showed that for each analysed hand, adding assistance from the robot did not have a statistically significant effect on travelled distance by tooltip (p = 0.096 and p = 0.545, respectively, for non-dominant and dominant hands). Simple effects analysis showed that for each robot condition (with and without), changing the analysed hand did not have a statistically significant effect on travelled distance by tooltip (p = 0.098 and p = 0.089).
A repeated measures two-way ANOVA was performed to analyse the effect of adding robot assistance and using dominant/non-dominant hands on the oscillation of the hand. The analysis showed a significant effect of the robot use (F(1,17) = 23.473, p < 0.001, η2 = 0.580), and a non-significant effect of the analysed hand (F(1,17) = 2.303, p = 0.147, η2 = 0.119). It also revealed a statistically significant interaction between the robot assistance and the analysed hand (F(1,17) = 8.037, p = 0.011, η2 = 0.321). Simple effects analysis showed that for each analysed hand, adding assistance from the robot has a statistically significant effect on the tool oscillation for both levels of the hand dominance factor (p < 0.001 and p = 0.005, respectively, for non-dominant and dominant hands). The robot use is indeed a significant main effect. Simple effects analysis showed that with robot there is no statistically significant effect (p = 0.804) between hands, but there is one without robot (p = 0.015).
A repeated measures two-way ANOVA was performed to analyse the effect of adding robot assistance and using dominant/non-dominant hand on the visibility of the instrument. The results showed a significant main effect of the robot use (F(1,17) = 9.547, p = 0.007, η2 = 0.360): a non-statistical significance of the hand dominance (F(1,17) = 3.994, p = 0.062, η2 = 0.190), and no interaction effect (F(1,17) = 0.502, p = 0.488, η2 = 0.029).
Emergence of an ex1pertise: Eye-tracking
Eye-tracking results are represented in Fig. 7.Fig. 7 Results of two-way ANOVA for Emergence of Expertise. a For mean duration of fixations (sec), b For mean number of fixations, c For mean fixation rate
A repeated measures two-way ANOVA was performed to analyse the effect of adding robot assistance and Peg Transfer phase on the mean duration of fixation. The analysis showed a significant effect of the robot use (F(1,17) = 5.162, p = 0.036, η2 = 0.233) and a significant effect of the Peg Transfer phase (F(1,17) = 7.536, p = 0.014, η2 = 0.307). It also revealed a statistically significant interaction between the robot assistance and the phase (F(1,17) = 6.256, p = 0.023, η2 = 0.269). Simple effects analysis showed that adding assistance from the robot have a statistically significant effect only during the drop phase (p = 0.021) and not during the Grab phase (p = 0.675). Simple effects analysis showed that without robot assistance the phase has a statistically significant effect on mean duration of fixations (p = 0.007), but the effect is not statistically significant with robot assistance (p = 0.078).
A repeated measures two-way ANOVA was performed to analyse the effect of adding robot assistance and Peg Transfer phase on the mean number of fixations. The results showed a significant main effect of the phase (F(1,17) = 20.342, p < 0.001, η2 = 0.545): a non-statistical significance of the robot assistance (F(1,17) = 1.690, p = 0.211, η2 = 0.09), and no interaction effect (F(1,17) = 0.094, p = 0.763, η2 = 0.006).
A repeated measures two-way ANOVA was performed to analyse the effect of adding robot assistance and Peg Transfer phase on the mean fixation rate. There was a significant main effect of the robot (F(1,17) = 6.318, p = 0.022, η2 = 0.271): a non-statistical significance of the phase (F(1,17) = 1.014, p = 0.328, η2 = 0.056), and no interaction effect (F(1,17) = 1.432, p = 0.248, η2 = 0.078).
Questionnaires
Over all participants, the mean score at NASA TLX questionnaire is of 59.78/100. This represented a high perceived workload [27].
Results of the UEQ comparing Classic and Robot repetitions showed no significant difference between Robot regarding attractiveness (1.18 ± 0.99 vs. 0.83 ± 0.99, p = 0.31), perspicuity (1.31 ± 1.03 vs. 0.78 ± 1.07 p = 0.14), efficiency (0.99 ± 0.79 vs. 0.56 ± 1.15 p = 0.20), dependability (0.76 ± 0.8 vs. 0.67 ± 1.13, p = 0.77), and stimulation (1.19 ± 1.16 VS 1.47 ± 0.95, p = 0.44). However, novelty (0.29 ± 1.47 vs. 1.88 ± 1.01, p = 0.0007) was significantly higher in Robot repetitions. Those results of UEQ questionnaires are represented in Fig. 8.Fig. 8 Results of UEQ questionnaire
Discussion
The present study assessed the impact of comanipulated robotic assistance with adaptative damping algorithm on a bimanual task in laparoscopic simulation. The results suggest that adaptative damping improves gesture’s performance, with a significant diminution of hand oscillations on both dominant and non-dominant hands, but did not impact task’s realisation or emergence of an expertise. Moreover, subjective perception of workload was high according to NASA TLX, but robotic help appeared as more modern than Classic approach without influencing efficiency or perspicuity.
In surgical context, damping has shown its benefits in microsurgery by tremor filtering [8, 28] but have not been experienced in other fields of surgery. To our best knowledge, only our team have worked on adaptative damping for laparoscopic tasks.
It has been shown in two studies that damping had a positive effect on tremor filtration and on precision for point-to-point trajectories [12, 18]. The second study [18] concluded on an improvement of task’s performance with damping, but without significant difference, due probably to a lack of power because this question was not the main research question of this study.
Gesture analysis has been demonstrated as an objective reflection of operative ability, in simulation as well as in clinical situations [16]. In the present study, gestures amelioration by adaptative viscous force was expected, as the first application of this algorithm is tremor filtration. The present study confirms this role in bimanual laparoscopic simulation with an amelioration of gesture performance of both hands. Also, it was expected that the gesture amelioration could be more efficient on the non-dominant hand, as it is the less precise hand, and this hypothesis has been confirmed by this protocol, with the loss of statistical difference regarding hand oscillations between the two hands when adding the robotic assistance (Fig. 6b), while non-dominant hand had significantly more oscillations than the dominant hand in the Classic set-up.
However, contrary to what was expected, the task realisation was not ameliorated by adaptative damping. It has been shown that Peg Transfer is a good exercise to assess objectively laparoscopic technical skills, in terms of efficiency and precision [20]. As well, Peg Transfer is a good exercise to evaluate both hands individually and symmetrically, and so represent well a bimanual task. However, one hypothesis that can explain this result is the simplicity of the task and the lack of precise motions needed to complete it, which did not allow demonstrating the use of damping in this task particularly. Further research with more precise and complex tasks should be considered.
Interestingly, it has been shown in this study that gesture is improved, but the task realisation is not. However, it should be noted that the task is not deteriorated and moreover that the time of realisation is not increased. One of the criticisms about telemanipulation, which is nowadays the most common type of robotic assistance in laparoscopic surgery, is the increased operative time compared to classic laparoscopic surgery [28]. Here, comanipulation with adaptative damping algorithm permitted an amelioration of gesture with no longer time of realisation, or difference in terms of performance of the task. Moreover, telemanipulation tends to lengthen preoperative time, due to the installation of the robotic arms [29, 30]. Comanipulated device, as shown in this protocol, is easily installed and connected to the laparoscopic instruments with the help of magnets, and can be connected or disconnected easily whenever needed.
The negative result regarding eye-tracking measuring, reflecting emergence of an expertise, was less expected. Previous work showed a trend (but not significant) towards improved hand–eye coordination and reduce eye fixation rate per second, reflecting a faster emergence of expertise, with this type of robotic assistance in a laparoscopic exercise [18]. In the present study, this result is even weaker, as no trend seems to appear. Our participants were all novices and had no experience of laparoscopic surgery. Also, the Peg Transfer’s learning curve is known in the literature, showing that novices need to perform an average of 57 repetitions to reach an expert level [31]. The number of repetitions in this protocol may not have been sufficient to show the emergence of an expertise in novices, but we were unable to increase this number due to the already long duration of the session. This could explain the difference of results with the previous study, which included three sessions of exercises to analyse task’s learning.
Moreover, the results showed a significant deterioration of the mean duration of fixations, as well as the mean visibility of the instruments. As our participants were novices, already discovering laparoscopy, adding another factor as the robotic assistance could complexify the acquisition of expertise, and disturb the participants. Another hypothesis is that participants rely on the robotic assistance to have better results, which could unveil less accurate movements and comportments.
A specificity of this study was to evaluate self-perceived workload during the robotic-assisted exercises, which was high, indicating a lack of comfort for the participants. However, the participants were naive subjects. Laparoscopic surgery is a particular effort, being standing for a long time and discovering new motions and visualisations in laparoscopy can quickly lead to fatigue [32]. The duration of the 14-exercise session was approximately two hours, so it is not surprising that the workload was perceived to be high, even though rest periods between exercises were imposed. The perceived workload could have been due to the discovery of this surgery and its constraints. Nevertheless, the UEQ questionnaires revealed that there was no significant difference between the Classic and Robotic repetitions in terms of perceived efficiency and controllability. It is important to investigate this result in further studies to know if this perceived workload is due to the task itself, the discovery of laparoscopy or the robotic assistance. Perceived comfort and ergonomic are described as one of the strengths of telemanipulated robotic assistance compared to classic laparoscopic approach [33, 34]. The present protocol raises the question of compromise between gesture performance and comfort perception, as gesture is significantly improved by damping, but with a high perceived workload. Feedback on the perceived workload during the use of comanipulated robotic arms by people used to the effort of laparoscopy is therefore necessary in further research.
This study has several limitations. First, choice of novices does not allow determining the use of this assistance for surgeons, but it limits the potential bias of different level of skills between residents in different years of residency and experts. Also, unfortunately, only four on 18 participants were female, which is not representative of today’s representation of genders in the surgical environment. Furthermore, this study is a first step to assess the impact of comanipulated assistance on bimanual tasks. The task chosen, Peg Transfer, has no need of real precise movements, and as a consequence is maybe not adapted to demonstrate the impact of adaptative damping algorithm in laparoscopic surgery. Further researches are needed with more precise clinical tasks to determine the real-life impact of viscous force in comanipulated robotic-assisted laparoscopic surgery, and also with young and senior surgeons to study this contribution to professionals and the impact of experience on flexibility in this assistance use. Also, further research should investigate the perception of comanipulated robots and adaptative damping by professional used to laparoscopy, to have their feedback on this device and its potential use in operating rooms.
In conclusion, the present study assessed the impact of comanipulated robotic assistance with adaptative damping algorithm on a simple bimanual task in laparoscopic training performed by novices. This assistance improved gesture performance, without impacting task’s performance, without allowing the emergence of comportments associated with an expertise, at the cost of a high workload. This study raises the questions of the task’s choice, which should be more realistic and complex in future protocols to study the clinical impact of this robotic assistance. It also unveils the limits of the choice of naive participants. Further research should be conducted with professionals, used to laparoscopic surgery, and therefore more able to be confronted to a new technology, while performing a more precise task.
Author’s contribution
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by AN, FP and FV. The first draft of the manuscript was written by AN, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
No funding was received to assist with the preparation of this manuscript.
Declarations
Conflict of interest
The authors have no competing interests to declare that are relevant to the content of this article.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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7. Avellino I, Bailly G, Canlorbe G, Belgihti J, Morel G, Vitrani M-A (2019) Impacts of Telemanipulation in Robotic Assisted Surgery. In: Proceedings of the 2019 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA, pp 1–15
8. Taylor R Jensen P Withcomb L Barnes A Kumar R Stoianovici D Gupta P Wang Z Dejuan E Kavoussi L A steady-hand robotic system for microsurgical augmentation Int J Robot Res 1999 10.1177/02783649922067807
9. Troccaz J Medical Robotics 2013 Wiley
10. Gijbels A, Vander Poorten EB, Gorissen B, Devreker A, Stalmans P, Reynaerts D (2014) Experimental Validation of a Robotic Comanipulation and Telemanipulation System for Retinal Surgery. In: 5th IEEE RAS/EMBS International Conference on Biomedical Robotics and Biomechatronics. pp 144–150
11. Roizenblatt M Grupenmacher AT Belfort Junior R Maia M Gehlbach PL Robot-assisted tremor control for performance enhancement of retinal microsurgeons Br J Ophthalmol 2019 103 1195 1200 10.1136/bjophthalmol-2018-313318 30573495
12. Dong L Assistance to laparoscopic surgery through comanipulation 2017 These de doctorat
13. Erden MS Marić B Assisting manual welding with robot Robot Computer-Integr Manuf 2011 27 818 828 10.1016/j.rcim.2011.01.003
14. Tsumugiwa T, Yokogawa R, Hara K (2002) Variable impedance control based on estimation of human arm stiffness for human-robot cooperative calligraphic task. In: Proceedings 2002 IEEE International Conference on Robotics and Automation (Cat. No.02CH37292). pp 644–650 vol.1
15. Derossis AM Fried GM Abrahamowicz M Sigman HH Barkun JS Meakins JL Development of a model for training and evaluation of laparoscopic skills 11this work was supported by an educational grant from united states surgical corporation (auto suture Canada) Am J Surgery 1998 175 482 487 10.1016/S0002-9610(98)00080-4
16. Smith SGT Torkington J Brown TJ Taffinder NJ Darzi A Motion analysis Surg Endosc 2002 16 640 645 10.1007/s004640080081 11972205
17. Wilson M McGrath J Vine S Brewer J Defriend D Masters R Psychomotor control in a virtual laparoscopic surgery training environment: gaze control parameters differentiate novices from experts Surg Endosc 2010 24 2458 2464 10.1007/s00464-010-0986-1 20333405
18. Ferrier-Barbut E, Gauthier P, Luengo V, Canlorbe G, Vitrani M-A (2018) Measuring the quality of learning in a human-robot collaboration: a study of laparoscopic surgery. Woodstock ’18: ACM Symposium on Neural Gaze Detection. 10.1145/1122445.1122456
19. Dong L, Morel G (2016) Robust trocar detection and localization during robot-assisted endoscopic surgery. In: 2016 IEEE International Conference on Robotics and Automation (ICRA). pp 4109–4114
20. Ritter EM Scott DJ Design of a proficiency-based skills training curriculum for the fundamentals of laparoscopic surgery Surg Innov 2007 14 107 112 10.1177/1553350607302329 17558016
21. Feldman LS Cao J Andalib A Fraser S Fried GM A method to characterize the learning curve for performance of a fundamental laparoscopic simulator task: Defining “learning plateau” and “learning rate” Surgery 2009 146 381 386 10.1016/j.surg.2009.02.021 19628099
22. Law B, Atkins SM, Kirkpatrick AE, Lomax AJ (2004) Eye gaze patterns differentiate novice and experts in a virtual laparoscopic surgery training environment | Proceedings of the 2004 symposium on Eye tracking research & applications. Association for Computing Machinery. doi: 10.1145/968363.968370
23. Harvey A Vickers JN Snelgrove R Scott MF Morrison S Expert surgeon’s quiet eye and slowing down: expertise differences in performance and quiet eye duration during identification and dissection of the recurrent laryngeal nerve Am J Surgery 2014 207 187 193 10.1016/j.amjsurg.2013.07.033
24. Hart SG Nasa-task load index (NASA-TLX); 20 years later Proc Human Factors Ergonomics Soc Annual Meet 2006 50 904 908 10.1177/154193120605000909
25. Laugwitz B Held T Schrepp M Holzinger A Construction and evaluation of a user experience questionnaire HCI and usability for education and work 2008 Springer
26. Schrepp M, Hinderks A, Thomaschewski J (2014) Applying the User Experience Questionnaire (UEQ) in Different Evaluation Scenarios. pp 383–392
27. Hart SG Staveland LE Hancock PA Meshkati N Development of NASA-TLX (task load index): results of empirical and theoretical research Advances in psychology 1988 North-Holland 139 183
28. MacLachlan RA Becker BC Tabares JC Podnar GW Lobes LA Riviere CN Micron: an actively stabilized handheld tool for microsurgery IEEE Trans Rob 2012 28 195 212 10.1109/TRO.2011.2169634
29. Prete FP Pezzolla A Prete F Testini M Marzaioli R Patriti A Jimenez-Rodriguez RM Gurrado A Strippoli GFM Robotic versus laparoscopic minimally invasive surgery for rectal cancer: a Systematic review and meta-analysis of randomized controlled trials Ann Surg 2018 267 1034 1046 10.1097/SLA.0000000000002523 28984644
30. Ruurda JP Visser PL Broeders IAMJ Analysis of procedure time in robot-assisted surgery: comparative study in laparoscopic cholecystectomy Comput Aided Surg 2003 8 24 29 10.3109/10929080309146099 14708755
31. Scott DJ Ritter EM Tesfay ST Pimentel EA Nagji A Fried GM Certification pass rate of 100% for fundamentals of laparoscopic surgery skills after proficiency-based training Surg Endosc 2008 22 1887 1893 10.1007/s00464-008-9745-y 18270774
32. Berguer R Forkey DL Smith WD Ergonomic problems associated with laparoscopic surgery Surg Endosc 1999 13 466 468 10.1007/pl00009635 10227943
33. Zihni AM Ohu I Cavallo JA Cho S Awad MM Ergonomic analysis of robot-assisted and traditional laparoscopic procedures Surg Endosc 2014 28 3379 3384 10.1007/s00464-014-3604-9 24928233
34. Hubert N Gilles M Desbrosses K Meyer JP Felblinger J Hubert J Ergonomic assessment of the surgeon’s physical workload during standard and robotic assisted laparoscopic procedures Int J Med Robot 2013 9 142 147 10.1002/rcs.1489 23529792
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==== Front
Diabetologie
Die Diabetologie
2731-7447
2731-7455
Springer Medizin Heidelberg
980
10.1007/s11428-022-00980-8
Einführung zum Thema
Update Diabetestechnologie
Diabetes technology updateStulnig Thomas M. [email protected]
Schütz-Fuhrmann Ingrid [email protected]
grid.487248.5 0000 0004 9340 1179 3. Medizinische Abteilung und Karl Landsteiner Institut für Endokrinologie, Stoffwechselerkrankungen und Nephrologie, Klinik Hietzing, Wolkersbergenstr. 1, 1130 Wien, Österreich
5 12 2022
2022
18 8 851852
7 11 2022
© The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
issue-copyright-statement© The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2022
==== Body
pmcDiabetestechnologie hat unterschiedlichste Anwendungsmöglichkeiten und expandiert sehr schnell
Diabetestechnologie erfährt derzeit immense Entwicklungsschritte und rückt in den Diabeteskongressen zunehmend in den Fokus. Während das Management des Typ-2-Diabetes geprägt wird von laufenden pharmakologischen Entwicklungen, die die kardiorenovaskuläre Prognose verbessern, stehen die neuen Technologien besonders beim Typ-1-Diabetes im Vordergrund, sind aber bei weitem nicht auf diesen beschränkt. Die hohe Frequenz, mit der neue Produkte verfügbar werden, macht es praktisch-diabetologisch tätigen Ärztinnen und Ärzten, Diabetesberaterinnen und Diabetesberatern sowie weiteren involvierten Berufsgruppen zunehmend schwierig, up to date zu bleiben. Das vorliegende Themenheft soll allen Leserinnen und Lesern einen Überblick über das „cutting edge“ der Diabetestechnologie liefern, wohlwissend, dass mit seinem Erscheinen möglicherweise schon die eine oder andere Weiterentwicklung verfügbar geworden ist.
Diabetestechnologie ist ein weites und rasch expandierendes Feld mit sehr unterschiedlichen Anwendungen. Die Glukosespiegelmessung durch repetitive Bestimmungen des Blutzuckerspiegels wird für eine zunehmende Anzahl von Menschen mit Diabetes durch die intermittierend abgelesene oder kontinuierliche Glukosespiegelmessung in Echtzeit („real-time“) abgelöst. Dies führt zur Frage des Stellenwerts der dadurch verfügbaren neuen Parameter wie der Zeit im Zielbereich („time in range“) und der Glukosespiegelvariabilität für die Therapieeinstellung. Bei der Insulinapplikation finden Smartpens mit laufender Integration weiterer Funktionalitäten ihren Weg in die klinische Praxis. Und schließlich gibt es als Krönung die verschiedenen Insulinpumpensysteme, die durch zunehmende Automatisierung der Insulinabgabe in einer rasanten Entwicklung einem immer größeren Teil der mit Insulin therapierten Menschen mit Diabetes angeboten werden können.
Nicht zu vergessen sind die zahlreichen Softwareentwicklungen. Einerseits arbeitet die Software im Hintergrund der erwähnten Geräte und ermöglicht die neuen Funktionen der modernen Hardware. Darüber hinaus erlaubt sie die Integration verschiedener Devices zu (teil-)automatisierten Systemen, die in der automatisierten Insulinabgabe ihren Höhepunkt findet. Die Prinzipien der dahinterliegenden Algorithmen zu verstehen, ist – zumindest bis die Systeme weiter ausgereift sind – auch für die beratenden Diabetesgesundheitsdienste essenziell, um bei spezifischen Fragestellungen hilfreiche Handlungsempfehlungen geben zu können.
Diabetestechnologie umfasst aber auch Software, die die Anwender direkt unterstützen. Dazu gehören z. B. Insulindosiskalkulatoren, die als Apps auf Smartphones benützt werden, und Wearables zur Dokumentation der körperlichen Aktivität. Dazu kommen telemedizinische Anwendungen, die besonders seit der Einschränkung persönlicher Kontakte durch die COVID-19-Pandemie (COVID-10. „coronavirus disease 2019“) die Betreuung von Menschen mit Diabetes maßgeblich unterstützen.
In dieser Ausgabe versuchen wir, Ihnen den aktuellen Stand besonders praxisrelevanter Themen der Diabetestechnologie prägnant darzustellen. Der speziellen Situation des Do-it-yourself-Loopings wurde ein eigenes Kapitel gewidmet. Praxisnah richten wir die Diskussion über Diabetestechnologien nach verschiedenen Lebensabschnitten aus und thematisieren spezielle Lebenssituationen wie Schwangerschaft und Sport.
Wir wünschen Ihnen viel Spaß beim Lesen – und überraschende neue Erkenntnisse!
Thomas Stulnig & Ingrid Schütz-Fuhrmann
Interessenkonflikt
T.M. Stulnig und I. Schütz-Fuhrmann geben an, dass kein Interessenkonflikt besteht.
QR-Code scannen & Beitrag online lesen
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==== Front
BDJ In Pract
Bdj in Practice
2057-3308
2520-8675
Nature Publishing Group UK London
1816
10.1038/s41404-022-1816-6
Feature
Preparing for the (un)expected
Dickson Thomas [email protected]
Wealthwide, Birmingham, United Kingdom
5 12 2022
2022
35 12 2425
© British Dental Association 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
issue-copyright-statement© British Dental Association 2022
==== Body
pmc
By Thomas Dickson, Chartered Financial Planner at Wealthwide
We are often advised to 'prepare for the unexpected' and as a Chartered Financial Planner, that sounds eminently sensible. However, I'm not sure how useful this advice would be. COVID-19 was an unexpected event - but how could anyone have prepared for that? More recently, the repercussions of Kwasi Kwarteng's mini budget on the value of the pound or mortgage interest rates wasn't something any of us could have predicted. It strikes me it would be much more useful establishing what might realistically happen in our lives and careers and preparing for that.
We advise hundreds of principal dentists and there are several issues I can pretty much guarantee are going to crop up. Here's just a few we've seen over the years:Your star employee is going to get sick and have some time off work, or even worse leave for another position
You'll realise one of your employees isn't engaged with your practice and patients, and you'll need to extract them from your team. Getting, and keeping, the right people 'on the bus' is crucial to building a successful dental practice
Some patients are going to be late for their appointments or not show up at all. An orthodontist told me recently that she used to lose about 2½ hours a week to 'Did Not Attends' (DNAs) - since the lockdowns, this has doubled to five hours a week
One of your patients is going to be difficult and potentially even make a formal complaint
Your equipment is going to fail and will need fixing or replacing
This will probably happen when you are hundreds of miles away on holiday
As well as the general routine maintenance and renovation of your practice building, it's likely it will need urgent repairs at some point
Interest rates on your practice loans are going to increase (given where rates have been for the last decade - it doesn't seem likely they'll go down any time soon)
Laboratory bills and other equipment are going to increase in price - and probably above inflation
The UK is going to enter into a recession and some private patients are going to decide they can't afford your treatment plan
Tax is going to increase (the Autumn Statement delivered last month was no exception - with the additional rate income tax threshold reduced from £150,000 to £125,140, a Corporation Tax rate increase, reduction in the Capital Tax exemption, as well as other threshold freezes)
At some point before, during or maybe even after this recession, the stock market's going to fall… and then at some point bounce back again.
These issues are all fairly common and predictable and as a dentist or practice owner, you need to accept these are problems you should be expecting, and crucially making sure you're prepared for them.
Worst-case scenario planning
As a cyclist, I'm conscious of my vulnerability on the road and as a result, my ability to continue to run the business in the event of an accident. We therefore have a continuity plan for either my premature death or disability. This detailed written document confirms who takes over the senior management positions, which advisers will look after which clients and how they'll get paid - both in the short and if necessary, the longer term, all the professional advisers that need to be contacted such as accountant, solicitor, IT, and compliance - and their contact details, and how the team will continue to get paid every month so the business can continue to function as smoothly as possible. I very much hope no-one ever has to open up that document and go through those steps - but it's still important to have a plan - I certainly feel I owe it to our loyal team and clients.
One of the crucial agenda points in our monthly team meetings is to discuss risk factors to the business and ask ourselves some questions: What could go wrong? What's the impact of it going wrong? What processes do we need to change so we can reduce the chances of something going wrong, or at the very least minimise the impact?
Your health and ability to work and earn as a dentist is also at risk. Dentists' Provident - the leading income protection provider to dentists in the UK, announced in their latest annual report that they had paid out a total of £5.4m of income protection benefits to members - that's a total of 1,190 claims in 2021. I like one of their straplines which suits the title of this article - 'Plan for the future. Live for today'.
So how can you prepare for some of the above events?
Key issues for principals
Ensure you're constantly recruiting and looking out for great people who could join your team
Look after your existing team members - it's not just about giving them bonuses or salary increases, sometimes it's just making sure they're doing ok and have enough (but not too much) challenge and stress in their job, or have other benefits such as flexibility to vary their hours or for example buying additional holidays
Accept that great people will move on and that this present an opportunity to find someone else who might be an even better fit with your team
Give your team increasing responsibility, so they have the competency, experience and authority to deal with difficult situations
As a principal dentist, make sure you have regular time set aside to deal with issues - if you're working clinically five days a week, you'll end up squeezing all the emergency issues (that are almost certainly going to happen) into your evenings and weekends. You can also use some of this time to check you're working with the right suppliers and getting the best deals
With regards to the inevitable increase in costs - it's important to have cash savings, over and above what you might realistically need for normal working capital.
If you're struggling to put cash aside in the business and, understandably, you don't want to reduce your drawings, it's very possible you need to increase your prices, or make other improvements to the business such as providing more high value treatments, reducing your costs or attracting more patients.
Cost of living
We're already experiencing energy price rises, and inflation is impacting dentists personally and professionally. A key principle that might have helped, or could help you in the future, is to get used to spending less than you earn. If your income's variable (often the case for those that are self-employed) you can still create structure by setting up standing orders for different accounts such as for holidays, tax bills, emergency funds and longer-term savings such as ISAs or pensions.
This is all key to ensuring you spend less than you earn - during a period when your costs are higher than your income, you can cut back on your savings or even dip into them, to ensure your practice continues to run smoothly and you can maintain your lifestyle.
Stock market
You should only be investing in stocks and shares (also called equities - as you have a small stake or equity in the business) for the long term - that's at least five years and preferably a 10-year horizon. The reason this is so important is that the values of companies (and the value of the stock market) rises and falls in cycles - we just never know when, how high or low it's going to go.
Over a short period of time, cash often outperforms the stock market, but in the longer term you're very unlikely (provided you're invested appropriately) to be better off by keeping cash. You should also ensure you're taking the right level of investment risk - take too much and you might just want to bail out when the market starts to fall. Make sure you have enough money set aside in cash savings for the inevitable 'rainy day' - so you don't have to cash-in any equity investments at the wrong time in the cycle
Insurance
I met a dentist many years ago who owned a building that burnt down and unfortunately the property wasn't sufficiently insured, creating a significant amount of stress and financial anxiety. Although it's likely you've insured your property against fire, natural disasters and burglary, when was the last time you checked your insurance was set up correctly?
We almost always recommend principals take out Practice Expenses cover. This means that if you can't work for up to a year (due to illness or an accident), the practice has a regular income to cover the additional costs of management, recruitment and ensures all the salaries and any loans, continue to be paid - protecting the value of the goodwill.
It's also important to check your personal insurances, such as income protection, life cover and critical illness cover, are sufficient. It's interesting that the youngest dentist to make a claim with Dentists' Provident in 2021 was just 26 years old and the average age was only 48.
To make sure your insurance pays out when you need it, you should ensure you've disclosed all relevant details when you apply. Common areas you need to get right on application are telling the insurer if you've even been advised to reduce your alcohol intake, your smoking status, weight, existing medical conditions and any impending medical tests.
In my opinion, insuring your health is arguably one of the most important factors. If events happen outside of your control - such as a patient complaint, or the economy crashing, within reason you can do something about it - albeit it might mean extra work and stress. But, if you can't work as a dentist because of an accident or illness, you are totally reliant on savings, support from family and friends and any insurances to cover your monthly expenses.
Life has a habit of turning out differently from our expectations. While we have no control over events such as wars, mini-budget fiascos or global pandemics, there are some things that happen with sufficient regularity that they can be reliably predicted. It's important to set aside time to think through these risk factors and put in place a plan to 'prepare for the expected'.
On a final note, I would highly recommend investing in a Financial Plan. This will enable you to model various predictable but unwelcome events such as the stock market falling substantially, your earnings not keeping pace with inflation, or having to retire earlier than you'd hoped. This investment of time can provide the foundations and security to allow you to live life without worrying about money, and make important decisions with confidence and peace of mind.
Please be aware of the following investment risks
The value of your investment can go down as well as up and you may not get back the full amount invested
When investing your capital is at risk
Levels and bases of, and reliefs from taxation are subject to individual circumstances and may be subject to change
The Financial Conduct Authority does not regulate taxation and trust advice
Information is provided only as an example and is not a recommendation to pursue a particular strategy
| 0 | PMC9735192 | NO-CC CODE | 2022-12-14 23:29:52 | no | BDJ In Pract. 2022 Dec 5; 35(12):24-25 | utf-8 | null | null | null | oa_other |
==== Front
Acta Neurol Belg
Acta Neurol Belg
Acta Neurologica Belgica
0300-9009
2240-2993
Springer International Publishing Cham
36472796
2157
10.1007/s13760-022-02157-y
Letter to the Editor
FUEL for an ‘Alice in Wonderland’ syndrome
http://orcid.org/0000-0001-7032-4412
Maramattom Boby Varkey [email protected]
grid.501408.8 0000 0004 4664 3431 Department of Neurology, Aster Medcity, Kochi, Kerala India
6 12 2022
13
4 8 2022
28 11 2022
© The Author(s) under exclusive licence to Belgian Neurological Society 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
==== Body
pmcSir,
Alice in Wonderland syndrome (AIWS) is a perceptual disorder with distortions of visual perception (metamorphopsias), body schema or the experience of time [1]. AIWS is associated mostly with migraine or encephalitis. Non-ketotic hyperglycemia (NKH) is not known to be associated with AIWS. We describe a case of AIWS occurring in the setting of hyperglycemia and with MRI findings mimicking Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).
A 54-year-old man presented us with complaints of distortion of visual images of 3 days duration and right sided headache. The headache had a gradual onset and gradually increased and was associated with nausea and vomiting. His wife noticed that he had intermittent episodes of disorientation and slurring of speech during these 3 days. He was a long-standing diabetic on oral hypoglycemic agents. An MRI brain with MRA was normal, and he was started on dual antiplatelets for presumed transient ischemic attacks. As his events did not subside, he was admitted and blood glucose levels were noticed to be 440 mg/dl. He was started on insulin three times a day, and an EEG was performed which showed multiple right posterior head region electro-clinical events. The possibilities considered were hyperglycemic seizures or a focal encephalitis. He was started on three anticonvulsants (levetiracetam, sodium valproate and Clobazam). CSF examination was normal. Considering the possibility of a viral/autoimmune encephalitis, Acyclovir and methyl Prednisolone injections were also started. However, as his visual complaints increased, he was referred to us.
On admission, he complained of persistent metamorphopsias [micropsia (seeing things and people smaller than they are), macropsia (seeing things and people larger than they are), proso-metamorphopsia (distortion of faces) and polyopia (seeing multiple images of each person)] for 3 days, and persisted throughout the day.
On examination, there were no focal deficits. Repeat continuous EEG showed only right hemispheric slowing. Repeat blood sugars were in the range of 350–440 mg/dl. HbA1c was 12.3%, and SARS CoV-2 RT PCR was negative. A repeat CSF examination was also normal. Serum and CSF NMO & MOG antibodies were negative. A repeat MRI brain on the 7th day showed asymmetric gyral DWI and FLAIR hyperintensity along the cortex and the intervening sulci, in the right posterior temporal and parietal cortex, with corresponding thin leptomeningeal enhancement suggestive of FLAIR-variable Unilateral Enhancement of the Leptomeninges (FUEL) as well as FLAIR-hyperintense lesions, which are characteristically associated with MOGAD (FLAIR hyperintense lesions in anti-MOG associated encephalitis with seizures [(FLAMES)][2]. Serum anti-neuronal and paraneoplastic antibodies were also negative. He was continued on IV anticonvulsants and intensive glucose control with insulin infusions. On day 9, after controlling his blood glucose, 18FDG PET-CT showed hypermetabolic areas in the right posterior temporal and adjoining parietal cortex corresponding to the MRI detected areas of leptomeningeal enhancement. There were no other FDG avid foci anywhere else. Due to the MRI changes suggestive of FUEL and FLAMES, 1 g of Rituximab was administered for possible MOGAD on day 10. Serum NMO and MOG antibodies were negative on repeated testing on day 11. Over the next 3 days, his symptoms completely resolved and he was transitioned to thrice a day insulin therapy. His anticonvulsants were tapered over 3 months.
The combination of side-locked headache, seizures and focal cortical deficits localizing to the MRI area showing FUEL or FLAMES pattern is a distinct clinico-radiographic syndrome associated with Myelin oligodendrocyte glycoprotein antibody disease [2]. Our patient had features of AIWS, FUEL, FLAMES and NKH without detectable MOG antibodies.
Alice in Wonderland Syndrome (AIWS) is a perceptual disorder that perturbs the sensory associative cortices integrative pathways involved in modulating our internal–external relationship. The relationship between self and ‘not self’ (the external world) is impaired, such that patients erroneously misinterpret the external world with respect to their own body size or vice versa.
External visual distortions [Metamorphopsias] (rather than fleeting visual illusions or hallucinations) along with internal ‘somesthetic symptoms’ are the core features of AIWS. Other complex psychic symptoms (derealization, depersonalisation, chronotaraxis, somatopsychic duality) may also occur [3]. The predominant area involved in AIWS is the carrefour of three major areas, the temporooccipital, parietooccipital, and temporoparietal junctions [TPO-C] [4]. Visual and somatosensory information is integrated in the TPO-C to generate an internal as well as an external representation of self. Thus, misintegration of somatosensory input with the external visual input leads to AIWS [1]. A large number of metamorphopsias (visual disturbances) have been described in AIWS.
The neurological complications of NKH include focal seizures, epilepsia partialis continua, chorea-hemiballismus, hemiparesis, hemianopia, ocular flutter, encephalopathy and coma [5]. Occipital seizures are associated with reversible subcortical T2/fluid attenuation inversion recovery (FLAIR) hypointensities. Infrequently cortical or leptomeningeal T1 or FLAIR enhancement accompanies these transient findings. FLAIR imaging may show overlying gyral hyperintensities, and diffusion-weighted imaging shows mildly restricted diffusion in these regions.
Although NKH is an unusual cause of FUEL, FLAMES or an Alice in Wonderland syndrome, it should be considered in the differential diagnosis [2] (Fig. 1). Fig. 1 A and B T2 weighted axial sequences showing subcortical hyperintensity (arrows). C and D FLAIR sequences showing gyral hyperintensity with subcortical hyperintensity (arrows). E and F Axial T1 post-contrast images showing leptomeningeal and sulcal hyperintensity (arrows). G Axial FDG PET CT image showing right temporo-occipital hypermetabolism (arrow)
Declarations
Conflict of interest
No conflict of interest.
Data availability
Any further data is available on request.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References
1. Blom JD Alice in Wonderland syndrome Neurol Clin Pract 2016 6 3 259 270 10.1212/CPJ.0000000000000251 27347442
2. Budhram A Mirian A Le C Hosseini-Moghaddam SM Sharma M Nicolle MW Unilateral cortical FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures (FLAMES): characterization of a distinct clinico-radiographic syndrome J Neurol 2019 266 10 2481 2487 10.1007/s00415-019-09440-8 31243540
3. Blom JD Nanuashvili N Waters F Time distortions: a systematic review of cases characteristic of Alice in Wonderland syndrome Front Psychiatry 2021 10.3389/fpsyt.2021.668633/full
4. Brumm K Walenski M Haist F Robbins SL Granet DB Love T Functional magnetic resonance imaging of a child with Alice in Wonderland syndrome during an episode of micropsia J Am Assoc Pediatr Ophthalmol Strabismus. 2010 14 4 317 322 10.1016/j.jaapos.2010.03.007
5. Nysten C Vanhee A Govaerts A Demeestere J Ocular flutter and myoclonus in hyperosmolar hyperglycemic state Acta Neurol Belg 2021 121 2 595 596 10.1007/s13760-020-01540-x 33170432
| 36472796 | PMC9735193 | NO-CC CODE | 2022-12-14 23:29:52 | no | Acta Neurol Belg. 2022 Dec 6;:1-3 | utf-8 | Acta Neurol Belg | 2,022 | 10.1007/s13760-022-02157-y | oa_other |
==== Front
J Glob Entrepr Res
Journal of Global Entrepreneurship Research
2228-7566
2251-7316
Springer Berlin Heidelberg Berlin/Heidelberg
339
10.1007/s40497-022-00339-9
Review
Enhancing the productive engagement of COVID-19-driven workers’ exodus through micro-entrepreneurship: accentuated role of de-globalization and local innovations
http://orcid.org/0000-0001-9663-163X
Chaturvedi Ramesh Kumar [email protected]
[email protected]
grid.440550.0 0000 0004 0506 5997 School of Management and Commerce, Department of Management Studies, Babasaheb Bhimrao Ambedkar University (A Central University), VidyaVihar, Rae Bareilly Road, Lucknow, 226025 Uttar Pradesh India
7 12 2022
110
18 10 2022
2 12 2022
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Komboltz’s happenstance learning theory (HLT) posits that uncertainty in the environment has a deep impact on occupational choices. Accordingly, the choice of occupation is the outcome of planned and unplanned events during the life cycle of a person. Through evidence from literature, this article draws theoretical strength to a conceptual framework in which the affective status of COVID-19-driven workers’ exodus (an unplanned event) could encourage them to undertake micro-entrepreneurship as an occupational choice. The framework extends the HLT by adding risk propensity in a mediating role and evaluates de-globalization and local innovation as exogenous changes in influencing micro-entrepreneurial initiatives. The interplay between affective status, risk propensity, and micro-entrepreneurship in light of de-globalization and local innovation is conceptualized uniquely, and in this manner, the study presents a novel application of HLT. As an outcome, the framework supports the idea that in a situation of forceful reverse migration, affective status along with risk propensity, in an environment of reducing globalization as well as local innovations, is advantageous for micro-entrepreneurship. The proposed framework offers insight into the productive engagement of COVID-19-driven workers’ exodus, thus abating the remigration of workers, which would be a win–win situation for rural and urban societies.
Keywords
Workers’ exodus
Micro-entrepreneurship
Affective status and distress
Risk propensity
De-globalization, Local innovation
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pmcIntroduction
Uncertain and unexpected circumstances such as COVID-19-driven lockdown made large number of skilled/semi-skilled people lose employment and unwillingly relocate to rural or small towns from where they hailed, we call this as workers’ exodus (Yeganeh, 2021). There is continuing interest in how this workers’ exodus could be re-engaged in economically productive activities at the place of their relocation, which also falls under goal eight “i.e. decent work and economic growth” of the United Nations’ sustainable development goals. The happenstance learning theory (HLT) explains occupation choices cannot be completely planned and emerges as an outcome of unplanned and unexpected situations (Krumboltz, 2009). The workers’ exoduses amidst COVID-19 and subsequent lockdown were forced to a similar unplanned and unexpected situation. In this changed socio-economic situation, affective status (AS) of this workers’ exodus is altered due to dislocation and job loss. These people, facing occupational choice distress, are emotionally aroused with an element of anger (Thomas, 2020).
COVID-19 pandemic is not only putting an effect on workers’ exodus, but international business is also being affected (Yeganeh, 2021). The world is witnessing a change in the global economic scenario. There are reports about reducing pace of globalization which we are referring to as “de-globalization” (DG) (Gygli et al., 2019). The undesired consequences of globalization on domestic trade have been expressed by scholars over time (Georgieva et al., 2013; Chan et al. 2018; Chishti, 2020). Contributing to the conversation, many authors have also explained the positive effect of de-globalization on domestic small and micro-entrepreneurial initiatives (Petrova, 2013; Crona et al., 2015; Sindhe, 2015; Yeganeh; 2019).
The state of workers’ exodus under the COVID-19 environment and reducing globalization levels has presented such an unexpected and uncertain situation, which is certainly a reason for worry. But do these situations present any opportunity for productive engagement of workers’ exodus through micro-entrepreneurship and local innovations? This question is critically reviewed, and available opportunities are explored in this article.
Since HLT mainly focuses on external situations, occupational choices are also known to be influenced by personal characteristics (Holland, 1959; Hoyte, 2019)), so we extend HLT by adding two more components, affective status (AS) and risk propensity (RP). We propose since affective status attenuates risk judgment (Kahneman & Tversky, 1979; Li & Ahlstrom, 2020); workers’ exodus may undertake micro-entrepreneurship, an unplanned occupational choice, which otherwise they would have avoided considering as a risky engagement. Since long back and even today innovation is known to underpin entrepreneurial initiatives (Schumpeter, 1942: 83–84; Zastempowski, 2022), we also propose to examine the impact of COVID-19 on encouraging local innovations in developing countries through specific examples from India. To examine the local innovations and their impact on micro-entrepreneurial initiatives of workers’ exodus, we conducted two field interviews, one with a reverse migrated worker and the other with a person who intermediated the productive engagement of workers’ exodus. For this, purposive sampling technique was adopted, and the respondents were contacted during field visits in September and October 2021 regarding a research project on the rural population.
Finally, there is also a lack of literature on this new theme of investigation. For example, Durlauf et al. (2005) and Meyer (2004) long back in their review found a lack of articles primarily studying the relationship between foreign direct investment (FDI), de-globalization, and domestic micro-industry/entrepreneurship. When it comes to presenting the combined relationship of AS, RP, DG, and local innovations with micro-entrepreneurial initiative (MEI) in the context of unexpected events such as workers’ exodus during and post-COVID-19, to the best of our knowledge, no prominent citable study is there in extant literature. Thus, we see there is a noticeable gap in the literature.
Addressing this gap is pertinent in today’s scenario because among many measures that are expected to be taken by governments during and post-lockdown to boost domestic economic growth, one of them will be reconfiguring international trade-related policies, and another will be enhancing small and micro-entrepreneurship at the local level (Paul, 2020; Ferrannini et al., 2021). Moreover, the socio-economic benefits and subsistence-employment opportunities that micro-entrepreneurship could bring to society is so much important that it is worth studying its antecedents (Thomas & Mueller, 2000; Busenitz et al., 2003). Therefore, to address this important missing element in literature, we posit a framework expressing the relationship between the “affective status of workers’ exodus” with “intentions for micro-entrepreneurial initiatives” in the light of their risk propensity, reducing pace of globalization and local innovations. Accordingly, the following objectives are stated for this study:Develop a framework based on theoretical justifications to explain the role of affective status and risk propensity in micro-entrepreneurial initiatives of workers’ exodus during and post-COVID-19 in an environment of reducing pace of globalization and local innovations.
Analyze the impact of reducing pace of globalization during COVID-19 on local innovations and to examine the potential of local innovations in providing opportunity for initiating micro-entrepreneurship by workers’ exodus.
We present this article as a concept paper, and the proposed framework, duly supported by literature and field interviews, could be a starting point for conceptualizing empirical evidence-based strong theory. The subsequent sections of the article are constructs of study, development of framework, discussion, limitations and scope for future research, followed by conclusion and implications.
Constructs of study
Affective status: emotional arousal and distress
Affect is closely approximated to emotions or subjectively experienced feelings that could be triggered by innate or external stimuli. Affect theory originally attributed to Tomkins (1962) describes nine different types of affective states clubbed into three groups called positive, neutral, and negative. People tend to maximize the positive affect and minimize the negative affect. Tomkins (2014) as part of affect theory mentioned that arousal (ager) and distress affects are part of the negative group and these are usually stimulated by a continuing unrelieved stimulus. He subsequently proposed script theory where he argued that “scenes” are the sequence of events linked to affect which are triggered by experiences that people have during certain events. Wiederman (2005) continuing the argument explained that “scripts” follow “scenes” to identify patterns and provide direction in the selection of responses and behaviors to social settings. COVID-19-driven lockdown is one such event that has brought significant change in social settings, particularly for workers’ exodus. A large number of workers (industrial/non-industrial) who lost their job due to COVID-19 had been forced to relocate from urban centers to their native place of residence mostly in rural regions. Among them, employment and dislocation-related distress as well as emotional arousal (anger), which are part of the negative group affective state, are quite visible (Yeganeh, 2021).
Risk propensity
Risk propensity is the tendency of a person to assume or deter risk while decision-making (Sitkin & Pablo, 1992). Risk researchers have presented two perspectives of risk: first variability of outcome (possibility of occurrence of unwanted outcome) (Kahneman & Tversky, 1979; Mishra, 2014) and second loss due to unwanted outcome (Fox et al., 2015). There are two prominent sources of risk propensity: one as a person’s predisposition (domain-general) (Highhouse et al., 2017; Mata et al., 2018, Zhang et al., 2019) and the other governed by situations (domain-specific) (Tversky & Kahneman, 1986; Scholer et al., 2010; Figner & Weber, 2011). A recent work by Crawford et al. (2021) and the classical work of Knowles et al. (1973) both presented risk propensity as a trait that remains stable across the domains. Authors also posited that when people are exposed to situations that are beyond their control as well as put the undesired impacts on their lives, then under these circumstances, such people exhibit high domain-specific risk propensity.
Micro-entrepreneurship initiative
Micro-entrepreneurship is sometimes also referred as subsistence entrepreneurship. The goal of micro-entrepreneurship is to provide self-employment or at the most employment to other family members mostly when they could not find suitable employment or face loss of employment (Lerner et al. 2010). Szaban & Lubasińska (2018) in their review concluded that though self-employment must be differentiated from entrepreneurship, it could also be closely approximated to micro-entrepreneurship where subsistence and income generation are the primary goal. Small and micro-entrepreneurship offers huge productive engagement opportunities around the world, and it has the potential to bring inclusive and pervasive growth in society. For example, MSME sector in India employs about 111 million people and contributed about 30.27% of India’s gross domestic product (GDP) for 2018–2019 (Ministry of MSME, 2021). Another noticeable fact is, despite being just 44% of total MSMEs, micro-enterprises generate 109.6 million employments which accounts for about 97% of total employment generated in the sector and nearly half of that is generated through rural micro-enterprises. Moreover, there is a strong upward trend in the registration of new micro-enterprises in India (Ministry of MSME, 2021; Statista Research Department, 2021). Thus, there is huge potential for rural employment generation through micro-entrepreneurship initiatives by workers’ exodus at their native place.
De-globalization
De-globalization is the weakening of the interdependence between nations (New York University Department of Sociology, 2013; Verbeke et al., 2018). De-globalization is not some new phenomenon, and the world has witnessed de-globalization many times in the past, but two noticeable eras are 1930 and 2010 (O’Rourke, 2018; Peter & Bergeijk, 2018; Witt, 2019; Gygli et al., 2019). These authors claimed that de-globalization will be expressively noticeable in the future also. Despite these sporadic events of de-globalization, globalization kept rising sturdily until the recent past when the KOF globalization index reported globalization slowing down (Gygli et al., 2019). Now COVID-19 has severely impacted international trade (Yeganeh, 2021), and the globalization process is expected to further slowdown.
Conceptualization of framework
Taking support of existing theories to identify variables and understanding their relationship is a good way to present a new conceptual framework (Jabareen, 2009). Therefore, based on the relevant literature we seek support for the proposed framework (Fig. 1) comprising of variables such as affective status (AS), risk propensity (RP), and micro-entrepreneurship initiatives (MEI) of workers’ exodus in light of de-globalization (DG) and local innovation under COVID-19 environment. AS has two sub-dimensions, distress and emotional arousal (EA), where EA encapsulates anger. In this section, first, we present propositions based on co-integration between pairs of variables, and then, all variables are taken together to represent the complete framework.Fig. 1 Framework for role of AS on MEI of workers’ exodus in light of RP: in an environment of de-globalization and local innovations (authors source)
Affective status of workers’ exodus and micro-entrepreneurial initiatives
The unexpected emergent socio-economic situation such as COVID-19 and accompanying uncertainties is known to influence the occupational choices of people (Krumboltz, 2009). In India and other similar countries, large numbers of laborers and workers returned to their villages/native residences during the COVID-19 pandemic. Due to the unprecedented complete lockdown, this exodus is facing job and dislocation-related distress and emotional arousal (Thomas, 2020; Yeganeh 2021). The negative affect (distress and anger) in workers’ exodus was rooted in COVID-19 (stimulus) which could continue unrelieved due to new strains of coronavirus and recurring waves of the pandemic. As per the script theory, in this changed social and economic setting, to minimize the “negative affect,” the sequence of events (script) will direct workers’ exodus (behavior) towards productive engagement which could be self-employment and micro-entrepreneurship (Wiederman, 2005; Tomkins, 2014). In another research, it was concluded that people facing lifestyle as well as occupation choice challenges are more receptive to self-employment and micro-entrepreneurship (Vanessa, 2020). Based on these arguments, we propose that:P1: Affective status of COVID-19 workers’ exodus is a favorable antecedent to their micro-entrepreneurial initiatives.
Affective status (emotional arousal and distress) and risk propensity
Multiple qualitative and empirical studies found a significant role of affective status in risk judgment especially when affective status is underpinned by distress and anger (Johnson & Teversky, 1983; Isen & Jeva, 1987; Forgas & Bower, 1987). In situations of distress, people up to some extent are expected to compromise rationality and discount risk; hence, they are more receptive to risky behavior (Kahneman, 1973; Li & Ahlstrom, 2020). Ness & Klaas (1994) particularly found that people with aroused affect status such as anger, fear, and anxiety are known to diverge from thoughtful decision-making and exhibit elevated risk propensity. Other researchers also found distress (sadness) and arousal (anger) accentuate risk propensity and thus up to some extent suppress the sense of fear for outcomes of risky decisions such as entrepreneurship (Lerner & Keltner, 2000; Steiner & Driscoll, 2005). Notably, it has been found that the expectation of pleasantness in a distressing decision outcome could polarize the judgment and enhance the positive evaluation of decision outcome (Isen & Jeva, 1987; Mano, 1992). These findings are especially relevant in our setup where workers’ exodus is facing aroused affective status such as anger and distress due to unexpected job loss and dislocation. Under aroused affective status, they are expected to display a high domain-specific risk propensity for initiating micro-entrepreneurship. Workers’ exodus will also have a preference towards micro-entrepreneurial initiatives due to the associated pleasantness of productive engagement through their decision. Based on these arguments, we state the following proposition:P2: Affective status of workers’ exodus will positively influence their risk propensity.
Risk propensity and micro-entrepreneurial initiative
Though there is no dearth of literature explaining that entrepreneurship inherently involves risk and high-risk propensity leads to strong entrepreneurial intentions (Stewart & Roth, 2001; Laurent, 2012), there is little research that relates risk propensity directly with micro-entrepreneurial initiatives. Since risk propensity, the tendency of a person to assume or deter risk while decision-making, is an inner psychological character (Sitkin & Pablo, 1992) and considered a personality trait, it could be studied through theories of personality and occupation choices. Therefore, we seek support from the classical vocational/career choice theory by Holland (1959) which explicitly explains that people with “enterprising personality” are attributed with high-risk propensity. Such people have a strong inclination towards self-employment and entrepreneurship. Another noticeable recent work by Nieß & Niemann (2014) specifically argued for the positive causal type relationship of RP with self-employment tendency. Because self-employment and micro-entrepreneurship both are related to subsistence (Lerner et al. 2010; Szaban & Lubasińska, 2018), we could reasonably extend the positive relationship of RP with MEI also. After establishing the relation between RP and MEI, the question arises about its applicability to workers’ exodus context. For this, the arguments and framework by Norton & Moore (2002) and McMullen & Shepherd (2006) are worth considering. Both presented significant theoretical models explaining the risk propensity of people towards small and micro-entrepreneurship is underpinned by the skills that they possess and the availability of relevant information that they have. These theories from extant literature strengthen the proposition that skills and prior knowledge of workers due to their productive employment in urban centers positively influence their specific risk propensity which in turn could accentuate their micro-entrepreneurial initiative, thus giving strength to the proposed framework. Based on these arguments, we present the following proposition:P3: The risk propensity of COVID-19 affected workers’ exodus will positively influence their micro-entrepreneurial initiatives, and this relationship is positively moderated by the skill and knowledge they gained through their pre-COVID-19 productive engagement in urban centers.
De-globalization, local innovations, and micro-entrepreneurship opportunities
In contrast, to mainline globalization propagators, de-globalization has been presented by some researchers as conducive to both developed and developing economies (Petrova, 2013; Yeganeh 2019). Cherry (2020) expressed the negative impact of globalization on developed and exporting countries through an example of the tight current financial situation in Europe that was linked to the high dependence of the European economy on exports to emerging markets than internal consumption. Some studies have specifically explained the detrimental role of high globalization on small and micro-entrepreneurship in host countries. In a study conducted by Asiedu & James (2007) in America, globalization was found to be negatively impacting small and medium entrepreneurial ventures of non-whites. Many authors noticed a positive impact on small and micro-industries of host countries when the business of MNCs and the flow of FDI get constrained (Caves, 1996; Petrova, 2013; Yeganeh, 2019). Liu et al. (2013) and Crona et al. (2015) described the negative impacts of globalization as “tele-connected vulnerabilities” that affect economies, livelihood, culture, and the environment. Muralidhar & Mamatha (2011) and Sindhe (2015) in their study found that as Indian trade policy became liberal to globalization, the cost of agriculture input increased, but output cost did not. They further explained that agriculture-based employment in India has been found to decrease and at the same time indebtedness of farmers increased. Cornelia (2007) expressed that activities of MNCs may lead to contrived inflation and allow easy availability of ready-made solutions, thus mitigating economic growth opportunities and loss of appetite for technological innovation among research and development institutes of developing countries. High financial interdependence among nations has also been noticed as a reason for global economic crises such as the one witnessed in 2010 (Georgieva et al., 2013). In times of global economic crisis, the funding by the banks to small and micro-enterprises in host countries dries up, and these local enterprises face credit difficulty (Bruno, 2010). Therefore, it could reasonably be derived that de-globalization strengthens self-employment and micro-entrepreneurial opportunities in the host country.
Innovations that occurred in India during COVID-19
COVID-19 posed challenges to the global supply chain, and many countries had to find alternate local sources to meet emergent demands. Moreover, one of the main challenges that reverse migrant workers as well as the administration faced during and post-COVID-19 was ensuring productive engagement of these workers. Under such a situation, during and post-COVID-19, many countries witnessed local innovations that could encourage entrepreneurial initiatives over there. In the following section, we present certain examples from India to support this view.
Some innovations that reverse migrant workers did for productive engagement at their native place (from field interviews):Market innovation through product extension to a new market: We interviewed a person from Sirsi village in Sonbhadra district, Chatra block of Uttar Pradesh Province, India, who innovated by introducing a cuisine (considered to be of a fast-food category) popular in Indian cities to a rural market where it was almost unknown. This person was working with a fast food restaurant in Mumbai. While interacting with him, we came to know that, based on his prior skill and knowledge, he has started his own food point in Chatra.“When I reached my village in May 2020, I was feeling helpless with no job and no hope of a future. I could manage to get ration in July under a government scheme. I was constantly worried for my family, with whom I returned to my village. I noticed that local people were fond of ‘Chinese’ food (a group of fast food in India, which is popularly believed to be of Chinese origin). Since I was working with a fast food restaurant that also served ‘Chinese’ food, believing in my cooking skills, I felt, I could serve new and better tastes to locals. So, I decided to start my own fast food joint with help from family and some savings that I had. Now my stall is quite popular and I am doing well. I do not plan to go back.”
Process innovation: One example of innovative practice for productive engagement was witnessed in the Basti district of Uttar Pradesh Province in India. In an interview with a local block development officer, a first-line officer for rural development in India, we were told that the local administration engaged some reverse-migrated workers to dig ponds on their land under a guaranteed government employment scheme. This led to immediate earnings for these workers. Then, those who dug the ponds were encouraged and guided, with the help of a government research institute, to undertake fish farming in those ponds. Among those who initiated fish farming, some workers, due to their previous work exposure, had an understanding of market dynamics and took charge of selling fish in nearby markets or attracting clients from nearby cities. The officer further told us that these migrants were happy with their engagements and had no intention to leave their village in the future in search of a job. We found some media reports that also substantiate the findings of our interview (Hindustan Times, 2020).
Some other instances of local innovations due to pandemic-driven stressed global supply chain and concurrent lockdown:Drones: Engineers are coming out with plenty of innovative applications for drones made locally. Be it food delivery, grocery delivery, fumigation, or monitoring compliance with lockdown, drones are being used everywhere. Many rural reverse migrant workers are using drones for drone camera shooting of private and public events, which was almost unknown in rural regions prior to the pandemic (NDTV, 2020).
Testing kit: When India was struggling to get testing kits for COVID-19 and imports were also not available, a firm in Noida named DNA Xperts has come out with a testing kit that was quick as well as cheap. It could perform a coronavirus test in about 50 min at one-third cost, whereas earlier, a similar test would take 10 to 12 h to complete (Gupta, 2020). Similarly, another NOIDA-based firm New Life Company got approval from the Indian Council of Medical Research (ICMR) for a rapid testing kit at a cost of about 7.5 USD. Big companies also contributed to innovation; for example, Bangalore-based biotechnology firm has come out with a strip-based testing kit that was clinically tested and evaluated by ICMR as a deployable solution (Puri et al., 2020).
Ventilator: IIT, Roorkee (a Technology institute from India) in collaboration with AIIMS, New Delhi (a medical science institute), innovated a ventilator called “Praan-Vayu” suitable for Indian conditions and costs as low as 300 USD, much lower than any available ventilator in the market. It could work well in open spaces, thus deployable at many makeshift hospitals that were developed across the country to tackle corona pandemic (Design and Development-team, 2020; Puri et al., 2020).
Robotics: Kerala, Bangalore, NOIDA, and Delhi along with many other Indian states deployed robots to aid health workers at hospitals. Fortis Hospital, Bangalore, deployed a “Mitra” robot for screening every visitor to the hospital including medical staff for COVID. The Kerala government has deployed Robots named “Nightingale-19” at its hospital in the Kannur district to aid medical staff in attending COVID patients. Nightingale-19 is designed by a local engineering college in support of the health department. Also, Indo-Tibet Border Police have taken robotic services from a Gurgaon-based local robotics company Hi-Tech Robotic Systemz to provide robots that could support food and medicine dispensing to COVID patients (Puri et al., 2020).
Solar drier: A young student after completing an internship at a non-government organization (NGO) in Indore district of Madhya Pradesh Province decided to help farmers to reduce the wastage of their fresh produce and subsequently designed a portable solar drier that could dry the fresh farm produce such as rose petals and some vegetables, at very affordable cost, thus increasing their shelf life for more than a year. This innovation, which is portable and easily installable, helped many farmers to save their farm produce during the lockdown by enabling them to sell it later on when the markets opened. This innovation which supported farmers during the pandemic subsequently became a popular product as a micro-food processing unit. The farmers claim that by using solar driers, they have the flexibility to sell their produce out of season and get a better price for their produce (Agarwal, 2022).
Thus, based on these illustrations, P4 is stated as follows:P4: De-globalization and local innovation enhance the domestic micro-entrepreneurship opportunities and serve as positive independent moderators (Montoya, 2019) in the proposed framework which strengthen the effect of AS on MEI.
Discussion
A massive workers’ exodus was witnessed in emerging economies such as India during COVID-19. This workers’ exodus had an altered affective status in terms of emotional arousal and distress due to dislocation, job loss, and livelihood issues. However, if these workers’ exodus could be productively engaged in rural entrepreneurship, this situation also presents an opportunity (North & Smallbone, 2006). We found literature support for a positive criteria-predictor type relationship between affective status and risk propensity (P2) as well as between risk propensity and micro-entrepreneurial initiatives (P3). Extant literature also supports (P1) that the affective status of workers’ exodus which is related to employment and livelihood distress is in favor of their micro-entrepreneurial initiatives (Lerner & Keltner, 2000; Steiner & Driscoll, 2005). From the literature, we also infer that some domain-general risk propensity preexists in workers’ exodus and domain-specific risk propensity is stimulated due to COVID-19; thus, both the contexts of risk propensity (situation independent and context-specific) are relevant for workers’ exodus (Highhouse et al., 2017; Mata et al., 2018; Ness & Kjess, 1994), and it has a potential mediating effect on the relationship between AS and MEI. This implies that distressed and emotionally aroused workers’ exodus whose risk propensity is also elevated are more likely to initiate micro-entrepreneurship, an unplanned occupational choice. Since the occupational choice is unplanned and emerged from unexpected situations, the proposed framework is in confirmation with extended HLT.
These workers before COVID-19 lived in urban centers and had productive engagement over there. Their productive engagement indicates they possess certain skills and knowledge, which underpin their entrepreneurial risk propensity (McMullen & Shepherd, 2006). Therefore, in the framework (Fig. 1), we presented prior skills and knowledge of workers’ exodus as moderators (M1) for the relationship between RP and MEI.
While examining the literature on de-globalization and local innovations, it is visible that de-globalization accentuates opportunities for small and micro-entrepreneurship. Similarly, examples of local innovations witnessed in India during COVID-19 present evidences indicating opportunities for micro-entrepreneurship in a de-globalizing and stressed global supply chain environment. It is visible that, where AS of workers’ exodus positively influences their MEI, the exogenous factors, de-globalization, and local innovations also play independent positive moderator roles in the process. Furthermore, the field interviews also indicate that local innovations are providing opportunities to workers’ exodus to initiate micro-entrepreneurship. Therefore, based on these inferences, we get strength for P4 and conclude that de-globalization and local innovations positively influence the MEI. Thus, through propositions P1 to P4, it is the epistemological conclusion that the framework proposed is valid and explains the productive engagement of reverse migrant workers through micro-entrepreneurship.
During our interaction with reverse migrant workers, although it was short and brief, we found a mixed response from them; some were able to get a productive engagement for themselves and adjust to the conditions at their native place, while many others intended to return to cities. To meet this challenge, government took many steps; for example, the central government announced a long-term measure to integrate reverse migrant workers with productive engagement by earmarking Rs 50,000 crore (USD 6.9 billion) “Garib Kalyan Rozgar Abhiyan” (poor welfare employment mission). Under this scheme, to enhance the employment opportunities of migrant workers, they are to be connected with self-help groups for which their skill mapping is being done (Ministry of Rural Development, 2020). The government has also announced certain schemes for providing financial support to migrant workers, such as providing a loan of Rs 10,000 under the prime minister’s street vendor “AtmNirbhar Nidhi” (self-reliance fund) popularly known as “PM-SVANidhi” to those who want to work as a registered vendor (https://www.india.gov.in/spotlight/pm-street-vendors-atmanirbhar-nidhi-pm-svanidhi) and micro-unit development and refinancing (MUDRA) loan under “prime minister mudra scheme” to start occupation of their choice (https://www.mudra.org.in/).
In our view, a lot more needs to be done for proper productive engagement to reverse migrant workers; simultaneously, we also see a promising prospect in this context. Therefore, the framework presented in this study could play an important role in furthering our understanding of this challenging and complex domain of knowledge pertaining to the productive engagement of reverse migrant workers.
Limitations and scope for future research
The primary limitation of this article is a simplified representation of relationships between the variables, but in real world rarely, it is so monocausal. Therefore, it will be worthwhile to substantiate the arguments through quantitative data to strengthen our understanding of the interaction among variables. Globalization is studied as a detrimental factor in this article for the development of micro-entrepreneurship in developing economies such as India; however, future research could bring forth a comparative outlook on this aspect. Another limitation worth mentioning is that though the proposed framework does explain the possibilities of growing micro-entrepreneurship in current the COVID-19 environment, methods for growing micro-entrepreneurship are not covered. Hence, it could be an agenda for future work. We presented the cases of reverse migrant workers who have adjusted to local conditions and started their micro-enterprises. Despite these encouraging findings, there are cases of workers going back to urban centers. The opinion and sentiments of those who returned back to cities could shed more light on the migrant workers’ issues. Therefore, to address a larger generic issue, future research could extend the proposed framework beyond COVID-19 caused workers’ exodus to migrant workers in general by changing the content and criterion of affective status and risk propensity constructs.
Implications and conclusion
Social implications
Indian laborers and workers flouted the COVID-19-driven lockdown preventive measures and outrageously traveled from cities to their villages. These workers’ exodus now presents many opportunities in rural areas to grow local micro-entrepreneurship by leveraging their skills and economic potential. The framework proposed (Fig. 1) presents a scenario of transforming the workers’ exodus into potential micro-entrepreneurs in their native place. Keeping in mind that the main beneficiaries of rural micro-entrepreneurship are local communities, the adoption of micro-entrepreneurship could change the socio-economic structure of rural regions. Moreover, it will reduce the load of rural immigrants on urban infrastructure; thus, urban societies will also be benefited from this, whereas, in the absence of suitable employment/self-employment opportunities at the local level, workers will be forced to return back to cities, and ultimately, an opportunity to boost rural micro-entrepreneurship and community development will be lost.
Industry implications
Since workers’ exodus may undermine the associated risk in undertaking micro-entrepreneurship, capacity-building intermediation by microfinance institutions/NGOs would be vital in making the process successful. This situation brings responsibility as well as a business opportunity for the microfinance and NGO sector. In a scenario of de-globalization, it has been noticed that institutions and companies put great efforts to be creative, innovative, and productive, thus supporting micro-entrepreneurial initiatives. Moreover, by making cost-effective input supplies to mainstream enterprises and, in turn, achieving greater purchasing power, micro-entrepreneurial initiatives by workers’ exodus could help in building a virtuous macroeconomic environment. Additionally, the framework presented by us paves a roadmap to boost micro-entrepreneurship at the local level, in other situations similar to COVID-19, causing large-scale reverse migration of workers.
Academic implications
There are elaborate discussions in the literature on the role of affect in consumer decision-making (Sofi et al., 2020); however, its role in entrepreneurship is not much known. At the same time, there is a continued interest in academia to understand the diversity of determinants of entrepreneurship intention among reverse migrant workers. Therefore, there is a need to address these requirements of academia. The framework presented in this study is a step in this direction by augmenting our initial understanding of the role of affect in micro-entrepreneurship-related decisions. Additionally, those researchers and academicians focusing on perspectives of inclusive development through micro-entrepreneurship could also conceive fresh scholarly ideas by looking through the prism of the framework presented here. This article could also be a starting point for a fresh academic discourse on a critical examination of the role of globalization and MNCs towards small and micro-entrepreneurship, especially in the context of emerging economies.
The challenge of unemployment and laborer migration lies mainly in rural areas, and alongside the maximum consumption, economic growth potential also lies over there. Taking into consideration the challenges that rural economy faces and the potential it possesses, as a concluding remark, we recommend that economic policy in India and similar countries must promote and propagate local industries as much as possible. They must tap the entrepreneurial potential of workers’ exodus in the current COVID-19 environment and let the micro-enterprises play a significant role in economic growth.
Author contribution
This work was carried out as sole work of the author. All sections of the article are written and compiled by author Ramesh Kumar Chaturvedi.
Data availability (data transparency)
Data is collected by the author.
Code availability (software application or custom code)
No programming/coding is done for this research work.
Declarations
Ethics approval
No human or animal subjects are used in this study.
Competing interests
The author declares no competing interests.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Wetlands (Wilmington)
Wetlands (Wilmington)
Wetlands (Wilmington, N.c.)
0277-5212
1943-6246
Springer Netherlands Dordrecht
1642
10.1007/s13157-022-01642-7
Wetland Ecology
Appearance of a population of the mangrove rail Rallus longirostris (Rallidae) in salt marshes invaded by the exotic tanner grass Urochloa arrecta (Poaceae) and its disappearance after plant management
Bornschein Marcos R. 12
Teixeira Larissa 12
de Morais Guerra Bruno 1
Melchiori Bianca L. 1
Reinert Bianca L. 1
http://orcid.org/0000-0001-6557-5081
Sandretti-Silva Giovanna [email protected]
12
1 grid.410543.7 0000 0001 2188 478X Departamento de Ciências Biológicas e Ambientais, Instituto de Biociências, Universidade Estadual Paulista (UNESP), Praça Infante Dom Henrique s/no, CEP 11330-900 São Vicente, São Paulo, Brazil
2 Mater Natura – Instituto de Estudos Ambientais, Rua Emiliano Perneta 297, conjunto 122, CEP 80010-050 Curitiba, Paraná Brazil
8 12 2022
2022
42 8 12425 8 2022
17 11 2022
21 11 2022
© The Author(s), under exclusive licence to Society of Wetland Scientists 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Biological invasions cause species extinction but can also provide benefits. Wetlands, such as salt marshes, include little-known but important ecosystems that are sometimes severely invaded by exotic plants. Salt marshes in eastern South America are increasingly impacted by invasions of the African grass Urochloa arrecta. This study investigated the appearance of a population of the mangrove rail Rallus longirostris in areas dominated by U. arrecta and its disappearance with the eradication of this plant. We monitored four areas (54.47 ha) in the Guaratuba Bay estuary in southern Brazil, from 2006 to 2022, two of which contained four patches of U. arrecta as the dominant species. In 2012, we started to eradicate U. arrecta with mechanical management, and in 2020, it was eradicated locally. We recorded R. longirostris for the first time within a patch of U. arrecta in 2007. In subsequent years we saw the species in two other patches of the exotic plant. Rallus longirostris was no longer observed once U. arrecta was eradicated. Differences in patch occupancy between invaded and uninvaded habitats observed for R. longirostris and Pardirallus nigricans, and the disappearance of R. longirostris following the exotic plant management suggest competitive advantage and/or differential habitat preference and population density as hypotheses to explain observed patterns. The invasion of U. arrecta can increase the local populations of R. longirostris. Since this bird is not endangered, we encourage the management of U. arrecta because of its impact on salt marshes, including an endemic endangered bird.
Supplementary information
The online version contains supplementary material available at 10.1007/s13157-022-01642-7.
Keywords
Competition
Ecological trap
Estuary
Nesting site
Pardirallus nigricans
Restoration
http://dx.doi.org/10.13039/100009472 Fundação Grupo Boticário de Proteção à Natureza 0682/20052 0740/20071 0908_20112 BL0001_20111 0004_2012 1110_20172 Reinert Bianca L. Fundo Brasileiro para a Biodiversidade (FUNBIO) and 1ª Vara Federal de Paranaguá50005063420184047008 Reinert Bianca L. issue-copyright-statement© The Author(s), under exclusive licence to Society of Wetland Scientists 2022
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pmcIntroduction
The introduction of alien species has intensified with globalization in recent decades (Meyerson and Mooney 2007). Exotic species are defined as species that are not native to an ecosystem and that cause or are likely to cause economic, environmental, and/or human health damage (Catling 2005). They can change the composition of ecosystems rapidly and profoundly (Hobbs et al. 2009) and, through their direct and indirect effects, contribute substantially to species extinction (Vitousek et al. 1997; Bellard et al. 2016). Consequently, biological invasions are considered the second most common cause of biodiversity loss (Simberloff 2007). However, the effects of invasive species are not all negative, and the “native good/alien bad” dichotomy has been questioned (Goodenough 2010). Exotic species can benefit native species through habitat modification, trophic subsidy, pollination, competitive release, and predator release mechanisms (Lees and Bell 2008; Overton et al. 2014), besides having educational potential (Battisti 2016; Battisti et al. 2018). Comprehending and studying the responses of native species to invasive alien species and their management is essential for understanding impacts and deciding conservation actions (Schlaepfer et al. 2002; Lees and Bell 2008).
Wetland ecosystems can be greatly disturbed by biological invasions (Levin et al. 2006; Reinert et al. 2007; Norbdy et al. 2009; Cuassolo et al. 2012). These environments are vital, and despite covering only 6% of the Earth’s surface, they host 24% of the most invasive species on the planet (Zedler and Kercher 2004). Salt marshes, as a type of wetland, are possibly the most important and least understood of the world’s major ecosystems (Gedan et al. 2011). They are dynamic coastal areas (Watson and Byrne 2009; Gedan et al. 2011) that host salt-tolerant plant species (Doody 2001). They are regularly flooded by tides, have rapid sediment accumulation, and include transitions to non-tidal vegetation in the absence of human interference (Doody 2001). They occur in temperate areas across the globe, are more extensive in the northern hemisphere, and support seagrass Spartina spp. as the most common plant species (Doody 2001). Recently, some marshes on the South American Atlantic coast have been recognized as salt marshes—specifically subtropical salt marshes (Bornschein et al. 2017). They are characterized by the dominance of the crinum lily Crinum americanum L. and the California bulrush Schoenoplectus californicus (C. A. Mey.) Soják; therefore, the presence of smooth cordgrass Spartina alterniflora Loisel is rare (Bornschein et al. 2017). Subtropical salt marshes are associated with mangroves, distributed thinly in Brazil from the estuaries of the central-south coast of São Paulo to the north coast of Santa Catarina (Bornschein et al. 2017).
Currently, South American salt marshes are being invaded and dominated by tanner grass Urochloa arrecta (Hack. ex T. Durand and Schinz) Morrone and Zuloaga, which causes major problems for the region (Reinert et al. 2007). This species, when established, profoundly alters the communities in the environment (Casatti et al. 2009; Michelan et al. 2010; Carniatto et al. 2013). This poses a great threat to the conservation of endemic birds in southern Brazil, such as the marsh antwren Formicivora acutirostris (Bornschein, Reinert & Teixeira, 1995), which was first described in 1995 (Bornschein et al. 1995; Reinert et al. 2007). Environments completely invaded by this exotic grass are no longer occupied by the bird, which is why the impact is considered an area suppressor (Reinert et al. 2007). In contrast, marshes in California, in the United States, were invaded by a hybrid species of Spartina that benefited populations of the threatened Ridgway’s rail Rallus obsoletus Ridgway 1874 (taxonomy according to Maley and Brumfield [2013]). The hybrid increased the survival of this bird by providing refuge against predators during extreme tides that inundated native vegetation, particularly during winter, when native vegetation entered senescence (Overton et al. 2014). Hybrid plant management programs have reduced the survival rate of R. obsoletus and plans for its conservation suggest offering refuge against the high tides caused by rising sea levels (Overton et al. 2014).
In 2006–2022, salt marshes in southern Brazil were studied as part of a long-term project aiming to monitor and conserve F. acutirostris—a vulnerable (VU) species at risk of extinction in Brazil (Ordinance 148 of the Brazilian Ministério do Meio Ambiente [MMA], June 7, 2022). This bird is included in the Brazilian National Action Plan for the conservation of Atlantic Forest Birds, one of the specific objectives of which is to deter and control alien species in the bird’s natural habitat (Ordinance 208 of the Brazilian MMA and Instituto Chico Mendes de Conservação da Biodiversidade [ICMBio], March 3, 2018). In 2012 conservation efforts to protect F. acutirostris involved a challenging program that aimed to eradicate U. arrecta (Bornschein 2013), which impacted a local population of the mangrove rail Rallus longirostris Boddaert 1783. Rallus longirostris is generally restricted to mangroves (Vieira 2015) and is distributed across small portions of the Pacific coastal region, Central America, northern South America, and vast stretches of the Atlantic coast in South America (Maley et al. 2016). The species’ geographic distribution primarily occurs along the Atlantic coast of Brazil—a country in which its conservation status was officially considered to be of least concern (LC; ICMBio 2018), although it may be threatened with extinction (Vieira 2015). In this article, we report on the appearance and distributional expansion of R. longirostris in subtropical salt marshes invaded by U. arrecta and its disappearance after the plant was eradicated. We also discuss the possible causes of this event.
Methods
Study species
The target species was the mangrove rail Rallus longirostris, which is considered a separate species from the North American R. obsoletus and the clapper rail R. crepitans Gmelin 1789 (Maley and Brumfield 2013; Chesser et al. 2014).
Study areas and field time
We worked at the Ramsar Site Guaratuba in the Guaratuba Bay estuary in Guaratuba Municipality, which is on the southern coast of Paraná in southern Brazil. Specifically, we studied four areas: Jundiaquara Island (c. 25°52’25”S, 48°45’32”W; 11.30 ha), the confluence of the Claro and São João Rivers (“Continente”; c. 25°52’28 “S, 48°45’44”W; 8.47 ha), Folharada Island and its surroundings (c. 25°51’58”S, 48°43’23”W; 30.72 ha), and the Riozinho River mouth (“Riozinho”; c. 25° 52’00”S, 48°45’05”W; 3.98 ha; see Favretto et al. 2022). Folharada Island and its surroundings are located downstream, and the remaining areas are further upstream, in the São João river.
The study areas are estuarine marshes (Doody 2001: 65), tidal marshes (Reinert et al. 2007), or subtropical salt marshes (Bornschein et al. 2017). According to the criteria for the classification of Brazilian vegetation proposed by the RADAMBRASIL Project (Veloso et al. 1991), marshes are pioneer formations with fluviomarine influences. The following herbaceous species dominate: C. americanum (Amaryllidaceae), S. californicus, Fuirena robusta Kunth, Cladium mariscus (L.) Pohl (Cyperaceae), Acrostichum danaeifolium Langsd. and Fisch. (Pteridaceae), and Stephostachys mertensii (Roth) Zuloaga and Morrone (Poaceae) (Reinert et al. 2007). The herbaceous southern cattail Typha domingensis Pers. also occurs locally (Typhaceae; Fig. 1 A) together with trees such as Calophyllum brasiliense Cambess. (Clusiaceae), Annona glabra L. (Annonaceae), and Laguncularia racemosa (L.) C.F. Gaertn. (Combretaceae) (Reinert et al. 2007). The areas are characterized by mixed semi-diurnal tides (Lee and Chang 2019), with two high tides and two low tides of different amplitudes on all lunar days.
Fig. 1 (A) Subtropical salt marsh dominated by the crinum lily Crinum americanum L. and the southern cattail Typha domingensis Pers. (Crinum-Typhetum), with mangroves of Laguncularia racemosa (L.) C.F. Gaertn in the background on the left of the image (Laguncularietum; Folharada Island). (B) A subtropical salt marsh invaded by the alien Urochloa arrecta (Hack. ex T. Durand and Schinz) Morrone and Zuloaga (Urochloetum; Patch 1, Riozinho). Guaratuba Bay, Guaratuba Municipality, Paraná, southern Brazil. Photograph: Marcos R. Bornschein
We characterized the vegetation (phytophysiognomy) according to one or two dominant plant species. We consider as becoming a phytophysiognomy the vegetation with at least three plant species, but two of them in dominance, with the living aerial parts of each covering at least 20% of the soil surface. For this evaluation, we defined more than 1,000 phytosociological description plots of 1 m2 (Braun-Blanquet 1979; see Favretto et al. 2022). We also estimated the soil coverage by the living aerial parts of the plants systematically, according to Bolòs et al. (1991). We refer to each phytophysiognomy using the suffix “etum”, according to Braun-Blanquet (1979).
The studies began in January 2006 on Jundiaquara Island and at Riozinho, in 2007 at Continente, in 2009 on Folharada Island, and in 2011 in the surroundings of Folharada Island. In all areas, we carried out the work until August 2022. Between January 2006 and May 2008, we worked in the areas daily from September to February and for 6–8 days per month for the rest of the year. From 2009 onward, we worked in the areas for 3–8 days per month, every month. We did not work in the areas for six straight months (March–August) in 2020 due to the COVID-19 pandemic. Fieldwork was carried out by 2–7 people (usually three) accessing the areas by boat. On each fieldwork day, we worked from dawn until 12 p.m. or 1 p.m., and for a further 2–3.5 h in the afternoon, before dusk.
This work occurred in concert with research focused on F. acutirostris (see Reinert et al. 2012; Bornschein et al. 2015), the wren-like rushbird Phleocryptes melanops (Vieillot 1817), and the many-colored rush tyrant Tachuris rubrigastra (Vieillot 1817) (see Favretto et al. 2022). Our quantitative sampling consisted of point counts of all species of birds seen or heard within a 50 m radius of the observer (Bibby et al. 1998; see also Bornschein et al. 2017), for 15 min at each point. We established two bird censuses, each with six-point counts in subtropical salt marshes. Six points were allocated to Jundiaquara Island and Continente and six to Folharada Island and its surroundings. The edge of each point was at least 45 m from the edge of the closest point. The census was conducted on consecutive days each month, with sessions starting at sunrise and interrupted only by rain. Rainy days or extremely low tides downstream prevented us from conducting many censuses or completing bird counts at all six points of each census. The census results were recorded as punctual abundance index (PAI) values, which were obtained by summing all recorded individuals per species and dividing the number by the number of points in each census (Uezu et al. 2005).
Local impact of Urochloa arrecta
In patches in the studied areas, the alien African grass Urochloa arrecta (or Brachiaria subquadrippara) was the dominant species (Urochloetum; Fig. 1B). In these patches, native species co-occurred with this alien species but at low frequencies, because U. arrecta had become a dominant species due to the accumulation of stolons that shade and crush native vegetation, killing native plants (Fig. 2B; Reinert et al. [2007]). This process replaces the normal salt marsh vegetative structure and impairs bird displacement in the vegetation understory by obstructing ground space with intermixed stems that prevent movement through the marsh. (Fig. 2 A; Reinert et al. [2007]). Urochloa arrecta also advances on the water as floating banks of vegetation that are sometimes ripped out by floods and transferred to other areas previously free of their presence (Reinert et al. 2007).
Fig. 2 Comparison of the vertical structure of a subtropical salt marsh (A) dominated by the crinum lily Crinum americanum L. and the southern cattail Typha domingensis Pers. (Crinum-Typhetum) with a place (B) dominated by the alien Urochloa arrecta (Hack. ex T. Durand and Schinz) Morrone and Zuloaga (Urochloetum; Patch 1) and hosting the California bulrush Schoenoplectus californicus (C.A. Mey) Soják. In B, the edge of the vegetation was resulted from partial cutting, due to management intervention. Guaratuba Bay, Guaratuba Municipality, Paraná, southern Brazil. Photographs: Marcos R. Bornschein
Management of Urochloa arrecta
Urochloa arrecta was mechanically managed to ensure its complete local eradication, with permissions from the Instituto Ambiental do Paraná (357/11) and Instituto Água e Terra (12.20). The eradication was achieved by clear-cutting vegetation with brush cutters and stacking plant biomass without using herbicides (Bornschein 2013). The stacked biomass was contained with stakes to prevent movement by high tides (Fig. 3).
Fig. 3 Management of Urochloa arrecta (Hack. ex T. Durand and Schinz) Morrone and Zuloaga that invaded the subtropical salt marsh in southern Brazil. Management consisted of clear-cutting the vegetation with brush cutters and piling up the biomass, which was stacked with bamboo supports to prevent it from being carried away by high tides (since the water usually almost reached the tops of the highest piles). The managed area was inspected to manually remove of sprouts of exotic grass up to six times, and the biomass piles were turned over regularly up to six times to ensure the death of sprouts. Photographs: Marcos R. Bornschein
Cut and stacked piles of biomass were mixed up to six times to isolate living material by pulling dead vegetation from the interior of the pile to the edge and removing and reburying rooted and sprouted fragments (Bornschein 2013). Urochloa arrecta does not form seed banks locally, which facilitated successful management techniques. As a fast-growing pioneer formation, with the sprouting of plants or germination of seeds, natural regeneration fully developed within about six months of management commencing. In 7 months, the landscape was completely changed, and in 10 months, the native vegetation covered the land again, free of alien species (Bornschein 2013). The resulting environment following the intervention was dominated by S. californicus. This is common in tidal marsh environments, especially along riverbanks (Bornschein 2001; Reinert et al. 2007). We delimited and measured polygons of areas invaded by U. arrecta and monitored them with the Google Earth Pro program (7.3.3.7786) for each year (2003–2006) for which images were available (Table 1).
Table 1 Sizes of Urochloa arrecta (Hack. ex T. Durand & Schinz) Morrone & Zuloaga patches (Urochloetum) on subtropical salt marshes before and after management in Guaratuba Bay, Paraná, southern Brazil. We present only the years with the availability of images from the Google Earth program (7.3.3.7786), used to measure the area of the patches. The years in which Rallus longirostris Boddaert, 1783 was recorded by patch are highlighted in bold. We also indicate the sizes of the patches of U. arrecta in 2003 as a reference value prior to the beginning of the fieldwork (in 2006)
Year Patches dominated by Urochloa arrecta (in bold the ones with records of Rallus longirostris)
#1a #2a #3a #4b
2003 0.38 ha 0.00 ha 0.11 ha 0.01 ha
2010 1.23 ha 0.22 ha 0.17 ha 0.1 ha
2012 1.00 ha 0.32 ha 0.18 ha 0.13 ha
2014 0.59 ha 0.45 ha 0.23 ha 0.15 ha
2016 0.01 ha 0.57 ha 0.00 ha 0.16 ha
2017 0.00 ha 0.40 ha 0.00 ha 0.01 ha
2018 0.01 ha 0.28 ha 0.00 ha 0.01 ha
2019 0.02 ha 0.30 ha 0.00 ha 0.00 ha
2020 0.25 ha 0.46 ha 0.00 ha 0.00 ha
2021 0.00 ha 0.00 ha 0.00 ha 0.00 ha
a Riozinho
b Continente
Results
Records of Rallus longirostris and nesting points
We recorded Rallus longirostris for the first time in the study region in 2007, one year after the beginning of our studies in Guaratuba Bay. We observed two individuals vocalizing in duet in a patch dominated by U. arrecta (Urochloetum) in Riozinho (Patch 1; Fig. 4). In 2010 this patch of Urochloetum covered 1.23 ha (Table 1). This bird was always observed in Patch 1, where it also nested, and in the surrounding salt marshes free of U. arrecta (Fig. 4 C). Two photographs on the WikiAves website (https://www.wikiaves.com.br/), one from 2007 and another from 2012 (WA280252 and WA832943)—document the presence of the bird in the surroundings of Patch 1.
Fig. 4 The area studied in 2006–2022 in Guaratuba Bay, Guaratuba Municipality, Paraná, southern Brazil (polygons with yellow limits; A–B), B) Indications of patches dominated by the alien Urochloa arrecta (Hack. ex T. Durand and Schinz) Morrone and Zuloaga (at their 2010 size; white polygons) C) Maximum area with the occurrence of Rallus longirostris Boddaert, 1783 (red polygons). Map generated with ArcGIS Pro. Imagery source: Instituto Brasileiro de Geografia e Estatistica (IBGE), National Aeronautics and Space Administration (NASA), National Geospatial-Intelligence Agency (NGA), United States Geological Survey (USGS), Esri, HERE, Garmin, Foursquare, GeoTechnologies, Inc, Maxar, Ministry of Economy, Trade, and Industry (METI)/NASA
In 2010, we recorded R. longirostris at the Continente in a 0.10-ha patch of Urochloetum (Patch 4; Table 1; Fig. 4), three years after the beginning of the studies in this area. We observed three nests containing eggs in subsequent years on a mass of U. arrecta stolons. We also observed lone individuals or pairs of R. longirostris in surrounding salt marshes free of U. arrecta up to 400 m away from Patch 4 (Fig. 4 C).
In 2016, we recorded R. longirostris for the first time in a 0.57-ha patch of Urochloetum (Patch 2; Table 1; Figs. 4), 10 years after the beginning of our studies in this area. On Patch 3, with up to 0.23 ha of Urochloetum (Table 1; Fig. 4), we recorded no R. longirostris.
In 2012, we started managing U. arrecta in Patch 1 (see Table 1). In 2015, we continued to record R. longirostris in this patch (Table 1), and on one occasion, we observed R. longirostris feeding on Uca mordax on the mudflat, but chased away by management brush cutters. The bird was nesting on top of a biomass pile of managed vegetation (but the eggs were preyed upon). In 2016, Patch 1 of Urochloetum was practically eliminated, and since then, R. longirostris has not been recorded at this location. At the end of 2016, we started managing U. arrecta in Patch 4, practically eliminating this grass in 2017, after which we no longer recorded R. longirostris there (Table 1). During 2017 and 2018, we managed U. arrecta on Patch 2, but we were unable to eliminate it before financial resources expired. When management ended, the Urochloetum patch started to expand again (Table 1). Finally, we resumed management in 2020, eliminating U. arrecta in the same year, and recording our last observation of R. longirostris in the study region (Table 1).
During the censuses (N = 151; Table S1), we recorded R. longirostris occasionally in 2013–2015, in small numbers in subtropical salt marshes, but only in censuses conducted near patches of Urochloetum (Table 2). On Folharada Island and in the surrounding area, where U. arrecta was absent, we recorded no R. longirostris (Table 2; Fig. 4). In this area, we started our studies in 2009 and the censuses in 2011.
Table 2 Average of Rallidae punctual abundance index (PAI) recorded in censuses in subtropical salt marshes in Guaratuba Bay, Paraná, southern Brazil. There was N = 12 points of 50 m radius, with N = 6 points per census in Continente and Jundiaquara Island (upstream region) and N = 6 per census in Folharada Island and surroundings (downstream region). PAI = sum of individuals of each species recorded by census divided by the number of count point (N = 6). We indicated the N of censuses made by region per year
Year / region N Mangrove rail
Rallus longirostris
(Boddaert, 1783) Blackish rail
Pardirallus nigricans
(Vieillot, 1819) Gray-necked wood-rail
Aramides cajaneus
(Statius Muller, 1776) Rufous-sided crake
Laterallus melanophaius
(Vieillot, 1819) Common gallinule
Gallinula galeata
(Lichtenstein, 1818)
Upstream
2011 3 0.00 1.11 0.00 0.00 0.00
2012 9 0.00 2.18 0.00 0.00 0.00
2013 12 0.01 2.72 0.00 0.00 0.01
2014 12 0.08 2.75 0.00 0.00 0.00
2015 12 0.04 2.86 0.00 0.00 0.04
2016 12 0.00 2.25 0.00 0.00 0.01
2017 10 0.00 1.85 0.00 0.00 0.00
2018 5 0.00 2.83 0.00 0.00 0.03
2022 2 0.00 2.83 0.00 0.00 0.00
Downstream
2011 3 0.00 2.00 0.11 0.00 0.00
2012 10 0.00 1.97 0.12 0.02 0.00
2013 12 0.00 0.92 0.03 0.00 0.00
2014 12 0.00 1.07 0.08 0.01 0.04
2015 11 0.00 0.95 0.05 0.00 0.06
2016 10 0.00 1.03 0.07 0.00 0.05
2017 9 0.00 0.93 0.04 0.00 0.02
2018 5 0.00 0.57 0.10 0.00 0.03
2022 2 0.00 0.92 0.00 0.00 0.17
Use of the environment by Rallus longirostris and its relationship with other Rallidae
We observed R. longirostris occupying mudflats where the management had removed U. arrecta from patches of Urochloetum, and in native subtropical salt marsh vegetation. The subtropical salt marshes phytophysiognomies used by R. longirostris were the ones dominated by S. californicus (Schoenoplectetum), C. americanum and S. californicus (Crinum-Schoenoplectetum), C. americanum and F. robusta (Crinum-Fuirenetum), C. americanum and T. domingensis (Crinum-Typhetum), C. americanum and C. mariscus (Crinum-Cladietum), and, finally, by A. danaeifolium (Acrostichetum). Regarding these phytophysiognomies, we observed R. longirostris in the lower layer of the vegetation (Fig. 5 A), occupying the sediment between the plants and accumulated dead leaves, and in the intermediate layer, which contained a high density of live and dead leaves (Fig. 5 A). We did not observe R. longirostris in the upper layer of vegetation, where the plants were vertical and less dense than in the lower layers. In Urochloetum, we observed R. longirostris only on top of the plant mass. Because this bird does not occupy areas with dense stolons of U. arrecta (Fig. 5B), the Urochloetum surface functions as the lower layer of vegetation, which is quite open and exposed. It was in this layer that we observed the R. longirostris nests (see above). The remaining native vegetation in Urochloetum constitutes the upper layer, with no intermediate layer.
Fig. 5 Schematic representation of subtropical salt marsh vegetation layers (A) and an area invaded and dominated by the alien Urochloa arrecta (Hack. ex T. Durand and Schinz) Morrone and Zuloaga (B), according to its use by the mangrove rail Rallus longirostris. Blue vertical bars indicate the lower layer, red vertical bars indicate the intermediate layer, and black vertical bars indicate the upper layer. Created with BioRender.com
We also observed blackish rail Pardirallus nigricans (Vieillot 1819), associated with the same phytophysiognomies and vegetation layers as R. longirostris, except on Urochloetum and mudflats (Fig. 6). We observed that coexisted only in Schoenoplectetum, with no evidence of aggression between them (Fig. 6). Pardirallus nigricans is the most abundant non-migratory species in the subtropical salt marshes (Table S2), and we saw this bird nesting in the intermediate layers of vegetation in all phytophysiognomies, except Schoenoplectetum and, obviously, Urochloetum. Other Rallidae are exceptional in subtropical salt marshes (Table 2) and we never observed them coexisting with R. longirostris.
Fig. 6 Schematic representation of subtropical salt marshes invaded and not invaded by the alien Urochloa arrecta (Hack. ex T. Durand and Schinz) Morrone and Zuloaga (right third) relative to the occurrence and nidification of Rallus longirostris Boddaert, 1783 and Pardirallus nigricans (Vieillot, 1819). Created with BioRender.com
Discussion
This long-term study allowed us to verify (1) the appearance of a population of R. longirostris occupying and nesting in patches dominated by the exotic grass U. arrecta; (2) an increase in the population’s local distribution, occupying of other patches dominated by this plant and surrounding salt marshes free from the alien species; and (3) its local disappearance after the eradication of the plant, in salt marshes free from the alien plant. This constitutes a further case of a native species benefiting from an alien species invasion (Overton et al. 2014; Casazza et al. 2014) and provides evidence of a preference for an altered environment over a natural environment for nesting. This suggests that the subtropical salt marsh structurally impedes the nesting of R. longirostris (Hypothesis 1) or there is an ecological impediment to nesting in an environment not invaded by U. arrecta (Hypothesis 2).
Regarding Hypothesis 1, the most abundant resident bird at the study sites was P. nigricans (Table S2), which is similar in size to R. longirostris (Dunning 2008) and nests in subtropical salt marshes (Fig. 6). Locally, these two birds build nests as baskets constructed from fragments of native herbaceous plants of similar size, supported above the herbaceous vegetation (4 nests of R. longirostris; c. 150 nests of P. nigricans [unpublished data]). Thus, subtropical salt marshes are environments in which herbaceous plants support the construction of relatively large birds nests. However, it is known that due to rising tides, tidal marshes have far fewer nesting sites than foraging areas, and this characteristic shape the social organization of the environment (Post 1974). So, there is a high likelihood of disputes over reproductive sites between these birds in subtropical salt marshes (Hypothesis 2), with P. nigricans dominating R. longirostris. We suggest that R. longirostris could have occupied patches of Urochloetum as vacant nesting niches to avoid disputes with P. nigricans. There were other rail species in the subtropical salt marshes of the study region, but they occur in low numbers and only occasionally (Table 2); therefore, we did not expect that any ecological interaction with R. longirostris that influence its local ecology and preferences.
Rallus longirostris and P. nigricans do not seem to use the interiors of areas dominated by U. arrecta, possibly due to the high density of stolons (Fig. 2B) limiting their movements and access to food (MRB per. obs.). The non-use of this part of the very dense vegetation means that the invaded environment, regarding to its use by the rails, has only two layers—not three, as in non-invaded environments (Fig. 5). Hence, the invaded areas have vegetation with reduced structural complexity. Likewise, the lower and upper layers of areas invaded by U. arrecta are quite open (Fig. 5), which seems to be why P. nigricans do not occur or nest there. Rallus longirostris, in turn, seems to prefer less dense vegetation, since it breeds in the lower layer of invaded areas, and occurs in mangroves and even on mudflats.
The layers of native vegetation in the phytophysiognomies in which R. longirostris occurs comprise: a lower layer with low to moderate vegetation density, an intermediate layer with moderate to high vegetation density, and an upper layer with low vegetation density (Fig. 6). As a consequence of the rosette shape of this species, the phytophysiognomies where C. americanum is dominant are characterized by increments of leaves overlap in the intermediate layer of the vegetation, forming several “Ys” side by side. The top of each “Y” supports the dead leaves of other plant species, contributing to the high density of vegetation in the intermediate layer. The erect plants T. domingensis and C. mariscus develop leaves from their stems, which touch at mid-height of the vegetation and support dead leaves, contributing to increased vegetation density in the intermediate layer of phytophysiognomies where these species are the dominant plant species. In Schoenoplectetum, although S. californicus has smooth leaves without ramification, the three layers still have different vegetation densities because the leaves of intersect, forming multiple intersecting “Xs”. Additionally, the points of intersection of S. californicus leaves also accumulate dead leaves, contributing to increased density in the intermediate layer. However, this density tends to be much lower than that associated with other phytophysiognomies (Teixeira and Bornschein unplublished data).
Birds such as R. obsoletus generally prefer more complex environments for nest building (Rush et al. 2010). The apparent advantages of nesting in the lower layer in Urochloetum are the support for the nests and the buoyancy of the biomass under high-tide conditions, which could potentially reduce reproductive losses from flooding—an impact that is quite significant for wetland birds (Marshall and Reinert 1990; Shriver 2002; Greenberg et al. 2006; Reinert 2006; Norbdy et al. 2009). In the study region, high tides flood the nests of F. acutirostris (Reinert et al. 2012), the least bittern Ixobrychus exilis (Gmelin, 1789), P. nigricans, Phleocryptes melanops, the yellow-chinned spinetail Certhiaxis cinnamomeus (Gmelin, 1788), Tachuris rubrigastra, and the Brazilian tanager Ramphocelus bresilia (Linnaeus, 1766; MRB per. obs.).
The principle of equal opportunity (MacArthur 2002) predicts that the occupation of environments by species depends on the relationship between the resources in those habitats and the pressure to use them, meaning that individuals to a certain extent prefer less competitive environments, could be a factor in the choice of the environment by R. longirostris and P. nigricans and their consequent nesting in patches of U. arrecta by the former. The occupation of environments depends on competition (Cody 1985), and few species can occupy resource-poor habitats, such as patches of Urochloetum with impoverished flora and a simple vegetation structure, which leads to reduced competition (Cody 1985). Rallus longirostris could have benefited from the occupation of patches containing exotic plants. Although R. longirostris and P. nigricans coexist in vegetation free of exotic plants without apparent mutual aggression, even when they are side by side, the similarity between these species suggests that they compete silently without obvious aggression (MacArthur 2002).
Benefits were verified for the congeneric R. obsoletus following the invasion of a hybrid form of Spartina grass, which increased the survival rate of individuals by offering refuge against predators (Overton et al. 2014). Following the introduction of an exotic-plant eradication program, the bird population declined (McBroom 2013), as observed in the present study of R. longirostris. Conversely, biological invasions of clonal grass Phragmites australis (Cav.) Trin. ex Steud. in Canada had long-term negative impacts on birds, decreasing species richness and changing community compositions (Robichaud and Rooney 2017).
Rallus longirostris is not threatened with extinction either globally (BirdLife International 2016) or in Brazil (Ordinance 148 of the Brazilian MMA, June 7 2022), but it has been deemed VU in that country (Vieira 2015). Regionally, R. longirostris is considered VU in the state of Paraná (Decree 1.797/2018 of the State of Paraná, November 22, 2018), where the present research was carried out. The fact that R. longirostris has benefited from areas dominated by an exotic plant, allowing it to colonize a previously uncolonized environment (Vieira 2015), does not seem to justify interrupting or preventing the management of U. arrecta. It is a distinctly aggressive species (Kissman 1997; Thomaz et al. 2009) that reduces the functional diversity of native species due to the presence of allelopathic compounds and its high energy efficiency, resistance to drought periods, and high rates of germination, growth, regrowth, and regeneration (Freitas and Pivello 2005; Bianchini Jr. et al. 2010). The impacts of this grass on native macrophyte (Michelan et al. 2010) and fish (Casatti et al. 2009; Carniatto et al. 2013) communities have been reported, as well as the impact of habitat suppression on F. acutirostris (Reinert et al. 2007)—a species at risk of extinction in Brazil (Ordinance 148 of the Brazilian MMA, June 7, 2022). Moreover, the high cost of management and the difficulty of raising funds for this activity make it impossible to implement a program with the objective of eradicating some areas invaded by U. arrecta, but not all of them to sustain a population of R. longirostris. Permanent management of the Urochloetum to keep them with the same extension would make the program very expensive and unrealistic. The cost of restoring 1 ha dominated by the alien U. arrecta varies from 13,404 to 29,356 USD, depending particularly on the traveling distance by boat to access the areas requiring management (Teixeira and Bornschein unpublished data).
The use of subtropical salt marshes and areas dominated by exotic grasses by R. longirostris demonstrates ecological plasticity. With the advancing invasion of U. arrecta in estuaries, this new nesting niche of R. longirostris may increase its population and warrant reversion to its previously endangered status (Vieira 2015). Conversely, invasive plants can be ecological traps, attracting species but not sustaining them in the long term (Norbdy et al. 2009; Kloskowski 2012; Stinson and Pejchar 2018). Long-term monitoring of different estuaries is encouraged because it may reveal this or other population trends of R. longirostris, as confirmed by those presented here, in addition to allowing a deeper assessment of the impacts of U. arrecta invasions.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Supplementary Material 1
Supplementary Material 2
Acknowledgements
We obtained management permissions from the Instituto Ambiental do Paraná (357/11) and Instituto Água e Terra (12.20). This study was supported by Fundação Grupo Boticário de Proteção à Natureza (FGBPN; projects 0682/20052; 0740/20071; 0908_20112; BL0001_20111, 0004_2012, and 1110_20172), Fundo Brasileiro para a Biodiversidade (FUNBIO), and 1ª Vara Federal de Paranaguá (process 50005063420184047008). Most of these projects were developed by Mater Natura—Instituto de Estudos Ambientais, with special financial management support from Helena Zarantonielli. Ricardo Belmonte-Lopes, Daiane D. Sobotka, Cláudia Golec, Leandro Corrêa, Mario Arthur Favretto, Tiago Machado-de-Souza, and Ailton Degues helped with the fieldwork. We thank the two anonymous reviewers who carefully reviewed our manuscript and made valuable suggestions for improving the quality of the study.
Author contributions
Conceptualization: Marcos R. Bornschein. Field procedures: Marcos R. Bornschein, Larissa Teixeira, Bruno de Morais Guerra, Bianca L. Reinert and Giovanna Sandretti-Silva. Funding acquisition: Bianca L. Reinert. Field administration: Marcos R. Bornschein, Larissa Teixeira, Bianca L. Reinert and Giovanna Sandretti-Silva. Writing: Marcos R. Bornschein, Larissa Teixeira, Bruno de Morais Guerra, Bianca L. Melchiori and Giovanna Sandretti-Silva. Preparing figures and/or tables: Marcos R. Bornschein, Larissa Teixeira and Bruno de Morais Guerra.
Funding
This study was supported by Fundação Grupo Boticário de Proteção à Natureza (FGBPN; projects 0682/20052; 0740/20071; 0908_20112; BL0001_20111, 0004_2012, and 1110_20172), Fundo Brasileiro para a Biodiversidade (FUNBIO), and 1ª Vara Federal de Paranaguá (process 50005063420184047008).
Data availability
The raw data in this article are included in the tables and figures.
Statements & declarations
Competing interests
The authors have no relevant competing interests to disclose.
†Bianca L. Reinert In memoriam.
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Favretto MA, Machado-de-Souza T, Golec C, Reinert BL, Bornschein MR (2022) Habitat selection in many-colored rush tyrant (Tachuris rubrigastra) and wren-like Rushbird (Phleocryptes melanops) in the subtropical salt marshes of Brazil. Stud Neotrop Fauna Environ. https://doi.org/10.1080/01650521.2022.2101351 .
Freitas GK Pivello V Freitas GK Pivello VR A ameaça das gramíneas exóticas à biodiversidade O o cerrado Pé-de-Gigante: ecologia e conservação - parque Estadual de Vassununga 2005 São Paulo SMA 234 246
Gedan K Altieri A Bertness MD Uncertain future of New England salt marshes Mar Ecol Prog Ser 2011 434 229 237 10.3354/meps09084
Goodenough A Are the ecological impacts of alien species misrepresented? A review of the “native good, alien bad” philosophy Community Ecol 2010 11 1 13 21 10.1556/ComEc.11.2010.1.3
Greenberg R Elphick C Nordby JC Gjerdrum C Spautz H Shriver G Schmeling B Olsen B Marra P Nur N Winter M Flooding and predation: trade-offs in the nesting ecology of tidal-marsh sparrows Stud in Avian Biol 2006 32 96 109
Hobbs RJ Higgs E Harris JA Novel ecosystems: implications for conservation and restoration Trends Ecol Evol 2009 34 11 599 605 10.1016/j.tree.2009.05.012
ICMBio Livro vermelho da fauna brasileira ameaçada de extinção 2018 Brasília ICMBio & MMA
Kissman KG Plantas infestantes e nocivas 1997 São Paulo BASF
Lee SH Chang YS Classification of the global tidal types based on auto-correlation analysis Ocean Sci 2019 52 2 279 286 10.1007/s12601-019-0009-7
Kloskowski J Fish stocking creates an ecological trap for an avian predator via effects on prey availability Oikos 2012 121 10 1567 1576 10.1111/j.1600-0706.2011.19942.x
Lees AC Bell DJ A conservation paradox for the 21st century: the european wild rabbit Oryctolagus cuniculus, an invasive alien and an endangered native species Mammal rev 2008 38 4 304 320 10.1111/j.1365-2907.2008.00116.x
Levin LA Neira C Grosholz ED Invasive cordgrass modifies wetland trophic function Ecology 2006 87 2 419 432 10.1890/04-1752 16637367
MacArthur RH Geographical ecology: patterns in the distribution of species 2002 Princeton Princeton University Press
McBroom J California Clapper Rail surveys for the San Francisco estuary invasive Spartina Project 2013 2013 Oakland State Coastal Conservancy
Maley JM, Brumfield RT(2013) Mitochondrial and next-generation sequence data used to infer phylogenetic relationships and species limits in the Clapper/King Rail complex. Condor115(2):316–329. 10.1525/cond.2013.110138
Marshall RM Reinert SE Breeding ecology of seaside sparrows in a Massachusetts salt marsh Wilson Bull 1990 102 501 513
Meyerson LA, Mooney HA (2007) Invasive alien species in an era of globalization. Front Ecol Environ 5(4):199–208. 10.1890/1540-9295(2007)5[199:IASIAE]2.0.CO;2
Michelan TS Thomaz SM Mormul RP Carvalho P Effects of an exotic invasive macrophyte (tropical signalgrass) on native plant community composition, species richness and functional diversity Freshw Biol 2010 55 1315 1326 10.1111/j.1365-2427.2009.02355.x
Norbdy JC Cohen NA Beissinger SR Effects of a habitat-altering invader on nesting sparrows: an ecological trap? Biol Invasions 2009 11 565 575 10.1007/s10530-008-9271-9
Overton CT Casazza ML Takekawa JY Strong DR Holyoak M Tidal and seasonal effects on survival rates of the endangered California Clapper Rail: does invasive Spartina facilitate greater survival in a dynamic environment? Biol Invasions 2014 16 1897 1914 10.1007/s10530-013-0634-5
Post W Functional analysis of space-related behavior in the seaside sparrow Ecology 1974 55 564 575 10.2307/1935147
Reinert BL Belmonte-Lopes R Bornschein MR Sobotka DD Corrêa L Pie MR Pizo MA Nest and eggs of the Marsh Antwren (Stymphalornis acutirostris): the only marsh-dwelling thamnophilid Wilson j ornithol 2012 124 2 286 291 10.1676/11-099.1
Reinert BL Bornschein MR Firkowski C Distribuição, tamanho populacional, hábitat e conservação do bicudinho-do-brejo Stymphalornis acutirostris Bornschein, Reinert e Teixeira, 1995 (Thamnophilidae) Rev Bras Ornitol 2007 15 493 519
Reinert SE(2006) Avian nesting response to tidal-marsh flooding: literature review and a case for adaptation in the red-winged blackbird. In: Greenberg R., Maldonado JE, Droege S, McDonald MV (eds). Terrestrial vertebrates of tidal marshes: Evolution, ecology, and conservation. Stud Avian Biol 32:77–95
Robichaud CD Rooney RC Long-term effects of a Phragmites australis invasion on birds in a Lake Erie coastal marsh J Great Lakes Res 2017 43 3 141 149 10.1016/j.jglr.2017.03.018
Rush AS Woodrey MS Cooper RJ Variation in the nesting habitats of Clapper Rails in tidal marshes of the northern Gulf of Mexico Condor 2010 112 2 356 362 10.1525/cond.2010.090078
Schlaepfer MA Runge MC Sherman PW Ecological and evolutionary traps Trends Ecol Evol 2002 17 474 480 10.1016/S0169-5347(02)02580-6
Shriver WG(2002) Conservation ecology of salt marsh birds in New England. Dissertation, State University of New York
Simberloff D Given the stakes, our modus operandi in dealing with invasive species should be “guilty until proven innocent” Conserv Magazine 2007 8 1819
Stinson LT Pejchar L The effects of introduced plants on songbird reproductive success Biol Invasions 2018 20 1403 1416 10.1007/s10530-017-1633-8
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Vitousek PM Antonio CMD Loope LL Rejmánek M Westbrooks R Introduced species: a significant componente of human-caused global change NZJ Ecol 1997 21 1 16
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| 0 | PMC9735195 | NO-CC CODE | 2022-12-14 23:29:53 | no | Wetlands (Wilmington). 2022 Dec 8; 42(8):124 | utf-8 | Wetlands (Wilmington) | 2,022 | 10.1007/s13157-022-01642-7 | oa_other |
==== Front
Lancet Reg Health Am
Lancet Reg Health Am
Lancet Regional Health. Americas
2667-193X
The Authors. Published by Elsevier Ltd.
S2667-193X(22)00225-3
10.1016/j.lana.2022.100408
100408
Viewpoint
Health in colour: Black women, racism, and maternal health
Dayo Elizabeth a∗
Christy Kayonne b
Habte Ruth c
a Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
b Department of Sociology, University of Michigan, Ann Arbor, MI, USA
c Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
∗ Corresponding author. University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada.
10 12 2022
10 12 2022
10040814 3 2022
16 11 2022
21 11 2022
© 2022 The Authors
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Keywords
Black women
Maternal health
Race-based data
Canadian healthcare
Medicalized racism
Colourblind healthcare
==== Body
pmcIntroduction
The COVID-19 pandemic, in addition to the racial reckoning that took place in the summer of 2020, has placed racial disparities at the forefront of contemporary discourses. Mounting research suggests that Black women bear a disproportionate burden of global maternal mortality and morbidity rates. These disparities in maternal health have persisted through the coronovirus pandemic, as new and existing barriers to healthcare access and utilization have emerged.1 According to the CDC, Black mothers in the United States (U.S.) die at three-to-four times the rate of white mothers,2 mirroring statistics observed in other settings, including the United Kingdom (U.K.).3 In Canada, national vital statistics report that the country's Maternal Mortality Ratio (MMR) rates remain one of the lowest in the world.4 Unlike the U.S. and U.K., who collect and report statistics on racial disparities in women's health, few Canadian health agencies collect racial data – an approach that reflects hegemonic ‘colour-blind’ attitudes towards race in Canada. Structural racism, which refers to historical, institutional, and cultural practices that reinforce racial inequities, can manifest through exclusions of minority populations in health data.5
Applying a racial justice lens is critical to contextualizing and addressing racial disparities in maternal health in Canada. To this end, the purpose of this article is to highlight the drivers of the black maternal mortality crisis, explore the shortfalls of Canada's colourblind approach to healthcare for racialized pregnant people, and to advocate for the collection of disaggregated racial data to better support advancements in Black maternal health.
Historical & contemporary drivers
Current racial disparities in maternal health originate from the deep roots that American gynaecology has with anti-Black racism. An understanding of this history is necessary to contextualize the maternal health disparities reflected by race-based data. The historical wrongdoings of the field of Obstetrics & Gynaecology encompass the exploitation, experimentation, and abuse of enslaved Black women. James Marion Sims is credited as the “Father of Modern Gynaecology” in part for pioneering a surgical technique to repair vesicovaginal fistula.6 It is widely known that Sims performed his crude experiments on enslaved Black women without any form of anaesthesia, due to his misguided and racist beliefs that Black people did not experience pain like their white counterparts.6 Few know the roots of the modern Caesarean section, a procedure perfected on Black enslaved women by Francois-Marie Prevost, the “Father of the Caesarean Section.”7 It is critical for maternal health providers to understand that present-day inequities in women's health are, in part, shaped by the legacy of these historical systems of medicalized racism.
Decolonizing health research through the collection of race-based data, also necessitates a review of contemporary drivers of Black maternal mortality. The intersection of race with other social determinants, including education and socioeconomic status, is especially relevant to this discussion. Poor maternal health outcomes for Black women exist across educational and social economic factors. Current literature reports that a college-educated Black woman is three times more likely to experience severe maternal complications than a white woman without a high school education.8 The impact of social inequity on Black health is also supported by Geronimus’ weathering hypothesis. The weathering theory suggests that Black women experience accelerated ageing and poorer health outcomes, because of their cumulative exposure to racism.9 To support this psychosocial framework, Geronimus published a study on telomere length, which reported that black women between the ages of 49–55 were an estimated 7.5 years older, biologically, than white women of the same chronological age.9 These findings highlight the important contributions that systemic racism has on Black women's health – namely, in compromising health. Perceptions related to the quality of care are important determinants of black maternal health. Studies have shown that relative to white women, black women receive lower quality of obstetrical care, including the undertreatment of pain,10 , 11 delayed or inaccurate diagnoses,12 and feeling mistreated or ignored by their healthcare providers.12 Such factors are of concern, considering that most pregnancy-related deaths are preventable and are largely due to provider-level practices.13 , 14 In summary, this research indicates that health professionals must recognize how their roles as gatekeepers to health services and treatment disproportionally harm Black women.
Race-evasive health
Understanding the unique social context in which such racial inequalities emerge is imperative, as structural racism manifests uniquely across time and space.15 Structural racism is pervasive in Canada institutions, as evidenced by Canada's race-evasive approach to health care delivery. Race-evasiveness, a broad ideological perspective that captures ideas such as “colourblind racism”16 and “laissez-faire racism,”17 denies, minimizes, and ignores how race, as a socially constructed category of difference, structures inequalities. Race evasiveness constitutes the dominant discourse on race in Canada and is reflected in Canadian healthcare practices. While Canada's universal healthcare system is understood to represent a national commitment to health equity, there is evidence that racial inequities do exist within the Canadian healthcare system. A 2005 study by researchers at McGill University found that Black women have substantially higher rates of preterm birth than white women, similar to patterns of maternal health disparities reported in the U.S.18 Yet still, there remains a dearth of race-based data on maternal and infant health in Canada.
There is robust evidence of the adverse implications of racial evasive ideologies. Emerging studies have found that evasiveness reduces sensitivity to racism and discrimination19 and subverts institutional diversity efforts.20 , 21 One study also found that physicians who adhere to evasive ideologies were more likely to use race in medical decision-making.22 These findings are consistent with reports of implicit bias among healthcare professionals, which is positively correlated with lower quality of care.23 A colourblind approach to healthcare also minimizes the significance of race within the healthcare context.24 For pregnant Black women in Canada, this often leads to poor healthcare experiences, such as providers not being knowledgeable about health issues more prevalent among Black communities, and providers not being able to recognize symptoms on darker skin.24 By refusing to acknowledge race, whiteness is usually the assumed norm. This often results in the health interests of Black women being disregarded in medical encounters.
Given the pervasiveness of structural racism, we can look at examples of how race-based data has addressed health disparities internationally. The documentation of high rates of HIV among African Americans and Hispanics in the U.S. has helped stimulate the development of federal programs that target these racially and ethnically minoritized groups at risk.25 Similarly, in response to published reports of black maternal mortality in the U.K., an All-Party Parliamentary Group consisting of members of the House of Commons and the House of Lords, alongside community leaders, was formulated to tackle institutional racism in the UK healthcare system.26 Following reports of Influenza vaccine hesitancy among racialized populations in Canada, the TAIBU Community Health Center, which serves predominantly Black populations, implemented culturally relevant resources for Black Ontarians. These measures were found to increase influenza vaccine rates from 8% in 2013 to 53% in 2018.27
As the research reviewed in this viewpoint shows, race-based data help provide measurable indicators of health disparities. Canada's lack of race-based data perpetuates systemic racism by evading any responsibility to rectify contemporary health inequities. Afterall, one cannot address a problem that has not been identified. As such, the real extent of racial disparities in maternal outcomes in Canada are not yet known. Acknowledging the impact of ‘Blackness’ on health outcomes, healthcare access and delivery, is a needed critical step to improving the quality of healthcare.
Recommendations
Addressing inequities in Black maternal health requires the collection and dissemination of racially disaggregated data. In Canada, the term visible minority has been adopted in health research as a way of identifying “persons, other than Aboriginal peoples, who are non-Caucasian in race or non-white in color.”28 While this proxy for racialization was established to reduce inequalities resulting from perceptions of race, it nevertheless reinforces systemic racism in healthcare. The rationale for data disaggregation is well established in the literature and offers compelling evidence that homogenizing the experiences of racialized people under a single umbrella fails to account for variations in health outcomes for different subgroups.29 Disaggregated race-based data is therefore crucial to providing targeted health interventions and legislative change for Black maternal health. Special considerations must also be taken for Black populations within national proposals for race-based data collection. Hassen et al. noted that the process of race-based data collection “can be unsafe for and exploitative of certain groups”.30 As such, it is recommended that data collection occurs in partnership with Black communities, to mitigate exploitation and facilitate collective ownership. Decolonizing health data also requires that Black-led research is supported. As such, Canadian health agencies should also seek to engage members of the Black community in the collection, dissemination, and ownership of their racial and ethnic data.
Following the height of the pandemic, there has been some groundwork in advancing racial data in Canada. Most recently, the Canadian Institute for Health Information (CIHI) released guidelines on the collection of race-based data.31 While this publication demonstrates progress in prioritizing racial data, the adoption of this collection system remains voluntary. As such, we recommend that the collection of race-based data be mandated by all provincial governments in Canada.
Conclusion
In conclusion, the responsible collection of race-based data is imperative to have an accurate understanding of racial disparities in health within the Canadian context. Not only this, but the collection of such data must incite action. It must be used responsibly by clinicians, administrators, policy, and other stakeholders to address the health outcomes of Black, Indigenous, and other people of color in Canada.
Contributors
Elizabeth Dayo – Writer & Editor.
Kayonne Christy – Writer & Editor.
Ruth Habte – Editor.
Declaration of interests
No conflicts of interest to disclose.
==== Refs
References
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3 Limb M. Disparity in maternal deaths because of ethnicity is “unacceptable" BMJ 2021 372
4 Allen V.M. Campbell M. Carson G. Maternal mortality and severe maternal morbidity surveillance in Canada J Obstet Gynaecol Can 32 12 2010 1140 1146 21176325
5 Bailey Z.D. Krieger N. Agénor M. Graves J. Linos N. Bassett M.T. Structural racism and health inequities in the USA: evidence and interventions Lancet 389 10077 2017 1453 1463 28402827
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7 Owens D.C. Medical Bondage: Race, Gender, and the Origins of American Gynecology 2017 The University of Georgia Press Retrieved from: https://library.oapen.org/bitstream/handle/20.500.12657/30659/644220.pdf?sequence=1&isAllowed=y
8 New York City Department of Health and Mental Hygiene Severe maternal morbidity in New York, 2008-2012 Retrieved from: https://www1.nyc.gov/assets/doh/downloads/pdf/data/maternal-morbidity-report-08-12.pdf 2016
9 Geronimus A.T. Hicken M.T. Pearson J.A. Seashols S.J. Brown K.L. Cruz T.D. Do US black women experience stress-related accelerated biological aging?: a novel theory and first population-based test of black-white differences in telomere length Hum Nat 21 1 2010 19 38 20436780
10 Hoffman K.M. Trawalter S. Axt J.R. Oliver M.N. Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites Proc Natl Acad Sci USA 113 16 2016 4296 4301 27044069
11 Badreldin N. Grobman W.A. Yee L.M. Racial disparities in postpartum in pain management Obstet Gynecol 134 6 2019 1147 1153 31764723
12 Vedam S. Stoll K. Taiwo T.K. The Giving Voice to Mothers study: inequity and mistreatment during pregnancy and childbirth in the United States Reprod Health 16 1 2019 77 31182118
13 Dyer O. Most pregnancy related deaths in US are preventable, says CDC BMJ 365 2019 l2169 31076464
14 Kieltyka L. Mehta P.K. Schoellmann K. Lake C. Louisiana maternal mortality review report 2011-2016 Retrieved from: https://ldh.la.gov/assets/oph/Center-PHCH/Center-PH/maternal/2011-2016_MMR_Report_FINAL.pdf 2018
15 Omi Michael Howard Winant Racial Formation in the United States: From the 1960s to the 1990s 1994 Routledge NY
16 Bonilla-Silva E. Racism Without Racists 2nd ed. 2006 Rowman & Littlefield Lanham, MD
17 Bobo L. Kluegel J.R. Smith R.A. Laissez-Faire racism: the crystallization of a kinder, gentler, antiblack ideology Racial attitudes in the 1990s: continuity and change vol 15 1997 Praeger Westport, CT 23 25
18 McKinnon B. Yang S. Kramer M.S. Bushnik T. Sheppard A.J. Kaufman J.S. Comparison of black-white disparities in preterm birth between Canada and the United States CMAJ (Can Med Assoc J) 188 1 2016 E19 E26 26553860
19 Neville H.A. Lilly R.L. Duran G. Lee R.M. Browne L. Construction and initial validation of the color-blind racial attitudes scale (CoBRAS) J Counsel Psychol 47 1 2020 59 70
20 Purdie-Vaughns V. Steele C.M. Davies P.G. Ditlmann R. Crosby J.R. Social identity contingencies: how diversity cues signal threat or safety for African Americans in mainstream institutions J Pers Soc Psychol 94 4 2008 615 630 18361675
21 Wilton L.S. Good J.J. Moss-Racusin C.A. Sanchez D.T. Communicating more than diversity: the effect of institutional diversity statements on expectations and performance as a function of race and gender Cult Divers Ethnic Minor Psychol 21 3 2015 315 325
22 Okah E. Thomas J. Westby A. Cunningham B. Colorblind racial ideology and physician use of race in medical decision-making J Racial Ethn Health Disparities 9 5 2021 2019 2026 34491564
23 FitzGerald C. Hurst S. Implicit bias in healthcare professionals: a systematic review BMC Med Ethics 18 1 2017 19 28249596
24 Christy K. Minimizing race through colourblind healthcare: examining Black women's experiences of medical racism during prenatal care (T) [Internet] 2021 University of British Columbia Retrieved from: https://open.library.ubc.ca/collections/ubctheses/24/items/1.0401854
25 Shapiro M.F. Morton S.C. McCaffrey D.F. Variations in the care of HIV-infected adults in the United States: results from the HIV cost and services utilization study J Am Med Assoc 281 1999 2305 2315
26 FivexMore All-Party Parliamentary Group on Black Maternal Health. [Internet] Retrieved from: https://www.fivexmore.com/appg 2021
27 Jain A. Akor N. Nnorom O. Use of a quality improvement strategy to increase flu immunization rates among racialized groups [poster] Fam Med Forum 2015 11 14 Toronto
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29 Kauh T.J. Read J.G. Scheitler A.J. The critical role of racial/ethnic data disaggregation for health equity Popul Res Pol Rev 40 1 2021 1 7
30 Hassen N. Lofters A. Michael S. Mall A. Pinto A.D. Rackal J. Implementing anti-racism interventions in healthcare settings: a scoping review Int J Environ Res Publ Health 18 6 2021 2993
31 Canadian Institute for Health Information Guidance on the Use of Standards for Race-Based and Indigenous Identity Data Collection and Health Reporting in Canada 2022 CIHI Ottawa, ON
| 0 | PMC9735204 | NO-CC CODE | 2022-12-14 23:29:53 | no | Lancet Reg Health Am. 2022 Dec 10;:100408 | utf-8 | Lancet Reg Health Am | 2,022 | 10.1016/j.lana.2022.100408 | oa_other |
==== Front
Childs Nerv Syst
Childs Nerv Syst
Child's Nervous System
0256-7040
1433-0350
Springer Berlin Heidelberg Berlin/Heidelberg
36484829
5754
10.1007/s00381-022-05754-7
Abstracts
48th Annual Meeting of the International Society for Pediatric Neurosurgery
Singapore, 6 - 10 December 2022
9 12 2022
178
© Springer-Verlag GmbH Germany, part of Springer Nature 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
==== Body
pmcISPN 2022 Meeting Chair: Wan Tew Seow
ISPN 2022 President: Frederick Boop
ISPN 2022 Scientific Chair: Abhaya Kulkarni
ISPN 2022 Scientific Co-Chair: Benedetta Pettorini
Platform Presentation Abstracts
PF-001
Neuroendoscopy
Prediction of 6 months endoscopic third ventriculostomy success rate in patients with hydrocephalus using a multi-layer perceptron network
Mohammad Sadegh Masoudi1, Elahe Rezaeia2, Amirhossein Tahmouresic3, Sousan Taleghani4, Reza Taheri5
1Department of Neurosurgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3Kerman University of Medical Sciences, Machine Learning Expert, Kerman, Iran
4Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
5Department of Neurosurgery, Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
BACKGROUND AND AIM: Discrimination Between Patients Most Likely to Benefit From Endoscopic Third Ventriculostomy (ETV) and Those at Higher Risk of Failure Is Challenging. Compared to Other Standard Models, We Have Tried to Develop a Prognostic Multi-Layer Perceptron Model Based On Potentially High-Impact New Variables for Predicting the ETV Success Score (ETVSS).
METHOD: Clinical and Radiological Data of 128 Patients Have Been Collected, and ETV Outcomes Were Evaluated. The Success of ETV Was Defined As Remission of Symptoms and Not Requiring VPS for Six Months After Surgery. Several Clinical and Radiological Features Have Been Used to Construct the Model. Then the Binary Gravitational Search Algorithm Was Applied to Extract the Best Set of Features. Finally, Two Models Were Created Based On These Features, Multi-Layer Perceptron, and Logistic Regression.
RESULTS: Eight variables have been selected (age, callosal angle, bifrontal angle, bicaudate index, subdural hygroma, temporal horn width, third ventricle width, frontal horn width). The neural network model was constructed upon the selected features. The result was AUC:0.913 and accuracy:0.859. Then the BGSA algorithm removed half of the features, and the remaining (Age, Temporal horn width, Bifrontal angle, Frontal horn width) were applied to construct models. The ANN could reach an accuracy of 0.84, AUC:0.858 and Positive Predictive Value (PPV): 0.92, which was higher than the logistic regression model (accuracy:0.80, AUC: 0.819, PPV: 0.89).
CONCLUSIONS: The research findings have shown that the MLP model is more effective than the classic logistic regression tools in predicting ETV success rate. In this model, two newly added features, the width of the lateral ventricle's temporal horn and the lateral ventricle's frontal horn, yield a relatively high inter-observer reliability.
Keywords: Hydrocephalus, Endoscopic Third Ventriculostomy, Multi-layer Perceptron Network
PF-002
Neuro-Oncology
Characterization of the BBB in DIPG murine models and effect of ultrasound on its specificities and permeability to AsiDNA™
Adam Biard1, Ludivine Le Dret1, Marie Dutreix2, Alexandre Carpentier3, Manon Lancien1, Alexandre Plessier1, Yassine Ajlil1, Marie Anne Debily1, David Castel1, Jacques Grill1, Kevin Beccaria4
1U981—INSERM UMR 981 « Prédicteurs moléculaires et nouvelles cibles en oncologie»—Équipe « Génomique et oncogenèse des tumeurs cérébrales pédiatriques», Gustave Roussy, Villejuif, France
2Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France
3Department of neurosurgery, Pitié Salpétrière Hospital, Sorbonnes University, Paris, France
4Department of pediatric neurosurgery, Necker Enfants Malades Hospital, Paris Cité University, Paris, France
BACKGROUND AND AIM: The poor prognosis of pediatric diffuse midline gliomas, including diffuse intrinsic pontine gliomas (DIPGs), is partly due to the blood–brain barrier (BBB). The BBB can be opened by ultrasound (US), but few studies have focused on its characteristics in DIPGs, especially when submitted to US. We aimed to characterize the BBB in DIPGs and the influence of US on its characteristics, and to evaluate the effect of US-induced BBB opening on the kinetics of AsiDNA™ in DIPG murine models.
METHOD: US-induced BBB opening was performed with the SonoCloud® device and controlled with Evans blue dye. Permeability of DIPGs’ BBB was assessed with fluorescent dextrans. A histological evaluation of BBB markers was carried out by immunohistochemistry and immunofluorescence, including endothelial markers (CD34, GLUT1, PLAVP), tight junctions proteins (claudin 5, Zona occludens 1), and the efflux transporter ABCB1. An in vivo and ex vivo kinetic study of AsiDNA™ was performed with fluorescence.
RESULTS: We could repeatedly open the BBB with low intensity US (acoustic pressure 0.4 Mpa). In vivo, 3 kDa and 70 kDa dextrans delivery to DIPG tissue was increased by US-induced opening of the BBB, while 500 kDa dextrans did not cross the BBB spontaneously or after US. ABCB1 gene expression was variable at baseline in different DIPGs but was downregulated after US-induced BBB opening. The spontaneous passage of AsiDNA™ through the BBB was limited but could be increased after US-induced BBB opening.
CONCLUSIONS: We have shown that the BBB was specific in DIPG murine models, particularly in the expression of ABCB1. This BBB can be modulated and permeabilized by US, a technique that could allow for an improved delivery of AsiDNA. This study is a preliminary step before the introduction of a such technique and treatment in future clinical trials in children and adolescents with DMGs.
Keywords: DIPG, Blood Brain Barrier, Pediatric, Glioma, Ultrasound
PF-003
Neuro-Oncology
Results of a Phase Ib Trial of Recombinant Polio:rhinovirus Immunotherapy for Recurrent Pediatric High Grade Glioma
Eric M Thompson1, Daniel Landi2, Matthias Gromeier1, Michael Brown1, Henry Friedman1, Roger Mclendon3, Dani Bolognesi4, Kristin Schroeder2, Oren Becher5, Allan Friedman1, Ashley Walter6, Stevie Threatt6, Denise Jaggers6, Annick Desjardins1, Darell Bigner1, David Ashley1
1Department of Neurological Surgery, Duke University, Durham, USA
2Department of Pediatrics, Duke University, Durham, USA
3Department of Pathology, Duke University, Durham, USA
4Department of Surgery, Duke University, Durham, USA
5Department of Pediatrics, Mount Sinai Health System, New York, USA
6Preston Robert Tisch Brain Tumor Center, Duke University, Durham, USA
BACKGROUND AND AIM: Outcomes of recurrent pediatric high grade glioma (pHHG) are poor with a median overall survival (OS) of less than 6 months. Viral immunotherapy such as the polio:rhinovirus chimera, PVSRIPO, is a novel approach for treatment of recurrent pHHG. PVSRIPO is genetically engineered to prevent neurovirulence. In adults with recurrent glioblastoma treated with PVSRIPO, 21% survived at least 36 months. The poliovirus receptor, CD155, is ubiquitously expressed in malignant pediatric brain tumors and is a target in pHHG.
METHOD: The primary objective of this Phase 1b clinical trial was to evaluate the safety and feasibility of PVSRIPO for recurrent pHGG. PVSRIPO was given at a single dose, 5 × 107 50% tissue-culture infectious dose (TCID50) administered by convection enhanced delivery (CED) to children with biopsy-confirmed recurrent pHHG between ≥ 1 and ≤ 5.5 in diameter. 3 mL of PVSRIPO was delivered at 0.5 mL/hr via a single catheter.
RESULTS: Eight patients were treated with PVSRIPO. Five males and 3 females with a median age of 16.5 (range 9–19) were enrolled. Six patients had recurrent glioblastoma, 2 had recurrent anaplastic astrocytoma. The median number of previous recurrences prior to enrollment was 3.5 (range 1–5). Four patients received bevacizumab on-study for treatment-related peritumoral inflammation/edema. Six of 8 patients experienced 26 treatment related adverse events (AEs) possibly, probably, or definitely related to protocol treatment. There were no Grade 4 or 5 AEs. There were 3 Grade 3 AEs: 2 headaches and 1 seizure. There were no AEs related to biopsy or CED catheter insertion/removal. Median OS was 4.13 months (range 1.23-NA). One patient is currently alive at > 20 months.
CONCLUSIONS: CED of PVSPRIO is both safe and feasible for the treatment of recurrent pHHG. Updated immune monitoring and histologic correlative results will also be presented.
Keywords: Oncolytic virus, Convection enhanced delivery, High grade glioma, Viral immunotherapy, Clinical trial
PF-004
Neuro-Oncology
Treating the “Untreatable”: Enhancing CAR T-Cell Therapy for Paediatric High-Grade Glioma
Louise Frances Steele Saukila1, Matteo Righi2, Alice Piapi1, Manav Pathania3, Alastair Hotblack1, Karin Straathof1
1UCL Cancer Institute, London, UK; UCL Great Ormond Street Institute of Child Health, London, UK
2UCL Cancer Institute, London, UK
3Cambridge University, Cambridge, UK
BACKGROUND AND AIM: Diffuse midline glioma (DMG) carries a devastating prognosis, with therapies limited by anatomical location and chemoresistance, and palliative radiotherapy the mainstay of treatment. Chimeric antigen receptor (CAR) T-cell therapy has shown promising pre-clinical results in treating these infiltrative tumours whilst leaving interspersed normal brain cells intact. Early clinical outcomes of GD2-CAR T-cell therapy for H3K27M-altered DMG demonstrate short-lived neurological and radiological improvement. Here, I aim to assess which molecules, co-expressed with the CAR, can potentiate CAR T-cell therapy, by improving trafficking, tumour penetration, and durability of therapeutic response.
METHOD: A co-expressing candidate molecule library was generated, including chemokine receptors (CCRs) to improve tumour homing towards tumour-secreted chemokines, adhesion molecules to increase extravasation across the blood–brain-barrier, and molecules to degrade upregulated tumour extracellular matrix components to improve tumour penetration. Co-expressing CAR constructs were cloned, labelled with unique DNA barcodes, and validated for co-expression with flow cytometry, and function when transduced into murine splenocytes. CAR T-cells co-expressing different molecules were administered simultaneously to tumour-bearing mice to in vivo select those CAR constructs which enhance ability to traffic to and penetrate high-grade gliomas. Both orthotopic syngeneic murine models of EGFRvIII-expressing GL261 (representing glioblastoma) and GD2-expressing H3K27M-altered DMG are being used.
RESULTS: Co-expression of enhancing module components alongside the CAR and retained function of the CAR has been confirmed. Pooled CAR T-cells co-expressing different CCRs have been administered to GL261-EGFRvIII tumour-bearing mice. Tumour, normal brain and non-CNS tissues were harvested and DNA extracted. Next Generation Sequencing is being used to determine CAR T-cells co-expressing which CCR (utilizing DNA barcodes) preferentially trafficked to the gliomas. Results from this and further experiments testing the full breadth of co-expressed molecules will be presented.
CONCLUSIONS: The multi-modular design of CAR constructs, allowing co-expression of potentiating molecules, has enormous scope for tailored optimisation of CAR T-cell therapy for DMG and other tumours.
Keywords: Paediatric high-grade glioma, Diffuse midline glioma (DMG), H3K27M-alteration, CAR T-cell therapy, T-cell trafficking
PF-005
Neuro-Oncology
Early Surgical Intervention Improves Central Nervous System Tumor Outcomes in Children with Li-Fraumeni Syndrome: Children’s National Hospital Experience and Literature Review
Nirali Patel1, Kathleen Felton2, Surajit Bhattacharya3, Maria Isabel Almira Suarez4, Joyce Turner5, Robert Keating1, Chima Oluigbo1, Lindsay Kilburn6, Roger Packer7, Miriam Bornhorst6, John S. Myseros1
1Department of Neurosurgery, Children's National Hospital, Washington, DC, USA
2Department of Pediatric Hematology/Oncology, University of Saskatchewan College of Medicine, Saskatchewan, Canada
3Center for Genetics Medicine Research, Children's National Hospital, Washington, DC, USA
4Department of Pathology, Children's National Hospital, Washington, DC, USA
5Department of Genetics and Metabolism, Children's National Hospital, Washington, DC, USA
6Department of Hematology/Oncology, Children's National Hospital, Washington, DC, USA
7Department of Neuroscience, Children's National Hospital, Washington, DC, USA
BACKGROUND AND AIM: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline mutations in the TP53 gene. CNS tumors are the fourth most common tumor type in LFS and recent screening guidelines, the Toronto Protocol, have proven that early tumor detection is associated with improved long-term survival7,8. Given the paucity of data in the literature, we highlight our experience with surgical resection of brain lesions, especially low-grade gliomas, identified on surveillance imaging in asymptomatic patients.
METHOD: Our cohort is comprised of children seen in the Pediatric Cancer Genetics Program ast Children’s National Hospital (CNH) from August 2012 to August 2021. We also include a literature search related to surveillance and CNS tumors in LFS patients.
RESULTS: Between August 2012 and August 2021, 10 children with germline TP53 mutations and CNS tumors were assessed at CNMC: four were known carriers of the TP53 mutation and found to have CNS lesions on surveillance imaging, while six were patients with symptomatic CNS lesions who were either known or subsequently found to have germline TP53 mutations. When added to the patients found in our literature review, we had a total of 56 CNS lesions: 24 low-grade and 26 high-grade lesions. The majority of the low-grade CNS lesions (22/24, 92%) were found on surveillance protocols in asymptomatic patients, while most of the high-grade CNS lesions (22/26, 85%) presented with symptoms in patients not undergoing routine surveillance or as the initial diagnosis of LFS. We noted a significant survival advantage in pediatric patients with a low-grade lesions, with an overall survival of 100% at 50 months.
CONCLUSIONS: Data presented in this study supports surveillance protocols in Li Fraumeni syndrome. In our experience, early surgical resection of low-grade lesions identified on surveillance imaging in asymptomatic patients leads to a significant survival advantage.
Keywords: Li Fraumeni Syndrome, brain tumor, Screening
PF-006
Neuroendoscopy
Endoscopic endonasal transsphenoidal surgery in children: widening the spectrum of oncological indications in the pediatric age group
Vincenzo Mastropasqua1, Mario Rigante2, Luca Massimi1, Paolo Frassanito1, Federico Bianchi1, Gianpiero Tamburrini1
1Pediatric Neurosurgery, A. Gemelli Hospital, Rome, Italy
2ENT Surgery, A. Gemelli Hospital, Rome, Italy
BACKGROUND AND AIM: Endoscopic endonasal transsphenoidal surgery (EETS) is increasingly used in children to treat skull base lesions. The aim of this study is to present our institutional experience.
METHOD: Sixty-eight children (mean age: 11.4 years) were operated on with the EETS in our institution from 2008 to date. All the procedures were performed by a team including neurosurgeons and ENT surgeons. Hormonal tests were conducted before and after surgery. Perioperative ophthalmic examinations were carried out in patients with visual impairment. Multidisciplinary follow-up was conducted in all patients variably according to pathology.
RESULTS: Overall 86 procedures were performed, including tumor residuals/recurrences after a previous craniotomic approach (6), biopsies (1). Gross total tumor resection was achieved in 45 (54.2%) cases, while a subtotal and a partial resection were performed in 17 (20.5%) and 21 (25.3%) cases, respectively. Craniopharyngioma was the most common histotype (25), followed by pituitary adenoma (22), pilocytic astrocytoma (7), Rathke cleft cyst (6), chordoma (5), chondrosarcoma (4), germ cell tumor (3), angiofibroma (2). No surgical mortality or neurological morbidity or late nasal complications were observed. Postoperative CSF leak occurred in 6 patients (7%), 3 of which required a sellar floor duroplasty. Out of 38 children with tumor residuals, 18 (47.4%) had tumor progression that needed a second surgery, performed in 10 cases through EETS and in 8 cases through a craniotomic approach. Ten out of 45 children (22.2%) who underwent gross total resection had tumor recurrence, that required a second intervention (EETS in 7, craniotomic approach in 1 cases).
CONCLUSIONS: EETS has an increasing number of indications in children. Thanks to its safety and efficacy it has subsided the craniotomic approach as first surgical route in many skull base oncological diseases at diagnosis, as well as the main alternative in children with residual or recurrent anterior skull base lesions, initially operated through a craniotomy.
Keywords: Neuroendoscopy, Neuro-oncology
PF-007
Neuro-Oncology
Transcriptome Characterization of Pediatric Adamantinomatous Craniopharyngioma at the Cellular Level
Eric W. Prince1, John Apps4, Oscar Chatain2, Susan Staulcup1, Carsten Georg2, Juan Pedro Martinez Barbera3, Todd C. Hankinson1
1Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, USA
2University of Colorado School of Medicine, Aurora, USA
3University College London Great Ormond Street Institute of Child Health, London, UK
4University of Birmingham, Birmingham, UK
BACKGROUND AND AIM: Adamantinomatous Craniopharyngioma (ACP) is a neurologically devastating brain tumor that affects children and adults. It is histologically heterogeneous with epithelial populations that are characterized by the nuclear accumulation of mutated β-catenin and activated Wnt signaling. Current models suggest that ACP growth is driven through paracine mechanisms characterized by the senescence-associated secretory phenotype (SASP). However, detailed pathogenic mechanisms remain unknown. Improved definition of the various cellular phenotypes that compose ACP will inform and advance our understanding of this disease.
METHOD: Single cell RNA-sequencing (scRNA-seq) and multiplex ELISA were performed on pediatric ACP tissue and cyst fluid, respectively. Reference scRNA-seq data was obtained from PanglaoDB. Preprocessing and standard analyses were conducted using Seurat software. Cellular phenotypes were annotated using the Human Primary Cell atlas. Differential expression and functional enrichment analyses were utilized to identify Wnt-signaling activation and epithelial subpopulations. Paracrine signaling was inferred via CellChatDB. SASP Atlas was utilized to query marker gene lists. Pseudotemporal ordering was performed using the dynamo software package.
RESULTS: ACP tissue is heterogenous and contains multiple distinct immune signatures. ACP tissue contains 2 unique epithelial subpopulations, which demonstrate canonical Wnt-signaling and SASP, respectively. Pseudotemporal ordering suggests the initial oncogenic event to be of epithelial character, with subsequent aggressive behavior from a separate epithelial cell population.
CONCLUSIONS: Based on gene expression, cell populations that correspond to the histologically identifiable epithelial whorls and palisading epithelium can be identified. These subpopulations display unique functional signatures. Simultaneous and synergistic therapeutic targeting of these separate epithelial populations may lead to improved patient care.
Keywords: Craniopharyngioma, Single cell RNA Sequencing, Pediatric craniopharyngioma, Deep sequencing, Gene expression
PF-008
Neuro-Oncology
Phase 0 and feasibility single-institution clinical trial of intravenous tocilizumab for adamantinomatous craniopharyngioma
Todd C. Hankinson1, Lindsey Hoffman4, Ashley Mettetal2, Molly Hemenway2, Nathan Dahl1, Shelby Winzent Oonk2, Eric Prince3, Trinka Vijmasi3, Jennifer A. Mcwilliams3, Kimberly Jordan3, David Mirsky1, Kathleen Dorris1
1Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, USA
2Children's Hospital Colorado, Aurora, USA
3University of Colorado School of Medicine, Aurora, USA
4Phoenix Children's Hospital, Phoenix, USA
BACKGROUND AND AIM: Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. ACP lacks medical antitumor therapies. Current standard therapy with surgery and radiation is associated with poor quality of life. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control.
METHOD: Children aged 2–21 years with newly diagnosed or previously treated ACP with measurable disease are eligible for the Phase 0/feasibility single-institution clinical trial (NCT03970226) of intravenous (IV) tocilizumab at Children’s Hospital Colorado. The phase 0 stratum involves IV tocilizumab prior to a standard-of-care surgical resection. The feasibility portion of the trial involves IV tocilizumab every two weeks for up to 13 28-day cycles. Tocilizumab is administered at the established weight-based pediatric dosage of 8 mg/kg for patients who weigh ≥ 30 kg or 12 mg/kg for patients who weigh < 30 kg.
RESULTS: To date, three patients have been enrolled on the Phase 0 component of the trial. These patients demonstrated clinically relevant levels of tocilizumab (≥ 4 µg/mL) in serum, cyst fluid, and/or tumor tissue, compared to undetectable levels in control samples. Two patients (1 male and 1 female; median age 10.5 years) have enrolled on the feasibility stratum; one patient had best response of minor response but met definition of progressive disease at cycle 11. One patient with extensive disease required dose reduction for myelosuppression.
CONCLUSIONS: Systemic delivery of tocilizumab at the established pediatric dosage is promising for treatment of ACP based on preclinical work and its demonstrated penetration into cystic and solid portions of ACP tumors. The therapy to date has been well tolerated overall. Further study is planned through a CONNECT consortium international Phase II trial.
Keywords: Craniopharyngioma, Tocilizumab, Clinical tria, Pediatric craniopharyngioma, Adamantinomatous craniopharyngioma
PF-009
Neuro-Oncology
Cerebellar mutism syndrome (CMS) following posterior fossa surgery in children below 18 years, what we have learnt over the last 10 years
Stephanie Sally Schmidt1, Edina Kovacs1, Felix Sahm2, Till Milde3, Andreas Unterberg1, Ahmed El Damaty1
1Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany
2Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany
3Department of Paediatric Neurooncology, Heidelberg University Hospital, Heidelberg, Germany
BACKGROUND AND AIM: The aim is to evaluate our institutional experience with tumor resection in the posterior fossa in children and the incidence of CMS postoperatively, and to analyze association with multiple risk factors, such as tumor entity, size and location, surgical approach, usage of ultrasonic cavitation device and hydrocephalus.
METHOD: All patients below 18 years, who received a tumor resection in the posterior fossa between January 2010 and March 2021 were included for retrospective analysis. Various data points, including demographic, tumor-associated, clinical, radiological, surgery-associated, complications and follow-up data were collected and statistically evaluated for association with CMS.
RESULTS: 60 patients were included with a median age of 8 years (range 0–18). Integrated diagnosis showed 48% pilocytic astrocytoma, 32% medulloblastoma, 10% anaplastic ependymoma and 13% other tumor entities. Complete resection was achieved in 68%, 23% underwent subtotal resection and 7% underwent partial resection.
43% were operated using a telovelar approach, 8% using a transvermian approach and 48% using other approaches. 16% developed CMS postoperatively, following telovelar approach in 15% and 60% following a transvermian approach. Medulloblastoma patients and midline tumors showed a higher incidence of CMS, though not significant. Tumor size and infiltration of the brainstem did not differ significantly in our cohort.
Presence of acute hydrocephalus was associated with a significantly higher risk for developing CMS (p 0.01) as well as need for a ventriculoperitoneal shunt (p 0.04). Usage of an ultrasonic cavitation device was not associated with CMS. All patients with CMS showed marked improvement during follow up but with residual deficits.
CONCLUSIONS: Our CMS rates compare to those described in literature. CMS was not only associated with a transvermian approach, but also occurs using a telovelar approach, but to a lesser extent. Presence of acute hydrocephalus prior to tumor surgery is associated with higher incidence of CMS.
Keywords: Cerebellar mutism syndrome, posterior fossa syndrome
PF-010
Neuro-Oncology
Clinicohistoradiological And Surgical Outcome In Diffuse Midline Glioma
Arvind Kumar Suman
Nizam's institute of medical sciences, Hyderabad, India, 500,082
BACKGROUND AND AIM: Diffuse midline glioma’s (DMGs) include central nervous system tumors, containing a characteristic H3K27M mutation and found in the midline location of brain and spinal cord.
To determine the clinical, pathological, radiological & surgical outcome, disease severity of DMG patients who have undergone surgery and to find better therapeutic options.
METHOD: 29 diffuse midline glioma patients were recruited. Clinical, pathological, radiological & surgical outcomes were noted and correlated with survival.
RESULTS: KI67% was compared between < 18 and > 18yrs age groups, it was found that KI67% was higher in < 18yrs age group (24.92 ± 13.66, p = 0.08) compared to > 18yrs age group (16.47 ± 10.19) and found to have trend towards significance and it was also found that KI67% was significantly low in the population with > 6 months disease duration (12.2 ± 4.712mnths, p = 0.012) compared to < 6 months disease duration population (21.58 ± 12.79mnths).
Survival duration was significantly high in patients with age > 18 years (232.06 ± 265.75 days; p = 0.02) compared to < 18 years age (50.16 ± 47.79 days). The patients who took radiation therapy found to show significantly higher survival rate (341.25 ± 318.05 days, p = 0.05) compared to those who were not taken (69.89 ± 71.5). Patients who required shunt placement found to have significantly lower survival duration (43.6 ± 30.35 days, p = 0.02) compared to patients who did not require shunt placement (215.56 ± 263.55 days). Patients with improved post op outcome (10.8 ± 4.08, p = 0.002) were having significantly low level of KI67% compared to not improved cases (21.87 ± 12.58) and KI67% was negatively correlated with survival duration (r = -0.40; p = 0.0358).
CONCLUSIONS: Our study concludes that KI67% and H3K27M serves as the markers and prognosticates the survival duration in pediatric population and also pediatric population has more severe disease compared to Adult population.
Keywords: Diffuse midline glioma, KI67%
PF-011
Neuro-Oncology
Is external ventricular drainage (EVD) necessary? The role of temporary CSF diversion for management of posterior fossa tumor resection: a 17-year experience at a single institution
Hasan Raza Syed1, Nirali Patel2, Sukhjeevan Nijhar3, Kelsey Chesney2, Katherine Hoffmann1, Daniel Donoho1, Chima Oluigbo1, Robert Keating1, John Myseros1
1Department of Neurosurgery, Children’s National Hospital, Washington DC
2Department of Neurosurgery, MedStar Georgetown University Hospital, Washington DC
3Georgetown University School of Medicine, Washington DC
BACKGROUND AND AIM: Children with posterior fossa tumors commonly present with obstructive hydrocephalus (80% in literature). Conventional doctrine has dictated external ventricular drainage (EVD) pre- or perioperatively for various purposes. Here, we highlight our experience with a less invasive approach that avoids EVD in the neurologically stable patient and decreases associated complications and hospital length of stay.
METHOD: We retrospectively collected data on all pediatric patients with posterior fossa tumors treated at Children’s National Hospital (CNH) from 2005–2021. Diagnostic and treatment variables included hydrocephalus at presentation, placement of external ventricular drain pre- or perioperatively, and final pathology. Outcome variables included complications, placement of permanent shunt, and length of stay (LOS).
RESULTS: 110 of 137 patients with posterior fossa tumors (80.3%) had hydrocephalus. All patients underwent resection that was volumetrically significant enough to reestablish the CSF pathways. Of the 65 patients (59.1%) that had pre- or peri-operative EVD placement, 10.8% experienced a complication, including infection, hemorrhage, or CSF leak, with 40% requiring permanent CSF diversion. Of those patients with no EVD (n = 45, 40.9%), 4.4% had either a CSF leak or pseudomeningocele, and only 15.6% required treatment for unresolved hydrocephalus (p < 0.01). None of these patients required pre-, peri-, or post-operative emergent procedures for untreated hydrocephalus. Length of stay was also significantly less compared to those patients with EVD (mean LOS 4.2 vs 9.1 days, p < 0.01).
CONCLUSIONS: Although relative risks of EVD are low in general, our experience shows that avoiding placement of an EVD decreases these risks even further, including the need for permanent CSF diversion post-resection. As such, depending on the surgeon’s comfort and the presenting symptoms, even in children with significant radiographic hydrocephalus, EVD may not be necessary, and adequate resection offers excellent chances for resolution of the hydrocephalus with decreased complications and a significant reduction in permanent CSF diversion and LOS.
Keywords: Posterior fossa tumor, Brain tumor, Hydrocephalus, Shunt, External ventricular drain, Complications
PF-012
Neuro-Oncology
Thalamic Tumors in Children: Surgical Outcome, Genetic and Clinical Features in a Retrospective Series of 110 Patients
Lelio Guida1, Kevin Beccaria1, Thomas Blauwblomme1, Volodia Dangouloff Ros2, Nathalie Boddaert2, Stephanie Puget1
1Department of Neurosurgery, Hôpital Necker Enfants Malades, Université de Paris Cité, Paris, France
2Department of Neuroradiology, Hôpital Necker Enfants Malades, Université de Paris Cité, Paris, France
BACKGROUND AND AIM: The treatment of tumors arising from the thalamus has changed over the decades, surgery gaining an important role in the management of these patients, especially in the case of low-grade tumors. In case of high-grade thalamic lesions, the relevance of surgery remains controversial, notably in the subgroup of patients with histone H3F3A K27M mutated tumors. We aimed to find radiological features that may predict high grade and H3F3A K27M mutated lesions, to define the outcome of histone-mutated patients and eventually to clarify the role of surgery in these patients.
METHOD: This is a monocentric, retrospective study. Clinical, neuroradiological and histological features were analyzed, as well as surgical strategy and clinical outcome. Univariate and multivariate analysis was performed for continuous and categoric variables. Survival analysis was made with according to the Kaplan–Meier method and Cox model.
RESULTS: 110 children were enrolled into the studies (50 unilateral thalamic tumors, 43 thalamopeduncolar, 17 bithalamic). In multivariate analysis, intra-tumoral cysts were associated with a decreased likelihood of high grade gliomas, while hyperperfusion and diffusion restriction were more likely to be found in aggressive lesions (Fig. 1). Seventy-nine percent of patients underwent debulking surgery of whom 55% had subtotal or gross-total resection. In survival analysis, bithalamic tumors, K27M histone mutation and EGFR mutation were associated to the poorest prognosis (Fig. 2). A significative difference of mean survival time was found (13,7 ± 5,9 vs 24,1 ± 5,3) among histone mutated patients according to extent of resection.
CONCLUSIONS: Molecular profile of thalamic tumors is essential in defining patient prognosis and management. Surgery has a prominent role in both low-grade and high-grade tumors in improving the outcome of patients with thalamic tumors.
Keywords: Thalamic tumors, Thalamopeduncular tumors, Bithalamic tumors, H3F3A K27M mutation
PF-013
Neuro-Oncology
HDAC inhibitor, PI3K mTOR and combined HDAC/PI3K inhibitors in treatment of mutant P53 Medulloblastoma
Tolga Sursal1, Jose Dominguez1, Raphael Salles Scortegagna De Medeiros2, Sidnei Epelman2, Michael E Tobias1, Avinash L Mohan1, Nelci Zanon3, Chirag D Gandhi1, Meena Jhanwar-Uniyal1
1Department of Neurosurgery, New York Medical College/Westchester Medical Center, Valhalla, New York, USA
2Department of Pediatric Oncology, Hospital Santa Marcelina, Sao Paulo, Brazil
3Department of Pediatric Neurosurgery, Hospital Santa Marcelina, Sao Paulo, Brazil
BACKGROUND AND AIM: Medulloblastoma (MB) is the most common primary pediatric malignant brain tumor. Molecular analysis classifies MB into 3 groups, classic (WNT), sonic hedgehog (Shh), and non-WNT/non-SHH. Abnormal p53 signaling is associated with disease progression and confers poor prognosis. This study examined the correlation of p53 mutation and status of iSO17q status with disease progression and metastatic potential and studied the effect of HDAC inhibitor, PI3K, mTOR and combined HDAC/PI3K inhibitors in aim of finding a novel therapeutic agent for p53-mutant MBs.
METHOD: MB tumors (n = 53) were assessed for the of GLI-1, GAB-1, NPR, KV1, YAP expression and mutant p53 via immunohistochemistry and correlated to patient outcomes. Fluorescence in-situ hybridization (FISH) was used to determine the Isochromosome 17q(iso(17q)). Effect of small molecule inhibitors, targeting HDAC (LBH-589), PI3K (Buparlisib), mTOR inhibitor (Torin1, Torin2) and combined HDAC/PI3K inhibitor (CUDC-907) was assessed via functional assays (cell proliferation, migration, cell cycle, and drug resistance).
RESULTS: High expression of GAB-1 and YAP in SHH group while KV1 expression was present in all subtypes. Mutant p53 was present in various subset of MB with no apparent correlation with metastasis or disease progression, however, one atient displaying iso17q exhibited metastatic disease. LBH-589, Buparlisib, Torin1, Torin2 and CUDC-907, caused a dose and time dependent inhibition of MB cell proliferation and migration. MB cells were resistant to PI3K inhibitor Buparlisib demonstrated by drug-resistance studies. These inhibitors function by targeting components of mTOR pathway.
CONCLUSIONS: GLI-1, GAB-1, NPR, KV1, YAP expression, and mutant p53 are essential criteria for defining metastatic potential of the MB sub-groups. While a significant number of MB samples displayed mutant p53, their association with the disease remains unclear however the presence of iso17q may define metastatic potential in MB. Furthermore, small molecule inhibitors of PI3K, Torin1, Torin2 and HDAC provide a novel option for treatment of MB.
Keywords: Medulloblastoma p53 sonic hedgehog (SHH) HDAC inhibitor PI3K mTOR
PF-014
Vascular
Delayed recurrence of pediatric arteriovenous malformations after radiologically confirmed obliteration
Soliman Oushy, Hannah E Gilder, Cody L Nesvick, Giuseppe Lanzino, Bruce E Pollock, David J Daniels, Edward S Ahn
Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota
BACKGROUND AND AIM: Arteriovenous malformations (AVMs) are a major cause of intracerebral hemorrhage in children, resulting in significant morbidity and mortality. Moreover, the rate of AVM recurrence in children is significantly higher than in adults. The aim of this study was to define the risk of delayed pediatric AVM (pAVM) recurrence following confirmed radiological obliteration. Further understanding of this risk could inform the role of long-term radiological surveillance.
METHOD: The authors conducted a retrospective review of ruptured and unruptured pAVM cases treated at a single tertiary care referral center between 1994 and 2019. Demographics, clinical characteristics, treatment modalities, and AVM recurrence were analyzed.
RESULTS: 102 children with intracranial AVMs, including 52 (51%) ruptured cases, were identified. The mean patient age at presentation was 11.2 ± 4.4 years, and 51 (50%) patients were female. Mean nidus size was 2.66 ± 1.44 cm. The most common Spetzler-Martin grades were III (32%) and II (31%). Stereotactic radiosurgery was performed in 69.6% of patients. AVM obliteration was radiologically confirmed in 68 (72.3%) of 94 patients [AQ? See query in Results, Radiological AVM Obliteration.], on angiography in 50 (73.5%) patients and on magnetic resonance imaging in 18 (26.5%). AVM recurrence was identified in 1 (2.3%) of 43 patients with long-term surveillance imaging over a mean follow-up of 54.7 ± 38.9 months (range 2–153 months). This recurrence was identified in a boy who had presented with a ruptured AVM and had been surgically treated at 5 years of age. The AVM recurred 54 months after confirmed obliteration on surveillance digital subtraction angiography. Two other cases of presumed AVM recurrence following resection in young children were excluded from recurrence analysis because of incomplete sets of imaging available for review.
CONCLUSIONS: AVM recurrence is a rare phenomenon, though it occurs more frequently in children. Regular long-term follow-up with dedicated angiography is recommended following resection.
Keywords: Pediatric, AVM, Arteriovenous malformations, Recurrence, Obliteration, Vascular disorders
PF-015
Moya-Moya disease
Neurosurgical management of Proton Beam Therapy-induced Moyamoya Syndrome
Catherine Zhang1, William Muirhead1, Adikarige Silva1, Claire Toolis1, Fergus Robertson3, Adam Rennie3, Sanjay Bhate2, Dominic Thompson1, Vijeya Ganesan2, Greg James1
1Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
2Department of Paediatric Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
3Department of Neuroradiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
BACKGROUND AND AIM: Proton beam therapy(PBT) is being increasingly used to treat paediatric brain tumours. Moyamoya syndrome (MMS) is a well-recognised complication following photon radiotherapy, however its association with PBT is less well documented. We describe our experience with the neurosurgical management of post-PBT MMS in a single institution in the United Kingdom.
METHOD: Retrospective review of patients diagnosed with post-PBT MMS within the past 20 years at Great Ormand Street Hospital, London. Patient details including demographics, oncological history and treatment, MMS diagnosis and treatment were recorded. Clinical outcome was classified as “Good” if mRS 2 or less, or attending mainstream school without additional assistance. “Poor” grade was deemed to be mRS 3 or more, or requiring assistance at school.
RESULTS: 10 patients were identified. Tumour types were 6craniopharyngiomas, 2sarcomas, 1optic pathway glioma, and 1ependymoma. Median age at PBT was 4.4 years (IQR 1.9—6 years), and MMS diagnosis was 7.8 years (IQR 5.7 – 9.3 years) (Fig. 1). Median time between PBT and diagnosis of MMS was 20 months (IQR 14.5 – 41.0 months). 6 patients had poor functional outcome at the end of their initial oncological treatment, and prior to the diagnosis of MMS. All patients had pituitary dysfunction, 8 had visual impairment, and 4 had behavioural issues prior to MMS diagnosis.
3 patients had an ischaemic event during a peri-operative period: 2 following tumour surgery, and 1 following MMS surgical revascularisation(SR). 1 patient had an ischaemic event following general anaesthetic for oncological surveillance MRI scan.
3 patients’ MMS were managed medically, and 7 underwent SR. Number of ischaemic events were reduced following SR (Fig. 2).
CONCLUSIONS: MMS can occur following PBT, with a clinical profile which can place these patients at high risk of ischaemic events. In selected patients, SR can prevent further neurological insults to a group of patients who frequently have neurodisabilities consequent upon their primary brain tumour.
Keywords: Moya moya syndrome, Proton beam therapy, Surgical revascularisation, Post-radiation moya moya syndrome
PF-016
Moya-Moya disease
Outcome prediction of pediatric moyamoya disease using midterm cerebral blood flow measured between staged anastomoses
Sadahiro Nomura, Fumiaki Oka, Natsumi Fujii, Hideyuki Ishihara
Department of Neurosurgery, Yamaguchi University, Ube, Japan
BACKGROUND AND AIM: Cognitive outcomes of pediatric moyamoya disease are variable and difficult to predict on the basis of initial neurological signs and examinations. To determine the best early time point for outcome prediction, we retrospectively analyzed the correlation between cognitive outcomes and the cerebrovascular reserve capacity (CRC) measured before, between, and after staged bilateral anastomoses. ±
METHOD: Twenty-two patients aged 4–15 years were included in this study. CRC was measured before the first hemispheric surgery (preoperative CRC), 1 year after the first surgery (midterm CRC), and 1 year after the surgery on the other side (final CRC). The cognitive outcome was the Pediatric Cerebral Performance Category Scale (PCPCS) grade more than 2 years after the final surgery.
RESULTS: The 17 patients with favorable outcomes (PCPCS grades 1 or 2) showed a preoperative CRC of 4.9% ± 11.2%, which was not better than that of the five patients with unfavorable outcomes (grade 3; 0.3% ± 8.5%, p = 0.5). The 17 patients with favorable outcomes showed a midterm CRC of 23.8% ± 15.3%, which was significantly better than that of the five patients with unfavorable outcomes (–2.5% ± 12.1%, p = 0.004). The difference was much more significant for the final CRC, which was 24.8% ± 13.1% in the patients with favorable outcomes and –11.3% ± 6.7% in those with unfavorable outcomes (p = 0.00004).
CONCLUSIONS: Cognitive outcomes were first clearly discriminated by the CRC after the first-side unilateral anastomosis, which is the optimal early timing for prediction of individual prognosis.
Keywords: Cerebral ischemia, Cerebrovascular reserve capacity, Prognosis, Single photon emission computed tomography
PF-017
Vascular
Multi-modality Treatment Approach for Paediatric AVMs with Quality of Life Outcome Measures
John C. Duddy1, Natasha Aziz2, Danial Saeed3, Dawn Hennigan1, Anil Israni4, Mani Puthuran3, Arun Chandran3, Conor Mallucci1
1Department of Neurosurgery, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK
2School of Medicine, University of Liverpool, UK
3Department of Neuroradiology, The Walton Centre NHS Foundation Trust, Liverpool, UK
4Department of Neurology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK
BACKGROUND AND AIM: Intracranial AVM rupture is the leading cause of spontaneous childhood intracerebral haemorrhage (ICH). AVM rupture is associated with a 30–50% risk of neurological deficit and 5–10% risk to life. The aim of this study is to evaluate management strategies of paediatric intracranial AVMs at our institution and to measure long-term quality-of-life outcomes.
METHOD: This retrospective case-series included all patients aged 0-18 years diagnosed with intracranial AVM from July 2007-March 2021. Multiple AVMs in one patient were treated separately. We collected data on: presenting symptoms; Spetzler-Martin Grade(SMG); time to treatment; type of treatment; post-operative complications; post-treatment obliteration rates; and quality of life outcomes measured using the PedsQL score.
RESULTS: We identified 57 patients between June 2007-March 2021. 8 patients were excluded due to insufficient data. 49 patients with 50 AVMs were included. 40(80%) AVMs presented with acute ICH. Of the remaining 10(20%), 4(8%) were incidental scan findings. The mean time to definitive treatment was 144 days.
25(50%) patients were surgically treated. Complete obliteration was achieved in 22(88%). There was no AVM recurrence and 1 rebleed reported on follow-up (mean 2.9 years). 15 children underwent endovascular embolization as either standalone treatment or multimodal AVM treatment strategy. Complete obliteration was achieved in 67%. 15 children underwent SRS as either a standalone treatment or multimodal AVM treatment strategy. Complete obliteration was achieved in 8(42%).
20(41%) patients completed the PedsQL outcome measurement model. PedsQL measures health-related quality of life in children and adolescents on a scale from 0–100. The average total score was 63.08 with average physical and pyschosocial scores of 64.5 and 62.375, respectively (Median scores:77.5; 66.25; 64.165).
CONCLUSIONS: A multi-modality treatment approach achieves a high rate of complete obliteration of paediatric AVMs. AVM recurrence and rebleed rates are low. Quality of life for children is significantly impacted by AVM diagnosis.
Keywords: AVM, Haemorrhage, Surgery, SRS, Endovascular, Quality-of-life
PF-018
Dysraphism
Motor-sensory disconnect in fetal myelomeningocele closure patients: intraoperative neurophysiological monitoring in tethered cord release
Tracy M. Flanders1, Alier J. Franco2, Kristen L Lincul3, Samuel Pierce3, Katie M. Schmidt4, Kaitlin R. Lehmann5, Ena A. Agbodza5, Deborah M. Zarnow6, Edward R. Oliver6, Beverly G. Coleman6, Jesse A. Taylor7, Julie S. Molenhauer8, N. Scott Adzick8, Gregory G. Heuer1
1Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
2Division of Pediatric Intraoperative Neuromonitoring, SpecialtyCare, Nashville, TN, USA
3Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA, USA
4The Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA, USA
5Center for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
6Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
7Division of Plastic and Reconstructive Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
8Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
BACKGROUND AND AIM: Patients after MMC closure can develop symptomatic spinal cord tethering, i.e. tethered cord syndrome (TCS), in as many as 30% of patients. Our goal was to better understand the clinical course and impact of tethered cord release surgery on patients who have previously undergone open spinal dysraphism closure in utero.
METHOD: This is a single-center retrospective observational study on patients undergoing tethered cord release after having previously had open fetal myelomeningocele (MMC) closure. All patients underwent tethered cord release surgery with a single neurosurgeon. A detailed analysis of the patients’ preoperative presentation, intraoperative neuromonitoring (IONM) data, and postoperative course was performed with a particular emphasis on motor and sensory function during these periods.
RESULTS: From 2009 to 2021, 51 patients who had previously undergone fetal MMC closure had tethered cord release surgery performed. On both preoperative and postoperative manual motor testing, patients were found to have on average 2 levels better than would be expected from the determined anatomic level from fetal imaging. The electrophysiologic functional level was found on average to be 2.5 levels better than the anatomical fetal level. Postoperative motor levels when tested on average at 4 months were largely unchanged when compared to preoperative levels. Unlike the motor signals, 46 (90%) of patients had unreliable or undetectable lower extremity somatosensory evoked potentials (SSEPs).
CONCLUSIONS: Tethered cord surgery can be safely performed in patients after open fetal MMC closure without clinical decline in manual motor testing. Patients often have functional nerve roots below the anatomic level. Sensory function appears to be more severely affected in patients leading to a consistent motor-sensory imbalance. This imbalance may affect strategies for physical therapy and rehabilitation.
Keywords: Fetal, Intraoperative neuromonitoring (IONM), Myelomeningocele, Tethered cord
PF-019
Dysraphism
Transitional Care for Spina Bifida: A Systematic Review
Nathan A Shlobin, Klaudia Dziugan, Joshua Simon, Sandi Lam, Michael Decuypere, Robin Bowman
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Division of Pediatric Neurosurgery, Lurie Children’s Hospital, Chicago, IL, USA
BACKGROUND AND AIM: Transition from pediatric to adult care presents challenges for people with spina bifida (SB) and families. However, there is a paucity of synthesis regarding transitional care for this patient population. We performed a systematic review to delineate the current state of transitional care; identify barriers, facilitators, and needs for transitional care; and characterize best practices for transitional care for people with SB
METHOD: PubMed, Embase, and Scopus were searched. After deduplication, articles were screened by title and abstract. Remaining articles were screened by full text. Bibliographic data were extracted.
RESULTS: Of 1,745 resultant articles, 32 were included. Transition of care was most often discussed within the context of urology, with no articles focusing on neurosurgical aspects. People with SB experience multiple transitions of care that may occur at different timeframes. Approximately 53–58% of transition-age people with SB are unemployed, 16–26% live independently, and 71% do not have a partner. Contributing factors include type of SB, presence of hydrocephalus, level of lesion, and activity limitations. Similarly, youth with SB who progress toward transition have higher cognitive functioning, interest in being independent, exposure to a independence-facilitating parenting style, and proficiency in negotiating primary care responsibilities with adult healthcare providers. Transition readiness, transition completion, and transition success represent key steps in the transition process. Physicians often do not discuss transitional care, while existing transitional care clinics often provide inadequate services. Effective transitional care models lead to regular home visits and appointments with SB specialists, allow easy access to medical care, and promote good quality of life.
CONCLUSIONS: Transitioning from child to adult care is an essential step for people with SB. Transitional care gaps exist, particularly on the level of providers. Adequate transitional care practices are necessary to address the needs of people with SB and families.
Keywords: Dysraphism, Spinal dysraphism, Spina bifida
PF-020
Other
Separation of conjoined spinal cords in 2 cases of rachipagus and pyopagus twins: Technical notes and the value of IONM
Llewellyn Padayachy
Department of Neurosurgery, University of Pretoria, Pretoria, South Africa
BACKGROUND AND AIM: Separation of conjoined twins presents a unique challenge, due to the anatomical and physiological complexity involved. Outcomes have improved, largely due to advances in imaging, virtual planning, surgical proficiency and monitoring techniques. The incidence of spinal cord attachment in pyopagus twins is 1: 100, 000, and rachipagus twins are even rarer. This work therefore represents valuable planning and technical surgical details acquired from a series of exceptionally rare cases of twin separation.
METHOD: The rachipagus twin involved an attachment of the head and spine of the parasitic twin at the T6-T8 level of the live twin, with a bony spur splitting the spinal cord. The spinal cord attachment for the pyopagus twins was at the level of L4/ L5, with no other visceral sharing. The surgical planning for both these cases were novel and innovative, including 3D printing of the models for bony and soft tissue anatomy, advanced MRI and 3D CT sequencing, as well multidisciplinary team involvement. Adjuncts to the surgery included, neuronavigation, intra-operative neurophysiological monitoring and imaging.
RESULTS: Separation of the rachipagus twin was done microsurgically. The parasitic twin remnant included an encephalocoele, with a bony spur splitting the spinal cord. This was circumferentially dissected under motor evoked potential monitoring. The pyopagus twin separation was done under more emergent conditions as one of the twins developed necrotising enterocolitis. Lower limb function in both cases were preserved and our rachipagus twin demonstrated further neurological improvement after pediatric neurorehabilitation.
CONCLUSIONS: The application of advanced surgical planning strategies, as well as appropriate intra-operative adjuncts can greatly assist in optimising surgical outcomes. This is well demonstrated in this series of incredibly rare and complex spinal cord separation in twins.
Keywords: Rachipagus, Pyopagus twins
PF-021
Dysraphism
Dysraphisms: towards a new European classification
Timothée De Saint Denis1, Ferdinand Dhombres2, Pauline Lallemant3, Catherine Garel4, Federico Di Rocco5, Jean Marie Jouannic2
1Department of Neuro-Orthopedic Surgery, Trousseau Hospital, Paris, France
2Department of Fetal Medecine, Trousseau Hospital, Paris, France
3Department of Rehabilitation Medecine, Trousseau Hospital, Paris, France
4Departmendt of Radiology, Trousseau Hospital, Paris, France
5Department of pediatric neurosurgery, HCL, Lyon, France
BACKGROUND AND AIM: Spinal dysraphisms classifications are mainly anatomical and based on embryological assumptions. However, we also need a prognosis classification for prenatal counselling and a therapeutic classification for management and follow-up. In order to design such classifications, we intend to dissect dysraphisms in different features which all together can coincide with already known categories such as Myelomeningocele, MyeLDM, LDM or Conus Lipoma.
METHOD: We reviewed 47 dysraphism cases treated in our Rare Disease center with skin, bone or spinal cord features. Using a specific ontology-based model, we created a data bank that can aggregate all reviewed features into a whole malformation. Known association has been made under 7 commonly used terms for spinal dysraphisms. Validation of terms has been discussed during ERN experts committee before evaluation of reproducibility by a multidisciplinary medical panel.
RESULTS: 35 features have been used to describe the whole combinations that compose the variety of spinal dysraphisms. Each feature can be associated with a grade of prognosis and management, more than closed categories actually used. Overlap of the currently used categories of dysraphism can lead to confusion in diagnosis and treatment decisions.
CONCLUSIONS: Rethinking the way we describe dysraphism cases can help to homogenate and improve prenatal counselling and medico-surgical management. This new composition of classification is proposed to revise existing classification such as Orphanet Classifications of Rare diseases and Orphanet Ontology of Rare Diseases (ORDO). This could help both improve medical decision making and patients knowledge about their condition.
Keywords: Dysraphism, Classification, Rare Disease
PF-022
Antenatal diagnosis and treatment
Fetal myelomeningocele repair: is open hysterotomy still the standard approach?
Carlos Eduardo Barros Jucá1, Francisco Edson De Lucena Feitosa4, Francisco Herlânio Costa Carvalho4, Antonio Aldo Melo Filho3, Tainã Brito Siebra De Oliveira5, Carolina Carmona Pinheiro Machado2
1Department of Pediatric Neurosurgery, Albert Sabin Children’s Hospital, Fortaleza, Brazil
2Medical School, Universidade de Fortaleza, Fortaleza, Brazil
3Department of Pediatric Surgery, Albert Sabin Children’s Hospital, Fortaleza, Brazil
4Department of Obstetrics and Gynecology, Maternidade Escola Assis Chateaubriand, Fortaleza, Brazil
5Department of Women, Child and Youth Health, Universidade Federal do Ceará, Fortaleza, Brazil
BACKGROUND AND AIM: Since the onset of Management of Myelomeningocele Study (MOMs) in 2011, prenatal intervention for myelomeningocele repair is becoming the standard once its advantages regarding motor improvement and lower risk of hydrocephalus have been demonstrated. However, some alternative approaches have been developed, the fetoscopic one. The aim of this study is to evaluate if the open hysterotomy approach is still the standard technique.
METHOD: We analyzed 25 cases of prenatal myelomeningocele repair operated in a regional reference center in Brazil using the open hysterotomy technique with the externalized uterus. The first case was operated on May 2019 and the last one on April 2022. Comparisons between our outcomes and those documented in the literature for MOMs’ trial, other series and fetoscopic treatment were performed.
RESULTS: The average maternal age in our series was 31,7 years old. Medium gestational age was 26 weeks. There was fetal bradycardia in 4% of cases and there was only one perinatal death, due to rapidly progressive hydrocephalus after surgery. Birth after 37 weeks occurred in 16% of cases and the average gestational age at birth was 33,8 weeks. Until this moment, it was necessary to perform shunt placement in 12% of the born operated children. The need for shunting for hydrocephalus was substantially lower than MOMS and fetoscopy. We also had less cases of chorioamniotic separation. There was no dehiscence at the repair site. Fetoscopic treatment has a risk of 20% of surgical dehiscence of myelomeningocele according to literature.
CONCLUSIONS: Open hysterotomy technique for prenatal myelomeningocele repair has similar fetal outcomes than the fetoscopic approach but has fewer local complications and less cases of dehiscence and fistula. Once the defect closure is a major goal of the intervention, open hysterotomy remains preferable based on available data. However, the fetoscopic approach tends to evolve soon to improve and gain space.
Keywords: Myelomeningocele, Prenatal surgery, Fetoscopy, Pediatric neurosurgery, Pediatric surgery
PF-023
Dysraphism
Postoperative Tethered Cord After Open and Fetoscopic Spina Bifida Repair
Ibrahim Alatas1, Seyhmus Kerem Ozel4, Bahattin Ozkul1, Huseyin Canaz3, Revna Cetiner2, Nafiye Sanlier2, Teoman Karakurt2, Mehmet Ozgur Yilmaz2, Oguz Alp Cakir2, Okan Turk2, Doga Ugurlar2
1Baskent University Hospital, Istanbul, Turkey
2Istanbul Training and Research Hospital, Istanbul, Turkey
3Medilife Hospital, Istanbul, Turkey
4Goztepe Training and Research Hospital, Istanbul, Turkey
BACKGROUND AND AIM: Spina bifida is the most common neural tube defect and its treatment options are evolving day by day. Fetal surgical repair of this defect and its clinical outcome are gaining interest and are increasingly seen as subjects of research even though early postnatal repair is routinely recommended for meningomyelocele.
The aim of this study was to evaluate the postoperative outcome of three cases of open and three fetoscopic repair of spina bifida in our spina bifida center since 2015.
METHOD: The data of cranial and vertebral MRI, urodynamics, neurological examination and ambulation scales were investigated in all six patients while evaluating the thickness of the granulation tissue at the surgical site from the perspective of tethered cord syndrome.
RESULTS: Findings of this study reveal that tethered cord detection in MRI was higher in patients after fetoscopic repair than open repair. Dermoid inclusion cysts have been accused in the development of tethered cord after fetal spina bifida repair. Our results point that high incidence of tethered cord after fetoscopic repair may be due to the foreign body reaction to the dura patch used in this procedure.
CONCLUSIONS: Fetal surgical repair of spina bifida is gaining popularity and different techniques may cause different outcomes in these patients. More common tethered cord after fetoscopic repair should be regarded as one of these issues.
Keywords: Spina Bifida, Meningomyelocele, Fetal Surgery, Tethered cord syndrome
PF-024
Spine
Cranio-cervical mobility assessment in dynamic magnetic resonance imaging in children
Flavie Grenier Chartrand, Maxime Taverne, Giovanna Paternoster, Raphaël Levy, Kévin Beccaria, Timothée De Saint Denis, Nathalie Boddaert, Thomas Blauwblomme, Roman H. Khonsari, Syril James, Sandro Benichi
Hôpital Universitaire Necker enfants malades, Assistance publique hôpitaux de Paris, Paris, France. Université Paris-Cité, Paris, France
BACKGROUND AND AIM: Dynamic MRI (dMRI) might be effective and safe to assess the stability of the cranio-cervical junction (CCJ) in children, but its interpretation is still an issue since no diagnostic criteria of instability is provided in the current literature. Our goal was to determine morphometric static and dynamic MRI criteria of mobility to distinguish stable and unstable patients.
METHOD: Monocentric retrospective analysis of all the cranio-cervical dMRI from 2017/01/01 to 2021/12/31. Patients underwent 2D sagittal T2 MRI with acquisitions in neutral position, flexion and hyperextension of the head. To assess CCJ mobility in dynamic conditions, delta (difference between extension and flexion) of seven morphometric parameters were measured in all positions: basion-dens interval (BDI), basion-axis interval (BAI), clivo-axial angle (CXA), C1-C2 cobb angle, PbC2 line (PbC2), Klaus index and C2-opisthion distance. We performed a hierarchical clustering on principal component analysis to define groups given their mobility similarities. Logistic regression was used to predict mobility in static neutral position.
RESULTS: 47 children were included (26 females, 21 males; mean age of 10 years): 17 patients with Chiari I, 10 complex craniosynostosis and 20 constitutional bone diseases. BDI delta (dBDI), CXA delta (dCXA) and PbC2 delta (dPbC2) were indicators of mobility between patients, and two groups were identified: Group 1 with “normal mobility” (n = 40) and Group 2 with “hypermobility” (n = 7). Cut-off with high predictability of mobility (area under curve of 1, 1, and 0,975 respectively) were established for dBDI (3 mm), dCXA (18°) and dPbC2 (3 mm). No predictor of cranio-cervical mobility was found in static neutral assessment.
CONCLUSIONS: This study distinguished 2 groups of patients, according to their CCJ mobility, with cut-off for dBDI, dCXA and dPbC2. Further studies comparing our findings with healthy controls or with a standardized modality (e.g. dynamic radiographs) are needed to assess if these criteria are predictors of cranio-cervical instability.
Keywords: Cranio-cervical instability, Dynamic MRI, Morphometric parameters, Children
PF-025
Spine
Timing of clinical and intraoperative neurophysiological monitoring (IONM) recovery after termination of pediatric spinal deformity surgery due to loss of IONM signals: When is it safe to return to the OR?
Richard C E Anderson1, Travis S Crevecoeur2, Rajiv R Iyer6, Hannah E Goldstein7, Lawrence G Lenke2, Benjamin D Roye2, Michael G Vitale2, Benjamin Kennedy3, Patrick Cahill3, Lindsay Andras4, David Skaggs4, Alex Powers5
1New York University, New York, USA
2Columbia University, New York, USA
3Children's Hospital of Philadelphia, Philadelphia, USA
4Children's Hospital of Los Angeles, Los Angeles, USA
5Wake Forest University, Winston-Salem, USA
6University of Utah, Salt Lake City, USA
7University of Washington, Seattle, USA
BACKGROUND AND AIM: IONM is used to reduce the risk of spinal cord injury during pediatric spinal deformity surgery. Significant reduction or loss of IONM potentials may lead the surgeon to abort the case. The goal of this study is to investigate the correlation between clinical and IONM recovery after aborted cases and help determine when it is safe to return to the operating room.
METHOD: A multicenter, retrospective study of pediatric patients undergoing spinal deformity surgery was conducted whose surgery was aborted due to a significant reduction or loss of IONM potentials. Data are still being collected, with analysis of 45 patients at this time. Baseline data, operative reports, clinical outcomes, and IONM data were analyzed to investigate the relationship between IONM loss, clinical outcome, and clinical and IONM recovery.
RESULTS: All patients had partial or complete loss of MEPs. 24/45 patients had loss of SSEPs. At the end of the aborted surgery, IONM potentials returned completely in 18/45 of patients, partially in 24/45, and no return in 3/45. Immediately post-operatively, 17/45 of patients developed new weakness, but only 9/45 had weakness > 72 h. Upon return to the OR, only 7/45 had insufficient signals to proceed with surgery. Overall, patients who had complete neurological recovery within 24 h were able to return to the OR at an average of one week with complete return of their IONM potentials. However, patients that required > 72 h for complete neurological recovery averaged greater than one month before return of monitorable IONM signals.
CONCLUSIONS: Significant reduction or loss of IONM signals can occur during pediatric spinal deformity surgery. These preliminary data suggest there is a correlation between the time of clinical recovery and IONM recovery. Additional data from this study will further clarify this association and help determine the safest time for returning to the operating room.
Keywords: Spine, Intraoperative neuromonitoring, SSEPs, MEPs, Spinal cord injury, Scoliosis
PF-026
Spine
Bony Anatomy of Foramen Magnum in Achondroplasia Patients: A CT based Comparison with Age-matched Controls and FGFR3 craniosynostosis syndromes
Catherine Zhang1, Felice D'arco2, Alessandro Borghi3, Moira Cheung4, Melita Irving5, Dominic Thompson1
1Department Of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
2Department of Neuroradiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
3UCL Great Ormond Street Institute of Child Health & Craniofacial Unit, London, UK
4Department of Paediatric Endocrinology, Evelina London Children's Hospital, London, UK
5Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
BACKGROUND AND AIM: Achondroplasia is the commonest non-lethal skeletal dysplasia, caused by FGFR3 mutation which accelerates endochondral growth plate ossification at the skull base. Foramen magnum stenosis is a well recognized complication of achondroplasia, however the bony anatomy and patterns of suture fusion have not been widely quantified. We evaluated the anatomy and fusion patterns of achondroplasia foramen magnum score (AFMS) 4 patients using pre-operative CT scans, and compare these with age-matched control patients and other FGFR3 craniosynostosis conditions.
METHOD: Pre-operative CT scans of AFMS 4 patients who underwent foramen magnum decompression were used, and compared with age-matched controls, Muenke and Crouzon Syndrome with Acanthosis Nigricans (CSAN) patients. Measurements obtained include: sagittal diameter (SD), transverse diameter (TD), foramen magnum area, opisthion thickness (Fig. 1). Anterior and posterior interoccipital synchondroses (AIOS and PIOS) were assessed and graded by extent of fusion.
RESULTS: 23 achondroplasia, 23 controls, 20 Muenke and 15 CSAN CT scans were used to obtain measurements. Achondroplasia had significantly smaller SD and TD compared with other groups (p < 0.0001), with 3.4 times smaller surface area compared with control group (Fig. 2). CSAN had the thickest average opisthion (9 mm), followed by achondroplasia (6.9 mm); both were significantly higher than Muenke and Control. All FGFR3 groups had higher PIOS fusion grades compared with controls, however achondroplasia patients had the highest fusion grades of all groups and this included both PIOS and AIOS (Fig. 3). Distinct bony opisthion spurs were seen in achondroplasia patients, giving rise to characteristic crescent and clover shapes (Fig. 4).
CONCLUSIONS: Patients with AFMS grade 4 achondroplasia have significantly reduced foramen magnum dimensions compared with control, Muenke and CSAN patients. This is associated with premature fusion of AIOS and PIOS. The presence of a bony opisthion spur also contributes to foramen magnum stenosis and its associated morbidity and mortality in achondroplasia patients.
Keywords: Achondroplasia, Foramen magnum, FGFR3, Foramen magnum stenosis
PF-027
Global Pediatric Neurosurgery
Pediatric neurosurgery fellowship program-an academic and public health join venture in Chile a 20 years experience
Sergio R Valenzuela 1,2
1Pediatric Neurosurgery Service, Dr Asenjo Neurosurgical Institute, Santiago,Chile
2Neurological Sciences Department, University of Chile, Santiago, Chile
BACKGROUND AND AIM: Our 20 years experience with a pediatric neurosurgical post graduate education program (fellowship) at the Dr Asenjo Neurosurgical Institute pediatric neurosurgical service and Neurological sciences department of the University of Chile is presented.
METHOD: The academic program, clinical objectives, financial source and technical abilities ara evaluated as well as the public health impact on children neurosurgical care in Chile.
RESULTS: The actual geographical distribution of pediatric neurosurgery facilities and neurosurgeons with full or partial dedication is compared with the previous situation in 2000 before this program started and the positive effect of it in the reference, counter reference and primary care of patients.
CONCLUSIONS: This presentation shows the great utility of having a post graduate program to enhance neurosurgical pediatric specific knowledge and abilities for general post graduated neurosurgeons working in places and cities far from the main neurosurgical centers in a very long country with long distances between mayor cities and difficult transfers and references or weather difficult conditions.
Keywords: Fellowship-pediatric-neurosurgical-children-care-reference
PF-028
Global Pediatric Neurosurgery
Nonsyndromic craniosynostosis in Vietnam: initial surgical outcomes of subspecialty mentorship
Can Dang Do Thanh
Department of Neurosurgery, University of Medicine and Pharmacy at Ho Chi Minh city, Vietnam; Department of Neurosurgery, Children's Hospital No 2, Ho Chi Minh City, Vietnam
BACKGROUND AND AIM: There is a global deficit of pediatric neurosurgical care, and the epidemiology and overall surgical care for craniosynostosis is not well characterized at the global level. This study serves to highlight the details and early surgical results of a neurosurgical educational partnership and subsequent local scale-up in craniosynostosis correction.
METHOD: A prospective case series was performed with inclusion of all patients undergoing correction of craniosynostosis at Children’s Hospital 2, Ho Chi Minh City, Vietnam, between January 1, 2015, and December 31, 2019.
RESULTS: A total of 76 patients were included in the study. The group was predominantly male, with a male-to-female ratio of 3.3:1. Sagittal synostosis was the most common diagnosis (50%, 38/76), followed by unilateral coronal (11.8%, 9/76), bicoronal (11.8%, 9/76), and metopic (7.9%, 6/76). The most common corrective technique was anterior cranial vault remodeling (30/76, 39.4%) followed by frontoorbital advancement (34.2%, 26/76). The overall mean operative time was 205.8 ± 38.6 min, and the estimated blood loss was 176 ± 89.4 mL. Eleven procedures were complicated by intraoperative durotomy (14.5%, 11/76) without any damage of dural venous sinuses or brain tissue. Postoperatively, 4 procedures were complicated by wound infection (5.3%, 4/76), all of which required operative wound debridement. There were no neurological complications or postoperative deaths. One patient required repeat reconstruction due to delayed intracranial hypertension. There was no loss to follow-up. All patients were followed at outpatient clinic, and the mean follow-up period was 32.3 ± 18.8 months postoperatively.
CONCLUSIONS: Surgical care for pediatric craniosynostosis can be taught and sustained in the setting of collegial educational partnerships with early capability for high surgical volume and safe outcomes. In the setting of the significant deficit in worldwide pediatric neurosurgical care, this study provides an example of the feasibility of such relationships in addressing this unmet need.
Keywords: Global pediatric neurosurgery, Craniosynostosis
PF-029
Other
Perinatal features of myelomeningocele patients after folate fortification in Costa Rica, a 25 year experience
Adrian Caceres1, Ana Laura Jimenez Chaverri2, Paula Alpizar Quiros3, Juan Luis Segura Valverde1, Justiniano Zamora Chaves1, Ariadnna Caceres Alan2
1Neurosurgery Division, Spina Bifida Clinic, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
2General Pediatrics, Spina Bifida Clinic, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
3Nursing division, Spina Bifida Clinic, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
BACKGROUND AND AIM: 2021 marked the 30 anniversary of the landmark clinical trial by the British Medical Research Council Vitamin Study unequivocally demonstrating that folic acid prevents spina bifida and anencephaly, two serious neural tube defects. Costa Rica started its folate staple food fortification program in 1997 with a dramatic response in the decrease of spina bifida cases (74%) that has been sustained with minimal variations over the last 25 years.
METHOD: A retrospective analysis of the database from the spina bifida clinic allowed to determine the gestational age, delivery method and time to myelomeningocele closure and shunt insertion in those patients who required CSF diversion. Additional information regarding the size of the spina bifida defect, neurological level at birth, the presence of kyphosis and symptomatic Chiari were determined.
RESULTS: 396 patients with complete medical records were analyzed, 47% were male and 53% were female. Gestational age at birth was 39 weeks. 57% were delivered vaginally vs 43% cesarean Sect. 18% were paraplegic, 62% were L3, 9%L5, 11% sacral. Defect size was > 5 cm in 23%, 3–5 cm in 67% < 3 cm in 9% and 1% were non closable rachischisis. There were 2 patients with severe kyphosis and 6 patients (1.5%) with symptomatic Chiari at birth. Average time to closure was 8–12 h. in 17%, 12–24 h. in 72% and 24 to 48 h. 11%. Average time to shunt insertion was 8.7 days. Perinatal mortality was seen in 9 patients who harbored major congenital defects.
CONCLUSIONS: Folate fortification of food staples including wheat, maize, rice and dairy products have been instrumental in decreasing not only the rate but the clinical impact in patients born with myelomeningocele, while kyphosis and symptomatic Chiari are very low, the presence of hydrocephalus requiring shunting is still present, however there was a timely management of defect closure and shunt insertion.
Keywords: Spina bifida, Folate fortification, Hydrocephalus, Symptomatic chiari, Prevention, Surgery
PF-030
Global Pediatric Neurosurgery
Global pediatric neurosurgery: pilot in developing a multidisciplinary pediatric epilepsy surgery program in Uganda
Emmanuel Wegoye1, Humphrey Okechi1, Erik Padilla2, Mariana Vincenteno2, Khrystyna Moskalyk2, Jeffrey Raskin2, Michael Decuypere2, Roxanna Garcia2, Sandi Lam2
1Pediatric Neurosurgery, CURE Uganda Hospital, Mbale, Uganda
2Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, USA; Division of Pediatric Neurosurgery, Lurie Children's Hospital, Chicago, USA
BACKGROUND AND AIM: Epilepsy is the most common neurologic condition in the world, with a disproportionate burden of disease in low and middle income countries. Drug-resistant epilepsy patients with lesional epilepsy have the chance of a cure by surgery. We aimed to establish a global neurosurgery pilot program to develop an epilepsy surgery program at a pediatric hydrocephalus surgery training center in subSaharan Africa.
METHOD: An established, accredited electroencephalography training program was modified for web-based, real-time video-conferencing, and hands-on training. Development, implementation, and preliminary results of this pilot program to diagnose, identify, and treat pediatric patients with drug-resistant epilepsy were tracked and descriptive narrative provided.
RESULTS: Through the global initiatives program by ASET—The Neurodiagnostic Society, online educational modules for electroencephalography training were donated for a cohort of 10 participants in Mbale, Uganda. EEG instructors in an accredited apprenticeship training program in Chicago, USA taught in the interactive modified Zoom-based curriculum over 6 months. Weekly knowledge and skills assessments were conducted for EEG recording, troubleshooting, and interpretation. Ugandan patients for epilepsy surgery conference discussion were identified, prepared, and discussed in weekly epilepsy conference with the Chicago partner program.
A local needs assessment revealed > 500 patients on anti-seizure medications in need of EEG One pediatric neurologist in this country of 24 million population works 7 h away. These gaps were addressed with the arrangement and training above, with continuing web-based peer mentorship and weekly multidisciplinary epilepsy surgery conference discussion. Metrics of the process of surgical candidate identification, intervention, and epilepsy outcomes are tracked over time.
CONCLUSIONS: Global pediatric neurosurgery extends to development of a scalable, sustainable, peer-mentored pediatric epilepsy surgery program. The work is ongoing for knowledge and skill transfer: such a model holds potential to address some of the disease burden of epilepsy and help elevate quality of life for patients, families, and communities.
Keywords: Epilepsy, Epilepsy surgery, Program development, Multidisciplinary, EEG, Global health
PF-031
Global Pediatric Neurosurgery
Pediatric Craniopharyngioma Management Modalities and Outcomes Across the Globe
Busha Hika, BS, Alan Tang, BA, Olivia Prosak, BS, Joseline Haizel Cobbina, MBChB, MPH, Michael Dewan, MD, MSCI
Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN 37,232–8605 USA
BACKGROUND AND AIM: Pediatric craniopharyngiomas (CP) are challenging lesions with wide variations in treatment approach. Limited controlled data and variable surgical and oncologic capacity worldwide result in disparate treatment regimens. Here, we sought to compare management strategies for CP across global regions and income groups.
METHOD: A systematic literature search was performed for pediatric craniopharyngioma articles published in PubMed between 2000 and 2022. Patient demographics, tumor characteristics, treatments, and outcomes were extracted and compared across different income-level countries and geographic regions.
RESULTS: Twenty-nine articles with 2270 CP cases from six continents and 26 countries met the inclusion criteria and were analyzed. All but two articles were from high-income countries (HIC) or upper middle-income (UMIC) (27, 93%). 1762 children (77%) were from HIC, 193 (8.5%) from UMIC, and 199 (8.8%) from lower middle-income (LMIC); there were no studies from low-income countries (LIC). In HIC, 56% of patients underwent surgery only, 2.4% underwent radiation only, and 35% underwent surgical resection followed by radiation therapy (RT). In UMIC, 64% underwent surgery only and 15.5% underwent surgical resection followed by RT. In LMIC, 61% underwent surgery only, 1% radiation only, and 39% surgical resection followed by RT. Intracystic therapy was infrequently reported and differed across time epochs, not income groups: bleomycin was used in manuscripts published before 2015, while interferon was used in reports published after 2016. Tumor progression was seen in 48% and 31% of cases in LMIC and UMIC, respectively, compared to 10% in HIC (p-value 0.02).
CONCLUSIONS: A paucity of data from LMIC/LIC precluded a reasonable comparison of treatment modalities between high- and low-income settings, which calls for action regarding the reporting of how such patients are treated. HIC utilized more conservative approaches with favorable outcomes than UMIC, with fewer resections (53% vs 90%). Other factors, other than financial resources, may explain differences in CP management among HIC/UMIC.
Keywords: Global neurosurgery, Pediatric, Craniopharyngioma, Treatment Outcome, Worldwide
PF-032
Global Pediatric Neurosurgery
Impact of the COVID-19 pandemic on pediatric neurosurgical care in a developing country setting
Raquel Queiroz Sousa Lima1, Vitória Cristina Almeida Flexa Ribeiro1, Gabrielle Benevides Lima1, Patrícia Pereira De Andrade1, Carlos Eduardo Barros Jucá2
1Universidade de Fortaleza (UNIFOR), Fortaleza, Brazil
2Department of Pediatric Neurosurgery, Hospital Infantil Albert Sabin (HIAS), Fortaleza, Brazil; Universidade de Fortaleza (UNIFOR), Fortaleza, Brazil
BACKGROUND AND AIM: The aim of this study was to identify the impact of the coronavirus pandemic on a reference center for pediatric neurosurgery in Brazil’s Northeast, regarding the number and types of procedures performed before and after the COVID-19 pandemic onset, identifying the main losses to children’s neurosurgical assistance.
METHOD: Retrospective, cross-sectional study of neurosurgical procedures performed in a reference pediatric hospital in Northeast Brazil between 2017 and 2021. Data were obtained from surgical block records and were assessed according to the type of procedure. The impact of COVID-19 pandemic was assessed by comparison between pre-pandemic period and pandemic period. Analysis of the most frequent canceled operations in 2020 was performed.
RESULTS: 1550 interventions in the pre-pandemic period (from 2017 to 2019, with a yearly increase of 6%) and 941 surgeries in the pandemic period. Comparison between 2019 and 2020 showed 551 and 493 respectivelly (10.5% reduction in a previous scenario of 6% yearly increase). When comparing two biannual periods, 2018–2019 and 2020–2021, there was a decrease in the total amount of surgeries (1.068 to 941—11,9%), mainly craniostenosis (19 to 13—31,5%), brain tumor (116 to 85—26,7%) and dysraphism (45 to 38—15,5%). Most frequently cancelled procedures were elective surgeries: closed dysraphism (30 to 17—43.3%), craniostenosis (10 to 6—40%) and tumors (48 to 41—14.6%).
CONCLUSIONS: In the context of a pediatric neurosurgery service in a developing country, which was passing through a transition from low complexity procedures to higher complexity ones, the COVID-19 pandemic caused a decrease in the total amount of interventions, representing a pushback in the previous trend. Pandemic had a negative influence in the number of elective procedures and lead to an important social negative impact on children care.
Keywords: Pediatric neurosurgery, Neurosurgery, Covid-19 pandemic, Covid-19
PF-033
Global Pediatric Neurosurgery
Update on Global Pediatric Neurosurgery
Nelci Zanon1, Eylem Ocal2, Martina Messing Jünger3, Suchanda Battacharjee4, Nabila Taghlit5, Wirginia Maixne6, Milagros Niquen Jimenes7
1Nelci Zanon, Pediatric Neurosurgeon, Universidade Federal de São Paulo: Sao Paulo, São Paulo, Brazil
2Eylem Ocal, Pediatric Neurosurgeon, 1 Children’s Way Slot#838 Little Rock, AR, 72,202—USA
3Martina Messing—Jünger, Pediatric Neurosurgeon, Head of neurosurgery Chefärztin der Abteilung Neurochirurgie Zentrum für Kinderchirurgie,—orthopädie und—neurochirurgie Asklepios Klinik—Arnold—Janssen—Straße 29 53,757 Sankt Augustin—Germany
4Suchanda Battacharjee, Neurosurgeon Nizams Institute of Medical Sciences (NIMS), Panjagutta, Hyderabad—India
5Nabila Taghlit, Pediatric Unit of Neurosurgery, Specialized Hospital in Neurosurgery Ali AIT DIR, Algiers, Algeria; Algeri
6Wirginia Maixner, Neurosurgeon at t he Royal Children's Hospital Melbourne 50 Flemington Road Parkville Victoria 3052 Australia
7MilagrosNiquen Jimenez, Medical Student, Facultad de Medicina Alberto Hurtado, Universidad Peruana Cayetano Heredia, Lima, Peru
BACKGROUND AND AIM: Review on the Pediatric Neurosurgery background, creation of pediatric neurosurgical societies, current status and futures perspectives.
METHOD: The co-authors, from each continent, update the information’s from the local Pediatric Neurosurgery Societies and publications. The major difficulty was to find who is a pediatric neurosurgeon between the general neurosurgeons. The pediatric neurosurgery is still not recognized "officially" as a subspecialty in several countries.
RESULTS: In Europe, no official specialist degree for pediatric neurosurgeons exists. So far there is also no unified education system that defines an European standard.
In Australia, training in pediatric neurosurgery is supervised through the Neurosurgical Society of Australasia Training Board, regulated by the Royal Australasian College of Surgeons.
The lack of neurosurgeons in Africa led to a deficit in management of pediatric neurosurgical diseases except in North Africa (Morocco, Algeria, Tunisia and Egypt) and the Republic of South Africa. There are very few countries where there are pediatric neurosurgeons.
In Latin America, until the 1990's the neurosurgeons were seeking the pediatric neurosurgery fellowship training in Europe or in the USA. Nowadays, there are pediatric neurosurgery training centers in the large cities in several countries.
In USA, the Accreditation Council for Pediatric Neurosurgical Fellowships was created in 1992 to oversee and regulate pediatric neurosurgical training /fellowship programs in USA and Canada. The American Board of Pediatric Neurological Surgery is a nonprofit corporation that is now a well- established and accepted certifying body, and has become the standard accreditation authority for pediatric neurological surgery in the United States and Canada.
CONCLUSIONS: The challenge of pediatric neurosurgery starts on a basic level. Around 51 million births remain unregistered every year in LMIC according to the UNICEF. Much more work are waiting for this specialty.
Keywords: Pediatric neurosurgery, Training centers, Pediatric neurosurgery certification, Global neurosurgery
PF-034
Other
Craniosynostosis surgery: Vietnamese experiences
Truc Trung Vu1, Anh Mai Bui2, Ha Hong Nguyen2, Manh Huy Bui3, Hung Manh Ngo3, He Van Dong3
1Department of Maxillofacial-Platic-Aesthetic Surgery, Viet Duc University Hospital, Hanoi, Vietnam; Department of Plastic Surgery, Hanoi Medical University, Hanoi, Vietnam; Department of Oral and Maxillofacial Surgery, University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
2Department of Maxillofacial-Platic-Aesthetic Surgery, Viet Duc University Hospital, Hanoi, Vietnam
3Department of Neurosurgery, Viet Duc University Hospital, Hanoi, Vietnam
BACKGROUND AND AIM: Up to now, there are currently no guidelines for the optimum age of surgical treatment for craniosynostosis. In Vietnam, there are few surgical center can perform that kind of surgery. It required a team work, machines, and some deep specialty like neurosurgery, plastic surgery, anesthesiologist… Recently, age of patient at time of surgery is getting younger. The goal of this study was to review the current application and status of craniosynostosis surgery in Vietnam.
METHOD: A cross sectional study was performed at Viet Duc University Hospital—the biggest surgical center in Hanoi, Vietnam to evaluate all craniosynostosis cases which were suffered from surgical treatment from 2016 to 2021.
RESULTS: A total 21 cases of craniosynostosis were included in this study. There were 12 cases with single suture premature and 8 cases with multiple suture premature. At time of surgery, the youngest patient was 3 months and oldest patient is 10 years old (20.3 months in average). The patients were divided to two groups: under 1 year old (younger group) and over 1 year old (older group). All patient was smoothly recovery without any major complications and the satisfaction of younger groups is significant higher comparing with older group (interview patient's family members).
CONCLUSIONS: Although, craniosynostosis surgery can be safely performed at early age but the beneficial is still unknown. Our study showed that the surgical results and complications are similar at any age but the satisfaction of younger groups is significant higher. The authors recommend that future research use agreed-upon parameters for: age-at-surgery cut-offs, follow-up times, and outcome measures.
Keywords: Craniofacial, Craniosynostosis, Neurodevelopmental, Surgery, Timing
PF-035
Global Pediatric Neurosurgery
Treatment of Sagittal Synostosis in Children Older than Two Years of Age—Long-term Follow-up
Hamilton Matushita, Daniel Dante Cardeal, Felipe Hada Sanders, Vitor Nagai Yamaki, Renata Harumi Gobato Yamashita, Manuel Jacobsen Teixeira
Pediatric Neurosurgery, Hospital das Clinicas, São Paulo University, São Paulo, Brazil
BACKGROUND AND AIM: Surgical techniques for correcting sagittal synostosis are very diverse and controversial, especially for children under one year. However, there is a consensus for children over two years of age that reconstructive techniques of the cranial convexity are necessary. This work aims to evaluate the surgical results of children operated on over two years of age, using a non-radioactive method, since excellent agreement has been found between the direct (anthropometric) and indirect (cephalometric) measurements.
METHOD: We report 46 consecutive cases of children with sagittal synostosis, older than two years of age, who underwent surgical treatment. Since 2004 we have followed all patients with craniosynostosis, with anthropometric measurements, during the pre-and post-operative follow-up.For sagittal synostosis, the primary measure was Cephalic Index. The measurements were performed in the hospital outpatient clinic by members of the pediatric neurosurgery team using an anthropometric caliper (Paleo-Tech).
RESULTS: The surgical treatment techniques applied to these patients were: Total reconstruction in 19, partial reconstruction (parietal and frontal) in 16 and partial reconstruction (parietal and occipital) in 11. The mean age at surgery was 34,2 months (24–84 months). The mean cephalic index (CI) in the pre-op was 0,64 (range 0,58–0,70), and at the postoperative period up to 3 months follow-up was 0,74 (range 0,69–0,84). The average percentage of improvement was 15% (range 1%—27%) (p < 0,05). The mean follow-up was 47,8 months (range 24 – 94 months). After the first measure of CI during three months of surgery, the percentage of variation ranged from -1% to + 1%, indicating stabilization of the CI.
CONCLUSIONS: Cranial morphology can be improved in late surgical correction of sagittal synostosis.
The final morphological results may be the early measurements taken up to 3 months of post-op, as no improvement of the cephalic index was seen after this period.
Keywords: Sagittal synostosis, Scaphocephaly, Craniosynostosis, Cephalic index, Anthropometric measurement
PF-036
Innovation and technology
Noninvasive nanotherapy for Crouzon syndrome based on allele-specific FGFR2 knockdown through recombinant human ferritin nanocarrier
Federica Tiberio1, Martina Salvati1, Lorena Di Pietro1, Elisabetta Falvo2, Luca Massimi3, Giada Tisci4, Pierpaolo Ceci2, Ornella Parolini1, Alessandro Arcovito5, Gianpiero Tamburrini3, Wanda Lattanzi1
1Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
2Istituto di Biologia Molecolare e Patologia, Consiglio Nazionale delle Ricerche, Rome, Italy
3Dipartimento Scienze dell'invecchiamento, neurologiche, ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
4Dipartimento di Scienze Biochimiche, Università La Sapienza, Rome, Italy
5Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche, e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
BACKGROUND AND AIM: Crouzon syndrome (CS) is a rare craniofacial malformation caused by gain-of-function mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2) gene and characterized by craniosynostosis as a hallmark. The treatment is based on multiple surgeries to release the skull constraint that impairs the child’s brain growth. The aim of this project is to develop a noninvasive therapy for CS using allele-specific siRNAs targeting the mutant FGFR2 allele, delivered by recombinant human ferritin (HFt) as a highly biocompatible nanocarrier to restore FGFR2 signaling and the fusion-timing pattern of sutures.
METHOD: Calvarial mesenchymal stromal cells (CMSCs) were isolated from calvarial tissue from FGFR2 mutation-positive CS patients. A set of siRNA specifically targeting the mutant FGFR2-alleles of each patient was designed and tested in patient cells. The efficiency of each siRNA was evaluated through real time PCR. The expression of the receptor of ferritin CD71 in CMSCs was investigated using real time PCR. CMSCs were incubated with fluorescein isothiocyanate-labeled HFt and analysed using fluorescence microscopy. siRNAs have been encapsulated within ferritin cavity performing pH-dependent procedure and the complexes were tested in CMSCs using Incucyte Live-cells analysis system.
RESULTS: Gene expression analysis allowed identifying specific siRNAs with differential knockdown efficiency between wild-type and mutant FGFR2 alleles in CMSCs derived from CS patients. Expression analysis revealed that CD71 was up-regulated during osteogenic differentiation of CMSCs. Fluorescence microscopy showed an efficient internalization of HFt within CMSCs cytoplasm. Preliminary results with HFt-based nanoparticles showed so far that, though siRNAs can be encapsulated in HFt, their intracellular trafficking is poorly detectable.
CONCLUSIONS: Our data suggested that allele-specific FGFR2 knockdown by siRNA represents a desirable strategy to silence FGFR2 mutant allele in CS patients. We demonstrated that HFt is suitable for delivery in CMSCs. Future studies aim to optimize the intracellular trafficking of HFt-siRNAs construct.
Keywords: Craniosynostosis, Gene silencing, Mesenchymal stromal cells, Nanotherapy, Ferritin
PF-037
Global Pediatric Neurosurgery
Autism-like traits in children with trigonocephaly
Daniela Pia Rosaria Chieffo1, Federica Moriconi1, Valentina Arcangeli1, Cristina Giansanti1, Sofia Vannuccini1, Federico Bianchi3, Paolo Frassanito3, Luca Massimi2, Gianpiero Tamburrini2
1Clinical Psychology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy (A)
2Università Cattolica Sacro Cuore Rome Italy (B)
3Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy (C)
BACKGROUND AND AIM: Children with non syndromic trigonocephaly might present cognitive and behavioural disorders more frequently than children affected by other forms of single suture craniosynostosis and, independently from the surgical treatment and the age it is performed, cognitive disorders might persist during the child growth. The aim of the present study has been to describe the specific cognitive and behavioural profile of children with trigonocephaly and its clinical course according to preoperative findings.
METHOD: All children operated on for a trigonocephaly between Jan 2015 and Dec 2020 were included. A complete set of neurocognitive and behavioural tests was administered in all cases before surgery (0), 6 months (T1) and 1 year (T2) after surgical treatment, at 3 years of life (T3) and at time of their entry to primary school (T4).
RESULTS: 84 children with trigonocephaly were included in our study. At diagnosis (T0) 10/84 ( 11%) children had a general cognitive development below normal range. The scales with higher level of impairment were those inherent to personal-social areas (12%) which are compatible with behavioral problems, and hearing skills (19%).
At 1 year 8/12 (67%) children who presented disorders inherent to personal social areas at diagnosis developed autistic traits. An early rehabilitation allowed an improvement only in 2 of these cases.
CONCLUSIONS: An impairment at diagnosis in personal social areas skills is highly predictive of the development of autism spectrum traits in children with metopic synostosis. These traits might persist over time in spite of an early rehabilitation programme suggesting a congenital functional impairment of the frontal regions, independent from the release of the local constriction due to the premature fusion of the metopic suture.
Keywords: Trigonocephaly cognitive autism rehabilitation surgery development
PF-038
Other
Clinical interest of molecular study in cases of isolated midline craniostenosis
Federico Di Rocco1, Sofia Guernouche1, Massimiliano Rossi2, Alexandru Szathmari1, Pierre Aurélien Beuriat1, Julie Chauvel Picard3, Carmine Mottolese1, Mathieu Vinchon1, Isabelle Verlut1, Corinne Collet4
1Pediatric Neurosurgery Department, Craniosynostosis National Reference Center, Hôpital Femme Mère Enfant-Hospices Civils de Lyon,, Lyon, France
2Genetics Department, Competence centre for constitutional bone diseases, Hôpital Femme Mère Enfant-Hospices Civils de Lyon, Lyon, France
3Maxillofacial Surgery and Stomatology Department, Hôpital Femme Mère Enfant-Hospices Civils de Lyon, Lyon, France
4Genetics department of Robert Debré hospital-Paris University hospital, Paris, France
BACKGROUND AND AIM: An underlying mutation can be found in some cases in infants with an apparently isolated single suture synostosis. Our objective was to determine the molecular substratum in isolated sagittal and metopic craniosynostosis.
METHOD: Our cohort included all infants who presented an isolated midline synostosis (sagittal or metopic) who have been operated on at the craniosynostosis national reference center of Lyon University Hospital from 2018 to 2020. All patients presented a clinically and radiologically confirmed premature fusion of the sagittal or the metopic suture. Children with a teratogenic exposure were excluded as well as patients with clinical and radiological signs of syndromic craniosynostosis. All patients were examined by a multidisciplinary team including neurosurgeons, clinical geneticists and neuropsychologist.
RESULTS: Among 101 children tested, a total of 13 variants were found in 13 patients, in other words, 12.8% of the patients displayed a variant in genes known in craniosynostosis. We found 6 patients with a SMAD6 variants (4.6%), 2 in FGFR2 (1.5%), 2 in TWIST1 (1.5%), one in FREM1 (0.8%), one in ALX4 (0.8%) and one combination of variants in TCF12 and ALX4 (0.8%). All variants were detected at heterozygous level in genes associated with an autosomal dominant craniosynostosis. No homozygous or compound heterozygous genotypes were identified.
CONCLUSIONS: We found herein a high percentage of affected young children who carry SMAD6 variants especially in isolated trigonocephaly. Moreover, variants in other genes were also represented in midline craniosynostosis. The interpretation of their pathogenicity has to take into account the incomplete penetrance, usually observed in craniosynostosis.
Our results highlight the interest to realize molecular analysis in the context of isolated sagittal and/or metopic craniosynostosis to enhance understanding the physiopathology of midline craniosynostosis.
Keywords: Neurosurgery, Isolated midline craniostenosis, Molecular study
PF-039
Other
Secondary cranial suture fusion after craniosynostosis surgery: prevalence with different surgical methods
Fehid Habalrih1, Sangjoon Chong2, Jong Woo Choi3, Young Shin Ra2
1Department of Neurosurgery, Asan Medical Center, Seoul, South Korea
2Department of Neurosurgery, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea
3Department of Plastic Surgery, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea
BACKGROUND AND AIM: Secondary suture fusion can develop after cranial surgery in children. The occurrence of secondary craniosynostosis (CS) of uninvolved suture after craniosynostosis surgery is retrospectively reviewed, with analyzing its relation to the surgical methods and the age at the time of surgery.
METHOD: A retrospective study of all non-syndromic craniosynostosis patients who underwent surgical management from 1995–2021. Patients were analyzed according to the age at the time of surgery and to the surgical methods, which are: 1- cranial vault reconstruction (CVR), 2- suturectomy and 3- distraction osteogenesis (DO). The occurrence of secondary CS was investigated on 3-D computed tomography scan with 1-year minimum follow-up. Surgical technique and age at the time of surgery were statistically analyzed. We reviewed our management to secondary CS patients.
RESULTS: Among 179 patients who underwent craniosynostosis surgery, 21 patients (11.7%) were found to have secondary craniosynostosis with mean follow up of 17-months interval. The most common secondary CS was sagittal suture (47.6%), it developed in 10 patients, followed by bicoronal suture 19% (4), unicoronal suture 14.4% (3) and bilambdoid suture 9.5% (2). Two patients developed multiple sutures fusion (9.5%). It occurred in 7.5% with cranial vault reconstruction, 8.9% with suturectomy and 15.6% with DO (p-value 0.326). There was no significant relation between the secondary CS and the age at the time of surgery (p-value 0.723). Only 2 patients with secondary CS required another surgery due to increased intracranial pressure. The first patient underwent CVR for bilambdoid CS and secondarily developed sagittal CS, then needed to have expansive CVR. The second patient underwent suturectomy for sagittal CS and developed secondary bicoronal CS and expansive DO was performed.
CONCLUSIONS: Secondary craniosynostosis is not uncommon and should be considered during follow up. Mostly, it doesn’t require surgical intervention unless increased intracranial pressure develops.
Keywords: Secondary, Craniosynostosis, Children, Cranial suture, Surgery
PF-040
Hydrocephalus
Optical neuromonitoring and volumetric imaging for early assessment of surgical efficacy in infantile hydrocephalus: a multi-center investigation
Ajay Rajaram1, Rutvi Vyas1, Taylor Vadset1, Miriah Kemigisha Katungi2, Chuan Heng Hsiao1, Marvin Seruwu2, Luis Neri Perez1, Joshua Magombe2, Brian Kaaya Nsubuga2, Julia Tatz1, Davis Natukwatsa2, Moses Wabukoma2, Mallory Peterson3, Esther Nalule2, Michael Woglom1, Rachel Lippman1, Ronald Mulundo2, Jennifer Queally4, Steven Schiff3, Aaron Fenster6, P. Ellen Grant5, Jason Sutin1, Edith Mbabazi Kabachelor2, Benjamin C Warf7, Pei Yi Lin1
1Division of Newborn Medicine, Boston Children’s Hospital; Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Boston, USA
2CURE Children's Hospital of Uganda, Mbale, Uganda
3Center for Neural Engineering, Pennsylvania State University, State College, USA.
4Department of Psychiatry, Boston Children’s Hospital, Boston, USA.
5Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Boston, USA; Department of Radiology, Boston Children’s Hospital, Boston, USA
6Robarts Research Institute, Western University, London, Canada
7Department of Neurosurgery, Boston Children’s Hospital, Boston, USA
BACKGROUND AND AIM: The prevalence and etiology of infantile hydrocephalus varies globally: America admits 39,000 patients annually [1], while sub-Saharan Africa sees over 100,000 new cases each year, most occurring post-infection. Traditionally, ventriculoperitoneal shunts are implemented to drain CSF from the ventricles but 40% fail within two years [2]. Endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), pioneered at CURE Children’s Hospital of Uganda (CCHU), is an effective, low-resource alternative to drain CSF while minimizing its production. ETV/CPC avoids a permanent fixture, requires less post-operative care, and has lower rates of infection [3]; however, early treatment failure remains a significant problem that is challenging to assess with imaging alone.
Biomedical optics offers non-invasive and cost-effective bedside monitoring of cerebral physiology. Frequency-domain near-infrared and diffuse correlation spectroscopy (FD-NIRS/DCS) can quantify cerebral blood flow (CBF) and metabolism, which have shown potential as early indicators of development/injury in premature infants and post-hemorrhagic hydrocephalus [4,5].
METHOD: Infants undergoing ETV/CPC at Boston Children’s Hospital (BCH) and CCHU were monitored pre-/post-operatively using FD-NIRS/DCS to quantify CBF and metabolism in six brain regions. CCHU subjects were imaged pre-/post-operatively with 3D-ultrasound and pre-operatively/6-months with CT to quantify brain tissue/ventricle volumes. BCH subjects were imaged pre-/post-operatively and at 6-months with MRI. Surgical failure was assessed at 6-months.
RESULTS: In 37 subjects at BCH significant post-operative increases in CBF and metabolism were found only for the failure-free cohort (n = 21); no change was observed in patients experiencing surgical failure (n = 16). At CCHU, outcome assessment is ongoing. Significant post-operative increases were observed for CBF and metabolism across all subjects (n = 43).
CONCLUSIONS: Optical brain monitoring has demonstrated strong potential for early prognosis and timely evaluation of surgical efficacy following ETV/CPC and could alter patient management surrounding the development and treatment of infantile hydrocephalus.
1) Simon, J.Neurosurg.Ped., 2008; 2)Kulkarni, J.Neurosurg.Ped, 2013; 3)Warf, J.Neurosurg.Ped., 2011; 4)Rajaram, Sci.Rep., 2022; 5)Rajaram, Brain Sci., 2020.
Keywords: Hydrocephalus, Optical neuromonitoring, Endoscopic third ventriculostomy and choroid plexus cauterization, Surgical efficacy, Volumetric imaging
PF-041
Hydrocephalus
ENdoscopic Lavage after IntraVEnticular haemorrhage in Neonates (ENLIVEN): Interim report from a randomized controlled trial
William Dawes, Sarah Olney, Malak Mohamed, Aswin Chari, Greg James, Kristian Aquilina
Department of Neurosurgery, Great Ormond Street Hospital
BACKGROUND AND AIM: Neuroendoscopic lavage (NEL) may improve outcomes in premature neonates with intraventricular haemorrhage (IVH). We report interim results from a single centre open label randomized controlled trial of NEL + ventriculosubgaleal shunt (VSGS) vs VSGS alone.
METHOD: All premature neonates with IVH undergoing VSGS were eligible for inclusion. NEL was performed using a flexible endoscope with lavage, gentle mobilization, aspiration of intraventricular clot and septostomy. The primary outcome was the rate of VP shunt insertion at 6 months’ corrected age. The trial was designed to detect a 40% reduction in shunt rate with 80% power.
RESULTS: To date, seventeen neonates have been recruited. Median gestational age at birth was 25.6 weeks (range 23.6–29.0). Median gestational age and weight at operation were 27.9 weeks (range 27.9–34.0) and 1090 g (range 800–1660). Nine neonates were randomized to the NEL + VSGS arm, eight to the VSGS arm. There were no intra-operative complications. Median length of stay was 2 days in the NEL + VSGS arm and 2.5 days in the VSGS arm. VP shunt insertion was performed in 7/9 (78%) in the NEL + VSGS arm and 6/8 (75%) of the VSGS arm. At last follow-up, 4/7 (57%) in the NEL + VSGS arm and 3/6 (50%) in the VSGS arm had undergone shunt revision. At median age of 2.9 years (range 1.5–4.2), 5/8 (63%) in the NEL + VSGS arm and 4/7 (57%) in the VSGS arm had a favourable developmental outcome.
CONCLUSIONS: This interim report from an open label randomized controlled trial shows that NEL is a safe procedure. Given the emerging evidence that NEL may have a positive impact on cognitive and developmental outcomes without affecting shunt rates, trials with robust developmental primary endpoints are warranted.
Keywords: Intraventricular haemorrhage, Hydrocephalus, Post-haemorrhagic hydrocephalus
PF-042
Hydrocephalus
Choice of valve in infant hydrocephalus: where to start?
Benjamin J. Hall1, Conor Gillespie2, Geraint J. Sunderland3, Elizabeth J. Conroy4, Dawn Hennigan1, Michael D. Jenkinson2, Benedetta Pettorini1, Conor Mallucci1
1Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, UK
2Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
3Institute of Infection Veterinary and Ecological Sciences, University of Liverpool
4Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK
BACKGROUND AND AIM: Infant hydrocephalus is the most common indication for ventriculoperitoneal (VP) shunts, with failure and revisions leading to significant patient morbidity, economic burden and increasing surgical workload. The aim of this paper was to review the use of different valve types in infants with hydrocephalus; attempting to determine whether an optimal valve choice exists for this patient cohort.
METHOD: We conducted (1) a retrospective review of data from the pivotal BASICS trial for infant patients (≤ 2 years) with hydrocephalus, (2) a separate, institutional cohort study from Alder Hey Children’s Hospital NHS Foundation Trust (England, UK, 2010–2018), and (3) a literature review for all studies describing valve types used (programmable vs. non-programmable, valve size, pressure). The primary outcome was 2-year revision not due to infection.
RESULTS: The BASICS data identified 391 infants, with no statistically significant difference in failure rates between gravitational (36.1% vs 30.5%, p = 0.294) and programmable subgroups at 24 months (29.6% vs 33.2%, p = 0.713). The institutional data did not reveal any significant difference in 2-year failure rate between fixed and programmable subtypes overall (25% vs 28.5%, p = 0.95), and after correction for shunts that had failed within 3 months of insertion (12.4% vs 22.6%, p = 0.2). Nineteen studies were included in the review. Most did not identify a superior valve choice between programmable and non-programmable, small compared to ultra-small, and differential pressure compared to flow-regulating valves. Five studies investigated a single-valve type without a comparator group.
CONCLUSIONS: There appears to be no difference in non-infective failure rates between valve subtypes. However, this is limited by a lack of direct comparison in the literature. Direct comparison via randomised trials is required to address the significant heterogeneity amongst the available treatment choices.
Keywords: Hydrocephalus, Ventricle-peritoneal shunt, valve, Infant
PF-043
Hydrocephalus
Endoscopic Third Ventriculostomy in Previously Shunted Patients
Brandon G Rocque1, Hailey Jensen2, Ron W Reeder2, Abhaya V Kulkarni3, Ian F Pollack4, John C Wellons Iii5, Robert P Naftel5, Eric M Jackson6, William E Whitehead7, Jonathan A Pindrik8, David D Limbrick9, Patrick J Mcdonald10, Mandeed S Tamber10, Todd C Hankinson11, Jason S Hauptman12, Mark D Krieger13, Jason Chu13, Tamara D Simon14, Jay Riva Cambrin15, John R. W Kestle16, Curtis J Rozzelle1
11Department of Neurosurgery, Children’s of Alabama, The University of Alabama at Birmingham, Birmingham, Alabama, USA
2Department of Pediatrics, University of Utah, Salt Lake City, Utah
3Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada
4Department of Neurosurgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania
5Department of Neurosurgery, Vanderbilt University Medical Center; and Surgical Outcomes Center for Kids, Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tennessee
6Department of Neurosurgery, The Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland
7Department of Neurosurgery, Texas Children’s Hospital, Houston, Texas
8Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, Ohio
9Department of Neurosurgery, Washington University School of Medicine in St. Louis, Missouri
10Division of Neurosurgery, British Columbia Children’s Hospital, The University of British Columbia, Vancouver, British Columbia, Canada
11Department of Neurosurgery, Children’s Hospital Colorado, Colorado Springs, Colorado
12Department of Neurosurgery, Seattle Children’s Hospital, University of Washington, Seattle, Washington
13Department of Neurosurgery, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California
14Department of Pediatrics, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California
15Division of Neurosurgery, Alberta Children’s Hospital, University of Calgary, Alberta, Canada
16Department of Neurosurgery, University of Utah, Salt Lake City, Utah
BACKGROUND AND AIM: Endoscopic Third Ventriculostomy (ETV) is an option for treatment of hydrocephalus, including for patients who have a history of previous treatment with cerebrospinal fluid shunt insertion (CSF shunt). The purpose of this study is to report the success of post-shunt ETV using a multi-center, prospective registry.
METHOD: Prospectively collected data in the Hydrocephalus Clinical Research Network Core Data Project were reviewed. Children who underwent ETV between 2008 and 2019 and had a history of previous treatment with a CSF shunt were included. A Kaplan–Meier survival curve was created for the primary outcome: time from post-shunt ETV to subsequent CSF shunt placement or revision. Univariable Cox proportional hazards models were created to evaluate for association between clinical and demographic variables and subsequent shunt surgery. Post-shunt ETV complications were also identified and categorized.
RESULTS: A total of 203 children were included: 57% male, 43% female; 74% White, 23% Black, 4% other race. The most common hydrocephalus etiologies were post-intraventricular hemorrhage secondary to prematurity (56, 28%) and aqueductal stenosis (42, 21%). ETV Success Score ranged from 10 to 80. Median age was 4.1 years. The overall success of post-shunt ETV at 6 months was 41%. Only report of a clear view of the basilar artery was associated with lower likelihood of failure (HR 0.43, 95% CI 0.23–0.82, p = 0.009). None of the following were associated with success: age at the time of post-shunt ETV, hydrocephalus etiology, sex, race, ventricle size, number of previous shunt operations, shunt infection, and use of external ventricular drainage.
CONCLUSIONS: Post-shunt ETV was successful in treating hydrocephalus, without subsequent need for a CSF shunt, in 41% of subjects, with a clear view of the basilar artery the only variable significantly associated with success. Complications occurred in 22%. ETV is an option for treatment of hydrocephalus in children who have previously been shunted.
Keywords: Hydrocephalus, Ventriculoperitoneal shunt, Endoscopic third ventriculostomy, ETV revision, Hydrocephalus Clinical research network
PF-044
Hydrocephalus
Prolonged clearance of cerebrospinal fluid (CSF) ferritin and bilirubin following preterm severe intraventricular hemorrhage (IVH) predicts post-hemorrhagic hydrocephalus
Kelly Mahaney1, Venkata Ravindra Pothineni1, Zhe Wang3, Jahanbanoo Shahryari3, Jayakumar Rajadas3, Diego Morales2, David Limbrick, Jr.2, Summer Han4, Jennifer Strahle2
1Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA
2Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO
3Advanced Drug Delivery and Regenerative Biomaterials Laboratory, Stanford University School of Medicine, Stanford, CA
4Quantitative Sciences Unit, Stanford Center for Biomedical Informatics Research (BMIR), Stanford University, Stanford, CA
BACKGROUND AND AIM: Post-hemorrhagic hydrocephalus following severe intraventricular hemorrhage (IVH) is among the most devastating sequelae of premature birth. While many infants die during the birth hospitalization with hydrocephalus, among those that survive, early differentiation of post-hemorrhagic ventricular dilation that subsequently resolves from permanent hydrocephalus requiring a shunt has been challenging.
In this study we sought to determine if levels of CSF hemoglobin or hemoglobin degradation products from serial ventricular taps discriminate between neonates with post-hemorrhagic ventricular dilation following severe IVH and those with post-hemorrhagic hydrocephalus requiring a shunt.
METHOD: In this nested case–control study, CSF samples were collected from serial ventricular taps of 23 premature neonates with severe IVH and subsequent post-hemorrhagic ventricular dilation at St. Louis Children’s Hospital and Lucille Packard Children’s Hospital. CSF samples were analyzed for iron levels, quantified by mass spectrometry, and hemoglobin, bilirubin, ferritin, and heme oxygenase-1 (HO-1) levels quantified by ELISA. The composite outcome of “post-hemorrhagic hydrocephalus or death” was met by placement of a ventriculoperitoneal shunt or death during the neonatal period with hydrocephalus (determined by severe ventriculomegaly on imaging).
RESULTS: Fourteen patients developed post-hemorrhagic hydrocephalus or died with hydrocephalus during the neonatal period; 9 patients had resolved post-hemorrhagic ventricular dilation and did not require a shunt. Initial levels of CSF hemoglobin, iron, bilirubin, ferritin, and HO-1 did not differ between the two groups. However, infants that developed post-hemorrhagic hydrocephalus or died with hydrocephalus in the neonatal period had prolonged clearance of CSF bilirubin and ferritin compared to infants who did not require a shunt (11 vs. 8.5 weeks; 13 vs. 8.75 weeks respectively, p < 0.05).
CONCLUSIONS: Among preterm neonates with post-hemorrhagic ventricular dilation, earlier clearance of CSF ferritin and bilirubin may predict resolution of ventriculomegaly and lower risk of post-hemorrhagic hydrocephalus.
Keywords: Cerebrospinal fluid, Intraventricular hemorrhage, Ferritin, Bilirubin, Post-hemorrhagic ventricular dilation, Post-hemorrhagic hydrocephalus
PF-045
Hydrocephalus
Volumetric analysis in post-haemorrhagic ventricular dilatation: a retrospective cohort study
Matthew Kane1, Jonathan O’muircheartaigh2, Malak Mohamed1, Cristine Sortica Da Costa3, William Dawes3, Gregory James3, Aswin Chari3, Kristian Aquilina3
1UCL Great Ormond Street Institute of Child Health, London, UK
2King's College London Department of Forensic and Neurodevelopmental Sciences, London, UK
3Great Ormond Street Hospital, London, UK
BACKGROUND AND AIM: To identify the factors influencing brain volumes at term-equivalent age (TEA) and to determine how these brain volumes and other factors correlate with neurodevelopmental outcome (NDO) among infants with post-haemorrhagic ventricular dilatation (PHVD).
METHOD: This was a retrospective cohort study conducted in a single paediatric neurosurgical department in the UK.
The study included all preterm infants with PHVD who required ventriculosubgaleal shunt (VSGS) insertion at Great Ormond Street Hospital (GOSH) between January 2012 and December 2020. These infants received standardised management according to the local treatment protocol, with VSGS as the first-line temporising device.
Brain volumes were extracted from MRI scans performed at TEA using semi-automated segmentation. NDO was retrospectively classified using the grading system developed by Resch et al. (1996).
RESULTS: 84 infants with median gestational age of 26.00 weeks (range 23.14–33.71) and birth weight of 857.50 g (range 533–2500) were evaluated. 31 infants had segmented MRI scans at TEA (31–62 weeks post-menstrual age), while the remaining 53 infants had brain volumes entered via multiple imputation.
On multivariate analyses, cerebellar volume decreased by 12.75 mL (95% CI 7.61–17.90) among infants with sepsis and by 10.46 mL (95% CI 3.87–17.05) among those with multiloculated hydrocephalus. Deep grey matter (dGM) volume decreased by 0.09 mL (95% CI 0.04–0.15) per day of intubation and by 3.19 mL (95% CI 0.20–6.18) among infants requiring inotropes. Time from intraventricular haemorrhage to first VSGS insertion was a non-significant factor in the multivariate model for dGM volume (p = 0.102). Greater dGM volume was associated with reduced odd of adverse NDO at two-year follow-up (odds ratio 0.873; 95% CI 0.793–0.960).
CONCLUSIONS: dGM volume at TEA could provide a useful prognostic marker for NDO among infants with PHVD. Addressing modifiable factors that adversely influence dGM volume may improve outcomes for these infants.
Keywords: Hydrocephalus, Intraventricular haemorrhage, Neonate, Ventriculosubgaleal shunt, Brain volume, Neurodevelopmental outcome
PF-046
Hydrocephalus
A Standardised Protocol for Neuro-endoscopic Lavage for Post-haemorrhagic Ventricular Dilatation: A Delphi Consensus Approach
Saniya Mediratta, Aswin Chari, Kristian Aquilina
Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, UK
BACKGROUND AND AIM: Neuro-endoscopic lavage (NEL) has shown promise as an emerging procedure for intraventricular haemorrhage (IVH) and post-haemorrhagic ventricular dilatation (PHVD). However, there is considerable variation with regards to the indications, objectives, and surgical technique in NEL. There is currently no randomised trial evidence that supports the use of NEL in the context of PHVD. This study aims to form a consensus on technical variations in the indications and procedural steps of NEL.
METHOD: A mixed methods modified Delphi consensus process was conducted between consultant paediatric neurosurgeons across the United Kingdom. Stages involved literature review, survey, focused online consultation, and iterative revisions until > 80% consensus was achieved.
RESULTS: Twelve consultant paediatric neurosurgeons from 10 neurosurgical centres participated. A standardised protocol including indications, a 3-phase operative workflow (pre-ventricular, intraventricular, post-ventricular) and post-operative care was agreed upon by 100% of participants. Case- and surgeon-specific variation was considered and included through delineation of mandatory, optional, and not recommended steps.
CONCLUSIONS: Expert consensus on a standardised protocol for NEL was achieved, delineating the surgical workflow into three phases: pre-ventricular, intraventricular, and post-ventricular, each consisting of mandatory, optional, and not recommended steps. This work provides a platform for future trials, training, and implementation of NEL.
Keywords: Neuro-endoscopic lavage, Post-haemorrhagic ventricular dilatation, Post-haemorrhagic hydrocephalus, Delphi consensus, Neurodevelopmental outcome
PF-047
Neurotrauma/Critical Care
Impairment in neurotransmitter balance after acute mild traumatic brain injury
Andrei Manzhurtsev1, Maxim Ublinskiy2, Tolib Akhadov3, Natalia Semenova1
1Clinical and Research Institute of Emergency Pediatric Surgery and Trauma
2Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences
3Moscow State University
BACKGROUND AND AIM: The mechanisms underlying functional disorders in the central nervous system (CNS) caused by traumatic brain injury (TBI) require intensive research. The balance between major neurotransmitters (excitatory – glutamate, and inhibitory – ?-aminobutyric acid, GABA), is crucial for the normal functioning of CNS. However, GABA concentrations vary in different cerebral zones [1] responsible for different cerebral tasks. In this study, [GABA] is measured in the posterior cingulate cortex (PCC) of children with acute mTBI.
METHOD: Seventeen patients with acute mTBI (12–70 h since the injury, aged 15.7 ± 1.9) and fifteen healthy age- and sex-matched subjects participated in the study. MRI scanner Philips Achieva dStream 3.0 T was used. Standard MRI protocol for TBI patients was applied, no pathological lesions in brain tissue of any subject were found. Magnetic resonance spectroscopy (MEGA-PRESS pulse sequence [2]) was applied in order to obtain GABA signal not contaminated by macromlecules. Spectroscopy voxel location is demonstrated on Fig. 1. The intensities of GABA, glutamate + glutamine, creatine and water signals were calculated in Gannet program [3]. Absolute concentrations of GABA and Glx were calculated. Statistical analysis was performed in STATISTICA 12. The Mann–Whitney criterion was used to reveal the significance of between-group differences.
RESULTS: The values of [GABA] in PCC in mTBI are statistically significantly increased by 22%, p = 0.0077. No changes in Glx were found.
CONCLUSIONS: The result obtained in current work is in agreement with the result of our previous study, where GABA was found increased (p < 0.005) in the anterior cingulate cortex of children with mTBI when comparing to healthy controls [4]. This indicates to a necessity of further data collecting in order to be ensured in the presence of [GABA] alterations in various cerebral loci. This would help to identify the causes of an inhibition/excitation imbalance and to predict possible dysfunctions of the CNS following mild TBI.
Keywords: mTBI, GABA, MRS
PF-048
Neurotrauma/Critical Care
Technical adaptations and applications of microdialysis in paediatric neurocritical care
Anthony Figaji1, Rentia Lourens1, Jill Combrinck1, Phophi Tshavhungwe1, Lindizwe Dlamini1, Shamiel Salie2, Nqobile Thango1, Nico Enslin1, Ursula Rohlwink1
1Division of Neurosurgery and Neuroscience Institute, University of Cape Town
2Division of Paediatric Critical Care, University of cape Town
BACKGROUND AND AIM: Microdialysis (MD) is an advanced tool to monitor targeted metabolites in brain extracellular fluid (ECF), but little is known about its application in children. Current limitations of the conventional method (tissue-MD) include compartmentalization and the poor quantification of true concentrations (relative recovery). We report our experience using MD with high molecular weight cut-off membranes to examine macromolecules as well as our recent adaptation to enable continuous CSF analysis to address tissue-MD limitations.
METHOD: We conducted a prospective study of children with severe traumatic brain injury (TBI) and meningitis (bacterial and tuberculous [TB]). Standard MD biochemistry was performed hourly at the bedside; remnant MD fluid was frozen for offline analysis. 100 kDa MD catheters were used for tissue MD. A novel adapted method of CSF MD monitoring was developed with CSF drainage flow-controlled through a Liquorguard pump (CSF-MD) using 20 kDa and 100 kDa catheters. We performed in vitro experiments to determine the influence of multiple variables (eg, flow rate and pressure) on sample analysis.
RESULTS: We performed MD monitoring in 82 children: 72 with conventional tissue-MD (61 TBI, 11 meningitis); 10 with the new CSF-MD method (8 meningitis; 2 TBI). Of the standard biochemistry, the lactate/pyruvate ratio was most useful: increases correlated with compromised brain tissue oxygenation. Offline analysis of proteomics and inflammatory mediators was successful. The limitations of tissue-MD were addressed by the new CSF-MD method. This enabled, for the first time, high quality data of bound and unbound drug in hourly sampling. We analysed antibiotics (anti-TB drugs, Ceftriaxone, Cefazolin), analgesics and sedatives (morphine, midazolam, ketamine) and anti-convulsants (levetiracetam).
CONCLUSIONS: This is the first large scale MD study in children, demonstrating examination of metabolites, proteins, inflammatory mediators, and drug penetration. Our CSF-MD adaptation has enabled, for the first time, high frequency quantitative drug recovery in the CSF, both for research and potentially individualized management.
Keywords: Microdialysis, Neurocritical care, Neurotrauma, Meningitis, Pharmacokinetics, Microdialysis
PF-049
Neurotrauma/Critical Care
Analysis of infantile subdural hematoma based on a nationwide multicenter retrospective study in Japan
Young Soo Park1, Nobuyuki Akutsu2, Ayumi Narisawa3, Atsuko Harada4, Mihoko Kato5, Masahiro Nonaka6
1Department of Neurosurgery and Children’s Medical Center, Nara Medical University, Nara, Japan
2Department of Neurosurgery, Hyogo Prefectural Kobe Children’s Hospital, Hyogo, Japan
3Department of Neurosurgery, Sendai City Hospital, Miyagi, Japan
4Department of Pediatric Neurosurgery, Takatsuki General Hospital, Osaka, Japan
5Department of Neurosurgery, Aichi Children's Health and Medical Center, Aichi, Japan
6Department of Neurosurgery, Kansai Medical University, Osaka, Japan
BACKGROUND AND AIM: It is an undeniable truth that subdural hematoma (SDH) in infants is caused by shaken baby syndrome (SBS), and the possibility of abusive head trauma (AHT) should be considered. However, it should not be ignored that SDH is also caused by accidents inside the house. The recent confusion in AHT's judgment is derived from the fact that the actual occurrence of SDH due to accidents has not been fully verified. The purpose of this study was to investigate SDH by an all-cases survey.
METHOD: This multicenter, retrospective study reviewed the clinical records of children younger than 4 years with any abnormal findings on CT between 2014 and 2020. The accidental group was judged by the child protection team and/or the child guidance center. Multivariate analysis was conducted to identify which factors increase the risk of nonaccidental injury.
RESULTS: Of the 452 patients, 158 were diagnosed with SDH. A total of 51 patients were classified into the nonaccidental group, and 107 patients were classified into the accidental group. The age of patients with SDH showed a bimodal pattern. The mean age of the accidental group was significantly older than that in the nonaccidental group (10.2 months vs 5.9 months). The details of the injury mechanism were self-inflicted fall in 30 cases and falling from a bed or sofa in 19 cases, which is consistent with Nakamura's type 1 hematoma well known in Japan. Multivariate analysis showed patients under 5 months old, retinal hemorrhage, and seizure were significant risk factors for nonaccidental injury. Further unexplained convulsion was significantly associated with increased odds of nonaccidental injury. Of the 23 cases with so-called trias, 11 were actually accident cases.
CONCLUSIONS: Infantile SDH was frequently observed in accidental injuries. SDH is a powerful discovery for detecting AHT, but careful consideration and comprehensive understanding should be required to determine AHT.
Keywords: Infantile subdural hematoma, Abusive head trauma, Nakamura Type 1 Intracranial Hemorrhage, Nationwide multicenter retrospective study
PF-050
Neurotrauma/Critical Care
Non accidental head and body injury patterns in Costa Rica during Covid-19 lockdown and post-lockdown periods
Adrian Caceres1, Esteban Granados Fonseca2, Andrea Monge Sanabria3
1Neurosurgery department, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
2Social Work department, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
3Trauma unit, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
BACKGROUND AND AIM: Diverse social and family dynamics were observed during the compulsory lock down period due to the Covid 19 epidemic.
Our purpose was to analyze the patterns of accidental and non accidental head and body injuries and to correlate the documented cases of non accidental severe head injury before and after the lockdown period in order to establish if these exceptional circumstances influenced the occurrence of inflicted severe head injury in infants.
METHOD: We performed a retrospective analysis of all children referred with trauma related injuries to the sole institution for pediatric neurosurgical care in Costa Rica. We reviewed all admissions related to trauma at the ED and did a retrospective analysis of age, trauma related injuries, cases suspected to be non accidental and the overall impact of these lesions during the 2 strict lockdown periods in Costa Rica.
RESULTS: there was a significant decrease on the number of trauma related cases referred to our trauma unit. A 57% and 48% decrease of total cases was observed during the first and second 3 month lockdown periods of 2020. A significant decrease in the number and severity was observed in MVA and a increase in household burns, dog bites and falls. There was a total 44% decrease of cases of non accidental injuries. There were only 4 children who died due to accidental trauma in 2020 as opposed to 10 in 2019. None of the patients who died during 2020 were related to non accidental severe head injury.
CONCLUSIONS: Contrary to the suspected increase in domestic violence during the 2020 lockdown a family protective environment was observed in households probably by preventing the aggressors to be left alone with infants and therefore preventing severe non accidental head injury. Most injuries observed were related to household conditions (burns, dog bites, falls).
Keywords: Non accidental head injury, Covid-19 lockdown, Domestic violence, Trauma, Children
PF-051
Epilepsy
Long-term outcome of surgery in children with drug resistant epilepsy and focal cortical dysplasia
Manas Panigrahi1, Sitajayalakshmi Sattaluri2, Sailiaja Mudumba3
1Dept of Neurosurgery, KIMS
2Dept of Neurology, KIMS
3Dept of Pathology, KIMS
BACKGROUND AND AIM: To evaluate factors affecting outcome in children with drug resistant epilepsy and focal cortical dysplasia (FCD) who underwent surgery.
METHOD: We analyzed data of 112 consecutive children operated at a tertiary referral centre for drug resistant epilepsy and a diagnosis of FCD on histopathology between January2005 and December 2015. The inclusion criteria were 1) isolated type I and/or type II FCD within the surgical specimen 2) at least five years post-surgery follow-up.
RESULTS: The average age at onset of epilepsy was 4.56 ± 3.88 (0 – 18) years with mean duration of epilepsy of 6.50 ± 5.02 (0.3– 18) years. The average age at surgery was 10.27 ± 5.14 (2 – 18)years. Delayed development was observed in 39 (34.8%), while 56 (50.0%) had below average intelligence. Associated psychiatric disorder and /or behavioural problems were diagnosed in 67 (59.8%) patients. Inter-ictal EEG showed focal/regional epileptiform discharges in 55 (49.1%). Seizure semiology was lateralizing in 77 (68.8%) while 52 (46.4%) had regional ictal EEG onset. MRI showed clear cut FCD in 96 (85.7%). At the latest follow-up 73 (65.2%) patients had a favourable Engels outcome. Onset of seizures below two years of (30.1 vs 53.8%; p = 0.024,) multiple types of seizures at presentation (21.9% vs 46.2%; p = 0.010), developmental delay (23.3% vs 56.4%; p = 0.001), generalized seizure semiology (54.8% vs 79.5%; p = 0.013) and acute post-operative seizures (19.4% vs 48.7%; p = 0.002), were associated with unfavourable outcome. Complete resection of the FCD (91.8% vs 46.2%; p < 0.001), type II FCD (51.4% vs 21.2%; p = 0.027), lateralizing semiology (75.3% vs 56.4%; p = 0.054) were associated with favourable outcome. The predictor for favourable outcome was complete resection.
CONCLUSIONS: Favorable outcome after surgery for DRE and FCD in children was seen in 65% and complete resection was the predictor of favourable outcome.
Keywords: Focal cortical dysplasia, Epilepsy surgery
PF-052
Epilepsy
The MAST Trial: Prospective evaluation of a machine learning algorithm for the planning of SEEG trajectories
Aswin Chari1, Sophie Adler5, Konrad Wagstyl5, Kiran Seunarine5, Zubair Tahir1, Friederike Moeller3, Rachel Thornton3, Stewart Boyd3, Krishna Das3, Gerald Cooray3, Felice D'arco4, Torsten Baldeweg5, Christin Eltze2, Helen Cross2, Martin Tisdall1, Ido Ben Zvi1
1Department of Neurosurgery, Great Ormond Street Hospital
2Department of Neurology, Great Ormond Street Hospital
3Department of Neurophysiology, Great Ormond Street Hospital
4Department of Neuroradiology, Great Ormond Street Hospital
5Institute of Child Health, University College London
BACKGROUND AND AIM: Despite a plethora of machine learning algorithms that have been developed in the field of epilepsy, few have undergone prospective clinical evaluation with a view to being integrated into routine clinical practice. Here, we report results of a prospective evaluation a lesion detection algorithm designed to detect focal cortical dysplasia (FCD) in children undergoing stereoelectroencephalography (SEEG) at a single centre.
METHOD: This was a prospective single arm interventional (IDEAL phase 1/2a) study of 20 patients. Children undergoing SEEG were enrolled. Following routine SEEG planning, T1 and Flair MRI scans were run through the MELD lesion detection algorithm to identify putative lesion clusters, which were merged with the planned electrode trajectories. If the top 3 MELD-identified lesion clusters were not already sampled, up to 3 additional SEEG electrodes were added. The primary outcome measure was the proportion of patients that had additional electrode contacts in the SEEG-defined seizure onset zone. Secondary outcomes included safety and efficacy end points.
RESULTS: Twenty patients (median age 12, range 4–18) were enrolled over 2 years, one of whom did not end up undergoing SEEG implantation. Additional electrode contacts were part of the SOZ in 1/19 (5.3%) whilst 2/19 (10.5%) had lesions clusters that were part of the SOZ but already implanted. A total of 63 lesion clusters were identified (range 0–11), of which 23 fulfilled criteria for implantation. A total of 16 additional electrodes were implanted in 9 patients and there were no adverse events from the additional electrodes implanted.
CONCLUSIONS: We demonstrate early-stage prospective clinical validation of a machine learning lesion detection algorithm in aiding the identification of the seizure onset zone in children undergoing SEEG. Further multi-centre validation will build the rationale for incorporating such technology into routine clinical use.
Keywords: Epilepsy, Seeg, Machine learning
PF-054
Epilepsy
Quality of life of children with surgically treated epilepsy-the patient’s perspective
Ido Ben Zvi, Aswin Chari, Martin Tisdall
Department of Neurosurgery, Great Ormond Hospital for Children
BACKGROUND AND AIM: Clinical trials and studies in epilepsy surgery commonly use the seizure outcome (Engel or ILAE Classification) as the primary outcome measure, with the focus being on the proportion of patients achieving seizure freedom. However, little data exists as to what outcomes are important to patients and their carers. We sought to ascertain the most important outcomes for patients and their carers.
METHOD: An international online anonymous survey was conducted through patient advocacy groups. The survey consisted of 18 multiple choice questions. In addition to demographic questions about the patient and the management of their epilepsy, the survey asked what the most important outcomes were across multiple domains including seizure-related, cognition and developmental, quality of life and other long-term outcomes.
RESULTS: 204 patients or parents/carers responded to the survey. 61% were children or their carers. 72% report focal seizures (30% of them have generalized seizures as well). 53.4% currently have more than one seizure a month (23.5% daily). 37.2% of patients had undergone surgery. Half of them reported seizure freedom, and 90% reported postoperative improvement. When asked what outcome measure was most important, 44.6% responded being seizure free and 26% desired improvement in quality of life. When asked about the timing of potential surgical treatment, 64.7% would consider having surgery soon after the diagnosis of epilepsy; this percentage was higher among operated patients (72%), but without statistical significance (p = 0.077).
CONCLUSIONS: More than third of our cohort had an operation, with half reporting seizure freedom. Across this large sample, the most important outcome measure is being seizure-free, reinforcing focus on seizure freedom in clinical trials. The second most important outcome measure was quality of life, emphasizing the need to measure these outcomes in clinical studies of epilepsy and epilepsy surgery. Many would consider early surgery and the risks and benefits of this warrant further study.
Keywords: Epilepsy surgery, Quality of life, Seizure outcome, Patient perspective
PF-055
Epilepsy
Detection of focal cortical dysplasia in drug-resistant epilepsy using Raman Spectroscopy
Trang Tran1, Frederic Dallaire2, Romain Cayrol3, Joshua Sonnen4, Frederic Leblond1, Roy Dudley4
1Research Institute of the McGill University Health Centre; Polytechnique Montréal; Centre Hospitalier Universitaire de Montréal (CRHUM)
2Département Imagerie Optique, Polytechnique Montréal
3Department of Pathology, Centre Hospitalier Universitaire de Montréal (CHUM)
4Department of Neurology and Neurosurgery, McGill University Health Center (MUHC)
BACKGROUND AND AIM: Focal cortical dysplasias (FCD), characterized by abnormal cortical architecture, are the most common cause of drug-resistant focal epilepsy in the pediatric population. Children with this disorder can have tens to hundreds of seizures per day, and only surgery can remove FCD lesions to cure focal epilepsy, but surgical success depends on the ability to resect the lesion completely while minimizing damage to perilesional normal tissues. However, these lesions and/or their borders are usually not well seen on MRI, making them very difficult to remove completely. Thus, new imaging techniques for detecting FCD margins during surgery are needed to improve surgical results. Raman spectroscopy (RS) is a nondestructive, label-free optical method, that allows the characterization of the tissue composition. The goal of this ex-vivo and on-going in-vivo study is to use Raman spectroscopy to discriminate between normal and dysplastic brain tissue.
METHOD: 85 stained sections of biopsy specimens from 30 patients with focal epilepsy were acquired ex-vivo, 5 in-vivo specimens were probed by the neurosurgeon in areas believed to contain FCD based on the presurgical evaluation data and pre-operative plan, and all the specimens were assessed by a pediatric neuropathologist. In the ex-vivo, Raman map points were recorded from targeted abnormal regions with structures characterizing FCD: dysmorphic neurons, balloon cells and cortical dyslamination using a Raman microscope.
RESULTS: With more than 2000 spectra acquired, significant spectral differences were observed between the dysplastic tissue regions and normal regions in the cortex. Indeed, FCD tissues exhibited significantly increased spectral at the peaks of proteins (DNA, RNA and phenylalanine) and interestingly, lower in lipids. We then trained a machine learning model capable of detecting FCD tissues with a 96% accuracy, 100% sensitivity and 95% specificity.
CONCLUSIONS: By accurately detecting dysplastic tissues, quantitative RS holds the potential for improving the accuracy of brain epilepsy surgery in real-time.
Keywords: Epilepsy, Focal cortical dysplasia, Raman spectroscopy, Neurosurgery
PF-056
Functional
Predicting success in selective dorsal rhizotomy (SDR): past, present and future
Benedetta Pettorini1, Conor S. Gillespie2, Chris Sneade1, Benjamin J. Hall1
1Department of Neurosurgery, Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, UK
2The University of Liverpool
BACKGROUND AND AIM: Patient selection for selective dorsal rhizotomy (SDR) is complex, depends on a number of variables and has little international consensus: resulting in significant heterogeneity. We reviewed previous attempts at predicting SDR outcomes and present our attempt at designing a predictive scoring tool to aid in patient selection.
METHOD: All SDR patients at a UK paediatric neurosurgical centre operated between 2014–2020, with minimum 12-months follow-up, were included. ‘Success’ was defined as: at least one ‘patient reported’ improvement (pain reduction, quality of life score) plus one ‘patient observable improvement’ (clinically significant increase in GMFM, PEDI, MAS, or 6MWT scores). Univariable logistic regression analysis was performed to determine factors associated with SDR success, before incorporation into a multivariable regression model if p < 0.01. Literature review was performed utilising search terms: ‘predicting’, ‘outcome’, ‘SDR’ and ‘cerebral palsy’.
RESULTS: 73 children were included (median age 6.2 years, IQR 4.75–8.00). 61.6% female (n = 45). SDR success was observed in 58.9% of children at 6 months (n = 43/73) and in 67.1% of children at 12 months (n = 49/73). The only factor associated with success on univariable analysis was ‘lack of dystonia’ (Odds ratio [OR] 5.06, 95% confidence interval [CI] 0.85–30.23, p = 0.076). Non-significant (p > 0.05) factors on univariable analysis were: age (OR 1.02, 95% CI 0.86–1.20), Female sex (OR 1.82, 95% CI 0.64–5.19), Baseline GMFCS (OR 0.69, 95% CI 0.37–1.27), Baseline GMFM (OR 1.04, 95% CI 0.99–1.10), and Pain score (OR 1.03, 95% CI 0.86–1.19). Literature review identified 10 articles identifying preoperative factors predictive of outcome, though no clinically applicable scoring system currently exists.
CONCLUSIONS: ‘Success’ following SDR remains challenging to define and predict. Few preoperative factors accurately predict success; preventing development of any clinically useful predictive tool. Consensus meetings and high-quality follow-up data are required to better define ‘success’, identify associated factors and allow more rigorous statistical analysis to aid in future patient selection.
Keywords: Selective dorsal rhizotomy, Success, Predict, Outcomes
PF-057
Functional
Ultrasound Level Check in Selective Dorsal Rhizotomy – Experience in 152 cases
Chloé Louise Gelder1, Ieva Sataite2, Rebecca Sarah Chave Cox1, John Robert Goodden1
1Regional Neurosciences Centre, Department of Neurosurgery, Leeds Children's Hospital, Leeds, United Kingdom
2Department of Neurosurgery, Royal Hospital for Children and Young People, Edinburgh, United Kingdom
BACKGROUND AND AIM: Selective Dorsal Rhizotomy (SDR) surgery typically requires a level check for L1, to identify the conus location using on-table x-ray, pre-operative marking and/or ultrasound. We present a case series of 152 SDR operations undertaken using pre-operative (percutaneous) and intra-operative ultrasound as the main modality for the level check.
METHOD: The Leeds Children’s Hospital prospective SDR database was used to identify patients. All operation notes were reviewed, recording the method used for level check.
RESULTS: In total 152 SDR patients have had SDR, mean age 6.48 years (range 2.63–19.06); 76 GMFCS II, 76 GMFCS III; M:F 95:57. Pre-operative level check was performed with ultrasound alone in 141 patients; 11 had combined x-ray & ultrasound level check. The 11 patients who had combined x-ray & ultrasound level checks, were the first patients having SDR in our centre. This allowed the surgeon to assess accuracy and establish the feasibility of percutaneous ultrasound at the start of surgery instead of x-ray. For the subsequent 141 patients, ultrasound alone was sufficient for both pre-operative (percutaneous) and intra-operative level-check, even for those aged > 10-years. During the course of surgery, once the wound was opened, all 152 patients had an intra-operative ultrasound level check to confirm the level of the conus before opening the dura. There were no instances of wrong-level surgery with this technique.
CONCLUSIONS: In our experience, following a short period of learning, ultrasound has proven to be safe and effective for perioperative identification of the conus level for SDR surgery in all ages. This has the advantage of avoiding a radiation dose, saving x-ray cost and improving theatre workflow efficiency.
Keywords: Selective dorsal rhizotomy, Ultrasonography, Intra-operative level check, Cerebral palsy
PF-058
Dysraphism
Characterizing syringomyelia and its clinical significance in 140 patients with lipomyelomeningocele
Ananth P Abraham1, Tarang K Vora1, Bernice T Selvi2, Vedantam Rajshekhar1
1Department of Neurological Sciences, Christian Medical College, Vellore, India
2Department of Radiology, Christian Medical College, Vellore, India
BACKGROUND AND AIM: The aim of this study was to characterize syringomyelia in patients with lipomyelomeningocele (LMMC) and determine its association with their neurological deficits.
METHOD: A single-centre, observational study included a retrospective chart review of children with LMMC diagnosed between 2007 and 2020. Those who had synchronous dysraphic conditions such as split-cord malformations or dermoid cysts were excluded. Syringomyelia on magnetic resonance imaging (MRI) was classified into 3 groups – true syrinx, early syrinx and pre-syrinx based on clearly defined criteria. Correlation of neurological deficits (at birth, new onset and progressive) with the presence and type of syrinx was studied.
RESULTS: A total of 140 patients met the inclusion criteria. The median age of the patients was 2.5 (IQR 1.3–9) years. Neurological deficits were present at birth in 75 (53.6%) patients while 67 (47.9%) had new-onset deficits or progression of their birth deficits. The most common type of spinal lipoma was the transitional type (75.7%). Thirty nine (27.8%) patients had syrinx (37 had true syrinx, 2 had early syrinx) and 25 (17.9%) patients had pre-syrinx. There was no significant correlation between the presence of a syrinx (true and early) or pre-syrinx and patients’ neurological deficits. However, patients with a syrinx that was not adjacent to the lipoma (≥ 1 vertebral level away) had a higher incidence of deficits at birth (p = 0.04) while those with a syrinx spanning ≥ 5 vertebral levels had a higher incidence of progressive neurological deficits (p = 0.04). Six of 8 (75%) patients in whom serial MRI showed progression of syrinx had clinical worsening.
CONCLUSIONS: Syrinx location with respect to the spinal lipoma, syrinx length and progressive syringomyelia may have clinical significance in patients with LMMC.
Keywords: Syringomyelia, Syrinx, Characterization, Lipomyelomeningocele, Dysraphism
PF-059
Spine
Pediatric congenital atlantoaxial dislocation: Our experience, challenges and solutions
Karthigeyan Madhivanan, Pravin Salunke, Sushanta Sahoo, Narasimhaiah Sunil
Department of Neurosurgery, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India
BACKGROUND AND AIM: The management aspects of pediatric congenital atlantoaxial dislocation (CAAD) differ from that of the adults. Softer bones, highly deformed joints, and fusion of multiple vertebral levels with potential for spinal growth impairment in younger age are a few unique challenges pertaining to this age group. We describe our experience and the related challenges along with solutions, following multiplanar realignment and short-segment C1-C2 fusion in children with CAAD.
METHOD: A total of 56 pediatric patients with congenital AAD underwent C1-C2 posterior reduction and fixation. The oblique C1-C2 joints were drilled, and remodeled to achieve multiplanar realignment. The baseline clinico-radiological data were compared with that of the follow up.
RESULTS: The series included 35 cases with irreducible and 21 cases with reducible AAD; the former had a higher incidence of bony anomalies, and the joints were more oblique and deformed. Nine patients had lateral angular dislocation, 3 had C1-C2 spondyloptosis and 5 had significant vertical dislocation. The C1-C2 joint drilling and manipulation was feasible in all patients. The operative techniques were modified to achieve an optimal bony purchase secondary to the drilling of relatively small bones and also avoid screw pull out during intraoperative manipulation. Despite some challenges in few initial cases, realignment could be achieved in all. At follow up, there was a significant improvement in mJOA score in 95.8% of cases, with 28 patients being independent.
CONCLUSIONS: Children show relatively high oblique C1-C2 joints and therefore a frequent occurrence of spondyloptosis, severe vertical dislocation and lateral tilt. Despite the soft and small pediatric bones, a multiplanar realignment could be achieved by C1-C2 joint drilling and manipulation. The short segment C1-C2 fusion offers satisfactory clinical and imaging outcome in pediatric CAAD.
Keywords: Craniovertebral junction, Atlantoaxial, Pediatric spine, C1-C2, Basilar invagination, Multiplanar
PF-060
Spine
Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari I malformation and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium
Syed Hassan Abbas Akbari1, Alexander Yahanda2, David Delmar Limbrick2, The Park Reeves Syringomyelia Research Consortium Contributors3
1Department of Neurosurgery, Johns Hopkins University School of Medicine, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
2Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
3The Park-Reeves Syringomyelia Research Consortium Contributors
BACKGROUND AND AIM: Chiari I malformation with syringomyelia (CM1-SM) is commonly treated with either a posterior fossa decompression with (PFDD) or without (PFD) duraplasty. The aim of this study was to determine differences in complications and outcomes between PFDD and PFD for pediatric CM1-SM.
METHOD: Surgically treated CM1-SM patients with on-year follow-up data were identified using the Park-Reeves Syringomyelia Research Consortium database. Preoperative, treatment, and postoperative characteristics were compared.
RESULTS: 692 patients met inclusion criteria. PFD was performed in 117 and PFDD in 575 patients. The mean age at surgery was 9.86 years and follow-up time was 2.73 years. There were no differences in presenting signs or symptoms between groups, though preop syrinx size was smaller in the PFD group. The PFD group had shorter OR time (p < 0.0001) and hospital stays (p = 0.0001), and lower blood loss (p = 0.04). There were 4 intraoperative complications, all within the PFDD group (0.7%, p = 1.00). PFDD patients had a higher 6-month complication rate (24.3% versus 13.7%, p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% versus 8.5%, p = 0.004). PFDD showed greater improvements in headaches (89.6% versus 80.8%, p = 0.04) and back pain (88.3% versus 59.1%, p = 0.01). There were no group differences for improvement in neurological exam findings. PFDD showed greater reduction in AP syrinx size (43.7% versus 26.9%, p = 0.0001) and syrinx length (18.9% versus 5.6%, p = 0.04) compared to PFD. Among PFDD patients, allograft was associated with higher rates of pseudomeningocele (p = 0.041) and chemical meningitis (p = 0.002) compared to autograft.
CONCLUSIONS: PFD is associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications. However, PFDD was associated with better symptom improvement, reduction in syrinx size, and lower revision rates. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.
Keywords: Chiari I malformation, Posterior fossa decompression, Duraplasty, Complications, Revision
PF-061
Global Pediatric Neurosurgery
Comparison of long-term survival of pediatric patients with drug-resistant epilepsy: continued medical therapy, vagus nerve stimulation, and cranial epilepsy surgery
Lu Zhang1, Matt Hall2, Sandi Karen Lam1
11Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA &Division of Pediatric Neurosurgery, Ann & Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, USA
2Data and Biostatistics, Children's Hospital Association, Lenexa, KS, USA
BACKGROUND AND AIM: The mortality of pediatric patients with drug-resistant epilepsy (DRE) is higher than the general population and adult patients. A better understanding of the treatment effect on mortality is needed for healthcare decision making. This study compared the long-term survival rate associated with different types of therapy in pediatric patients with DRE.
METHOD: Patients aged 0–17 years and diagnosed with DRE between January 1, 2004 and December 31, 2020 were identified from the Pediatric Health Information System Database. Patients treated with anti-seizure medications (ASMs) only or ASMs plus vagus nerve stimulation (VNS) or ASMs plus cranial epilepsy surgery were included in the study and were followed until the date of their last clinical encounter, in-hospital death, or December 31, 2020. Kaplan–Meier and log-rank test were used to estimate and test the difference in the unconditional probability of survival. Cox proportional hazards model was performed to compare time to death in the follow-up period.
RESULTS: This study included 10,240 patients treated with ASMs only, 5,019 patients treated with VNS, and 3,033 patients treated with cranial epilepsy surgery. The unconditional probability of surviving beyond 10 years were 89.93% for medical therapy cohort (95% CI, 88.56% to 91.30%), 93.38% for VNS cohort (95% CI, 91.81% to 94.95%), and 98.29% for cranial surgery cohort (95% CI, 97.31% to 99.27%). The difference in the estimates of survival probabilities was statistically significant (p < 0.001). Compared with patients in the medical therapy cohort, the risks of overall death were reduced by 33% (HR = 0.660; 95% CI, 0.506 to 0.863) and 83% (HR = 0.168; 95% CI, 0.106 to 0.207) for patients in the VNS cohort and the cranial epilepsy surgery cohort, respectively.
CONCLUSIONS: Our findings suggest survival benefit with surgical treatments for DRE and point to the need for increased and more timely evaluations and referrals to comprehensive epilepsy centers where surgical treatments are available.
Keywords: Pediatric, Drug-resistant epilepsy, Survival, Anti-seizure medication, Vagus nerve stimulation, Epilepsy surgery
PF-062
Hydrocephalus
Genetically-determined alterations in inflammation and infection-associated genes cause hydrocephalus in patients of African Ancestry
Andrew T Hale1, Steven J Schiff2, Eric R Gamazon3
1Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA
2Centers for Neural Engineering and Infectious Disease Dynamics, Departments of Neurosurgery, Engineering Science and Mechanics, and Physics, Penn State University. University Park, PA, USA
3Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
BACKGROUND AND AIM: The genetic mechanisms underlying hydrocephalus risk and pathogenesis are complex. Our group recently completed a comprehensive human genetic and functional genomics study of pediatrc hydrocephalus in patients of European ancestry (Hale et al., ‘Multi-omic analysis elucidates the genetic basis of hydrocephalus.’ Cell Reports, 2021), identifying genes involved in regulation of chromatin structure underlying hydrocephalus risk. However, the disease burden of hydrocephalus is amongst the highest in the world in Sub-Saharan Africa. Here we apply human genetics and functional genomics approaches to delineate the genetic basis of hydrocephalus in patients of African ancestry.
METHOD: We perform a transcriptome-wide association study (TWAS) in pediatric patients of African ancestry with hydrocephalus across 3,388 individuals (146 cases and 3,242 controls). Gene set enrichment analysis (GSEA) was performed to identify genetically-determined pathways conferring hydrocephalus risk.
RESULTS: After multiple-testing correction (false discovery rate < 0.05) across all genes tested, we identify decreased expression of TMEM208 as an outlier. TMEM208 met the highly-stringent Bonferroni threshold for statistical-significance based on the total number of genes tested (OR = 2.07, p < 5.22 × 10–8) indicating that TMEM208 is a transcriptome-wide predictor of hydrocephalus. GSEA of all nominally-associated genes (p < 0.05) revealed a marked association with genes regulating inflammatory and infection-related processes.
CONCLUSIONS: We perform the first systematic genetic study of hydrocephalus in patients of African ancestry. Whereas our previous study (Hale et al. Cell Reports, 2021) demonstrated that the genetic underpinnings of hydrocephalus in Europeans are largely driven by alterations in DNA structure, here we identify perturbations in inflammation and infection-associated genes underlying hydrocephalus in patients of African descent. Co-evolution of humans and pathogen-imposed selection pressures have differentially shaped the genetic etiology of hydrocephalus across ancestral populations.
Keywords: Hydrocephalus, Human genetics, Functional genomics, African
PF-063
Moya-Moya disease
Surgical Revascularization Decreases Stroke and TIA Risk in Children with Sickle Cell Disease and Moyamoya Syndrome: Results of the Stroke in Sickle Cell Revascularization Surgery Study (SiSCRS)
Philipp Aldana1, Ricardo Hanel2, Joseph Piatt3, Sabrina Han4, Corinna Schultz3, Manisha Bansal3
1Wolfson Children's Hospital/University of Florida Jacksonville
2Lyerly Neurosurgery, Baptist Neuroscience Institute
3Nemours Children's Health
4University of Florida College of Medicine
BACKGROUND AND AIM: Recent studies have suggested that surgical revascularization may be a safe and effective therapy to reduce risk of cerebrovascular complications in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). These studies have been limited by small sample size and lack of a control group for comparison.
AIM: To investigate whether revascularization surgery reduces the risk of cerebrovascular events (CVEs) in comparison to conservative management alone in a retrospective cohort of children with SCD-MMS.
METHOD: A retrospective review of data from 15 major U.S. pediatric neurosurgery centers of SCD-MMS patients (< 18 y.o.) was performed. Detailed information on sickle cell disease, stroke and surgical histories were extracted. The incidence of CVEs (stroke and TIAs) between patients treated with surgical revascularization was compared to those with conservative management alone. Multivariate regression models were generated and logistic regression analyses were performed.
RESULTS: A total of 141 patients with SCD-MMS were studied. 78 (55.3%) were treated with conservative management and revascularization surgery (Surgery group) and 63 (44.7%) were treated with conservative management alone (Conservative group). Patients in the Surgery group had reduced odds of developing a CVE over the duration of their risk period (odds ratio = 0.27, 95% CI: 0.08–0.94, P = 0.040). Furthermore, when comparing patients in the Surgery group during their pre-surgical periods and post-surgical periods, patients had markedly reduced odds of developing a CVE after surgery (odds ratio = 0.22, 95% CI = 0.08–0.58, P = 0.002). Postoperatively, 3 patients had CVEs and 4 had non CVE complications.
CONCLUSIONS: Our retrospective study provides strong evidence that revascularization surgery can be performed safely and reduce risk of CVEs in patients with SCD-MM. This is the largest study of its kind to date. A prospective study will be needed to validate our findings.
Keywords: Sickle cell disease, Moyamoya syndrome, Stroke, Transient ischemic attack, Cerebrovascular events
PF-064
Global Pediatric Neurosurgery
Global Alliance for the Prevention of Spina Bifida (GAPSBIF); Organization, Evolution and Early Progress toward Global Folic Acid Fortification
Jeffrey P Blount1, Gail Rosseau2, Vijaya Kancherla3, Frederick A Boop4, Kemel Ghotme5, Adrian Caceres Chacon7, Marinus Koning12, Anastasia Smith1, Eylem Ocal6, Sylvia Roozen10, Jogi Patissipu13, Pedram Maleknia1, Amanda Dorsey3, Nathan Shlobin8, Helena Pachon3, Yakob Ahmed3, Sylvia Roozen13, Walter Johnson15, Dan Peterson14, Ken Anselmi16, Martina Gonzalez17, Priyanka K Mathur8, Homero Martinez11, Godfrey Oakley2, Kee Park9
1University of Alabama at Birmingham Department of Neurosurgery
2George Washington University Department of Neurosurgery
3Center for Spina Bifida Prevention, Rollins School of Public Health, Emory University
4St. Jude Children's Research Hospital
5Santa Fe Foundation of Bogota Colombia
6University of Arkansas Department of Neurosurgery
7National Hospital for Children, San Jose, Costa Rica
8Northwestern University Department of Neurosurgery
9Harvard Program in Global Surgery and Social Change
10International Federation for Prevention of Spina Bifida
11Nutrition International
12ReachAnother Foundation
13University of Central Florida
14G4 Alliance
15Center for Global Surgery, Loma Linda University
16East Carolina University
17Kings College, London
BACKGROUND AND AIM: Despite three decades of class I evidence demonstrating safety and effectiveness of folic acid fortification to prevent Spina Bifida (SB) less than 25% of prevented SB is prevented. Over 300,000 new cases of SB occur annually world-wide and the majority are preventable. GAPSBIF is a global alliance of neurosurgeons, epidemiologists and other clinical and public health professionals dedicated to science-based advocacy to attain global folic acid fortification. This presentation summarizes current initiatives, progress and key goals.
METHOD: Five enabling objectives are being purused. First, a resolution based upon an ISPN resolution supporting global fortification was introduced at WHA in June 2022. A primary objective will be adaptation by World Health Assembly of the resolution recently proposed. Second, updated publications, webinars and special events are occurring to inform key policy makers. Third, salt is being evaluated for feasibility to deliver sufficient folic acid to women of childbearing age. Fourth, high-risk intervention (and after-care) is being pursued in regions of high endemic SB prevalence. Finally, key relationships and individual partnerships with lead countries (Colombia, Ecuador, Ethiopia, India and Turkey) and other clinical stake holders are being fostered.
RESULTS: In June 2022 Colombia sponsored a resolution at WHA supporting global fortification. At the same time a review paper by GAPSBIF members was published in Lancet-Global Health. Other monographs are in production. Passage of the WHA resolution will require robust advocacy of WHA member states. Active advocacy and fostering of health ministers continue in targeted partnership countries. Salt is being investigated in at least 3 clinical trials. Supplementation and multi-disciplinary after care programs are expanding in Ethiopia and models for after care are being implemented.
CONCLUSIONS: ISPN neurosurgeons are central to GAPSBIF and are making progress toward global fortification. Opportunities for involvement and further engagement will be detailed.
Keywords: Advocacy, Folic acid, Spina bifida, Prevention
Flash Presentation Abstracts
FL-001
Neuro-Oncology
Lumbar Fenestration to Temporize Hydrocephalus after Craniotomy for Posterior Fossa Tumors in Children
Alex Y Lu, Peter P Sun
University of California, San Francisco
BACKGROUND AND AIM: Pediatric patients with newly diagnosed posterior fossa tumors frequently present with hydrocephalus. Even after external ventricular drainage and craniotomy for tumor resection, hydrocephalus may persist in the postoperative period. Lumbar fenestration, a technique that creates a temporary lumbar pseudomeningocele, can be performed under local anesthesia and may act as a temporary pressure release valve. This study investigates whether lumbar fenestration can reduce the postoperative incidence of cerebrospinal fluid diversion after craniotomy for posterior fossa tumor resection in children.
METHOD: A retrospective review of pediatric patients (presenting age < 18 years) was conducted at the University of California, San Francisco and Children’s Hospital Oakland between January 1st, 2010 and January 1st, 2022. Inclusion criteria for this single surgeon series includes patients with newly diagnosed posterior fossa tumor with evidence of hydrocephalus at presentation that subsequently underwent craniotomy for tumor resection and external ventricular drain placement. Exclusion criteria included supratentorial lesions, insufficient medical records, pre-operative ventriculoperitoneal shunting, or first craniotomy at external facility.
RESULTS: After evaluation, 55 patients with newly diagnosed posterior fossa tumors were identified who underwent craniotomy for tumor resection. 43 patients (78.2%) had hydrocephalus at presentation. The diagnoses of these patients included medulloblastoma (53.3%), pilocytic astrocytoma (23.3%), ependymoma (13.3%), atypical teratoid rhabdoid tumor (6.7%), and ganglioglioma (3.3%). Of the 43 patients with hydrocephalus, 30 patients underwent lumbar thecal sac fenestration. 14 (46.7%) of these patients have not required CSF diversion at last follow-up. No patients had complication attributed lumbar thecal sac fenestration nor did any patient require a blood patch postoperatively.
CONCLUSIONS: Lumbar fenestration has a low complication profile and may be a promising technique to reduce the incidence of cerebrospinal fluid diversion after craniotomy for posterior fossa tumor resection in pediatric patients.
Keywords: Lumbar fenestration, Posterior fossa tumor, Hydrocephalus
FL-002
Neuro-Oncology
Role of extent of resection in Medulloblastoma in context of molecular subgrouping—a retrospective audit
Prakash Shetty, Ujwal Yeole, Rajesh Krishna, Vikas Singh, Aliasgar Moiyadi
Department of Neurosurgery, Tata Memorial Hospital, and Homi Bhabha National Institute, Mumbai, India
BACKGROUND AND AIM: Extent of resection, along with age and metastatic status are important factors for risk stratification for deciding treatment in medulloblastomas.This study aims to look at the role of extent of resection in medulloblastomas in the context of molecular subgrouping.
METHOD: It is a retrospective audit of medulloblastoma patients looking at the role of extent of resection(EOR) in terms of PFS(progression free survival) and OS(overall survival) for the entire cohort and molecular subgroups (WNT/SHH/Group3/Group 4).The extent of resection was defined as gross total (GTR), Near total (NTR < 1.5 cc residue) and subtotal resection (STR > 1.5 cc residue).
RESULTS: 437 patients data over 15 year period, with molecular subgrouping data of 296 patients was available.221 cases were selected after removing the patients lost to follow up. The gender and metastasis were different in each molecular subgroup(statistically significant), however treatment factors like EOR, adjuvant and radiation therapy were similar. The distribution for molecular subgroups were- (WNT-38, SHH-83, Group 3–34,Group 4–66) and the survival was best for WNT subgroup, followed by SHH and then group 4 and 3.
For the entire cohort (221),there was no statistical difference in the PFS and OS when considering the EOR. Taking the molecular group into consideration, in the WNT and SHH subgroup,PFS and OS were not influenced by EOR. In group 3, the PFS was tending towards significance, while the OS was influenced with EOR, with GTR doing better than STR(statistically significant).In group 4,OS was tending towards significance, by the EOR.
CONCLUSIONS: EOR in group 3 medulloblastoma influenced the overall survival in our cohort. Hence a safe maximal resection is advocated and results should be interpreted with the limitations of a retrospective audit.
Keywords: Medulloblastomas, Extent of resection, Molecular subgrouping
FL-003
Neuro-Oncology
The supraorbital eyebrow approach in pediatric neurosurgery—patient characteristics, clinical course and outcome
Ulrich Wilhelm Thomale1, Aminaa Sanchin1, Pablo Hernaiz Driever3, Anna Tietze4, Eckhardt Bertelmann2
1Pediatric Neurosurgery, Charité Universitätsmedizin Berlin, Germany
2Department of Ophtalmology, Charité Universitätsmedizin Berlin, Germany.
3Pediatric Hematology and Oncology, Charité Universitätsmedizin Berlin, Germany
4Neuroradiology, Charité Universitätsmedizin Berlin, Germany
BACKGROUND AND AIM: Supraorbital craniotomy via an eyebrow incision provides access to both orbital and intracranial pathologies in a minimally invasive technique with clinically and cosmetically favorable outcome. We describe the indication, surgical technique and clinical course using this surgical approach in a cohort of patients from a single pediatric neurosurgery unit.
METHOD: In a retrospective analysis, all surgical cases, who underwent the supraorbital craniotomy via an eyebrow incision were identified in the time period between January 2013 and April 2022. The craniotomy was performed using piezosurgery ultrasonic bone incision. Orbital pathologies were operated with an interdisciplinary team of orbital surgeon and neurosurgeon. Clinical and surgical characteristics, perioperative data, possible complications or redo surgeries as well as ophthalmologic status were acquired.
RESULTS: The clinical data of 37 cases in 30 patients (age: 7.9 ± 6.6 yrs.) were collected. The supraorbital craniotomy established the access to the cranial, lateral and central portions (n = 19) of the orbit and frontomedial and ipsilateral portions of the skull base (n = 18). 32 patients suffered from tumor disease of whom 14 patient needed adjuvant therapy. Mean duration of surgery was 163 ± 95 min and hospital stay was 6.2 ± 2 days. 5.6% experienced complication of a local infection treated by puncture and antibiotics and an eyelid hematoma resolved spontaneously over time. Cosmetic result was still excellent. Visual function was stable compared to preoperative status in all patients. Long-term outcome of oncology cases was CR in 14, SD in 15, PD in 1 and death in 2 patients.
CONCLUSIONS: The supraorbital eyebrow approach is feasible and safe in pediatric neurosurgical cases and should be considered for intraorbital as well as fronto-basal pathologies especially extending towards the upper lateral quadrant as well as ipsilateral intracranial lesions adjacent to the skull base. Interdisciplinary cooperation enables a broader spectrum of surgical options in complex, frontobasal, skull base pathologies.
Keywords: Orbit, Supraorbital craniotomy, Keyhole surgery, Skull base
FL-004
Germ Cell Tumors
Paediatric pineal region tumours: a surgical case series demonstrating the harmonious use of microscopic and endoscopic approaches
David Rowland1, Ladina Greuter1, Anca Vasilica2, Ahmed Raslan1, Cristina Bleil1, Bassel Zebian1
1Department of Paediatric and Adult Neurosurgery, King’s College Hospital NHS Foundation Trust, London, UK
2University College London Medical School, London, UK
BACKGROUND AND AIM: Surgery on pineal region tumours is challenging. Traditionally, this was performed using open microsurgical approaches. Following recent improvements in neuroendoscopic techniques and instrumentation, transventricular approaches have become a useful addition to our armamentarium. Here we describe our experience of microscope, endoscope-assisted and fully endoscopic approaches to pineal region tumours in paediatric patients to demonstrate their harmonious use.
METHOD: Single-centre retrospective case series from 01/09/2014–01/01/2022 of all patients 16 years or younger who underwent microsurgical and/or endoscopic surgery for a pineal region tumour. Endoscopic biopsy/debulking/resection was performed via a transventricular transchoroid approach to the pineal region in combination with endoscopic third ventriculostomy (ETV) for CSF diversion. Open microsurgical resection was performed via the supracerebellar infratentorial (SCIT) or occipital interhemispheric approach.
RESULTS: 10 patients were included, with a mean age of 11.9, all of whom were male. At presentation, all patients had a GCS of 15 and had hydrocephalus. One patient underwent insertion of an external ventricular drain; the remaining 9 underwent either an ETV (1, 10%) or ETV and endoscopic tumour biopsy/debulking/resection (8, 80%). 7 (70%) underwent open microsurgical tumour surgery after their initial endoscopic biopsy and 2 (20%) underwent more than one microsurgical procedure. In one patient the tumour was completely removed using the endoscopic transventricular transchoroid approach. Histopathological analysis of the tumours showed 8 germ cell tumours and 2 pineal parenchymal tumours. Mean post-operative GCS was 13.2, and at discharge all patients were GCS 15. One patient died 187 days after the first surgery due to tumour recurrence and progression.
CONCLUSIONS: This is the first case series describing the combined endoscopic and microsurgical management of paediatric pineal tumours. The majority were managed with a combination of ETV and biopsy as a first procedure followed by a SCIT approach depending on the tumour histology. Complete resection was possible endoscopically in one patient.
Keywords: Pineal, Germ Cell Tumours, Neuroendoscopy, Microscope
FL-005
Neuro-Oncology
11C-Methionine (11C-Met) PET/MRI Imaging Study in children with posterior fossa tumors: a feasibility study
Pierre Aurelien Beuriat1, Federico Di Rocco1, Matthieu Vinchon1, Marc Hermier3, Sylvie Lorthois Ninou2, Christian Schaeffer4, Anthyme Flaus4, Alexandre Vasiljevic5, Alexandru Szathmari1, Carmine Mottolese.1
1Pediatric Neurosurgical Unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
2Pediatric Radiology department, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
3Radiology department, Hôpital Pierre Wertheimer, Hospices Civils de Lyon, Bron, France
4Nuclear Medicine department, Hospices Civils de Lyon, Bron, France
5Pathology Department, "Groupement Hospitalier Est" Hospices Civils de Lyon, Bron, France
BACKGROUND AND AIM: Magnetic Resonance Imaging (MRI) is the cornerstone of brain tumor evaluation but is not lacking of limitations. Imaging methods capable of providing more reliable and quantitative information on the biological activity of the tumor are necessary. Hybrid PET/MRI imaging has demonstrated its contribution to the management of brain tumors in adults. However, PET data acquired in adult cannot be transposed to children. Thus, due to the lack of studies in children especially in a context of emergency, we aimed to evaluate to feasibility to perform 11C-Methionine (11C-Met) PET/MRI scans pre-operatively in children with a newly diagnosed posterior fossa tumor.
METHOD: From November 2019 to November 2021 all consecutive children admitted in the pediatric neurosurgical unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon for a newly diagnosed posterior fossa tumor were screened for inclusion. The primary endpoints were: 1) proportion of eligible patient who did have the PET/MRI scanner before the tumor removal, 2) interpretability of the PET/MRI images. The secondary endpoints were: 1) description of the PET/MRI parameter, 2) percentage of eligible patient who gave consent to the study. All participants were imaged on a fully integrated hybrid Biograph mMR PET/MRI 3 T scanner with an intravenous bolus injection of 11C-Methionine.
RESULTS: Fifteen patients were included in the study with a mean age of 8.9 years (min5, max 16) and a 8 to 7 male to female ratio. Five patients did not perform the PET/MRI exams (1 because of a 11C-Met synthesis failure, 4 because of technical/programming issues). There was a significant difference in the Mean SUV and the max SUV value between WHO grade I and IV (p < 0.05.
CONCLUSIONS: Hybrid PET/MRI imaging is a promising technique in the management of pediatric brain tumor. More data are needed to be able to use it in a clinical set up.
Keywords: Posterior fossa tumor, Hydrib PET/MRI, Feasability, Children
FL-006
Neuroendoscopy
Neuroendoscopy for intraventricular tumors
Luca Massimi, Paolo Frassanito, Federico Bianchi, Achille Solimene, Vincenzo Mastropasqua, Gianluca Galieri, Gianpiero Tamburrini
Fondazione Policlinico Universitario A. Gemelli IRCCS
BACKGROUND AND AIM: Thanks to recent progresses, the indication to the endoscopic management of intraventricular tumors (IT) has significantly changed, ranging from the treatment of the hydrocephalus or the biopsy (in the past) to the gross total resection of the tumor (currently). However, some limitations of this surgery are still present, as rich vascularization of the tumor, its paraventricular extension or large size, small ventricles. Herein, we present the personal experience with the pure endoscopic management of intraventricular tumors together with a review of the pertinent literature.
METHOD: All children with IT consecutively managed by purely neuroendoscopic approach in the last 5 years were enrolled for this study. The 2015–2020 time period was considered to have a 2-year minimum follow-up and a homogeneous management (dedicated ultrasound aspirator, laser etc.).
RESULTS: 16 children compose the present series. The M/F ratio was 1.5, the mean age at surgery was 7 years (range: 3–18 years). SEGA (6 cases) craniophryngioma (5 cases), astrocytomas (4 cases), choroid plexus papilloma (1 case) were the treated histotype. The accuracy of the biopsy was complete (100%). Gross total/near total resection of the tumor was realized in 70% of the cases (> 90% when SEGA was operated on). No surgical mortality occurred. The main complications were represented by transient seizures (5 cases), mild intraoperative bleeding (3 cases), subdural hygroma (1 case), closure of a previous ETV (1 case). All patients are alive after a mean 3.8-year follow-up.
CONCLUSIONS: The endoscopic excision of IT is safe and effective as long as a correct indication is given. However, in the literature, the risk of mortality and major permanent morbidity is 2.2% and 3.5%, respectively. Although all IT are a potential indication for neuroendoscopy, currently, some limits must be aknowledged such as diameter > 2.5–3 cm, cisterna invasion, very small ventricles and involvement of the IV ventricle.
Keywords: Intraventricular tumors, neuroendoscopy, children
FL-007
Neuro-Oncology
Multidisciplinary Management of Optic Pathway Glioma in Children with Neurofibromatosis Type 1
Laura Nanna Lohkamp1, Patricia Parkin2, Allan Puran2, Ute Katharina Bartels3, Eric Bouffet3, Uri Tabori3, James Thomas Rutka1
1Division of Neurosurgery, Department of Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
2Division of Paediatric Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
3Division of Haematology / Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
BACKGROUND AND AIM: Neurofibromatosis type 1 (NF1) is in 15% is associated with optic pathway glioma (OPG). Given its variability in clinical presentation, a multidisciplinary approach for diagnosis and management is required, but often lacks coordination and regular information exchange. Herein we summarize our experience in treating children with NF-1 and OPG and describe the provided multidisciplinary care network including the roles of the distinct team members.
METHOD: We performed a retrospective single-center observational study, including children treated between 1990 and 2021. Inclusion criteria were clinical diagnosis of NF1, radiographic and/or histopathological diagnosis of OPG and age below 18 years. Data were abstracted from each child’s health record using a standardized data collection form. Patient characteristics were described using means (SD) and percentages. Outcomes were determined using Kaplan–Meier estimates.
RESULTS: From 1990 to 2021, 1337 children were followed in our institution. Of those, 195 were diagnosed with OPG (14,6%), including 94 (48.21%) females and 101 (51.79%) males. Comprehensive data were available in 150 patients. The mean (SD) age at diagnosis was 5.31(4.08) years (range: 0.8—17.04 years). Sixty-two (41.3%) patients remained stable and did not undergo treatment, whereas 88 (58.7%) patients required at least one treatment. The mean (SD) duration of follow up was 8.14 (5.46) years (range: 0.1–25.9 years; median 6.8 years). Overall survival was of 23.6 years (± 1.08), comprising 5 deaths. A dedicated NF clinic provides regular follow up and plays a central role in the management of children with NF1, identifying those at risk of OPG, coordinating referrals to Neuroradiology and other specialists as indicated. Comprehensive care was provided by a multidisciplinary team consisting of Dermatology, Genetics, Neuro-oncology, Neuroradiology, Neurosurgery, Ophthalmology and Pediatrics.
CONCLUSIONS: The care of children with NF1 and OPG is optimized with a multidisciplinary team approach, coordinated by a central specialty clinic.
Keywords: Optic pathway glioma, Neurofibromatosis type 1, Diagnosis, Management, Multidisciplinary
FL-008
Neuro-Oncology
Defective and downregulated mitochondria in pediatric craniopharyngiomas
Engy Abd El Rahman1, Basma Yassen1, Aya El Khodiry1, Eman Khorshid3, Mohamed El Beltagy2, Sameh Ali1
1Department of Neurosurgery Children’s Cancer hospital Egypt
2Department of basic research Children’s Cancer hospital Egypt
3Department of Pathology Children’s Cancer hospital Egypt
BACKGROUND AND AIM: INTRODUCTION: Adamantinomatous craniopharyngiomas (ACPs) are benign tumors that are associated with high morbedity and the lowest quality of life scores relative to any other pediatric brain tumor. This is mainly due to their close proximity to many vital structures, tendency for cyst formation and hypothalamic infiltration that predispose many children to a life of serious disability. Although complete resection of the tumor remains the mainstay of treatment and is associated with a > 85% progression-free survival rate, the potential for postoperative recurrence of ACP is very high. Evidence are clustering around an important role of inflammatory processes and immune response in the patholgy of ACP but whether these factors are contributors to the ACP tumorgenesis is enigmatic. Hypothesizing that mitochondrial defects and mitochondrial mediated oxidative stress are important players in the ACP pathogenesis we conducted a pilot study exploring mitochondrial functions in freshly excised ACP tumors.
METHODS: We used high-resolution oximetry, fluorescence imaging and microscopy, in addition to molecular techniques to interrogate mitochondrial respiratory function and ROS production.
RESULTS: Interestingly, we discovered that mitochondrial complex I is completely scilent thus leaving the ROS-leaky complex II as the only bioenergetic entry to the electron transport chain (ETC) in ACP tumors. We also analyzed mitochondrial protein expression levels of the electron transport chain complexes which were found significantly downregulated in ACP tumors relative to HEK cells. Moreover, a significant dependence of ACP tumors on ROS-producing fatty acid metabolism is readily observable. Indeed, fluorescence imaging indicated that relative to HEK cells, primary cells derived from ACP tumor exhibited remarkably higher cellular and mitochondrial ROS. The role of defective mitochondria in Wnt-signaling pathway and accumulation of β-catenin is currently under investigation.
CONCLUSIONS: Current preliminary data places mitochondria at the root causes of the ACP tumor origination and possibly recurrance.
Keywords: Mitochondria, Adamantinomatous craniopharyngioma
FL-009
Neuro-Oncology
A comparison of intraoperative ultrasound and postoperative MRI in paediatric intra axial tumours
Nadiah Ahmad Fuad1, Azmi Alias1, Fadzlishah Johanabas Rosli1, Lim Mei Sin1, Rohazly Ismail2, Adi Afiq Md Anour2
1Department of Neurosurgery, Hospital Tunku Azizah, Kuala Lumpur, Malaysia
2Department of Radiology, Hospital Tunku Azizah, Kuala Lumpur, Malaysia
BACKGROUND AND AIM: Malignant tumours of the Central Nervous System (CNS) is the second most common paediatric malignancy, following haematological malignancy. CNS tumours depend significantly on the extent of tumour resection. In the past decade, intraoperative ultrasound (IOUS) has evolved into a widespread neuroimaging tool that offers real-time surgical guidance, and is a widely accessible imaging modality with minimal identified risk or additional operative time, and also lower economic investment. The objective of our study is to compare correlation and reliability of the ultrasound as compared to MRI for tumour resection in paediatric population. We also evaluated IOUS as a real-time navigation tool during surgical resection of intra axial tumours in paediatric patients.
METHOD: This is a prospective observational study done in a Hospital Tunku Azizah, Kuala Lumpur. Patients aged less than 12 years old, admitted between 1st December 2019 to 30th November 2021 with preoperative MRI diagnosis of intra-axial brain tumour were recruited in this study. IOUS was performed intraoperatively, and post-operative MRI performed within 24–72 h post-op. IOUS utility assessment scoring was performed intraoperatively.
RESULTS: We analysed a total of 25 paediatric patients that met the inclusion criteria. Concordance analysis between IOUS evaluation and MRI showed good agreement (kappa = 0.527). A multivariate logistic regression analysis was performed to look for any significant factors of discordance, and none of the variables were found significant for discordance. Hosmer and Lemeshow goodness of fit test was performed, and showed that our model is a good fit, with a good prediction value of 0.497.
CONCLUSIONS: The use of IOUS may allow reliable intra operative imaging modality to achieve more successful gross total resection of brain tumours in paediatrics.
Keywords: Intraoperative ultrasound, Realtime navigation, Paediatric tumours, Intra axial, Post operative MRI
FL-010
Neuro-Oncology
The use of novel in vitro models to study Adamantinomatous Craniopharyngioma disease biology and drug response
Eric W. Prince1, Oscar Chatain2, Keanu Chee2, Stephen Medlin2, James Johnston4, Roy Dudley3, David Limbrick5, Joshua Chern9, Robert Naftel10, Toba Niazi13, Annie Drapeau14, Neil Feldstein6, Richard C.E. Anderson12, Eric Jackson11, Lindsay Kilburn8, Kevin Ginn7, Amy Smith15, Sandi Lam16, Todd C. Hankinson1
1Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, USA
2University of Colorado School of Medicine, Aurora, USA
3Montreal Children's Hospital, Montreal, Canada
4Childrens Hospital of Alabama, Birmingham, USA
5St. Louis Children's Hospital, St. Louis, USA
6Children's Hospital of New York, New York, USA
7Mercy Children's Hospital, Kansas City, USA
8Children's National Medical Center, Washington D.C., USA
9Children's Healthcare of Atlanta, Atlanta, USA
10Monroe Carrell Children's Hospital, Nashville, USA
11Johns Hopkins Medicine, Baltimore, USA
12Hassenfeld Children's Hospital at NYU Langone, New York, USA
13Miami Children's Hospital, Miami, USA
14Nationwide Children's Hospital, Columbus, USA
15Orlando Health Arnold Palmer Hospital for Children, Orlando, USA
16Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA
BACKGROUND AND AIM: Challenges around the design and investigation of cell culture models of ACP have arisen from the cellular heterogeneity of these tumors, with populations that harbor disparate requirements in culture. Novel approaches to in vitro modeling of ACP are needed.
METHOD: Intraoperatively collected tumor specimens were mechanically digested, and plated under conditions tailored to the cell population of interest. ACP tumor derived fibroblasts and epithelial cells were isolated using serum-containing and keratinocyte-specific media respectively. Cell line validation included immunofluorescence with markers appropriate for the cell population of interest. Genomic signatures generated using qPCR were compared to a novel single cell RNAseq dataset of ACP tumor tissue.
RESULTS: ACP fibroblasts and ACP epithelial cells maintained spindle-like and cobblestone morphologies respectively, even after passaging. Immunofluorescence confirmed high levels of Vimentin expression in ACP-derived fibroblasts, and panCK and B-catenin in ACP-derived epithelial cells. Point mutation in exon 3 of the CTNNB1 gene was identified in ACP-derived epithelial cells. STR analysis indicated each cell line to be genetically unique.
CONCLUSIONS: Initial limits related to cell line development in ACP may be addressed through the isolation and culture of specific ACP cell populations. This experience demonstrates the maintenance of validated marker of the cell populations of interest ex vivo. While preliminary, such cell lines offer promise as tools for the identification and study of potential therapeutic vulnerabilities in ACP.
Keywords: Craniopharyngioma, Cell culture, Ex vivo culture, Pediatric craniopharyngioma
FL-011
Neuro-Oncology
Novel model for pediatric glioma: H3K27M tumor with inducible TGFB/LAG3 immunotherapy
Vladimir A Ljubimov1, Sara Sabet2, Paul W Linesch2, David Rincon Fernandez Pacheco2, Shaunt Mehdikhani2, Viktoria O Krutikova3, Moise A Danielpour1, Joshua J Breunig2
1Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
2Department of Regenerative Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
3Tuoro University School of Medicine, Henderson, Nevada, United States of America
BACKGROUND AND AIM: Gliomas are considered immunologically “cold” tumors that mask themselves from the immune system. Immunotherapy, a breakthrough for cancer treatment, remains inefficient for gliomas. H3K27M mutant diffuse midline glioma has poor survival. Using our innovative mosaic analysis with dual recombinases technology (Cell 2019), we further created a novel murine model of H3K27M glioma with an inducible expression of LAG3 and TGFBR2 to make the tumor recognizable by the immune system. This allows studying molecular mechanisms of “perfect” immunotherapy in pediatric gliomas with histone H3.3 mutations.
METHOD: To make a novel murine model, H3K27M plasmids with doxycycline-inducible expression for TGFBR2 and LAG3 were designed, sequenced, and replicated. For in vitro validation, murine neuronal stem cells were nucleofected with these plasmids, grown and sorted. Doxycycline was added to the experimental group in vitro to induce expression. The plasmids were then electroporated into neonatal MGMT mice (n = 21) of both genders. Control mice were used on a standard diet (n = 9) and experimental mice (n = 12) were given doxycycline in food to induce TGFBR2 and LAG3 expression in vivo. Mice were followed up for survival.
RESULTS: Plasmid sequencing validation demonstrated their high purity. In vitro nucleofected neuronal stem cells showed significant increase in TGFBR2 and LAG3 expression by immunofluorescent staining after addition of doxycycline. The mouse survival study showed a significant benefit with treatment group surviving 46% longer (135 ± 41.9 days vs. 92.6 ± 32.7 days in the control group, p = 0.030).
CONCLUSIONS: We have successfully modified H3K27M glioma to have inducible expression of TGFBR2 and LAG3 to simulate “perfect” immunotherapy. The survival study showed a significant survival benefit. The development of organoid transplants for more uniform testing is ongoing. This can lead to the emergence of novel immune therapies and uncover novel mechanisms of tumor response to treatment.
Keywords: Glioma, H3K27M, Immunotherapy, LAG3, TGFBR2, Model
FL-012
Germ Cell Tumors
Surgical Approaches for Pineal Region Tumors: 151 pediatric cases
Sergio Cavalheiro, Linoel Curado Valsechi, Marcos Devanir Silva Da Costa, Paricia Alessandra Dastoli, Jardel Mendonça Nicácio, Andrea Maria Cappellano, Nasjla Saba Da Silva, Silvia Toledo Caminada, Lorena Pavon, Tatiana Sibov
Neurosurgery Department, Escola Paulista de Medicina, Universidade Federal de São Paulo. Neuro-Oncology, Instituto de Oncologia Pediatria, GRAACC, São Paulo—SP, Brazil
BACKGROUND AND AIM: Analyze the difference between the main surgical approaches for pineal region tumors in children regarding overall survival, progression free-survival, improvement of the surgical technique during the last 30 years.
METHOD: Retrospective analysis of 151 medical records of children with pineal region tumors treated at GRAACC in São Paulo between 1991–2020.
RESULTS: Prevalence of tumors in the pineal region was 7.32%. Germinomas were the most frequent tumors with 33.1%, followed by non-germinomatous germ cell tumors (NGGCT) 27%, pinealoblastomas 22.5%, gliomas 12.5% and embrionary tumor 3.3%. These 151 patients underwent 194 surgical procedures, from those 70 biopsies, 63 infratentorial supracerebellar approaches, 28 occipito-transtentorial approaches, and 33 other approaches. Total resection was achieved in 69%, surgical mortality of 0,6%. Eighty two percent of the patients underwent endoscopic biopsy, the sensibility of the biopsy was 90%. There was statistical diference between the surgical approaches regarding of mortality, morbidity, grade of resection or progression-free-survival in 5 years. The overall survival in 5 years was compared between the three decades, the first (1991–2000) presented OS of 76% in 5 years, the second (2001–2010) OS 53% in five year, and the third (2011–2020) presented OS of 77% in 5 years. Progression-free-survival in 5- years in germinomas was 77%, NGGCT 50%, pinealoblastoma 38.9%, glioma 72.6%.
CONCLUSIONS: Pineal region tumors require a multimodal approach in which surgery plays important role. The best approach depends on size of the lesion, direction of the lesion’s growth and surgeon’s skills.
Keywords: Pineal region tumor, Supracerebellar infratentorial approach, Occipto transtentorial approach, Endoscopic biopsy
FL-013
Neuro-Oncology
Survival and Neurological Outcomes after Stereotactic Biopsy of Diffuse Intrinsic Pontine Glioma: A Systematic Review
Prottusha Sarkar1, Sunny Abdelmageed1, Manasa Pagadala1, Nathan A. Shlobin1, Mandana Behbahani2, Melissa A. LoPresti3, Sandi Lam2, Michael DeCuypere2
1Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
2Division of Pediatric Neurosurgery, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA
3Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA
BACKGROUND AND AIM: Diffuse intrinsic pontine gliomas (DIPG) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy helps obtain molecular and genetic information for diagnostic and potentially therapeutic purposes. However, there is no consensus on the safety of biopsy nor effect on survival. We aimed to characterize neurological risk associated with and the effect of stereotactic biopsy on survival among patients with DIPG.
METHOD: A systematic review was performed in accordance with PRSIMA guidelines to identify all studies examining pediatric patients undergoing stereotactic biopsy with DIPG. Bibliographic, demographic, clinical, and outcome data were extracted from studies meeting inclusion criteria.
RESULTS: Of 569 resultant articles, 14 were included. A total of 384 patients underwent biopsy. Of these biopsies, children had a weighted mean age of 7.2 years (range 4.8–8.8) at diagnosis. There was an overall complication rate of 25.5% (98/384), of which 51% (50/98) were neurological complications. The most common neurological complication was cranial nerve palsy (40%, 20/50), of which cranial VII was the most common (40%, 4/10). Hemiparesis (38% of neurologic complications) was also frequently reported. Dysarthria, dysphasia, and dysphagia were also notable. Diagnostic yield of biopsy was 92% (range 71–100%). Of the studies reporting survival data, 105 patients (30.9%) died within study follow-up periods (range 1 to 35.9 months). The mean overall survival was 10.2 months (SD = 1.88, Median = 10.3, range = 9–20.4 months). Progression-free survival (PFS) was a mean of 6.75 months (SD = 1.25, Median = 6.5, range = 5.6–8.4 months). No morbidity was specifically attributed to biopsy.
CONCLUSIONS: Children with DIPG undergoing brainstem biopsy have low rates of neurologic deficits and no excessive morbidity. With quantification of relatively low surgical risk in this morbid condition, the rationale for tissue biopsy is that ongoing characterization of patient-specific, molecular, and genetic factors influencing prognosis will improve risk stratification and catalyze the development of therapeutic strategies.
Keywords: Brainstem biopsy, Dipg, Stereotactic biopsy, Diffuse intrinsic pontine glioma, Stereotactic, Pediatric brain tumor
FL-014
Neuro-Oncology
Impact of the COVID-19 pandemic on 30-day mortality and unplanned reoperation rates for pediatric central nervous system tumors
Diana Jovett Sanchez1, Ceri Jane Homillano Talan2, Sally Andrea Dunton Gaspi3, Ana Patricia Angeles Alcasabas2, Ronnie Enriquez Baticulon1
1Division of Neurosurgery, Department of Neurosciences, Philippine General Hospital, University of the Philippines Manila, Manila, Philippines
2Section of Hematology and Oncology, Department of Pediatrics, Philippine General Hospital, University of the Philippines Manila, Manila, Philippines
3Section of Pediatric Neurology, Department of Pediatrics, University of the Philippines Manila, Manila, Philippines
BACKGROUND AND AIM: Unplanned reoperations and mortality within 30 days are important indicators when evaluating the quality of care provided by surgical systems. We reviewed these outcomes among children with primary central nervous system (CNS) tumors treated during the COVID-19 pandemic.
METHOD: This is a retrospective study of all pediatric patients who underwent neurosurgery for primary CNS tumors at the Philippine General Hospital, the national university hospital, from January 1, 2020 until December 31, 2021. Their clinical presentation, perioperative course, and outcomes were analyzed. During this time, our hospital concurrently served as a COVID-19 referral center, thus, the workforce was restructured, and resources were reallocated to care for COVID-19 patients.
RESULTS: A total of 92 pediatric patients with CNS tumors underwent 140 neurosurgical operations during the study period. Two-thirds of the patients were males, and mean age was 9.3 ± 5.0 years (range: 3 months to 18 years). Average preoperative length of stay was 3.9 ± 2.6 days. Tumor resection was performed in 73 patients (79%). Most common histologic diagnoses were medulloblastoma (20%) and low-grade glioma including pilocytic astrocytoma (20%). Overall, the 30-day mortality and unplanned reoperation rates were 12% and 22%, respectively. Eight patients died from brain herniation and/or tumor progression. Reasons for unplanned reoperations were postoperative hydrocephalus (20%), infection (9%), hematoma (7%), and tumor residual (3%).
CONCLUSIONS: Worldwide, the COVID-19 pandemic has altered hospital protocols and shifted resources considerably. The observed high rates of death and reoperation are likely due to delays in seeking care leading to worse neurologic status at presentation, delays in performing essential surgery within the hospital, and shortage of health workers providing specialist care. It is important to periodically assess perioperative outcomes to improve the quality of surgical care given to children with CNS tumors, who remain a vulnerable population during the COVID-19 pandemic.
Keywords: COVID-19, Pandemic, Mortality, Reoperation, Pediatric central nervous system tumors, 30-day mortality
FL-015
Neuro-Oncology
Evolution of surgical management of pineal region tumors in the pediatric population: a 17-year experience at a single institution
Hasan Raza Syed1, Nirali Patel2, Alexandria Marino3, Kelsey Chesney2, Katherine Hoffmann1, Daniel Donoho1, Chima Oluigbo1, Robert Keating1, John Myseros1
1Department of Neurosurgery, Children’s National Hospital, Washington DC
2Department of Neurosurgery, MedStar Georgetown University Hospital, Washington DC
3Georgetown University School of Medicine, Washington DC
BACKGROUND AND AIM: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients. Here, we describe a single institution’s experience over a 17-year-period and the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients.
METHOD: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children’s National Hospital (CNH) from 2005–2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others.
RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). 27 of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior-interhemispheric (PIH, transcallosal). Gross total resection was achieved in 50%; recurrence occurred in 20.9%; and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011–2021. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies.
CONCLUSIONS: This series describes surgical approaches and outcomes over a 17-year-period. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. In our series, outcomes of these patients have not significantly changed over that time.
Keywords: Pineal tumors, Endoscopic third ventriculostomy, ETV, Hydrocephalus, Biopsy, Resection
FL-016
Neuro-Oncology
Robotic alignment system Cirq (Brainlab) for navigated brain tumor biopsies in children
Kirsten Van Baarsen1, Darwin Woodley1, Mariam Slot2, Peter Woerdeman1, Sen Han1, Eelco Hoving1
1Princess Máxima Center for Pediatric Oncology, department of neurooncology, Utrecht, the Netherlands; Wilhelmina Children's Hospital, department of neurosurgery, Utrecht, the Netherlands
2Amsterdam University Medical Center, Amsterdam, the Netherlands
BACKGROUND AND AIM: With the incorporation of the robotic alignment system Cirq (Brainlab, Munich, Germany) into our neurosurgical armamentarium, we deemed it important to study the application accuracy of this new device. As a baseline, we retrospectively reviewed our historical data on brain tumor biopsies with the non-robotic alignment instrument Varioguide (Brainlab, Munich, Germany). We also sought to improve our registration when we introduced Cirq.
METHOD: All patients (0–19 years old) who underwent a brain tumor biopsy at the Princess Máxima Center, Utrecht, were included. Over the period 2019–2020, data were collected retrospectively (cohort “Varioguide” in which patient-to-image registration was based on preoperative MRI with adhesive skin fiducials). From 2021 onwards, data were collected prospectively (cohort “Cirq”). For both cohorts, Euclidian distances and in-plane distances were calculated between the intended target and the obtained target using postoperative MRI scans (“target error”, TE).
In some patients from the “Cirq” cohort, patient-to-image registration was done using 1. a preoperative MRI with adhesive skin fiducials and 2. an intraoperative CT scan with bone screw fiducials. The registration errors of both methods were compared.
RESULTS: Twenty-three patients were biopsied with Varioguide and twelve patients with Cirq. The Cirq robotic system, combined with bone fiducial registration, resulted in a high target accuracy with a maximum target error of 2,1 mm, as compared to 3,8 mm for Varioguide (difference not significant). However, patient-to-image registration was significantly more accurate when based on bone screw fiducials as compared to skin fiducials.
CONCLUSIONS: The Cirq robotic alignment system is convenient and safe. Although Cirq seems more precise than Varioguide, the sample size was too small to reach statistical significance. Patient-to-image registration is significantly more accurate with bone screws as compared to skin fiducials. Registration based on adhesive skin fiducials does not offer the level of precision that is mandatory for brainstem tumor biopsies.
Keywords: Cirq—robotics—biopsy—brain tumor—target accuracy—pediatrics
FL-017
Neuro-Oncology
Choroid plexus tumours: a study on prognosticating factors on clinical and educational outcome
John Ong1, Rishil Patel1, Pasquale Gallo2, Desiderio Rodrigues2, Richard Walsh2, Guirish Solanki2, William B Lo2
1College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
2Department of Paediatric Neurosurgery, Birmingham Children’s Hospital, Birmingham, UK
BACKGROUND AND AIM: The optimal management of choroid plexus tumours (CPTs) of various grades is unclear, because of their rarity, young age of presentation, variable gross total resection (GTR) rate and the challenging risk/benefit balance regarding adjuvant therapy. Most patients require cerebrospinal fluid shunt insertion. This study investigates the clinical, oncological, and surgical factors affecting clinical outcomes.
METHOD: 15-year retrospective study (2006–2021). Patient demographics, tumour characteristics and treatment data were collected. Event-free survival [EFS] was performed using Kaplan–Meier analysis and compared with log-rank test. Events were defined as recurrence or death from disease.
RESULTS: Seventeen patients were included. The 9 patients with choroid plexus papillomas (WHO grade I) had a 5-year EFS of 89%(8/9). The one event was in the only child who did not have GTR of her bilateral ventricular lesions and received adjuvant therapy; her tumour regrew 2 years following surgery. Out of the 5 atypical choroid plexus papilloma (II), and 3 choroid plexus carcinoma (III) cases, 50%(4/8) achieved GTR and one mortality occurred at 6 months of a child with a partially resected grade II tumour. Shunt insertion rates were greater in grade I than grade II/III tumours (6/9 vs 4/8), as well as shunt revision rates (4/6 vs 1/4). All 5 patients receiving preoperative embolisation achieved GTR, compared to 58%(7/12) of patients not undergoing embolisation. Where data were available, three children out of eight attended special educational needs schools, all of whom had Grade I disease. The same 2 of the 3 children developed post-operative epilepsy and had shunt insertion.
CONCLUSIONS: Children with choroid plexus papillomas treated with surgery alone achieved a high EFS. 8 children with grade II/III disease, who received adjuvant therapy following surgery, based on an individualised approach, achieved a 75% EFS and 88% overall survival. Post-operative epilepsy and shunt may be associated with poorer cognitive and educational outcome.
Keywords: Choroid plexus tumour, Gross-total resection, Adjuvant therapy, Event-free survival, Educational outcome
FL-018
Neuro-Oncology
Navigated Transcranial Magnetic Stimulation in Pediatric Brain Tumor Surgery
Ladina Greuter, Sabina Patel, Cristina Bleil, Bassel Zebian, Francesco Vergani, Jose Lavrador
Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, United Kingdom
BACKGROUND AND AIM: Transcranial Magnetic Stimulation (TMS) is a diagnostic tool increasingly used in neurosurgery for identification of motor and language eloquent regions prior to surgical intervention. Although commonly utilised and well tolerated in adult patients, there is little data regarding the tolerability and accuracy of data in paediatric patients. This study evaluates the safety, tolerability, and accuracy of TMS in paediatric patients.
METHOD: Using the trust patient database, we identified all paediatric patients (< 18 years) who underwent TMS for pre-surgical evaluation of motor and/or language eloquent areas between 1.1.2019-0.1.12.2021. Electronic patient records were reviewed to confirm demographical data including histological diagnosis.
RESULTS: A total of 7 patients were identified who underwent TMS for pre-surgical mapping of motor and/or language eloquent areas (motor = 6, language = 1). Mean age was 13.57 (± SD 3.74, range 7–18 years), with four (57%) male patients. Four tumours (57%) were located in the parietal region, three (43%) in the temporal lobe and one was a brainstem tumour. All patients tolerated the full extent of the mapping. No TMS related complications were observed either during or following the exam. One patient developed postoperative hydrocephalus, which was treated with an endoscopic third ventriculostomy on the third postoperative day. Postoperative histology resulted in six (86%) high grade gliomas (WHO IV) and one ependymoma RELA fusion positive (WHO II). None of the patients had a significant drop of motor or sensory evoked potentials intraoperatively.
CONCLUSIONS: Diagnostic TMS for pre-surgical motor and language mapping was shown to be tolerable in the paediatric population with no immediate or lasting complications. Furthermore, the cortical excitability score calculated from TMS can positively predict tumour grading and facilitate early discussions regarding neurological recovery, diagnosis, and treatment.
Keywords: Transcranial magnetic stimulation, TMS, Pediatric brain tumor, Neurooncology
FL-019
Neuro-Oncology
Semisitting position for posterior fossa tumors in children
Oscar Garcia González, Oscar Guerrero, Edgard Lozada Hernandez, Sergio Orozco Ramirez
Hospital Regional de Alta Especialidad del Bajio
BACKGROUND AND AIM: The semi-sitting position is one of the preferred positions for resection of posterior fossa midline tumors. Nevertheless, it harbors some risks, with the most dreaded beeing air embolism. In small children another additional risk is rigid head fixation. Here we report about our experience with the semi-sitting position in children.
METHOD: Nineteen children younger than 17 years of age were operated in the semi-sitting position (mean age: 6.5 years; range between 1.8 m and 16y). Persistent foramen ovale was excluded preoperatively in 15/19 patients. Intraoperative incidents were recorded and patients course followed postoperatively with a special focus on possible complications.
RESULTS: The histopathological diagnoses included ependymoma (n = 5), pilocytic astrocytoma (n = 2), exofitic brainstem glioma (n = 2), medulloblastoma (n = 10). CSF shunt/ETV were done in 17 of 19 children who presented with hydrocephalus preoperatively. No major intraoperative complications occurred. Air embolism was detected in 2 patients during surgery, the air embolism was recorded in TEE without cardiovascular or respiratory signs or symptoms. In one patient arterial hypotension with reduction of pCO2 occurred and it was treated successfully with chatacholamin infusion and suction of air embolism via a central venous catheter without postoperative complications due to the embolism. Postoperatively all children showed pneumocephalus and one of them developed a subdural hygroma and was treated by burr-hole drainage. Revision surgery was necessary in one child with subtotal resection. Only one child did not require any surgical diversion because of presenting hydrocephalus pre or postoperative tumor resection (ETV or ventriculoperitoneal shunt).
CONCLUSIONS: The semi-sitting position for tumor resection of the posterior fossa in children under 16 years of age entails certain risks, however, it can be successfully performed taking special caution to detect and treat potential complications in an interdisciplinary teamwork with specialized neuroanaesthesiologists.
Keywords: Posterior fossa tumors, Semisitting position, Foramen ovale, Venous air embolism
FL-020
Neuro-Oncology
Cerebellopontine angle tumours in the pediatric population – An original series of 43 patients
Amr Abdelhakam1, Sandro Benichi1, Arnault Tauziède Espariat2, Pascale Varlet2, Christelle Dufour3, Jacques Grill3, Léa Guerrini Rousseau3, Samuel Abbou3, François Doz4, Franck Bourdeaut4, Nathalie Boddaert5, Christian Sainte Rose1, Stephanie Puget1, Thomas Blauwblomme1, Kevin Beccaria1
1Pediatric Neurosurgery Department, Necker Enfants Malades Hospital, Paris Cité University, Paris, France
2Department of Neuropathology, Sainte-Anne Hospital, GHU Paris Neurosciences, Paris, France
3Department of children and adolescent oncology, Gustave Roussy, Villejuif, France
4SIREDO Center (Care, research, innovation in pediatric, adolescent and young adult oncology), Institut Curie, Paris, France; Université Paris Cité, Paris, France
5Pediatric Neuroradiology Department, Necker Enfants Malades Hospital, Paris Cité University, Paris, France
BACKGROUND AND AIM: Posterior fossa tumours account for almost 40 to 50% of brain tumours in children, but less than 10% are in the cerebellopontine angle (CPA). We aimed to report characteristics and surgical management of CPA tumours in a referral center.
METHOD: Patients less than 18 years old treated for a CPA tumour from 2010 to 2020 at Necker Enfants Malades Hospital were retrospectively included. CPA tumours were defined as tumours entirely or predominantly developed in the CPA. Clinical, radiological, histological, and surgical data were collected. Statistics were performed with BiostaTGV, based on R software.
RESULTS: Forty-three patients were included (median age = 6.9 years; 7 days—16.5 years). The most frequent symptoms leading to diagnosis were facial nerve palsy (25%), hearing loss (25%), and intracranial hypertension (18.41%). Hydrocephalus was observed in 20 cases (46.5%) and was treated before tumour resection in 14/20 cases (shunt, endoscopic third ventriculostomy, cyst puncture or debulking in emergency). Tumour resection was performed in 37/43 cases (partial = 23; complete = 14). The tumour was malignant in 20/37 cases. The most frequent histology were ATRT (n = 6), neurinoma (n = 6) and pilocytic astrocytoma (n = 5). Patients with a benign tumour were significantly older than those with a malignant tumour: 9.1 years vs 4.7 years, respectively (p = 0.007). After surgery, improvement or stability of cranial nerve palsy was observed in 14/37 cases and permanent worsening in 2 cases. Most common long-term sequelae were facial palsy, hearing loss, and swallowing disorders.
CONCLUSIONS: CPA tumours are a rare entity in children. The histological findings are diverse. The surgical strategy must consider the age of patient, the existence of hydrocephalus at diagnosis and the histology. Monitoring of the cranial nerves should become systematic to limit complications and to optimise tumour resection.
Keywords: Cerebellopontine angle, Tumor cranial nerves, Hydrocephalus
FL-021
Vascular
Gamma Knife Radiosurgery for Pediatric Brain Arteriovenous Malformation: a Single Institute experience of 40 patients
Jun Kyu Hwang1, Eun Kyung Park2, Kyu Won Shim2, Dong Seok Kim2, Won Seok Chang3
1Department of Neurosurgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
2Department of Pediatric Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
3Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
BACKGROUND AND AIM: This study investigated the factors contributing obliteration of brain arteriovenous malformations (AVM) in pediatric patients who underwent Gamma Knife Radiosurgery (GKRS).
METHOD: From Jan 2001 to Aug 2021, 40 pediatric patients (23 male and 17 female) underwent GKRS for bAVMs. The median age was 7 ± 3 years old (range: 2–19) and volume was 2.4 ± 9.7 cm3 (range: 0.3–51.6). Marginal dosage was 16 ± 1.4 Gy (range: 13–18) at 50% iso-dose curve line. Follow-up MRI was requested at 6 months, and then annually. Digital Subtraction Angiogram (DSA) was performed to investigate complete obliteration. Each factor associated with complete obliteration was analyzed.
RESULTS: The median follow up period was 25 ± 30 months (range: 5–157). Twenty-three patients (54.8%) showed complete obliteration and no new deficit. Sex, age, volume, AVM type, hemorrhage, location, AVM grade, AVM score were.
analyzed using Cox proportional hazard model. AVM volume over 3cm3 has 4.3 times higher rate of residual nidus (p = 0.009). The modified rankin score showed that 30 patients (70.5%) lived without symptoms or no significant disability after GKRS. One patient (2.5%) underwent rebleeding and two patients (5%) underwent recurrence.
CONCLUSIONS: This study revealed that GKRS for pediatric bAVMs is a safe and effective treatment considering the high obliteration rate and acceptable risk of radiation-induced complication. Volume below 3cm3 is an important factor for expecting obliteration.
Keywords: Arteriovenous malformation, Radiosurgery, Stereotactic
FL-023
Vascular
Spontaneous thrombosis of VOG malformation managed with surgical resection: a case-based review
Yahya H Khormi
Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia
BACKGROUND AND AIM: Vein of Galen (VOG) malformation is a rare congenital intracranial vascular malformation. Spontaneous thrombosis of this lesion is extremely rare.
METHOD: The author reports a clinical presentation, images as well as surgical management of a child diagnosed with Spontaneous thrombosis of VOG malformation. Furthermore, a literature review of all published cases was conducted and summarized.
RESULTS: A 2-year- old boy presented with symptoms and signs secondary to mass effect, hydrocephalus, and high Intracranial Pressure (ICP). Location of the lesion was off the pineal region which make it atypical for VOG malformation. Patient was managed successfully with surgical resection and intra-operative finding and pathology confirmed the diagnosis of spontaneous thrombosis of VOG malformation. Patient had a complete neurological recovery at follow up. A literature review revealed only eleven cases were reported, clinical presentation included: headache, irritability, vomiting, seizures, 6th nerve palsy, hemiparesis and decrease in level of consciousness. Six patients underwent surgical excision of aneurysm, four patients underwent CSF diversion and two patients underwent both. The overall outcome was good.
CONCLUSIONS: Spontaneous thrombosis of VOG malformation is a rare pathology. It is associated with delayed and variable clinical presentations likely due to low flow shunt mural type VOG malformation. It has a favorable prognosis with surgical treatment.
Keywords: Vein of Galen malformation, Arteriovenous malformation, Aneurysm, Spontaneous thrombosis, Surgical resection
FL-025
Vascular
Long-term health-related quality of life in patients with ruptured arteriovenous malformations treated in childhood
Elias Oulasvirta1, Anni Pohjola1, Päivi Koroknay Pál1, Ahmad Hafez1, Risto Roine2, Harri Sintonen3, Aki Laakso1
1Department of Neurosurgery, Helsinki University Hospital, Helsinki, Finland
2Department of Health and Social Management, University of Eastern Finland, Kuopio, Finland
3Department of Public Health, Helsinki University Hospital, Helsinki, Finland
BACKGROUND AND AIM: To reveal the long-term health-related quality of life (HRQoL), educational level, and impact on occupation in 55 ruptured and treated pediatric brain arteriovenous malformation (AVM) patients.
METHOD: In 2016, questionnaires including the 15D instrument were sent to patients over 18 years of age (n = 432) in the Helsinki AVM database. The cohort was further specified to include only patients with ruptured AVMs who were under 20 years of age at the time of diagnosis (n = 55). Educational level was compared to the age-matched general population of Finland. The mean 15D scores were calculated for independent variables (Spetzler-Ponce classification, admission age, symptomatic epilepsy, multiple bleeding episodes) and tested using the independent samples t-test or ANCOVA. Linear regression was used to create a multivariate model. Bonferroni correction was used with multiple comparisons.
RESULTS: The mean follow-up time from diagnosis to survey was 24.2 (SD 14.7) years. The difference in the mean 15D scores between SPC grades did not reach statistical significance. The youngest age group (< 10 years at the time of diagnosis) did less well on the dimension of usual activities than the older patients. Multiple hemorrhages significantly reduced the scores on three dimensions: mobility, speech, and sexual activity. In the regression model, symptomatic epilepsy was the only significant predictor for a lower 15D score. The educational level of the cohort was for the most part comparable to that of the general population in the same age group. AVM was the reason for early retirement in 11% of the patients, while lowered performance because of the AVM was reported by 37% of the patients.
CONCLUSIONS: Patients with ruptured AVM treated in childhood can live an independent and meaningful life, even in the case of the highest-grade lesions. Symptomatic epilepsy significantly reduced the long-term HRQoL, highlighting the need for continuing support in these patients.
Keywords: Arteriovenous malformation, AVM, Hemorrhage, Pediatric, Health-related quality of life, Educational level
FL-026
Moya-Moya disease
Surgical Revascularizations for Pediatric Moyamoya: A Systematic Review, Meta-Analysis and Meta-Regression Analysis
Keng Siang Lee1,2, John JY Zhang3, Sanjay Bhate2,4, Vijeya Ganesan2,4, Dominic Thompson1,2, Gregory James1,2, Adikarige Haritha Dulanka Silva1,2
1Department of Neurosurgery, Great Ormond Street Hospital for Childrent, London, UK
2Great Ormond Street Institute of Child Health, University College London, London, UK
3Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore
4Department of Paediatric Neurology, Great Ormond Street Hospital, London, UK
BACKGROUND AND AIM: There is no clear consensus regarding the technique of surgical revascularization for moyamoya disease and syndrome (MMD/MMS) in the pediatric population. Previous meta-analyses have attempted to address this gap in literature but with methodological limitations that affects the reliability of their pooled estimates. This meta-analysis aimed to report an accurate and transparent comparison between studies of indirect (IB), direct (DB) and combined bypasses (CB) in pediatric patients with MMD/MMS.
METHOD: In accordance with PRISMA guidelines, systematic searches of Medline, Embase and Cochrane Central were undertaken from database inception to 7th October 2022. Perioperative adverse events were the primary outcome measure. Secondary outcomes were rates of long-term revascularization, stroke recurrence, morbidity and mortality.
RESULTS: 37 studies reporting 2460 patients and 4432 hemispheres were included in the meta-analysis. Overall pooled mean age was 8.6 years (95%CI: 7.7;9.5), and 45.0% were male. Pooled proportions of perioperative adverse events were similar between the DB/CB and IB groups except for wound complication which was higher in the former group (RR = 2.54(95%CI: 1.82;3.55)). Proportions of post-surgical Matsushima Grade A/B revascularization favored DB/CB over IB (RR = 1.12 (95%CI 1.02;1.24)). There was no significant difference in stroke recurrence, morbidity and mortality. After meta-regression analysis, year of publication and age were significant predictors of outcomes.
CONCLUSIONS: IB, DB/CB are relatively effective and safe revascularization options for pediatric MMD/MMS. Low-quality GRADE evidence suggest that DB/CB was associated with better long-term angiographic revascularization outcomes when compared with IB, although this did not translate to long-term stroke and mortality benefits.
Keywords: Cerebrovascular accident, Hemorrhagic stroke, Ischemic stroke, Moyamoya disease, Revascularization
FL-029
Dysraphism
Ventral anchoring of the conus medullaris to prevent repeated tethering following re-untethering in spina bifida: technical note
Nobuhito Morota
Department of Neurosurgery, Kitasato University Hospital, Sagamihara, Japan
BACKGROUND AND AIM: Repeated tethering following the untethering after initial surgery for spina bifida can develop. Surgical technique to prevent repeated tethering is expected.
METHOD: Untethering after initial repair of spina bifida (SB) was performed 83 times in 72 patients during the last 20 years. Among them, 13 patients (M:F = 3:10, age: 5–37 yrs, mean: 12.2 yrs) have undergone ventral anchoring (VAnch) of the untethered conus medullares since 2014. After untethering and myeloplasty of the conus medullaris, the termina end was fixed to the ventral dura loosely using 8–0 thread. Results of VAnch was analyzed retrospectively.
RESULTS: Original SB was MMC in 7, spinal lipoma 5 and one limited dorsal myeloschisis. VAnch was performed at the 1st re-untethering surgery in 11, 2nd in 1 and 3rd in 1. Duration from the previous surgery to VAnch ranged from 1 to 23 years (average 9.2 years) and follow-up period was 4 to 96 months (average 40.4 months). All but one showed improved preoperative symptoms and no complication relating the VAnch procedure was observed. Postoperative MRI showed restored dorsal subarachnoid space in 12 patients, but the space became obscure in the follow-up MRI in 2. No patients have experienced recurrence of tethered cord syndrome after VAnch for the present.
CONCLUSIONS: VAnch was effective to restore the dorsal subarachnoid space after untethering the conus medullaris. This preliminary study suggests that VAnch seems a promising procedure to prevent re-tethering after untethering the spinal cord in SB children.
Keywords: Re-tethering, Untethering, Tethered cord syndrome, Spina bifida, Conus medullaris
FL-030
Innovation and technology
One hundred cases of spinal lipoma: Surgical procedure with Ultrasonic bone curette and High frequency bipolar forceps
Akira Gomi1, Hirofumi Oguma2, Taku Uchiyama2
1Department of Pediatric Neurosurgery, Jichi Children's Medical Center Tochigi, Jichi Medical University, Tochigi, Japan
2Department of Neurosurgery, Jichi Medical University, Tochigi, Japan
BACKGROUND AND AIM: The purpose of spinal lipoma surgery is to prevent worsening of symptoms. Therefore, it is required to be less invasive, have no complications, and provide good long-term results. Here, we introduce our surgical procedures and results.
METHOD: A retrospective study of 100 cases of spinal cord lipoma (51 cases of conus lipoma and 49 cases of filar lipoma) who underwent initial surgery at our institute from 2006 to 2021. Surgical indications were all cases of conus lipoma, and filar lipomas that were symptomatic or had low-set conus or spinal cord abnormalities.
Surgical procedure) We introduced ultrasonic osteotomy SONOPET® in 2007, partial laminectomy by longitudinal-torsional vibration tip was performed for filar lipomas. Since 2011, laminotomy for conus lipomas was performed with scalpel- type tip, and the spinous process was fixed by suturing with the supraspinous ligament and paraspinal fascia. Since 2012, lipomas of conus have been removed using the high-frequency bipolar VESALIUS® according to the method of Pang et al.
RESULTS: Hemilaminectomy by SONOPET could be performed even in older children, and had no complication. It has the advantage of preserving the vertebral arch and posterior supporting tissue. SONOPET laminotomy and reconstruction are considered to be less invasive than laminectomy in that they can preserve supporting tissue. No patients had spinal deformities and the long-term results were good. VESALIUS is capable of incision and coagulation without heat diffusion, which is particularly useful for the dorsal type to confirm the white plane while avoiding spinal cord injury. Determining the cut surface with the transitional type or caudal type remains an issue.
CONCLUSIONS: Our surgical procedure was considered to be useful in terms of invasiveness and long-term results. We would like to continue to develop it in the future.
Keywords: Spinal lipoma, Surgery, Ultrasonic bone curette, High frequency bipolar forceps
FL-031
Occult tethered cord
Urological outcome following surgery for primary tethered cord syndrome
Navneet Singla
Department of Neurosurgery, PGIMER, Chandigarh
BACKGROUND AND AIM: Primary Tethered Cord Syndrome (TCS) is a congenital disorder due to defect in central neurulation and usually presents with pain, sensory and motor deficits, urological symptoms, foot deformities, scoliosis, cutaneous stigmata. The main aim of surgical detethering is to release the tethering structure and the chronic tension on the cord. Urological recovery and good outcome depends upon pre-operative deficits and timing of surgery.The Main objective of this study is to analyze the urological outcome at 6 months post-operative period after detethering for Primary TCS and its association with type of anomaly.
METHOD: A total of 48 patients of Primary TCS with age ranging from 2 to 12 years were taken. They were assessed with pre-operative symptoms, USG KUB and urodynamic study (UDS) and then re assessed at 6 month post-operative.
RESULTS: Out of 48 patients, 26 (54%) had pre operative urological symptoms. 38 patients showed abnormal UDS. 29 (60%) patients had improvement in UDS score while 17% showed worsening of UDS score. Younger patients and patients having pre operative urological symptoms improved more. Patients with LMMC having Neural Placode did not show significant benefit.
CONCLUSIONS: Early age of presentation and patients without Neural placode show better urological outcome. Urodynamic studies should be considered as one of the first line investigation in evaluation of patients of TCS.
Keywords: Tethered cord syndrome, Urodynamic study
FL-032
Occult tethered cord
Normal to abnormal: Reappraisal of Significant Event criteria. Deduction from electrophysiological correlation in 264 cases of Intraoperative monitoring for surgery for the tethered cord
Suhas Udayakumaran1, Sneha R Ramakrishnan2
1Division of paediatric Neurosurgery, Department of Neurosurgery, Amrita Institute of Medical Sciences and Research Centre, Kochi, India
2Division of Neurophysiology, Department of Neurology, Amrita Institute of Medical Sciences and Research Centre, Kochi, India
BACKGROUND AND AIM: The current recommendations for warning criteria during intraoperative neuromonitoring (IONM) are largely empirically derived. It remains challenging to define the parameters to keep it adequately sensitive to intraoperative neurophysiologic monitoring. Moreover, the present set of alarm criteria is a comparison with a baseline that can be abnormal by itself.
In this work, we identify the age-specific normative baseline of IONM and based on this, we try to clarify the significant event criteria.
METHOD: This is a prospective and retrospective study performed at the Amrita Institute of Medical Sciences and Research Centre, Kochi, India. We collected data from consecutive patients, under the age group 15 years who underwent surgery for tethered cord, under IONM, during the study period of March 2011 to July 2021.
RESULTS: We had a total of 39 events (n = 264 patients), operated for tethered cord, 117 muscles are involved in the event, out of which 12 muscle MEP (n = 4) 10.25% had deterioration and 105 muscle MEP (n = 35) 89.75% had improvement. In cases of improvement, amplitude increased by 40–100%, latency reduced by 40–100%, and duration increased by 70–100%. In the case of deterioration when compared to the baseline of that patient's amplitude is reduced by 20–60%, latency increases by 70–100%, and duration is reduced by 40–80%. With our alert criteria, we had a positive predictive value of 88.2% and a negative predictive value of 97.1%.
CONCLUSIONS: We conclude that any significant change (as defined) in amplitude, latency, and duration in comparison with the patient-specific baseline vis-à-vis the age-specific normative baseline is important. Changes in these parameters are simultaneous, hence, the amplitude is a convenient reasonable change as it can be easily identified and monitored. Keeping the low threshold of change for warning criteria is probably important for early or complete recovery.
Keywords: Tethered cord syndrome, Intraoperative neuromonitoring, Outcome, Spinal dysraphism
FL-033
Antenatal diagnosis and treatment
Histological study of the removed membranous area in fetal myelomeningocele repair: implications for dermoid cyst prevention
Frank Van Calenbergh1, Raf Sciot2, Philippe De Vloo1, Jan Deprest3
1Department of Neurosurgery, University Hospitals, Leuven, Belgium
2Department of Pathology (Neuropathology), University Hospitals, Leuven, Belgium
3Department of Obstetrics and Gynaecology, University Hospitals, Leuven, Belgium and Research Department of Maternal Fetal Medicine, UCL Institute for Women’s Health, University College London, U.K
BACKGROUND AND AIM: After fetal myelomeningocele (MMC) repair, several authors have noticed the occurrence of later spinal cord tethering caused by inclusion dermoid cysts, possibly more frequent than after postnatal MMC closure. This is probably caused by incomplete removal of epithelial remnants when releasing the neural placode from the skin by cutting the membranous area, considered to be of arachnoid origin. After having encountered 3 cases of postnatal dermoid cysts in our fetal neurosurgery program, we decided to perform a histological examination of the removed membrane fragments in the later patients.
METHOD: The standard technique consists of an incision at the border between skin and area membranosa, followed by removal of these membranes as close to the placode edge as possible. In 24 cases of fetal MMC repair (November 2020—May 2022), this membranous area was examined using staining for prekeratin (epidermis), EMA (meningothelial cells) and GFAP (glial tissue).
RESULTS: In all but 2 cases, immature cells were seen in the tissue. Ten cases consisted of only immature skin, 12 cases contained skin elements mixed with either glial (5), meningothelial (2) cells or both (5). There was no statistical relationship with the morphological type (flat ‘myeloschizis’ type or raised sac ‘myelomeningocele’). However, the 2 cases without skin cells were of the myeloschizis type. As yet no dermoid cyst has been seen in these recent cases.
CONCLUSIONS: In the membranous area between the neural placode and the readily identifiable skin border, skin cells are usually present. Therefore, meticulous neurosurgical technique is required to remove these thin membranes, not limiting the removal to tissue that “looks epidermal” but cutting the thin membranes as close as safely possible at the border of the placode.
Keywords: Fetal repair, Myelomeningocele, Dermoid cyst
FL-034
Dysraphism
Effectiveness of onlay dural implants in prevention of CSF leak and wound breakdown in paediatric spinal dysraphism surgery: A single centre experience
Azam Ali Baig, Fardad T Afshari, Wai C Soon, William B Lo, Richard A Walsh, Desiderio A Rodrigues, Guirish A Solanki
Department of Neurosurgery, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
BACKGROUND AND AIM: To report and compare the efficacy of DuraGen and Duraform onlay dural implant usage in dysraphism surgery.
METHOD: A 13-year retrospective review of all paediatric spinal dysraphism surgeries from the surgical database and operative implant logbooks was conducted. 439 patients underwent surgical correction for all spinal dysraphisms from 2006–2019. The types of dural implants used were confirmed through the operative implant logbooks. The incidence of post-operative CSF leak and/or wound breakdowns requiring re-exploration were identified through the operative database. Reasons for reoperations were explored. 3 groups (duragen, duraform, no dural substitute) are evaluated.
RESULTS: 439 children underwent dysraphic repair procedures. 392 had onlay dural implants and 47 did not. All primary leaking Myelomeningocoele repairs were performed within 48 h of birth. DuraGen was used in 270/392 (69%). Duraform in 122/392 (31%). DuraGen had 4 (1.5%) and Duraform had 18 (14.8%) reoperations. The reoperations in the Duragen group were due to 1(0.37%) CSF leak and 3 (1.1%) wound-breakdowns. The CSF leak in the duraform group was 9% but accounted for 61% (11/18) of reoperations. Wound dehiscence was 5.7% (7/18). In the non-onlay dural group, the CSF leak was 4.3% (2) and 30% (14) had wound-breakdowns. The relative risk for CSF Leak in the non-onlay group versus duragen is 11.48. The relative risk ratio of wound breakdown in the non-onlay versus onlay implant is 11.7, and this rises to 26.8 if compared with duragen alone.
CONCLUSIONS: The use of onlay dural implants to achieve dural closure that prevents CSF leak is safe and effective. Duragen was particularly effective and associated with significantly fewer complications requiring revision surgery compared to Duraform. Repairs without use of onlay dural substitutes compared with duragen were 11.5 times more likely to have a CSF leak and 26.8 times more likely to have a wound-breakdown.
Keywords: Dural graft, Pediatrics, Spinal dysraphism
FL-035
Dysraphism
Diagnosis, clinical presentations, and outcome determinants of surgically treated children with neural- tube defect: A prospective cohort study in a high-volume centre
Abenezer Tirsit Aklilu1, Yemisirach Bizune Aklilu1, Bethelehem Yesehak Worku1, Mahlet Yigaramu Gebremariam3, Asrat Demetse A.4, Filmon Mengesha A.5, Samuel Masresha Fetene1, Eyob Zenebe Wondemagawu1, Samuel Getahun E.1, Tsegazeab Laeke Teklemariam1, Bente E. Moen6, Morten Lund Johansen2, Ruby Mahesparan Rupavathana2
1Division of Neurosurgery, Addis Ababa University, Addis Ababa, Ethiopia
2Department of Neurosurgery, university of Bergen, Bergen,Norway
3Department of Gyobs, Addis Ababa University, Addis Ababa, Ethiopia
4Department of paediatrics, Addis Ababa University, Addis Ababa, Ethiopia
5Department of psychiatry, Addis Ababa University, Addis Ababa, Ethiopia
6Department of Global Public Health and Primary Care, University of Bergen, Norway
BACKGROUND AND AIM: Neural tube defects (NTDs) are developmental malformations caused by defects in neurulation or modifications in neural tissue morphogenesis. Treatment and prevention of various complications associated with NTDs require multidisciplinary care. Surgery is usually the first line of treatment.
METHOD: We prospectively investigated all children surgically treated for NTD closure from April 2019 to May 2020 at the paediatric neurosurgical specialty centre in Addis Ababa, Ethiopia, over a period from the primary admission until one year. We investigated outcomes in-hospital and at follow-up, and analyzed predictors of complications and mortality. The outcomes were compared with those of a recently published retrospective study from the same centre.
RESULTS: A total of 228 children were included. The mean age at presentation was 11 days (median 4, (1–105)). The commonest anatomical location of defects was the lumbar (57%). Half of the children (49%) had paraplegia in their lower extremities. During a one-year follow-up of 143 (62.7%) children, 123 (83%) were alive. Hydrocephalus (P = 0.05) and younger age (P = 0.02) were identified as risk factors for mortality. The wound-related complication rate was 55% at one year and was associated with large defects (mean, 162.9 mm3 & P = 0.04), intraoperative blood loss (mean 50.42 ml & P = 0.02), and late presentation to the hospital (mean age 13 days & P = 0.01). The readmission and reoperation rates were 40 and 20% and associated with hydrocephalus and open defects; 80% of the re-admissions were related to hydrocephalus treatment (P = 0.04) and 87% of the re-operated children had an open defect (P = 0.05). When comparing with a recently published retrospective study from the same institution, we found a significant improvement in outcomes.
CONCLUSIONS: NTD closure is a very common procedure in Addis Ababa. Overall survival after surgery is acceptable, but one-year mortality, complication, and re-admission rates were still high.
Keywords: Neural tube defect, Outcome, Low-income country, Ethiopia
FL-036
Dysraphism
Social, Psychological, and Economic Burdens Experienced by People with Spina Bifida and Their Caregivers: Review of 50 cases from a developing country
Mansur Idris Muhammad1, Salman Ayodeji Yusuf1, Nasiru Jinjiri Ismail2, Ali Lasseini2, Aliyu Muhammad Koko2, Muktar Isah Teli1, Bello Bala Shehu2
1Division of Neurological Surgery, Department of Surgery National Hospital Abuja Nigeria
2Regional Center for Neurosurgery, Usmanu Danfodio University Teaching Hospital Sokoto Nigeria
BACKGROUND AND AIM: Areas of peoples’ lives affected by Spinal Bifida (SB) included physical and role functioning, activities of daily living, bodily pain, vitality, emotional functioning, mental health, self-esteem, self-image, social functioning, relationships, and sexual functioning. Areas of caregivers’ lives affected included activities of daily living, work impact, time consumption, parental responsibilities (including responsibilities to other children), confidence, feelings and emotions, mental health, stress, social impact, psychological adjustment, relationships (with SB child, siblings, other family members), social support, coping strategies, and termination decisions. Cost burdens on patients and caregivers also include out-of-pocket costs, lost wages, or household production due to increased morbidity and mortality, transportation and other nonmedical costs.
METHOD: Review of case and follow-up notes with telephone conversations of all patients who presented and had repaired of spinal bifida between March 2017 to March 2022 (Five years) at the Regional Center for Neurosurgery, Usmanu Danfodio University Sokoto (UDUTH) and National Hospital, Abuja (NHA) Nigeria were carried out.
RESULTS: Myelomeningocele associated with skeletal deformity and bi-sphincteric dysfunctions constituted 60% (30 cases) of the reviewed cases, with a male to female ratio of 1:2. Only 8 patients (4%) are covered by health insurance. Parental work absenteeism or drop out especially by working mothers is alarming. Majority of the parent required psychological counselling. Very few parents (11%) wish to carry another pregnancy again. They described societal stigmatization as a fundamental encumbrance.
CONCLUSIONS: This review highlights the need to provide care and support to individuals with SB and their caregivers. Results also emphasize the importance of effective long-term public health campaigns and/or newer strategies to prevent NTDs, such as SB.
Keywords: Spinal bifida, Psychological, Social, Economic, Myelomeningocele
FL-037
Dysraphism
Lessons Learnt In Retethered Spinal Cords in Dysraphism- experience of 20 years
Sandip Chatterjee
Dept of Neurosurgery, Park Clinic, Kolkata, India
BACKGROUND AND AIM: Was to retrospectively review our series of surgery for SYMPTOMATIC retethering in spinal dysraphism performed in children and young adults up to the age of 30 years over a 20 year period from 2001 to 2020. This was done to try and identify a)Causes of retethering and how to prevent the same, and b)To try and devise a classification system of cases of retethering.
METHOD: 66 cases of retethering were identified over this period. Of these 28 were following repair of open neural tube defects, 26 following repair of lipomas, and 12 were following surgery for other conditions. Intentionally no distinction was made between primary surgery performed by the author and surgery performed elsewhere.
The age of patients of retethering ranged from 3 to 30 years, and the presentation occurred from 2 to 30 years after the first surgery.
RESULTS: We were able to classify retethering into Type 1 or early when this occurred within 2 years of the first surgery, and which we termed “Early retethering” and Type 2 or “Late retethering” which occurred more than 2 years after the first surgery. In each case an attempt was made to try and determine the exact cause of retethering.
CONCLUSIONS: We were able to conclude that Type 1 retethering is a fault of surgical technique- Failure to recognize the tethering elements, improper dural closure, failure to remove adequate abnormal tissue; whereas Type2 retethering was caused by growth spurt, increase in weight, Chiari malformation, trauma or even a congenital narrow spinal canal.
It was also established that using intraoperative neuromonitoring was an important adjunct to prevent retethering.
Keywords: Retethering dysraphism
FL-038
Dysraphism
Association of Jarcho-Levin Syndrome with Spina Bifida in Children: Its Prevalance and Urological Outcome in a Cohort of 837 Patients
Seyhmus Kerem Ozel1, Ibrahim Alatas2, Doga Ugurlar3, Revna Cetiner3, Nafiye Sanlier3, Teoman Karakurt3
1Goztepe Training and Research Hospital, Istanbul, Turkey
2Baskent University Hospital, Istanbul, Turkey
3Istanbul Training and Research Hospital, Istanbul, Turkey
BACKGROUND AND AIM: Jarcho Levin Syndrome (JLS) is diagnosed when vertebral and costal anomalies are associated with prominent short stature and kyphoscoliosis. The aim of this study was to delineate the clinical features and prevalence when JLS is observed with spina bifida.
METHOD: Patients who were treated in our Spina Bifida Center were enrolled retrospectively. Patients who had the diagnosis of JLS and spina bifida (SB) and only SB were compared. Age, gender, urinary tract infection (UTI), clean intermittent catheterization (CIC), constipation, anticholinergic usage, presence of hydronephrosis, renal scarring, vesicoureteral reflux, bladder wall thickness, bladder capacity, compliance, detrusor activity, sphincter activity and residual urine were compared with student’s t test and chi square test.
RESULTS: A total 60 patients (7,17%) were diagnosed as JLS among 837 SB patients. Patients with JLS were compared with the rest of 777 SB patients. The diagnosis was SB aperta in 78,3% of JLS and 68% of SB patients (p = 0,099). UTI was present in 42,9% of JLS patients and 45,3% of SB patients (p < 0,0001). CIC was necessary in 31,6% of JLS patients and 40,4% in SB patients (p < 0,0001), anticholinergic was used in 25,9% of JLS patients and 32,2% in SB patients (p = 0,027). Constipation was present in 38,6% of JLS patients and 43,9% of SB patients (p = 0,003).
CONCLUSIONS: More need for CIC, more frequent anticholinergic usage, decreased compliance, more underactive detrusor and detrusor sphincter dyssynergia in SB may show that bladder is more affected in SB than JLS. General prevalence of JLS in SB is 7,17% in this cohort. Patients should be carefully evaluated clinically and urodynamically to justify proper treatment indications in these patients.
Keywords: Jarcho-levin syndrome, Spina bifida, Urodynamics
FL-039
Dysraphism
Management of hydrocephalus associated with myelomeningocele: Can we efficiently reduce the rate of the shunt?
Nabila Tighilt, Nazim Boumahdi, Farid Bouchenaki, Souad Bakhti
Pediatric Neurosurgery Unit, Ali Ait Idir Hospital, Faculty of medicine, University of Algiers1, Algiers, Algeria
BACKGROUND AND AIM: Myelomeningocele is the most serious and complex birth defect affecting the CNS compatible with life. The shunt rate of associated hydrocephalus reached 80%, but the complications of the shunt constitute an additional morbidity. Nowadays, many neurosurgeons seek to reduce the shunting rate in order to decrease morbidity.
METHOD: We report a retrospective series of 100 cases of myelomeningocele. All the patients were operated on for myelomeningocele, except one patient who presented with laryngeal stridor. In our series, treatment of hydrocephalus was motivated by progressive macrocrania in 59 cases, inspiratory stridor in 4 cases, poor sucking in 3 cases, motor deficit in 1 case and a postoperative fistula in 5 cases.
RESULTS: Shunt was performed postoperatively in all patients, except for the patient who presented with severe brainstem dysfunction, that requires ventricular drainage as a first step in emergency. In our series, 33 patients did not require treatment of hydrocephalus. Indications for treatment of hydrocephalus in myelomeningocele are progressive macrocrania and brainstem dysfunction. The heavy morbidity associated with the shunt will be responsible of poor quality of life. This has resulted in the current trend which is in favor of a more tolerant management of hydrocephalus and a reduction in the shunt rate which has reached 51.9 to 40% depending on the series. In our series, treatment for hydrocephalus is still high at 67%, but selection bias impacted our results.
CONCLUSIONS: Indications for the treatment of hydrocephalus are well defined and are limited to evolutive intracranial hypertension signs and brainstem dysfunction. Ventricular dilatation and CSF leak are not valuable indications for ventricular drainage. Monitoring criteria allowed us to tolerate a certain increase in the size of the ventricles. This attitude will lead to a reduction in the rate of the shunt in children with myelomeningocele and thus reduce the morbidity linked to the shunt.
Keywords: Myelomeningocele, Hydrocephalus, Ventricular diversion, Macrocrania, Brainstem dysfunction
FL-040
Spine
Operated spinal lipomas: single centre experience
Ahmed Aly1, Libby Van Tonder2, Helen Fiona Mcandrew3, Dawn Hennigan2, Benjamin J. Hall2, Benedetta Pettorini2
1Department of Neurosurgery, Royal Stoke Hospital, Stoke, UK
2Department of Neurosurgery, Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, UK
3Department of Urology, Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, UK
BACKGROUND AND AIM: The role of surgery in managing lumbosacral lipomas is controversial, with little standardization in practice. We aim to demonstrate our single center experience in the surgical management of lumbosacral lipomas, by applying recently suggested criteria for low-risk lesions and comparing outcomes.
METHOD: Operated lipoma patients between 2012 and 2017 were extracted from a prospective data base. Pre- and post-operative clinical data were collected and analyzed. A subcategory of patients with MRI findings compatible with recently suggested ‘Thompson criteria’ were identified. Outcome measures included were also compared between this subcategory and the general cohort.
RESULTS: 13 patients diagnosed with spinal lipoma underwent operative management during this time. 6 patients reported pre-operative urological dysfunction, of whom 1 worsened postoperatively and one improved. Another patient developed urological complications postoperatively. 7 patients reported preoperative neurological deficits, 3 of whom improved post-operatively. No patient developed a new neurological deficit postoperatively. One patient had total resection of their lipoma, 9 had subtotal or near total resection and 3 had partial resection. No major difference in outcome between low-risk and high-risk lesions according to Thompson criteria were identified in our cohort.
CONCLUSIONS: Surgical resection of lumbosacral lipomas is feasible and safe; proving effective in those achieving total resection. We hope in the future a more profound understanding of natural history and more developed classification criteria will help in counselling and managing patients more safely and predictably.
Keywords: Spinal, Lipoma, Operative, Paediatric
FL-041
Dysraphism
Fetoscopic repair of open neural tube defects: a case series of 16 patients who underwent fully percutaneous or open fetoscopic repairs
David Rowland1, Ladina Greuter1, Susan Mash3, Claire Cairns1, Anca Vasilica4, Chula Goonasekera2, Sarah Nour2, Matthew Brown3, Marta Santorum Perez3, Kypros Nicolaides3, Cristina Bleil1, Bassel Zebian1
1Department of Paediatric and Adult Neurosurgery, King’s College Hospital NHS Foundation Trust, London, UK
2Department of Anaesthesia, King’s College Hospital NHS Foundation Trust, London, UK
3Fetal Medicine Unit, King’s College Hospital NHS Foundation Trust, London, UK
4University College London Medical School, London, UK
BACKGROUND AND AIM: Myelomeningocele is a significant cause of morbidity world-wide; it affects 33–48 per 100,000 live births. Antenatal repair is gaining in popularity driven by the MOMS trial. Open fetal repair is associated with maternal complications. There is an increased drive towards more minimally invasive / fetoscopic procedures with an increasing number of centres performing these. We report the UK’s first experience of fetoscopic repairs (fully percutaneous and open fetoscopic).
METHOD: Retrospective case series.
RESULTS: 16 fetuses underwent repair at KCH using materno-fetal anaesthesia between September 2018 and May 2022. They were diagnosed on routine antenatal ultrasound scans and had subsequent fetal MRI. They fulfilled the eligibility criteria and informed consent was obtained after discussion of all the available options. We initially performed fully percutaneous fetoscopic closure for all patients then elected to exteriorise the uterus for patients with a completely anterior placenta to allow port insertion. Two weekly assessments were performed, and fetal MRI scan planned 4 weeks postoperatively. We report the maternal and fetal outcomes and compare with the published literature.
CONCLUSIONS: Fetoscopic myelomeningocele repair has already been shown to be a valuable addition to the armamentarium for repair of open spinal neural tube defects. The evidence so far suggests there is reduction in the risk to mothers and subsequent pregnancies and much work has taken place to reduce the rates of premature delivery and improve fetal/neonatal outcomes.
Keywords: Myelomeningocele, Open neural tube defects, Dysraphism, Fetoscopy
FL-042
Dysraphism
Multidisciplinary approach for the treatment and management of lipomyelomeningoceles: a single centre experience with long-term surgical, neurological and urological outcomes
Benjamin James Hall1, Maria Rosaria Scala2, Raenette David1, Helen Fiona Mcandrew1, Benedetta Pettorini1
1Department of Neurosurgery, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
2Department of Neurosciences and Reproductive and Odontostomatological Sciences, Division of Neurosurgery, University of Napoli Federico II, Naples, Italy
BACKGROUND AND AIM: Lipomyelomeningoceles (LMMC) are a form of spina bifida occulta, composed of a subcutaneous lipomas connected to the spinal cord through a midline defect in the lumbosacral fascia Prophylactic surgery in LMMC is debated, therefore, we present ten years of operatively managed LMMC at our centre.
METHOD: Electronic case notes of all patients diagnosed with LMMC between January 2012 and May 2022 were retrospectively reviewed. Data collection included: sex, age, indication for surgery, pre- and postoperative urological status (catheterisation, urinary tract infections, urodynamics), pre- and postoperative neurological status (weakness, deformity) and complications.
RESULTS: Of the twenty-three (23) patients included, the median age at surgery was 8.8 months (range: 1 month—12 years). 69.5% of patients were female with five patients diagnosed antenatally, sixteen at birth and the remainder later in childhood. 91% of patients presented with lumbosacral fatty lumps; three patients were also diagnosed with Chiari malformations. Prophylactic surgery was undertaken in 73.9% (17) of cases, with the remainder performed for urological or neurological decline.
Regarding urological function, 34.8% demonstrated abnormal preoperative parameters and 60.9% (14) underwent preoperative urodynamics. Of these, 30.4% showed clinical improvement while all other patients remained stable. Of all patients who presented with neurological impairment (30.4%), three patients (42.9%) improved neurologically: two of whom had motor improvement and one a reduction in pain.
There were three (3) complications encountered – one cerebrospinal fluid leak, one wound dehiscence and one superficial wound site infection. Mean follow-up was 33.5 months from surgery, during which time no patients required further surgery for their LMMC.
CONCLUSIONS: Operative management for LMMC remains controversial, particularly in the context of prophylactic surgery. A multi-disciplinary approach to surgical management of LMMC is paramount to achieving good results. Our series demonstrates surgery, in select patients, can positively impact on both urological and neurological function.
Keywords: Lipomyelomeningocele, Prophylactic, Spinal, Dysraphism, Urodynamics
FL-043
Dysraphism
Surgical Outcomes of Myelomeningocele Repair: a 20-Year Experience from a Single Center in a Middle-Income Country
Mohammad Sadegh Masoudi, Sina Zoghi, Maryam Feili, Mohammad Amin Mosayebi, Mohammad Amin Afifi, Afrooz Feili, Reza Taheri
Shiraz university of medical sciences, school of medicine, neurosurgery department
BACKGROUND AND AIM: Background.
Spina bifida is the second major cause of congenital disorders following congenital heart defects and the most common central nervous system malformation compatible with life, which primarily affects populations of low socioeconomic status.
OBJECTIVE: To describe the outcome of myelomeningocele surgical management and predictors of its postoperative complications and mortality.
METHOD: This retrospective chart review studies the children who underwent surgical management for myelomeningocele in our institution from May 2001 to September 2020.
RESULTS: 256 patients were enrolled. The median age at the operation was roughly eight days (IQR: 7). The most common site of involvement of Myelomeningocele (MMC) was Lumbosacral (86%, n = 204). At the evaluation conducted prior to operation, CSF leaking was observed in 7% (n = 16) of the patients. Postoperatively, 5.7% of the patients were expired in the 30 days following the operation (n = 14), while 24% needed readmission (n = 47). The most common complications leading to readmission included wound dehiscence (n = 10, 42%) and wound purulence (n = 6, 25%). No variable was significantly associated with postoperative complication except for the site of the lesion (p-value = 0.035) and the presence of the lipid content in the defect (p-value = 0.044).
CONCLUSIONS: The presence of lipid compartment in the lesion and the site of the lesion are the two factors that were associated with the rate of mortality. However, further investigations into preoperative interventions and risk factors to mitigate the risk of complications and mortality are highly encouraged.
Keywords: Myelomeningocele, MMC, Neural tube defect, Spina bifida, Surgical outcome, Pediatric neurosurgery
FL-044
Spine
CSF leak after intradural spinal surgery in the pediatric population
Emma M.H. Slot1, Tristan P.C. van Doormaal2, Kirsten van Baarsen3, Menno R. Germans4, Nick Krayenbühl4, Luca Regli4, Eelco W. Hoving5
1Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Translational Neuroscience, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands
2Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Translational Neuroscience, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands; Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland
3Department of Neuro-oncology, Princess Maxima Center for Paediatric Oncology, Utrecht, the Netherlands
4Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland.
5Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht; Department of Neuro-oncology, Princess Maxima Center for Paediatric Oncology, Utrecht, the Netherlands
BACKGROUND AND AIM: Cerebrospinal fluid leakage is a potentially serious complication after intradural spinal surgery. This study aims to establish the incidence of CSF leakage and associated complications after intradural spinal surgery and describe the treatment strategies applied.
METHOD: All patients aged 18 years or younger who underwent intradural spinal surgery between 2015 and 2021 in three tertiary neurosurgical referral centers with complete follow up to at least 6 weeks and a complete surgical report were retrospectively reviewed. The primary outcome measure was CSF leakage within 6 weeks after surgery, defined as leakage of CSF through the skin. Secondary outcome measures included: presence of pseudomeningocele (PMC), meningitis and surgical site infection (SSI).
RESULTS: We identified 80 procedures, representing 68 individual patients. The most frequent indication was tumor resection (n = 43), followed by spina bifida correction (n = 35) and vascular surgery (n = 2). The mean age was 6.3 (SD 6.2) years. CSF leakage occurred in 2.5% (2/80) of cases. These leakages occurred at day 3 and 21 after the index procedure. One patient was treated with pressure bandage and an external lumbar drain on day 3 after diagnosis of the leak, the other was treated with wound revision surgery on day 1 after diagnosis of the leak. Three patients developed a PMC (3.8%). There was one case of PMC without a CSF fistula, which was treated with wound revision surgery. SSI occurred in 11.3%, including both cases of CSF leak. There were no cases of meningitis.
CONCLUSIONS: CSF leakage after intradural spinal surgery in a pediatric population is relatively rare (2.5%). Nevertheless, the clinical consequences with respect to secondary complications such as infection and necessity for invasive treatment are serious. Development of preventative strategies for spinal surgery in the pediatric population is mandatory.
Keywords: Cerebrospinal fluid leakage, Pediatrics, Infection, Spinal surgery, Spina bifida
FL-045
Spine
Surgical management of different types mucopolysaccharidosis -related orthopedics pathology
Polina Ochirova
Federal State Budgetary Institution "National Ilizarov Medical Research Centre for Traumatology and Ortopaedics" Ministry Healthcare, Russian Federation
BACKGROUND AND AIM: Spinal pathology in patients with mucopolysaccharidosis a problem requiring early treatment.
METHOD: We analyzed 15 cases of mucopolysaccharidosis (MPS), treated in Ilizarov Center in 2012 – 2022. There were 1 patient with MPS IH-type, 2 patient with MPS IHS-type, 8 patients with IVA-type and 4 patients with MPS type VI. The age of the patients ranged from 2,5 to 26 years-old. All patients had spinal deformity with primary and/or secondary stenosis of the spinal canal. Various surgical treatments were used: 1) two staged surgery was perfomed in one patient with cervical myelopathy and scoliosis: C0-C7 decompression with occipitospondylodesis (OSD) firstly and dual growing rod construction secondly; 2) final fusion in 2 patients with scoliosis; 3) decompression at the stenosis level (cervical spine) with OSD in 12 patients with cervical myelopathy.
RESULTS: Scoliosis value was from 20° to 65° Cobb, kyphosis from 15° to 80° Cobb. Four patients had vertebral stenosis and myelopathy (Frankel C). All patients had pulmonary and cardiac dysfunctions: vital capacity of the lungs was from 21 to 50% and abnormal ECG. Imbalance in the frontal and sagittal planes was present in 60% of patients. Through surgical treatment correction of the kyphosis was by 68% and scoliosis by 85%. In 4 (50%) patients with spinal stenosis neurologic status improved to Frankel E.
CONCLUSIONS: Patients with MPS quite often have vertebral stenosis and myelopathy, in such patients with combined stenosis of the spinal canal, it is necessary to combine decompression and fusion.
Keywords: Mucopolysaccharidosis, Spinal deformity, Scoliosis, Stenosis, Cervical myelopathy, Decompression
FL-046
Spine
Outcome Analysis of Surgical Management of Paediatric Cervical Kyphotic Deformity (CKD): an Institutional Experience
Sivaraman Kumarasamy, Pankaj Kumar Singh, Dattaraj P. Sawarkar, Rajinder Kumar, P. Sarat Chandra, Shashank Sharad Kale
Department of Neurosurgery, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, India
BACKGROUND AND AIM: Paediatric cervical kyphotic deformity (CKD) is extremely rare and occurs due to congenital, traumatic, metabolic or neoplastic processes which mandates surgical correction. Most outcomes analysis following surgery are small retrospective case series and are limited to specific etiology or surgical technique. The objective of our study is to analyse a single-centre operated paediatric CKD, highlighting (a) the clinical and radiological outcomes (b) the safety and efficacy of different surgical approaches (c) change in the quality of life in terms of neck pain, myelopathy and deformity correction.
METHOD: Patients (aged ≤ 18 years) operated at a tertiary centre between January 2009 to April 2022 were included. Besides demographic details, the outcome measures assessed were clinical (Nurick grading, mJOA score), radiological (Cobb’s angle) and operative complications.
RESULTS: A total of twenty-two patients were included, with mean age of 12.90 ± 4.02 years (3 – 18) of which ten were syndromic, three were metabolic, seven were post-traumatic and one post-infective. Thirteen patient had features of myelopathy on presentation. All underwent surgical correction, of which nine patients underwent Antero-posterior approach, eight patients underwent Posterior only approach and four patients underwent Anterior only approach. Clinically, patients improved postoperatively with – Nurick grade (pre vs. post: 3.24 vs. 2.24, p – 0.172), mJOA score (pre vs. post: 10.19 vs. 12.71, p – 0.679). There was significant deformity correction from 37.086° to 13.725° (p – 0.045). Mean blood loss encountered was 680 ± 671.93 cc. Early complications included intraoperative hemodynamic instability (4) and lung collapse (1). Late complications included junctional kyphosis (1). Mean follow-up was 49.38 ± 44.15 months.
CONCLUSIONS: Pediatric CKD are rare, debilitating condition which can be managed surgically. Antero – posterior approach provides circumferential decompression and better correction compared to Anterior only and posterior only approach. Patients should be screened for syndromic association and regularly followed.
Keywords: Cervical kyphotic deformity, Antero-posterior, Junctional kyphosis
FL-047
Spine
Congenital cervicothoracic dislocation: a rare condition with a high risk of complications
Olga M Sergeenko, Alexey V Evsyukov, Egor Yu Filatov, Sergey O Ryabykh, Alexander V Burtsev, Alexander V Gubin
Ilizarov Center
BACKGROUND AND AIM: Congenital cervicothoracic dislocations are rarely described in the literature. The exact causes of their occurrence poorly studied and treatment tactics vary. The main goal of our work was to analyze the world experience and our own experience in the treatment of congenital pediatric cervicothoracic dislocations and understand what type of treatment is optimal for these patients.
METHOD: We performed a literature review and found seven literature sources that describe congenital cervicothoracic dislocations and its treatment. In addition, we analyzed the data of five own patients.
RESULTS: Only eight patients from seven sources with congenital cervicothoracic dislocations and a description of treatment tactics were found. The treatment was long and accompanied by a large number of complications. Among five own patients four had Klippel-Feil syndrome (Figs. 1 and 2) and one had neurofibromatosis. All patients had preoperative neurological disorders. Posterior instrumental fixation with posterior vertebral body resection was performed in four cases and one patient had combined surgery. Neurological deterioration happened in two patients, neurological improvement was in two patients and one patient was stable. We have divided all complications according to the Clavien-Dindo-Sink: four patients Grade II, five Grade IIIB and one Grade IV types. The total number of surgeries related to complications was four. Average follow-up time was five years (from one to 9.8 years).
CONCLUSIONS: Congenital cervicothoracic dislocations are an extremely rare and difficult to treat pathology that manifests in early age and requires early treatment. Tactics of treatment is determined individually, but according to the literature and our own experience, early multi-stage combination treatment is preferred, although it requires more effort.
Keywords: Congenital cervical thoracic dislocation, Cervical thoracic spondyloptosis, Cervical thoracic spondylostesis, Cervocothoracic instability, Segmental spinal dysgenesis
FL-048
Spine
Traumatic rotatory subluxation of C1C2 joint -a review of 36 cases
Siddharth Dipakbhai Mistry, Sandip Subirkumar Chatterjee
Park Clinic 4 Gorky terrace,Kolkata,West Bengal, India
BACKGROUND AND AIM: To study the clinical presentation and management strategies for traumatic rotatory subluxation. Brief introduction-Traumatic rotatory subluxations are rare and may be caused by trivial trauma and may present with torticollis. They represent a rotatory deformity of the atlas on a fixed axis.
METHOD: We retrospectively reviewed all cases of rotatory C1C2 subluxations and we could identify 36 traumatic rotatory subluxation cases from January 2000 till December 2020. All these cases were thoroughly evaluated clinicoradiologically by means of CT and MRI scans.In all cases preliminary skull traction(Holter) was applied. The patients were evaluated for etiology, associated trauma, loss of consciousness, treatment undertaken, and neurological status before and after reduction.
RESULTS: The average time from trauma to treatment ranged from 3 days to 6 months(average). 19 patients had trivial trauma and presented with traumatic torticollis and only one presented after 6 months as his injury was missed due to polytrauma. The remaining 16 patients presented after falls. Only 7 out of 36 patients had any neurodeficit. In all cases CTScans of the atlantoaxial junction were done. After preliminary skull traction to all cases 6 cases reduced but later recurred and these were treated with halo vest fixation for three months. Of the rest only 5 which were irreducible were treated with operative methods, and all the remaining 25 were treated conservatively by Holter traction followed by application of Philadelphia collar for 8 weeks. It is interesting to point out a special category of patients we encountered where there was rotation of the axis about a fixed atlas, and although we had 8 of these patients we excluded them from this study.
CONCLUSIONS: Patients presenting early with traumatic rotatory subluxation can be treated only conservatively by traction if they present early.
Keywords: Rotatory Subluxation of C1C2 joint
FL-049
Spine
Management outcome (5 years or more) of paediatric vertebral hemangiomas presenting with myelopathy
Pankaj Kumar Singh, Sarat P Chandra, Shashank Sharad Kale
Department of neurosurgery, All India institute of medical sciences, New Delhi, India
BACKGROUND AND AIM: Vertebral hemangiomas are very rare in pediatric age group. In this study we analysed the outcomes of patient treated at department of neurosurgery, All india institute of medical sciences New Delhi since may 2010 to January 2022 with at least 5 year follow up.
METHOD: All patients up to 18 years age of vertebral hemangioma treated at our hospital from may 2010 to january 2022 with at least 5 year follow up. All had features of myelopathy.Patients demography, clinical details and follow up and complications were retrieved from hospital records. Functional clinical outcomes were measured using ASIA score. Mean age was 14.21 years with range of 12 years to 18 years. All patients had magnetic resonance imaging and computed tomography of spine in preoperative and postoperative period. Mean follow up was 78 months with range from 60 to 144 months.
RESULTS: There were 6 male and 8 female patients with sex ratio of 3:4. All were located in dorsal spine with single level involvement. Upper dorsal spine involvement was more common (10 cases 71.43%) than lower dorsal spine involvement (4 case 28.57%). All patients had weakness of lower limbs with features of myelopathy, urinary bladder symptoms were present in 6 patients local site pain in 1. D1 involvement was present in 1, D3 in 2, D4 in 2, D5 in 2, D6 in 3, D8 in 1,D10 in 1,D11 in 1 and D12 in 1. All patients have improvement in power of both lower limbs after surgery. Bladder symptom and pain resolved in all patients.
CONCLUSIONS: Good postoperative results can be achieved in pediatric symptomatic vertebral hemangioma with minimal complications. Individualization of treatment for each patient should be done with avoidance of selecting more blood loss procedures like corpectomies.
Keywords: Vertebral hemangioma
FL-050
Global Pediatric Neurosurgery
Development and validation of a Fast Spine Protocol for Use in Paediatric Patients
Winnie (Shu Yu) Wu1, Elka Miller2, Julie Hurteau Miller2, Madhura Thipse3, Cassandra Kapoor2, David McAuley4, Albert Tu4
1Department of Medicine, University of Ottawa, Ottawa, Canada
2Department of Medical Imaging, CHEO, Department of Radiology, University of Ottawa, Canada
3Clinical Research Unit, CHEO, University of Ottawa, Ottawa, Canada
4Division of Neurosurgery, CHEO, University of Ottawa, Ottawa, Canada
BACKGROUND AND AIM: Conventional pediatric spine MRI protocols have multiple sequences resulting in long acquisition times. For many patients, sedation is consequently required. In brain imaging, indications such as hydrocephalus are now acceptably evaluated using a limited number of sequences resulting in shorter scan times and avoiding the need for sedation. This study evaluates the diagnostic capability of a limited MRI spine protocol for selected common pediatric indications.
METHOD: After REB approval, records of pediatric patients under 4 years of age who underwent a spine MRI at CHEO between 2017 and 2020 were reviewed. A blinded retrospective review by two neuroradiologists, limited to the T2 sagittal sequences from the craniocervical junction to sacrum and T1 axial sequence of the lumbar spine, was performed to answer specific questions regarding cerebellar ectopia, syrinx, level of conus, filum < 2 mm, fatty filum, and spinal dysraphism. The results were independently compared to previously reported findings obtained from the complete series of imaging sequences.
RESULTS: 105 studies were evaluated in 54 male and 51 female patients (mean age of 19.2 months). The estimated combined scan time of the limited sequences was 9–18 min compared to 24–36 min for conventional protocols (delta = 20–30 min). The average percent agreement between full and limited sequences was > 93% in all but identifying a filum < 2 mm, where the percent agreement was 87%. Using limited MR sequences had high sensitivity (> 0.97) and specificity (> 0.99) for the detection of cerebellar ectopia, syrinx, fatty filum, and spinal dysraphism.
CONCLUSIONS: This study demonstrates that highly selected sequences of spine imaging allows for consistent and accurate diagnosis of specific clinical conditions. The time required to obtain these sequences is substantially less than traditional imaging protocols and potentially avoids the need for sedation while increasing patient throughput. Further study is required to determine the utility of selected imaging for other clinical indications.
Keywords: Spine, Technical advances
FL-051
Spine
Efficacy of Selective Dorsal Rhizotomy and Intrathecal Baclofen Pump in the management of spasticity
Pramath Kakodkar1, Hidy Girgis2, Perla Nabhan3, Sharini Sam Chee4, Albert Tu5
1Department of Laboratory Medicine and Pathology, University of Saskatchewan, Saskatoon, Canada
2Department of Neurosurgery, University of Ottawa, Ottawa, Canada
3Faculty of Science, University of Ottawa, Ottawa, Canada
4Schulich School of Medicine & Dentistry, Western University, London, Canada
5Department of Pediatric Neurosurgery, Children’s Hospital of Eastern Ontario, Ottawa, Canada
BACKGROUND AND AIM: Neurosurgical indications and interventions provided in the management of spasticity have evolved significantly over time. Selective Dorsal Rhizotomy (SDR) and Intrathecal baclofen (ITB) pumps have been used to improve mobility, reduce lower extremity spasticity, and increase quality of life in patients with various diagnoses.
METHOD: Studies describing ITB and SDR outcomes in adult and pediatric patients identified from Medline and Embase databases. Publications between January 1990–2021 were included. Combinations of search terms ‘Selective Dorsal Rhizotomy’, ‘Selective Posterior Rhizotomy’, 'functional posterior rhizotomy’, ‘intrathecal baclofen pump’, and ‘spasticity’ were used. Studies in English language and those that included parameters for lower extremity outcome (ie. Spasticity, ambulation) were included. Studies describing follow up 12 months or greater were included. Case reports, reviews without primary data, or inaccessible publications were excluded.
RESULTS: 290 publications between January 1990 to January 2021 were identified. Of these, 62 fit inclusion and exclusion criteria for a total of 1291 adult and 2263 patients. Predominant spasticity etiologies in the adult cohort comprised of multiple sclerosis, cerebral palsy, and trauma. In pediatric patients, cerebral palsy was the predominant etiology of spasticity. While outcomes after SDR and ITB varied, both are effective for long term tone reduction. SDR shows a greater effect on functionality compared to baseline in relatively similar subgroups. The complication rates for either intervention were significant; ITB had a greater incidence of wound and hardware adverse events whereas SDR had a not insignificant incidence of new bladder or sensory deficit.
CONCLUSIONS: ITB and SDR demonstrated efficacy and utility for tone reduction in a variety of conditions. The selection of a specific intervention may have a variety of determining features including the etiology of spasticity, age of patient, as well as balancing benefit and complication profiles of each technique. Appropriate patient selection is essential to providing optimal patient outcomes.
Keywords: Rhizotomy, Intrathecal baclofen pump, Adult, Pediatric, Spasticity, Selective dorsal rhizotomy
FL-053
Global Pediatric Neurosurgery
Incidence of Frontal Encephalocele in Brazil public health system: A 11-year analysis
Aline Rabelo Rodrigues1, Carolina Carmona Pinheiro Machado2, Ana Monize Ribeiro Fonseca3, João Victor Carvalho Da Paz4, Valdecir Boeno Spenazato Júnior5, Gabriel Bagarolo Petronilho7, Danielly Maximino Da Rocha7, Álvaro Alves De Sá Júnior1, Matheus Fernando Manzolli Ballestero6
1Medical School, Federal University of Jataí, Goiás, Brazil
2Medical School, University of Fortaleza, Fortaleza, Brazil
3Medical School, University of Tiradentes, Aracajú, Brazil
4Medical School, University of CEUMA, São Luís, Brazil
5Medical School, University of Vale do Sapucaí, Pouso Alegre, Brazil
6Assistant Professor, Department of Medicine, Federal University of São Carlos, São Carlos, Brazil
7Medical School, University Center of Assis Gurgacz Foundationn, Cascavel, Brazil
BACKGROUND AND AIM: Encephalocele is a common extracranial herniation of the meninges and brain tissue through a defect in the skull and dura. Is mostly common in the occipital region but has a classification based on the affected site: frontal (80% of western cases), occipital, sincipital (associated with craniofacial clefts), basal and posterior fossa. The aim of this study is to analyze the incidence of Encephalocele registered in Brazil in eleven years.
METHOD: We obtained the data in the Brazilian epidemiologic database (DATASUS) using the section for anomaly or congenital defect in live births with a number of diagnoses by the ICD-10 for congenital anomalies: Frontal Encephalocele (Q01.0), from 2010 to 2020, regardless of gender, maternal age and number of previous prenatal consultations.
RESULTS: There were a total of 107 cases of frontal encephalocele observed. There wasn't any increasing or decreasing pattern found during those eleven years gap, although the incidence was constant with a standard deviation of 2,1. There was a highest annual incidence of 12 cases, which occurred in 2010, 2016, 2018 and 2019, while the lowest number of cases occurred only in 2012, with 6 cases. All the data is on a 1 per 100.000 inhabitants scale.
CONCLUSIONS: The incidence of frontal encephalocele in Brazil, despite having years with higher and others with lower cases, a causal factor was not identified, moreover, was considered constant and It can be concluded that it is a prevalent comorbidity which can complicate. There is a need for early diagnosis, for better prevention, as well as better preparation of health professionals regarding rapid management in the emergency.
Keywords: Frontal encephalocele, Pediatric neurosurgery, Neural tube, Cranial vault
FL-054
Global Pediatric Neurosurgery
Pediatric Neurosurgery in an Indonesian Referral Hospital: A 4-Year Epidemiological Study
Yudistira Wardana, Andi Nugraha Sendjaja, Gumar Jaya Saleh
Department of Neurosurgery, Badan Pengusahaan Batam Hospital, Batam, Indonesia
BACKGROUND AND AIM: Indonesia faces various pediatric neurosurgery cases throughout the country. This retrospective study aimed to portray pediatric neurosurgery cases based on the data obtained from one of the Indonesian referral hospitals in the Riau Islands in hopes of providing useful information through epidemiological data.
METHOD: Registries and medical records from Badan Pengusahaan Batam Hospital, Batam, Indonesia, from January 2018 to December 2021 were compiled. Age, sex, and diagnoses were then analyzed and will be further discussed.
RESULTS: We obtained a total of 241 neurosurgery cases in children up to 17 years of age. We observed that most of the cases were male-dominated (61.4%), with the most affected age group in the range of 0–2 years old (34%), and the average was 7 years old. In a 4-year time period, the most cases that we found were trauma (47.7%), followed by hydrocephalus (19.1%), neoplasm (12%), infection (9.1%), dysraphism (5.4%), vascular (4.6%), and spine (2.1%).
CONCLUSIONS: Based on the study, we revealed that there were numerous pediatric neurosurgery cases that predominantly affected male patients, with trauma as the most common case found throughout the 4 years.
Keywords: Neurosurgery, Pediatric, Epidemiology
FL-055
Global Pediatric Neurosurgery
Outcome analysis in various indications for a pediatric decompressive craniectomy- Ambidirectional cohort study
Kashyap D Vyas, Arivazhgan Sathiaprabhu, Rameshkumar Ramchandran
Department of Neurosurgery, Jawaharlal Institute of Post-graduate medical education and research, Pondicherry, India
BACKGROUND AND AIM: In India, children < 15 years constitute 35% of the total population and contribute to 20–30% of all head injuries. To study the mortality and neurological outcome in pediatric patients undergoing decompressive craniectomy for various indications like traumatic and nontraumatic and to find out the Glasgow outcome scale (GOS) after 6 months of intervention.
METHOD: It was an Ambidirectional cohort study involving children aged ≤ 18 years who underwent decompressive craniectomy for traumatic and nontraumatic indications during the study period of the last 10 years retrospectively (before 2019) and prospectively up to December 2020 in our hospital.
RESULTS: We observed that 65 percent survived after decompressive craniectomy regardless of the indication. Out of those who survived, more than 70 percent have a better outcome scale. Our study shows a mortality rate of 35%, and the 48% of the patients showed good outcome (good recovery or moderate disability). The rest of the patients have a severe disability (17%), who are followed up for six months. Among non-traumatic indications coagulopathy group has poor outcome in terms of GOS. The most common indication of decompression in the pediatric group is a traumatic brain injury.
CONCLUSIONS: Traumatic patients fare well in terms of the outcome at six months as compared to the non-traumatic group. Out of the nontraumatic group, infective and cerebrovascular accident (CVA) etiologies are associated with better outcomes at six months and the coagulopathy group had the least favorable outcome. Henceforth, we suggest that decompressive craniectomy can be an effective way to reduce ICP and improve survivors' quality of life.
Keywords: Pediatric decompressive craniectomy, Glasgow outcome scale, Mortality and outcome analysis
FL-056
Global Pediatric Neurosurgery
Pediatric Neurosurgery in the Philippines
Manilyn Ann Hong
Division of Neurosurgery, Department of Neurosciences, Philippine General Hospital, Manila, Philippines
BACKGROUND AND AIM: It is known that there is great disparity to access to neurosurgical care between low-middle income and high income countries, with low-middle income countries having the heavier burden of pediatric neurosurgical diseases, such as hydrocephalus and myelomeningocele. The aim of the study was to describe the neurosurgical workforce in the Philippines managing these conditions.
METHOD: Cross-sectional analysis of the Academy of Filipino Neurosurgeons database as of December 2021 was performed, specifically focusing on the ratio of neurosurgeon per 100,000 population, ratio of male to female neurosurgeons and on the number of formally trained pediatric neurosurgeons practicing in the Philippines.
RESULTS: There are 128 licensed neurosurgeons in the Philippines, serving a population of 112,408,859 peoples, which is the 13th most populous in the world. The ratio is 0.11 neurosurgeon per 100,000 Filipinos. Of these 128 neurosurgeons, only 14 (10.9%) are practicing female neurosurgeons. There are 11 accredited neurosurgery residency training programs in the whole country, and within these training programs, there are 23 (29.9%) female neurosurgery residents. There are only 4 formally trained pediatric neurosurgeons in the country with a ratio of 0.01 pediatric neurosurgeon per 100,000 Filipino children. All 4 accomplished their fellowship training internationally since there is no pediatric neurosurgery fellowship training program in the Philippines.
CONCLUSIONS: In LMICs (e.g., Philippines, and others) where the number of neurosurgeons is scarce, general neurosurgeons manage both pediatric and adult conditions. Patients are managed by disease‐specialty instead of by age. Further bolstering of the neurosurgical workforce is needed in the Philippines, especially for pediatric neurosurgeons.
Keywords: Pediatric neurosurgery, Low-middle income countries
FL-057
Global Pediatric Neurosurgery
Current status of Myelomeningocele in Peru: A scoping review
Milagros Niquen Jimenez1, Jesabelle De J. Dominguez Garcia2, Danny Campos3
1Facultad de Medicina Humana Alberto Hurtado, Universidad Peruana Cayetano Heredia, Lima, Peru
2Neuroscience Research Laboratory, Faculty of Health Sciences, Pontificia Universidad Católica Madre y Maestra, Santiago de los Caballeros, Dominican Republic
3Department of Neurosurgery, Instituto Nacional de Salud del Niño San Borja, Lima, Peru
BACKGROUND AND AIM: Neural tube defects (NTDs) are common congenital neurological defects in peruvian children. Our aim is to describe the current evidence regarding Myelomeningocele to highlight the gaps and interventions.
METHOD: We performed a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review guidelines on peer-reviewed studies across the following databases: sciELO, LILACS, Redalyc, National Register of Research Projects, PubMed, and Google Scholar. A priori search criteria were established, we identify all articles related to Myelomeningocele in Peru published over the last twenty years. In addition, articles written in Spanish and English were included. Lastly, studies without a specific discussion regarding Myelomeningocele, focused on a different country, abstracts and case reports were excluded on the final analysis.
RESULTS: Of 3152 search results, 23 full text- articles were included. The main topic discussed was epidemiology, the second topic was treatment, and public health policy was the third topic. There is not a study that described the national epidemiology of myelomeningocele. Most of the epidemiological studies are based on the main city in Peru. According its results, Spina bifida-Myelomeningocele is the most common NTD. The prevalence of Myelomeningocele is related to low-socioeconomic status, low check-ups in the prenatal care, folate-deficiency, low maternal education, early and advanced maternal age, and overweight. The most frequent pathology associated was anemia. Neurological disorder was the main long-term side effects, followed by bladder dysfunction, and orthopedic disorders. The surgical treatment is delayed and the hydrocephalus is the most common surgical complication. The impact of fortifying wheat flour with acid folic was positive and effective at reducing folate-sensitive NTDs.
CONCLUSIONS: The present study represents the first overview regarding Myelomeningocele in Peru. There is currently a deficit of literature surrounding this topic. A national comprehensive approach should be incorporate to address this important unmet need.
Keywords: Myelomeningocele, Global pediatric neurosurgery, Public health, Peru
FL-058
Global Pediatric Neurosurgery
Low cost production of cranial moulding helmet in a LMIC setting
Jason Labuschagne1, Denis Mutyaba1, Wickus Neethling2
1Nelson Mandela Children's Hospital
2University of the Witwatersrand
BACKGROUND AND AIM: Endoscopic suturectomy accompanied by the postoperative usage of a moulding helmet has shown good results in promoting cranial growth patterns and cosmetic outcomes. The cost of standard orthotic helmet production is frequently prohibitive, ranging from $1000-$3000 per helmet and hence not available to many patients throughout the LMIC setting. We investigated the in-house ability to fabricate an inexpensive and simple cranial moulding helmet. The premise of the technique was the ability to produce a low cost helmet, that could be made with hand-held tools and inexpensive materials. The technique should be replicable in any LMIC with access to the most basic equipment.
METHOD: All post-operative patients requiring orthotic moulding helmets had their helmets produced by a neurosurgical team member, none of whom had prior training in orthotic helmet production. A temporary cranial mould was made with crepe bandage and Plaster of Paris (POP). From this a POP cast was made. A rigid and adjustable moulding helmet was constructed over this cast from basic materials, including commercially available polypropylene plastic, high density foam, contact adhesive and a simple Velcro strap. Equipment required included a modified home oven, pliers, scissors and a DIY electric jigsaw.
RESULTS: A cranial moulding helmet could be successfully constructed using inexpensive materials. To date 5 such helmets have been produced. The patients have all been compliant with the helmet therapy. Parental acceptance of the helmet has been high and no parents have reported any perceived pain or discomfort from the helmet. No local skin reactions or irritation has been reported and no child has needed to discontinue using the orthotic.
CONCLUSIONS: Orthotic cranial devices produced in a LMIC setting can be simple and cost effective, and by using this method, optimal adjuvant therapy can be provided for patients following minimally invase craniosynostosis repair.
Keywords: Helmet orthotic therapy, LMIC, Craniostenosis, Global neurosurgery
FL-059
Neuroendoscopy
Endoscopic Third Ventriculostomy with Choroid Plexus Coagulation in 104 children under 1 year age
Carolina Belen Maldonado Alejos1, Mariela Cecilia Salerno1, Angel Nicolas Tello Brogiolo1, Lucas Manuel Hinojosa1, Juan Pablo Emmerich1, Marcelo Osvaldo D´agustini1, Ramiro J. Del Rio2
1Sor Maria Ludovica Children´s Hospital, La Plata, Buenos Aires, Argentina
2National Pediatric Hospital Juan. P. Garrahan, Buenos Aires, Argentina
BACKGROUND AND AIM: The aim of this study is to demonstrate the efficacy of endoscopic third ventriculostomy (ETV) combined with choroid plexus cauterization (CPC) as the main treatment option in patients with hydrocephalus younger than 12 months and to describe the surgical technique.
METHOD: We followed patients with hydrocephalus less than 12 months of age whose hydrocephalus treatment from June 2013 to May 2022 was ETV with CPC. Patients were classified based on their etiology as: Hydrocephalus post infective (HPI), Hydrocephalus not after infection (HNPI), Posthemorrhagic hydrocephalus (PHH), and Myelomeningocele-related hydrocephalus (MMC-rH). The ETV Success Score (ETVSS) was used as a simplified means to predict the 6-month success rate of ETV in children with hydrocephalus based on age, etiology, and presence of a previous shunt.
RESULTS: We collected 104 patients with a mean age of 3.67 months and 39.42% were female. According to the etiology, 34 MMC-rH (32.69%), 33 PHH (31.73%), 24 HNPI (23.08%), and 13 HPI (12.5%) were found. The success rate was 64.42% for all procedures performed, regardless of etiology, with HNPI (70.83%), PHH (66.67%), HPI (61.65%), and MMC-rH. (58.82%). Success was more likely in infants less than 1 month of age. In 8 patients in whom ETV had failed, we performed RE- ETV and achieved resolution of hydrocefalus in 75% of them. Only in 29.81%, a shunt was required after ETV.
CONCLUSIONS: ETV-CPC Should be considered as a primary option in the treatment of hydrocephalus in patients less than one year of age, achieving shunt-free life in the majority of cases.
Keywords: Children, Endoscopic third ventriculostomy, Hydrocephalus, Surgical technique, Choroid plexus cauterization
FL-060
Other
Defining a taxonomical map for craniosynostoses: A unified functional-approach based nomenclature for interdisciplinary workflow in craniosynostoses management
Suhas Udayakumaran1, Dilip Panikar2, Pramod Subhash3
1Division of Paediatric Neurosurgery, Department of Neurosurgery, Amrita Institute of Medical Sciences and Research centre, Kochi, India
2Department of Neurosurgery, Aster Medcity, Kochi, India
3Division of Craniomaxillofacial surgery, Amrita Institute of Medical Sciences and Research Centre, Kochi, India
BACKGROUND AND AIM: Craniosynostoses is a complex clinical and management challenge. This is further complicated by varying phenotypes, genotypes and specific challenges. Most complex craniosynostoses are approached and managed the same way despite the clinical variability, and patients often experience similar problems.
The descriptive diagnosis does not shed light on the issues or priorities, and most specialists dealing with these conditions remain in their field of tunnelled vision.
AIM: To create a goal-based universal and interdisciplinary language among various specialists involved in the management of craniosynostoses.
METHOD: Articles were searched in literature until January 1st, 2022, using search engines Pubmed, Embase and google scholar, using MeSH terms syndromic craniosynostoses, multisutural craniosynostoses, complex craniosynostoses, categorisation, classification, workflow, algorithm.
RESULTS: In this article, the authors propose a concept of categorisation based on initial patient presentation. The treatment status and the aetiology, if available, are incorporated along with the presentation.
Categorisation follows the process described in Fig. 1.
It has three components (Fig. 2):
Functional status (ICP. Airway, Aesthetic).
Aetiological status.
Treatment status.
Depicting the nomenclature (Fig. 3).
The craniofacial surgeon evaluates any patient at presentation clinically and assigns the categories based on the evaluation (Table 1).
I. The letter “C” would represent the category.
The subsequent letter would describe the presentation issue of raised ICP represented “I” and “A” for airway.
II. Incorporating the aetiological and genetic information if identified.
We propose to include the aetiological information in the categorisation as follows.
CATEGORY (AETIOLOGICAL DIAGNOSIS)
Or, if the aetiological diagnosis is not available, it will be denoted as.
CATEGORY(NOI) refers to not otherwise identified.
III. Incorporating treatment status (Fig. 3).
A superscript “T” will be added to the initial entries if treated.
CONCLUSIONS: The utility of our proposed categorisation is to create a goal-based universal language among various specialists involved.
Keywords: Algorithm, Syndromic craniosynostoses, Categorization, Nomenclature
FL-061
Neuroendoscopy
Endoscopic Resection of Nasional, Frontal and Frontozygomatic Subgaleal Dermoid Cysts In Infants
David F Jimenez Md, Facs, Faans
El Paso Children's Hospital, El Paso. Texas, USA
BACKGROUND AND AIM: Inclusion cysts are benign lesions that grow overtime and when present on the face and forehead can lead to a significant cosmetic deformity. Early resection of the lesions is indicated.
METHOD: A total of 26 children presented with growing and enlarging masses located and one of the following locations: A) Nasion:3 B) Mid supra-orbital: 6 C) Lateral supra-orbital: 14 D) Mid-frontal: 3. There were 11 males and 15 females. A 1.5-cm incision was made behind the hairline. Subgaleal dissection to the lesion was done with lighted retractor, zero- and 30-degree rigid endoscopes. Bloodless dissection was done with an extended needle tip bovie. Complete resection was done by cauterizing the pericranium around the lesion and removing it with pituitary rongeurs and sharp dissectors. The galea was closed with absorbable sutures.
RESULTS: A total of 26 children presented with growing and enlarging masses located and one of the following locations: A) Nasion:3 B) Mid supra-orbital: 6 C) Lateral supra-orbital: 14 D) Mid-frontal: 3. There were 11 males and 15 females. A 1.5-cm incision was made behind the hairline. Subgaleal dissection to the lesion was done with lighted retractor, zero- and 30-degree rigid endoscopes. Bloodless dissection was done with an extended needle tip bovie. Complete resection was done by cauterizing the pericranium around the lesion and removing it with pituitary rongeurs and sharp dissectors. The galea was closed with absorbable sutures.
CONCLUSIONS: Presented is a novel endoscopic approach to growing lesions located prominently of the patient’s face and forehead. All lesions were successfully removed without the need for visible incisions on the patient’s face. Technique and videos will be presented.
Keywords: Endoscopy, Dermoid cysts, Inclusion cysts
FL-062
Global Pediatric Neurosurgery
Cranial Expansion with Bifrontal Advancement and Spiral Parieto-temporal Craniectomies sparing partial superior-sagittal-sinus exposure in Syndromatic Craniosynostosis
Liana Beni Adani1, Eran Regev2
1Division of Pediatrics, Pediatric Neurology and Neurosurgery, Share Zedek Medical Center, Jerusalem, Israel
2Maxillofacial surgery, Share Zedek Medical Center, Jerusalem, Israel
BACKGROUND AND AIM: Management strategies for Syndromic Craniosynostosis patients require multidisciplinary subspecialty teams to provide optimal care for complex reconstructive approaches. Different approaches of Cranial vault remodeling were offered, using one or more cranial-remodeling surgeries in a patient, with staged separated anterior–posterior surgeries or one-stage fronto-orbital advancement, using different techniques of reconstruction, all aiming to relieve restriction of cranial development and treat intracranial hypertension (ICH). While maxillofacial intervention is usually advocated at older age, craniotomies are performed during the first year or when ICH is diagnosed. In the presence of elevated intracranial pressure, risk of Dural tear, significant bleed due to venous congestion, superior-sagittal-sinus damage, air emboli and hypothermia are only some of the possible complications of surgery, which is far more risky than reconstructive surgery for non-syndromic craniosynostosis without ICH. Extreme cranial expansion may lead to problematic scalp recovery, and ever-lasting bone defects, while minimal approach will probably demand future craniotomies for recurrent ICH. Expectations regarding achieving normal morphology should be carefully discussed with parents as well as the possible need of multistage interventions.
METHOD: Our protocol for "cranial expansion" included Bifrontal advancement together with parieto-temporal spiral-craniotomy following thin-strip para-sagittal bilateral craniotomies. The order of stages enabled gradual opening of the "strangulated" intracranial content, with relatively minimal bleed, starting with tight Dura and ending with pulsatile relaxed Dura, leaving most of the superior sagittal sinus covered.
RESULTS: This method was applied in a cohort of patients with syndromic craniosynostosis, achieving quick improvement of fundoscopy findings with resolving papilledema, stabilization of vision and good cognitive outcome. Follow up of up to 20 years in babies operated before the age of 14 months showed that compared to 2-stage posterior-then-anterior remodeling was helpful in avoiding recurrent intra-cranial hypertension.
CONCLUSIONS: Cranial Expansion with Bifrontal Advancement and Spiral Parieto-temporal Craniectomies sparing partial sss exposure is safe and effective in Syndromatic-Craniosynostosis.
Keywords: Spiral craniectomy, Intra cranial hypertension, Syndromatic craniosynostosis, Superior sagittal sinus
FL-063
Other
The natural history of untreated metopic synostosis: a morphological study
Ahmed Elawadly1, Luke Smith1, Alessandro Borghi2, Adikarige Haritha Dulanka Silva1, N U Owase Jeelani1, David J Dunaway1, Juling Ong1, Greg James1
1Craniofacial Unit, Great Ormond Street Hospital, London, UK
2Great Ormond Street Institute of Child Health, University College London, London, UK
BACKGROUND AND AIM: The natural history of unoperated metopic synostosis is poorly understood, however crucial to answer the question of whether to treat such deformity. In this study, we used 3D surface scans to objectively evaluate morphological changes in unoperated trigonocephalic patients in different age groups.
METHOD: We screened our database for 3D scans of children with unoperated (pre-surgery or from children whose parents refused surgery) metopic synostosis between 2011–2021. Multisutural cases and benign metopic ridge were excluded. 3D surface scans (either 3D stereophotogrammetry or CT with skin reconstruction) for untreated patients were then enrolled for morphological analysis. 9 previously published parameters were used: frontal angle (FA30), antero-posterior volume ratio (APVR), antero-posterior area ratio (APAR), antero-posterior width ratio 1 and 2 (APWR1 and APWR2), and 4 antero-posterior diagonal ratios (rAPDR30, lAPDR30, rAPDR60, lAPDR60). We added a 10th parameter, the cranial vault asymmetry index (CVAI) for plagiocephaly.
RESULTS: 97 scans were identified for analysis from a total of 316 single metopic patients. Of the whole cohort, the male to female ratio was 2.7:1. Age at time of scan ranged from 9 days to 11 years stratified into 4 age groups: group 1: < 6 months, group 2: 6–12 months, group 3: 1–3 years, group 4: > 3 years. Posterior plagiocephaly was present in 35% of the cases, half of them were mild (CVAI category 2). Significant improvements were detected in 5 parameters (APVR, APAR, APWR1, rAPDR30, lAPDR30) over time (i.e. older children were less severe). No significant differences were found in CVAI, FA30, APWR2, rAPDR60, and lAPDR60 between age groups.
CONCLUSIONS: Forehead shape (surface area and volume), as well as narrowing and anterolateral contour at the medial supraorbital points, improved significantly over time without surgery. However, plagiocephaly, forehead angulation, narrowing, and anterolateral contour at lateral supraorbital points did not improve.
Keywords: Trigonocephaly, Metopic, Synostosis, Untreated, Morphological, Analysis
FL-064
Global Pediatric Neurosurgery
Long Term Cosmetic, Ophthalmological, Cognitive, and Parental Satisfactory Outcome after Open Sagittal Craniosynostosis Repair
Serife Maide Pinar1, Tim Jonas Hallenberger2, Maria Licci3, Benito K. Benitez4, Anja Palmowski – Wolfe5, Françoise Roulez5, Raphael Guzman2, Jehuda Soleman2
1Faculty of Medicine, University of Basel, Basel, Switzerland
2Department of Neurosurgery, University Hospital of Basel, Basel, Switzerland
3Department of Pediatric Neurosurgery, University Children's Hospital of Basel, Basel, Switzerland
4Department of Oral and Craniomaxillofacial Surgery, University Hospital of Basel, Basel, Switzerland
5Department of Ophthalmology, University Hospital of Basel, Basel, Switzerland
BACKGROUND AND AIM: The aim of this study was to investigate the long-term cosmetic, ophthalmological, cognitive, and parental satisfactory outcome of children after open surgical correction for non-syndromic sagittal craniosynostosis.
METHOD: Patients under the age of twelve months, who underwent surgical reconstruction with a follow up period of at least 3 years after surgery at the Department of Pediatric Neurosurgery, University Hospital of Basel were included in this single center study. The primary outcome was parent-reported satisfaction of the surgery (PRSS) assessed through a parental questionnaire. Secondary outcomes were neurocognitive development and health-related quality of life (HRQoL), measured using the Vineland Adaptive Behavior Score (VABS) and the KINDL® questionnaire, ophthalmological outcome, and cosmetic outcome based on 3D imaging of the patients.
RESULTS: We included 26 children with a mean age of 7.67 months at surgery (15% girls). Based on PRSS 25% of the parents were satisfied and 75% very satisfied with the surgical outcome. VABS showed a mean of 104.52, corresponding to an overall age-adequate adaptive level. Children aged 4–6 showed a mean score of 79.76/100 for HRQoL, while children aged 7–13 showed a mean score of 76.04/100, which is within the norm. Cosmetic outcome based on 3D photos, and ophthalmological outcome will be presented as well.
CONCLUSIONS: Our preliminary results demonstrate, high parental satisfaction with the surgical repair of open sagittal synostosis. The patients do not seem to have more intellectual or developmental disabilities than the average of normal population while the HRQoL is within the norm.
Keywords: Sagittal craniosynostosis
FL-065
Other
Surgical correction outcome and satisfaction survey of craniosynostosis: A review of 241 patients in a single center from Romania
Mihaela Andrei1, Sory Ibrahim Fofana2, Ancuta Negru2, Sorin Tarnoveanu2
1University Hospital, Bucharest
2Marie Curie Children's Hospital Bucharest
BACKGROUND AND AIM: Provide postoperative outcome and parents satisfaction data after open surgical techniques performed at the largest national pediatric neurosurgery reference center,by a neurosurgical team treating 241 patients with syndromic and non-syndromic craniosynostosis.
METHOD: This retrospective study comprises 241 patients with diagnosis of premature closure of one or more cranial sutures confined to Marie Curie Children’s Hospital from Bucharest, Romania, between 2015–2021. During this interval 2112 patients underwent surgery from wich 241 cases of craniosynostosis. The importance of parents satisfaction during follow-up period is also discussed; a questionnaire was developed to evaluate the grade of satisfaction after surgery.
RESULTS: There were 72 females and 169 males; age at operation ranged from 4 to 23 months. There were 232 non-syndromic and only 9 syndromic craniosynostosis; of the varieties encoutered most common was fusion of sagittal suture only (53,1%), metopic (17,8%), lambdoid (17%),involving 2 sutures (8,3%) and syndromic craniosynostosis (3,8). Two patients associated hydrocephalus and needed ventriculoperitoneal device; ten patients associated decreased neurocognitive function at the first medical examination in our institution. Complications included 2 wound infections, 4 patients requiring reoperation for residual deformity from wich 2 patients underwent second surgery in our institution. The two other patients had no reoperation because of parents refusal or consent. There was no major postoperative long-term morbidity and no mortality during or after surgery.
CONCLUSIONS: Our review of 241 patients with craniosynostosis demonstrated good long-term results with an overal low complication rate and high degree of satisfaction in postoperative follow-up.
Keywords: Craniosynostosis, Syndromic, Non-syndromic, Satisfaction questionnaire
FL-066
Other
Coronal and lambdoid sutures evolution following total vault remodeling for scaphocephaly
Pierre Aurelien Beuriat, Alexandru Szathmari, Julie Chauvel Picard, Arnaud Gleizal, Carmine Mottolese, Federico Di Rocco
French Referral Center for Craniosynostosis, Hôpital Femme Mère Enfant, Lyon, France
BACKGROUND AND AIM: There are only a few reports on the evolution of sutures after surgical correction of craniosynostosis. The objective of this study was to.
understand the evolution of the cranial bones in the area of coronal and lambdoid sutures that were removed for complete vault remodeling in patients with sagittal craniosynostosis. In particular, the investigation aimed to confirm the possibility of neosuture formation.
METHOD: CT images of the skulls of children who underwent operations for scaphocephaly at Hôpital Femme Mère Enfant, Lyon University Hospital,
Lyon, France, from 2004 to 2014 were retrospectively reviewed. Inclusion criteria were diagnosis of isolated sagittal synostosis, age between 4 and 18 months at surgery, and availability of reliable postoperative CT images obtained at a minimum of 1 year after surgical correction.
RESULTS: Despite removal of both the coronal and lambdoid sutures, neosutures were detected on the 3D reconstructions. All combinations of neosuture formation were seen: visible lambdoid and coronal neosutures (n = 20); visible lambdoid neosutures with frontoparietal bony fusion (n = 12); frontoparietal and parietooccipital bony fusion (n = 3); and visible coronal neosutures with parietooccipital bony fusion (n = 2).
CONCLUSIONS: This is the first study to report the postoperative skull response after removal of normal patent sutures following total vault remodeling in.
patients with isolated sagittal synostosis. The reappearance of a neosuture is rather common, but its incidence depends on the type of suture. The outcome of the suture differs with the incidence of neosuture formation between these transverse sutures. This might imply genetic and functional differences among cranial sutures, which still have to be elucidated.
Keywords: Craniosynostosis, Neosuture, Scaphocephaly, Total vault remodelling
FL-067
Other
Total cranial vault remodelling including pterional decompression: increased frontal bossing correction in non-syndromic scaphocephaly patients [single centre restrospective and prospective case series]
Edward Jozef Baert
Department of neurosurgery, Ghent University Hospital (UZ Gent), Gent, Belgium
BACKGROUND AND AIM: Background and importance: surgical techniques to correct scaphocephaly often rely on foreign material and/or postoperative helmet therapy and fall short in correcting frontal bossing. Foreign material and helmet therapy are associated with side effects. Frontal bossing is perceived as a prominent, disfiguring feature of scaphocephaly, especially by the patients’ parents. We present the results of a total cranial vault remodelling (TCVR) which obviates foreign material and postoperative helmet therapy and corrects frontal bossing with a unique pterioneal decompression.
METHOD: METHODOLOGY: all patients, operated at a single institution between 2012 and 2020, were included in a retrospective review. Operation time, transfusion need, hospital stay, complications, cephalic index, and bossing angle were analysed. A prospective questionnaire was sent to the patients’ parents to evaluate how they assess their child’s skull.
RESULTS: 65 patients were included. Mean cephalic index was 69,2% preoperatively, 74,6% postoperatively, and 75,5% one-year postoperatively. Bossing angle was 114,5° preoperatively, 111,6° postoperatively, and 108,9° one-year postoperatively. The parents of 14 patients answered the questionnaire. All parents assessed their child’s skull as normal or almost normal one-year postoperatively. The mean operating time was 2 h and 4 min, median blood transfusion volume 100 ml. There were no complications.
CONCLUSIONS: The presented TCVR is as effective in correcting cephalic index and, due to a unique pterional decompression, more effective in correcting frontal bossing compared to (minimally invasive) alternatives. It is at least as safe and total treatment burden is lower as no helmet therapy nor foreign material is needed.
Keywords: Scaphocephaly, Frontal bossing, Cephalic index, Operative cranioplasty
FL-068
Other
Free Flaps Cranial Vault Remodelling for Sagittal Synostosis
Laura Grazia Valentini1, Veronica Saletti2, Alessandra Erbetta3, Mirella Seveso1, Enrico Gambatesa1, Ignazio Gaspare Vetrano1
1Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan
2Department of Pediatric Neurologist, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan
3Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan
BACKGROUND AND AIM: Best technique for Scaphocephaly (mininvasive vs open) is still debated, due to difficulties comparing aesthetic and functional RESULTS: cosmesis is hard to objectivate; cognitive and behavioural deficits are mild and need long term observation and complex testing to be quantified. Due to this uncertainty even surgical indications are discussed.
METHOD: We quantified results of our technique. 170 children were operated for sagittal synostosis as documented by 3DCT, with a male prevalence (133/37). At surgery 142 children (A) were < 1 (mean 6,8 months), 28 > 1 year (B). Multiple craniectomies were performed with high speed drill, by zig-zag bicoronal approach; bone flaps were programmed on preoperative-CT; two broad, symmetric fronto-parieto-temporal free flaps were created, than each was divided, leaving a residual bone at vertex upon the sagittal sinus 2–4 cm wide, to prevent venous damage and late diastasis. To allow vertical growth, this bridge was interrupted by 2–4 transversal cuts. Final shape was obtained by molding effect of brain growth, without rigid fixation. Continuous asorbable suturing (“Denim”) to improve the scar.
RESULTS: There was no mortality, neither infections; 2 children were re-operated to improve cosmesis, 1 for progressive bone defect and for 1 CSF collection. Aesthetics was judged by doctors and parents in 150 children by serial photos, Eco 3D and scar quality. Neuropsycological results were evaluated on testing and school performance, resulted in no delay in A children. Improvement of shape and volume was measured by cranial index graphs and on volumetric CT in 100 cases. At late MRI none of 65 evaluable A children presented CM while it was documented in 6/25 B children.
CONCLUSIONS: The present technique had low morbidity rate and good efficacy, correcting cephalic and vertical index, increasing intracranial volumes, so preventing CM1, preserving cognition and improving aesthetics. Another advantage was feasibility at any age, also in older children.
Keywords: Sagittal synostosis, Cranial volume, Surgery, Cranioplasty, Cosmesis
FL-069
Other
Long term follow up of the Leeds Fronto-Orbital Advancement and Reconstruction technique (reverse frontal bone graft without the use of the orbital bar)
Rebecca Chave Cox, Ariyo Onafowokan, James Robins, Paula Carter, Ojas Krishnan, Mark Liddington, Paul Chumas
Leeds Teaching Hospitals Trust, Leeds, UK
BACKGROUND AND AIM: We present our technique and outcomes using a reverse frontal bone graft without the use of the orbital bar to perform FOAR surgery. Having previously used the Marchac template technique and reversed frontal bone method utilizing the reshaped orbital bar we were often dissatisfied with the final shape of the orbital bar. We have evolved our current technique of drilling the orbital bar for use as bone dust/on-lay grafts and used this as our standardized FOAR technique since mid-2014.
METHOD: Between 2014 to 2021 we have performed 45 FOARs using this technique (23 metopic; 12 coronal; 7 sagittal & 3 multi-suture synostosis). Follow ranges from 1 to 7 years.
In our technique the frontal bone flap is reversed and new orbital rims are fashioned. This is advanced in cases of coronal synostosis but not metopic. We remove the orbital bar & use it only as graft material for bone dust, applying this at the temporal area or to any exposed dura. This aids bone fusion and prevents future defects.
RESULTS: Our 45 patients undergoing FOAR with this technique had good cosmetic outcomes, all constructs are stable and no revisions for cosmetic indications have been required. One patient had a wound infection requiring multiple wash outs and remains under review. One patient sadly died 3 years following the FOAR of unrelated causes. The vast majority of scars are hidden well, two patients have widened scars for which future revision has been offered should the families wish.
CONCLUSIONS: Our results show it is safe to remove the orbital bar all together and use it’s bone dust to fill gaps with good long term cosmetic results. This method has allowed us to standardise our FOAR method irrespective of the suture that is synostosed. Allowing flattening of the forehead and enabling advancement whilst preventing parietal thinning.
Keywords: Craniosynostosis, Metopic, Coronal, FOAR, Orbital bar
FL-070
Other
Bone changes of the cranial vault associated with intracranial hypertension in patients with craniosynostosis
Hector Velazquez Santana1, Francisco J. Guerrero Jazo1, Adrian Santana Ramirez1, Martha Lilia Cisneros Avalos1, Jaime Mora Rosales1, Rodrigo Fraga Gonzalez1, Nancy Elizabeth Gutierrez Hernandez1, Yazmin Gisselle Figueroa1, Miguel Angel Andrade Ramos1, David Bañuelos Gallo2, Fernando Chico Ponce De Leon3, Luz Monserrat Almaguer Ascencio4
1Department of Neuroscience of Civil Hospital of Guadalajara Dr Juan I. Menchaca, Universidad de Guadalajara, Guadalajara Jalisco, Mexico
2Department of Radiology of Civil Hospital of Guadalajara Dr Juan I. Menchaca, Universidad de Guadalajara, Guadalajara Jalisco, Mexico
3Department of Pediatric Neurosurgery of Children’s Hospital Federico Gomez, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
4Department of Neuroscience of Civil Hospital of Guadalajara Dr Juan I. Menchaca, Universidad de Guadalajara, Guadalajara Jalisco, Mexico; Department of Pediatric Neurosurgery of Children’s Hospital Federico Gomez, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
BACKGROUND AND AIM: The identification of children with craniosynostosis at risk of increased intracranial pressure is a diagnostic priority. This pressure has been related to digital impressions, cranial lacunae and the appearance of a beaten copper skull by some authors, with conflicting evidence about its real association.
OBJECTIVE: To associate bone changes of the cranial vault with intracranial hypertension in patients with craniosynostosis.
METHOD: An analytical cross-sectional study is presented in a sample of patients with craniosynostosis compared to patients without craniosynostosis, who were clinically evaluated for intracranial hypertension data and underwent imaging studies to search for this association.
RESULTS: 55 patients were included. The mean age was 12.6 months (SD 9.2). Males prevailed in the sample (54.4%).
For analysis, the sample was divided into two groups; patients with craniosynostosis ( 50.9%) and patients without craniosynostosis (49.1%).Of the patients with craniosynostosis, 50% had digital impressions, 67.9% had cranial lacunae, and 17.9% had a copper skull.
In contrast, only one patient without craniosynostosis presented digitiform impressions (3.7%), 22% had cranial lacunae and none had a copper skull.
Of the patients with craniosynostosis, 37.5% presented intracranial hypertension (n = 10). A higher digital impression score (t(26) = -5.272, p < 0.005) was observed in the group of children with hypertension and craniosynostosis (x = 5.1) when compared to the group of children without hypertension and craniosynostosis (x = 0.6). Likewise, a higher copper skull score (t (26) = -2.748, p = 0.011) was observed in the group of children with hypertension and craniosynostosis (x = 1.7) when compared to the group of children without hypertension and craniosynostosis (x = 0.11).
CONCLUSIONS: A statistically significant, moderate and directly proportional association was evidenced between patients with craniosynostosis and intracranial hypertension with presenting digitiform impressions, compared to the control group.
Cranial vault changes lacks clinical relevance in patients without craniosynostosis. On the contrary, the presence of them in patients with craniosynostosis should be monitored.
Keywords: Craniosynostosis, Intracranial hypertension, Beaten copper skull, Cranial lacunae, Digital impressions
FL-071
Other
Spring-assisted cranial vault expansion in the setting of multisutural craniosynostosis
Tatiana Protzenko1, Antônio Bellas1, Claudia Ribeiro2, Fernanda Rolemberg3, Sayonara Gonzalez3, Dafne Horovitz4
1Department of Pediatric Surgery, Division of Pediatric Neurosurgery, Fernandes Figueira National Institute of Health for Women,Children and Adolescents, Oswaldo Cruz Foundation (IFF-Fiocruz), Rio de Janeiro, Brazil
2Radiological Department, Fernandes Figueira National Institute of Health for Women, Children and Adolescents, Oswaldo Cruz Foundation (IFF-Fiocruz), Rio de Janeiro, Brazil
3Laboratory of Genomic Medicine, Department of Medical Genetics, Fernandes Figueira National Institute of Health for Women, Children and Adolescents, Oswaldo Cruz Foundation (IFF-Fiocruz), Rio de Janeiro, Brazil
4Department of Medical Genetics, Fernandes Figueira National Institute of Health for Women, Children and Adolescents, Oswaldo Cruz Foundation (IFFFiocruz), Rio de Janeiro, Brazil
BACKGROUND AND AIM: Children with multi-sutural craniosynostosis are predisposed to small posterior cranial fossa due to the prematurely fusion of the cranial sutures. This can lead to intracranial hypertension, Chiari type 1malformation and hydrocephalus. The control of ICP was traditionally undertaken with FOA. However, this technique proved to be insufficient. Thus, posterior vault expansion plays a fundamental role in the initial approach of these patients. The aim of this study is to demonstrate the improvement of the compressive phenomenon of the posterior fossa in a cohort of 10 patients with complex craniosynostosis submitted to spring-assisted posterior vault expansion.
METHOD: Patients were selected from a cohort of complex craniosynostosis from march2018-dec2021. From a total of 100 patients with multisutural craniosynostosis, 10 patients underwent springs-assisted posterior expansion as a first approach. All patients underwent molecular analysis for craniosynostosis. All patients underwent a preoperative CTvenogram and a postoperative CTscan on spring removal. Posterior fossa volume, resolution of type 1Chiari malformation, need for reoperation and ossification extension were evaluated.
RESULTS: We identified patients with: Crouzon FGFR2 (2), Crouzon FGFR3 (2), Jackson-Weiss (1), Apert (1), Pfeiffer (1), non-syndromic (2 oxycephaly/1 brachycephaly).Age at spring installation ranged from 5–24 months (mean 11.8 m). As complication, 3 patients had spring exposure, without CSF leek or infection. Only 1 patient didn't receive blood transfusion. An important increase in the volume of the posterior fossa was seen. 5 patients had significant venous anomalies that would prevent open decompression of the foramen magnum. Of the 3 patients who had preoperative tracheostomy, 2 showed significant respiratory improvement and were decannulated. Control CT scan showed satisfactory ossification, without recurrences.
CONCLUSIONS: Spring-assisted expansion is a safe technique for cranial vault expansion in patients with multi-sutural craniosynsostosis. The increase in the posterior fossa volume can avoid the need for foramen magnum decompression, especially in patients with anomalous venous drainage patterns.
Keywords: Spring-assisted, Multi-sutural craniosynostosis, Syndromic craniosynostosis, Posterior vault expansion
FL-072
Other
Venous anomalies in hypoplastic posterior fossa: unsolved questions
Tatiana Protzenko1, Antônio Bellas1, Fernanda Rolemberg3, Claudia Ribeiro2, Sayonara Gonzalez3, Dafne Horovitz4
1Department of Pediatric Surgery, Division of Pediatric Neurosurgery, Fernandes Figueira National Institute of Health for Women,Children and Adolescents, Oswaldo Cruz Foundation (IFF-Fiocruz), Rio de Janeiro, Brazil
2Radiological Department, Fernandes Figueira National Institute of Health for Women, Children and Adolescents, Oswaldo Cruz Foundation (IFF-Fiocruz), Rio de Janeiro, Brazil
3Laboratory of Genomic Medicine, Department of Medical Genetics, Fernandes Figueira National Institute of Health for Women, Children and Adolescents, Oswaldo Cruz Foundation (IFF-Fiocruz), Rio de Janeiro, Brazil
4Department of Medical Genetics, Fernandes Figueira National Institute of Health for Women, Children and Adolescents, Oswaldo Cruz Foundation (IFFFiocruz), Rio de Janeiro, Brazil
BACKGROUND AND AIM: Venous hypertension is an important factor related to intracranial hypertension in complex craniosynostosis. It is associated with jugular foramen stenosis or atresia with the development of collateral emissary veins, which generate potential risks for surgical intervention. Therefore, the study of venous anatomy is essential for surgical planning.The aim of our study is to analyze the preoperative venous outflow pattern of patients with multi-suture craniosynostosis.
METHOD: A prospective study from March/2018-March/2022 of 70 children with complex/syndromic craniosynostosis was performed. Patients underwent molecular analysis and CT venogram as preoperative planning. Venous outflow were studied: major venous sinus, jugular foramina, collateral emissaries in 9 points: frontal, parietal, mastoid and condylar emissaries (both sides) and transosseous occipital. Collateral emissaries were classified as 0-absent; 1-present; 2-engorged; 3-anomalous, in each point, so that a single child could score 0 when they had no collateral and 27 points as the maximum score.
RESULTS: 70 patients (43 syndromic and 27non-syndromic) were studied. Syndromes identified were:Crouzon-FGFR2(11),Crouzon-FGFR3(2),Pfeiffer(6), Apert(20),Muenke(3),Jackson Weiss(1), Saerthre-Chotzen(1).Patients with Crouzon and Pfeiffer syndrome had the highest scores, reaching a maximum value of 22 and 21, respectively. Among them, only one patient with crouzon had bilateral jugular foramen atresia. Likewise, we found a patient with Apert syndrome and bilateral jugular atresia, but with score of only 4 points. Some patients with Crouzon and Pfeiffer syndromes and collateral circulation scores above 15 shared the same mutation position in the FGFR2-gene.
CONCLUSIONS: Crouzon and Pfeiffer syndromes FGFR2-related are associated with the presence of exuberant collateral venous circulation, not necessarily associated with bilateral jugular atresia.Patients with Apert syndrome do not have such exuberant collateral circulation. The role of the genetic mutation position in the FGFR2 gene still needs to be further studied.Muenke and Saerthre Chotzen syndromes resemble nonsyndromic multisutural craniosynostosis.Therefore,genetic screening is important in the preoperative period to define the best approach of these patients.
Keywords: Venous outflow, Syndromic craniosynostosis, Jugular atresia, Crouzon syndrome, Pfeiffer syndrome
FL-073
Other
The Influence of Cerebellar Tonsil Reduction in the Surgical Treatment of Chiari I Malformations in Children
Dale M Swift1, Bruno P Braga2, Eric Montgomery1, Bradley Weprin2, Angela Price2, Brett Whittemore2, Mark Pernik1, Rafael De Oliveira Sillero2
1Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, United States
2Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, United States; Children’s Medical Center, Dallas, United States
BACKGROUND AND AIM: The ideal surgical approach for type I Chiari malformations remains one of the great debates in the field of pediatric neurosurgery. The role of tonsil manipulation including cerebellar tonsil resection is controversial. We aim to compare surgical outcomes in Chiari I patients treated with and without cerebellar tonsil manipulation.
METHOD: We retrospectively reviewed the records of 456 children consecutively treated surgically for Chiari I malformations at Children's Medical Center Dallas. Preoperative variables included MRI measurements of the degree of cerebellar tonsil herniation as well as other craniovertebral junction measurements. Procedures were classified into four groups: bone decompression with duraplasty (PFDD), PFDD with arachnoid dissection (PFDD + AD), PFDD with coagulation of at least one cerebellar tonsil (PFDD + TC) and PFDD with subpial resection of at least one cerebellar tonsil (PFDD + TR). Efficacy was defined as improvement in patient-reported symptoms, greater than 50% reduction in syrinx by length or AP width, and the rates of reoperation. Safety was measured as the rate of postoperative complications.
RESULTS: The mean age was 8.4 years (range: 3 months to 18 years). Fifty-one percent had syringomyelia. Mean follow-up was 29.4 months. Patients who underwent surgical procedures resulting in cerebellar tonsil reduction (PFDD + TC or PFDD + TR) had improved outcomes postoperatively when compared to those in whom the tonsils were spared (PFDD or PFDD + AD). Statistically significant improvement was noted in headache resolution (85.5% vrs 74.2%, p = 0.008), syringomyelia reduction (80.4% vrs 58.8%, p = 0.001) and rates of reoperation (3.1% vrs 8.3%, p = 0.023). There was no difference in complications between the groups. The use of tonsil reduction procedures was associated with greater degrees of cerebellar tonsil herniation.
CONCLUSIONS: In this single center retrospective series, cerebellar tonsil reduction, by either coagulation or sub-pial resection, resulted in superior reduction of headaches and syringomyelia in Chiari I patients with less need for reoperation and without increased complications.
Keywords: Chiari I malformation, Syringomyelia, Cerebellar tonsil resection
FL-074
Other
CSF leak after intradural cranial surgery in the pediatric population
Emma M.H. Slot1, Tristan P.C. van Doormaal2, Kirsten van Baarsen3, Menno R. Germans4, Nick Krayenbühl4, Luca Regli4, Eelco W. Hoving5
1Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Translational Neuroscience, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands
2Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Translational Neuroscience, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands; Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland
3Department of Neuro-oncology, Princess Maxima Center for Paediatric Oncology, Utrecht, the Netherlands
4Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland
5Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht; Department of Neuro-oncology, Princess Maxima Center for Paediatric Oncology, Utrecht, the Netherlands
BACKGROUND AND AIM: Cerebrospinal fluid (CSF) leakage is a complication with potentially serious consequences. This study aimed to establish the incidence of CSF leakage after intradural cranial surgery in the pediatric population. In addition, potential risk factors and complications related to CSF leakage in the pediatric population were evaluated.
METHOD: We performed an international multicenter retrospective cohort study in three tertiary neurosurgical referral centers. All patients aged 18 years or younger who underwent intradural cranial surgery between 2015 and 2021 with complete follow up and complete surgical report available were included. Burr hole and transsphenoidal procedures were excluded. The primary outcome measure was the incidence of CSF leakage, defined as leakage through the skin, within six weeks after surgery. Uni- and multivariable logistic regression analysis was done to identify risk factors for, and complications related to CSF leakage.
RESULTS: We identified 844 procedures, representing 692 individual patients. The most common indication for surgery was tumor resection (50.1%). The incidence of CSF leakage was 6.8%. The odds ratio of pseudomeningocele (7.0, 95% CI 3.9–12.5), meningitis (25.5, 95% CI 11.8–55.0) and surgical site infection (7.6, 95% CI 2.7–21.1) was higher for patients with CSF leakage compared to patients without. Risk factors for CSF leakage were hydrocephalus (OR 4.2, 95% CI 2.1–8.2) and craniectomy (OR 8.6, 95% CI 3.3–22.1). Invasive treatment (defined as CSF diverting procedure, lumbar puncture, puncture of the pseudomeningocele or surgical wound revision) was performed in 49.1% of cases. A mean of 5.8 days of prolonged hospital stay was contributed to CSF leakage.
CONCLUSIONS: CSF leakage occurs in 6.8% of the pediatric population after intradural cranial surgery. It has a serious clinical impact due to increased risk of infection, development of pseudomeningocele, necessity for invasive treatment and prolonged hospitalization. Preventative strategies should aim at adequately controlling hydrocephalus and avoiding craniectomies.
Keywords: Cerebrospinal fluid leakage, Pediatrics, Infection, Cranial surgery, Hydrocephalus, Craniectomy
FL-075
Hydrocephalus
Ventriculopleural shunts in a pediatric population: a review of 170 consecutive patients
Eisha A Christian1, Jeffrey Quezada2, Edward F Melamed2, Carolyn Lai2, J. Gordon Mccomb3
1Department of Neurological Surgery, Kaiser Permanente Medical Center, Los Angeles, USA
2Division of Neurosurgery, Children's Hospital Los Angeles, USA
3Division of Neurosurgery, Children's Hospital Los Angeles, USA & Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, USA
BACKGROUND AND AIM: The authors sought to determine the outcome of using the pleural space as the terminus for ventricular CSF-diverting shunts in a pediatric population
METHOD: All ventriculopleural (VPl) shunt insertions or revisions done between 1978 and 2018 in patients were identified. Data recorded for analysis were: age, sex, weight, etiology of hydrocephalus, previous shunt history, reason for VPl shunt insertion or conversion from ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt, valve type, nature of malfunction, presence of shunt infection or pleural effusion, and conversion to a different distal site.
RESULTS: A total of 170 patients (mean age 14 ± 4 years) with a VPl shunt were followed up for a mean of 57 ± 53 months. The reasons for conversion to a VPl shunt for 167 patients were previous shunt infection in 57 (34%), multiple abdominal procedures in 44 (26%), inadequate absorption of CSF in 34 (20%), abdominal pseudocyst in 25 (15%), and obesity in 7 (4%). No VPl revisions were required in 97 (57%) patients. Of the 73 (43%) patients who did require revision, the most common reason was proximal obstruction in 32 (44%). The next most frequent complication was pleural effusion in 22 (30%) and included 3 patients with shunt infection. All 22 patients with a clinically significant pleural effusion required changing the distal end of the shunt from the pleural space. Pleural effusion was more likely to occur in VPl shunts without an antisiphon valve. Of the 29 children < 10 years old, 7 (24%) developed a pleural effusion requiring a revision of the distal catheter to outside the pleural space compared with 15 (11%) who were older (p = 0.049). There were 14 shunt infections with a rate of 4.2% per procedure and 8.2% per patient.
CONCLUSIONS: VPl shunts in children under 10 years of age have a significantly higher rate of symptomatic pleural effusion, requiring revision of the shunt’s terminus to a different location. VPl shunt complication rates are similar to those of VP shunts. The technical difficulty of inserting a VPl shunt is comparable to that of a VP shunt. In a patient older than 10 years, all else being equal, the authors recommend the distal end of a shunt be placed into the pleural space rather than the right atrium if the peritoneal cavity is not suitable.
Keywords: CSF, Hydrocephalus, Pediatric population, Pleural effusion, Ventriculopleural shunts
FL-076
Hydrocephalus
Endoscopic lavage and subgaleal shunt insertion for the treatment of neonatal hydrocephalus: a 10-year single-center experience
Katerina Apostolopoulou, Ben Hall, John Duddy, Raenette David, Abhishek Nadkarni, Arthur Kurzbuch, Benedetta Pettorini
Department of Neurosurgery, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK
BACKGROUND AND AIM: The purpose of the present study is to present our experience and access the effectiveness of endoscopic lavage and subgaleal shunt insertion in the treatment of neonatal hydrocephalus.
METHOD: A retrospective review of the clinical cases was performed through the medical records, from 2012 to 2021. 57 neonates (28 males, 29 females) were included in the study. The mean gestational age was 28 + 4 weeks and the mean age at surgery was 35 + 3 weeks. The underlying pathologies causing hydrocephalus included intraventricular hemorrhage (IVH, mainly grade III and IV) (86%), infection (5%), IVH with infection (3.5%), congenital hydrocephalus (3.5%) and IVH from a ruptured vein of Galen malformation (2%). The surgical management included insertion of subgaleal shunt in 42 patients (74%), endoscopic washout in 8 (14%) and a combination of the two in 7 (12%).
RESULTS: The subgaleal shunt has been diverted to a permanent one in 37 neonates and in 5 was removed, with no need for further neurosurgical intervention (88% and 12%, respectively). 7 neonates who had a washout required a permanent shunt insertion and one did well without further intervention (87% and 13%, respectively). All 7 patients who had a combined surgery also required a shunt. The mean time period of the second operation was 6 weeks. No major intraoperative complications were observed. CSF leak from the subgaleal pouch observed in 5 patients (10%).
CONCLUSIONS: Our findings are in agreement with the current literature and suggest that endoscopic lavage and subgaleal shunts can serve as excellent methods for temporizing hydrocephalus in neonates. Both are low risk procedures with very promising results and occasionally can offer a definitive treatment.
Keywords: Endoscopic lavage, Subgaleal shunt, Neonatal hydrocephalus
FL-077
Hydrocephalus
Predictive factors in the Management of Hydrocephalus and Cerebrospinal Fluid Related Complications in Pediatric Choroid Plexus Tumors: A Single-Center Experience
Mahmoud Abbassy, Mohamed Elbeltagy, Mohammad Elbaroody, Ahmed Atallah, Abd Elrhman Enayet, Madiha Awad, Mohamed Saad Zaghloul
Cancer Children hospital of Egypt, Cairo, Egypt
BACKGROUND AND AIM: The intimate relation between hydrocephalus and pediatric Choroid Plexus Tumors (CPTs) should attain special care owing to the high incidence of permanent Cerebrospinal Fluid (CSF) diversion in those patients with possible shunt related complications. To our knowledge, this is the first study that analyzes predictive factors that could be linked to permanent CSF diversion in children with CPTs.
METHOD: We included all cases who were treated between January 2012 and December 2018 upfront in our institute with a follow-up from 2 to 106 months. Children in whom ventriculoperitoneal shunts were placed before tumor excision were excluded. Demographic data, preoperative radiological findings, operative details, and postoperative management of hydrocephalus, and CSF-related complications were reviewed.
RESULTS: A total of 33 children with CPTs were included in our study, 22 children (67%) needed permanent CSF diversion methods. Age less than two years (p-value 0.016), CSF permeation in FLAIR/T2 sequence (p-value 0.03), and bilateral subdural hygroma (p-value 0.049) were related to the need for permanent CSF diversion. Location of the tumor, maximum tumor diameter; consistency of tumor, preoperative Evan’s index; preoperative midline shift, tumor pathology; extent of resection of tumor; postoperative duration of the external ventricular drain, and amount of blood in ventricles were not statistically significant. We found that CSF permeation in FLAIR/T2 sequence, vasogenic edema and intraoperative parenchymal invasion were statistically significant factors in relation to postoperative entrapped horn.
CONCLUSIONS: Hydrocephalus has an intimate relation with pediatric choroid plexus tumors. Placement of a shunt could be inevitable at the end in most of them. However, patients older than two years without CSF permeation in preoperative imaging, and who did not develop subdural hygroma or developed a mild form should be given a worthy trial of patience, and going for shunt placement should not be the first option.
Keywords: Choroid Plexus- Papilloma- Atypical- Carcinoma- Hydrocephalus
FL-079
Hydrocephalus
Do sensor reservoirs reduce radiation exposure and the invasive procedures to diagnose shunt dysfunction in children with complex hydrocephalus?
Stuart Sinclair Stokes, Jan Hardy, Liz Hinde, John Preston, Hesham Zaki, John Mcmullan, Veejay Bagga, Patricia De Lacy, Shungu Ushewokunze
Department of Neurosurgery, Sheffield Children's Hospital, UK
BACKGROUND AND AIM: A significant proportion of children with hydrocephalus can be very difficult to diagnose as shunt malfunction due to significant cognitive impairment and gastrointestinal co-morbidities. We sought to determine if there was a reduction in the radiation exposure, as well as the use of hospital resources after sensor reservoirs implantation and if the sensor reservoirs are reliable beyond the initial number of months.
METHOD: We reviewed 23 patients over the last 5 years who had a total of 28 Miethke reservoir sensors implanted on average 2.9 years ago. We reviewed their medical notes, the regional PACS database and the database of all sensor readings stored for each child. The radiological investigations were then screened for those requested for shunt malfunction. When patients underwent invasive investigations such as a Lumbar puncture or ICP monitor insertion due to ongoing symptoms despite shunt adjustments we used these events to check the precision of the sensor reservoirs and if they correlate with invasive readings.
RESULTS: The average radiation exposure for each child significantly dropped from 6.8 CT head scans/year before sensor implant, to 3.3 CT heads/year. There were 8 occasions when invasive intracranial pressures were determined and these closely correlated with the averaged sensor readings to within 3cmH20 despite an average of 2.3 years of being implanted, in the presence of good waveforms and baseline negative pressures with the shunt in a vertical position. The implantation of sensor reservoirs significantly reduced the exploration of functional shunts and invasive procedures to determine ICP by a magnitude of 4. However, an increase in infection presumably due to the increase in the length of the incision, shunt connections and foreign material.
CONCLUSIONS: The sensor reservoir is a useful tool in determining shunt dysfunction in children that are difficult to assess and reduce radiation exposure in investigating shunt malfunction in our institution.
Keywords: Shunt, Sensor Reservoir, hydrocephalus, complex hydrocephalus
FL-080
Hydrocephalus
CSF-space volumetric change following posterior fossa decompression in paediatric Chiari type-I malformation; a correlation with outcome
Sidharth Mantha1, Liam Coulthard2, Robert Campbell3
1Department of Neurosurgery, Princess Alexandra Hospital, Brisbane, Australia
2Department of Neurosurgery, Gold Coast University Hospital, Gold Coast, Australia
3Department of Neurosurgery, Queensland Children's Hospital, Brisbane, Australia
BACKGROUND AND AIM: We have previously reported inferior post-operative clinical outcomes in younger children with Chiari type-I malformation (CIM). We sought to quantify the CSF volumetric changes pre- and post-decompression, in a paediatric cohort, to determine whether cisternal volume change is associated with clinical outcomes.
METHOD: In this retrospective clinical study, the CSF spaces of the posterior fossa (supracerebellar/quadrigeminal, prepontine, fourth ventricle, cisterna magna) were measured on magnetic resonance images pre- and post-operatively using a semi-automated method. Additionally, we describe a novel CSF space of the upper cervical canal incorporating the subarachnoid space from the foramen magnum to inferior cortex of C2 body, FM-C2 cistern. Morphometric measurements included the pB-C2 distance, clivoaxial angle, clival length, clival angle and Boogard’s angle. Volumetric and morphometric data were correlated with clinical outcomes at 4–12 months post-operatively as measured by the Chicago Chiari Outcome Scale (CCOS).
RESULTS: Of 59 adequate clinical cases, 57 and 36 patients had acceptable imaging for morphometric and volumetric analysis respectively. All CSF spaces measured had a significant increase in volume post-operatively (p < 0.05). There was no correlation between the change in volume or post-operative CSF volumes and CCOS. The pre-operative volume of the FM-C2 was positively correlated with total CCOS (Wald χ2(1) = 4.07 p = 0.049) and was significantly smaller in the 0–6 year age group (2.38 ± 1.27 ml vs. 3.67 ± 1.56 ml p = 0.014). No morphometric measurement changed significantly after surgery or demonstrated a relationship with CCOS.
CONCLUSIONS: Volumetric changes in the CSF cisterns of the posterior cranial fossa and upper cervical canal do not correlate with the age-related differences in clinical outcomes in paediatric CIM. The pre-operative volume of the FM-C2 cistern may have a role in predicting the likelihood of a beneficial post-operative outcome in paediatric CIM.
Keywords: Chiari malformation, Volumetric analysis
FL-082
Global Pediatric Neurosurgery
Connective tissue hypermobility/EDS and Chiari 1 malformation: Surgical indications and outcomes
Katherine M Hofmann1, Nirali P Patel2, Lawrence Davidson1, Tiffany N Phan1, John S Myseros1, Chima O Oluigbo1, Hasan R Syed1, Daniel A Donoho1, Robert F Keating1
1Department of Neurosurgery, Children's National Hospital, Washington, DC, USA
2Department of Neurosurgery, Georgetown University, Washington, DC, USA
BACKGROUND AND AIM: The rise of incidental Chiari 1 malformation (CM1) radiographic findings has led to uncertainty about appropriate therapeutic approaches for children with concomitant connective tissue hypermobility/Ehlers-Danlos Syndrome (EDS) and their myriad symptomatology. A retrospective review of surgical treatments and outcomes of patients with EDS was undertaken to ascertain appropriate surgical indications.
METHOD: Demographics, surgical management, and long-term outcomes were observed for patients with EDS and CM1 at a single center (Children’s National Hospital) and compared to our cohort of general CM1 decompressions since 2003.
RESULTS: 36 patients with EDS and CM1 who underwent decompression were observed over 18 years. In this cohort, 88.9% were female vs. 54.3% in our overall cohort (232 CM1 patients) (p < 0.01). EDS patients underwent 44% bone-only and 56% duraplasty decompressions, similar to the general cohort (p = 0.66). The EDS failure rate was 11.1% vs. 10.3% for the overall cohort (p = 0.89), with follow-up of 4.72 years vs. 3.74 years (p = 0.11).
Surgical indications were similar for both cohorts (EDS vs. general): headache (67% vs. 65%, p = 0.85), neurological changes (28% vs. 24%, p = 0.59), and syringomyelia (50% vs. 63%, p = 0.12). Both cohorts (EDS vs. general) showed improvement for syringomyelia (77% vs. 82%), headache (85% vs. 80%), and neurological issues (60% vs. 79%), with no statistical difference in outcomes. Although most patients manifested headache improvement, resolution of EDS pre-op headaches often required more time. Complications were minimal for both groups.
CONCLUSIONS: Concomitant presentation of patients with connective tissue hypermobility/EDS and CM1 often presents a therapeutic dilemma. Somatic complaints frequently mimic symptomatic CM1; thus, we must differentiate clinically relevant etiology from the MRI finding. Failure to appreciate the true cause of symptoms may lead to ineffective treatment and morbidity. Our experience with EDS and concomitant CM1 demonstrates equivalent surgical therapeutic efficacy, although additional time is often necessary for resolution of preoperative headache, with improvement persisting over time.
Keywords: Chiari 1 malformation, Ehlers-danlos syndrome, Syringomyelia, Connective tissue hypermobility
FL-083
Neuroendoscopy
Intracranial arachnoid cysts: what is the appropriate surgical technique? a retrospective comparative study with 64 pediatric patients
Mohammed Issa, Filippo Paggetti, Andreas W Unterberg, Ahmed El Damaty
Department of Neurosurgery, University Hospital Heidelberg
BACKGROUND AND AIM: Symptomatic intracranial arachnoid cysts (iAC) should be treated whether through microsurgical (MS), endoscopic (ES) fenestration or implantation of a cysto-peritoneal shunt (CPS) system. The aim of this study is to compare the clinical and radiological courses with focus on the complication and revision rates between the three operative techniques in pediatric patients.
METHOD: All patients below 18 years with symptomatic iAC whom their first surgical treatment occurred in our center between 2004–2021 were included in this mono-central retrospective comparative cohort study. Initial symptoms, cyst location, complication rate, clinical and radiological improvement, revision rate and hospital stay were compared between the three operative techniques.
RESULTS: Sixty-four patients; 32 (50%) MS operated (mean age 7.6 years), 22 (34.4%) ES operated (mean age 6.0 years) and 10 (15.6%) with CPS (mean age 3.0 years) were found. The most common initial symptom was headache with 46.9%, followed by nausea and vomiting within 32.8%. The highest revision rate with 50% was seen in the CPS-group with a mean follow-up of 71.7 months compared to 5 patients (22.7%) in the ES-group and 11 (34.4%) patients in the MS-group with a mean follow-up of 32.7 and 80.3 months respectively. 3 patients (13.6%) from the ES-group needed later a CPS, in comparison to 8 (25%) patients from the MS-group. Clinical improvement immediately after surgery was observed in 19 (86.4%) patients in the ES-, 31 (96.9%) in MS- and by 10 (100%) in CPS-group. The patients could be discharged from hospital after 9.5 days in the CPS-, 12.77 days in the ES- and 17.3 days in the MS-group, 1.2–3.86 days of ICU-stay were necessary in average.
CONCLUSIONS: ES is a safe and efficient technique which is being widely used nowadays as a treatment of symptomatic iAC. Although CPS carries the least surgical risks but on the long-term shows the highest revision rate.
Keywords: Arachnoid cysts, Neuroendoscopy, Microsurgery, Cysto-peritoneal shunt
FL-084
Hydrocephalus
Defining the relationship between elevated cerebrospinal fluid protein and paediatric ventriculoperitoneal shunt infection
Charles Yates1, Michael Colditz3, Martin Wood1, Norman Ma2, Gert Tollesson1, Amelia Jardim1, Raymond Chaseling1, Robert Campbell1
1Department of Neurosurgery, Queensland Children's Hopsital, Brisbane, Australia
2Royal Brisbane and Women’s Hospital, Brisbane, Australia
3School of Medicine, University of Queensland, Brisbane, Australia
BACKGROUND AND AIM: Ventriculoperitoneal shunt (VPS) device infection is extremely common, and carries great morbidity for patients, their families, and the healthcare system. Clinically, elevated cerebrospinal fluid protein (CSFp) is a suspected risk for VPS infection, however this is widely debated, and definitive evidence is lacking. We aim to assess the role of CSFp in predicting VPS infection in a large paediatric cohort.
METHOD: A retrospective review of VPS procedures at the Queensland Children’s Hospital between 2014–2019 was conducted. Any future positive CSF culture was identified as an infection and correlated to the average retrospective CSFp levels more than 90-days prior to the positive culture. Relationships between patient age, gender, hydrocephalus aetiology and infection organism were similarly assessed. Prior culture-positive CSF samples were excluded from protein analysis. A logarithmic correction was applied to CSFp (nl-CSFp) for statistical modelling.
RESULTS: 563 procedures were assessed in 268 patients. Fourty-six (8.2%) VPS procedures were conducted for infected VPS devices, in thirty-eight (14.2%) patients. Historical nl-CSFp levels were significantly higher in patients with a VPS infection compared to those with no infection in the study period, and predicted future infection (OR 3.34, 955 CI 1.04–10.92, p = 0.042). Age at presentation was similar between patients with infection and those without infection (6.7 ± 5.8 versus 6.5 ± 5.4 years, p = 0.789), and no significant differences in gender (p = 0.067) or etiology for hydrocephalus (p = 0.513) were observed.
CONCLUSIONS: Patients with a historically elevated CSF protein may be at significantly increased risk for CSF infection following VPS device insertion. These findings support the need for prospective assessment of interventions to reduce VPS infection rates in this high-risk patient group.
Keywords: Paediatric, Hydrocephalus, VPS, Infection
FL-085
Hydrocephalus
Ventriculoperitoneal shunt (VPS) survival from the neonatal period into adulthood-a single-center long-term retrospective study
Ido Ben Zvi1, Elias Badin2, Aswin Chari1, Kristian Aquilina1
1Department of Neurosurgery, Great Ormond Street Hospital for Children
2Queen Mary University of London
BACKGROUND AND AIM: Insertion of a ventriculoperitoneal shunt is one of the most common procedures in pediatric neurosurgery. Nevertheless, it has one of the highest complication rates in the specialty, particularly in infants. Our objective was to define long-term survival for shunts inserted in infancy, and the factors related to VPS complications.
METHOD: This was a retrospective, single-center trial. Children aged less than one year upon VPS insertion with follow-up until transition to adult care (17-18yrs) were included. Kaplan–Meier (KM) & Cox-regression analyses were used to identify which factors, presurgical and surgical, were associated with shunt survival.
RESULTS: 291 infants who underwent insertion of VPS between 1990–2003 were included. The most common aetiology was intraventricular haemorrhage (43%), followed by congenital hydrocephalus (16.5%), myelomeningocele (10%) infection (5.8%) and others (24%). The vast majority of the VPS were parietal. During the follow-up period, 168 (57.7%) of the shunts were revised, at a median time of 14 months (IQR 4–71 months). Survival was 60% at 5 years, 45% at 10 years and 35% at 15 years. In univariable KM analyses, the location of the shunt (p = 0.81), hydrocephalus severity (p = 0.10) and aetiology (p = 0.87) were not associated with shunt survival. On Cox-regression analysis a longer length of the proximal catheter was significantly associated with decreased shunt survival (p = 0.002) with a hazard ratio of 1.24 (95% CI 1.05–1.46), whereas distance from the tip of catheter to the foramen of Monro was not (p = 0.54).
CONCLUSIONS: The only factor associated with VPS failure was proximal catheter length, possibly due to the proximity to the choroid plexus. VPS insertion in infancy has a very low long-term success rate that should be communicated to the parents of these infants. Although most revisions occurred within 1 year of insertion, 25% were performed more than 5 years post insertion, warranting long-term follow-up.
Keywords: Pediatric hydrocephalus, Ventriculoperitoneal shunt, IVH, Myelomeningocele
FL-086
Hydrocephalus
Risk Factors of Congenital Hydrocephalus: A Case–Control Study
Taher Ali1, Reem Elwy1, Bassante A El Razik2, Mohamed A.R. Soliman3, Mohamed F. Alsawy1, Ahmed Abdullah1, Eman Ahmed4, Shurouk Zaki1, Amany A Salem5, Mohamed A Katri1, Mostafa Elhamaky1, Haitham Kandel1, Ahmed A Marei1, Ahmed Almenabbawy6, Ahmed M.F. Ghoul1, Ahmed A Hafez1, Sarah Abdelbar1, Reham Khaled Moharam1, Ayman Hany7, Ahmed Hasanin8, Sascha Marx9, Steffen Fleck9, Joerg Baldauf9, Henry W.s. Schroeder9, Ehab Elrefaee6, Ahmed Zohdi1
1Department of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt
2Global Health, Global Health Institute, Heidelberg University, Heidelberg, Germany
3Department of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt; Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, United States; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, United States
4Department of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt, Faculty of Biotechnology, Badr University in Cairo, Cairo, Egypt
5Department of Public Health, Faculty of Medicine, Cairo University, Cairo, Egypt
6Department of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt Department of Neurosurgery, University Medicine Greifswald, Greifswald, Germany.
7Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
8Department of Anaesthesiology, Faculty of Medicine, Cairo University, Cairo, Egypt
9Department of Neurosurgery, University Medicine Greifswald, Greifswald, Germany
BACKGROUND AND AIM: Hydrocephalus is the commonest brain disorder in children and is more common in low- and middle-income countries. Research output on hydrocephalus remains sparse and of lower quality in low- and middle-income countries compared to high-income countries. Most studies addressing hydrocephalus epidemiology are retrospective registry studies entailing their inherent limitations and bias. We aim to investigate child-related, parental, and socioeconomic risk factors of congenital hydrocephalus (CH) in a lower-middle-income country.
METHOD: An investigator-administered questionnaire was used to query parents of CH patients and controls that visited our institution from 2017 until 2021. We excluded secondary hydrocephalus and children older than two years at diagnosis. Univariable and multivariable logistic regression was performed to identify the factors affecting the development of CH.
RESULTS: A total of 741 respondents (312 cases and 429 controls) were included. There was an independent higher odds of CH among children with a family history of other similar central nervous system conditions (odds ratio [OR] = 2.93, 95% confidence interval [CI] = 1.24–7.34), other congenital anomalies (OR = 2.57, 95%CI = 1.38–4.87), parental consanguinity (OR = 3.67, 95%CI = 2.40–5.69), conceived via assisted fertilization (OR = 3.93, 95%CI = 1.57–10.52), with a housewife mother (OR = 2.66, 95%CI = 1.51–4.87), suffering a gestational disease (OR = 3.12, 95%CI = 1.96–5.03), not using periconceptional folic acid (OR = 1.92, 95%CI = 1.32–2.81), and an illiterate father (OR = 1.65, 95%CI = 1.02–2.69). Contrarily, maternal hypertension (OR = 0.22, 95%CI = 0.09–0.48), older age at delivery (OR = 0.93, 95%CI = 0.89–0.97), and more abortions (OR = 0.80, 95%CI = 0.67–0.95) were protective from CH.
CONCLUSIONS: Multiple parental, socioeconomic and child-related factors were associated with higher odds for developing CH. However, other factors seem to be protective against hydrocephalus.
Keywords: Congenital hydrocephalus, Epidemiology, Maternal, Paternal, Socioeconomic, Risk Factors, Low and Lower-middle-income Countries (LMICs)
FL-087
Hydrocephalus
The Care Provider Experience for Hydrocephalus in Vietnam: A Social Media Survey
My Quang Le1, Can Do Thanh Dang1, Lepard Jacob R2, Dung Hanh Nguyen3, Thoa Thi To1, Thanh Minh Nguyen1, Thanh Van Tran3
1Department of neurosurgery, Children hospital 2, Ho Chi Minh city, Viet Nam
2Department of neurosurgery, University of Alabama at Birmingham, Alabama, United State of America
3Cure neuro, Cure international, Canada
BACKGROUND AND AIM: Hydrocephalus is a significant cause of pediatric morbidity and mortality worldwide. The clinical experience with hydrocephalus in Vietnam is not well understood.
METHOD: We utilized a popular Vietnamese hydrocephalus social media page to provide a link to an online survey regarding the clinical experience of hydrocephalus from the family perspective. Data were colected between April 1, 2022 and May 20, 2022.
RESULTS: We received a total of 73 responses. The majority of respondents were (91.8%) mothers of the patient and 5.5% were fathers. Most patients represented were female (44/73,60.3%). Approximately half of patients (34/73,46.6%) were the first child. Nearly half were born via vaginal delivery, (33/73,45.2%). The age of mothers ranged from 22 to 41. Twenty patients were diagnosed with hydrocephalus in utero (20/73,27.5%). Pre-term delivery was reported in 21 patients (21/73, 28.8%). The majority of patients (59/73, 80.8%) were treated at a national level pediatric neurosurgical hospital. Over half of patients required only one surgery for treatment of hydrocephalus (39/73,54.4). Thirty patients underwent endoscopic treatment of their hydrocephalus (30/73,41.1%). The majority of patients (48/73,65.8%) reported no post-operative complications. Over half of patients (42/73, 58.3%) attend regular follow-up visits. Forty patients reported access to physical therapy services (40/73,54.8%). For an improved treatment experience families requested: A Vietnamese website for hydrocephalus, better community for hydrocephalus patients, access to physical therapy videos, protocolized care, education regarding long-term treatment outcomes, and livestream webinars for answering questions, and access to latest surgical techniques and equipment in Vietnamese hospitals.
CONCLUSIONS: In the absence of comprehensive clinical databases the care provider experience provides important insight into the experience and needs of hydrocephalus patients and their families in Vietnam. Social media platforms can be an important means of accessing these patients and families for education and providing resources.
Keywords: Vietnam pediatric hydrocephalus, Children hospital 2, Social media survey
FL-088
Hydrocephalus
Optimal timing of definitive cerebrospinal fluid diversion for post-haemorrhagic ventricular dilatation in preterm infants
Ernest Lee1, Helen Smart2, Mohammad Naushahi2
1School of Clinical Medicine, University of Cambridge, Cambridge, UK
2Academic Department of Neurosurgery, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
BACKGROUND AND AIM: Intraventricular haemorrhage (IVH) remains a severe complication in preterm infants. Producing progressive post-haemorrhagic ventricular dilatation (PHVD), IVH can lead to brain injury and severe neurological disability. Temporising surgical interventions, such as insertion of ventriculosubgaleal conduits (VSGs) and ventricular access devices (VADs), aim to minimise damage by permitting intermittent diversion of cerebrospinal fluid (CSF), as required. For some infants, this progresses to requirement of definitive CSF diversion, most commonly in the form of ventriculoperitoneal shunts (VPSs). The optimal timing for VPS insertion is still debated as it is uncertain whether the benefits of intervening early outweigh the potential complications. This study aims to determine if the said complications are influenced by the timing of VPS insertion.
METHOD: We retrospectively reviewed all PHVD preterm infants managed surgically at our regional Paediatric Neurosurgical Centre since 2015. Outcomes and complications, including shunt mechanical failure, infection, need for revision and long-term neurodevelopment were compared between infants with different time intervals between temporising and VPS interventions.
RESULTS: We identified 48 infants with Grade II-IV IVH. Temporising interventions were performed in 34 patients, with 25/34 requiring subsequent VPS insertion. The time interval between interventions ranged from 12 to 181 days. VPS was the first-line intervention in the remaining nine patients. Complications occurred in patients across all time intervals, with the most common being shunt blockage, migration and infection. Eleven out of twenty-five patients required shunt revision. Similarly, we observed issues with hearing, vision, motor development and seizures in patients across all time intervals.
CONCLUSIONS: Our results indicate that complications occur both in patients who had a VPS inserted early or later following temporising measures. Given the complications observed and lack of evidence surrounding this important issue, this study should provide impetus for randomised control trials to ascertain optimal timing for definitive CSF diversion in these preterm infants.
Keywords: Intraventricular haemorrhage, Post-haemorrhagic ventricular dilatation, Ventriculoperitoneal shunts
FL-089
Neurotrauma/Critical Care
Admission for observation for children with isolated linear skull fractures. Is it really necessary?
Ido Ben Zvi1, Galal Imtiaz2, Martin Tisdall1
1Department of Neurosurgery, Great Ormond Street Hospital for Children
2University of East Anglia
BACKGROUND AND AIM: Pediatric head trauma is a common reason for emergency department (ED) referrals. Once a head CT scan demonstrates non-surgical pathologies, the UK national guidelines recommend admission for 24 h minimum observation and discharge based on neurological status and oral intake. We evaluated whether admissions for isolated skull linear fractures yielded additional benefit.
METHOD: This was a retrospective single-center analysis, based on the electronic referral database of a tertiary pediatric hospital. Pediatric patients (< 18) were included if they sustained a skull linear fracture on CT scan. Patients with additional traumatic intracranial findings on imaging (bleeding, pneumocephalus, edema, etc.) were excluded, as were patients with depressed, open or displaced fractures.
RESULTS: 258 patients met the criteria between 2019–2022. 209 fell, 17 had blunt-force trauma, 8 had road accidents and 27 had an unclear mechanism. Most children had parietal fractures (50.4%), followed by occipital (20%), frontal and temporal (7.7% each). 4% had skull-base fractures. 16% suffered from chronic illness at the time of injury. No cases of growing skull fractures were seen. Out of all the children presented to our institution, none needed neurosurgical intervention. Moreover, none of them needed a follow-up CT scan. Three were transferred from a first-tier hospital to our institution, none of whom because of a neurosurgical concern. Apart from these three, all the other children were admitted to a pediatric ward for 24 h observation and subsequently discharged. Non-accidental injury (NAI) was highly suspected in 6 children, 3/42(7%) with chronic illness, 3/216(1.4%) without. This difference was statistically significant (p = 0.017).
CONCLUSIONS: In this large cohort, none of the children presented had a change in management following their admission. None needed neurosurgical intervention or observation. NAI-suspicion was more prevalent in chronic illness. In children with isolated skull linear fractures, a short ED observation should be considered, followed by discharge based on neurological status.
Keywords: Linear skull fracture, Pediatric head trauma, Head injury observation
FL-090
Neurotrauma/Critical Care
Middle Meningeal Artery Embolization for the Treatment of Chronic Subdural Hemorrhage in the Pediatric Population
Marian Michael Bercu1, Casey J. Madura1, Paul A. Mazaris2, Justin A. Singer2
1Department of Pediatric Neurosurgery, Helen DeVos Children's Hospital, Spectrum Health, Grand Rapids, Michigan, USA
2Department of Neurosurgery, Spectrum Health, Grand Rapids, Michigan, USA
BACKGROUND AND AIM: Chronic subdural hematoma (cSDH) is a common condition in the adult population, associated with significant morbidity and mortality. Embolization of the middle meningeal artery (MMA-E) has been reported as an evolving treatment for the symptomatic or large cSDH in the adult population.
The treatment of cSDH in the pediatric population consists in surgical drainage of the large or symptomatic cSDH, either through fontanelle taps or with a subdural drains.
We report the only series of three infants treated with MMA-E, with no complications and initial promising outcomes.
METHOD: Three patients were treated with MMA-E: Patient 1: 8-month-old with an atypical presentation at the age of 5-month-old with bilateral extra-axial hygromas probably secondary to NAT, treated initially with a fontanelle tap followed by a right MMA-E due to a significant acute on-chronic, clinically asymptomatic hemorrhage. Patient 2: 8-month-old female, with a history of traumatic birth, was incidentally diagnosed with large bilateral cSDH and Frisen grade 3 papilledema as part of the work-up for newly diagnosed neuroblastoma. Patient was treated with fontanelle taps, Diamox, followed by bilateral MMA-E. Patient 3: Presented with increasing head circumferences, diagnosed with bilateral (left > right) cSDH in the probable setting of von Willebrand disease, treated concomitantly with a left MMA-E and a burr hole for surgical drainage.
RESULTS: Patient 1: No evidence of residual extra-axial collections at 3 months follow-up. Patient 2: Undergoing aggressive chemotherapy and stem cell transplantation with severe thrombocytopenia (< 25,000/uL); at one month of follow-up the cSDH were similar in size but with a more dominant chronic component; the papilledema has almost fully resolved. Patient 3: Post-op MRI revealed minimal residual cSDH, head circumferences decreased by approximately 1 cm at 2 weeks follow-up, MRI pending.
CONCLUSIONS: We report the only series of three pediatric patients, diagnosed with cSDH, treated with MMA-E with no complications and initial promising outcomes.
Keywords: Middle meningeal artery embolization, Pediatric, Infant, Chronic subdural hematoma
FL-091
Neurotrauma/Critical Care
Disturbances of functional connectivity between default mode network and cerebellar structures in patients with mTBI in acute stage. rsfMRI and DTI study
Maxim Ublinskiy1, Natalia Semenova2, Tolibdzhon Akhadov1, Andrei Manzhurtsev2, Ilya Melnikov1
1Clinical and Research Institute of Emergency Pediatric Surgery and Trauma
2 N. M. Emanuel Institute of Biochemical Physics (IBCP), RAS
BACKGROUND AND AIM: Mild traumatic brain injury (mTBI) occupies one of the first places in children injuries. Among all brain networks at the resting state, the Default Mode Network (DMN) is the most widely studied network. The aim of this study is to examine functional connectivity in normal-appearing cortex in acute period of mTBI using rsfmRI.
METHOD: 34 MR negative participants were studied in age from 12 to 17 years (mean age – 14.5 years). Group of patients consisted of 17 children with mild traumatic brain injury in acute stage. 17 age-matched healthy volunteers comprised control group. All studies were performed at Phillips Achieva 3.0 T MRI scanner using 32-channel head coil. fMRI data were processed using functional connectivity toolbox CONN. Seed-based analysis was performed in order to reveal disturbances in functional connectivity.Statistical processing was performed using Statistica 12.
RESULTS: DTI analysis didn't show any changes in values of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) between two groups (see Fig. 1). No statistically significant differences in correlation strength between DMN parts were observed in two groups (see Fig. 2). Intergroup seed-based analysis revealed statistically significant (p < 0,05) difference in neural correlations between DMN parts and vermis (cerebellum structural part): positive link in control group and negative link in group of patients.
CONCLUSIONS: One of the most common symptoms of mTBI is dizziness as a result of impaired movements coordination.Vermis as an essential cerebellum part plays an important role in the vestibulo-ocular system which is involved in the learning of basic motor skills in the brain. Vermis aids in the synchronization of eye and motor functions in order for the visual field and the motor skills to function together.Our results show that mTBI appears to be a possible reason of connectivity malfunction in normal-appearing vermis.
Keywords: mTBI, rsFMRI, DMN
FL-092
Neurotrauma/Critical Care
Pediatric blast induced neurotrauma model in rats: Functional and Biochemical study
Sachin Jose Pulickal, Dhananjaya I Bhat, Bhagavatula Indira Devi, Dhaval P Shukla
National Institute of Mental Health and Neurosciences, Bengaluru, India
BACKGROUND AND AIM: Our current understanding on blast induced neurotrauma pathophysiology stems from animal experiments. There is a paucity of knowledge on blast effects on young developing brain. The aim of the study is to assess the neurocognitive effects of blast induced neurotrauma in paediatric rats and to assess the tau protein levels in rat hippocampus and correlate with neurocognition.
METHOD: 30 Sprague Dawley rats of age 3–5 weeks were choosen which corresponds to post weaning period of humans. These rats were divided into three groups, two of which were subjected to mild blasts generated by a blast tube(modified Reddy’s Tube) to produce BINT in rats and the third group was used as control. Rats then underwent radial arms maze test to look for learning and memory functions after which they were sacrificed. The rat hippocampal isolates were then subjected to tau protein assesment.
RESULTS: The sham rats reached the acceptable level of training at the end of 12 days of training whereas the test rats took 16-days of training that is an additional three days to reach the acceptable level of training. The mean (SD) of tau protein levels (pg/100 mg Tissue) in the rat hippocampal homogenates. Group: High Pressure Blast group was 14.61 (8.46), Low Pressure Blast group was 7.72 (2.74) and 6.29(2.38) in the control group. Tau protien accumulation was noted in the blast exposed rats when compared to control rats.
CONCLUSIONS: Mild blast induced neurotrauma produces learning and memory impairment in rat pups which increase with the severity of the blast wave pressures. Blast induced neurotrauma produces accumulation of tau in hippocampus of rat pups. The aim of the study is to assess the neurocognitive effects of blast induced neurotrauma in paediatric rats and to assess the tau protein levels in rat hippocampus and correlate with neurocognition.
Keywords: Blast induced neurotrauma, Blast effects in peadiatric brain tau protien accumulation in TBI
FL-094
Innovation and technology
A novel MRI protocol for the assessment of MRI-negative/suspected focal cortical dysplasia in children. A single institution pilot study
Ido Ben Zvi1, Aswin Chari1, Martin Tisdall1, Zubair Tahir1, Sophie Adler2, Konrad Wagstyl2, Kshitij Mankad3, Felice D’arco3
1Department of Neurosurgery, Great Ormond Street Hospital for Children
2University college London
3Department of Radiology, Great Ormond Street Hospital for Children
BACKGROUND AND AIM: Focal cortical dysplasia (FCD) is a common cause of drug-resistant epilepsy in childhood. These are further subdivided into three types. The routine MRI epilepsy protocol includes 3D-T1, 3D-FLAIR, T2 and diffusion. While this suffices for many FCDs, up to a third of lesions are radiologically occult. Since there is a correlation between MRI-positive lesions and seizure prognosis, at Great Ormond Street Hospital a novel protocol was developed for improving FCD detection, which is assessed in this pilot study.
METHOD: Patients are assessed with the advanced protocol if they have a suspected FCD, or if they are lesion-negative, but have a presumed FCD based on either history or EEG findings. Children with hippocampal sclerosis are assessed as well. Patients are not candidates if they have gross clear abnormalities such as tuberous sclerosis, hemimegalencephaly, stroke etc. The advanced protocol consists of arterial spin labelling (ASL) with color mapping, magnetization prepared 2 rapid gradient echo (MP2RAGE) with edge-enhancing gradient echo (EDGE) enhancement and diffusion tensor imaging (DTI) hot-spots. Patients are also analyzed by the multi-centre epilepsy lesion detection (MELD), a machine-learning system designed to detect FCDs.
RESULTS: In this pilot study three patients with an MRI-negative lesion were proven as FCDs, two with EDGE-MP2RAGE and one with ASL color mapping. In two other cases suspected lesions on FLAIR were proven as false-positive by EDGE-MP2RAGE. One further patient was identified with gyral abnormality identified by MELD, that correlated with symptomatology and was then resected.
CONCLUSIONS: Using this novel approach, we were able to detect both so-called MRI-negative and false-positive lesions. We believe this approach will enable neurological/neurosurgical teams to acquire surgical targets more accurately and add invaluable information to the decision-making process of suspected CFDs. A prospective study is underway to assess the usefulness of this method.
Keywords: Focal cortical dysplasia, epilepsy, MRI-negative, MP2RAGE, EDGE
FL-095
Innovation and technology
The use of Contrast Clearance Analysis Software to differentiate Tumor from Radionecrosis in Pediatric Brain tumors: A Revolution?
Amanda De Oliveira López1, João Gabriel Ribeiro Gomes2, Henrique Queiroga Cartaxo5, Ernesto Henrique Rosler3, Francisco De Paula Ramos Pedrosa4
1Pediatric Neurosurgery Department, Real Hospital Português do Recife-PE, Brazil
2Pediatric Neurosurgery Department, Real Hospital Português do Recife-PE, Brazil; Radiation Oncology Department, Real Hospital Português do Recife-PE, Brazil
3Radiation Oncology Department, Real Hospital Português do Recife-PE, Brazil
4Pediatric Oncology Department, Real Hospital Português do Recife-PE, Brazil
5Neurorradiology Department, Real Hospital Português do Recife-PE, Brazil
BACKGROUND AND AIM: To evaluate the experience of the first center in Brazil, and second in South America, using Contrast Clearance Analysis Software (Brainlab) to differentiate tumor recurrence from radionecrosis in the management of pediatric brain tumors.
METHOD: We analyzed pediatric brain tumors images with Contrast Clearance Analysis (CCA) Software from April 2021 to April 2022 in a Pediatric Oncology Center in Brazil. From 87 patients and 244 CCA images at our institution, we selected the pediatric patients (10.34%) with 23 CCA images. All images were obtained with 3 T MRI (Verio, Siemens), and a T1 contrast enhanced volumetric sequence (MPRAGE) was acquired at 5 min and 60 to 105 min. The images were transfered to CCA software. A fusion between the 2 MPRAGE sequences was made and a CCA colored map was calculated. The lesion studied was evaluated according to the color on the map: blue (active tumor) or red (radionecrosis) (Fig. 1). The results of CCA software were compared to conventional MRI sequences (diffusion/perfusion/ spectroscopy).
RESULTS: The median age was 12 years (Range: 4–17) and mean follow up was 17,12 months (Range: 2–41). Patient diagnosis were malignant tumor (3 patients), benign tumor (5) and brainstem tumor without biopsy (1). 3/9 patients were treated with single fraction radiosurgery and 6/9 with conventional Radiotherapy. At follow up, 33,3% of patients developed new symptoms and Control MRI with conventional sequences demonstrated signs of disease progression, however, at CCA software was radionecrosis (Fig. 2,3). 100% had complete symptoms relief after radionecrosis treatment (steroids and vitamin E), and two lesions practically disappeared (Fig. 4).
CONCLUSIONS: The CCA software is a new technological approach providing efficient distinction between tumor/radionecrosis. The methodology provides high resolution and easy to interpret images with high accuracy. The present study is the first to describe the CCA software contribution specifically in the management of pediatric brain tumors.
Keywords: Radiotherapy, Pediatric brain tumors, Radionecrosis, Contrast clearance analysis, Recurrence
FL-096
Neurotrauma/Critical Care
Preventing Falls from Windows in the Children of British Columbia
Ruth Mitchell1, Meah Lamothe2, Stephano Chang3, Ashutosh Singhal1, Mandeep Tamber1
1Faculty of Medicine and the Division of Neurosurgery, University of British Columbia and British Columbia Children’s Hospital
2Faculty of Medicine, University of British Columbia
3Division of Neurosurgery, Department of Surgery, University of British Columbia
BACKGROUND AND AIM: Unintentional falls are the leading cause of non-fatal injuries in the pediatric population. Falls from windows commonly lead to serious injuries requiring costly, invasive interventions. We aim to describe the severe injuries sustained due to falls from windows in a province-wide pediatric population, to inform prevention initiatives.
METHOD: We searched the British Columbia Trauma Registry (BCTR) for patients treated at the provincial pediatric trauma service who had unintentional falls from January 1 2007 to December 31 2020. The trauma database, electronic and paper-based medical records were searched. Institutional ethics board approval was obtained.
RESULTS: We found 2420 patients admitted in the defined period with falls, 1605 having fallen from less than one metre. We focused on falls between one and six metres resulting in admission to the Intensive Care Unit, and falls more than six metres, for 168 patients in total. Falls from windows accounted for just over a third of the falls in this period, more than any other mechanism. The mode of transportation to hospital, length of hospital stay, and length of ICU stay were similar in falls from windows, and other falls. However falls from windows resulted in significantly greater rates of trauma team activation, and patients were more likely to have sustained a head injury. Falls were most common in the summer months, with a peak in August.
CONCLUSIONS: A significant proportion of falls in our pediatric population are falls from windows. Further analyses are planned with regard to the age, number of operative interventions, permanent disability, and death in this cohort when compared with other pediatric falls patients. If such a high incidence of falls from windows occurs in our relatively temperate climate, a similar injury pattern might be found in warmer climates. Seasonal patterns of injury may help inform prevention efforts.
Keywords: Trauma, Falls, Traumatic brain injury, Head injury, Window, Neurotrauma
FL-097
Innovation and technology
Feasibility and utility of Sodium Fluorescein in removal of brain and spine tumors in children: a pilot prospective study in 38 cases
Camilla de Laurentis1, Fred Bteich2, Alexandru Szathmari2, Pierre Aurélien Beuriat2, Matthieu Vinchon2, Federico Di Rocco3
1Università degli Studi di Milano Bicocca, Milan, Italy; Department of Pediatric Neurosurgery, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
2Department of Pediatric Neurosurgery, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
3Claude Bernard Lyon 1 University, Lyon, France; Department of Pediatric Neurosurgery, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
BACKGROUND AND AIM: Sodium fluorescein (SF) is currently considered a valid adjunct in the resection of high-grade brain lesions in adults. Experiences in pediatric groups and in low-grade lesions are still limited in literature.
METHOD: The study prospectively included all patients with tumoral lesions of brain and spine operated from September 2021 to June 2022 in the Pediatric Neurosurgery Unit of Hôpital Femme Mère Enfant, Lyon. We injected SF at the dose of 5 mg/kg just before positioning the patient. Surgery was performed using a YELLOW560 filter at crucial times. Possible adverse events were monitored and at the end of surgery the first operator completed a questionnaire on fluorescence perception and utility.
RESULTS: We included 38 patients (0.2–17.6 years old). Low-grade lesions were 25 (23 WHO grade I tumors, 2 benign mesenchymal lesions), high-grade lesions 12 (2 WHO grade III, 8 WHO grade IV, 2 malign mesenchymal tumors), and 1 lesion was unclassifiable. Location was supratentorial in 21 cases, infratentorial in 12, and spinal in 5. Only one case of late adverse reaction (hypotension) was noted, but causality could not be definitively determined, and no sequelae were registered.
SF enhancement was found in 34/38 cases (90%), but it did not add any further information to the standard white-light vision to allow distinction between tumor and healthy tissue in 14/38 (37%). However, a clear utility of SF emerged in 20/38 (53%) of the surgeries by helping in determining infiltration borders or individuating difficult-to-reach locations. In particular, the surgeon found SF a useful tool in low-grade tumors (60%,15/25), especially when infiltrating in nature.
CONCLUSIONS: Thanks to its safety profile and to its utility even in certain low-grade lesions, SF may often play a role as a valuable adjunctive tool in the pediatric neurosurgeon armamentarium.
Keywords: Sodium fluorescein, Low-grade tumors, High-grade tumors, Feasibility, Utility
FL-098
Innovation and technology
The Combination of Virtual Surgical Planning and the Use of a Mixed Reality Viewer and Patient-Specific 3D-Models for Patient Consultation in Complex Craniofacial Cases
Malte Ottenhausen1, Verena Fassl1, Julia Heider2
1Department of Neurosurgery, University Medical Center Mainz
2Department of Oral and Maxillofacial Surgery, University Medical Center Mainz
BACKGROUND AND AIM: The majority of patients with head shape anomalies due to craniosynostosis are presented within the first months of life, if presented later even single suture synostosis require extensive operations. Especially if the indication for surgery is mainly to prevent socialpsychological problems it is difficult for caregivers to balance the risk of the operation against the cosmetic result.
METHOD: We present our approach using VSP®solutions from Stryker in collaboration with 3D Systems to accurately plan the surgical procedure virtually with a 3D Systems Biomedical Engineer. We then transfer the data to Brainlab® Elements and present and discuss the preoperative CT scan and 3D photo as well as the virtually planned result interactively with the parents using the mixed reality viewer Magic Leap. During the operation we use patient-specific, disposable guides and splints to speed up the operation and achieve optimal results. Patients are followed up using 3D photography.
RESULTS: The possibility to demonstrate the expected results and the extent of the operation with the use of a Mixed Reality Viewer and Patient-Specific 3D models improves shared decision making.
CONCLUSIONS: The possibility to demonstrate the expected results and the extent of the operation with the use of a Mixed Reality Viewer and Patient-Specific 3D models improves shared decision making.
Keywords: Virtual surgical planing, Mixed reality viewer, 3D
FL-099
Innovation and technology
Laser Interstitial Thermal Therapy: preliminary results for the treatment of deeply seated brain tumors and focal epilepsies in children
Thomas Blauwblomme, Lelio Guida, Kevin Beccaria, Jeremy Peuchot, Marie Bourgeois, Rima Nabbout, Emma Losito, Nathalie Boddaert
Hôpital Universitaire Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France
BACKGROUND AND AIM: Laser Interstitial Thermal Therapy has emerged in the last decade as an innovative, successful minimally invasive surgical tool for the ablation of brain lesions. However it has been available in Europe only recently. Here, we wish to analyze our preliminary results in 14 children with deeply seated WHO grade I brain tumors or malformations of cortical development in term of clinical and radiological outcome.
METHOD: Monocentric retrospective study of a prospective database of 14 children consecutively treated with LITT in Necker. Surgery was performed with the VISUALASE system under MRI control, after robotic stereotactic placement of the laser fiber. We reviewed medical files and radiological imaging.
RESULTS: 14 children (16 procedures) were operated between February 2021 and may 2022 (M/F ratio = 1, mean age 10.6 yo;sd 3.9y). Indications for surgery were oncology in 3 cases (refractory to chemotherapy), and epilepsy surgery in 11 cases (tumor related epilepsy n = 5, FCD after SEEG recording n = 5, hypothalamic hamartoma n = 1). Two children had previous surgery (incomplete resection n = 1, stereotactic biopsy n = 1). Lesion localization was: left mesial temporo occipital (calcarine sulcus n = 2, fusiform gyrus n = 2), left insular cortex ( whole insula n = 1, anterior insula n = 2), left cingulum (n = 3), basal ganglia (n = 1), mesencephalon (n = 1), hypothalamus (n = 1). There were 2 perioperative complications: transient hemiparesis (insular case) and hydrocephalus (midbrain tumor) however no patients had permanent deficits. With a mean follow up of 7 months (sd 4.7 months) we noted: resolution of symptoms in 3/3 tumor cases, control of seizures (Engel Ia) in 10/12 cases. MRI evolution displayed after 3 months: a central T2 hypo intensity with a peripheral hyper T2 rim for MCD/hamartoma, and volume reduction in all tumor cases along reduction of the contrast enhancement.
CONCLUSIONS: This preliminary series shows that LITT is safe and efficient for children with deeply seated brain lesions both for oncologic and epilepsy treatments.
Keywords: Laser, LITT, Oncology, Epilepsy
FL-100
Neurotrauma/Critical Care
Diffusion-tensor imaging study of peadiatric acute mTBI
Andrei Manzhurtsev1, Maxim Ublinskiy2, Tolib Akhadov3, Natalia Semenova1
1Clinical and Research Institute of Emergency Pediatric Surgery and Trauma
2Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences
3Moscow State University
BACKGROUND AND AIM: Computed tomography and magnetic resonance imaging (MRI) are not sensitive to mild traumatic brain injury (mTBI). However, mTBI may cause changes in cerebral microstructure that could be found using diffusion tensor imaging (DTI). The aim of this study is to reveal possible microstructural disorders in grey and white cerebral matters of children in the acute phase of mTBI (no more than 72 h), not accompanied by any structural brain injury.
METHOD: 11 healthy subjects and 11 patients with mTBI (up to 41 + 19 h since the injury), mean age 16 + 2. Philips Achieva dStream 3.0 T and 32-channel SENSE head coil were used. The standard TBI MRI protocol was applied. No pathological changes in brain tissue of any subject were found.
DTI was performed in 32 directions and was processed in Philips Intellispace Portal software. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained in corpus callosum (CC), corticospinal tract (CST) and in thalamus.
Statistical analysis was performed in STATISTICA 12. The Mann–Whitney criterion was used to reveal the significance of group differences, p-value < 0.05 was considered significant.
RESULTS: FA and ADC measured in thalamus are sensitive to acute mTBI: FA is increased and ADC decreases. The trend to the FA increase in corpus callosum in mTBI group and the absence of any changes in this parameter in corticospinal tract were observed. ADC in both CC and CST is unchanged.
CONCLUSIONS: The results of this study signify the presence of microstructural damage in thalamus. The changes in diffusion parameters arise from the cytotoxic swelling that happens because of the alterations in metabolic processes caused by the traumatic impact. The trend to the growth of FA revealed in this work may witness for the process of microstructural damage “maturation”, causing these changes to be observed as significant at a later stage after injury.
Keywords: DTI, mTBI
FL-101
Neurotrauma/Critical Care
Safety and effectiveness of TINS (Trauma Infant Neurological Score) used by Pediatricians in the community primary care hospital in evaluating Infants with Head Injury
Liana Beni Adani, Nechama Sharon, Lucio Segal, Michael Ben Akun
Pediatric Division, Korall Children's Medical Center, Natanya, Israel; Assuta Medical Centers, Tel-Aviv, Israel
BACKGROUND AND AIM: Importance: Traumatic brain injury (TBI) is the major cause of disability and death among the younger population and Head trauma (HT) may be responsible for secondary and late brain damage. However, most infants will suffer from non-life threatening mild or moderate HT occurring in the community and will be evaluated by pediatricians in clinics or community hospitals. Minor falls, repetitive head injuries of the “starting to walk” infant, “unwitnessed” mechanism of trauma, shaken baby syndrome and “occult child abuse” are only few mechanisms that differentiate infants from older children. On the other hand, “defensive medicine” in developed countries often leads to unnecessary Brain Imaging (mainly CT), or transfer of infant to a tertiary care hospital in cases where conservative treatment and not neurosurgical intervention will be advocated. AIM: to validate TINS as an effective and reliable clinical tool for evaluating HT in infants and for decision making in the primary care community hospitals.
METHOD: Prospective study, in a primary care community hospital serving a population of 400,000 people. Case managers were pediatricians, with stand-by Senior Pediatric Neurosurgeonavailable 24/7 for Telemedicine or WhatsUp consultation. All CT scans performed were revised by neurosurgeon and senior radiologist. 200 Infants age < 2y were enrolled according to IRB approved protocol. TINS parameters (picture) clinical and radiological data were recorded, with follow-up at 1 and 12 months after HT.
RESULTS: TINS was reported by all pediatricians a “user-friendly” and practical tool in quick evaluation of infants in the pediatric emergency room of a primary care community hospital. 103 boys (51.5%) and 97 girls, age 11 + 6.6 months (median 11) (1- day to 24 months). TINS scored 1–3 in this population. CT was abnormal in 15, Follow-up (early/late) did not show focal neurological deficit.
CONCLUSIONS: TINS can be safely, easily and effectively used by Pediatricians in decision making for Infant-Head-Trauma.
Keywords: Tins, Infants, Head truma, Pediatric injury, CT
FL-102
Epilepsy
Chloride deregulation in Focal Cortical Dysplasia type 2
Naziha Bakouh1, Reyes Castano2, Cerina Chhuon3, Sorana Ciuria2, Alice Metais4, Giulia Barcia2, Emma Losito1, Anna Kaminska1, Marie Bourgeois1, Rima Nabbout1, Chiara Guerrera3, Edor Kabashi2, Thomas Blauwblomme1
1Hôpital Universitaire Necker Enfants Malades, APHP, Université de Paris Centre, Paris, France
2INSERM U1163. Imagine Institute, Paris, Franc
3Proteomic Plateform, SFR Necker, INSERM US 24
4GHU Sainte Anne, Paris, France
BACKGROUND AND AIM: Focal cortical dysplasia type II (FCDII) are emblematic malformations of cerebral cortical development associated with epilepsy in children. Somatic mutations in the PI3/AKT/mTOR pathways have been identified in FCD Type II, and recently we showed GABAergic dysfunction secondary to abnormal expression of chloride co-transporters (CCC) NKCC1 and KCC2. However, the pathways linking the genetic alterations to functional abnormalities and altered physiological excitability are missing.
Here, we investigate a possible link between mTOR activation, and CCC deregulation through abnormal control of the WNK1/SPAK/OSR pathway.
METHOD: Ex vivo electrophysiological recordings were performed with Microelectrode arrays (MEA) in acute human cortical slices from pediatric patients operated of FCDII. The physical interactions between PI3K/AKT/mTOR and WNK1/SPAK/OSR1 proteins were investigated by co-immunoprecipitation. Expression studies were completed by western blot.
RESULTS: First, we recorded spontaneous interictal spikes from human FCDII slices incubated with artificial cerebrospinal fluid (ACSF); they were abolished after administration of mTOR inhibitors demonstrating the involvement of mTOR pathway in the occurrence of epileptic activity. Second, we revealed a physical interaction between mTOR and mSIN1 of mTORC2 with WNK1 and SPAK/OSR1 respectively; consequently mTORC2 increases the activation and the degree of phosphorylation of WNK1/SPAK/OSR1. Third, western blot analysis showed reduced levels of KCC2/NKCC1 ratio in FCD cortical slices as compared to the controls. Interestingly, inhibition of WNK-SPAK kinases with Staurosporine and N-ethylmalemide (dephosphorylate the Thr233 and Ser373 of SPAK) induced an increased KCC2 expression and rescued the KCC2/NKCC1 ratio in FCDII, along with blocage of epileptic activities in FCD cortical slices on MEA recordings. Eventually, treatment with mTOR inhibitors restored the KCC2/NKCC1 ratio along with a decreased activity of WNK/SPAK/OSR.
CONCLUSIONS: This study shows that mutations of mTOR pathway activates WNK/SPAK/OSR kinases, resulting in deregulation of cation chloride cotransporters in FCD, supporting epileptogenesis through dysfunction of GABAa inhibition.
Keywords: Focal cortical dysplasia, GABA, Chloride cotransporters, Proteomics, Epileptogenicity
FL-103
Functional
Impact of Selective Dorsal Rhizotomy on Upper Extremity Functional Independence in Children with Cerebral Palsy: A Case Series
Elise J Yoon1, Erika Erlandson2, Melisa Concepcion3, Sarah Hoelton3, Tess Woehrlen3, Doris Tong1, Neena I Marupudi4
1Division of Neurosurgery, Michigan State University College of Human Medicine, Ascension Providence Hospital, Southfield, Michigan, United States of America
2Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine, Sparrow Hospital, East Lansing, Michigan, United States of America
3Department of Physical Medicine and Rehabilitation, Wayne State University, Rehabilitation Institute of Michigan, Detroit, Michigan, United States of America
4Department of Pediatric Neurosurgery, Wayne State University, Children’s Hospital of Michigan, Detroit, Michigan, United States of America
BACKGROUND AND AIM: Selective dorsal rhizotomy (SDR) is performed in children with cerebral palsy to reduce lower-extremity spasticity. Although nerve rootlet transection is limited to lumbosacral rootlets in SDR, unexpected observations of upper extremity (UE) spasticity improvements have been reported. These secondary suprasegmental effects on tone have been qualitatively or quantitatively described in select UE muscle groups in a number of case series. However, studies on postoperative improvement in UE function is limited. We present a comprehensive assessment of the effect of SDR on upper extremity function and independence in activities-of-daily-living (ADL).
METHOD: Data were collected on consecutive patients undergoing SDR from December 2017 to February 2022 at a single institution. Inclusion criteria were age of 3–11, baseline Gross-Motor-Function-Classification-System (GMFCS) score of I-IV, and interval functional independence data. All patients underwent SDR via minimally-invasive single-level or interlaminar approach. Patients were evaluated preoperatively and postoperatively at 3-month intervals by a multidisciplinary team. We analyzed UE function, lower extremity (LE) function, and independence in ADL using the Functional Independence Measure for Children (WeeFIM) instrument. One-way ANOVA and longitudinal analysis were used to analyze WeeFIM scores over time.
RESULTS: Thirty-two patients underwent SDR from 2017 to 2022. Twenty-seven patients met inclusion criteria; 5 patients were excluded due to lack of interval WeeFIM data. There were significant differences between timepoints in 3 WeeFIM categories. There was significant improvement in ADLs from baseline to 6 months (34.41 ± 5.46 versus 42.72 ± 10.64, p = < 0.001), LE dressing scores from baseline to 12 months (23.26 ± 11.60 versus 31.44 ± 9.71, p = 0.027), and baseline to 24 months (23.26 ± 11.60 versus 33.29 ± 11.18, p = 0.008).
CONCLUSIONS: Along with effectively improving lower extremity spasticity and function, SDR results in significant improvements in UE function and ADLs. The building evidence on suprasegmental effects may lead to expanded long-term functional benefits with SDR.
Keywords: Activities of daily living, Cerebral palsy, Functional independence, Rhizotomy
FL-104
Functional
Improvement of Breath Control after Selective Dorsal Rhizotomy in Children with Cerebral Palsy
Elise J Yoon1, Erika Erlandson2, Melisa Concepcion3, Sarah Choss3, Tess Woehrlen3, Doris Tong1, Neena I Marupudi4
1Division of Neurosurgery, Michigan State University College of Human Medicine, Ascension Providence Hospital, Southfield, Michigan, United States of America
2Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine, Sparrow Hospital, East Lansing, Michigan, United States of America
3Department of Physical Medicine and Rehabilitation, Wayne State University, Rehabilitation Institute of Michigan, Detroit, Michigan, United States of America
4Department of Pediatric Neurosurgery, Wayne State University, Children’s Hospital of Michigan, Detroit, Michigan, United States of America
BACKGROUND AND AIM: Selective dorsal rhizotomy (SDR) is performed in children with cerebral palsy to reduce spasticity. In addition to tone reduction and functional improvement, providers and caregivers anecdotally noted improvement in breath control and speech after SDR. Therefore, we sought to systematically evaluate for functional improvements in breath control and speech.
METHOD: Data were collected on consecutive patients who underwent SDR from December 2017 to February 2022 at a single institution. Inclusion criteria were age of 3–11, baseline Gross-Motor-Function-Classification-System (GMFCS) score of I-IV, and presence of both baseline and 12-month postoperative breath control data. All patients underwent SDR via minimally-invasive single-level or interlaminar approach. Breath control was measured by maximum phonation time (MPT), which assesses how long a patient can sustain an isolated vowel without a substantial decrease in volume. Patients were evaluated preoperatively and postoperatively at 3-month intervals by a multidisciplinary team including Neurosurgery, Physical Medicine and Rehabilitation, Speech Therapy, Physical Therapy, and Occupational Therapy. A paired t-test was used to compare baseline and 12-month MPT values. Longitudinal analysis was performed to assess the temporal change at the individual level.
RESULTS: Thirty-two patients underwent SDR from 2017 to 2022. Fifteen patients were excluded due to lack of interval breath control data. Seventeen patients had both baseline and 12-month MPT values. Thirteen patients increased in their interval MPT value; 2 remained the same, and 2 decreased. There was a statistically significant improvement in mean MPT values from baseline to 12 months after surgery (5.52 ± 2.86 versus 7.90 ± 5.03, p = 0.012).
CONCLUSIONS: To our knowledge, this is the first study reporting quantitative data demonstrating a significant improvement in breath control after SDR. Improvements in MPT may correlate with improvements in long-term breathing/lung function, endurance, communication, and cognitive skills. These findings may support counseling provided to caregivers on the expanded benefits of minimally-invasive SDR surgery.
Keywords: Breath control, Cerebral palsy, Rhizotomy
FL-105
Functional
Review of the targeting accuracy of robot-assisted deep brain stimulation electrode implantation in paediatric patients with use of Renishaw 3D Neurolocate module
Raenette David1, Maria Rosaria Scala2, Jonathan Ellenbogen1
1Department of Neurosurgery, Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom
2Department of Neurosciences and Reproductive and Odontostomatological Sciences, Division of Neurosurgery, University of Napoli Federico II, Naples, Italy
BACKGROUND AND AIM: Renishaw 3D neurolocate module is a frameless patient registration module that is designed for use with the Renishaw neuromate stereotactic robot. The long-term electrical stimulation via deep brain electrode implantation of the globus pallidus internus and subthalamic nuclei is particularly successful in a select group of pediatric patients. This study aims to provide an update on the review of targeting accuracy of deep brain stimulation (DBS) electrode implantation, in a single centre, comparing the use of standard frame-based techniques versus the Renishaw 3D neurolocate module.
METHOD: Twenty (20) patients underwent implantation of DBS electrodes under general anaesthesia during the period August 2018 through April 2022. All patients underwent robotic-assisted stereotactic implantation of the DBS electrodes with intraoperative 3D scanner confirmation of the final electrode position. These coordinates were compared to the planned entry and target; with attention to depth, radial, directional and absolute errors, in addition to Euclidean distance.
RESULTS: Of the forty (40) DBS electrode implantations, 55% employed Renishaw 3D neurolocate technology. 85% of targets were globus pallidus internus and the remaining 15% the subthalamic nucleus. The mean age was 11.0 years (range from 4 – 18 years), of which 75% were male. The median absolute errors in x-,y-,z- axes were 0.45 mm, 0.7 mm and 0.8 mm respectively with use of the Renishaw 3D neurolocate versus 0.4 mm, 0.8 mm and 1.3 mm with standard techniques. The median Euclidean distance from the planned target to the actual electrode position with Renishaw 3D neurolocate module was 1.55 mm vs standard frame-based techniques at 1.70 mm. No major perioperative complications occurred.
CONCLUSIONS: Stereotactic robot-assisted DBS implantation with the Renishaw 3D neurolocate module is safe for use in the pediatric population with good surgical accuracy. Renishaw 3D neurolocate module for robotic DBS surgery allows compatibility with the intraoperative 3D scanner and has the potential to improve surgical targeting accuracy and patient comfort.
Keywords: Neurolocate, DBS, Renishaw, Globus pallidus internus, Paediatrics
FL-106
Epilepsy
Responsive neurostimulation for pediatric epilepsy
Sandi Lam, Melissa Lopresti, Jeffrey Raskin
Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, USA; Division of Pediatric Neurosurgery, Lurie Children's Hospital, Chicago, USA
BACKGROUND AND AIM: Responsive neurostimulation is approved by the United States Food and Drug Agency for implantation as a medical device for neuromodulation treatment for drug-resistant epilepsy. The device is approved for patients over the age of 18 years. Use in children is relatively rare. We describe our experience with a series of 7 children treated with responsive neurostimulation.
METHOD: A retrospective chart review was conducted. Patient demographics, clinical characteristics, surgical details, and outcomes were recorded.
RESULTS: 7 pediatric patients, ages 7—17 years old, underwent placement of RNS devices for drug resistant epilepsy. All patients were not resective surgical candidates. 6/7 patients had phase 2 invasive intracranial electrode monitoring: of the 6, 3 were with stereoEEG and 3 were with subdural grid and strip electrodes. 1 patient had one-step RNS placement based on preoperative workup. 6/7 phase 2 patients went on to have placement of RNS. Postoperative follow up time ranged from 6 to 15 months. 3/7 patients (43%) had over 90% seizure control, 3/7 (43%) had over 50% seizure improvement, and 1/7 (14%) had 25–50% improvement. There were no intraoperative or postoperative complications or adverse events.
CONCLUSIONS: Responsive neurostimulation in this pediatric patient series is safe and provides possibility of improved seizure control in children who are otherwise not candidates for resective epilepsy surgery.
Keywords: Pediatric epilepsy, Epilepsy surgery, Neuromodulation, Responsive neurostimulation, RNS
FL-107
Functional
Microsurgical DREZotomy as an alternative to Intrathecal baclofen pump for decreasing tone in spastic cerebral palsy
Nishant Goyal
All India Institute of Medical Sciences, Rishikesh, India
BACKGROUND AND AIM: Intra-thecal baclofen pump(ITB)for severe refractory spastic cerebral palsy is not a viable option in resource-constraint settings. Therefore, authors assessed the role of microsurgical DREZotomy(MDT) as an alternative for patients in whom the circumstances did not allow ITB placement.
METHOD: A prospective clinical study was conducted from August2016 to July2020.All patients of spastic cerebral palsy(with III-IV Ashworth grade)who underwent MDT were included.Pre-operative and post-operative Ashworth grade and GMFCS level were assessed along with any change in power,sensation and bladder functions post-operatively.At last follow-up,patients’ main care-provider was asked to rate the effect of surgery(on scale of 0–5)on ease of providing care related to six activities of daily living.
RESULTS: Seven patients(5 males,2 females)of spastic cerebral palsy with age range 6–21 years underwent MDT over the study period.Six patients had spastic diplegia and one had spastic hemiplegia.Preoperative Ashworth grade in all patients was 3–4 in various involved muscle groups.Four patients with spastic diplegia underwent MDT at L3-S1 level bilaterally,two patients with spastic diplegia and spastic bladder underwent MDT at L3-S4 level bilaterally whereas one patient with right-sided spastic hemiplegia underwent MDT at C5-T1 level and L3-S1 level on the right side.Post-operative Ashworth grade in all patients improved to 0–1.The improvement in mean Ashworth grade was from 3.14 + 0.378 preoperatively to 0.29 + 0.488(p-value = 0.000).Most care-providers reported improvement in their ability to do physiotherapy, positioning, clothing, ambulation and to maintain patient’s personal hygiene.Care-providers of six patients reported that they were likely to recommend MDT to another similar patient.
CONCLUSIONS: MDT is a cost-effective tool in deceasing limb spasticity in spastic cerebral palsy especially for those who cannot afford ITB placement.
Keywords: Microsurgical DREZotomy (MDT), Intra-thecal baclofen (ITB) pump, Spastic cerebral palsy, Modified ashworth grade, GMFCS (Gross motor functional classification scale)
FL-108
Epilepsy
Single-Institution Comparative Study of MR-guided Laser Interstitial Thermal Therapy (MRgLITT) Versus Open Corpus Callosotomy
Jeffrey Steven Raskin1,2, Josue Ordaz3, Hailey Budnick3, Ramana Vishnubhotla5, Anthony Alfonso4, Quiting Wen5, Rupa Radhakrishnan5
1Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA
2Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
3Department of Neurological surgery, Indiana University, Indianapolis, Indiana, USA
4School of medicine, Indiana University, Indianapolis, Indiana, USA
5Department of Radiology, Indiana University, Indianapolis, Indiana, USA
BACKGROUND AND AIM: Open corpus callosotomy (CC) poses a higher risk of perioperative morbidity and hydrocephalus than MR-guided laser interstitial thermal therapy (MRgLITT) for treatment of drop and generalized seizures without documented superiority. We present a single-institution comparison between CC and MRgLITT.
METHOD: A two-year retrospective review was performed on patients at our institution who underwent CC and MRgLITT (January 2019-January 2021). Demographics, surgical outcome data, hospital costs and interhemispheric connectivity with diffusion tensor imaging (DTI) were compared (two-tailed t-test at α = 0.05).
RESULTS: The average age in years was 9.3 and 11.4 for CC (n = 4) and MRgLITT (n = 9), respectively. Preoperative drop seizure frequency was higher in CC (25 vs 14.5 seizures/day P = 0.59). At 10-month follow-up, the reduction in drop seizure frequency was better in CC, but not significantly (93.8% vs 64.3%, P = 0.21). The extent of ablation of the corpus callosum did not correlate with seizure reduction (Pearson’s Coefficient = 0.09), although an inverse correlation between interhemispheric connectivity change (DTI analysis) and drop seizure frequency reduction was noted (Pearson’s = -0.97). Total hospital cost was lower in MRgLITT ($67,754 vs $107,111, P = 0.004), attributed to lower ICU (1.1 vs 4 days, P = 0.004) and total hospital stay (1.8 vs 10.5 days, P = 0.0001). Furthermore, post-operative hydrocephalus present in 75% of patients in the CC group compared with zero in the MRgLITT group.
CONCLUSIONS: The results indicate MRgLITT is potentially a safer and cost-effective alternative to the traditional CC with therapeutic equipoise. This study is limited by the number of patients hence further patient enrollment or multicenter study is warranted.
Keywords: Epilepsy, LITT, Laser surgery
FL-109
Epilepsy
Ketogenic diet for management of refractory epilepsy: Cost effectiveness of a dietary subvention program
Adrian Caceres1, Priscilla Pereira Angulo2, Dina Arrieta Vega3, Monica Chavez Lavagni4, Kattia Rojas Leon5, Katherine Chan Grant6
1Epilepsy Surgery/Monitoring unit, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
2Epilepsy Surgery/Monitoring unit, Nutrition Department, National Childrens Hospital "Dr. Carlos Saenz Herrera", San Jose, Costa Rica
3Rheumatology Department, Hospital Mexico, San Jose, Costa Rica
4Dermatology Department, Hospital San Juan de Dios, San Jose, Costa Rica
5Psychology Department, Hospital San Vicente de Paul, Heredia, Costa Rica
6Colegio de Medicos y Cirujanos, San Jose, Costa Rica
BACKGROUND AND AIM: This study performed a clinical and economic evaluation among families enrolled in the Ketogenic diet program (KDP) in order to define the cost of each hospital admission related to status epilepticus (ER, ICU, general ward) and to contrapose these expenditures against the cost of maintaining the diet based on an average monthly expenditure by the health system and families of these patients.
METHOD: Descriptive retrospective study performed in 15 patients from the KDP from 2015 to 2020. We determined: the clinical and economic background of patients, cost of treating a decompensated refractory epilepsy patient in our institution, the institutional cost of treatment in KDP patients, the family monthly cost of maintaining an appropriate menu according to the KDP, analyzing cost/benefit ratio for patients and our health institution.
RESULTS: 15 patients were evaluated, ages from 4 to 13 Y, 11 (74%) were male and 4 (26%) female. The monthly pharmacological treatment of this group varied from $67 to $450 USD and the average monthly cost of purchasing nutritional items for maintenance of the KDP was between $225 and $257 USD.
100% of the patients showed a significant improvement in their clinical status, 2 are seizure free and 80% reduced their visits to the ER. Those who did require ER evaluation had 60% lesser admissions.
The average cost of ER evaluation and admission was calculated at $2159 USD, increasing to $4522 and $11,585 USD for patients requiring hospital and ICU admission per event.
CONCLUSIONS: Based on this cost analysis, the monthly subvention of a KDP for the treatment of refractory epilepsy is not only cost effective representing a 11.8, 5.6 and 2,2% of the cost of ER evaluation and treatment, hospital admission or ICU admission respectively, but also decreases the number of ER visits and hospital admissions by 80 and 60% respectively.
Keywords: Refractory epilepsy, Ketogenic diet, Seizure control, Cost ratio benefit, Status epilepticus, Epilepsy surgery
FL-110
Epilepsy
Non-pharmacological treatment options of refractive epilepsy in subcortical band heterotopia
Arthur R Kurzbuch, Benjamin J Cooper, Jonathan R Ellenbogen
Department of Neurosurgery, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
BACKGROUND AND AIM: Doublecortin (DCX) is a neuronal migration protein encoded by the DCX gene.
DCX-related and X-linked neuronal migration disorders comprise classic lissencephaly and subcortical band heterotopia (SBH) which primarily affects females and is often associated with refractory epilepsy. SBH is also also known as double cortex and subcortical laminar heterotopia.
The aim of this study is to review the literature for non-pharmacological treatment options of refractive epilepsy in SBH.
METHOD: Following PRISMA guidelines we performed a systematic review in Scopus and PubMed databases and describe a case report, managed at our institution.
RESULTS: Twenty-six patients who underwent 29 non-pharmacological treatments were reported.
Mean age at seizure onset: 6.5 years (range 0.2–23) with female sex predilection (5.25:1). Mean age at invasive or non-invasive treatment: 21.5 years (range 6.5–51).
Ten patients underwent corpus callosotomy, 8 had temporal lobectomy with amygdalohippocampectomy. Three patients had focal cortical resection. Two patients respectively had multiple subpial transections, insertion of a vagal nerve stimulator, or deep brain stimulation of the bilateral anterior nuclei of the thalamus. One patient underwent responsive focal neurostimulation, another had transcutaneous stimulation of the vagal nerve.
Sixteen patients reported a reduction or the disappearance of the seizures, 1 patient had no improvement. The outcome of 2 patients was Class I, of 1 patient Class II, of 1 patient Class III, and of 5 patients Class IV according to the Engel Epilepsy Surgery Outcome Scale.
CONCLUSIONS: Corpus callosotomy and temporal lobectomy with amygdalohippocampectomy have been the predominant non-pharmacological treatment. The small number of cases reported precludes drawing a firm conclusion as to which non-pharmacological treatment is the superior option for refractive epilepsy in patients with SBH. The future relevance of procedures such as deep brain stimulation, responsive focal neurostimulation, transcutaneous stimulation of the vagal nerve, and also stereotactic laser interstitial thermal therapy remain to be seen.
Keywords: Subcortical band heterotopia, Double cortex, Subcortical laminar heterotopia, Epilepsy, Seizure, Treatment
FL-111
Epilepsy
Early surgical approaches in pediatric epilepsy – a systematic review and meta-analysis
Nicole Alexandra Frank1, Ladina Greuter1, Raphael Guzman2, Jehuda Soleman2
1Department of Neurosurgery, University Hospital of Basel, Basel, Switzerland
2Department of Neurosurgery, University Hospital of Basel, Basel, Switzerland; Department of Pediatric Neurosurgery, University Children`s Hospital of Basel; Faculty of Medicine, University of Basel, Basel, Switzerland
BACKGROUND AND AIM: Pediatric seizures potentially have a severe negative impact on child’s development. Drug-resistant epilepsy occurs in up to 30% of children suffering from seizures and about 10% qualify for surgical treatment. The aim of this systematic review and meta-analysis is to analyze the potential benefit of early epilepsy surgery in children concerning primarily seizure and developmental outcome.
METHOD: PubMed and Embase databases were searched using a systematic search strategy to identify studies on pediatric epilepsy surgery under 3 years from their inception up to 2022. Outcome measures were seizure outcome, postoperative complications, seizure onset and reduction rate of antiepileptic drugs. A meta-analysis was thereafter performed for all included cohort studies. A p-value of < 0.05 was considered as statistically significant.
RESULTS: A total of 532 patients were analyzed with 401 patients (75%) receiving resective or disconnective surgery under the age of 3 years and 80 patients (15%) receiving surgery older than 3 years. The remaining 51 patients (9%) underwent VNS-implantation. Pooled outcome analysis for resective/disconnective surgery showed favorable outcome in 68% (95% CI [0.63; 0.73]), while comparative analysis between the age groups showed no significant difference (77% early group and 75% late group; RR 1.03, 95% CI [0.73; 1.46] p = 0.75). Favorable outcome for the VNS-cohort was seen in 52%, 65% in the early and 45.1% in the late group (RR 1.4393, 95% CI [0.87; 2.4] z = 1.42, p = 0.16). Developmental outcome was improved in 26%, 8.2% remained stable. Morbidity rate was moderate and showed no significant difference comparing the age groups, overall surgical mortality rate was very low (0.1%).
CONCLUSIONS: Epilepsy surgery in pediatric age, especially under the age of 3 years, is a feasible and safe way to treat intractable epilepsy and therefore to potentially prevent severe developmental and cognitive deterioration. Further comparative studies of prospective nature should be the focus of future studies.
Keywords: Pediatric epilepsy surgery, Intractable epilepsy, Drug-resistant epilepsy, Pediatric neurosurgery
FL-112
Epilepsy
Spatiotemporal Mapping and Characterization of Oculomotor Control in the Pediatric Frontal Eye Fields
Stephano J. Chang1, Mohammad Mashayekhi2, Hetshree Joshi1, Ash Singhal3, Mandeep Tamber3
1Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver, Canada
2Faculty of Medicine, University of British Columbia, Vancouver, Canada
3Faculty of Medicine and the Division of Neurosurgery, University of British Columbia, Vancouver, Canada
BACKGROUND AND AIM: The frontal eye fields (FEFs) are linked to oculomotor control and hypothesized to reside in the prefrontal cortex, where electrical stimulation reportedly evokes contraversive eye movements. The exact location and function of the FEFs in humans is controversial with studies implicating multiple putative regions, including the posterior middle frontal gyrus and the inferior precentral gyrus. Stereo-electroencephalography (SEEG) is a minimally invasive technique used to guide epilepsy surgery. It provides a unique opportunity to collect human neurophysiological data outside of the operating room and has been used by other groups to advance our understanding of specific brain functions.
METHOD: Four pediatric subjects undergoing non-lesional epilepsy workup were enrolled into this prospective, IRB-approved study, and received brain MRI prior to SEEG implantation, followed by post-operative CT head for electrode localization. Post-operative stimulation testing and SEEG recordings were performed along with time-aligned video of the subjects’ eyes while performing gaze-related tasks.
RESULTS: Stimulation testing elicited contraversive head turning with or without eye deviation, and hemifacial spasm, depending on the site of stimulation. Low-threshold sites eliciting these stereotyped movements were located just deep to the inferior precentral gyrus. Stimulation of sites in the posterior middle frontal gyrus did not elicit eye deviation movements in our two subjects in the post-operative setting. Preliminary univariate decoding of raw SEEG from electrodes in the inferior precentral gyrus revealed high correlations to eye movements at lower frequencies, which likely represent relevant features for eye movement control and will likely be an important component of multivariate decoding processes.
CONCLUSIONS: Our findings suggest that the FEFs are located more posteriorly than widely held, involving the motor cortex. Further testing in pediatric and adult subjects is warranted to confirm this hypothesis and test for differences in these populations.
Keywords: Frontal eye fields, Stereo-electroencephalography, Electrical mapping, Oculomotion, Neural decoding
FL-113
Dysraphism
5-year outcomes following Selective Dorsal Rhizotomy – the Leeds experience
Rebecca S Chave Cox, Kate Mccune, Katie Davis, Kit Tzu Tang, Shona Michael, Rajib Lodh, John R Goodden
Leeds Teaching Hospitals Trust, UK
BACKGROUND AND AIM: Selective Dorsal Rhizotomy surgery aims to improve function and mobility through reduction in lower limb tone. In the UK it is offered to suitable patients who have spastic diplegia with GMFCS levels II-III and meet the NICE selection criteria. We present the long term (5 year) Quality of Life (QoL) outcomes from the first patients treated in our centre.
METHOD: The first SDR procedure was in October 2012. Post-operative outcomes are prospectively recorded using a spreadsheet database, > 150 patients treated to date.
SDR is performed by a single surgeon with the same technique (single level) and standardized 3-week post-operative physiotherapy regime. Intra-operative neurophysiology is always used. Patient selection criteria are: spastic diplegia with dynamic spasticity limiting function, no dystonia, typical MRI changes, GMFCS Level 2 or 3. Orthopaedic input is provided as required in line with NHS guidance.
All patients have standardised pre- & post-op assessments with 3D Gait Analysis, GMFM-66, Ashworth grading, muscle power & joint range of movement. Quality of Life (QoL) is assessed using the CPQoL questionnaire.
RESULTS: Overall 152 patients have been treated with SDR in Leeds, with 5-year follow-up assessments completed for > 70. Early post-operative results have previously been presented.
In this presentation we present the multi-modal outcomes for QoL, tone, power and function for patients with completed 5-year follow-up – mapping their progress since surgery. All patients have a reduction in tone after SDR. At 2-years post-operatively the mean improvement in GMFM is 11.66%, improving to 12.35% at 5-years.
There were no significant complications.
CONCLUSIONS: SDR is an effective treatment for carefully selected patients with cerebral palsy with spasticity mainly affecting the legs. Multi-modal assessments demonstrate improvements that have been sustained over initial 5-year follow up.
Keywords: Selective dorsal rhizotomy (sdr), Spasticity, Cerebral palsy, Outcome, Quality of life
Nursing Symposium Abstracts
Freeze preservation of cranial bones after decompressive craniectomy for future cranioplasty. Our experience
Dulce Karolina Martinez Gonzalez1, Oscar Guillermo Garcia Gonzalez2
1Nursing department, Universidad Autonoma de Aguascalientes, Aguascalientes, México
2Department of Pediatric Neurosurgery, Hospital Regional de Alta Especialidad del Bajio, Leon Guanajuato, México
BACKGROUND AND AIM: Decompressive craniectomy is routinely performed to treat intracranial hypertension refractory to medical therapy as a result of head trauma, cerebrovascular accident (CVA) or brain tumors. It is later followed by a cranioplasty procedure (CP) in the surviving patients, with autologous bone graft or other reconstructive materials is considered to repair the skull defect.
This retospective study reviews the cases of decompressive craniectomies followed by later cranioplasty undertaken in the author experience since 2013 and describes the method used for preservation of removed bone flaps for future cranioplasty. To clarify the clinical outcomes of cranioplasty with cryopreserved bone flaps and identify risk factors related to bone flap infection and resorption after cranioplasty with cryopreserved bone flaps.
METHOD: 6 patients (5 children) underwent decompressive craniotomies and delayed autologous cranioplasty since 2013. A protocol was designed to prepare the removed bone flaps for freeze preservation. After removal, the bone flaps were transferred to the blood bank of our institution within 4 h, gently rinsed using 1–3 L of sterile saline (0.9% NaCl) supplemented with antibiotics (amikacyn), then flaps were wrapped in two layers of sterile plastic coverage and preserved at –25/28.7 °C.
RESULTS: The patient’s population will be presented. Since 2013 we have performed 6 cranioplasties using freeze preserved autologous bone graft. The median time from craniectomy to cranioplasty was 62.5 days. Up to now, no case of infection, osteomyelitis or complete bone resorption following cranioplasty have occurred.
CONCLUSIONS: Freeze preservation of autologous bone grafts to reconstruct skull defects after decompressive craniectomy is a useful procedure and has a low revision or complication rate and led to the unnecessary use of synthetic prostheses and increased health care costs.
Keywords: Freeze preservation, Bone flaps, Craniotomy
Moya Moya Disease- Case Study
Shani S D1, Jayanand Sudhir B2
1Neurosurgery I C U, S C T I M T
2Department of Neurosurgery, S C T I M S T
BACKGROUND AND AIM: Moyamoya disease is a rare disease which cause progressive narrowing of the intracranial internal carotid arteries, resulting in reduced blood supply to brain, leading to strokes. It is a major cause of childhood stroke.
METHOD: A 10-year- boy presented with recurrent left hemispheric transient ischemic attack and seizures. On evaluation, the child was diagnosed as having bilateral Moyamoya disease. The child was prescribed antiplatelets and antiepileptics and advised to drink 2 L of water a day and to avoid dehydration. He was admitted for an elective revascularization surgery. Left side Superficial Temporal Artery (STA) to Middle Cerebral Artery (MCA) bypass with Encephaloduroarteriomyosynangiosis (EDAMS) was done. The child was monitored in the post-operative neurosurgery intensive care unit for one day for any post procedure complications. Child was encouraged to talk and express preferences in diet, dress and play materials among the given alternatives. Ambulated out of bed after six hours. Allowed to walk around as preferred. Parents were allowed to visit and spend time with the child.
RESULTS: Post-operative course was uneventful and the child was discharged on 6th post-operative day with instruction to continue antiplatelets and antiseizure medications. The nursing care challenges included positioning in the post operative period, maintain invasive devices, providing child with a sense of control, understanding child’s preferences and promoting autonomy and intensive care unit policies regarding visiting hours and family presence. The patient should be monitored for seizure, stroke transient ischemic events and wound infection. Strict vigilance and adherence to infection control practices are necessary. Early ambulation and early initiation of feeds are done to prevent complications.
CONCLUSIONS: The outcome of cerebral revascularization in Moyamoya disease is good, with reduction in ischemic events and seizures. Post-operative nursing care in neuro surgery unit is important in preventing complications and better outcome.
Keywords: Moyamoya disease, Encephaloduroarteriomyosynangiosis, Revascularization surgery, Carotid arteries, STA-MCA bypass, Nursing care
Utilizing a Clinical Pathway For Coordination of Care of Infants with Myelomeningocele
Ashley Kelly Birch
Boston Children's Hospital, Boston, Massachusetts USA
BACKGROUND AND AIM: As of 2013, approximately 1.61 infants out of 10,000 live births were born in Massachusetts with spina bifida, an increasing number are being transferred to our NICU. Due to the medical complexities of infants with Spina Bifida, a standardized guideline to direct tcare was needed.
AIM:
• To discuss the need for coordination of care for infants born with myelomeningocele related to the medical complexities.
• To discuss the clinical pathway and orderset created as a result of a collaboration between Neurosurgery and the NICU.
METHOD:
• A review of the literature and existing protocols and pathways at Boston Childrens Hospital was performed prior to creation of the clinical pathway.
• Collaboration of the NICU and Neurosurgery to determine the needs of infants born with myelomeningocele immediately after birth and during the course of their admission.
• Review of the clinical pathway by the QI team and clinical pathway committee followed by Publication and Distribution.
RESULTS: • NICU and neurosurgery teams collaborate by using the pathway and orderset.
• Consultations are requested as part of the orderset and therefore routine health maintence and consultations required for infants with myelomeningocele are addressed early in course of treatment.
• Use of antibiotics and preop dressings have been standardized.
• The use of the clinical pathway offers clinical guidance and standardization for speciality clinicians based on evidence.
• Supports a seamless transition from the inpatient team to providers within the multidisciplinary clinic.
CONCLUSIONS: Due to the many medical complexities of infants with Spina Bifida, a standardized guideline to direct the management of care was needed. The complexities of care include management of the lesion, bladder management, bowel management, infection control, coordination of consultations and routine health maintence. Creating this streamlined approach did improve care for these patients by ensuring that the require consultations happened automatically, without long wait times and encouraged continuous collaboration of the specialties.
Keywords: Spina bifida, NICU, Pathway, Standardization, Nursing
Implementation of Multidisciplinary Spina Bifida Clinics in Low-and-Middle income Countries and the Important Role For Nurses in Maintaining Them
Ashley Kelly Birch
Boston Children's Hospital, Boston, Massachusetts USA
BACKGROUND AND AIM: Neural tube defects occur in approximately 300,000 neonates worldwide annually and are a leading cause of death and disability. They require frequent monitoring by neurosurgery, orthopedics, urology and physical therapy to maintain their quality of life and prevent illness. Due to the medical complexities of patients with Spina Bifida, the most comprehensive way to care for these children is through a multidisciplinary clinic which can provide coordination of care with nurses in a leadership role.
METHOD: A review of the literature was completed to accumulate all evidence regarding existing multidisciplinary clinics for patients with spina bifida globally.
• A review of the literature to establish the benefit of multidisciplinary clinics in care for patients with medical complexities, including spina bifida association and WHO recommendations.
• A review of the literature to establish the current utilization of nurses in existing clinics.
RESULTS: • A coordinator, such as a nurse coordinator allows for good communication and collaboration between the key providers.
• There has not been a consensus on what specialties should be included in these clinics in different socioeconomic settings.
• Access and integration of services are a main goal of multidisciplinary clinics, to allow for unfragmented essential care and improve outcomes.
CONCLUSIONS: • Due to the many medical complexities of infants with Spina Bifida, multidisciplinary clinics are needed, they increase access to care, decrease duplication of services, can reduce cost and improve outcomes.
• Care coordinators are a vital part of these clinics to allow for adequate coordination of care, this role can be filled by nurses.
• Establishment of standards for included specialties and services in various settings is required.
• In limited resource settings it is more difficult to establish these clinics, further research must be done to determine the needs in LMICs and recommendations on how to implement this method of care.
Keywords: Spina bifida, Multidisciplinary care, Nursing
Medical tourism in Pediatric Neurosurgery during the Covid pandemic: An observational study of a complex situation
Orna Friedman
Department of Pediatric Neurosurgery, Dana Children’s Hospital, Tel Aviv, Israel
During previous ISPN gathering, we have presented our nursing perspective of Medical Tourism (MT) in Pediatric Neurosurgery and coined it as “lost in translation..”
During Covid times, in addition to the local hospital chaos and uncertainty, it has become exceedingly rare to travel in general, and especially to receive medical care in another country.
These difficulties came from state (country) regulations, hospital protocols, and combined medical challenges (e.g. Covid in a child with a brain tumor).
Despite these enormous obstacles, we managed to bring and treat a significant number of children requiring neurosurgical care.
In this study, we systematically analyzed the steps that we needed to overcome from our perspective and from the perspective of the courageous families.
Planning intraoperative nursing assistance in the process of separation of craniopaguus siamese twins. An experience report
Allison Roberto Silva, Hélio Rubens Machado, Marcelo Volpon Santos
Department of Pediatric Neurosurgery, São Paulo University. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Brazil
INTRODUCTION: Siamese twins with anatomical conjugation by the head (craniopagus) are a rare condition in the history of medicine, only 28 attempts at separation in more than one stage were performed and of these, 03 successful cases occurred in Brazil. The multidisciplinary team for the separation of Craniópagus twins at HCFMRP-USP, takes on a new challenge in 2022 for the separation of craniopagus twins. OBJECTIVE: To describe the Nurse's activities for the planning of all stages and the performance of surgical procedures.
METHODOLOGY: This is an experience report, where the Nursing planning, the 3D simulations, the simulations in the operating room and the execution of the surgical steps of Craniopagus separation are performed.
RESULTS and DISCUSSION: The planning of the process is planned for five distinct surgical stages, the first stage of planning included the definition of the children's basic needs and the objectives of the surgical and clinical teams, which determined the Nursing Diagnoses and the necessary interventions to that the process becomes successful in its continuity. The following surgical steps will be planned using the first surgery as a support, as the staging is progressive and the evolution of children is concomitant.
CONCLUSION: For the separation process to be successful, nursing planning is essential, surgical simulations and clinical interventions for each stage will influence the final result and the children's recovery.
Keywords: Craniopagus twins, Pediatric Neurosurgery, Surgical nursing, Nursing planning
Surgical treatment of epilepsy in children, nursing assistance in building intraoperative excellence
Allison Roberto Silva, Hélio Rubens Machado, Marcelo Volpon Santos
Department of Pediatric Neurosurgery, São Paulo University. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Brazil
INTRODUCTION: Epilepsy is defined as a brain disorder characterized by a long-lasting predisposition to recurrent seizures and their consequences. For the most part, the treatment of choice is performed with the use of drugs that inhibit uncontrolled electrical discharges and when this does not achieve the desired effect, surgical treatments are considered. To guarantee excellence in these treatments, a multidisciplinary approach is necessary, the assistant nurse has a unique importance for this treatment to occur in the best possible way, ensuring safety and excellence in intraoperative care of children with epilepsy.
OBJECTIVES: To describe the activities of the Surgical Center nurse during the Epilepsy surgery process.
METHODS: This is an experience report, where aspects related to surgeries for the treatment of Epilepsy are addressed, as well as the main diagnoses and nursing interventions in children with surgical indication as the treatment of choice in this condition.
RESULTS and DISCUSSION: According to our experience, in a significant number of patients diagnosed with epilepsy during childhood, drug treatment does not have the desired effect. As a new perspective of coping, the Pediatric Neurosurgery team has available surgical techniques indicated for each patient individually. Thus, indications such as implantation of electrodes for monitoring and subsequent lesionectomy, partial or total lobectomies and implantation of vagus nerve stimulators (VNS) are options to be considered. In this context, nursing interventions reflect the care necessary for the treatment of patients based on the nursing diagnoses found, these are related to neurological, social interaction, cognitive, psychological and motor consequences.
CONCLUSION: The multidisciplinary interaction between Nursing and Pediatric Neurosurgery during the surgical process of children with Epilepsy, brings patients an expanded safety scope, where basic human needs are observed through two different prisms, obtaining greater safety in the process and quality assurance. in the procedure.
Keywords: Surgical nursing, Epilepsy, Pediatric neurosurgery, Pediatrics
An evaluative study to assess the outcome of neurorehabilitation among children's admitted in Neuro ICU king George hospital Visakhapatnam, Andhrapradesh, India
Purnima Pandrinki
Department of neurosurgery, andhra medical college king George hospital Visakhapatnam Andhrapradesh india
BACKGROUND AND AIM: The action of restoring someone to health or normal life through training and therapy after illness. The assessment begins with cognitive issues where is the child in the development spectrum, sensory issues need to be evaluated, are vision, hearing and other senses present and meeting the needs of the child. Starting rehabilitation as soon as a health condition is noted and continuing to deliver rehabilitation alongside other health interventions. Helps a child to be as independent as possible in everyday activities.
OBJECTIVES:
1. To assess the outcome of pediatric neuro rehabilitation among children's admitted in neuro icu kgh vsp.
2. To assess the effectiveness of rehabilitation in improving for a speedy recovery of children's admitted in neuro icu kgh vsp.
3. To help individual child to achieve the best best outcome.
4. To reduce the length of stay in hospitals.
5. To associate the demographic data with outcome of pediatric neuro rehabilitation.
METHOD: Sample size -30.
Sampling technique- simple random sampling technique.
Development of tool: consist of two sections.
Section A- demographic data.
Section B—questionnare on practice of rehabilitation.
An evaluation is done in all the pediatric cases admitted in the ICU with different diagnosis like trauma, rare MMC's in school going child, CCM and pediatric tumors and the need of rehabilitation for these children's have been identified and appropriate rehabilitation therapy was been given to the children's in the ICU.
RESULTS: Still working on it.
CONCLUSIONS: The need for pediatric neuro rehabilitation in the ICU was been recognised by the members of the health team and appropriate measures of therapies was been done and the outcome of speedy recovery was seen among the cases admitted in ICU. And also appropriate education was provided to the family members on the importance of rehabilitation.
Keywords: Rehabilitation, rspeedy recovery, hospital length of stay, impairme
List of posters presented at 48th ISPN Annual Meeting
Poster Session 1: Wednesday, December 7, 2022
Poster Number Topic Title Presenter Country
PP-001 Innovation and technology Development and validation of a remote video acquisition and analysis protocol using artificial intelligence for evaluation of gait Albert Tu Canada
PP-002 Innovation and technology Neurosurgery Cocktail -Its Impact on Neurosurgical Communication and Research Bipin Chaurasia Nepal
PP-003 Innovation and technology Technical Note on Inside-Out Approach for Foramen Magnum Decompression in Children with Achondroplasia Moise Danielpour United States
PP-004 Innovation and technology Brainstem Neuroenteric cyst: A novel management proposal Chandrasekaran Kaliaperumal United Kingdom
PP-005 Innovation and technology Music Therapy as a peri-operative intervention in Paediatric Neurosurgical patients( MuPeNS-Study) Chandrasekaran Kaliaperumal United Kingdom
PP-006 Innovation and technology Music Intervention for Paediatric peri-operative care: MuPeNS Study- Pilot feasibility study Chandrasekaran Kaliaperumal United Kingdom
PP-007 Innovation and technology Novel intraoperative neurophysiological techniques to preserve brain connectivity during asleep surgery: Implications for Pediatric Neurosurgery Francesco Sala Italy
PP-008 Innovation and technology Error in pediatric scoliosis curve measurement and the role of artificial intelligence and machine learning for accurate diagnosis: a pilot study from multi-institutional experience Hasan Raza Syed United States
PP-009 Innovation and technology Clinical Applications of focused ultrasound in pediatric neurosurgery: novel management for pediatric brain tumors Hasan Raza Syed United States
PP-010 Innovation and technology The evolution of Linear Accelerator Radiosurgery for Pediatric Central Nervous System lesions: The Hyperarc and OSMS João Gabriel Ribeiro Gomes Brazil
PP-011 Innovation and technology Case report of vagal nerve stimulator dysfunction from a mechanical toy and literature review of toy-related programmable device dysfunction Rebecca Chave Cox United Kingdom
PP-012 Innovation and technology Pediatric Neurosurgeons as Innovators: An Analysis of the Patents of North American Pediatric Neurosurgeons Sandi Lam United States
PP-013 Innovation and technology Minimal invasive treatment of non-syndromal craniosynostosis Thomas Hauser Austria
PP-014 Innovation and technology Gene therapy for pediatric neurologic diseases: New tools in neurosurgeon’s box to improve delivery Timothée De Saint Denis France
PP-015 Global Pediatric Neurosurgery Giant Calcified Cephalohematoma Crossing the Sagittal Suture: A Systematic Review with Case Illustration, Modified Classification and Management Algorithm Omar Aljohani Saudi Arabia
PP-016 Moya-Moya disease Identification of diagnostic biomarkers for pediatric Moyamoya disease based on plasma-derived extracellular vesicle miRNA Eun Jung Koh South Korea
PP-017 Hydrocephalus Effect of on shunt survival of the biochemical and cellular properties of cerebrospinal fluid among patients following ventriculoperitoneal shunting Benjamin Kasyoka Mutiso Kenya
PP-018 Hydrocephalus Pitfalls in diagnosis of shunt malfunction in children Chandrasekaran Kaliaperumal United Kingdom
PP-019 Hydrocephalus Management guidelines for Long tunnelled Ventricular drain in paediatric brain tumour: a medical and nursing perspective Chandrasekaran Kaliaperumal United Kingdom
PP-020 Hydrocephalus Neuroendoscopic Lavage in preterm infants with IVH Christian Auer Austria
PP-021 Hydrocephalus The Role of Ventriculoperitoneal Shunt Placements in Palliative Care Eylem Ocal United States
PP-022 Hydrocephalus Approaching hydrocephalus in pediatric posterior fossa tumors Hsin Hung Chen Taiwan
PP-023 Hydrocephalus A 25 years experience of Endoscopic Third Ventriculostomy (ETV). – a single institute retrospective analysis actively introduced ETV in infantile obstructive hydrocephalus - Kazuaki Shimoji Japan
PP-024 Hydrocephalus The management of hydrocephalus in median posterior fossa cystic collections: surgical outcome from a retrospective single-center series of 54 consecutive pediatric patients Lelio Guida France
PP-025 Hydrocephalus Abdominal Pseudocysts with Children with Ventriculoperitoneal Shunts: A Systematic Review and Proposed Approach to Management Melissa LoPresti United States
PP-026 Hydrocephalus Suggested Predictive Scoring System for Postresection Hydrocephalus in Pediatric Patients with Posterior Fossa Tumors Noor Ul Huda Ul Maria Pakistan
PP-027 Hydrocephalus Proposed Predictive Scoring System for Postresection Hydrocephalus in Pediatric Patients with Posterior Fossa Tumors Noor Ul Huda Ul Maria Pakistan
PP-028 Hydrocephalus Choroid Plexus endoscopic removal in children with hydrocephalus. Surgical technique and clinical outcome Oscar Garcia González Mexico
PP-029 Hydrocephalus "Shunt site pain with calcified catheter and functioning VP shunt – to operate or not?" Rehman Ali Baig United Kingdom
PP-030 Hydrocephalus Prevention of slit ventricle syndrome by the use of antisiphon devices in shunt-treated hydrocephalic children Ryo Ando Japan
PP-031 Hydrocephalus Retrospective Study comparing Outcomes between Ultrasound-guided VP shunt insertion and Free-hand insertion Shi Hui Ong Singapore
PP-032 Hydrocephalus Multiloculated hydrocephalus presenting as bobble doll head syndrome Shighakolli Ramesh India
PP-033 Hydrocephalus Role of neuroendoscopy (rigid and flexible) in management of hydrocephalus: Our experience in last 5 years Shighakolli Ramesh India
PP-034 Hydrocephalus Hydrocephalus associated with spinal dysraphism -which CSF diversion procedure is ideal ? Supriya Chauhan India
PP-035 Hydrocephalus Hydrocephalus associated with spinal dysraphism- which CSF diversion is ideal? Supriya Chauhan India
PP-036 Hydrocephalus Factors affecting the success of endoscopic third ventriculostomy in infective Hydrocephalus Sushanta Kumar Sahoo India
PP-037 Neuroendoscopy Endoscopic Suturectomy in Sagittal Craniosynostosis Treatment: Preliminary Case Series in the Indonesian National Referral Hospital Antari Rahmadani Harmani Indonesia
PP-038 Neuroendoscopy Endoscopic septostomy for post infectious multiloculated hydrocephalous to prevent multiple shunt surgeries in children – a case series Apinderpreet Singh India
PP-039 Neuroendoscopy Technical Considerations in Flexible Endoscopic Biopsy of Pediatric Brain Tumors Carolyn S Quinsey United States
PP-040 Neuroendoscopy Use of GOLD Laser in Endoscopic Third Ventriculostomies: Report of 30 Cases David F Jimenez Md, Facs, Faans. United States
PP-041 Neuroendoscopy Complete monoportal fully endoscopic resection of pineal region tumour via the transchoroid approach David Rowland United Kingdom
PP-042 Neuroendoscopy The role of CSF dynamics in the early morphological changes after endoscopy and helmet therapy for scaphocephaly Federico Di Rocco France
PP-043 Neuroendoscopy Intracranial Neuroendoscopy in Children and Adults: A Comparative Analysis Jehuda Soleman Switzerland
PP-044 Neuroendoscopy Trans Nasal Endoscopy in Paediatric Sella – Suprasellar Lesions – A Citadel for Varied Spectra Of Lesions, An Institutional Experience Gowtham Matham India
PP-045 Neuroendoscopy Flexible endoscope assisted suture release (FEASR) and barrel stave osteotomy for the correction of sagittal synostosis Jason Labuschagne South Africa
PP-046 Neuroendoscopy Endoscopic transorbital resection of a rare orbital alveolar soft part sarcoma in a 3-year old: a mimicker of haemangioma Joyce Shuk Wan Chow Hong Kong
PP-047 Neuroendoscopy Neuroendoscopy in the Management of Pineal Region Tumours in Children Chandrashekhar. E. Deopujari India
PP-048 Neuroendoscopy Neuroendoscopy and management of ruptured intracranial Sylvian arachnoid cysts Luca Massimi Italy
PP-049 Neuroendoscopy Endoscopic Management of Lateral Ventricle Arachnoid Cysts – Case Series with Proposed Classification Manas Panigrahi India
PP-050 Neuroendoscopy Ventricular Catheter Delivery Device in endoscopic procedures Manas Panigrahi India
PP-051 Neuro-Oncology Pediatric oncology neurosurgery, four years after centralization in the Princess Máxima Center Kirsten Van Baarsen Netherlands
PP-052 Neuro-Oncology Delay in the Diagnosis of Childhood Brain Tumours: Contributing Factors and Outcome A Systematic Review of the Literature Kristy Kehoe United Kingdom
PP-053 Neuro-Oncology Case Report: Childhood Intracranial Lesion Associated with Tonsoku-like DNA repair protein (TONSL) Mutation - A novel finding Kristy Kehoe United Kingdom
PP-054 Neuro-Oncology Paediatric Primary CNS Inflammatory Myofibroblastic Tumour: Two Cases of A Rare Paediatric Tumour Lin Wei Ooi Malaysia
PP-055 Neuro-Oncology Primary leptomeningeal medulloblastoma: a case-based review Maria Rosaria Scala Italy
PP-056 Neuro-Oncology Atypical ATRT With multiple Difusse lesions in posterior fossa and left Trigone Mayra Arce Lozoya Mexico
PP-057 Neuro-Oncology Papillary craniopharyngioma in an 8-year-old girl with BRAF V600E mutation Nivedh Dinesh Singapore
PP-058 Neuro-Oncology Management and outcomes of paediatric craniopharyngioma: A 15-year experience in Singapore Rambert Wee Singapore
PP-059 Neuro-Oncology The COMBAT Project - Core post operative morbidity set for paediatric brain tumours Sandhya Trichinopoly Krishna United Kingdom
PP-060 Neuro-Oncology Giant and rare cranial tumors in pediatrics – tips and tricks for successful Neurosurgical outcome Saraj Kumar Singh India
PP-061 Neuro-Oncology Application of neuroendoscopy in surgery for prepontine epidermoid cyst of children Sheng Che Chou Taiwan
PP-062 Neuro-Oncology Infantile Brainstem High Grade Glioma: A Case Report and Literature Review Shi Hui Ong Singapore
PP-063 Neuro-Oncology The outcome of children with craniopharyngioma treated in multidisciplinary team Sławomir Blamek Poland
PP-064 Neuro-Oncology Intraoperative MRI to improve accuracy of frameless biopsies in the pons Sonia Tejada Spain
PP-065 Neuro-Oncology Predictive factors for the occurrence of peri-surgical complications in pediatric posterior fossa tumors Stephanie Anetsberger Switzerland
PP-066 Neuro-Oncology Diffuse Leptomeningeal Glioneuronal Tumor of Childhood Tatiana Protzenko Brazil
PP-067 Neuro-Oncology Intraspinal cervical chondromesenchymal hamartoma as a presentation of DICER1 Syndrome in a newborn Victor Javier Fernández Cornejo Spain
PP-068 Neuro-Oncology Biopsy of paediatric brainstem intrinsic tumours: 10- year experience from a Singapore children’s hospital Yuan Guang Lim Singapore
PP-069 Neuro-Oncology Extracranial metastases from high-grade gliomas Yu-Cheng Chou Taiwan
PP-070 Neurotrauma/Critical Care Incidence of Shaken Baby Syndrome in Brazil public health over the last 6 years Carolina Carmona Pinheiro Machado Brazil
PP-071 Neurotrauma/Critical Care Protocolized management of isolated linear skull fractures at a Level 1 pediatric trauma center Christopher M Bonfield United States
PP-072 Neurotrauma/Critical Care Low Velocity Penetrating Injury Of The Central Nervous System in Children: A Report of Two Unusual Cases Debajyoti Datta India
PP-073 Neurotrauma/Critical Care Epidemiology Of Pediatric Traumatic Brain Injuries - Our institutional experience, Andhra medical college, Visakhapatnam,India Hema Swaroop Kurumella India
PP-074 Neurotrauma/Critical Care Global Epidemiology of Pediatric Traumatic Spinal Cord Injury: A Systematic Review and Meta-Analysis Joseline Haizel Cobbina United States
PP-075 Neurotrauma/Critical Care The Role of Virtual Planning and Modified CAD/CAM Implants in Cranioplasty Malte Ottenhausen Germany
PP-076 Neurotrauma/Critical Care Metabolic and microstructural changes in children with severe TBI. DTI and 1H MRS study Maxim Ublinskiy Russia
PP-077 Neurotrauma/Critical Care Growing Skull Fractures - An Uncommon Cause of Seizures Merry Francis Kallely India
PP-078 Neurotrauma/Critical Care Single Burr Hole Evacuation of Extradural Hematoma in Pediatric Population: An Experience from the biggest Children Hospital of Pakistan Mian Awais Pakistan
PP-079 Neurotrauma/Critical Care Long term outcomes in pediatric cranioplasty post decompressive craniectomy Tarunesh Sharma India
PP-080 Neurotrauma/Critical Care Pediatric retroclival hematomas: case series, systematic review, and a proposed novel approach for drainage Yahya H. Khormi Saudi Arabia
PP-081 Other Knowledge, Attitude and Practices Related to Craniosynostosis Among Physicians in Saudi Arabia: "A Cross-Sectional Study" Abdulrazaq Abdulmohsen Alojan Saudi Arabia
PP-082 Other Neurosurgical Management of Hydrocephalus and Cerebellar Tonsillar Herniation in the Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome Alon Kashanian United States
PP-083 Other Single Institution Feasibility Trial: Incorporating Pediatric Patient Reported Outcome Scales into Clinic Workflows Ben S Succop Jr United States
PP-084 Other Development of pediatric neurosurgery in Mongolia Byambatsend Byambaa Dorjsuren Mongolia
PP-085 Other Frontal Sinus Hypoplasia in Unoperated Older Patients with Craniosynostosis: A Pilot Study Chris Bonfield United States
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PP-087 Other Simple vaccum extractor treatment for ping pong skull depressed fractures Mauricio Daniel Puch Bolivia
PP-088 Other Intraoperative Monitoring in Pygopagus Separation: What We Have Learned So Far Nadya Zaragita Indonesia
PP-089 Other Imaging of Encephaloceles Peter Kalina United States
PP-090 Other 5 Years Follow up of Successful Craniopagus Separation Setyo Budi Premiaji Widodo Indonesia
PP-091 Other A Case of Encephalocele which Developed Hydrocephalus After the First Surgical Repairment Taekyun Kim Japan
PP-092 Other Muenke Syndrome - Unusual presentation Tatiana Protzenko Brazil
PP-094 Peripheral nerve Dynamic Reanimation of Facial Paralysis in Children by using Masseteric Nerve Anh Mai Bui Vietnam
PP-095 Vascular Our experience with pediatric vascular malformations Dan Aurel Nica Romania
PP-096 Vascular De-novo Arteriovanous malformation in a 8 year old and Neurosurgical implication: Case report and literature review Ieva Sataite United Kingdom
PP-097 Vascular Right side posterior interhemispheric transfalcine retrosplenial transprecuneus approach for the resection of bilateral periatrial cavernous malformation Jose Ascencion Arenas Ruiz Mexico
PP-098 Vascular Arare case of mirror arteriovenous malformation Suchanda Bhattacharjee India
PP-099 Vascular Ruptured ACA aneurysm in an infant with poor prognosis: case report and reviews of the literature You Nam Chung South Korea
Poster Session 2: Friday, December 9, 2022
Poster Number Topic Title Presenter Country
PP-100 Hydrocephalus Treatment of myelomeningocele in Japan: Analysis of the medical claims database in Japan Masahiro Nonaka Japan
PP-101 Antenatal diagnosis and treatment Developmental outcomes and peri-natal diagnosis of agenesis of the corpus callosum Fareha Khalil Ireland
PP-102 Antenatal diagnosis and treatment Proposal of a protocol for assessment of motor development of children submitted to antenatal myelomeningocele repair Renata Viana Brigido De Moura Jucá Brazil
PP-103 Dysraphism Neural Tube Defects cases in an Indonesian Industrial Area Referral Hospital during Covid-19 Pandemic Andi Nugraha Sendjaja Indonesia
PP-104 Dysraphism Early Experience during COVID 19 Pandemic: Multidiciplinary Management of Lipomyelomeningocele Astri Avianti Indonesia
PP-105 Dysraphism Congenital Midline Spinal Hamartoma in a 5-month-old Infant Elric Brahm Malelak Indonesia
PP-106 Dysraphism New mutation in hereditary Dandy-Walker with occipital cephalocele Frank Van Calenbergh Belgium
PP-107 Dysraphism Epidemiology of myelomeningocele- North coastal Andhra, India Genetic, Social,Economic,Environmental Factors affecting the occurrence Hema Swaroop Kurumella India
PP-108 Dysraphism Preventive Strategy For Spinal Dysraphism - Pilot Project In North Andhra, India, Salt Fortification With Folic Acid Hema Swaroop Kurumella India
PP-109 Dysraphism Supratentorial Anomalies in Spina Bifida Ibrahim Alatas Türkiye
PP-110 Dysraphism Multidisciplinary Clinic for Closed Spinal Dysraphisms Laura Grazia Valentini Italy
PP-111 Dysraphism Delayed Diagnosis of Cervical Dermal Sinus Tract in an Infant with Meningitis and Hydrocephalus Mary Angeline Luz Ubias Hernandez Philippines
PP-112 Dysraphism The challenging treatment of a giant anterior meningoencephalocele in the newborn: About one case Nabila Tighilt Algeria
PP-113 Dysraphism Surgical treatment of split cord malformation type I with scoliosis Olga M Sergeenko Russia
PP-114 Dysraphism Fronto-ethmoido-nasal cephalocele in Bamako what surgical approach Oumar Diallo Mali
PP-115 Dysraphism Spinal dysraphism:A way forward from our own experiences in treatment and prevention in LMIC’s Prashanth Thalluri India
PP-116 Dysraphism Are prophylactic surgeries for lipomyelomeningoceles really prophylactic? A case of an asymptomatic lipomyelomeningocele with contradictory neurophysiology findings Raenette David United Kingdom
PP-117 Dysraphism Incidence of neural tube defects in Bahrain Taha Ali Alderazi Bahrain
PP-118 Epilepsy An ex vivo model to study fast ripple high-frequency oscillations detected by SEEG using dedicated surgical specimens from pediatric focal epilepsy patients Adriano Cattani Canada
PP-119 Epilepsy Transitional Care for Epilepsy: A Systematic Review Sandi Lam United States
PP-120 Epilepsy Seizure control after surgery of temporal lobe pathology: An Institutional experience Suchanda Bhattacharjee India
PP-121 Functional Patient and Caregiver Reported Outcome Measures after Single-Level Selective Dorsal Rhizotomy in Pediatric Patients with Spastic Cerebral Palsy Jehuda Soleman Switzerland
PP-122 Functional Microsurgical DREZotomy in spastic cerebral palsy: For a child with a little, a little is a lot Nishant Goyal India
PP-123 Germ Cell Tumors Congenital intraventricular tumors: illustrative case and systematic review Manilyn Ann Hong Philippines
PP-124 Germ Cell Tumors Porencephaly with Suprasellar Dermoid Cyst- A Novel Illustrative Report Mitesh Karn Nepal
PP-125 Germ Cell Tumors A rare recurrent intramedullary immature teratoma, diagnostic and management dilemma: A case report and literature review Tarunesh Sharma India
PP-126 Global Pediatric Neurosurgery High definition 2-D VITOM (Video Telescope Operating Monitor) assisted brain and spinal surgery in paediatrics: Is it an acceptable substitute for microscopic surgery? Anand Kumar Das India
PP-127 Global Pediatric Neurosurgery Infantile macrocephaly: Complicated familial benign enlargement of subarachnoid space (BESS) in twins of suspected nonaccidental injury Azam Ali Baig United Kingdom
PP-128 Global Pediatric Neurosurgery Craniosynostosis: A comparative analysis between surgical and clinical incidence in public health in Brazil Carolina Carmona Pinheiro Machado Brazil
PP-129 Global Pediatric Neurosurgery Neurologist and Neurosurgeon: a ‘sine qua non’ in paediatric intracranial pathology management Chandrasekaran Kaliaperumal United Kingdom
PP-130 Global Pediatric Neurosurgery Incidental Intracranial arachnoid cysts in the paediatric population- An institutional longitudinal review Chandrasekhar Kaliaperumal United Kingdom
PP-131 Global Pediatric Neurosurgery Predictive outcome value of angular craniometry in surgical treatment of cerebellar tonsillar herniation Federico Di Rocco France
PP-132 Global Pediatric Neurosurgery Transitional Care in Pediatric Brain Tumor Patients: A Systematic Literature Review Jehuda Soleman Switzerland
PP-133 Global Pediatric Neurosurgery Vertebral and Costal Anomalies in Jarcho-Levin Syndrome: study of 121 cases Ibrahim Alatas Türkiye
PP-134 Global Pediatric Neurosurgery Reddit users seek medical information for pediatric neurosurgery conditions online: a descriptive study Jeffrey Steven Raskin United States
PP-135 Global Pediatric Neurosurgery Arachnoid cyst complicated by bleeding - case study Magdalena Zgoda Aleksandrowicz Poland
PP-136 Global Pediatric Neurosurgery Negative pressure epidural syndrom,Causes of hemodynamic instability in children after Applying Negative Pressure to epidural Draining catheter after Craniotomy Mohammad Sadegh Masoudi Iran
PP-137 Global Pediatric Neurosurgery Safety and Clinical Utility of Intraoperative cerebral angiography during surgery for paediatric arteriovenous malformations Natasha Aziz United Kingdom
PP-138 Global Pediatric Neurosurgery Brain imaging to identify possible resectable brain lesion is vital when dealing with drug resistant epilepsy: incidental finding of a right peri-rolandic mass in a 15 years old boy with failed medical seizure treatment for years Tee Tau Eric Nyam Taiwan
PP-139 Infection The Impact of Shunt Protocol on Reducing the Infection Rate Following Shunt Placement: "A Single Institutional Experience in Saudi Arabia" Abdulrazaq Abdulmohsen Alojan Saudi Arabia
PP-140 Infection The Association Between Procalcitonin Level In Children With Ventriculitis In Rural Hospital In Medan Year 2020-2021 Abdurrahman Mouza Indonesia
PP-141 Infection Use of non enhanced MRI for follow up of intracranial infections using diffusion weighted sequence Alya Hasan Kuwait
PP-142 Infection Causal Inference of Infectious Diseases on Hydrocephalus Andrew T Hale United States
PP-143 Infection Intracranial empyemas in the COVID-19 era: a new pandemic? A paediatric case series and review of the literature Benjamin J. Hall United Kingdom
PP-144 Infection Global Epidemiology of Central Nervous System Infections in Pediatric Patients: A Systematic Review and Meta-Analysis Joseline Haizel Cobbina United States
PP-145 Infection Comparison of Outcome in Neurosurgically Treated Pediatric Subdural Empyema with or without Simultaneous Source Control Surgery Ladina Greuter United Kingdom
PP-146 Infection Management of subdural empyemas Rajeev Kariyattil Oman
PP-147 Neuroendoscopy Pure endoscopic treatment for Sylvian arachnoid cysts Oscar Garcia González Mexico
PP-148 Neuroendoscopy Endoscopic third ventriculostomy with choroid plexus cauterization in treating infantile hydrocephalus: an experience from Mali Oumar Diallo Mali
PP-149 Neuroendoscopy Endoscopic ultrasonic aspiration as alternative to more invasive surgery in initial management of optic pathway gliomas in children Maria Rosaria Scala Italy
PP-150 Neuro-Oncology Frameless stereotactic biopsy for Midline lesions of the brain in Pediatric population Abhinith Shashidhar India
PP-151 Neuro-Oncology The elusive clinical behavior of low grade glioneural tumors Adrian Caceres Costa Rica
PP-152 Neuro-Oncology Cranial vault pediatric tumors: different technique to ensure total removal Cecilia Casali Italy
PP-153 Neuro-Oncology Posterior fossa pilocytic astrocytoma contributing to paedaitric obstructive sleep apnoea: A case report and review of literature Chandrasekaran Kaliaperuma United Kingdom
PP-154 Neuro-Oncology A 5-year outcome of Propranolol for the treatment of paediatric intracranial cavernoma: Case report and a review of the literature Chandrasekaran Kaliaperumal United Kingdom
PP-155 Neuro-Oncology Survival Outcomes of Primary CNS Brain Tumours in Children: a single-centred retrospective observational study Chandrasekaran Kaliaperumal United Kingdom
PP-156 Neuro-Oncology A rare presentation of a bilateral intracranial Parameningeal Embryonal Rhabdomyosarcoma in a 2-year-old child which mimicked Vestibular Schwannoma: a case report Chandrasekaran Kaliaperumal United Kingdom
PP-157 Neuro-Oncology Pediatric Brain Tumour: A Study of One-year Data from a Tertiary Neurosurgical Centre, Myanmar Ei Ei Khaing Myanmar
PP-158 Neuro-Oncology Case report of EBV associated smooth muscle intracranial tumour in a child Felicia Hui Zhuang Chua Singapore
PP-159 Neuro-Oncology Choroid plexus papillomas in the first year of life: The value of pre-operative embolization and the interpretation of leptomeningeal enhancement in atypical tumors Franceso Sala Italy
PP-160 Neuro-Oncology Trends in Pediatric Brain Tumor Incidence in Dr. Sardjito General Hospital, Yogyakarta, Indonesia, from 2020 – 2022 Handoyo Pramusinto Indonesia
PP-161 Neuro-Oncology Outcomes in surgical management of Craniopharyngiomas in pediatric age group at a high volume tertiary referral centre in India Harshal Nandlal Agrawal India
PP-162 Neuro-Oncology Second-look surgery for pineal region tumors Hideki Ogiwara Japan
PP-163 Neuro-Oncology Comparison of clinical features and treatment outcomes of pilocytic astrocytoma in pediatric and adult patients Joo Whan Kim South Korea
PP-164 Neuro-Oncology Central Nervous System Tumor in Children. The Cuban Experience Julio S. Brossard Alejo Cuba
PP-165 Neuro-Oncology Intratumoral bleed in pediatric primary spinal intradural Ewing’s sarcoma presenting with acute neurological decline Karthigeyan Madhivanan India
PP-166 Neuro-Oncology Place of neo/adjuvant chemotherapy and limited surgery in the treatment of non-metastatic childhood medulloblastoma Kévin Beccaria France
PP-167 Occult tethered cord Tethered cord diagnosis by MRI in supine and prone children positioning Cordula Scherer Switzerland
PP-168 Occult tethered cord Posttubercular Arachnoid Cyst and Syringomyelia with Severe Spastic Paraplegia: case report and review of literature Hsin Hung Chen Taiwan
PP-169 Occult tethered cord Elucidate surgical treatment criterias in tethered cord syndrome in patients with myelomeningocele Ibrahim Alatas Turkey
PP-170 Occult tethered cord Sudden deterioration in previously undiagnosed occult dysraphism Luca Massimi Italy
PP-171 Occult tethered cord Cervical spine dermal sinus tract in children Pi Doanh Ngoc Nguyen Vietnam
PP-172 Other Squamosal Suture Synostosis and Hydrocephalus: A Minor Suture with Major Implications Daphne Li United States
PP-173 Other Early Bone Reformation after Cranial Vault Remodelling for Sagittal Craniosynostosis Elie Hammam Australia
PP-174 Other Surgical Drain Induced Subgaleal Hematomas and Skin Necrosis in Pediatrics: a Case Report Gigih Aditya Wardana Indonesia
PP-175 Other A pediatric case of an intradiploic epidermoid cyst with cranial bone invasion Hema Swaroop Kurumella India
PP-176 Other Pragmatism in Pediatric Neurosurgery: A Systematic Literature Review and Analysis Jochem Spoor Netherlands
PP-177 Other Long-term results of minimally invasive strip craniectomy without helmet therapy for scaphocephaly - a single-center experience Katharina Lutz Switzerland
PP-178 Other Skull Base and Craniocervical Junction Abnormalities in Patients with Crouzon Syndrome Kerrin Sunshine United States
PP-179 Other Neurosurgical Treatment and Outcome of Pediatric Skull Base Lesions: A Case Series and Systematic Review of the Literature Ladina Greuter Switzerland
PP-180 Other Craniosynostosis in primary metabolic bone disorders: a 10-year single institution experience Maria A. Punchak United States
PP-181 Other Clinical variety and prognosis of arachnoid cysts in children Martina Messing Jünger Germany
PP-182 Other MR exams under drug-free sedation with fixation device Masahiro Kameda Japan
PP-183 Spine Laminotomy in Pediatric Spinal Surgery Abraham Ibarra De La Torre Mexico
PP-184 Spine Transverse Split Laminoplasty: A Novel Anatomy Preserving Technique with Long Term Follow-Up Daphne Li United States
PP-185 Spine Assesment of Vertebral Anomalies in Spina Bifida Patients: study of 422 cases Ibrahim Alatas Türkiye
PP-186 Spine Split laminotomy approach for multilevel spinal cord tumors Jose Ascencion Arenas Ruiz Mexico
PP-187 Spine Posterior ‘hemi-arch’ synchondral fracture of the atlas following penetrating neck injury in a child Karthigeyan Madhivanan India
PP-188 Spine Clear cell meningioma of the cauda equina in a pediatric patient: a case report Llex Chong Soriano Philippines
PP-189 Spine Surgical tactics in rare forms of aneurysmal bone cysts spine and skull bones in children Pavel Lobankin Russia
PP-190 Spine Children with idiopathic syringomyelia presenting with back pain treated with lumbar punctures, a review of the last 11 years Stuart Sinclair Stokes United Kingdom
PP-191 Spine Chronic recurrent multifocal osteomyelitis - a challenging diagnosis Tatiana Protzenko Brazil
PP-192 Spine EOS Modulable Halo Brace: the present of Halo Vest Timothée De Saint Denis France
PP-193 Spine Pediatric Tuberculous Spondylitis Surgery Using Adult Cervical Spine System In Limited Resources Vira Dwi Nisrina Indonesia
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| 36484829 | PMC9735206 | NO-CC CODE | 2022-12-14 23:29:53 | no | Childs Nerv Syst. 2022 Dec 9;:1-78 | utf-8 | Childs Nerv Syst | 2,022 | 10.1007/s00381-022-05754-7 | oa_other |
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Agric Human Values
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Agriculture and Human Values
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10.1007/s10460-022-10403-5
Article
LGBTQ+ food insufficiency in New England
http://orcid.org/0000-0003-4717-8132
Leslie Isaac Sohn [email protected]
1Isaac Sohn Leslie
is an Extension Assistant Professor of Community Development at the University of Vermont. Ike is a publicly engaged environmental sociologist specializing in justice, sustainability, and economic viability in food systems. They have a Ph.D. in sociology from the University of Wisconsin-Madison.
Carson Jessica [email protected]
2Jessica Carson
is a Research Assistant Professor at the University of New Hampshire’s Carsey School of Public Policy, where she studies how policy and practice decisions create or reduce patterns of inequity along the axes of demographic difference and neighborhood characteristics. She has particular interest in the multi-dimensional nature of food access and the functionality of the social safety net within and across places. She has a Ph.D. in sociology from the University of New Hampshire.
Bruce Analena [email protected]
3Analena Bruce
is the Director of the UNH Food Systems Lab and an Assistant Professor in the Department of Agriculture, Nutrition, and Food Systems at the University of New Hampshire. She is a sociologist with a research focus on the development of sustainable livelihood strategies for New England farmers and Values-Based Food Supply Chains designed to increase equity, transparency, and resilience in the food system.
1 grid.59062.38 0000 0004 1936 7689 University of Vermont Extension, 130 Austine Dr. #300, Brattleboro, VT 05301 USA
2 grid.167436.1 0000 0001 2192 7145 Carsey School of Public Policy, University of New Hampshire, 73 Main Street, Durham, NH 03824 USA
3 grid.167436.1 0000 0001 2192 7145 Department of Agriculture, Nutrition, and Food Systems, University of New Hampshire, 129 Main Street, Durham, NH 03824 USA
9 12 2022
116
17 11 2022
© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
As a group, LGBTQ+ people experience food insecurity at a disproportionately high rate, yet food security scholars and practitioners are only beginning to uncover patterns in how food insecurity varies by subgroups of this diverse community. In this paper, we use data from the U.S. Census Bureau’s Household Pulse Survey—which added measures of gender identity and sexuality for the first time in 2021—to analyze New Englanders’ food insufficiency rates by gender, sexuality, race, and ethnicity. We find that (1) in the past seven days, 13.0 percent of LGB + (lesbian, gay, bisexual, and other non-heterosexual) New Englanders experience food insufficiency—which is nearly twice the rate of heterosexual people—and 19.8 percent of transgender+ (transgender, genderqueer, gender non-binary, and other non-cisgender people) New Englanders experience food insufficiency—which is two to three times the rate of cisgender men and women. (2) Whereas cisgender New Englanders experience food insufficiency at a lower rate than their counterparts in the rest of the nation (about two percentage points lower for both cisgender men and women), transgender+ New Englanders experience no such New England advantage compared to transgender+ people in the country as a whole. (3) LGBTQ+ New Englanders of color experience devastatingly high rates of food insufficiency, with, for example, one in three Black transgender+ New Englanders not having enough food to eat in the past seven days. These findings suggest that addressing food insecurity in New England demands approaching the problem with an intersectional queer lens, with attention to the ways in which racism, cissexism, and heterosexism are creating a systemic, ongoing food crisis for LGBTQ+ New Englanders, especially those who are transgender+ and/or people of color.
Keywords
Food insecurity
Food justice
Gender
LGBTQ+
Queer
Race
Sexuality
==== Body
pmcIntroduction
LGBTQ+ people have a severe yet invisibilized relationship with food insecurity. Scholarship demonstrates that LGBTQ+ people as a group experience food insecurity at disproportionately high rates (e.g., Brown et al. 2016). LGBTQ+ people are also part of every other disproportionately affected group, yet scholarship has yet to sufficiently distinguish patterns of food insecurity across subgroups of this community. Furthermore, the research that does exist has only rarely been adopted into broader food insecurity scholarship and practice. Despite food systems researchers and practitioners’ longstanding interest in identifying inequities related to food security, stakeholders seldom approach the issue from a queer perspective. A queer lens encourages us to focus on how gender and sexuality—along with intersecting identities like race and class—relate to everyday things like eating (Leslie et al. 2019). Fortunately, there has been a recent surge in research on LGBTQ+ food insecurity (e.g., Conron and O’Neill 2021). However, aside from Russomanno and Jabson Tree’s (2020, p 5) survey of the Southeastern U.S. (n = 105), this body of work has yet to quantify this phenomenon with a regional lens, despite important food policy decisions being implemented at these regional levels (e.g., New England State Food System Planners Partnership 2022). Here, we focus on New England to offer locally actionable data for a region of 15 million people (authors’ own analysis of 2020 Decennial Census Redistricting Data). Doing so also sheds light on the experiences of LGBTQ+ people in a politically liberal region of the U.S., through the lens of food access. Four of the six New England states have food insecurity rates lower than the national rate (Coleman-Jensen et al. 2021), but does this New England exceptionalism hold for its LGBTQ+ residents?
In this paper, we analyze New England LGBTQ+ food insufficiency—across gender identity, sexuality, race, ethnicity, and income—using data from the U.S. Census Bureau’s Household Pulse Survey. The experimental survey, designed to capture information about how households are faring during the COVID-19 pandemic, began data collection in April 2020, but did not add measures of gender identity and sexual orientation until July 2021. According to Conron (2022), this inclusion of gender identity and sexuality questions “was directly related to the Biden administration’s executive orders about data collection and equity,” making this “one of the first times, to my knowledge, that we have information about food insufficiency for trans people in a big national survey data set.” This survey’s measure of food insecurity differs from the official measure in its reference period—asking respondents about their food situation in the past seven days, rather than the past 12 months—and in its complexity; our measure is a single question, whereas officially food insecurity is measured in a multi-stage series of up to 18 questions. Here, people who report sometimes or often not having enough to eat in the past seven days are described as experiencing “food insufficiency.”
Because this measure does not capture, for instance, people who did not have enough to eat last month but who did last week, our results likely underreport the extent of LGBTQ+ food insecurity in New England. Still, our three main findings speak to the severity of the problem:
First, we estimate that in the past seven days, 13.0 percent of LGB + New Englanders experience food insufficiency—which is nearly twice the rate of heterosexual people—and 19.8 percent of transgender+ New Englanders experience food insufficiency—which is two to three times the rate of cisgender men and women. Second, whereas cisgender New Englanders experience food insufficiency at a lower rate than their counterparts in the rest of the nation (about two percentage points lower for both cisgender men and women) transgender+ New Englanders experience no such New England advantage compared to transgender+ people in the country as a whole. Third, LGBTQ+ New Englanders of color experience devastatingly high rates of food insufficiency, with, for example, one in three Black transgender+ New Englanders not having enough food to eat in the past 7 days.
These findings indicate that even in a politically liberal region with a low overall food insecurity rate, existing policies fail to ensure food security for New Englanders who identify as people of color, transgender+ , and LGB +. As we will demonstrate, practice that relies on an income or class lens alone is insufficient for relieving these inequities. A socially just approach to addressing food insecurity demands explicit attention to the intersections of racism, cissexism, and heterosexism.
Literature review
Approaches to food insecurity in food systems literature
Much of the public health, nutrition, and interdisciplinary food systems scholarship addressing food insecurity is focused on food accessibility and availability by increasing individuals’ access to fresh fruits and vegetables (Allen 2004; Dailey et al. 2015; Hsiao et al. 2019; Lytle and Sokol 2017; Westengen and Banik 2016). This work is often centered on “food deserts,” a contentious concept that defines areas lacking easy access to supermarkets or full-size grocery stores that sell a wide range of healthy and fresh food (Caramaschi 2017; Meenar and Hoover 2012; Sadler et al. 2013). A more recent line of research focused on the impacts of food environments examines so-called food swamps, or areas with a high-density of high-calorie fast food and junk food stores, relative to healthier food options (Cooksey-Stowers et al. 2017; Cooksey-Stowers et al. 2020). Many intervention-oriented initiatives have accordingly utilized this physical proximity-focused approach and focused on increasing the availability of fresh foods in low-income neighborhoods, based on the assumption that these initiatives will improve individuals’ diet quality and food security (e.g. Blackmore 2013; Dailey et al. 2015; Hanson et al. 2022; Sadler 2016; Savoie-Roskos et al. 2016). For instance, an extensive line of research is focused on the potential of initiatives designed to increase the accessibility and availability of fresh produce in low income and underserved communities, including urban agriculture (Siegner et al. 2018), community gardens (Furness and Gallaher 2018), farmers markets and farm stands (Evans et al. 2012; Markowitz 2013; Sage et al. 2013), mobile markets (Leone et al. 2017); and related food assistance programs such as the farmers’ market nutrition program (Blumberg et al. 2022; Dimitri et al. 2015; Johnson et al. 2020; O’Dare 2017; Singleton et al. 2017).
However, studies examining the link between food access and food insecurity are often inconclusive (Kirkpatrick and Tarasuk 2010; Lytle and Sokol 2017; Ma et al. 2016). For example, an analysis of three waves of the Southeastern Pennsylvania Household Health Survey found that better neighborhood food access is associated with lower risk of food insecurity, yet most food insecure individuals reported good food access, suggesting that buying power, not access, may be the primary driver of food insecurity (Mayer et al. 2014). Other research demonstrates that financial constraints are the underlying cause of food insecurity (Loopstra and Tarasuk 2013; Kirkpatrick and Tarasuk 2011), and USDA (United States Department of Agriculture) researchers have estimated that a $10 increase in the price of a standard “basket” of key foods would increase food insecurity by about 2.5 percentage points among low-income households (Gregory and Coleman-Jensen 2013). Not surprisingly, studies evaluating the impact of programs and initiatives designed to increase individual access to fresh foods often have negligible or limited impacts on food insecurity (Dailey et al. 2015; Sadler et al. 2013).
The food justice approach to food insecurity is more systemic and focuses on the root causes of food insecurity. This research suggests that income and employment, housing, and transportation-based policy interventions would be more effective than approaches focused on increasing food availability and accessibility (Horst et al. 2017; Loopstra and Tarasuk 2013). Food justice scholars argue that food systems initiatives and scholarship focus on increasing the availability of fresh fruits and vegetables because this strategy is easier, politically feasible, and more appealing to mobilize around (such as planning a farmer’s market or community garden) and obtain funding to support, rather than advocating for policies to address the root causes of food insecurity or confronting class and racial inequities (Allen 2008; Guthman 2011). Guthman (2011) argues that because the importance of fresh, local, organic foods has been posed in opposition to all that is wrong with the food system, access to these foods is posed as the solution to food insecurity. This discursive strategy defines the problem of food insecurity as unequal access to high-quality food rather than disparities in wages, employment, or housing, yet Guthman notes that “bringing good food to others isn’t changing the conditions of exploitation and oppression or addressing the privilege that also results from pervasive inequality” (Guthman 2011, p 161).
Food justice scholars pay explicit attention to the role of structural racism and racial inequities in the root causes of food insecurity (Bowen et al. 2021; Garth and Reese 2020; Hatch et al. 2019; Reese 2019). For instance, food justice activists have challenged the term food desert because it suggests such inequity is “natural” (Bell et al. 2021) and implies barren emptiness, ignoring the cultural richness of the community and failing to acknowledge the context of structural racialization, segregation, and racial injustice that drives the lack of full-service grocery stores in communities of color (Corcoran 2021; Dickinson 2019; Usher 2015). Instead, some food justice activists and scholars have developed the concept of “American Apartheid” to refer to the lack of access to nutritious, affordable, culturally appropriate food in low-income communities of color (Akom et al. 2016; Dickinson 2019). The relationship between neighborhood food access and food security stems from the ways urban development patterns and housing discrimination have contributed to spatial inequities that separate communities along racial and class lines (Ball et al. 2009; Bruce et al. 2020; Raja et al. 2008), so that low-income communities of color who experience higher rates of food insecurity are also more likely to live in neighborhoods with less access to fresh foods. A line of related scholarship further unpacks the conception of food deserts and swamps, conceptualizing the centrality of sugar-sweetened foods and beverages as a form of environmental racism (Hatch 2016; Hatch et al. 2019). Other scholars have called for expanding conceptions of food access (Usher 2015) and connecting analyses of the food environment with structural racism and racial inequities in socioeconomic status (Bell et al. 2019; Dombrowski et al. 2022; Odoms-Young 2018). Food justice scholars and activists emphasize the self-determination and resilience of these communities and call for systems-level strategies to challenge and transform the structural conditions and policies that perpetuate food insecurity in these communities (Joyner et al. 2022; Leslie and White 2018; Reese 2019; White 2018). Food justice scholars have done important work on how these root causes intertwine with systemic discrimination based on race and nationality but are only beginning to uncover further intersections with gender identity and sexuality (Hoffelmeyer 2021; Leslie 2017, 2019; Leslie et al. 2019).
LGBTQ + food insecurity
Food insecurity is fundamentally an issue of inadequate resources, and LGBTQ+ food insecurity rates are fueled by gender and sexual oppression in areas like job and housing discrimination, which push people toward poverty. Despite common myths about affluent urban gay people, LGBTQ+ poverty rates average 22 percent compared to 16 percent for cisgender heterosexual people, with a transgender poverty rate of 29 percent (Badgett et al. 2019, p 2). Thirty one percent of Black LGBTQ+ people experience poverty compared to 25 percent of Black cisgender heterosexual people, and this pattern of higher poverty rates for people of color persists across LGBTQ+ subgroups (Badgett et al. 2019, p 3). A survey of transgender people in New York state found that transgender people’s rates of having lived below the poverty line and having been unhoused are more than twice those of cisgender people (Frazer and Howe 2015, pp. 9–10). Qualitative studies on LGBTQ+ food insecurity find job discrimination is a primary driver of food insecurity (McFadden 2020; Russomanno et al. 2019). Another qualitative study found that lack of transportation and stable housing are significant barriers to accessing emergency food relief (Wilson et al. 2020, p 2). Although there is insufficient data on LGBTQ+ poverty in New England, one study finds that LGBTQ+ people disproportionately live in poverty in Connecticut, Massachusetts, Rhode Island, and Vermont (data were not available for the other New England states) (Choi et al. 2019, pp. 18–23).
While these studies indicate that poverty resulting from discriminatory policy and practices are the main drivers of LGBTQ+ food insecurity, this oppression does not function solely through its effects on income. A national analysis of the same dataset we use here found that transgender people are nearly twice as likely as cisgender people to experience food insufficiency when their incomes are below 130 percent of the federal poverty threshold and are more than four times as likely as cisgender people to experience food insufficiency when their incomes are above twice the poverty threshold (Conron and O’Neill 2021, p 5). More than three quarters of both cisgender and transgender respondents “reported that their inability to afford more food was the cause of insufficient food in their households.” However, “Almost twice as many transgender people as cisgender people reported additional barriers to accessing food, including that they could not get out to buy food (24.1 percent and 12.3 percent, respectively) and safety concerns (22.0 percent and 11.8 percent, respectively)” (Conron and O’Neill 2021, p 7). Because these data were collected during the early phase of the COVID-19 pandemic when inability to get out to buy food and safety concerns were heightened for much of the population, these findings warrant further research to assess why these concerns were higher for transgender people. In sum, structural racism, cissexism, and heterosexism drive LGBTQ+ food insecurity by perpetrating poverty among LGBTQ+ people and people of color, but also when income levels are equivalent.
Since 2014, quantitative studies in nutrition and public health have documented LGBTQ+ food insecurity, finding patterns across race, gender identity, and sexuality. With data from a large and nationally representative survey, a pathbreaking study by the UCLA Williams Institute found 27 percent of LGBTQ+ people in the U.S. reported not having enough money for food at some point in the last year compared to 17 percent of cisgender heterosexual people (Brown et al. 2016, p 10). We see further disparities within the LGBTQ+ community by race, with LGBTQ+ food insecurity rates higher than cisgender heterosexual rates within each racial and ethnic group. Underscoring the essential intersection of race with gender identity and sexuality is the fact that even though LGBTQ+ food insecurity rates are elevated among white people, at 21 percent, Brown et al. (2016, p 15) found them lower than the food insecurity rates reported by cisgender heterosexual African American and Hispanic populations (24 and 28 percent, respectively) (see also Patterson et al. 2020, p 5). A study in New York found transgender people were nearly twice as likely as cisgender people to report being food insecure (Frazer and Howe 2015, pp. 9–10). One study of transgender and gender non-conforming people in the southeastern U.S. found 79 percent of respondents experiencing food insecurity (Russomanno and Jabson Tree 2020, p 5). While the numbers vary between these studies due to geography, data quality, and food insecurity measures, there are clear patterns in food insecurity rates by race, gender identity, sexuality, and their intersections.
However, existing studies on LGBTQ+ food insecurity rarely disaggregate gender identity from sexuality (lumping together LGB + with transgender+ individuals under the umbrella of LGBTQ+), which may inflate food insecurity estimates for LGB + people while underestimating those of transgender+ people. Furthermore, because it requires a very large sample size to quantitatively analyze differences not only by gender identity and sexuality, but also across racial groups, most of these studies rely on a national geographic scope, which may cloud disparities within and across regions. New England is a particularly interesting region to investigate for these types of inequities, given its reputation as a politically liberal region with a low overall food insecurity rate. In this analysis, we investigate whether deeper inequities are hidden by methods that aggregate the most marginalized groups into broader categories.
Methodology
Data and Sample
We drew data for this analysis from the U.S. Census Bureau’s Household Pulse Survey, specifically from Phases 3.2 through 3.5, which were collected between July 21, 2021 and August 8, 2022 (U.S. Census Bureau, 2021). The Household Pulse Survey utilizes the Census Bureau’s Master Address File of more than 145 million housing units to randomly select households for participation in the survey. Data for Phase 3.2 were collected over six two-week increments called “weeks,” as an artifact of earlier survey design. Data for Phases 3.3 through 3.5 were collected in three two-week increments, with two-week breaks in between. In each “week,” more than one million households were randomly selected to participate in the survey, and on average, about 64,000 did. The survey is completed online and requires about 20 min for the selected respondent to answer questions about themselves, their household, and their pandemic-era experiences. Each week’s sample is independently selected so that the six samples are made up of different respondents; to ensure a large enough group of LGBTQ+ respondents to generate statistically reliable estimates in this analysis, we pool the six samples from Phase 3.2 (Weeks 34–39) and the nine samples from Phases 3.3 through 3.5 (Weeks 40–48) to create one sample that covers approximately a one-year period (n = 971,836).
Although we included all respondents in the initial sample, not everyone answered each survey question. To ensure our analyses were among a consistent group of respondents, we created a subpopulation for analysis, only allowing those who answered the questions on gender identity, sexuality, race and ethnicity, age, food insufficiency, income, education, and state of residence to be included (n = 763,509). As noted throughout, we also limit most of the analysis to survey respondents who live in one of the six New England states (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, or Vermont). This final restriction yields our final sample size for most of the tables (n = 71,032).
Importantly, survey respondents are asked about food insufficiency in reference to their entire household. At the same time, characteristics about gender identity, sexual orientation, race-ethnicity, and age are all collected only about the individual responding to the survey on behalf of their household. As a result, it should be noted that we are deriving person-level estimates of food insufficiency from a measure designed to collect information about an entire household. We suggest here that while this technical difference should be borne in mind, the possibility that an LGB + or transgender+ person would live in a household where someone else experienced food insufficiency, but the respondent themselves did not, is minimal.
Among New England respondents, about 12 percent of the sample identifies as LGB + and about two percent as transgender+. State by state data collected by Gallup in 2015 and 2016 suggest that Vermont and Massachusetts have the highest share of residents identifying as LGBT in the nation, at around 5 percent of each state’s population (Gates 2017). Although the Gallup data are older and patterns of self-identification may have shifted over time, it is possible that LGB + and transgender respondents are over-represented in our sample, even after applying survey weights. However, since most of our analyses are within the LGBTQ+ groups, an underrepresentation of cisgender and heterosexual populations would not substantively change the findings here. In terms of racial-ethnic composition, the 2020 Decennial Census recorded that 73 percent of New England’s population identifies as white and 88 percent identifies as non-Hispanic (authors’ own analysis of 2020 Decennial Census redistricting data). In our sample, about 85 percent is white and 91 percent is non-Hispanic; applying survey weights partially addresses this bias, but people of color are still underrepresented in our sample. It is not possible to measure the effects of this nonresponse bias directly, although the Census Bureau finds that response rates to the survey were disproportionately high among people with higher incomes, and in communities with low poverty, low housing vacancy, and low rates of being uninsured (Peterson et al. 2021). Taken together, this suggests that our sample may exclude some of the most disadvantaged New Englanders.
Measures
The main “outcome” measure for this paper is food insufficiency. The specific survey question read “Getting enough food can also be a problem for some people. In the last 7 days, which of these statements best describes the food eaten in your household? Select only one answer.” Respondents could select from (1) enough of the kinds of food (I/we) wanted to eat; (2) enough, but not always the kinds of food (I/we) wanted to eat; (3) sometimes not enough to eat; or (4) often not enough to eat. For this paper, we consider those who sometimes or often do not have enough to eat to be experiencing food insufficiency.
Sexual orientation is measured with a single question asking respondents “which of the following best represents how you think of yourself?” Response options include gay or lesbian; straight, that is not gay or lesbian; bisexual; something else; or I don’t know. For this paper, respondents selecting any option other than “straight, that is not gay or lesbian” are considered LGB +.
Gender identity was collected as a series of questions asking respondents what gender they were assigned at birth and whether they describe themselves as male, female, transgender, or none of those. Here, respondents who identify as transgender or none of these, or whose current gender identity does not align with their reported sex assigned at birth, are considered transgender+.
Race and ethnicity were collected in two distinct questions. Respondents were first asked “Are you of Hispanic, Latino, or Spanish origin?” and allowed to select yes or no. Respondents were then asked “What is your race? Please select all that apply” with the options to select from “white, alone,” “Black, alone,” “Asian, alone,” or “Any other race alone, or race in combination.” The Census Bureau recodes the race responses before making the data public so that any respondents selecting multiple races are shifted into the fourth category (“race in combination”). We treat race and ethnicity separately here and make no revisions to either measure.
While this U.S. Census Bureau’s Household Pulse Survey’s measures of race, ethnicity, gender identity, and sexual orientation are far from capturing the actual diversity within each characteristic, the survey’s large sample size and recent addition of gender identity and sexual orientation questions (which previously were not included at all) offer a rare opportunity to analyze inequities among people with intersecting marginalized identities in a regional context.
Methods
To assess potential disparities in food insufficiency between LGBTQ+ and other respondents, we first conduct a series of chi-square tests assessing food insufficiency by gender identity and sexual orientation separately. We then assess the relationship between food insufficiency and race and ethnicity separately for LGB + and transgender+ respondents with another series of chi-square tests. We next utilize the bivariate results to identify measures for inclusion in the multivariable logistic regression models to follow. In these models, we focus on our key measures of interest: gender identity, sexual orientation, race, and ethnicity. We enter these measures in succession into a series of models, in order of theoretical interest, to estimate the independent contribution of each element on food insufficiency. Finally, to ground results in concrete examples, we calculate predicted probabilities following our final models to identify the probability of being food insufficient among specific groups.
All analyses are weighted using person-level replicate weights. Survey weights are designed to ensure that estimates calculated among the survey sample are representative of the population. Replicate weights provide multiple weights for each respondent and allow calculation of estimates using each weight in succession, then averaging the results. In this way, a single sample can be treated as multiple samples, generating more informed standard errors and more precise confidence intervals and significance tests. The Household Pulse Survey contains 80 replicate weights. All analyses were conducted in Stata/SE 17.0.
Results
Examining food insufficiency rates by sexual orientation reveals that 13 percent of LGB + New Englanders experienced food insufficiency in the past seven days, more than twice the rate among those identifying as straight. Looking at gender identity, 20 percent—or about one in five—transgender+ New Englanders experienced food insufficiency last week, twice the rate of cisgender women and three times the rate of cisgender men.
Table 1 shows that New England’s lower-than-national food insufficiency rate does not hold true for all New Englanders. Whereas cisgender New Englanders have lower food insufficiency rates than their counterparts in other regions, transgender+ New Englanders have a rate like transgender+ residents of other regions—that is, unlike cisgender New Englanders their rate does not reflect any New England advantage. To further disaggregate disadvantage within specific groups, we classify respondents by sexual orientation and gender identity, then estimate food insufficiency for these combinations, clarifying specifically for whom the New England advantage is unavailable. While cisgender men and cisgender women (across sexual orientation categories) have lower food insufficiency rates in New England than in other places, LGB + cisgender men, and transgender+ New Englanders (across sexual orientation categories) do not experience a New England advantage.Table 1 Percent Reporting Sometimes/Often Not Enough to Eat (Food Insufficiency) in Past 7 Days, by Respondent Characteristics and Geography
New England U.S., Outside New England
Estimate Low High Estimate Low High
Total 7.7 7.4 8.1 9.5 9.3 9.6***
Gender Identity
Cisgender Female 8.3 7.9 8.8 10.0 9.8 10.2***
Cisgender Male 6.5 6.1 7.1 8.3 8.1 8.5***
Transgender+ 19.8 16.4 23.7 22.3 20.7 24.0
Sexual orientation
LGB + 13.0 11.7 14.5 15.6 15.0 16.2**
Straight-identifying 7.0 6.7 7.3 8.7 8.5 8.8***
Sexual orientation & gender identity
LGB + Cisgender female 11.5 9.9 13.3 14.9 14.2 15.6***
LGB + Cisgender male 12.0 9.6 14.8 13.5 12.6 14.5
LGB + Transgender+ 21.7 17.5 26.6 23.8 21.9 25.8
Straight cisgender female 7.9 7.5 8.3 9.4 9.2 9.6***
Straight cisgender male 6.0 5.5 6.5 7.8 7.6 8.0***
Straight transgender+ 14.5 9.3 21.8 18.7 16.1 21.6
Age
18–24 10.0 8.1 12.3 11.8 11.0 12.6
25–34 9.0 8.0 10.1 11.2 10.7 11.7***
35–44 9.4 8.7 10.3 12.4 12.0 12.8***
45–54 10.1 9.3 11.0 11.5 11.1 12.0**
55–64 7.4 6.7 8.2 8.5 8.1 8.8*
65 or older 3.6 3.1 4.0 4.4 4.1 4.6**
Educational attainment
Did not graduate college 11.9 11.3 12.4 12.9 12.7 13.1**
Graduated college 2.2 2.0 2.4 2.9 2.8 3.0***
Ethnicity
Not Hispanic 6.8 6.5 7.2 8.5 8.3 8.6***
Hispanic 17.0 15.3 18.8 15.0 14.5 15.6*
Income
Under 25,000 25.1 23.6 26.8 27.7 27.0 28.3**
25,000 to 34,999 16.4 14.8 18.1 16.3 15.9 16.8
35,000 to 49,999 12.2 10.9 13.6 11.7 11.2 12.1
50,000 to 74,999 6.8 5.9 7.9 6.4 6.2 6.7
75,000 to 99,999 3.8 3.2 4.6 3.4 3.1 3.7
100,000 to 149,999 1.8 1.4 2.4 1.5 1.4 1.7
150,000 or more 0.8 0.5 1.2 1.0 0.9 1.2
Race
Any other race/combination 16.9 14.4 19.6 17.3 16.3 18.5
Asian alone 4.6 3.3 6.4 5.8 5.2 6.4
Black alone 18.1 17.5 18.8 18.4 15.8 21.2
White alone 6.7 6.4 7.1 8.0 7.8 8.1***
“LGB + ” category includes respondents identifying as lesbian, gay, bisexual, “something else,” or “I don't know.” “Transgender+ ” includes respondents identifying as transgender, “none of these,” or whose assigned sex at birth does not match their current gender identity. “Low” and “high” indicate the 95% confidence interval (i.e., estimate ± the margin of error). All estimates are calculated using person-level replicate weights. Asterisks indicate results of chi-square tests between geography and food insufficiency within respondent characteristics; *p < 0.05; **p < 0.01; ***p < 0.001
Source Carsey School of Public Policy analysis of Census Bureau Household Pulse Survey, Weeks 34–48, n = 971,836
What happens when we further dissect these numbers by race, ethnicity, income, and other characteristics? Table 2 first shows food insufficiency rates of LGB + vs. heterosexual New Englanders. Because the sample sizes are small for some subgroups, these estimates are not precise and include a large margin of error (range of possible values accounting for the margin of error is indicated in the “low” and “high” columns in Table 2). However, patterns of heightened food insufficiency rates are clear among some LGB + subgroups, including transgender+ people, low-income people, and people of color. Regarding the latter, about one in four Hispanic and Black LGB + New Englanders did not have enough to eat last week.Table 2 Percent of New Englanders Reporting Sometimes/Often Not Enough to Eat (Food Insufficiency) in Past 7 Days, by Demographics
Sexual orientation Gender identity
LGB + (n = 7426) Straight-Identifying ( n = 63,606) Cisgender Female (n = 41,579) Cisgender Male (n = 28,358) Transgender+ (n = 1095)
Estimate Low High Estimate Low High Estimate Low High Estimate Low High Estimate Low High
Total 13.0 11.7 14.5 7.0 6.7 7.3 8.3 7.9 8.8 6.5 6.1 7.1 19.8 16.4 23.7
Sexual orientation
LGB + 11.5 9.9 13.3*** 12.0 9.6 14.8*** 21.7 17.5 26.6
Straight-identifying 7.9 7.5 8.3 6.0 5.5 6.5 14.5 9.3 21.8
Gender identity
Cisgender female 11.5 9.9 13.3*** 7.9 7.5 8.3***
Cisgender male 12.0 9.6 14.8 6.0 5.5 6.5
Transgender+ 21.7 17.5 26.6 14.5 9.3 21.8
Age
18–24 12.9 9.4 17.6* 8.5 6.0 11.8*** 9.8 7.4 12.8*** 9.5 6.8 13.1*** 14.2 7.1 26.5
25–34 10.9 8.8 13.4 8.4 7.4 9.5 10.2 8.7 12.0 7.0 5.8 8.5 15.9 10.8 22.9
35–44 13.2 10.8 15.9 8.9 8.0 9.8 11.0 9.9 12.2 7.5 6.3 9.0 16.4 9.3 27.3
45–54 19.6 14.8 25.4 9.3 8.5 10.2 11.8 10.7 13.1 7.7 6.4 9.2 27.8 17.2 41.6
55–64 12.2 8.9 16.6 7.1 6.4 7.8 7.7 6.8 8.7 6.8 5.8 7.9 22.8 14.5 34.0
65 or older 13.7 10.1 18.3 3.0 2.6 3.5 2.7 2.2 3.5 3.7 3.0 4.4 27.8 16.9 42.1
Educational attainment
Did not graduate college 19.5 17.3 21.8*** 10.8 10.3 11.4*** 13.1 12.3 13.9*** 9.9 9.1 10.8*** 25.5 20.7 31.0***
Graduated college 4.4 3.6 5.4 1.9 1.7 2.1 2.3 2.0 2.6 1.8 1.4 2.2 8.5 5.8 12.5
Ethnicity
Not Hispanic 11.4 9.9 13.1*** 6.2 5.8 6.6*** 7.3 6.8 7.8*** 5.8 5.4 6.4*** 18.0 14.2 22.4*
Hispanic 25.8 20.4 32.1 15.4 14.0 16.9 18.8 16.8 21.1 13.9 11.3 17.1 30.7 19.8 44.3
Income
Under 25,000 31.8 27.7 36.3*** 23.5 21.8 25.4*** 24.4 22.6 26.4*** 24.6 20.9 28.8*** 36.7 28.8 45.4***
25,000 to 34,999 20.2 15.9 25.2 15.7 14.0 17.5 16.3 14.6 18.3 16.5 14.0 19.4 16.3 9.0 27.8
35,000 to 49,999 13.4 9.7 18.2 12.0 10.7 13.5 13.5 11.7 15.5 10.0 7.9 12.5 23.3 13.0 38.0
50,000 to 74,999 7.5 5.9 9.5 6.7 5.7 7.9 6.2 5.1 7.4 7.5 6.0 9.3 8.2 3.9 16.3
75,000 to 99,999 5.8 3.8 8.9 3.6 2.9 4.4 3.2 2.6 3.9 4.6 3.5 6.0 2.8 1.0 7.8
100,000 to 149,999 4.0 1.9 8.1 1.5 1.2 2.1 1.7 1.2 2.4 1.8 1.2 2.9 7.3 2.0 23.7
150,000 or more 6.5 3.7 11.8 0.3 0.1 0.5 0.5 0.2 1.3 0.4 0.2 0.7 25.1 14.3 40.1
Race
Any other race/combination 26.7 21.2 33.1*** 13.8 11.0 17.3*** 15.6 12.7 19.1*** 13.8 9.5 19.7*** 41.9 29.0 56.1***
Asian alone 16.4 8.8 28.3 3.2 2.2 4.6 5.1 3.3 7.8 3.8 2.3 6.2 16.6 6.0 38.4
Black alone 28.9 19.8 40.2 17.1 14.8 19.6 17.3 14.7 20.2 18.7 15.2 22.8 33.3 18.5 52.2
White alone 10.7 9.3 12.2 6.2 5.9 6.5 7.5 7.0 7.9 5.7 5.2 6.2 14.7 11.2 19.0
“LGB + ” category includes respondents identifying as lesbian, gay, bisexual, “something else,” or “I don't know.” “Low” and “high” indicate the 95% confidence interval (i.e., estimate ± the margin of error). All estimates are calculated using person-level replicate weights. Asterisks indicate results of chi-square tests. *p < 0.05; **p < 0.01; ***p < 0.001
Source Carsey School of Public Policy analysis of Census Bureau Household Pulse Survey, Weeks 34–48
Like with sexuality, Table 2 also presents food insufficiency rates for gender identity and compares transgender+ New Englanders to cisgender men and cisgender women New Englanders by race, ethnicity, income, and more. Although food insufficiency is uniformly higher among transgender+ respondents, for some subgroups, the disparity between cisgender and transgender+ New Englanders is especially wide. For instance, food insufficiency is about 1.5 times higher among transgender+ respondents than cisgender men respondents who are LGB +, who are young adults, or who are very low income. But among transgender+ respondents who are Hispanic, Black, or over age 65, rates are three or more times the rate of their cisgender men counterparts. Uniformly, multiracial, Black, and Hispanic New Englanders have higher rates of food insufficiency than their white or non-Hispanic neighbors, and so too do transgender+ New Englanders have elevated rates of food insufficiency compared with their cisgender neighbors. However, being transgender+ and Black, multiracial, or Hispanic is associated with extreme rates of food insufficiency, with transgender+ New Englanders of color experiencing food insufficiency at two to four times the already-high rates of cisgender New Englanders of color.
Finally, one of the most unexpected findings from Table 2—high rates of food insufficiency among the highest-income transgender+ respondents—offers an opportunity to consider the ways that even attempts to disaggregate estimates by group can still obscure important differences. Attempting to identify why these respondents are high income-high food insufficiency, we find that transgender+ people in this income bracket are substantially more likely to be under age 25 (18 percent, versus 3 to 4 percent of cisgender respondents), report an average of 5.2 people in their household (versus an average of 3 among cisgender respondents), and perhaps most alarmingly, are substantially more likely to describe their living quarters as a boat, RV, or van (25.2 percent, compared with less than 0.2 percent of cisgender respondents). Because the income measure here is collected at the household level, we suggest that these respondents may indeed be reporting the pooled resources of all household members (as instructed). However, as a full 30 percent of transgender+ respondents in this income category live in households of 8 or more people, we posit that reported income is not a proxy for income available to the respondent as in smaller households.
To better understand whether and how gender, sexuality, race, income, and other characteristics intersect to enhance risks for food insufficiency, we use logistic regressions to separately assess the effects of each characteristic. This is especially important since much of the existing scholarship aggregates gender identity and sexual orientation into a single measure, obscuring potential to examine independent effects of each on the overall experience of food insufficiency. In Table 3, Model 1, we first include just a measure of gender identity, and find that the odds of food insufficiency for transgender+ respondents are 3.5 times those of cisgender men respondents. To parse out the distinct effect of sexual orientation from gender identity, Model 2 includes an indicator of LGB + identity. That both measures have a sizable odds ratio that is statistically significant suggests that each characteristic contributes its own explanatory power to our estimation of food insufficiency. In Model 3, we also include measures of race and ethnicity and others to further isolate the effects of gender identity and sexual orientation. Model 3 shows that even after accounting for the effects of age, education, income, race and ethnicity, being LGB + increases a New Englanders’ odds of experiencing food insufficiency by 38 percent over a straight-identifying person’s odds, and being transgender+ increases the odds by 70 percent over cisgender men. The odds of food insufficiency shift with age, even accounting for income and more, with the odds increasing in middle adulthood, then declining sharply for adults age 65 and older. While identifying specific causes is beyond the scope here, young adults may be protected by living with their families of origin, while middle adulthood can bring the resource strains of childrearing. Both a college degree and higher incomes are consistently protective against food insufficiency, while being Black, multiracial, or Hispanic also increases the odds of food insufficiency as compared to a person who is white or non-Hispanic, respectively.Table 3 Logistic Regressions Predicting Food Insufficiency Among New Englanders (Odds Ratios)
Model 1 Model 2 Model 3
OR SE OR SE OR SE
Gender Identity
Cisgender female 1.30 0.07*** 1.28 0.07 1.03 0.06
Cisgender male Ref. Ref. Ref.
Transgender+a 3.52 0.42*** 2.45 0.35*** 1.70 0.26**
LGB +b 1.75 0.12*** 1.38 0.12***
Age
18–24 Ref.
25–34 1.29 0.20
35–44 1.51 0.21**
45–54 1.69 0.25**
55–64 1.18 0.17
65 or older 0.44 0.06***
Graduated college 0.35 0.03***
Income
Under 25,000 Ref.
25,000 to 34,999 0.62 0.05***
35,000 to 49,999 0.47 0.04***
50,000 to 74,999 0.26 0.03***
75,000 to 99,999 0.16 0.02***
100,000 to 149,999 0.08 0.01***
150,000 or more 0.04 0.01***
Hispanic 1.21 0.09*
Race
Any other race or combination 1.59 0.17***
Asian alone 0.79 0.17
Black alone 1.75 0.18***
White alone ref
Constant 0.07 0.00*** 0.07 0.00*** 0.27 0.04***
n 71,032 71,032 71,032
F (2,78) 46.73*** (3,77) 52.62*** (19,61) 89.71***
All analyses are weighted with person-level replicate weights
aIncludes those identifying as “transgender,” “none of these,” or as a gender different from sex assigned at birth
bReference is “not lesbian, gay, or bisexual”
*p < 0.05; **p < 0.01; ***p < 0.001
Source Carsey School of Public Policy analysis of Census Bureau Household Pulse Survey, Weeks 34–48
To help visualize the independent and converging effects identified in the regression models, we also calculate predicted probabilities of experiencing food insufficiency for a variety of groups. This approach allows researchers to hold constant the measures controlled in the final regression model (Table 3, Model 3) while “solving” the regression equation for different combinations of values on the included variables (e.g., for each income category or for Black respondents in each age group). As a baseline, Fig. 1 shows the predicted probability of reporting food insufficiency by membership in the listed groups (regardless of other identities).Fig. 1 Predicted probability of reporting food insufficiency by selected characteristics
Figure 2 shows the predicted probability of experiencing food insufficiency for straight-identifying New Englanders in dark blue and LGB + New Englanders in turquoise, with separate bars for white, Hispanic, and Black respondents. As in Fig. 1, these probabilities are calculated after controlling for gender, age, education, and income, as included in Table 3, Model 3.Fig. 2 Predicted probability of reporting food insufficiency by selected characteristics
After controlling for differences in age, education, income, and gender identity, the probability that a person of color is experiencing food insufficiency is significantly higher than among white respondents, and LGB + people of all race-ethnicities have a greater probability of experiencing food insufficiency than their straight-identifying counterparts.
Figure 3 takes the same approach as Fig. 2, and demonstrates that even protective factors like being white are not sufficient to buffer transgender+ New Englanders from a high probability of food insufficiency. Specifically, New Englanders are most protected if both white and cisgender, although having either of those characteristics lowers the probability of food insufficiency compared with those who have neither. Notably, being white does not protect transgender+ New Englanders from an elevated probability of food insufficiency. However, racism intersects with cissexism in such a way where Black and Hispanic transgender+ New Englanders face extreme probabilities of food insufficiency.Fig. 3 Predicted probability of reporting food insufficiency by selected characteristics
Comparing Figs. 2 and 3 yields a compelling reason to assess sexuality and gender identity separately. Figure 2 shows that while those identifying as LGB + certainly face higher probabilities of food insufficiency than their straight-identifying counterparts, the gap across sexual orientation is moderate, around two to three percentage points across racial-ethnic groups. By contrast, Fig. 3 shows that transgender+ identity is an even stronger predictor of food insufficiency, with the predicted probability of being food insufficient 4–5 percentage points higher among transgender+ respondents than their cisgender counterparts, regardless of race-ethnicity.
Discussion
In this paper, we document elevated rates of food insufficiency among New Englanders who identify as people of color, transgender+, and LGB +, examining how each characteristic predicts food insufficiency on its own. We also document how race, ethnicity, gender identity, and sexual orientation intersect to create differing portraits of risk that would be lost in an analysis that lumped gender identity and sexual orientation into a single measure, or that did not inspect race and ethnicity separately. We find that food insufficiency is elevated among LGB + New Englanders, transgender+ New Englanders, and New Englanders of color, but that in particular, transgender+ New Englanders face significant risk of food insufficiency.
The intersections of race, gender identity, and sexuality are essential to understanding LGBTQ+ food insecurity. Other scholarship has reported that elevated risks of food insecurity exist for white LGBTQ+ people, but that even those elevated rates are lower than among cisgender heterosexual African American and Hispanic populations (Brown et al. 2016; Patterson et al. 2020, p 5). We find evidence of that phenomenon here too, but by examining gender identity and sexuality separately, find that this only holds true for sexuality, and indeed, that membership in a privileged racial category is not sufficient to buffer transgender+ New Englanders from extreme food insufficiency.
A core finding of this study is that the oppression that drives LGBTQ+ food insufficiency operates both through and outside of income. LGBTQ+ people have higher poverty rates than cisgender heterosexual people (Badgett et al. 2019), which disproportionately limits LGBTQ+ people’s ability to achieve food security. These higher poverty rates are due to discrimination in the basic aspects of everyday life, especially in employment, transportation, and housing (Russomanno et al. 2019; Wilson et al. 2020).
However, this study demonstrates that even after holding income constant, transgender+ New Englanders still face disproportionate levels of food insufficiency. Explaining why demands further research, but we can still identify documented areas of discrimination against transgender+ people that offer clues. For example, job discrimination does not only mean lower income, but can also increase the frequency of economic instability that limits a person’s safety net and increases demand for food assistance (McFadden 2020). Housing discrimination limits where transgender+ people are able—and feel safe enough—to live, increasing instability (Grant et al. 2011). Binary gender markers on drivers’ licenses are an example of transportation discrimination that may also diminish the likelihood of transgender+ people applying for food assistance that requires identification (Maier 2020). Thanks to discrimination in the health care system, transgender+ people are often forced to travel extra distance and pay elevated costs to receive the care that they need, further limiting available resources (Kachen and Pharr 2020).
Furthermore, many Republicans are centering LGBTQ+ hate by fueling hysteria about unproven issues such as transgender+ bathroom use and sports participation (Hasenbush et al. 2019). The GOP is making a concerted effort to increase LGBTQ+ stigma, such as with The Texas Republican Party’s 2022 policy platform “defining homosexuality as an ‘abnormal lifestyle choice’ and also opposing ‘all efforts to validate transgender identity’” (Lavietes 2022). Taken together, this study suggests that these various ways anti-LGBTQ+ sentiments are institutionalized make people food insecure, which we have quantified here.
Coupled with the emerging literature on LGBTQ+ food insecurity, this study points to three areas for future research. First, due to data limitations, this work was unable to investigate the critical role of place, and in particular, of rurality. While the role of residence in a rural area is insufficiently addressed in existing food insecurity literature, several recent studies point to rurality as being an important factor for LGBTQ+ people. Whereas cisgender heterosexual poverty is about 16 percent in both rural and urban areas, poverty for LGBTQ+ people is 21 percent in urban and 26 percent in rural places (Badgett, Choi, and Wilson 2019: 9). One qualitative study comparing LGBTQ+ food insecurity in a rural and an urban county found that charitable food services in the rural county were more likely to be religious (Wilson et al. 2020, p 24), and churches are often the site for (even publicly funded) emergency food relief (Russomanno et al. 2019, p 94). Some of these sites even expect people to pray before receiving emergency food relief (Wilson et al. 2020, p 15), and some LGBTQ+ people are not comfortable seeking food assistance in these settings due to discrimination (Russomanno et al. 2019).
Second, age may be another factor related to food insecurity and the structural oppression of LGBTQ+ people over the life course. While our findings from Table 2 found uneven rates of food insufficiency across the life course, it was beyond the scope of this work to identify mechanisms behind those patterns. Earlier work finds that about one in three LGBTQ+ young people are food insecure (Wilson and Conron 2020, p 2). Another study found that 54 percent of LGBTQ+ 18- to 35-year-olds are food insecure, with trans men showing the highest rate at 65 percent (Arikawa et al. 2021, p 1235). LGBTQ+ poverty and job discrimination lead to increased likelihood of sex work among LGBTQ+ people, and one study finds that food insecurity increases young sex workers’ likelihood of being pressured into sex without a condom, increasing HIV risk among young sex workers (Barreto et al. 2017). Disproportionately high rates of food insecurity among LGBTQ+ youth persist among college students (Haskett et al. 2020) and among LGBTQ+ graduate students (Boncyk et al. 2021). LGBTQ+ seniors also may face unique challenges with food insecurity. For example, LGBTQ+ seniors are disproportionately poor, and are less likely to have adult children who act as caregivers (Viola et al. 2018; Wilson et al. 2020).
Third, there is a clear need for more qualitative research on LGBTQ+ food insufficiency, given the findings of quantitative analyses like this one and others cited here, that demonstrate higher rates of food insufficiency for these groups. Given that these broad patterns have been clearly identified, the next step is to better understand the processes and mechanisms that are driving higher food insufficiency rates for these groups. Our inability, for example, to be more specific about the living conditions of transgender+ New Englanders who have high household income but still experience food insufficiency offers a prime example of areas in which deeper understanding of circumstance and context is needed. In future work, better explaining how identity-based marginalization impacts food security will shed light on avenues for more impactful policy and practice to address these disparities.
Conclusion
In conclusion, these findings contribute to the literature on food insecurity by clearly demonstrating the need for greater attention to the root causes of food insecurity in the U.S. Our analysis supports food justice scholarships’ call for examining the role of structural racialization, segregation, and racial injustice that drives food insecurity. By examining food insufficiency with an intersectional analysis of gender identity and sexuality in addition to race and ethnicity, our findings indicate that structural patterns of gender and sexual discrimination and injustice play a significant role in increasing people’s risk of experiencing food insufficiency. The implications of this analysis are that research, policy and practice focused on food security that do not take identity-based discrimination and patterns of disadvantage into account may be leaving the most food insecure people behind. The effects of cissexism, heterosexism, and racism on food insufficiency persist even when we hold income constant; this oppression operates both through and outside of income. This suggests that income-based food insecurity programs alone are insufficient for addressing the problem. Our analysis shows that for food security scholars and practitioners to be successful in their goals, they must pay explicit attention to gender identity and sexuality. This study further supports the calls in food justice scholarship for increasing attention to structural oppression that drives employment, housing, and income disparities. Policy and practice that is based on income or food access alone is not addressing the problem, especially for people who belong to multiple marginalized groups.
Acknowledgements
We thank the Food Systems Lab at the University of New Hampshire and Angela Serrano at the Universidad de los Andes for their valuable support and feedback on this paper.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735207 | NO-CC CODE | 2022-12-14 23:29:53 | no | Agric Human Values. 2022 Dec 9;:1-16 | utf-8 | Agric Human Values | 2,022 | 10.1007/s10460-022-10403-5 | oa_other |
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J. Comput. Educ.
Journal of Computers in Education
2197-9987
2197-9995
Springer Berlin Heidelberg Berlin/Heidelberg
252
10.1007/s40692-022-00252-w
Article
A new trend of learning and teaching: Behavioral intention towards mobile learning
http://orcid.org/0000-0002-1109-3279
Hameed Farhina [email protected]
1Farhina Hameed
(Corresponding author) received her Ph.D. (Marketing) degree from SZABIST, Islamabad, and currently serving as an Assistant Professor at Faculty of Management Sciences, National University of Modern Languages, Islamabad, Pakistan. She is associated with the teaching profession for a decade. She is enthusiastic and passionate about research-based work. Her area of interest is the behavioral intention, mobile learning, social media marketing, and CSR. She has published several papers in renowned journals with numerous citations.
Qayyum Abdul [email protected]
[email protected]
2Abdul Qayyum
is an Associate Professor at the Faculty of Management Sciences, Riphah International University, Islamabad, Pakistan. He obtained his Ph.D. in Marketing from the School of Management, Asian Institute of Technology (AIT), Bangkok, Thailand. He secured indigenous and foreign scholarships from the Higher Education Commission (HEC) of Pakistan for his MS and Ph.D. degrees respectively. His areas of interest are services marketing, social marketing, marketing ethics, and marketing from an Islamic perspective. He has published his research in several well-reputed national and international journals.
Khan Faheem Ahmad [email protected]
3Faheem Ahmad Khan
is an Assistant Professor at COMSATS, Islamabad, Pakistan. He obtained his Ph.D. degree from SZABIST, Islamabad and associated with teaching profession from last 15 years. He has interest in research and hold strong strong grip on statistical analysis. He has published various research papers in well-reputed national and international journals.
1 grid.444798.2 0000 0004 0607 5732 Faculty of Management Sciences, National University of Modern Languages, Islamabad, Pakistan
2 grid.414839.3 0000 0001 1703 6673 Faculty of Management Sciences, Riphah International University, Islamabad, Pakistan
3 grid.418920.6 0000 0004 0607 0704 Department of Management Sciences, COMSATS University, Islamabad, Pakistan
5 12 2022
132
20 6 2022
20 9 2022
15 11 2022
© Beijing Normal University 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Mobile learning has expanded the reach of electronic and distance education, which has been made possible by modern technology and globalization. There is a need to identify the elements that are essential in determining behavioral intention towards mobile learning because there is a dearth of scientific justification for their importance. The goal of the study is to ascertain how behavioral intention towards mobile learning are affected by perceived entertainment, perceived informativeness, perceived irritation, perceived trust, and perceived value. Moreover, the study examines the mediating role of attitude among the aforementioned variables and behavioral intention towards mobile learning. Finally, the moderating impact of social influence on the relationship between attitude and behavioral intention towards mobile learning is investigated. The multistage cluster sampling technique is used to gather data from 586 students. Multiple regression analysis is utilized to test hypotheses, whereas AMOS-23 is used for confirmatory factor analysis. Hayes & Preacher’s macro is applied to assess mediation and moderation. The results show that perceived entertainment, informativeness, trust, and value significantly and directly influence attitude towards mobile learning, but perceived irritation has a negative effect. Additionally, perceived entertainment, trust, and value have a direct and significant impact on behavioral intention towards mobile learning, whereas perceived irritation has a negative and informativeness has an insignificant impact. Finally, the attitude is supported as a mediator, while social influence confirms its role as a moderator. The study offers significant theoretical and practical implications.
Keywords
Mobile learning
Attitude
Behavioral intention
Entertainment
Informativeness
Irritation
Perceived trust
Perceived value
Pakistan
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pmcIntroduction
Mobile learning is learning conducted outside of the classroom using mobile devices (Reychav et al., 2016). It is a learning that takes place on portable electronic devices, including smartphones, tablets, MP3 (music parameter) players, and all other mobile gadgets (Tan et al., 2014). Mobile learning is expected to play a significant role in many educational settings that provide students with timely and appropriate directions. Online learning is replacing traditional classroom teaching in the educational process, but it still depends on accurate information, appropriate delivery, and opportunity (Milosevic et al., 2015; Sophonhiranrak, 2021). The COVID-19 pandemic has made things worse and increased interest in mobile learning. Challenges are being faced by educational institutions worldwide as a result of this pandemic, and fewer students are taking exams (Alturki & Aldraiweesh, 2022). At the moment, educational institutions are fully accountable for implementing novel teaching methods and procedures (Naciri et al., 2020).
Informal education and the use of mobile technologies for education have both seen significant development. As mobile technology and the internet are combined, there is an increase in communication and learning engagement. The use of smartphones and tablets are a fundamentally beneficial addition to accessing educational resources due to the acceptability of mobile technology as a new tool for learning purpose by students (Al-Bashayreh et al., 2022). The adaptability of modern technology has both direct and indirect effects on how well students learn. Though mobile learning is fast expanding globally due to mobile technologies particularly designed for educational purposes, the research on behavioral intention toward mobile learning is still in its infancy (Naciri et al., 2020; Criollo-C, 2021). Zeithaml (1988) defined behavioral intention as the customer’s future conduct based on his or her subjective assessment and generally classified it into favorable and unfavorable behavioral intentions. In the past, behavioral intention has been extensively researched with the inclusion of a variety of variables, such as intrinsic and extrinsic motivation (Feng et al., 2016), adoption of mobile technologies (Sanakulov & Karjaluoto, 2015), trust (Luo et al., 2010), word of mouth, image and attitude (Jalilvand et al., 2012), and social norm (McDonald & Crandall, 2015). The potential for behavioral intention toward mobile learning in higher education is enormous given the development of technology, as shown by previous rearches (Prieto et al., 2015; Criollo-C et al., 2021; Humida et al., 2022). However, it is stated that the development of behavioral intentions toward mobile learning (BITML) is not straightforward and that a number of significant factors, including perceived entertainment, informativeness, irritation, trust, and value, may have an impact. Although it is thought to be one of the paradigms that is most rapidly changing, such a combination of factors has previously been overlooked (Chen, 2011; Viberg & Gronlund, 2013; Cheok & Wong, 2015; Mohammadi, 2015a, 2015b, 2015c; Reychav & Wu, 2015; Wong et al., 2015).
Furthermore, it is essential to comprehend the underlying mechanisms by which behavioral intentions toward mobile learning (BITML) may be influenced by perceived entertainment, informativeness, irritation, trust, and value. The extant literature indicates that attitude mediates the association between a variety of predictors, such as entertainment, relaxation, escape time, value, and quality, and dependent variables, such as behavioral intention, purchase intention, and buying intention (Curras-Perez et al., 2014; Hameed et al., 2018; Mohammadi, 2015a; Zhu & Chang, 2014); however, mediating role of attitude between perceived entertainment, informativeness, irritation, trust and value, and BITML has not been explored yet. Therefore, in order to provide a more comprehensive picture, this study aims to investigate the impact of the five factors described above on attitude toward mobile learning (ATML), which in turn influences BITML and mediating role of ATML between relathionship of entertainment (ENT), informativeness (INF), irritation (IRR), trust (PERT), value (PERV), and BITML.
Numerous studies have looked into the connection between social influence and behavioral intention in the past (Contractor & DeChurch, 2014; Jung et al., 2016; Yang Lu et al., 2012). Because the social group gives compelling information regarding a product’s suitability and aids in decision-making, social influence lowers the risk of adoption (Alzaidi & Shehawy, 2022). Most people are not impacted by the media, but the peer group they are surrounded by has a big effect on their decision-making process. In the age of technology and mobile education, however, the moderating impact of social influence (SI) on the relationship between attitude and behavioral intentions toward mobile learning is comparatively understudied. Thus, another purpose of the study is to ascertain how social influence moderates the said relationship.
Literature review
Theoretical foundation
The relationship of behavioral intention toward mobile learning is based on the Theory of Planned Behavior (TPB). The TPB declares that “behavior is a direct function of behavioral intention and perceived behavioral intention is formed by one’s attitude which reflects the feeling of favorableness or unfavorableness toward performing a certain behavior.” Previous literature showed that TPB has been used in various types of research to measure the planned behavior, attitude, and intentions toward mobile learning as mandated by Kolog et al., (2014) and Lee et al., (2015a, 2015b). Secondly, User & Gratification (U&G) theory has been used to evaluate the BITML. Blumler and Katz (1974) established the concept of mass media communication, which was based on a functionalist perspective. This hypothesis is employed in the media paradigm, which asks “why people use certain media and what gratifications they obtain from media access.” The theory is valuable for studies involving active media users because it incorporates the user’s psychological and social demands, which illuminate “how and why individuals choose to utilize specific media” (Kim Xu, & Gupta, 2012). As a result, mobile learning satisfies the U&G assumptions because U&G asks “what people do with media, not what media do to people,” it is particularly well suited to mobile learning research, which has the potential for both interpersonal and mass communication (Chen, 2011; Johnson & Yang, 2009; Reychav & Wu, 2015). The U&G theory has numerous fundamental constructs and various typologies have been used in different years to explore the effects with different mediums. The literature showed that the most prominent and frequently used dimensions include entertainment, informativeness, and irritation (Chen & Wells, 1999; Eighmey & McCord, 1998; Fenech, 1998; Korgaonkar & Wolin, 1999; Lim & Ting, 2012). Thus, in the present study for determining BITML, three antecedents of U&G theory have been considered, i.e., entertainment, informativeness, and irritation.
Behavioral intention toward mobile learning
BITML is evolving concept as mandated by Humida, (2022) with the increased use of smartphones. The advancement of technology has benefited the education sector and various studies have been undertaken from the perspective of students to analyze the success elements of the notion of mobile learning. Mobile learning has introduced new strategies that are significantly superior to those offered by electronic learning (i.e., time and space flexibility). Mobile learning presents enormous prospects in higher education as technology advances, and past study has shown a lot of interest in this field. Prieto et al., (2015) have expanded on the idea that mobile devices have become increasingly important in the teaching and learning process in recent years. In the realm of informal education and mobile technologies for educational purposes, mobile learning is well established and when mobile technology is combined with the internet, it has enhanced communication and learning engagement. Smartphones and tablets are extremely useful tools for accessing instructional resources (Al-Bashayreh, 2022). Mobile learning provides students with timely and suitable guidance and in a variety of educational settings, mobile learning is projected to play a key role that may affect behavioral intentions. Several factors can influence students’ deliberate conduct when it comes to mobile learning. It is not a choice; rather, it is a necessity for keeping up with evolving technology and innovation. Students may easily and rapidly access and use learning tools anywhere and whenever they want by adopting portable innovation. Cheng (2015) looked into the elements that influence mobile learning acceptability, namely the role of technological features and compatibility. Nikou and Economides, (2017) agreed with the findings in terms of acceptance and intention to use mobile learning. Although there have been a significant amount of research into mobile learning acceptance, there has been limited research into the driving factors that influence students’ intention to use mobile devices for assessment purposes. It also gave participants greater knowledge of how to create mobile-based evaluations that help learners, improve their learning experience, and promote learning. It is assumed that the adoption of behavioral intention toward mobile learning is a practical idea in the current study that can provide a clear explanation based on extensive literature and theories.
Perceived entertainment
“The ability to meet an audience’s need for escapism, diversion, esthetic satisfaction, or emotional enjoyment,” (Ducoffe, 1996). Customers’ loyalty and value can be increased through entertainment because when the media is viewed as enjoyable, a favorable attitude develops, which leads to positive behavioral intentions. Blumler and Katz (1974) divided 35 media needs articulations into five categories: cognitive needs, which reinforce data, information, and comprehension; affective needs, which strengthen stylish, pleasurable, and passionate experience; individual integrative needs, which reinforce believability, certainty, dependability, and status and join subjective and emotional; social integrative needs, which reinforce contact with family, companions, and the world; and tension needs, which reinforce contact with family, companions, and the world (Zolkepli & Kamarulzaman, 2011). The importance of entertainment in virtual communities on attitudes toward learning is stressed. A cheerful attitude is positively connected with a high entertainment factor in certain media (Haq, 2009). Chen et al., (2012) argue by stating that mobile devices have evolved into indispensable gadgets that are used for leisure as well as productivity enhancement through mobile apps (Islam, Kang, & Yang, 2013). Marketers have adopted this technology to provide information due to the rapid increase in mobile phone usage (Aslam, Batool, & Haq, 2016). Customers can access remote systems to peruse information whenever and wherever wanted. The evolution of communication has a significant impact on the opportunity to grow and learn. Games and other activities are included in learning and teaching methodologies to make education more enjoyable. This type of activity is used to entertain scholars in a variety of educational institutions. The relevance of leisure was further highlighted by Lu et al., (2016) as it is crucial for everyone, especially students, who are under a lot of pressure when studying and leisure time can help them relax. Consumers appear to be more engaged with digital media than with traditional media, even though digital media is more complex. Consumer attitudes and source reliability were both affected directly and significantly by entertainment (Gvili & Levy, 2016). Therefore, based on the literature following hypotheses have been developed:
H1
Entertainment has a positive and significant effect on attitude toward mobile learning.
H6
Entertainment has a positive and significant effect on behavioral intentions toward mobile learning.
Perceived informativeness
“The ability to advise consumers about product options so that purchases generate the best possible satisfaction” (Ducoffe, 1996). Informativeness is a perceptual construct that is typically tested using self-reported items and it contains logical appeal due to its potential to assist a consumer in making an informed decision about message recognition, and therefore it is conceptually distinct from “emotional appeal.” Customers on the internet usually demand subjective qualities in the educational content they expect from websites, such as accuracy, opportunities, and value, and those who can meet these requirements will enjoy favorable reception from their audiences (Lim & Ting, 2012; Richard & Habibi, 2016). According to Dehghani et al., (2016), informativeness is one of the key variables in defining customer value and loyalty which leads to positive behavioral intentions. Both informativeness and entertainment can influence customer behavior. It interacts with users and has an immense impact on purchase intention. In digital communication, informativeness is perceived as an important factor that has a gigantic impact on consumer attitudes (Gvili & Levy, 2016). According to the findings, the most important criteria impacting the intention to re-use mobile advertising were informativeness and credibility (Lin Hsu & Lin 2017; Arli, 2017). Upon the extensive literature following hypotheses have been constructed:
H2
Informativeness has a positive and significant effect on attitude toward mobile learning.
H7
Informativeness has a positive and significant effect on behavioral intentions toward mobile learning.
Perceived irritation
“The approaches that annoy, offend, insult, or are too manipulative, consumers are likely to see it as an unwanted and irritating impact” (Ducoffe, 1996). Irritation is similar to reactance to anything in that customers typically reject advertisements that they consider intrusive. Irritation is a feeling that is influenced by a variety of elements, such as ad frequency, ad content, and ad timing. It is a factor that determines mobile advertising adoption (Zedan & Salem, 2016). Furthermore, the increasing growth in mobile phone usage has led marketers to adopt this medium to provide information, which is a source of frustration (Aslam et al., 2016). Boateng et al., (2016) mandated that the negative consequences of irritation on attitudes toward mobile advertising can be reduced by personal innovativeness, which has a favorable effect on consumers’ attitudes toward mobile advertising. It has been identified as a key determinant of brand loyalty and value by several authors in the past. It has a severe detrimental influence on brand loyalty (Dehghani et al., 2016). Irritation is defined by Gvili and Levy (2016) as digital message avoidance, which is interpreted as message skepticism. The level of discomfort is determined by a variety of circumstances beyond the advertisers’ control. It depends on the attitude of the customers and the type of work he or she does. Consequently, based on the literature, the following hypotheses have been developed:
H3
Irritation has a negative and significant effect on attitude toward mobile learning.
H8
Irritation has a negative and significant effect on behavioral intentions toward mobile learning.
Perceived trust
Trust has received a lot of attention; its definition varies depending on the area, such as psychology, sociology, economics, and marketing. Each profession has its definitions and perspectives on what it means to be trustworthy. It has been around since human civilization and social interaction began. As a result, it serves humanity as both a benefit and a necessity. Morgan and Hunt (1994) defined trust as “existent when one party has faith in the reliability and integrity of a partner.” Trust is a critical construct catalyst in many transactional connections. In the context of a relationship characterized by uncertainty and vulnerability, trust is seen as a controlling mechanism. Additionally, customer sentiments have a significant impact on consumer behavior. Customers, in reality, develop positive feelings toward people with whom they have previously met. Behavioral intention determines planned to conduct, and behavioral intention is influenced by attitudes. In the same way, attitude acts as a link between beliefs and intentions. The topic of mobile trust has recently gotten a lot of attention from researchers. Vance et al., (2008) looked at the impact of mobile trust on users, including system quality, visual appeal, and navigational structure. The importance of perceived trust and privacy was explored using a technological acceptance model, and the report looked into variables influenced by perceived trust. As a result, there are concerns about the transaction’s security and privacy. As a result, clients are more likely to be exposed to danger and mistrust (Chen & Chang, 2013). Perceived trust can lower transaction costs that are not monetary and this cost considers factors, such as time and effort (Gao et al., 2015). According to Lee et al., (2015a, 2015b), privacy and security concerns increase the likelihood of perceived threats and uncertainty. Facilitation is required, as is its continuing use, to reduce perceived risk and build trust. The importance of trust on buy intent was further explained by Bonson Ponte et al., (2015), who discovered that trust has a considerable and favorable impact on behavioral intention. Positive trust emerges when a customer is satisfied, which leads to positive behavioral intentions. Additionally, trust is necessary for the formation of successful collaborations (Suki & Suki, 2017; Wang et al., 2015). People who talk about their trust in humanity imply that they care about other people in society and that those who have deep religion are more tolerant of others. Humans can choose whether or not to be trusting; as a result, trust has a major impact on behavioral intention (Chiu et al., 2017). Thus, based on the said discussion, the following hypotheses have been established:
H4
Perceived trust has a positive and significant effect on attitude toward mobile learning.
H9
Perceived trust has a positive and significant effect on behavioral intentions toward mobile learning.
Perceived value
ZEITHAML (1988) described perceived value as “the consumer’s subjective opinion of the trade-off between benefits acquired from a product or service and sacrifices made for it.” Perceived value is a complex and multi-dimensional concept. It has been identified as one of the most dependable constructs for predicting purchase behavior by researchers (Pura, 2005). Moreover, perceived value is considered and treated as one of the multi-dimensional constructs in the context of consumer value. In previous studies, the validity of four sub-values of customer perceived value was established (Walsh et al., 2014). Hsu and Lin, (2015) explored in greater depth the purchasing purpose of mobile apps. The number of subscribers using smartphones, as well as the use of mobile applications, is growing. The perceived value of an individual influence their attitudes and behavioral intentions significantly. Perceived value has a significant impact on behavioral intention, which is also used to predict repurchase intention (Suki & Suki, 2017). Hernandez-Ortega et al (2017) further discussed the importance of perceived value in post-acceptance behavior for mobile messaging services. Thus, the aforementioned discussion hypothesized perceived value as follows:
H5
Perceived value has a positive and significant effect on attitude toward mobile learning.
H10
Perceived value has a positive and significant effect on behavioral intentions toward mobile learning.
Attitude toward mobile learning
Various predictive and outcome variables, such as entertainment, relaxation, escape time, value, and quality, as well as dependent variables, such as behavioral intention, purchase intention, and buying intention, have been discovered in the literature to operate as mediating variables (Curras-Perez et al., 2014; Mohammadi, 2015a; Zhu & Chang, 2014). In today’s world, technology advances at a breakneck pace, and educational institutions must keep up. Students, teachers, and parents’ attitudes toward mobile learning are researched to achieve mobile-supported education in schools (Huseyin Uzunboylu & Tugun, 2016). Moreover, the study found that attitude is an important factor that influences learning intention. Technology is enabling a wide range of helpful learning opportunities for scholars. Different educational institutions are required to focus on such opportunities to aid people (Park et al., 2012). The rise of mobile devices in recent years has ushered in a new era in education known as mobile learning. Mobile learning, in general, refers to any sort of learning that is facilitated by a mobile device. In recent years, Donaldson (2012), Gan and Balakrishnan (2016), Montrieux et al., (2015), and Park et al., (2012) have all argued for the use of mobile learning. Understanding the factors that influence mobile learning adoption is crucial for success in higher education. It has been revealed that one’s mindset has a significant impact on one’s intention to use mobile learning in future (Yeap et al., 2016). The study employs BITML to investigate the mediating effects of ATML in the link between entertainment, informativeness, irritation, perceived trust, and perceived value, based on evidence that attitude mediates. Thus, the following mediating hypotheses have been developed:
H11
ATML mediates the relationship between entertainment and BITML.
H12
ATML mediates the relationship between informativeness and BITML.
H13
ATML mediates the relationship between perceived irritation and BITML.
H14
ATML mediates the relationship between perceived trust and BITML.
H15
ATML mediates the relationship between perceived value and BITML.
Social influence
According to Ajzen, (1991) “subjective standards are operationalized in a very generic way in terms of experiencing influence with other individuals whose opinions are significant as a source of expectations.” Societal influences and personality traits, such as individual inventiveness, are potentially essential elements for adoption, according to behavioral sciences and individual psychology, and they may be a more relevant aspect in potential adopters’ decisions. The role of social influence in technology acceptance decisions is complex and influenced by a variety of factors. Social influence has been found in several types of research to have a positive impact on behavioral intentions (Chong, 2013; Chong et al., 2012; Leong et al., 2013). M-commerce clients are inspired by their friends to establish behavioral intentions. The link between social influence and behavioral intention has been studied extensively (Jung et al., 2016; Yang et al., 2012), because social groups offer a product’s acceptability. Mobile phone users are often in socially oriented situations and their decisions are influenced by what others think about mobile phones. The desire to rely on others is the fundamental motivator for using social networking services. In recent years, the expansion of media has had a significant impact on decision-making. (Jung et al., 2016). Furthermore, according to Donaldson (2012) and Iqbal and Qureshi (2012), social influence (e.g., instructors, parents, and friends) is expected to have a significant impact on younger students’ willingness to accept the use of mobile devices for educational purposes in the context of mobile learning. During the early phases of mobile learning, it is claimed that social influence has a substantial impact on behavioral intention. Additionally, the inclusion of age and gender tempers social influence, with the results indicating that it has the largest impact on women. Sung et al., (2015) and Reychav et al., (2016) investigated the impact of social influence on mobile learning and mobile device behavioral intention and found that social influence has a positive and significant impact on BITML and that mobile devices are the most promising learning devices. This discussion, on the other hand, broadens the scope of social influence as a moderator in the relationship between attitude and behavior intention because social influence plays such a crucial role in developing the attitude and behavioral intention. Thus, it is hypothesized that.
H17
Social influence moderates the relationship between attitude toward mobile learning (ATML) and behavioral intentions toward mobile learning (BITML) in such a way that the relationship is strengthened when social influence is high.
Theoretical framework
The theoretical framework is developed based on an extensive literature review (see Fig. 1). The study achieves both theoretical and methodological gaps. Previously various theories and models have been used to measure behavioral intention (Chen & Wells, 1999; Eighmey & McCord, 1998; Fenech, 1998; Korgaonkar & Wolin, 1999; Lim & Ting, 2012). These variables have been drawn from the U&G theory. Henceforth, the present study extends the previous body of literature by investigating factors related to behavioral intention toward mobile learning from a motivational perspective in technology usage by applying U&G theory. The theory is previously used to explore the media, including the web (LaRose & Eastin, 2004; LaRose et al., 2001), blogging (Chua et al., 2012; Hollenbaugh, 2010), and social networking sites such as Twitter (Chen, 2011; Johnson & Yang, 2009), online games (Wu et al., 2010), Facebook (Joinson, 2008), and my space (Raacke & Bonds-Raacke, 2008). As per, the study is related to learning via mobile, so mobile is media and U&G is a suitable theory to study the model (Ha et al., 2015; Ku et al., 2013). The usage of mobile devices for learning purposes is increasing, thus, it is required to study the factors that could play an important role in mobile learning adoption (Viberg & Gronlund, 2013), especially in the framework of developing countries.Fig. 1 Theoretical framework
This theory has not specifically applied to this context. The suggestions by Mohammadi (2015b) are incorporated to unveil the impact of U&G theory in the mobile learning context as previously the TAM and IS model was incorporated (Hameed & Qayyum, 2018). BITML is the untouched part as mandated by Chen (2011); Cheok and Wong, (2015); Reychav and Wu (2015); Reychav et al., (2016); and Wong et al., (2015). It supports that U&G theory is appropriate in mobile learning context and paves the way for more research of this kind. For better predictive explanation, the study added perceived trust and perceived value as suggested by Wong et al., (2015) to measure the behavioral intention of individuals. Actual usage behavior is not incorporated in the present study because the user acceptance of mobile learning is uncertain, as the concept is novel in Pakistan. Prepositions developed by Bagozzi (2007), Cheng (2015), Lee et al. (2015a, 2015b), Suki and Suki (2017; and Prieto et al. (2015) have been followed by adopting behavioral intention as the suitable construct or dependent variable to determine the BITML. Moreover, the study introduced social influence as a moderator (Wong et al., 2015) to examine the impact on behavioral intentions toward mobile learning. It is considered one of the major constructs to study the behavioral intention of individuals because it has a strong impact on attitude and intention relationships (Papacharissi, & Rubin, 2000; Sung et al., 2015). From the methodological perspective, previous studies examine students’ behavioral intention precisely in first-degree programs; however, in this study students from various departments belonging to different semesters and universities are incorporated so that based on diverse populations generalizability could be increased.
Methodology
The study adopted a positivist philosophy with a deductive approach. It follows a correlational research design along with a descriptive research type. Cross-sectional data were gathered via survey technique (Uma Sekaran, 2005).
Instrument
A total of thirty-eight items of eight constructs were used in the study for the collection of data, along with five items related to demographics (see details of instrument in Annexure A). Five items scales of each construct, i.e., entertainment, informativeness, and irritation were adopted from Ducoffe (1996). The scale of perceived value comprising four items was adapted from Sirdeshmukh et al., (2002). Four items of perceived trust were adapted from Doney and Cannon (1997). The scale of six items of social influence was used developed by Thompson et al., (1991). The scales consisting of four items of attitude and five items of behavioral intention were adapted from Taylor and Todd (1995b). A 7-point Likert scale was used to collect data ranging from 1 strongly disagree to 7 strongly agree. It is assumed that a 7-point scale is more reliable, user-friendly, and a better representation of a respondent’s actual assessment. Furthermore, it is an ideal option for surveys as it gives the respondents two moderate opinions, two extreme opinions, two intermediate opinions, and one neutral opinion (Cheng, 2015; Mohammadi, 2015a).
Participants and data collection procedure
The study employed a multistage cluster sampling technique due to its connection with survey research. In the first stage, a basic random sampling strategy was used to make clusters (universities) from Rawalpindi, Islamabad, Lahore, Karachi, and Peshawar. The total number of universities located in these five cities is 150. The students were chosen from each cluster in the second stage using the convenience sampling technique, ensuring that the sample was as diverse as possible. The data was collected from all those students who were experiencing mobile learning due to the Covid-19 breakthrough. They had a better understanding of mobile technologies and were the largest group of users of new technologies. The study’s population was estimated to be around 42,300 students. The sample size calculation was based on the expected response rate and came out as 1056 invites with an estimated response rate of 30%. Thus, 1156 questionnaires were circulated to get the responses. So, the total sample size used for analysis was 586 after removing outliers and missing information.
Data analysis
The demographic analysis shows the majority of the respondents are male and in the age category of 15 to 25 years with bachelors in the context of education. Approximately all respondents have smartphones and experience of using smartphones of 4 to 6 years can be seen in Table 1.Table 1 Demographic analysis
Classification Frequency Percentage
Gender
Male 317 54
Female 269 46
Age
15–25 years 286 49
26–35 years 153 26
36–45 years 103 17
46–55 years 44 08
Qualification
Bachelors 309 53
Masters 213 36
Mphil 53 09
PhD 11 02
Smartphones
Yes 573 98
No 13 02
Experience in using smart devices
< 2 years
2–4 years 156 27
4–6 years 183 31
> 6 years 135 23
Common method bias
The common method bias (CMB) was calculated using Harman’s single factor test, which measures the variance that can be attributed to a single factor. All thirty-eight items from the eight constructs were loaded into a factor analysis to determine whether a single factor emerges and accounts for the majority of the covariance among the measures. If no single factor emerges and accounts for the majority of the covariance, then it means that common method variance is not a prevalent issue in the study. The variance percentage after extraction is 25.155, which is less than 50%, (see Table 2) indicating that there is no CMB in the study (Tehseen et al., 2017).Table 2 Harman’s single factor test (extraction method: principal component analysis)
Factor Initial eigenvalues Extraction sums of squared loadings
Total Variance % Cumulative % Total Variance % Cumulative %
1 10.259 26.998 26.998 9.559 25.155 25.155
2 3.688 9.706 36.704
3 2.365 6.223 42.927
4 1.964 5.168 48.095
5 1.644 4.326 52.420
6 1.320 3.475 55.895
7 1.078 2.837 58.732
8 .962 2.531 61.263
9 .902 2.373 63.635
10 .827 2.176 65.811
11 .803 2.113 67.924
12 .770 2.026 69.951
13 .735 1.934 71.885
14 .695 1.828 73.713
15 .611 1.608 75.321
16 .592 1.558 76.879
17 .580 1.526 78.405
18 .575 1.513 79.918
19 .550 1.447 81.366
20 .530 1.394 82.760
21 .517 1.359 84.119
22 .500 1.316 85.435
23 .490 1.288 86.723
24 .464 1.222 87.944
25 .432 1.138 89.083
26 .424 1.115 90.197
27 .407 1.072 91.269
28 .364 .958 92.228
29 .360 .947 93.175
30 .349 .920 94.094
31 .331 .870 94.964
32 .324 .854 95.818
33 .305 .803 96.620
34 .297 .781 97.402
35 .274 .722 98.124
36 .250 .657 98.780
37 .238 .627 99.408
38 .225 .592 100.000
The values of the mean and standard deviation of the variables are within the acceptable range. Skewness and kurtosis values are also within the limits, thus showing the normality of the data as can be seen in Table 3. Furthermore, the Pearson correlation of the variables is shown in Table 3 which describes inter-correlation among the variables. All variables have a positive and significant impact on each other except irritation which has a negative and significant correlation with all variables of interest.Table 3 Descriptive, Correlation analysis, and the square root of AVE
ENT INF IRR PERT PERV SI ATML BITML
ENT .731 – – – – – – –
INF .48** .717 – – – – – –
IRR –.21** –.21** .718 – – – – –
PERT .32** .43** − .06 .724 – – – –
PERV .42** .46** − .12** .55** .717 – – –
SI .29** .21** .05 .30** .38** .731 – –
ATML .46** .45** − .22** .43** .57** .45** .727 –
BITML .45** .42** − .21** .43** .55** .40** .69** .716
Mean 17.2 18.5 11.1 13.3 14.2 20.4 13.6 19.3
St Dev 6.1 6.2 5.3 5.1 6.7 6.2 5.9 5.5
Skewness − .460 − .773 − .480 − .713 − .410 − .732 − .632 − .726
Kurtosis .44 1.32 − 1.98 .313 .945 .482 .586 .436
ENT Entertainment, INF Informativeness, IRR Irritation, PERT Perceived trust, PERV Perceived value, SI Social influence, ATML Attitude toward mobile learning, BITML Behavioral intention toward mobile learning, Bold values are the square root of AVEs
*p < 0.001
Confirmatory factor analysis
For data analysis, SPSS-25 and AMOS-23 have been used. Confirmatory factor analysis (CFA) was conducted using AMOS-23; whereas multiple regression, mediation, and moderation have been measured via Process Macros of Hayes & Preacher (2014) using SPSS. The primary reason of conducting CFA using AMOS was to determine how well the construct indicators capture variables. The fit indices indicate how well the model fits with the data (see Fig. 2). It explains whether the variables are independent of each other or co-vary based upon maximum likelihood estimation. Moreover, it has the ability to handle non-parametric data. The goodness of fit statistics shows CMIN/ DF is 2.31, GFI 0.89, AGFI 0.86, RMSEA 0.4, CFI 0.88, and NFI 0.90, therefore the data are a good fit with the model as all values lie in an acceptable range. The factor loadings are loaded appropriately with each item and all items with a value less than 0.4 are removed.Fig. 2 Measurement model
The face validity of the instrument has been measured in three stages with the help of students, then educational specialists, and then students again. Construct validity is assessed via convergent and discriminant validity. CR and AVE values are assessed for convergent validity and can be seen in Table 4, all values of CR are greater than 0.7, and AVE values are greater than 0.5 as the value of all latent constructs is above the minimum threshold value of 0.5 (Hair et al., 2010), thus all values are in an acceptable range. Therefore, the study exhibits convergent validity (Hulland, 1999). The result also ensured the discriminant validity of the model by following Fornell and Larcker’s (1981) criteria. It is determined that a set of items measuring specifically their construct are not cross-loading on other constructs. Table 3 shows that the square root of Average Variance Extracted (AVE) values of ENT, INF, IRR, PERT, PERV, SI, ATML, and BITML are larger than the corresponding latent variables correlations. The establishment of discriminant validity is also confirmed by the values of HTMT (see Table 5). The HTMT method is a better approach to predict the discriminant validity between the constructs as it measures between trait correlations and within trait correlation of two constructs. All the values are below the threshold of 0.90 (Roemer et al., 2021). Therefore, it is concluded that discriminant validity has been established and the latent factors represent distinct constructs.Table 4 Confirmatory factor analysis
Construct Indicators Loadings CR AVE CFI
ENT ENT1 .59 .85 .53 .96
ENT2 .67
ENT3 .78
ENT4 .72
ENT5 .59
INF INF1 .71 .78 .51 .98
INF2 .69
INF3 .62
INF4 .58
IRR IRR1 .67 .89 .51 .93
IRR2 .81
IRR3 .82
IRR4 .73
IRR5 .62
PERT PERT1 .57 .75 .56 .97
PERT2 .72
PERT3 .63
PERV PERV2 68 .73 .52 .92
PERV3 .60
PERV4 .61
SI SINF1 58 .89 .51 .97
SINF2 .61
SINF3 .69
SINF4 .78
SINF5 .79
SINF6 .60
ATML ATML1 .70 .79 .53 .95
ATML2 .66
ATML3 .72
ATML4 .73
BITML BITML1 .78 .83 .52 .93
BITML2 .63
BITML3 .68
BITML4 .61
BITML5 .71
Table 5 Heterotrait–monotrait ratio (HTMT)
ENT INF IRR PERT PERV SI ATML BITML
ENT –
INF 0.603 –
IRR −0.25338 − 0.26911 –
PERT 0.552084 0.783886 − 0.1205 –
PERV 0.580951 0.666303 − 0.17876 0.71704 –
SI 0.346304 0.262301 0.057739 0.496135 0.512897 –
ATML 0.361437 0.593745 − 0.27543 0.761051 0.824706 0.543126 –
BITML 0.540906 0.52824 − 0.25444 0.736481 0.767855 0.471777 0.868293 –
Hypotheses testing
Linear relationships among variables were measured via multiple regression analysis. Hypotheses 1, 2, 4, and 5 state ENT, INF, PERT, and PERV has a significant and positive relationship with attitude, whereas H3 states irritation has a negative relationship with attitude. When ENT is increased by one unit, ATML increases by 0.19 units, as seen in Table 6. ATML will increase by 0.12 units if INF is increased by one unit. ATML will drop by − 0.10 units if IRR is increased by one unit. ATML will increase by 0.10 units if PERT is increased by one unit. ATML will increase by 0.36 units if PERV is increased by one unit. Table 6 demonstrates that ENT, INF, IRR, PERT, and PERV all exhibit significant positive beta values, indicating that students with higher scores are more likely to have greater ATML. With a beta value of 0.36, PERV has the greatest influence on ATML. Hence Hypotheses 1, 2, 3, 4, and 5 are accepted.Table 6 Multiple regression analysis (effect of all IVs on attitude)
Constructs B S.E β t P value R2 F
Constant 3.775 0.73 5.13 .000
ENT 0.14 0.02 0.19 5.43** .000
INF 0.11 0.03 0.12 3.31** .001
IRR − 0.07 0.02 − 0.10 − 3.33** .001 0.42 93.103**
PERT 0.11 0.03 0.10 2.89** .004
PERV 0.39 0.04 0.36 9.27** .000
ENT Entertainment, INF Informativeness, IRR Irritation, PERT Perceived trust, PERV Perceived value, ATML Attitude toward mobile learning, BITML Behavioral intention toward mobile learning
**p < .01
Hypotheses 6, 7, 9, 10 state ENT, INF, PERT, and PERV have a significant and positive relationship with BITML, whereas H8 states that IRR has a negative relationship. Table 7 shows that a one-unit increase in ENT results in a 0.20-unit increase in BITML. If INF is increased by one unit, BITML will increase by 0.08. BITML will drop by -0.10 units if IRR is increased by one unit. BITML will increase by 0.14 units if PERT is increased by one unit. BITML will increase by 0.33 units if PERV is increased by one unit. Table 7 demonstrates that ENT, PERT, and PERV have significant positive beta values, indicating that students with higher scores are more likely to have higher BITML scores; however, IRR has a negative significant influence. With a beta value of 0.33, the PERV in the model has a bigger effect on BITML. Therefore, H6 and 8, 9, and 10 are significant, whereas H7 is rejected because INF has an insignificant β value, the insignificant effect suggests that changes in BITML are not associated with a change in INF (see Fig. 3).Table 7 Multiple regression analysis (effect of all IVs on behavioral intention)
Constructs B S.E β T P value R2 F
Constant 4.83 0.96 5.01 .000 0.39 82.252**
ENT 0.19 0.03 0.20 5.51** .000
INF 0.09 0.04 0.08 2.07 .038
IRR 0.08 0.02 − 0.10 − 3.15** .002
PERT − 0.18 0.05 0.14 3.66** .000
PERV 0.47 0.05 0.33 8.48** .0000
ENT Entertainment, INF Informativeness, IRR Irritation, PERT Perceived trust, PERV Perceived value, ATML Attitude toward mobile learning, BITML Behavioral intention toward mobile learning
**p < .01
Fig. 3 Conceptual model with regression weights straight lines significant relationships, dotted lines insignificant relationship. (Color figure online)
Hypothesis 16 states that ATML has a positive and significant effect on BITML. If ATML is raised by 1 unit, the BITML will be increased by 0.70 units as can be seen in Table 8, thus accepting H16.Table 8 Linear regression analysis (effect of attitude on behavioral intention)
Constructs B S.E Β T P value R2 F
Constant 4.98 0.55 9.00 .000
ATML 0.89 0.03 0.70 24.7** .000 0.49 610.696**
ATML Attitude toward mobile learning
**p < .01
Mediation and moderation analysis
The study used Macro Process by Hayes & Preacher (2014). Model 4 with bootstrapping to boost the statistical power of mediation analysis (Inman & Nikolova, 2017). The current study uses 5000 samples to repeat the bootstrapping technique. If the indirect effect estimates’ 95 percent confidence interval does not include zero, the mediator is considered significant.
To determine the mediating effect of ATML between ENT and BITML, a path analysis was performed. Table 9 shows that the total impact (0.42, p < 0.05) and indirect effect (0.27, p < 0.05) are both significant (based on 5000-bootstrapped samples). ATML mediates the link between ENT and BITML, according to the data (lower 95 percent CI = 0.2065 and higher 95 percent CI = 0.3401). Because the direct effect (0.14, p < 0.05) is also strong, partial mediation is present. To determine the mediating effect of ATML between INF and BITML, a path analysis was performed. Table 9 shows that the total effect (0.47, p < 0.05) and indirect impact (0.33, p < 0.05) are both significant (based on 5000-bootstrapped samples). ATML mediates the association between INF and BITML, according to the findings (lower 95 percent CI = 0.2645 and higher 95 percent CI = 0.4212). Because the direct effect (0.14, p < 0.05) is also strong, partial mediation is present. To determine the mediating effect of ATML between IRR and BITML, a path analysis was performed. Table 9 shows that the total effect (− 0.18, p < 0.05) and indirect effect (− 0.13, p < 0.05) are both significant (based on 5000-bootstrapped samples). ATML mediates the link between IRR and BITML, according to the data (lower 95 percent CI = -0.1974 and higher 95 percent CI = − 0.0783). The direct effect (0.14, p < 0.05) is likewise substantial, indicating that there is full mediation. To determine the mediating effect of ATML between PERT and BITML, a path analysis was performed. Table 9 shows that the total effect (0.58, p < 0.05) and indirect impact (0.36, p < 0.05) are both significant (based on 5000-bootstrapped samples). ATML mediates the link between PERT and BITML, according to the findings (lower 95 percent CI = 0.2865 and higher 95 percent CI = 0.4510). Because the direct effect (0.21, p < 0.05) is also strong, partial mediation is present. To determine the mediating effect of ATML between PERV and BITML, a path analysis was performed. Table 9 shows that the total effect (0.77, p < 0.05) and indirect impact (0.46, p < 0.05) are both significant (based on 5000-bootstrapped samples). ATML mediates the link between PERV and BITML, according to the findings (lower 95 percent CI = 0.3763 and higher 95 percent CI = 0.5647) because the direct effect (0.31, p < 0.05) is also strong, partial mediation is present.Table 9 Mediation analysis
Path Total effect c Direct effect c′ Indirect effect 95% CI
IV-DV IV-DV IV-Ma X M-DVb
IV-Ma M-DVb Lower upper limit
ENT-ATML-BITML .27 (.03)
*R square = .51, F = 330.744, p < .05, n = 586 42 (.03) .14 (.02) .33 (.02) .80 (.04) .2065 .3401
INF-ATML-BITML .33 (.04)
*R square = .50, F = 320.1636, p < .05, n = 586 .47 (.04) .14 (.03) .40 (.03) .82 (.04) .2645 .4212
IRR-ATML-BITML − .13 (.02)
*R square = .51, F = 330.744, p < .05, n = 586 − .18 (.03) − .05 (.02) − .15 (.02) .88 (.03) − .1974 − .0783
PERT-ATML-BITML .36 (.04)
*R square = .51, F = 332.1265, p < .05, n = 586 .58 (.04) .21(.04) .4 (.03) .80 (.03) .2865 .4510
PERV-ATML-BITML .46 (.04)
*R square = .52, F = 348.017, p < .05, n = 586 .77 (.04) .31 (.04) .63 (.03) .73 (.04) .3763 .5647
*Standard errors of bootstrap in parentheses
Hypothesis 17 states that SI strengthens the association between ATML and BITML. To test Hayes & Preacher (2014) (Model 1)’s moderation study of SI between ATML and BITML via Process Macro, a route analysis was performed. First, the significance of the moderation effect is determined; if it is significant, then moderation exists and is meaningful, as evidenced by the values of the lower and upper limit confidence intervals. When zero does not fall between the two extremes, moderation is significant. The fact that the lower limit is − 0.024 and the higher limit is − 0.0013 indicates that zero does not lie between the two values, indicating that moderation exists. Table 10 demonstrates the low, medium, and high effect of SI in the relationship between ATML and BITML to determine which condition has a significant effect. SI dampens the impact on the link between ATML and BITML, as seen in Fig. 4.Table 10 Moderation analysis
Coefficient St error t value Lower limit Upper limit
SI .28 .09 3.0 .0974 .464
ATML 1.07 .11 9.2 .8444 1.300
Interaction (ATML x SI) − .012 .005 − 2.1 − .024 − .0013
Effect SI Coefficient St error t value Lower limit Upper limit
Low 15.166 .87 .04 19.75 .7889 .9631
Medium 19.968 .81 .04 19.62 .7324 .8953
High 24.769 .75 .05 13.49 .6424 .8612
R square = .50, F = 214.0041, p < 0.05, n = 626
Fig. 4 Moderation graph
Discussion
The study objective was to determine the factors related to behavioral intention toward mobile learning. Mobile devices have evolved into vital gadgets that are used as a source of pleasure, with their productivity boosted by a variety of mobile apps. Mobile apps play an important part in mobile commerce uptake and students find them entertaining. Students’ attitudes are influenced by the rapid growth of mobile applications, video games, and mobile commerce. The hypothesis postulated that entertainment significantly influences ATML and BITML is supported in the study. Students use technology to reduce stress and boost their leisure time while studying. It influences not only one’s attitude but also one’s behavior (Tuparov et al., 2015). The findings of research conducted by Arli (2017) and Lin et al., (2017) found that the spread of mobile devices and the internet have boosted students’ capacity to be informed and supported the current findings of the study. In contrast to the literature, informativeness does not affect BITML. The study’s findings differ from those reported in the literature by Shim and Youn (2013) and Zedan and Salem (2016) on the direct association between informativeness and behavioral intention. The purpose of this research is to perceive if there is a direct relationship between informativeness and BITML. As a result, it is deemed inconsequential in the context of this study, indicating that it does not affect students’ behavioral intentions. This suggests that informativeness does not encourage students to behave positively. This could be because the mobile learning concept is emerging in Pakistan, and many individuals, even educational institutions, are unfamiliar with it.
The findings of this study support Zedan and Salem’s (2016) hypothesis that irritation is similar to reactance and that individuals generally respond badly when they are uncomfortable and considered intrusive. With the advancement of technology, the component of aggravation and irritation has increased, which can have a detrimental impact on people’s attitudes and behavioral intentions (Hasan, 2016). Furthermore, studies performed by Ponte et al., (2015) and Lee et al., (2015a, 2015b) discovered that trust is critical for building connections, whereas security and privacy issues raise risk and ambiguity. Trust was identified as a key determinant of attitude, and it was discovered that trust has a favorable and significant impact on attitudes toward mobile learning. As a result, as recommended by Suki and Suki (2017) and Wang et al., (2015), it is critical to establish positive consumer trust. People have a favorable attitude and behavioral intention when they view mobile learning to be of great value. As a result, developing positive student attitudes is a crucial endeavor (Naciri et al., 2020; Shin & Kang, 2015).
The study postulated that ATML mediates the relationships between entertainment, informativeness, irritation, perceived trust, and perceived value with BITML. In today’s world, technology is evolving at a breakneck pace, forcing educational institutions to adopt cutting-edge technology, particularly in the field of education. The findings of the study showed that attitude has been found to mediate relationships between predictors, such as entertainment, informativeness, irritation, value, and trust, with behavioral intention (Curras-Perez et al., 2014; Mohammadi, 2015a; Zhu & Chang, 2014). In general, mobile learning may be defined as any type of learning that occurs through the use of a mobile device, and it has gotten a lot of attention in recent years (Donaldson, 2012; Montrieux et al., 2015; Park et al., 2012). For mobile learning to succeed in higher education, it is critical to understand the elements that drive its adoption. Attitude has been shown to have a major impact on students’ behavioral intentions toward learning (Yeap et al., 2016; Criollo-C, 2021).
Social influence moderates the relationship between ATML and BITML. According to Chong et al., (2012), Chong (2013), and Leong et al., (2013) social influence has a favorable effect on students’ behavioral intentions because social groups provide substantial evidence regarding the appropriateness of a certain product, social impact minimizes the risk of adoption. This aids students in their decision-making process (Alzaidi & Shehawy, 2022). As a result, the evidence strongly suggests that social influence is a determinant of attitude and behavioral intention and it moderates the connection. However, it moderates the relationship in the current investigation, but negatively. This is due to the differences in culture and industry because mobile learning is a relatively new phenomenon in Pakistan, and people lack sufficient information and evidence to support it. Since social groupings have a negative reaction to it thus people do not consider mobile learning to be an appropriate learning tool. Another argument could be that because mobile users are young and have the requisite abilities to operate mobile technology, they do not require the influence of a social group to navigate in the context of mobile learning. The study is comparable to Tan et al., (2014) that social factors did not affect the behavioral intention to adopt mobile learning. As a result, it is concluded that social impact moderates negatively rather than strengthening the association between ATML and BITML in students.
Theoretical implications
In social and psychological situations, behavioral intention is a common manifestation but in the context of mobile learning, it is at the embryonic level. The theoretical implication of the study is three-fold: firstly, the study developed and measured a comprehensive theoretical framework based on literature to measure BITML. Secondly, the mediating effect of ATML is explored between perceived entertainment, informativeness, irritation, trust, and value with BITML. Taken together these findings suggest that developing a favorable attitude among learners positively affects BITML. Lastly, the study measured the moderating effect of social influence in the relationship between ATML and BITML.
Practical implications
The study exhibits various practical implications: firstly, it will assist educational institutes that how BITML has emerged and how it is shaping the attitude of learners. They must accurately depict the concept of mobile learning and devise tactics to encourage learners to embrace mobile learning by demonstrating that it not only entertains but also gives comprehensive information. Educational institutions should provide user-friendly apps with improved reading layouts so that students may learn on the go. Secondly, the study is imperative for service providers because internet services are the prerequisites for mobile learning. The internet should be made more accessible to make it easier to get learning materials. Thirdly, the study is vital for the telecom industry as mobile learning is associated with technology, thus they need to make the devices compatible with learning features and simple to operate for the general public. They should build screens that are large and faultless, allowing for a clear display.
Limitations and future research
The study might have numerous limitations and based upon limitations future directions are provided. Firstly, the study has incorporated various factors to measure behavioral intention but in future studies, one may add personality traits of individuals who are supposed to practice mobile learning along with various other variables to depict the BITML. Secondly, the study is majorly based on U&G theory and TPB, thus the conceptual model needs to be tested in comparison to TAM and UTAUT models. Thirdly, the study is based upon cross-sectional data that hinder generalizability thus in future, time lag data can be used to measure the behavior of individuals. Lastly, in the context of analysis techniques, the latest software might be used for more generalizability.
Conclusion
In general, the study started with the design of the research model, which was accomplished by the analysis of relevant literature and the formulation of research hypotheses that may provide answers to the research questions. The study investigated the effect of perceived entertainment, informativeness, irritation, trust, and value on ATML and BITML. Moreover, the study determined the mediating role of attitude in the aforementioned relationships and moderating role of social influence in the relationship between ATML and BITML. The findings showed that perceived entertainment, perceived informativeness, perceived trust, and perceived value have direct and significant effects on attitude toward mobile learning, whereas perceived irritation has a negative effect. For the direct effect on BITML, all variables showed significant impact except informativeness. Furthermore, the study confirmed the role of ATML as a mediator and social influence as a moderator. Consequently, significant advances have been facilitated by modern technology and globalization, and mobile learning has expanded the scope of electronic and distance education, particularly with the pandemic Covid-19 worldwide. The shift to mobile learning will be successful, and it will be useful for a long time.
Annexure
Entertainment
Mobile learning is entertaining to me.
I think that mobile learning is fun to use.
I feel excited while using mobile learning.
I enjoy it when I do mobile learning.
I think that mobile learning is cool.
Informativeness
Mobile learning gives me quick and easy access to large volumes of information.
Information obtained from mobile learning is useful.
I learned a lot from using mobile learning.
The information obtained from mobile learning is helpful.
Mobile learning makes acquiring information inexpensively.
Irritation
I think that mobile learning is irritating.
Mobile learning is annoying to me.
I feel that mobile learning is confusing.
I think that mobile learning is messy.
Mobile learning is deceptive to me.
Perceived trust
The mobile learning systems are trustworthy.
The mobile learning systems have a good reputation as other systems.
The mobile learning systems are competent and effective as other systems.
I do not doubt the reputation of mobile learning systems.
Perceived value
Compared to the fee I need to pay, the use of mobile learning offers value for money.
Compared to the effort I need to put in, the use of mobile learning is beneficial to me.
Compared to the time I need to spend, the use of mobile learning is worthwhile to me.
Overall, the use of mobile learning delivers me good value.
Social influence
People who influence my behavior think, I should use mobile learning.
People who are important to me think I should use mobile learning.
My close friends think I should use mobile learning.
My colleagues think I should use mobile learning.
My peers think I should use mobile learning.
People whose opinion I value prefer that, I should use mobile learning.
ATML
I think that using mobile learning is a good idea.
I think that using mobile learning for learning purposes would be a wise idea.
I think that using mobile learning is a pleasant experience.
In my opinion, it is desirable to use mobile learning.
BITML
I am very likely to have mobile learning in future.
I intended to use mobile learning for learning purposes.
I intended to use mobile learning frequently for learning purposes.
I would seriously contemplate mobile learning for learning purposes.
I am likely going to have mobile learning.
Funding
No third party/funding source is associated with research paper except the authors with no conflict of interest.
Declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Ethical considerations
I hereby declare that this research paper is the authors' own original work, which has not been previously published elsewhere. The research paper is not currently being considered for publication elsewhere. The paper reflects the authors' own research and analysis in a truthful and complete manner. The responsibility of this statement shall be borne by the authors of the paper.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Pediatr Res
Pediatr Res
Pediatric Research
0031-3998
1530-0447
Nature Publishing Group US New York
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2405
10.1038/s41390-022-02405-0
Correspondence
The Advanced Research Projects Agency—Health (ARPA-H): a new model for research in child health
Varisco Brian M. [email protected]
12
Devaskar Sherin U. 3
Murray Kristy O. 4
Cheng Tina L. 12
On behalf of the Pediatric Policy CouncilShah Shetal 5
Patel Mona 6
Raphael Jean 6
Keller David 7
Chamberlain Lisa 7
Devaskar Sherin U. 8
Cheng Tina 58
Javier Joyce 9
Lee Lois 9
1 grid.24827.3b 0000 0001 2179 9593 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH USA
2 grid.239573.9 0000 0000 9025 8099 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH USA
3 grid.19006.3e 0000 0000 9632 6718 Department of Pediatrics, David Geffen School of Medicine at UCLA and the UCLA Mattel Children’s Hospital, Los Angeles, CA USA
4 grid.416975.8 0000 0001 2200 2638 Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX USA
5 Pediatric Policy Council, Mc Lean, VA USA
6 grid.420325.2 0000 0001 0690 4201 Academic Pediatric Association, Mc Lean, VA USA
7 American Pediatric Society, Washington, DC USA
8 Association of Medical School Pediatric Department Chairs, Mc Lean, VA USA
9 Society for Pediatric Research, Houston, TX USA
8 12 2022
12
8 11 2022
9 11 2022
© The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
==== Body
pmcThe Advanced Research Projects Agency—Health (ARPA-H) is being formed and will be a new vehicle for biomedical research under the National Institutes of Health. ARPA-H is intended to “foster the development of new, breakthrough capabilities, technologies, systems and platforms to accelerate innovations in health and medicine that are not being met by Federal programs or private citizens” and to “promote high-risk, high-reward innovation for the development and translation of transformative health technologies”.1 As Congress and the present White House Administration work to establish ARPA-H, this agency must ensure that its structure supports innovation focused on child and adolescent health and health across the lifespan. As highlighted by articles in this issue of Pediatric Research, research early in the life course critically affects population health outcomes and these articles suggest potential moonshot projects for ARPA-H.
ARPA-H has been modeled on the Defense Advanced Research Projects Agency (DARPA), a flexible and nimble strategy that has led to Department of Defense breakthrough advances for over 60 years. Undeterred by failure, this approach involves program managers from academic institutions or industry who are given independence and resources toward clear goals supporting innovative research, applied research, and advanced technology development. Examples of DARPA-like projects at National Institutes of Health (NIH) include the Human Genome Project, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program, and the COVID-19 Rapid Acceleration of Diagnostics (RADx) program. These programs accelerated progress through collaborations among academic researchers, industry, non-profit organizations, and government.
Leaders at the NIH and the Office of Science and Technology Policy have written about the limitations of the current science lifecycle.2 NIH supports incremental, hypothesis-driven research while business translation requires a timely return on investment to attract investors. They note that promising ideas may never be pursued or mature because “(1) the risk is too high; (2) the cost is too large; (3) the time frame is too long; (4) the focus is too applied for academia; (5) there is a need for complex coordination among multiple parties; (6) the near-term market opportunity is too small to justify commercial investment given the expected market size challenges in adoption by the health care system; or (7) the scope is so broad that no company can realize the full economic benefit, resulting in underinvestment relative.” These challenges are especially true for prevention and research early in the life course which have longer time frames for return on investment.
The ARPA-H authorizing legislation does not focus the agency’s work on any specific diseases or conditions or areas of research, but instead it empowers the agency’s director and leadership team to make those decisions. The history of funding for pediatric research indicates that without strong advocacy, it is likely that pediatric-focused research will again be left behind. When the Clinical and Science Translation Awards (CTSA) Program was developed in 2006, pediatric focused co-principal investigators were not permitted. While this has been remedied, CTSA funding continues to be heavily skewed towards adult medicine. Four years into the All of Us Precision Medicine Initiative, no pediatric participants have been enrolled. Although children comprise 20% of the US population, only 12–14% of NIH funding is directly or indirectly related to their health needs.3,4 Of the 71 designated national cancer centers, only 1 is located at a free-standing children’s hospital. Such disparities are inequitable and represent short-sighted policy since no area of research has a greater return on investment.
By funding transformative “moonshots,” ARPA-H can change the landscape of health in this country and address some of the most difficult to solve problems in society from novel approaches to cure genetic diseases to eliminating health disparities. From a diagnostics perspective, ARPA-H could bridge the gap between various -omics approaches to characterizing and predicting disease and the development of precision diagnostics and therapeutics. In this issue of Pediatric Research, Beheshti and colleagues show that a variety of host, viral, and bacterial factors in saliva are predictive of future wheezing episodes.5 Could an integrated platform be developed for both prediction and phenotypic characterization of wheezing phenotypes and could it be adapted for other respiratory diseases? Developing such a platform and the methods needed for its widespread implementation is the type of high-risk, high-reward project better suited for ARPA-H than traditional NIH funding mechanisms. Also, in this issue, Holgerson and colleagues characterize the oral, fecal, and breast milk microbiome in the first 5 years of life.6 Is there any correlation of these factors with maternal and infant mortality? Are these factors modifiable? Socioeconomic and racial disparities in maternal and infant mortality are deeply engrained in society, and “moonshot” approaches to addressing this recalcitrant problem are needed.
ARPA-H could broadly improve the overall wellbeing of children in ways that targeted approaches cannot. In this issue, Lucchini and colleagues document how the pandemic adversely impacted children’s sleep habits.7 Sleep is a key element of well-being that can be influenced by a host of other important factors, such as mental health, relationships with technology, and socioeconomic factors. Could an integrated system be devised that could provide an assessment of all these different domains of child and adolescent well-being, identify high-risk individuals, and develop individualized strategies that would stem the mental health crisis in our children?
In addition to the research articles presented in this current issue, there are other critical areas of high-risk, high-reward research worthy of exploration. Cell-based therapies and gene-editing technology have the potential to transform the lives of children with some relatively common (i.e., Type 1 diabetes, sickle cell disease and cystic fibrosis) and uncommon (i.e., Tay–Sachs disease and severe combined immunodeficiency syndrome) diseases. The development of common platforms to deliver DNA- or RNA-based therapies or stem cells could be developed and modified in a disease or patient-specific manner. Instead of focusing on a disease, could we focus on an approach applicable to a family of diseases? Like for coronavirus disease 2019 (COVID-19) boosters, could nucleotide modifications be approved by the Food and Drug Administration without submitting an entirely new application? Could we develop high throughput in utero or newborn screening with digital genomics? Or a microneedle patch platform to deliver all childhood immunizations avoiding current cold chain obstacles? Finally, with children at the forefront of demographic change with increasing diversity, developing platforms to reduce health disparities in maternal and infant mortality by identifying individuals and communities at high risk and intervening is a worthy moonshot.
As ARPA-H becomes established, child and adolescent health researchers should be aware of this new approach and funding opportunity (see https://www.nih.gov/arpa-h). Growing research demonstrates that many conditions have their origins early in the life course with the opportunity for ARPA-H to prevent or change the trajectory of disease. ARPA-H should address inclusion of children in all research projects and assess the impact of research on health and disease across the lifespan and intergenerationally. ARPA-H should focus on prevention as well as cures, leveraging burgeoning technology developments. Finally, ARPA-H should focus on health equity starting early in the life course and examine the multiple ways that health disparities negatively impact children’s development and predisposition to acute and chronic diseases.
Acknowledgements
The authors appreciate the contributions of many who participated in two virtual working group sessions that discussed ARPA-H and Pediatrics. No financial assistance was received to support this paper. This work is original, is not previously published and is not submitted for publication or under consideration elsewhere.
Author contributions
B.M.V. conceptualized and wrote the manuscript, revised each draft, and approved the final manuscript. S.U.D., K.O.M., and T.L.C. wrote portions of the manuscript, revised each draft, and approved the final manuscript.
Competing interests
The authors declare no competing interests.
Ethics approval and consent to participate
No human subjects’ consent was required for this commentary.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Kristy O. Murray, Tina L. Cheng.
A list of authors and their affiliations appears at the end of the paper.
==== Refs
References
1. U.S. Government Publishing Office. H.R. 5585, 117th Congress: to establish the Advanced Research Projects Agency-Health, and for other purposes. https://www.govinfo.gov/content/pkg/BILLS-117hr5585rfs/html/BILLS-117hr5585rfs.htm (2022).
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3. NIH Research Portfolio Online Reporting Tools. Estimates of funding for various Research, Condition, and Disease Categories (RCDC). https://report.nih.gov/funding/categorical-spending#/ (2022).
4. NIH Research Portfolio Online Reporting Tools. NIH awards by location and organization - NIH Research Portfolio Online Reporting Tools (RePORT). https://report.nih.gov/award/index.cfm?ot=&fy=2020&state=&ic=&fm=&orgid=&distr=&rfa=&om=n&pid=#tabic (2022).
5. Beheshti, R., Halstead, E. S., McKeone, D. & Hicks, S. D. Multi-omic factors associated with future wheezing in infants. Pediatr. Res. 10.1038/s41390-022-02318-y (2022).
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Educ Inf Technol (Dordr)
Educ Inf Technol (Dordr)
Education and Information Technologies
1360-2357
1573-7608
Springer US New York
11487
10.1007/s10639-022-11487-6
Article
Exploring the effect of improved learning performance: A mobile augmented reality learning system
http://orcid.org/0000-0002-1448-7433
Wang Wei-Tsong [email protected]
Lin Ying-Lien [email protected]
Lu Hsin-En [email protected]
grid.64523.36 0000 0004 0532 3255 Department of Industrial and Information Management, National Cheng Kung University, No.1, University Road, Tainan City, 701 Taiwan, Republic of China
5 12 2022
133
28 7 2022
24 11 2022
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Students are commonly in a high cognitive load state when they encounter sophisticated knowledge. Whether the novel augmented reality (AR) technology can be utilized in an online learning course to explain complicated scientific concepts in a more understandable manner to students during the COVID-19 period is an unaddressed issue. This study aims to investigate the influences of reducing the physical touch or face-to-face teaching/learning practices via using mobile augmented reality learning systems (MARLS) on students’ perceived learning effectiveness. The information feedback viewpoint, flow theory, and cognitive load theory are integrated to examine the effects of the information feedback of MARLS on students’ learning effectiveness. This study recruited 204 participants from ten universities to complete a learning task via a MARLS and fill out a questionnaire to collect data for the proposed research model. The empirical results revealed information feedback positively and significantly affected flow experience, perceived learning effectiveness, and continued intention. The improved learning performance of learners was positively related to their continued intention. Also, the extraneous cognitive load negatively and significantly moderated the relationship between information feedback and perceived learning effectiveness. This study proposes meaningful implications and suggestions for future research based on the findings of this experiment.
Keywords
Extraneous cognitive load
Flow experience
Information feedback
Perceived learning effectiveness
Continued intention
Improved learning performance
http://dx.doi.org/10.13039/501100004663 Ministry of Science and Technology, Taiwan MOST 109-2511-H-006-006-MY3 Wang Wei-Tsong
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pmcIntroduction
Using digital technologies, such as augmented reality (AR), has covered a wide field of instructional and learning approaches during COVID-19. AR is a frequently utilized tool via simulating or authentic scenarios to combine complex conceptions and vague images to clarify teaching/learning materials. AR allows learners to follow the information feedback to complete their learning activities supported by the interactive formats of visual or tactile related information to achieve the learning objectives. Information feedback is defined as the already evaluated/corrected and provided information transmitted to learners based on their learning processes and outcomes by AR applications (Liu et al., 2021). AR-based learning is ubiquitous in various digital applications, including photographs, games, and other means, enhancing the effectiveness of the learning experience (e.g., Bressler et al., 2013; Demitriadou et al., 2020; Ibáñez et al., 2014; Lai et al., 2019; Shin, 2019). The users do not necessarily possess knowledge of in-depth and broad digital technologies. Generally, AR-based learning applications often assist learners to obtain knowledge by offering them reliable guidance or materials (e.g., information feedback), which is relatively more interesting and diverse than the traditional teaching approach (Bressler et al., 2021; Chang et al., 2022).
The AR-based learning applications may help learners understand abstract concepts and reduce their misperception of the learning materials and extraneous cognitive overload through offering high-quality information feedback (Nikou et al., 2022). Extraneous cognitive load refers to how information is presented to an individual, which can result in the need for the individual to devote additional efforts to learning it (Liao et al., 2019; Sweller, 1994). Research indicates that more studies are needed to further investigate whether learning applications supported by different technologies (e.g., AR, three-dimensional (3D), fingertip-movement-based interactions, virtual/computing object) or interactive approaches can enhance learners’ learning outcomes because most AR-supported virtual or real-world interactive learning activities rarely provide users with timely and informative feedback when they make mistakes in order to facilitate effective learning (Alhonkoski et al., 2021; AlNajdi et al., 2020; Wang et al., 2022; Westerfield et al., 2015; Yu et al., 2019). Faqih and Jaradat (2021) also state that more AR-related studies regarding user/learner adoption of AR applications are needed because AR applications enable students to think more creatively to understand learning content after the Covid-19 pandemic. Nevertheless, studies that investigate this research issue based on the information feedback perspective are scarce. Additionally, AR-based learning processes may involve the interactions among the use of various information feedback, the formation of human cognition, and the resulting learning effectiveness in an immersing learning situation based on a flow experience perspective, while the research findings may not always generate a positive learning performance or experience in the literature of other research contexts (e.g.,Karelaia & Hogarth, 2008; Lerch & Harter, 2001; Lin & Wang, 2021). Flow experience refers to an individual psychological or motivational state of complete focused attention, sense of control, and enjoyment of a given learning task, facilitating their cognitive capacities (e.g., Csíkszentmihályi, 1990; Hohnemann et al., 2022). Regarding the learners’ cognitive capacity, learners who need to accomplish both visual and tactile tasks may need to put additional efforts into the learning process, which may negative affect their learning effectiveness if the tasks were not appropriately designed.
Based on cognitive load theory, AR-based learning must give adequate feedforward that may reduce the formation and increase extraneous cognitive loads when an individual attempts a task. Therefore, the level of learners’ perceived learning effectiveness is generally high when they sense the learning tasks include an appropriate level of challenges (Chang, 2018; Hamari et al., 2016). Perceived learning effectiveness refers to the learning results of learners regarding the formative and summative evaluations. Accordingly, extraneous cognitive load may increase the capacity of individuals working memories (i.e., knowledge, skills, and abilities) when the work/learning processes involve high levels of task complexity. Individuals’ high level of working memories might inhibit their work/learning effectiveness (Martin et al., 2020; Song & Sparks, 2019; Sweller et al., 1998).
In this study, mobile augmented reality learning systems (MARLS) are referred to as mobile-based learning applications that include designing text, video content, and fingertip-to-contact screen to rotate the 3D graphics and can thus enable learners to understand the knowledge of computer motherboard architecture. Therefore, learners’ use of MARLS are expected to lead to favorable learning outcomes. Although MARLS mainly convey basic concepts, the learning content and materials delivered through them may be inherently complex. MARLS with 3D graphics are appropriate for instructors or learners to conveniently understand sophisticated knowledge and develop specific expertise. Therefore, evaluating the success of MARLS is highly dependent on learners’ continued intention to use MARLS and their perceived learning effectiveness. However, technologically enhanced learning (i.e., AR-based learning) is not always effective in terms of delivering knowledge to learners from the perspectives of information feedback and flow theory in different learning contexts (Cruz & Uresti, 2017; Guo & Ro, 2008). There is still a lot of ambiguity (e.g., interactive mode and degree of fidelity) in the findings of prior studies regarding the usefulness of MARLS, and there is a need for more studies on such applications (Maier et al., 2016, Jiu et al, 2022; Skulmowski et al., 2022). Based on the literature review, the flow theory and cognitive load theory can help us disclose hidden information related to learners’ learning experience, including the improvement of their logical reasoning skills, the utilization of their cognitive resources, and the impact of information overload on the learners’ learning effectiveness (e.g., Chang et al., 2017; Hohnemann et al., 2022; Sun et al., 2019; Tang et al., 2022). In addition, the quality of information feedback and flow experience is essential in ensuring good understanding eventuates. This formative assessment can help stakeholders deeply understand and connect the requirements of users in the teaching/learning process (Tu & Chu, 2020).
Chang et al. (2017) argue that integrating an AR learning environment into the learning material or context elements can add diversity of experience and knowledge and enrich the learning material. In the learning process, the learner’s perceived challenge of MARLS is a determining factor: the more fantastic the flow experience of the challenge, the greater the perceived learning effectiveness. The flow experience facilitates positive and pleasant psychological elements or emotional states, which are crucial in helping students adjust their behavior and achieve effective learning (Tang et al., 2022). Additionally, adequate instructional design can reduce the formation of the extraneous cognitive load of learners, which tends to unnecessarily consume the learners’ cognitive resources (Sweller et al., 1998). Thus, this study evaluated the MARLS to practice the basic concepts of computer motherboard architecture. MARLS offer a novel and 3D learning space through visual and tactile interaction with the learning materials to enhance learner flow experiences. In this study, task-oriented learning materials could be accessible via the navigation hyperlinks, and the MARLS structure is thus based on the AR application. MARLS can provide dynamic visual and tactile guidance by information feedback to aid learners’ understanding and higher-order thinking in achieving predictable perceived learning effectiveness (Chiang et al., 2022; Ebadi & Ashrafabadi, 2022). Nevertheless, studies that evaluate the effectiveness of the use of MARLS for supporting student learning in higher educational contexts by adopting a comprehensive perspective that incorporate the concepts of information feedback, flow experience, and cognitive load theory are missing from the existing literature.
Therefore, this study aims to fill this gap by focusing on investigating the effectiveness of the use of the MARLS that are developed to help students learn via mobile devices (i.e., smart phones, tablets, or other mobile computing devices). To be specific, the investigation of this study is rooted in the interaction between MARLS, learning materials, and the learner. Such interaction determines learners’ perception of whether the MARLS are an effective learning tool. Consequently, we propose that the learning content and environment can achieve a good integration to enhance the learning process and increase the benefits of using MARLS in higher education settings. Therefore, our research questions (RQs) are as follows:RQ: 1) Does information feedback of MARLS significantly influence learners’ flow experience, perceived learning effectiveness, and continued intention to use MARLS?
2) Does the extraneous cognitive load significantly moderate the relationship between information feedback and perceived learning effectiveness?
To answer those two primary research questions, this study developed the MARLS using the AR-based technologies to assist college students in learning important knowledge related to the computer hardware architecture. A total of 204 students that were recruited from ten universities and had no experience in learning the subjects covered by the MARLS of this study served as the research participants. Those students were asked to take a pre-test first, and then to use the MARLS. After completing the learning processes of the MARLS, they were asked to take a post-test and then fill out a survey in order to offering sufficient and valid data that could be used to evaluate their perception regarding the MARLS and their learning effectiveness. Details of the research design, including the sampling method, specification of the MARLS, and the data collection procedures, are presented in the subsequent sections.
Literature review and hypotheses development
Information feedback
Information feedback is critical to smooth task learning and perceiving a sense of interaction in the knowledge acquisition process when learners use MARLS (Burns et al., 2021; Fang, 2020). MARLS are specific instruction-based learning systems that offer knowledge-related information to learners. Thus, the information feedback of learning materials from MARLS regarding computer motherboard architecture is reliable, stable, and makes sense. MARLS may assist learners in evaluating their flow experience or observing extraneous cognitive load when they obtain high-quality information feedback (Zou et al., 2021). As mentioned above, the intervention of extraneous cognitive load on the effects of information feedback on learning-related outcome variables is an under-addressed issue in the MARLS literature.
Some studies indicated that AR-based applications could provide learners with various types of real-time information feedback, including visual and haptic feedback, in order to enhance their learning effectiveness (Belda-Medina & Calvo-Ferrer, 2022; Chiang et al., 2022; Jaszczur-Nowicki et al., 2021; Rodríguez et al., 2022; Wang et al., 2022; Yilmaz et al., 2022). Such timely and interactive feedback can help students better understand their learning goals, enhance their concentration and learning motivation, and arouse their interest or curiosity (Steele & Fullagar, 2009; Windasari & Lin, 2021).
However, AR-based learning may differ from other educational contexts, and different findings regarding the effects of information feedback on learning performance in other educational contexts have been reported in the literature. For example, some studies of other educational contexts found that the feedforward and outcome feedback offered by teachers are insignificantly related to students’ learning effectiveness (Burns et al., 2021; Lerch & Harter, 2001). Additionally, students’ competence did not significantly improve in the VR-supported project when they receive unfavorable cognitive feedback from their peers (Lin & Wang, 2021). Moreover, Karelaia & Hogarth (2008) found that cognitive and outcome feedback did not help for learning (i.e., judgmental consistency). Finally, information feedback did not affect flow experience in the context of learning about business simulation systems (Yen & Lin, 2020).
Based on the discussion above, the effects of information feedback on students’ learning effectiveness vary across different educational contexts. Thus, we can infer that more studies of information feedback are needed to better understand its impact on learning outcome in the MARLS context, because the effects of information feedback are dependent on the features of learning tasks, the design of learning materials and processes, and the tools or technologies used to support learning.
Additionally, AR-based applications offer individualized information feedback regarding students’ learning progress to the instructors, which can thus assist the instructors to identify the students’ misperceptions of learning materials or learning difficulties (Ng, 2022; Nikou et al., 2022). Information feedback of MARLS can overcome these obstacles, including videos demonstrating the multimedia learning materials and correct operations regarding the concepts of the computer motherboard architecture that help learners to engage in a personalized learning process. The procedures may reduce misunderstanding or enable them to learn at their own pace. In other words, MARLS provide personalized learning feedback to learners, giving them more opportunities to improve their knowledge acquisition and guide learning.
Flow theory
The flow experience is a significant issue in the context of higher education in terms of examining the learning outcomes of various educational activities (Buil et al., 2019; Yen & Lin, 2020), game-based learning (Hsieh et al., 2016; Li et al., 2021), and continued intention (Goh & Yang, 2021). Csíkszentmihályi (1975) proposed the fundamental concept of flow and explained how individuals feel highly focused attention, a sense of control, and enjoyment of work or during activities (i.e., learning, games, sports, adventure recreation, etc.). Based on flow theory, individuals who experience flow states at work or during activities can be nervous and concentrate on what they do in a unique context. Some researchers further indicated that if the presentation of learning content/material matches learners’ needs, the learning goals can be achieved by consuming less efforts, which can lead to high levels of the learners’ feeling of a sense of control, satisfaction regarding the learning process, and subsequent learning motivation (Cheng, 2017; Koç et al., 2022; Okai-Ugbaje et al., 2022). Additionally, the timely feedback may benefit learners by keeping them focused, increasing their interest or enjoyment in the knowledge acquisition process, thus inducing higher-order thinking or learning effectiveness (Chiang et al., 2014; Ebadi & Ashrafabadi, 2022; Lin & Chen, 2020; Mystakidis et al., 2022; Wu, 2019). This is because individuals can perceive a sense of control exceeding their experiences. In summary, it can be inferred that individual flow experience plays an important mediating role in the relationship between information feedback and learning effectiveness, which is rarely examined in educational settings in which mobile AR applications are applied. Therefore, this study, by using an experimental research design, intends to specifically address this research gap in the literature.
In this study, the flow experience is considered to be composed of three main categories (Goh & Yang, 2021). First, focused attention refers to the degree to which individuals immerse and concentrate their attention on the visual screen and execute an action by forgetting everything around them. Second, a sense of control refers to an individual’s control exceeding activity requirements without conscious effort. Third, enjoyment refers to how individuals assess a particular feeling of well-being due to cognitive and affective evaluations of a specific activity. We propose the three elements of a flow state can be applied to learning activities through the learning content of MARLS because learners’ flow state of MARLS during the learning process is positively associated with their perceived learning effectiveness and continued intention (AlNajdi et al., 2020; Ibáñez et al., 2014).
Cognitive load theory
Cognitive load theory is one of the famous theoretical perspectives that concerns the relationship between cognition and educational instructions in educational psychology (e.g., Cheng, 2017; Leppink-Heuvel & van den Heuvel, 2015; Liao et al., 2019; Paas et al., 2003; Skulmowski & Xu, 2022). It has been adopted in research dealing with the design of multimedia learning materials. Learning is tending conscious; thus, the learning process is complicated and full of effort (Sweller, 1994). This learning process may be considered cognitive. Similarly, it heavily relies on a limited amount of working memory and relevant data from vast amounts of information in the long-term memory. Learners’ possession of critical knowledge and information feedback in advance (i.e., the form of information presented in 3D) can decrease their extraneous cognitive load in learning contexts (Lai et al., 2019; Moreno & Mayer, 2007; Sweller et al., 1998). Thus, for video-based social media platforms (e.g., MARLS), the visual content that delivers the learning materials must match the tactile operations of the learners to decrease their cognitive load. Additionally, the learning task complexity relates to individuals’ previous knowledge constituting their cognitive load (Sweller, 1994). The use of an inappropriate instructional method for teaching or learning may increase the extraneous cognitive load of learners. In this study, MARLS were considered a learning system that integrates learning materials and the virtual environment and links what individuals learn in real-world settings to their prior knowledge. The provision of adequate information feedback to learners in MARLS-supported educational contexts can strengthen learners’ concentration, cognition, and reflective processes.
Hypothesis development
Based on the information feedback, flow, and cognitive load theories, this study proposes the learners’ psychological states of continued intention to use MARLS and perceived learning effectiveness are influenced by their flow experience and information feedback in technology-enhanced learning. Following the fundamental notion of flow theory, this study considers the MARLS attributes of information feedback, visual and tactile information, and learning content as evaluation criteria among learners to examine the variables as aforementioned (Fig. 1).Fig. 1 Conceptual research model
Feedback is a resource (Bakker, 2005). The potential learning experience is weakened if the learner does not receive clear goals or explicit information regarding completion, the amount, or timing of the content (Maier et al., 2016). Researchers indicated immediate feedback (i.e., feedforward) is one of the preconditions of the flow state (e.g., Buil et al., 2018, 2019). Useful information feedback is a required component of favorable flow experience derived from individual tasks (Csíkszentmihályi, 1990). Steele and Fullagar (2009) found a significant relationship between performance feedback and flow exists when students engage in various academic activities. Therefore, some challenges and skills are necessary for tasks or activities, resulting in an optimal learning experience in a virtual learning environment. Similarly, information feedback (i.e., feedforward, cognitive, outcome) is meaningful and valuable for learners, improving their flow state (i.e., concentration, a sense of control, and enjoyment) (Csíkszentmihályi, 1975, 1990; Hattie & Timperley, 2007; Windasari & Lin, 2021). It can be inferred feedback is positively related to flow experience (e.g., Buil et al., 2018; Guo & Ro, 2008; Kajitani et al., 2020; Wang & Wang, 2008). Accordingly, the hypothesis is as follows.H1a. Information feedback is positively associated with the flow experience.
In the virtual learning context, visual or tactile advanced learning technologies can assist students to enhance immersion and engagement (e.g., Ibáñez et al., 2014; Petersen et al., 2022; Shin, 2019). This can facilitate their engagement in and enhance their concentration on the learning tasks. Therefore, learners with experiencing a high level of flow state were more likely to identify or develop feasible solutions for problem-solving (Liu et al., 2011; Yang et al., 2019). Additionally, learners are likely to immerse themselves in learning tasks facing challenges when they achieve a flow state, thus, exhibiting better learning achievement (Hsieh et al., 2016; Sun et al., 2017; Wang & Hsu, 2014). The positive information feedback (i.e., audio-visual effects) may strengthen their confidence in obtaining future achievements (Teng, 2018). Some studies reported accurate responses or assessment feedback can significantly affect learners’ academic performance (Connolly et al., 2012; Zhao et al., 2021). Specifically, MARLS are an interactive teaching system that can provide immediate feedback and guidance for learners, influencing their cognitive processing (Müller & Wulf, 2022), behavioral engagement (Sun et al., 2019), and learning performance or perceived learning effectiveness (Alexiou et al., 2020; Eckes & Wilde, 2019; Yen & Lin, 2020). Accordingly, the hypothesis is as follows.H1b. Information feedback is positively associated with perceived learning effectiveness.
Previous studies reported the flow experience positively affects perceived learning effectiveness in a computer-based instructional environment (e.g., Ebadi & Ashrafabadi, 2022; Wang & Hsu, 2014; Yen & Lin, 2020). For example, Rachmatullah et al. (2021) found a game-based environment promotes students’ flow experiences of genetics learning and thus positively influences their posttest scores. Li et al. (2021) reported enjoyment leads to optimal learning, and thus positively impact learners’ perceived learning effectiveness (Alexiou et al., 2020). Therefore, it can be considered the flow experience can appraise the benefits in a virtual learning environment. Accordingly, the hypothesis is as follows.H2a. Flow experience is positively associated with perceived learning effectiveness.
In traditional instruction, learners typically must spend a lot of time and physical energy to engage in the learning content or skills. Nowadays, technology-enhanced applications give learners immediate access to learning materials. In a specific learning system, learners have less at risk when they engage in their learning tasks. In such a case, they will be more likely to browse and collect information for their learning. In this study, MARLS provide learners with an opportunity to learn and apply AR applications for obtaining focused attention, a sense of control, and pleasure. Thus, researchers may need to consider the aspects of flow experience and continued intention. This may be why learners’ willingness to continue using MARLS to improve their academic performance needs to examine their decision-making behaviors. Several studies indicated learners perceived flow experience while using a learning system or service affects their continued intention (e.g., Choi, 2022; Goh & Yang, 2021; Tuncer, 2021; Yang et al., 2014). When learners are in an optimum emotional state of the learning experience, they will have concentration, a sense of control, and enjoyment, influencing their continued intention to use MARLS (Zha et al., 2016). Accordingly, the hypothesis is as follows.H2b. Flow experience is positively associated with the learner’s continued intention to use MARLS.
Currently, online learning has spread widely to various levels of learners. However, continuing to use technology-enhanced systems is still a critical issue (e.g., Liao et al., 2015; Lin et al., 2014; Wang & Lin, 2021). This study considers the actual success of MARLS to be related to learners' continued usage behaviors that can assist learners’ perceptions and improve their perceived learning effectiveness. They will be willing to use MARLS to support their learning and enhance their effectiveness. Previous studies on the continued intention to use online learning systems suggest perceived learning effectiveness significantly affects learners’ behavioral intention (Liaw & Huang, 2016; Liu et al., 2021; Tawafak et al., 2020). In this study, the purpose of MARLS is to facilitate learners’ learning of the knowledge of the computer motherboard architecture, making them feel confident to engage in learning tasks and subsequent assessments, thus promoting their intention to continue using MARLS. It can be inferred perceived learning effectiveness is associated with learners’ intention to continue using the MARLS. Accordingly, the hypothesis is as follows.H3. Learners’ perceived learning effectiveness is positively associated with their continued intention to use MARLS.
The impact of AR technology has widely influenced learners’ behavioral patterns in education settings. For example, some prior studies argue a guide/guideless video or game can significantly affect a learner’s academic performance in a learning activity (e.g., Lai et al., 2019; Tawafak et al., 2020). Therefore, the design of learning technologies may involve a variety of information feedback to meet the users’ learning goals and desired academic performance success. Research has shown these technologies aim to achieve faster information feedback and flexibility for learners; similarly, they have to take on challenging learning tasks in their learning process (Wang & Lin, 2021). Previous studies argued learners’ learning performance/outcome is associated with their continued intention (Wongwatkit et al., 2020). Accordingly, the hypothesis is as follows.H4. Learners’ improved learning performance is positively associated with their continued intention to use MARLS.
Previous research indicated extraneous cognitive load is negatively associated with academic performance or the effectiveness of cognitive processes (Cheng et al., 2021; Su, 2016). However, a study stated proper task demands or characteristics in a learning procedure or instructional design could alter the extraneous cognitive load of learners (Skulmowski & Rey, 2017). In this study, the learning material is not pure text-based which may generate additional cognitive load for most participants. Additionally, most of them are using MARLS for the first time in their learning tasks at a high level of thinking about the new information, and thus, the impact of extraneous cognitive load cannot be neglected (Hollender et al., 2010; Jiang et al., 2018). They need to integrate the visual and tactile sensations and follow the given information from MARLS, which may influence their cognitive load (Makransky et al., 2019; Petersen et al., 2022). Lee and Hong (2022) found cognitive load has a moderating effect on the relationship between epistemic prompting and students’ multimodal multiple text comprehension. Accordingly, the hypothesis is as follows.H5. Extraneous cognitive load negatively moderates the relationship between information feedback and perceived learning effectiveness.
Methodology
Experiment
The experiment conducted for this study aimed to understand the impact of MARLS in learning the knowledge of computer motherboard architecture. In this study, information feedback and flow experience were examined to discover their effects on perceived learning effectiveness and to understand their continued intention on learners’ improved learning performance in the contexts of using MARLS. The design of the MARLS developed for this study was described in the subsequent sections.
The MARLS used in this study were developed to help student learn about the technical specifications of the motherboard of a personal computer and the key components of the motherboard, which is one of the learning subjects of the course of “Computer Architecture.” The research participants were able to use the MARLS using a mobile device running on the Android operating system, including smart phones and tablet computers. To avoid the potential disturbance in the surrounding environment, the research participants of this study were asked to complete the learning processes of the MARLS using a tablet computer in a lab designated by the researchers. The research participants were asked to take a pre-test and a post-test before and after using the MARLS in order to offer us sufficient data to evaluate how well their knowledge of the focal learning subjects was improved. After completing the learning processes of the MARLS, they were also asked to fill out a survey in order to offering data that could be used to evaluate their perception regarding the MARLS and their perceived learning effectiveness.
Before using the MARLS, the designed system would give the learners five questions to evaluate their prior knowledge regarding computer motherboard architecture (i.e., the pre-test). The feedback included three parts. First, regarding feedforward, MARLS presented some instructions to learners regarding how to operate and control the MARLS functions as well as the learning objectives of the MARLS. Then, the learner could begin the learning tasks and read the learning materials via the MARLS interface to gain new knowledge. The research participants could immerse themselves in the learning content through the guidance of the feedforward that included information for helping them understand the relevant concepts of computer motherboard architecture. Second, after completing all learning content, the system showed a number of exam questions to assess the levels of the students’ learning effectiveness (i.e., the post-test). Third, MARLS automatically provided students with different cognitive feedback and outcome feedback based on the learners’ post-test scores. The former provided the relevant instructions for the post-test response, while the latter provided learners with post-test scores. To be specific, when a participant’s post-test score was 100 of out 100, the MARLS provided a message to the participant to indicate that they had understood the learning materials very well. Additionally, MARLS offered instructions (i.e., cognitive feedback) to a participant by referring to the exam questions that the participant got the answers to wrong in order to help him/her improve his/her understanding of the focal learning materials when his/her post-test scores were between 60 and 99. Finally, MARLS provided a participant who scored lower than 60 in the post-test with instructions (i.e., cognitive feedback) related to the exam questions that he/she got the answers to wrong in order to help him/her improve his/her understanding of the focal learning materials, and then asked him/her to take the post-test again (see Fig. 2). While the MARLS were designed to repeat the same process of retaking the post-test until the post-test score of a participant was 60 or above out of 100 (since the score of 60 out of 100 is the minimum score required to pass an exam in Taiwan), none of our participants was required to take the post-test for more than two times.Fig. 2 The learning procedures
System overview of the MARLS used
The MARLS included three major components: (1) interactive interfaces that include fingertip videos, interactive visual functions, and information rendering overlay; (2) hardware components that include camera, interactive semantics, and interactive data for introducing the hardware components (i.e., mainframe computer motherboard architecture, central processing unit, and random access memory (RAM)); (3) communication tools that include a fingertip interactive information acquisition module and an online registration function for the authentication of user identities (Jiu et al., 2022; Westerfield et al., 2015). In other words, the critical elements of the MARLS designed for this study include integrated real-world and virtual content using 3D AR-based technology and functions of real-time interaction (Belda-Medina & Calvo-Ferrer, 2022). The participants can use their fingertips as a virtual pen to get more information or knowledge feedback from the MARLS. Several researchers found that using 3D AR-based learning applications can enhance students’ learning effectiveness by enabling students to acquire enhanced visuospatial perception that can help them better understand the learning materials, and thus result in better flow experiences in terms of enhanced cognitive skills, enjoyment, interest, and engagement (e.g., Belda-Medina & Calvo-Ferrer, 2022; Koç et al., 2022; Demitriadou et al., 2020; Mystakidis et al., 2022). The reason is that when students perceive the learning processes are under their control and do not beyond their cognitive abilities because of the provision of appropriate and timely information feedback, they are likely to be interested and concentrated in the focal learning tasks and perceive their learning experience to be enjoyable.
In this study, the participants can perform their learning tasks through 3D models and interactive omnidirectional videos that may increase their learning motivation and keep their cognitive resources available for learning (Skulmowski & Xu, 2022). A worth noting advantage of 3D-based learning functions, although they are more challenging for the human brains to process, is that they can overcome the disadvantages of the learning processes supported by two-dimensional (a flat object) visual presentation, such less effective and less interesting human–computer interactions and poor virtual control ability regarding the interactive assembly instructions (Alhonkoski et al., 2021; Jiu et al., 2022). Additionally, the main learning processes of the MARLS were performed by providing the learners with feedforward feedbacks for reducing unnecessary cognitive efforts devoted prior to the actual learning processes, and with cognitive feedbacks for enhancing learners’ odds of acquiring the accurate knowledge via a smart mobile device.
Additionally, the research participants followed the instructions given by the MARLS to complete the learning tasks by performing fingertip movement via a tablet computer running on the Android operating system (Fig. 3). Such conditions can enable the participants to focus on the learning tasks for acquiring the knowledge related to physical objects, such as computer hardware, more easily and provide them with a sense of control and enjoyment. Therefore, the design of the MARLS of this study may facilitate learners’ critical/analytical thinking, particularly in the process of learning sophisticated knowledge. Additionally, the design of the MARLS used allowed the research participants to use the smart mobile device to freely observe the pictures of the components of a motherboard using different angles, which could increase the learners’ perceived level of quality of interacting with the virtual learning content of the MARLS, and thus enhance the immersion effects on the learners and produce a better flow experience for the learners. The learning content and information feedback were immediately demonstrated through dialogues or guidance. The key concepts of the focal learning topic was incorporated into both the MARLS learning instructions (i.e., feedforward and cognitive feedback) and the exam questions in an interactive and more interesting manner to motivate participants to use the MARLS to achieve their learning goals. In other words, the MARLS enable learners to learn in a comfortable and enjoyable environment by performing the AR-supported interactive learning processes using mobile devices. Moreover, the feature of ubiquity of the MARLS, similar to that of many different mobile applications, makes it possible for learners to learn anytime and anywhere based on an informal curriculum and a flexible schedule and to learn the knowledge that they need more thoroughly by repeatedly performing those learning processes of the MARLS as many times as they want.Fig. 3 The MARLS design
Data collection
This study aims to examine the effects of information feedback on flow experience, perceived learning effectiveness, and learners’ continued intention regarding using the MARLS for their learning tasks. Ethics approval for this study was obtained from the University Governance Framework for Human Research Ethics of the authors’ institute approved (HREC-109–088-2). Additionally, all participants were informed of the research purposes and volunteered to participate in the survey, treating their information as confidential.
This study uses a psychometric survey to examine the proposed research model and hypotheses. By distributing the information of the experiment of this study through the online student forums of ten randomly selected universities in Taiwan, the authors recruited 204 students from those universities who had no experience with MARLS or no experience in taking courses related to computer hardware architecture to ensure there were no significant differences in the respondents’ prior knowledge regarding the use of the system or the learning subjects. All participants were asked to finish a pre-test exam and fill out a survey immediately to examine their prior knowledge. Each qualified participant was asked to download the MARLS application using their tablet or mobile when it was convenient to participate in this experiment. Additionally, the participation in the experiment of this study was totally voluntary to the potential participants, and none of the authors have any conflicts of interest or noticeable relationships with the 204 participants.
No interaction or conversations were allowed; each participant had to independently complete the subjects’ learning process during the experiment to avoid affecting the results. Moreover, they were asked to finish a post-test exam and fill out the questionnaire when they completed their learning tasks. Each participant received a coupon of around USD 3.5 as a gift for their voluntary participation in the experiment of this study. Finally, a total of 204 valid responses were analyzed to validate the proposed hypotheses. The demographic details showed male participants comprised 107 (52.45%), 202 (99.02%) participants were in the age group of 20–25 years, 94 (46.08%) had a bachelor's degree, and 104 (50.98%) had a master’s degree or above.
Instrument
The constructs of information feedback, flow experience, perceived learning effectiveness, continued intention, and improved learning performance were measured using multi-item scales (see Appendix Table 3). The operationalization variables are as follows.
Information feedback was measured by nine items (three items each for feedforward, cognitive feedback, and outcome feedback) whose wordings were modified to fit with the research context of this study (Brooks et al., 2019; Faber et al., 2017; Hattie & Timperley, 2007; Maier et al., 2016). Flow experience was evaluated by nine items (three items each for focused attention, sense of control, and enjoyment), slightly edited by an adapted version of the studies (Ahn et al., 2007; Buil et al., 2019; Rodríguez-Ardura & Meseguer-Artola, 2017). These items of flow experience are also studied in the context of computer-based learning/instruction (Ibáñez et al., 2014; Li et al., 2021; Wang & Hsu, 2014). Moreover, a total of twelve items were adopted to assess perceived learning effectiveness to examine students’ response (three-item), learning (three-item), behavior (three-item), and achievement (three-item). The aforementioned items were employed and modified from Chrysafiadi and Virvou (2013) and Huang et al. (2015). Three items measured extraneous cognitive load employed by Leppink-Heuvel and van den Heuvel (2015). Continued intention was evaluated by three items that modified the version of Mohammadyari and Singh (2015). A seven-point scale ranging from 1 (“strongly disagree”) to 7 (“strongly agree”) scored all items. Additionally, the improved learning performance was measured by the normalized scores of the post-test and pre-test of the research participants.
Additionally, a pilot test was conducted to evaluate the reliability of the survey items adopted. A total of thirty participants were invited to participate in the pilot test, and the data collected was assessed by checking the Cronbach’s alpha coefficients of the first-order latent constructs. The results indicated the Cronbach’s alpha coefficients of all the first-order latent constructs were greater than the recommended threshold value of 0.7 (ranging from 0.71 to 0.89), indicating the survey items of all the constructs had acceptable levels of reliability. All items were thus used in the subsequent data collection procedure.
Data analysis method
The proposed research model performed a confirmative factor analysis by Smart PLS 3.0 to assess these scales’ psychometric properties in terms of adequacy, including reliability, convergent, and discriminant validities. By using the partial least square structured equation modeling (PLS-SEM) approach, this study examines the validity and reliability of the data collected, and then validates the developed research hypotheses. Additionally, PLS-SEM can thoroughly explain the content validity using its latent indicators of the second-order formative construct. Therefore, the proposed hypotheses were tested through a bootstrapping procedure with resampling at 5,000 times and a 95% confidence interval.
Results and discussion
Hypothesis testing results and discussion
All the proposed hypotheses were supported (Fig. 4). The information feedback is positively and significantly associated with flow experience (H1a: β = 0.39, t = 6.54) and perceived learning effectiveness (H1b: β = 0.48, t = 10.23). There was a positive and significant relationship between flow experience and perceived learning effectiveness (H2a: β = 0.30, t = 5.58), and continued intention (H2b: β = 0.22, t = 3.14), respectively. Perceived learning effectiveness is positively and significantly associated with continued intention (H3: β = 0.56, t = 8.95. Improved learning performance is positively and significantly associated with continued intention (H4: β = 0.13, t = 2.32). Extraneous cognitive load negatively and significantly moderated the relationship between information feedback and perceived learning effectiveness (H5: β = -0.14, t = 2.51).Fig. 4 Results of hypotheses testing of the research model. Note: * p < 0.05; ** p < 0.01; *** p < 0.001
In examining H1a, the finding indicated information feedback is positively related to perceived learning effectiveness, consistent with the previous studies (Buil et al., 2018; Guo & Ro, 2008; Kajitani et al., 2020; Wang & Wang, 2008). This suggests learners with more information feedback will reduce the uncertainty of the learning requirements and increase the strength of belief in the learning environment of MARLS. Particularly in this study, relative information feedback may make them engage in and do their best; thus, potentially improving their incentive to study and leading to better-perceived learning effectiveness. Similarly, the result of H2a reveals a learner with a higher flow experience is associated with perceived learning effectiveness, which is in line with previous studies (e.g., Ebadi & Ashrafabadi, 2022; Li et al., 2021; Wang & Hsu, 2014; Yen & Lin, 2020). This study suggests MARLS can enhance learners’ flow experience (i.e., focused attention, sense of control, and enjoyment), resulting in better-perceived learning effectiveness.
In examining H1b, the findings indicated information feedback is positively associated with flow experience, consistent with the findings of previous studies (e.g., Alexiou et al., 2020; Alexiou et al., 2020; Eckes & Wilde, 2019; Yen & Lin, 2020). Real-time or detailed information feedback may facilitate the flow experience in the MARLS context while promoting focused attention, a sense of control, and fun in MARLS learning practices.
In examining H2b and H3, the results revealed learners with a high level of flow experiences would have a higher level of continuance intention to use MARLS for their learning. H2b is consistent with previous studies (e.g., Choi, 2022; Goh & Yang, 2021; Tuncer, 2021; Yang et al., 2014) and H3 is in line with previous studies (e.g., Liaw & Huang, 2016; Liu et al., 2021; Tawafak et al., 2020). Flow experience is mainly derived from focused attention, a sense of control, and enjoyment to maintain or build high levels of positive psychological state in a learning activity. Thus, learners with a higher flow experience will promote their continuance intention positively. In the case of visual- and tactile-based learning, enjoyment and continuance intention are associated with each other. Additionally, MARLS reveal it can enable and support learner tasks, leading to a strong continued intention to use MARLS.
The confirmation of H4 is in line with the result of Wongwatkit et al. (2020). This means MARLS can assist learners to improve learning performance, leading to the development of a high willingness to use this learning system.
H5 is a novel finding that can provide a reference opportunity to improve the teaching/learning design. H5 reveals extraneous cognitive load significantly and negatively moderates the influences of information feedback on perceived learning effectiveness. Additionally, extraneous cognitive load is significantly negatively related to perceived learning effectiveness (β = -0.12, t = 2.55), consistent with a previous study (Chang, 2018). This study suggests the MARLS developers and course instructors need to carefully design the mechanisms for offering information feedback in the MARLS use context (i.e., learning materials and teaching practices) to diminish learners’ cognitive load (Ebadi & Ashrafabadi, 2022; Moreno & Mayer, 2007). Offering more ongoing feedback for instructions, clear visual presentations, and rearranging the sequence/range of examples might help them to improve their perceived learning effectiveness.
Overall, the findings of this study have pointed out the important influences of information feedback on perceived learning effectiveness by enhancing the flow experience of MARLS users. Therefore, pedagogical methods that are supported by MARLS may offer timely and adequate information feedback to students in order to arouse their interest toward learning tasks, which will lead to more favorable flow experience and better learning outcomes of the students.
The validity of measurement model
First, in the measurement model, convergent validity primarily examines the proposed constructs that are well reflected by its measured items, consisting of the factor loadings, internal consistency reliability, composite reliability (CR), and average variance extracted (AVE) (Fornell & Larcker, 1981). As shown in Appendix Table 3, the values of factor loadings show all items were significantly greater than 0.7. Table 1 shows the Cronbach's alpha values ranged from 0.7 to 0.89, the CR values ranged from 0.83 to 0.93, and the AVE ranged from 0.62 to 0.81, exceeding the criteria of 0.7, 0.7, and 0.5, respectively (Hair et al., 2019). The results revealed all constructs with excellent reliability and convergent validity were obtained in this study.Table 1 The results of discriminant validity
Construct 1 2 3 4 5 6 7 8 9 10 11 12 13
1.Feedforward 0.68
2.Cognitive 0.15
(0.5)
0.69
3.Outcome 0.20
(0.57)
0.4
(0.79)
0.72
4.Focus attention 0.09
(0.38)
0.13
(0.46)
0.05
(0.28)
0.75
5.Sense of control 0.04
(0.25)
0.04
(0.29)
0.03
(0.23)
0.16
(0.5)
0.62
6.Enjoyment 0.07
(0.33)
0.06
(0.3)
0.01
(0.16)
0.19
(0.52)
0.07
(0.32)
0.77
7.Response 0.21
(0.64)
0.3
(0.75)
0.18
(0.56)
0.23
(0.63)
0.06
(0.33)
0.15
(0.5)
0.63
8. Learning 0.19
(0.56)
0.27
(0.65)
0.13
(0.43)
0.05
(0.28)
0.02
(0.17)
0.11
(0.4)
0.4
(0.83)
0.72
9. Behavior 0.11
(0.43)
0.14
(0.47)
0.07
(0.33)
0.11
(0.41)
0.07
(0.34)
0.18
(0.51)
0.37
(0.81)
0.39
(0.78)
0.70
10. Achievement 0.19
(0.53)
0.26
(0.62)
0.2
(0.54)
0.12
(0.41)
0.08
(0.35)
0.13
(0.41)
0.46
(0.86)
0.44
(0.78)
0.56
(0.89)
0.81
11. Extraneous cognitive load 0.04
(0.24)
0.03
(0.21)
0.04
(0.24)
0
(0.09)
0
(0.1)
0
(0.06)
0.03
(0.25)
0.08
(0.35)
0.01
(0.15)
0.05
(0.26)
0.72
12.Continued intention 0.07
(0.35)
0.14
(0.49)
0.06
(0.33)
0.19
(0.54)
0.12
(0.46)
0.13
(0.44)
0.32
(0.76)
0.27
(0.65)
0.34
(0.74)
0.4
(0.76)
0.01
(0.14)
0.71
13Improved learning performance 0
(0.11)
0.01
(0.12)
0.02
(0.18)
0
(0.07)
0
(0.06)
0.02
(0.14)
0.01
(0.14)
0
(0.11)
0
(0.06)
0
(0.08)
0
(0.02)
0.02
(0.17)
1
Mean 5.54 5.82 5.29 5.38 5.09 5.08 5.46 5.86 5.56 5.66 3.13 5.69 1
SD 0.95 0.91 1.15 0.98 0.86 0.98 0.83 0.79 0.88 0.85 1.28 0.94 -
Composite reliability 0.86 0.87 0.89 0.9 0.83 0.91 0.84 0.89 0.87 0.93 0.89 0.88 1
Cronbach’s alpha 0.76 0.77 0.8 0.83 0.7 0.85 0.71 0.81 0.78 0.89 0.8 0.79 1
N = 204; SD = standard deviation; Heterotrait-Monotrait (HTMT) ratios are in parentheses; the average variance extracted (AVE) were at the diagonal, and the values of the squared correlation coefficients were at the non-diagonal. Boldface highlights the diagonals
Additionally, discriminant validity evaluates the structural model and whether the survey constructs are empirically distinct from other constructs (Hair et al., 2019). According to the criteria (Fornell & Larcker, 1981), the AVE value of each construct should be larger than the squared inter-construct correlation coefficients between the others in the research model; similarly, no AVE value is less than 0.50. Table 1 shows the AVE of each construct was larger than the squared inter-construct correlation coefficients between each construct.
Further, Henseler et al. (2015) stated the correlations’ Heterotrait-Monotrait (HTMT) ratio could be used to assess the discriminant validity of the measurement model. High HTMT values in the research model reveal the discriminant validity is debatable. They suggest the HTMT values did not exceed 0.90 for structural models with constructs, and thus, the conceptual meaning of these constructs are similar. The results indicated all HTMT values were less than 0.89, which didn’t exceed the criteria of 0.9; moreover, the HTMT values are significantly different from 1 in the bootstrapping procedure (Table 1). The results support the presence of the discriminant validity was acceptable.
Finally, information feedback, flow experience, and perceived learning effectiveness formed a concept of second-order formative constructs. They were formed by the weighted sum of their first-order reflective constructs. The principal component analysis weights are better than evaluating by the factor loadings of indicators suggested by Petter et al. (2007). To meet the basic requirements for research analysis, the authors further examined the variance inflation factor (VIF) of all items to avoid excessive multicollinearity, enhancing the validity of the formative model. Table 2 indicates none of the VIFs exceeded the criteria of 3.3 (Petter et al., 2007); thus, serious multicollinearity was not present in this study.Table 2 Testing the multicollinearity by weight and variance inflation factor (VIF)
Second-order construct First-order first-construct VIF Standard error Weight (t-value)
Information feedback Feedforward 1.28 0.04 0.42*** (11.92)
Cognitive 1.69 0.03 0.47*** (15.39)
Outcome 1.81 0.03 0.34*** (11.10)
Flow experience Focused 1.38 0.04 0.50*** (11.61)
Control 1.2 0.05 0.36*** (6.58)
Enjoyment 1.25 0.05 0.44*** (8.75)
Learning effectiveness Response 2.1 0.01 0.31*** (20.25)
Learning 2.09 0.02 0.27*** (18.34)
Behavior 2.5 0.02 0.27*** (16.08)
Achievement 2.95 0.02 0.31*** (21.2)
*** p < 0.001
The validity of structural model
This study uses the bootstrapping procedure by partial least squares SEM to evaluate all hypotheses of the structural model. The authors use nonparametric bootstrapping with 5,000 samples and bias-corrected 95% confidence intervals to assess all hypotheses of the structural model. Additionally, predictive relevance (Q square) can assess the structural model’s goodness of fit. According to the studies (Geisser, 1974; Stone, 1974), all endogenous constructs should be above 0. The results of the Q square values ranged from 0.02 to 0.83, which did not include 0. Additionally, Fig. 4 shows the R squared values of flow experience, perceived learning effectiveness, continued intention, and improved learning performance were 0.15, 0.49, 0.49, and 0.03, respectively.
Conclusion
MARLS incorporate mobile devices and AR applications in the instruction/learning on computer motherboard architecture, allowing learners with a positive flow state to complete their learning tasks, improving perceived learning effectiveness and continued intention. MARLS use visual and tactile information feedback to assist learners in completing their tasks in the learning procedure. The positive flow state can help their absorption, memory, and cognitive abilities. Therefore, appropriate approaches (i.e., strategies, tools, and information feedback) are needed to facilitate learner awareness, reflection, intention, or action. This study suggests new learning material content incorporated into technologically-enhanced learning design could significantly increase perceived learning effectiveness and continued intention among learners of MARLS. Such digitized MARLS facilitate learners’ interest and motivation toward learning knowledge of a specific challenging learning area by offering them an interesting and interactive learning environment (Bressler et al., 2021). The finding of this study can provide us with important insight and valuable information for future studies and various stakeholders to use as guidelines for developing new tools.
This study proposed a technologically-enhanced learning process that strengthens learners’ perceived learning effectiveness through MARLS to offer suitable learning support by enhancing the understanding of the learning materials. The findings of this study have some implications and limitations described as follows.
Theoretical implications
In the context of using MARLS in higher educational institutes, this study is among the first group of studies that integrate the theoretical views of information feedback, flow experiences, and cognitive loads to explain how MARLS can positively influence students’ perceived learning effectiveness. The validation of the causal relationships among information feedback, flow experience, perceived learning effectiveness, improved learning performance, and continued intention to use MARLS can help us better understand learners’ learning experiences and behaviors in AR-based learning environments. The results significantly contribute to the existing literature, and offer implications regarding how the learners in higher educational institutes can be motivated to use the AR-based learning applications that are similar to the MARLS.
To be specific, the research results imply that when the level of the quality of the information feedback of the MARLS is high, the MARLS users can be more immersed in the learning processes (i.e., flow experience), thus resulting in better learning outcomes (Chen et al., 2021; Müller & Wulf, 2022). To elaborate on the statement above, the research results of this study contradicted some of the prior studies (e.g., Burns et al., 2021; Lerch & Harter, 2001; Lin & Wang, 2021; Yen & Lin, 2020) and indicate that information feedback are helpful for supporting learning, as found in some other prior studies (e.g., Kajitani et al., 2020; Eckes & Wilde, 2019; Rodríguez et al., 2022). Those results thus contribute to the theory development of future MARLS studies by confirming the significant positive effects of information feedback on students learning effectiveness in MARLS contexts, and highlight the importance of including the concept of information feedback in future studies that specifically examine the effectiveness of using MARLS to support student learning in various educational contexts, which, to the best of our knowledge, has not been done in prior studies of MARLS.
Additionally, our findings reveal that when the MARLS are easily accessible and provide learners with timely and useful feedback, the learners are more likely to develop a more thorough understanding of the learning subjects. This is because the learners can feel more motivated to learn, be more immersed in the learning tasks, and find the learning processes to be more enjoyable (i.e., flow experience), thus resulting in better learning outcomes (Chen et al., 2021; Müller & Wulf, 2022). Therefore, MARLS users can be benefited by an AR-supported student-centered pedagogical method that can eliminate the obstacles of traditional learning, such as external distractions in the learning environment and less enjoyable learning processes, via the formation of flow experience (Okai-Ugbaje et al., 2022).
Finally, the significant direct and moderating effects of extraneous cognitive loads indicate educators cannot avoid the negative influence of extraneous cognitive loads on the learning process. While digital learning materials and teaching approaches have widely spread to various educational settings nowadays, extraneous cognitive loads' direct and intervening effects cannot be neglected. The extraneous cognitive loads are an obstacle to effective learning, and educators should devote themselves to eliminate the learning materials that may result in increases in learners’ extraneous cognitive loads when developing their teaching content and tools.
Practical implications
This study also has practical implications for instructors, students, and other stakeholders. First, regarding the intervention of extraneous cognitive load, this study suggests researchers and instructors should design and build a clear relationship between the figures, diagrams, and text. In such a case, it may reduce learners' cognitive load and be helpful for them to build learning concepts, facilitating their perceived learning effectiveness.
Second, from the viewpoint of information feedback, MARLS can effectively support instructors’ teaching by offering prompt information feedback, in various kinds of format, that may be used as guidelines for learning and eventually contribute to the enhancement of the learners’ learning effectiveness. To elaborate on this, using the functions of MARLS helps instructors to monitor the learning progress of students by referring to the MARLS feedback. In such a learning situation, learners can move forward or backward to understand the episode of learning content to deepen their impression. Additionally, instructors may align appropriate teaching approaches (e.g., situational teaching) with the use of information feedback in a MARLS-based educational context. In other words, MARLS are capable of presenting learning instructions (i.e., information feedback) at any stage of the learning processes. Therefore, instructors can thus develop useful feedback and offer it to the learners at the appropriate points of time based on the learners’ progress in the MARLS learning processes in order to ensure the learners achieve the focal learning objectives in an effective manner. For example, instructors may use automatic message generation functions that can automatically generate useful information feedback (e.g., feedforward and cognitive feedback) at the appropriate points of time during the MARLS learning processes in order to help students reflect on what is learned and/or concentrate on what is to be learned (Rodríguez et al., 2022), thus enhancing their flow experience and learning effectiveness.
Finally, regarding flow experience, a learner’s engagement or immersion in MARLS can symbolize a flow state (Bressler & Bodzin, 2013; Tang et al., 2022). If learners perceive learning tasks involving meaningful experiences, they may maintain a sense of control and pay more focused attention to learning goals. Flow experience promotes learners' perceived learning effectiveness or performance (i.e., decreased technological frustrations, made information or navigation easier by vision-based AR, and enjoyed having to think) and continued intention to use MARLS. In summary, this study revealed the important role that learners’ flow experience plays in facilitating learners’ learning effectiveness in MARLS-supported educational contexts. Therefore, future MARLS developers should carefully consider how to design the MARLS that adequately align the learning processes with the primary learning objectives, which can eliminate users’ learning pressure in order to facilitate the formation of their flow experience and improve their learning outcome (Chang et al., 2022; Kajitani et al., 2020; Skulmowski & Xu, 2022; Yu et al., 2019).
Limitation
Some limitations exist in this study. The learning material content only focuses on computer motherboard architecture. The results of this experiment suggest future studies could improve learning material content design by incorporating more conceptual diagrams, tables, and quizzes into their experiment planning regarding IT-related or other science curricula. Additionally, the participants only focused on the first-time use of MARLS and the conception of computer motherboard architecture; thus, the technical and practical conceptions are simple. Future study can increase the difficulty in the curriculum with more depth and breadth of materials to strengthen the learners’ abilities. Moreover, undergraduate students or above were invited to participate in this study. Concerning the information feedback mechanism of MARLS, subsequent researchers can design the appropriate feedback based on the learners’ age, gender, or familiarity levels with computers. For example, using diverse images may stimulate positive emotional responses with complete information feedback for learners. Further, this study uses mobile devices and AR applications for this experiment. Subsequent researchers can combine diverse technologies and techniques to develop a more optimal learning system to strengthen the feasibility and development of potential limitations in various educational settings, including space, time, etc.
Appendix
See Table 3
Table 3 List of survey items of this study
Factor Item Factor loading
Feedforward (Brooks et al., 2019) Before the experiment, providing the…
IFF1 knowledge of the computer motherboard architecture was helpful to me 0.87
IFF2 knowledge of the computer motherboard architecture did not help me learn and better understand it. ** 0.78
IFF3 operational content gave me a preliminary understanding of the relevant knowledge of the computer motherboard architecture 0.82
Cognitive feedback (Maier et al., 2016) IFC1 I am not interested in the cognitive feedback provided by MARLS. ** 0.70
IFC2 The MARLS can provide detailed feedback on answering questions and that is a great thing 0.91
IFC3 The MARLS technology can provide detailed feedback on answering questions and that is helpful for me 0.86
Outcome feedback (Faber et al., 2017; Liu et al., 2021) IFO1 The outcome feedback provided after the exam did not give me a better understanding of computer motherboard architecture. ** 0.70
IFO2 The outcome feedback provided after the quiz made me more familiar with the computer hardware 0.93
IFO3 The outcome feedback provided after the quiz allowed me to understand better which parts of my knowledge are still lacking regarding computer hardware 0.90
Focused attention (Rodríguez-Ardura & Meseguer-Artola, 2017) FEF1 I can block out most other distractions when using the MARLS 0.88
FEF2 I am absorbed in what I am doing when using the MARLS 0.83
FEF3 I have a feeling of concentration when using the MARLS 0.88
Sense of control (Rodríguez-Ardura & Meseguer-Artola, 2017) FEC1 I feel in control when I use the MARLS 0.76
FEC2 I was influenced when I used the MARLS. ** 0.85
FEC3 I was dominated when I used the MARLS. ** 0.76
Enjoyment (Ahn et al., 2007; Buil et al., 2019) FEE1 I really enjoyed it when I used the MARLS 0.84
FEE2 I felt good when I used the MARLS 0.90
FEE3 Using the MARLS made my learning task more fun 0.89
Response (Chrysafiadi & Virvou, 2013) LER1 MARLS helps me understand the concept of computer motherboard architecture 0.78
LER2 I think MARLS are useful as general educational tools 0.85
LER3 I understand all the learning content while using the MARLS 0.75
Learning (Huang et al., 2015) LEL1 I think MARLS can make mainframe computer motherboard architecture courses more interesting 0.87
LEL2 I think courses on MARLS are worth trying 0.88
LEL3 If everyone is serious about their studies, I think they will complete the computer motherboard architecture quiz in MARLS 0.80
Behavior (Chrysafiadi & Virvou, 2013) LEB1 MARLS affect my positive perception of the computer motherboard architecture 0.86
LEB2 MARLS inspired me to learn more about computer motherboard architecture 0.81
LEB3 MARLS affect my positive perception of other AR learning courses 0.83
Achievement (Chrysafiadi & Virvou, 2013) LEA1 MARLS helped me learn other computer mainframe architecture-related courses 0.91
LEA2 MARLS helps me learn 0.90
LEA3 MARLS helped me become more aware of other activities related to learning about computer motherboard architecture 0.90
Extraneous cognitive load (Leppink-Heuvel & van den Heuvel, 2015) ECL1 Instructions and explanations in the MARLS Interactive Learning course are of no avail to aid learning 0.88
ECL2 I find the instructions and explanations in the MARLS interactive learning course incomprehensible 0.91
ECL3 In this MARLS interactive learning course, I put a lot of effort into understanding the unclear instructions and explanations 0.75
Continued intention (Mohammadyari & Singh, 2015) CI1 I will continue to use MARLS 0.92
CI2 I will continue to use MARLS rather than traditional learning methods 0.88
CI3 If possible, I would like to stop using MARLS. ** 0.71
Improved learning performance DLP1 The normalized scores of the post-test minus pre-test 1
** reverse score
Acknowledgements
This research was supported by the Ministry of Science and Technology [grant number: XXX].
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Declarations
Conflict of interest
None
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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735210 | NO-CC CODE | 2022-12-14 23:29:53 | no | Educ Inf Technol (Dordr). 2022 Dec 5;:1-33 | utf-8 | Educ Inf Technol (Dordr) | 2,022 | 10.1007/s10639-022-11487-6 | oa_other |
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Adv Fiber Mater
Adv Fiber Mater
Advanced Fiber Materials
2524-7921
2524-793X
Springer Nature Singapore Singapore
231
10.1007/s42765-022-00231-x
Research Article
Processing Nomex Nanofibers by Ionic Solution Blow-Spinning for Efficient High-Temperature Exhausts Treatment
Cheng Zekun 1Zekun Cheng
is a Ph.D. student under the supervision of Prof. Hui Wu at the School of Materials Science and Engineering, Tsinghua University. His research interests mainly focus on developing novel methods for preparing nanofibers and the multifunctional applications of nanofibers.
Wang Haiyang 1Haiyang Wang
received his B.S. degree from Northwestern Polytechnical University in 2015. He is currently pursuing his Ph.D. degree under the supervision of Prof. Zhen Xu at Tsinghua University, China. His research focuses on nanofibers.
Li Ziwei 1Ziwei Li
is a graduate student at Tsinghua University under the supervision of Prof. Hui Wu. His research interests focus on the fabrication and applications of nanofiber materials.
Yang Chong 1Chong Yang
received his Ph. D. degree from Huazhong University of Science and Technology (P.R. China) in 2020. He is currently a postdoctoral fellow in the laboratory of Prof. Hui Wu at Tsinghua University. His research focuses on fabricating various nanofibers and their application in air filtration.
Zhang Baopu 1Baopu Zhang
received his B.E. degree under the guidance of Prof. Hui Wu from Tsinghua University in 2022. His research focused on the preparation and application of nanofibers. He is going to pursue his Ph.D. degree at the Chemical Engineering Department of the Massachusetts Institute of Technology.
Zhou Yiqian 1Yiqian Zhou
received her B.E. degree from Tsinghua University in 2022. She is currently pursuing her Ph.D. degree under the supervision of Prof. Hui Wu at Tsinghua University, China. Her research focuses on high-temperature thermal insulation and brain-computer interface electrode.
Wang Yuxuan 1Yuxuan Wang
is currently pursuing his B.S. degree and B.Eng degree at Tsinghua University, China. His research focuses on the mass production and application of low-dimensional materials.
Jia Chao [email protected]
3Chao Jia
is an associate professor at the College of Materials Science and Engineering, Donghua University. He obtained his Ph.D. degree from the Beijing Institute of Technology in 2018. He worked as a postdoctoral research associate at Tsinghua University from 2018 to 2021. His research interests focus on nanofibers, cellulose nanomaterials, and wood-based functional materials.
Li Lei [email protected]
2Lei Li
is an assistant professor at the School of Mechanical Engineering, Beijing Institute of Technology. He received his Ph.D. from the Beijing Institution of Technology in 2020. He worked as a postdoctoral research associate at School of Materials Science and Engineering, Tsinghua University from 2020 to 2022. His research interests include the battery safety, biodegradable polymer preparation, and ceramic nanofibers.
http://orcid.org/0000-0002-4284-5541
Wu Hui [email protected]
1Hui Wu
is an associate professor at the School of Materials Science and Engineering, Tsinghua University. He obtained his Ph.D. degree from Tsinghua University in 2009. He worked as a postdoctoral research associate at Stanford University from 2009 to 2013. His research interests focus on nanofibers, energy storage materials, and flexible electronics.
1 grid.12527.33 0000 0001 0662 3178 State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084 China
2 grid.43555.32 0000 0000 8841 6246 National Engineering Research Center of Electric Vehicles, Beijing Institute of Technology, Beijing, 100081 China
3 grid.255169.c 0000 0000 9141 4786 State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620 China
8 12 2022
117
18 8 2022
26 10 2022
© Donghua University, Shanghai, China 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Hard-to-dissolve polymers provide next-generation alternatives for high-performance filter materials owing to their intrinsically high chemical stability, superior mechanical performance, and excellent high-temperature resistance. However, the mass production of hard-to-dissolve nanofibers still remains a critical challenge. A simple, scalable, and low-cost ionic solution blow-spinning method has herein been provided for the large-scale preparation of hard-to-dissolve Nomex polymeric nanofibers with an average diameter of nearly 100 nm. After rapidly dissolving Nomex microfibers in the lithium chloride/dimethylacetamide (LiCl/DMAc) solution system, the conductive solution can be stably and conductivity-independently processed into nanofibers. The method optimizes electrospinning and avoids spinnability degradation and potential safety hazards caused by high electrical conductivity. Owing to nanofibrous structure and high dipole moment, Nomex nanofibrous filters show a stable high filtration efficiency of 99.92% for PM0.3 with a low areal density of 4.6 g m−2, as well as a low-pressure drop of 189.47 Pa. Moreover, the flame-retardant filter can work at 250 °C and 280 °C for a long and short time without shrinking or burning, respectively, exhibiting a high filtration efficiency of 99.50% for PM0.3−10.0. The outstanding properties and low cost enable the efficient capture of PM from various high-temperature exhausts, making Nomex nanofibrous membrane an even more ideal industrial-grade air filter than polypropylene, polytetrafluoroethylene, polyimide, and ceramic nanofibrous filters.
Graphical abstract
Hard-to-dissolve nanofibers provide alternatives for high-efficiency and low-resistant air filtration but are limited by the universality and economics of fabrication methods. A scalable and efficient ionic solution blow-spinning strategy has herein been proposed in preparing hard-to-dissolve nanofibrous filters.
Supplementary Information
The online version contains supplementary material available at 10.1007/s42765-022-00231-x.
Keywords
Nomex nanofibers
Solution blow-spinning
High-temperature filtration
Flame-retardant
http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China 51788104 Wu Hui http://dx.doi.org/10.13039/501100004826 Natural Science Foundation of Beijing Municipality JQ19005 Wu Hui China Postdoctoral Science Foundation2021M691713 Li Lei
==== Body
pmcIntroduction
Most hard-to-dissolve polymetric nanofibers enjoy the luxury of being attractive nanomaterials with inherent high-temperature resistance, corrosion resistance, excellent flame retardancy, and superior mechanical properties due to their rigid and stable molecule structures [1–4]. Although the production of hard-to-dissolve polymers is booming, the preparation of hard-to-dissolve nanofibers has been a stumbling block due to their limited solubility in common solvents, mainly restricted by numerous intermolecular and intramolecular hydrogen bonds. For example, poly(m-phenylene isophthalamide) (PMIA), commonly known as Nomex or meta-aramid, comprises a benzene ring and an amide group. The amide group is connected to the amide group meta-position on the benzene ring, where the amide groups on different backbones are connected by hydrogen bonds [5]. Although the intractable structure limits dissolution in common solvents, it endows Nomex with a high melting point and glass transition temperature, low combustion heat release rate, excellent flame retardancy, stable chemical properties, and agreeable mechanical properties [6]. Therefore, hard-to-dissolve nanofibers have a broad potential for a wide range of areas, such as high-temperature thermal insulation, modern textile, electronic material, and others [7–9].
High-temperature exhausts, mainly related to industrial fuel gas, coal furnace combustion, and automobile exhausts, seriously affect environmental governance and public health. The temperature of industrial exhausts is usually between 70 and 250 °C. For instance, the temperature of the exhausts from gas boilers, coal furnaces, glass factories, coke ovens, and fuel vehicles is typically 150–200 °C, 70–180 °C, 140–200 °C, 190 °C, and 70 °C, respectively [10, 11]. On the other hand, most high-temperature exhausts contain several acid-corrosive gases, such as H2S, HCl, and Cl2 [12]; and more than 70% of dust is combustible, which is easily ignited by fire or electrostatic discharge, causing dangerous explosions [13]. Particulate matter (PM) with a diameter less than 0.3 μm (PM0.3) is considered the most hazardous contaminant [14]. As is well known, PM0.3 can penetrate the bronchi and lungs and enter the extrapulmonary organs and central nervous system through the blood, thus posing a severe threat to human health [15, 16]. Globally, up to 91% of the population lives in an environment where air pollution exceeds World Health Organization (WHO) guidelines, and 6.7 million people die yearly from air pollution [17]. Air pollution can even contribute to the spread of global epidemics, as PMs can be transmission carriers for viruses such as COVID-19 [18, 19]. Improving filtration technology is crucial to alleviating air pollution [20]. Many strategies have been adopted to deal with the PM0.3 emitted by high-temperature exhausts, such as sedimentation tanks, cyclone separators, electrostatic precipitators, and filtration technologies [21].
Filtration technologies are considered to be the most economical technical route as they do not require the introduction of additional energy or a complex post-treatment [22]. However, traditional commercial fibrous filters have an average fiber diameter of 1–10 μm and an average pore size of 3–20 μm, making it extremely difficult to capture PM0.3 efficiently while maintaining a low air resistance [10]. In recent years, many studies have shown that reducing the fiber diameter effectively improves filtration performance [23]. When the fiber diameter is lowered to the range between a few tens and hundreds of nanometers, the PM capture capacity of fibrous filters is considerably improved without significantly increasing the air resistance [24, 25]. Many methods have reported excellent filtration performances of nanofibrous membranes for PM0.3, such as the preparation of hierarchical dual-nanonet fibrous membranes based on solution blow-spinning (SBS) and self-assembly strategies [26], the preparation of high-performance nanofibrous network filters inspired by biological hybridization based on the combination of novel blend electrospinning/netting method and self-polymerization method [27], the preparation of polysulfonamide/polyacrylonitrile (PSA/PAN) composite nanofibrous filters based on electrospinning method [28], the preparation of ZnO nanowires@poly(vinylidene fluoride) (PVDF) nanofibrous membrane inspired by the grass growth based on hydrothermal method and chemical vapor deposition (CVD) [29]. Thus, nanofibrous filters are promising candidates for superior filtration materials [30, 31]. For filters of different materials, metallic filter materials can be easily oxidized and corroded in high-temperature and corrosive gas environments [32], which limits their practical applications. Ceramic fibrous filters have attracted considerable attention for high-temperature filters due to their chemical stability and high-temperature resistance [33]. However, expensive, fragile ceramic fibrous filters often cause additional debris. As for polymers, the vast majority of polymer nanofibrous filters have a working temperature lower than 200 °C [10], not meeting the requirement of high-temperature filtration. Coupled with excellent chemical and physics stabilization, hard-to-dissolve polymetric nanofibers are up-and-coming candidates for use in high-temperature industrial filters, working in harsh environments of high temperature, combustible dust, acid, and corrosiveness with low cost [34].
Finding a universal method for dissolving hard-to-dissolve polymers is essential for preparing high-performance nanofibrous membranes. Using “naked anions” as nucleophilic bases to disrupt intermolecular and intramolecular hydrogen bonds is considered an effective strategy for dissolving hard-to-dissolve polymers [35]. Many studies have shown that the LiCl/DMAc system can generate large amounts of “naked anions,” which break down intramolecular and intermolecular hydrogen bonds [35–37], and is successfully used to prepare polybenzimidazole (PBI), polyimide (PI), silk, cellulose, and chitin solution [38–41]. However, for the LiCl/DMAc system, the commonly used electrospinning method is not the preferred technology because high electrical conductivity will deteriorate the spinnability and bring safety concerns. Ionic SBS is a facile, safe and straightforward preparation method, owing to the airflow driving force [42, 43]. In our study, the low-cost Nomex nanofibrous filter from the ionic SBS method with an areal density of only 4.618 g m−2 exhibits a high filtration efficiency (99.92%) and a low-pressure drop (189.47 Pa) for PM0.3 at an airflow velocity of 5.33 cm s−1. Moreover, at 250 °C, the Nomex nanofibrous filter with an areal density of 4.631 g m−2 retains a high filtration efficiency (> 99.5%) for PM0.3−10.0. Furthermore, the other hard-to-dissolve fibrous precursor solution including PI, PBI, silk, cellulose, and chitin has been successfully prepared. It provides great potential in preparing nanofibers on a large scale via the ionic SBS method.
Experimental Section
Materials and Chemicals
Commercial Nomex microfibers were purchased from Yantai Tayho Advanced materials Co., Ltd (China). Silkworm cocoons were picked from mulberry trees beside Gongshanjian in Hangzhou, Zhejiang province (China). Chitin (1398–61–4, Industrial pure grade) was purchased from Tianjin Xiensi Biochemical Technology Co., Ltd. PI (Thermoplastic 5218, 99.9% purity) was purchased from BASF SE (Germany). PBI (99.95% purity, Mw ≈ 51,000) was purchased from Danish Power Systems (Danmark). Cotton pulp (M30, DP = 500) was purchased from Beijing North Century Cellulose Technology Development Co., Ltd. (China). LiCl (99% purity) was purchased from Meryer Chemical Technology Co., Ltd. (China). DMAc (99.9% purity) was purchased from Rhawn Chemical Reagent Co., Ltd. Polyethylene oxide (PEO, Mv ≈ 1,000,000) was purchased from Xi Ya Reagent Co., Ltd. (China). The commercial polypropylene (PP) fibrous filters and glass fibrous filters used for comparison were purchased from Hollingsworth & Vose (USA). In addition, the commercial PTFE fibrous filters were purchased from Jiangsu Xiankai (China). Commercial ceramic nanofibrous filters were purchased from Xianning Youwei Technology Co., Ltd. (China).
Preparation of Nomex Nanofibrous Membranes
The Nomex solution was prepared by dissolving commercial Nomex microfibers (1.5 g) and a small amount of LiCl (0.6 g) in DMAc (18.5 g) while magnetically stirring the mixture at 90 °C for 2.3 h. Subsequently, a small amount of PEO (0.035 g) was added to the Nomex solution. The mixed solution was stirred at 90 °C for about 0.2 h to obtain a well-mixed precursor solution. The solution was prepared in a glove box to prevent absorption of moisture. The configuration process of other precursor solution such as silk, PI, chitin, and cotton was shown in Supplementary Information. The Nomex nanofibrous membranes were prepared using a custom-built SBS system. In a typical procedure, the precursor solution was drawn into a 20–mL plastic syringe and extruded into a needle tip with a 0.2–mm inner diameter using a syringe pump at a fluid rate of 1.5 mL h−1. The pressure of the compressed air was set to 80 kPa, and the distance between the tip and the roller collector was fixed at 30 cm. The roller collector was continuously reciprocated left and right to obtain a uniform Nomex nanofibrous membrane. The drum collector rotated at 200 rpm at a reciprocating speed of 1 cm s−1. The blow-spinning process was assisted in a heated environment. A heating platform (20 cm × 20 cm in size) was kept 5 cm away from the needle tip, and an infrared heating lamp with a power of 150 W was located 20 cm away from the needle tip. Finally, the prepared uniform Nomex nanofibrous membrane was removed from the roller collector and heated in an oven at a temperature of 60 °C for 1 h.
Characterization
A field-emission scanning electron microscope (Zeiss, Germany) was used to observe the morphology of the samples, and an energy-dispersive spectrometer (EDS) detector (Zeiss, Germany) was used to determine the elemental composition. The distribution of the fiber diameters was obtained by measuring the diameter of more than 100 fibers in the scanning electron microscope (SEM) images using the Image-Pro Plus software (Media Cybernetics, USA). The pore diameter and porosity of a typical Nomex nanofibrous membrane with an areal density of 4.251 g m−2 at room temperature (25 °C) and high temperature (200 °C) were measured using an automatic mercury porosimeter (MicroActive AutoPore V 9600 2.03.00, Micromeritics Inst Inc., USA). The conductivity of the Nomex precursor solution was measured by conductivity benchtop meters (VSTAR20 series, ThermoFisher Scientific, USA). An X-ray diffractometer (XRD, D/max-2500/PC, Rigaku, Japan) with a Cu Kα radiation source was used to obtain the XRD patterns of the samples in the 2θ range of 10°–60° at a scanning rate of 10°min−1. The blow-spinning process was observed using a high-speed camera (Os7, IDT Vision, USA) equipped with an F-mount lens (atx-i 100 mm F2.8 FF MACRO, Tokina, Japan). All high-speed images were captured at a frame rate of 8,000 fps with an exposure time of 60 μs and eventually played back at a frame rate of 24 fps. Other characterization can be seen in Tests S1 and S2.
Dipole Moment Calculation
Density functional theory (DFT) calculations were performed using the Gaussian 09 software package [44]. The repeating units of the Nomex, polytetrafluoroethylene (PTFE), PAN, and PP filters were fully optimized at the B3LYP/6–311+G (d, p) level without an imaginary frequency.
Room Temperature Filtration Test
The filtration efficiency and pressure drop at room temperature were measured using an automatic filtration tester (8130A, TSI, USA). A 2% sodium chloride (NaCl) solution was used to generate a NaCl aerosol with a mass median diameter of 0.26 μm and a median count diameter of 0.075 μm. Unless otherwise specified, the filtration efficiency and pressure drop in this work were measured at a continuous airflow rate of 32 L min−1 (5.33 m s−1). All filter performance test results were obtained by averaging three sets of data. The quality factor (QF) was derived according to the following equation:1 QF=-ln1-η/ΔP,
where ΔP is the pressure drop before and after the airflow through the membrane, η is the efficiency of capturing PMs.
High-Temperature Filtration Test
A high-temperature filtration test device has been customized. Firstly, two quartz glass tubes 500 mm in length and 42 mm in inner diameter have been designed and Nomex nanofibrous membrane between the two quartz glass tubes has been placed. Subsequently, the quartz glass tubes were placed in a temperature-adjustable tube furnace (OTF-1200X, HF-Kejing, China). Two ends of the quartz glass tubes were connected with the air inlet pipe, the air outlet airflow was generated by an air compressor (1500X4, OTS, China), and PM was produced by burning incense. The inflow of the compressed air flow along the intake pipe was controlled by a flow meter, causing PM to enter the quartz glass pipe. Two PM particle counters (DT-9880 M, CEM, China) were connected to the inlet and outlet of the quartz glass tube to measure the number of PM particles of different sizes. The PM particle counters comprised six channels, which could detect the number of PM particles with diameters of 0.3, 0.5, 1.0, 2.5, 5.0, and 10.0 μm. The accumulation mode of the particle counters has been used in measuring the PM0.3–10 value with an acquisition time of 30 s. Finally, the high-temperature filtration efficiency of the Nomex nanofibrous membrane was calculated by taking the difference between the number of PM particles with a given size before and after filtration. The cumulative mode of the PM particle counters has been used in measuring the PM0.3−10 value at the exhaust port when the vehicle engine speed was 3,000 rpm. The test duration was 30 s. By denoting the particle number of each channel obtained before and after installing the Nomex nanofibrous membrane filter as C1 and C2, respectively, η can be calculated as follows:2 η=1-C1C2.
In the high-temperature filtration stability test, the Nomex nanofibrous membrane was continuously heated in a muffle furnace at 250 °C for 15 consecutive days and tested their filtration performance daily using a TSI 8130A filtration tester. All filter performance test results were obtained by averaging three sets of data.
Results and Discussion
Preparation of Nomex Nanofibrous Membranes
A DMAc solution system containing anhydrous LiCl was used to dissolve Nomex microfibers (Fig. 1a). After electromagnetic stirring in LiCl/DMAc solution system at 90 °C for 2.5 h, Nomex microfibers were completely dissolved and a translucent precursor solution was successfully prepared (Fig. 1b). The anhydrous LiCl in DMAc can break the hydrogen bonds between the Nomex molecular chains through complexation, which resulted in the dissolution of the commercial Nomex microfibers into the solvent. In this system, Li+ and DMAc form an ion–dipole complex: [DMAc + Li]+. Due to the polar aprotic property of DMAc and the inability of hydrogen atoms in DMAc to form hydrogen bonds, Cl− cannot be solvated [45]. Therefore, Cl− will have greater freedom to break the intermolecular and intramolecular hydrogen bonds in hard-to-dissolve polymers (Fig. 1c) [37]. In addition, a small amount of PEO was added to increase the spinnability of the precursor solution. Based on the same mechanism, PBI, silk, cellulose, chitin, and PI polymer have been dissolved successfully by the LiCl/DMAc system, all of which are expected to be converted into nanofibers (Fig. 1d).Fig. 1 Preparation of Nomex and other hard-to-dissolve nanofibrous precursor solution. a Schematic diagram of the preparation process of Nomex precursor solution. b A 20-mL bottle of successfully prepared clear Nomex precursor solution. c Dissolution mechanism of Nomex in LiCl/DMAc solution. d Different hard-to-dissolve fibrous precursor solution was successfully prepared in LiCl/DMAc system. e The relationship between conductivity, dissolution time, and LiCl concentration of LiCl/DMAc solution system: the electrospinning process of solution system is accompanied by a large number of electric sparks, and relatively high conductivity represents high spark risk, relatively low conductivity represents low dissolution efficiency
Through the ionic SBS method, hard-to-dissolve nanofibers can be prepared stably to uniform nanofibers driven by the high-speed airflow on a large scale in the whole dissolvable range in LiCl/DMAc system (Fig. S1). However, the key to electrospinning is the accumulation of free charges at the solution interface and liquid stretching induced by the tangential electric field. Thus, the Nomex nanofibrous membrane cannot be easily prepared by electrospinning when the solution conductivity is relatively high. Moreover, the generation of electric sparks during electrospinning introduces potential safety hazards. Specifically, when the mass fraction of LiCl is 2% (Fig. 1e: Region 1), the solution has relatively high conductivity (4.35 mS cm−1) with an excessively long dissolution time. When the mass fraction of LiCl is 3–5% (Fig. 1e: Region 2), the solution conductivity is 5.62–5.72 mS cm−1 with a higher dissolution rate. However, the relatively high conductivity makes the solution difficult to form stable Taylor cones, and thus Nomex nanofibrous membrane cannot be prepared readily. When the mass fraction of LiCl is 5–10%, the conductivity of the solution decreases. Although Nomex fibers can be prepared in this region, many fibers are bundled together to form micron-sized fibrous bundles due to the limited traction caused by the conductivity of the solution (Fig. 1e: Region 3 and Fig. S2) [46, 47].
In the ionic SBS process, the polymer precursor solution is drawn by the airflow, and a jet is first formed when the drawing force is greater than the surface tension (Figs. 2a and S3). Then, benefiting from heating and the strong gas–liquid interface disturbance, the solvent volatilizes rapidly to form ultra-fine nanofibers, enabling a safe, scalable, simple, and cost-effective process. Here, we readily refined Nomex microfibers (diameter ≈ 19 μm) into Nomex nanofibers (diameter ≈ 100 nm), which implies that a commercial Nomex microfiber has been successfully processed into more than 30,000 Nomex nanofibers (Fig. 2b). These Nomex filters composed of nanofibers are expected to achieve a highly efficient filtration of PM in exhausts (Fig. 2c). Moreover, solution jetting and fiber whipping were visualized through high-speed videography (Fig. 2d–f, Video S1). Under the action of high-speed airflow in the ionic solution blow-spinning process, the sheer force induced by the airflow refines the solution extruded from the needle tip, and first forming a Taylor cone, then forming a liquid jet along the flow direction, and finally whipping violently. Strong gas–liquid interface disturbance and temperature gradient field promote the volatilization of DMAc, ultimately leaving high-quality nanofibers.Fig. 2 Preparation of hard-to-dissolve nanofibrous membranes via ionic SBS. a Schematic diagram of the preparation process of blow-spinning Nomex nanofibrous membranes. b Commercial Nomex microfibers with an average fiber diameter of 19 µm were successfully fabricated into Nomex nanofibers with an average fiber diameter of 98 nm by ionic SBS. c Schematic diagram of the fire-retardant, high-temperature resistant Nomex nanofibrous filter used for high-efficiency filtration. d Image of spinneret nozzle part during spinning. e Enlarged image of spinneret nozzle part during spinning. f High-speed camera image of spinneret nozzle part during preparation, it could be seen that the solution forms a jet and then starts to whip
A typical Nomex nanofibrous membrane with different thicknesses is presented in Fig. S4; these membranes can be widely used in automotive exhaust filters, industrial exhaust filters, masks, and other scenarios (Fig. S5). Alternatively, a breathable cage-like collector can be placed behind the drum collector, where excess nanofibers can form a porous three-dimensional nanofiber sponge. Based on multi-needle integrated spinning devices and roll-to-roll collection devices, the large-scale production of Nomex nanofibrous membranes can be easily achieved [48]. Moreover, Nomex nanofibrous sponges prepared by vacuum freeze-drying technology can be used for thermal insulation, photocatalytic, energy storage, and wound healing (Fig. S6) [49–52].
Structure and Properties of Nomex Nanofibrous Membranes
The microscopic size of the Nomex nanofibrous membrane was observed via SEM. The SEM images show that these Nomex nanofibers have uniform morphologies, smooth surface, and high aspect ratio (Fig. 3a). Through adjusting parameters, including precursor solution injection rate, polymer solution concentration, and airflow velocity, the average diameter of the Nomex fibers is consistent in the range of 100–200 nm, highlighting the reliability of the spinning process (Fig. S7). It is proved that under the action of strong gas–liquid interface disturbance and temperature gradient field, the solvent volatilizes rapidly, and the nanofibers are well formed. It is also fully demonstrated that the solution and the ionic SBS method have excellent stability, laying a good foundation for large-scale production. The fiber structure of a single Nomex nanofiber was also observed via transmission electron microscopy (TEM), and its electron diffraction pattern consists of an amorphous diffraction ring (Fig. 3b). An amorphous peak appears in the XRD pattern of a typical Nomex nanofibrous membrane, indicating that the prepared Nomex nanofibers are amorphous (Fig. S8). The Fourier-transform infrared spectroscopy (FTIR) spectrum of the precursor solution and Nomex nanofibers demonstrate their successful preparation. (Fig. S9, Fig. 3c, see Test S3 for details).Fig. 3 Characterization of the Nomex nanofibrous membranes. a SEM image of a Nomex nanofibrous membrane. b TEM and diffraction ring images of a Nomex nanofiber. c FTIR spectrum of blow-spinning Nomex nanofibers. d Histogram showing the Nomex nanofibers' diameter distribution based on measurements of more than 100 fibers. e Area pore size distribution of a typical Nomex nanofiber membrane measured by an automated mercury porosimeter before and after being heated at 200 °C for 25 h. f Comparison of the areal density and filtration efficiency for PM0.3 of the Nomex nanofibrous membranes with other air filter materials. g Image showing the flame retardancy and fire safety of the Nomex nanofibrous membrane after burning for 5 s. h TGA and DTA curves of the Nomex nanofibrous membrane. i Demonstration that a Nomex nanofibrous membrane with dimensions of 70 mm (length) × 20 mm (width) × 0.05 mm (thickness) can stably lift a 0.5-kg bottle
Many studies have shown that the finer the nanofiber diameter, the better the filtration performance of the nanofibrous filters [53]. To achieve an excellent filtration performance, a typical Nomex nanofibrous membrane with an average fiber diameter of 111 nm (Fig. 3d) was prepared, and the porosity of this nanofibrous membrane was around 92.36% at room temperature (Fig. 3e, Table S1). The relatively high porosity of the Nomex nanofibrous membrane can provide channels for airflow [54], thereby reducing air resistance during filtration. After heat treatment at 200 °C for 25 h, the Nomex nanofibrous membrane maintained a high porosity (86.78%) (Fig. 3e, Table S1). In addition to the potential excellent filtration performance and thermal stability, the consumption and cost are also relatively low. The raw material cost of Nomex nanofibers is 63.36 $ kg−1, which is lower than other potential high-temperature filter materials, including PI, poly(1,4-phenylene sulfide) (PPS), and PTFE powders (Fig. S10). In addition, the Nomex nanofibrous membranes have minimal consumables, capturing more than 99.9% of PM0.3 with an areal density of only 4.618 g m−2. The consumables are quantified in terms of the areal density. At the same filtration efficiency of over 99.5% for PM0.3, the areal density of the Nomex nanofibrous membranes is considerably lower than that of PI nanofibrous membranes (6.61 g m−2), polyvinyl chloride/polyurethane (PVC/PU) fibrous membranes (21 g m−2), commercial PP filters (40.88 g m−2), and commercial glass fibrous filters (80.54 g m−2) (Fig. S11). In other words, to achieve the same level of filtration efficiency, Nomex nanofibrous membranes consume 88.7% and 94.3% less material compared to current commercial PP and glass fibrous filters, respectively.
A Nomex nanofibrous membrane with an areal density of 1.890 g m−2 can capture 95.42% of PM0.3, and that of 3.780 g m−2 can capture 99.6% of PM0.3. To demonstrate the advantages of Nomex nanofibrous membranes in terms of low areal density, the filtration performance and areal density of Nomex nanofiber membranes were compared with other fibrous air filters, as shown in Fig. 3f. The performance of the Nomex nanofibrous membrane is better than most of the polymer-based fibrous filter materials, such as PVDF/graft (83.00%, 8 g m−2) [55], PP (99.36%, 60 g m−2) [56], PVC/PU (99.50%, 21 g m−2) [57], PAN (98.89%, 7.49 g m−2) [58], PI (99.73%, 6.61 g m−2) [53], fluorinated polyurethane/PAN/PU (FPU/PAN/PU, 95.91%, 12.02 g m−2) [58], polyamide6/soy protein isolate (PA6/SPI, 99.53%, 11.4 g m−2) [59]. Additionally, the performance of the Nomex nanofibrous membranes is better than most of the ceramic-based fibrous filter materials, such as γ-alumina (99.85%, 9.28 g m−2) [60] and TiO2 (96.05%, 7.1 g m−2) [61], and is apparently superior to that of commercial glass fibrous filters (99.89%, 80.542 g m−2). After calculation, the raw material cost for preparing Nomex nanofibrous membrane is 1561.74 RMB kg−1. The filtration efficiency for PM0.3 is 99.92%, 99.60%, 98.51%, and 95.40%, and the corresponding areal densities are 4.618 g m−2, 3.780 g m−2, 2.865, and 1.890 g m−2, respectively. Converting to area production cost, the area production cost of a Nomex nanofibrous membrane with a filtration efficiency of 99.92%, 99.60%, and 98.51% is 7.21 RMB m−2, 4.47 RMB m−2, and 2.95 RMB m−2, respectively, which is close to the area production cost of bulk industrial commodity PP melt-blown cloth and lower than that of high-temperature resistant PTFE filter.
We conducted a simple flame-burning test to evaluate the excellent flame retardancy of Nomex nanofibrous membranes. Figure 3g and Video S2 show that no delayed combustion or melting occurs when the membrane encounters the flame. Furthermore, Fig. 3g and Video S2 also demonstrate the excellent self-extinguishing properties of the Nomex nanofibrous membranes. After igniting a Nomex nanofibrous membrane with a small fire extinguisher for 5 s, the flame went out immediately when the fire extinguisher was turned off. Further, thermal gravimetric analysis (TGA) and differential thermal analysis (DTA) were conducted to investigate the thermal stability and high-temperature resistance of Nomex nanofibrous membranes (Fig. 3h). The DTA result shows that in the argon atmosphere, the Nomex nanofibrous membranes exhibit a gentle exotherm without any clear melting endothermic peaks below 700 °C during the heating process. The TGA results show that in the air atmosphere, the Nomex nanofibrous membranes only lose 5% of mass at 376 °C, which is higher than that of most polymer nanofiber membranes, such as PTFE (368 °C), PAN (295 °C), and PP (221 °C) membranes (Fig. S12). According to the differential scanning calorimeter (DSC) results, the glass transition temperature (Tg) of the Nomex nanofibrous membranes is around 245 °C (Fig. S13). The above tests demonstrate the high-temperature resistance of Nomex nanofibrous membranes. The absence of molten droplets at high temperature indicates the high-temperature safety of the Nomex nanofibrous membranes.
It is essential to analyze their flame retardancy further to investigate the safety of the Nomex nanofibrous filters when used at high temperature. Generally, materials with a limiting oxygen index (LOI) greater than 27% are considered flame-retardant. The oxygen index test reveals that the LOI value of the Nomex nanofibrous membranes is 28.39% (Tables S2–S3), which proves that it is a flame-retardant material (Fig. S14). The heat release rate (HRR) is one of the most critical thermal parameters for evaluating the flame retardancy and fire safety of polymers [62]. The peak value of the heat release rate (pHRR) of the Nomex nanofibrous membranes (27.608 W g−1) was obtained by conducting a micro-scale combustion calorimetry (MCC) measurement; the obtained value is lower than that of most polymer nanofibrous membranes, such as PTFE (401.280 W g−1), PAN (121.533 and 27.608 W g−1), and PP (447.361 W g−1) membranes. The total heat release (total HR) value of the Nomex nanofibrous membranes was calculated to be 4.9 kJ g−1, which is lower than those of PTFE (19.1 kJ g−1), PAN (11.6 kJ g−1), and PP (341.0 kJ g−1) membranes (Fig. S15). Low pHRR and total heat release (total HR) values indicate that the filter is less likely to present a fire hazard. In addition, the HRR curves of Nomex nanofibrous membranes are flatter, which suggests that Nomex nanofibrous membranes burn more slowly.
Mechanical tensile tests were performed using a universal testing machine. The test results show that the average tensile strength of the Nomex nanofibrous membranes at room temperature is 4.36 MPa, corresponding to an average elongation of 68.05% (Fig. S16). Fig. S17 shows the stress–strain curve of a typical Nomex nanofibrous membrane at room temperature. Figure S16 shows the average tensile strength and elongation of Nomex nanofibrous membranes heated at 200 °C for a different time. The test shows that the tensile strength of the membranes remains close to 80% after heating at 200 °C for 50 h. In addition, the dynamic thermodynamic analyzer (DMA) test results reveal that the Nomex nanofibrous membranes can maintain a tensile strength of more than 4 MPa while operating at a high temperature of 250 °C for 10 min (Fig. S18). The mechanical properties of the Nomex nanofibrous membrane are also displayed in Fig. 3i, indicating a typical Nomex nanofibrous of 70 mm (length) × 20 mm (width) × 0.05 mm (thickness) can stably lift a 0.5-kg bottle of water (Video S3). In addition, considering the acidity of industrial flue gas [63, 64], a Nomex nanofibrous membrane was soaked in a 3 mol L−1 hydrochloric acid solution for 24 h to test its acid corrosion resistance. Its surface morphology and structure via SEM and FTIR were investigated to demonstrate the stability of the membrane after being corroded in an acidic solution. The SEM image shows that the membrane retains a smooth surface morphology. All characteristic peaks in the FTIR spectrum are consistent with those shown in Fig. 3c, demonstrating the well acidic-corrosion resistance (Fig. S19).
To demonstrate the excellent filtration performance of the Nomex nanofibrous membranes, their filtration performance for different areal densities at different airflow velocities was tested. The relationship between the spinning time, areal density, filtration efficiency (η), pressure drop (∆P), and QF is shown in Fig. S20. A higher QF value means a better filtration performance of a filter. Figure 4a shows that as the areal density of the membrane increases, the filtration efficiency gradually increases, while the rate of increase gradually decreases. For instance, at an airflow velocity of 5.33 cm s−1, Nomex nanofibrous membranes with areal densities of 1.553, 1.890, 2.865, 3.780, and 4.618 g m−2, exhibit η = 92.24%, 95.42%, 98.51%, 99.60%, and 99.92%. Further, the airflow velocity has little influence on the filtration efficiency of the Nomex nanofibrous membranes, especially when the areal density is greater than 1.890 g m−2 (Fig. 4b). For example, the Nomex nanofibrous membrane with an areal density of 4.618 g m−2 still has η = 99.76% at a high-speed airflow of 15.83 cm s−1. The test results indicate that Nomex nanofibrous membranes are able to capture PM0.3 with high efficiency regardless of the airflow speed. It reflects the strong capture ability of the Nomex nanofibrous membrane and that Nomex nanofibrous membrane can still maintain an excellent physical structure under high shear stress brought by high-speed airflow.Fig. 4 Filtration performance of the Nomex nanofibrous membranes at room temperature. a, b Dependence of the filtration efficiency of the Nomex nanofibrous membranes with different areal densities on the airflow velocity. c, d Dependence of the pressure drop of the Nomex nanofibrous membranes with different areal densities on the airflow velocity. e, f Dependence of the QF values of the Nomex nanofibrous membranes with different areal densities on the airflow velocity. g Molecular model of the Nomex, PTFE, PAN, and PP filters and corresponding calculated dipole moments. h, i SEM images of the NaCl aerosols with PM0.3 size captured by the Nomex nanofibers. j Comparison of the filtration efficiency before and after isopropyl alcohol fumigation for 24 h. k Results of the long-term filtration efficiency stability test of the Nomex nanofibrous membranes
The pressure drop of the Nomex nanofibrous membranes increases approximately linearly with the increase of area density and airflow velocity (Fig. 4c, d). For example, the pressure drop of the Nomex nanofibrous membrane with an areal density of 4.618 g m−2 increases significantly from 152.88 to 638.63 Pa as the airflow velocity increases from 4.17 to 15.83 cm s−1. The results show that the directly proportional relationship between the airflow velocity and the pressure drop satisfies Darcy's law [65]. It means that the airflow is in the form of laminar flow through the porous Nomex nanofibrous membrane. Moreover, the QF is not significantly affected by the areal density at a constant airflow velocity (Fig. 4e), meaning that Nomex nanofibrous membranes with different areal densities all have excellent filtration quality. For example, the QF of the Nomex nanofibrous membrane decreases from 0.043 to 0.038 Pa−1 as the areal density increases from 1.553 to 4.618 g m−2 at an airflow rate of 5.33 cm s−1. However, the QF values of the Nomex nanofibrous membranes decrease significantly with the airflow rate (Fig. 4f). Compared with a commercial glass fibrous filter commonly used for high-temperature filtration (areal density of 80.542 g m−2, η = 99.89%, ΔP = 264.60 Pa, and QF = 0.026 Pa−1), the Nomex nanofibrous membrane with an ultra-low areal density of 4.618 g m−2 exhibits a higher filtration efficiency for PM0.3 (η = 99.92%) with a lower pressure drop (ΔP = 189.47 Pa) and a higher QF value (QF = 0.038 Pa−1) at an airflow rate of 5.33 cm s−1 (Table S4). The above advantages can be attributed to the two following points: (1) the outstanding physical structure and strong polarity improve the PM capturing efficiency; (2) the strong slip effect reduces air resistance.
Efficient Filtering Mechanism
In the actual filtration process, the PM capture mechanisms through nanofibers can be classified into the following five categories: direct interception, Brownian diffusion, inertia impact, gravity settling, and electrostatic deposition [66]. The filtration efficiency contributed by the first four capture mechanisms depends on fiber diameter, particle size, and airflow velocity. The first four mechanisms could be collectively referred to as intrinsic mechanisms [13, 24, 43]. Regarding the electrostatic deposition mechanism, many studies have shown that several polar functional groups are enriched on the PM surface, such as C–O, C=O, and C–N groups [24, 53]. When the polymer repeating unit has a stronger dipole moment, the polymer fiber behaves with stronger dipole–dipole and dipole-induced intermolecular forces, improving capture efficiency and capture stability for PM [67, 68]. The dipole–dipole and dipole-induced intermolecular forces between polar molecules are actually an electrostatic attraction between intrinsic dipole moments, we refer to this mechanism of electrostatic attraction to PMs as an intrinsic electrostatic deposition mechanism. The dipole moments of repeating units of Nomex, PTFE, PAN, and PP membranes were calculated through DFT. The calculation results show that the dipole moment of the repeating unit of Nomex reaches 4.87 D, which is greater than those of PTFE (0 D), PAN (4.05 D), and PP (0.43 D) (Fig. 4g). Therefore, the Nomex nanofibrous membranes are characterized by a more significant contribution of the intrinsic electrostatic deposition mechanism to capturing PM. Secondly, when the fibers are sufficiently thin, the occurrence of the slip effect will reduce the air resistance [69]. According to the air filtration theory, the dimensionless Knudsen number (Kn) is often used to characterize the flow state of the gas around the fiber, which is affected by the mean free path of air molecules (λ) and the average fiber diameter (d). Kn is written as:3 Kn=2λ/d.
When 0.25 < Kn < 10, the airflow state belongs to the transition flow regime between the slip and free molecular flow [25]. The average diameter of the Nomex nanofibers is 111 nm, and the corresponding Kn value is 1.19; thus, the airflow state on the fiber surface belongs to the transition flow regime. In this case, the airflow is dominated by the large slip, and the mass transfer is dominated by the strong molecular diffusion [70], which means that gas molecules will be subjected to a strong slip flow effect as they move with the airflow over the fiber surface [71]. The slip flow effect reduces the resistance caused by the interaction between gas molecules and the fiber surface. Therefore, even if the average diameter of the Nomex nanofibers is greater than the mean free path of air molecules, it will not increase the airflow resistance. Due to the slip flow, Nomex nanofibrous membranes with a high Kn value can achieve a high-efficiency filtration with a low-pressure drop, thus possessing a high QF value. To demonstrate the filtration performance of the Nomex nanofibrous membrane for PM0.3, the membrane with QF = 0.043 Pa−1 was continuously tested for 10 min with a tested airflow rate of 5.33 cm s−1. The SEM images demonstrate that the Nomex nanofibers can capture a large quantity of the PM0.3 NaCl aerosol (Fig. 4h, i), and the capturing mechanism is illustrated via the elemental mapping images obtained through SEM–EDS (Fig. S21a–d). The results demonstrate that the Nomex nanofibrous membrane with an average fiber diameter of 94 nm and an areal density of 4.618 g m−2 successfully captures a large amount of PM0.3 (Fig. S21e–f). In addition, Nomex nanofibrous membrane has an excellent dust-holding capacity. The membrane with an areal density of 1.720 g m−2 can capture 6.046 g PM0.3 per square meter, which is more than three times its own weight per unit area (Fig. S21g–h). A more intuitive demonstration is that the Nomex nanofibrous membrane can completely block smoke diffusion to the adjacent bottles (Fig. S22).
To explore the stability of the capturing efficiency of the membranes contributed by the intrinsic electrostatic deposition mechanism, the Nomex nanofibrous membranes were fumigated in isopropanol (IPA) for 24 h according to the ISO 16890 standard to remove static electricity [72]. The test result shows that the filtration efficiency of the Nomex nanofibrous membrane did not decrease significantly after IPA fumigation for 24 h (Fig. 4j). The filtration efficiency of the Nomex nanofibrous membrane with an areal density of 4.312 g m−2 for PM0.3 only decreased from 99.79 to 99.60% after fumigation, which means that the filtration efficiency of the membrane for PM0.3 is highly stable. A Nomex nanofibrous membrane with an areal density of 3.022 g m−2 was also soaked in deionized water for 24 h. After washing, its filtration efficiency for PM0.3 remained at around 99% (Fig. S23). Therefore, it can be expected that the Nomex nanofibrous membranes have a high filtration efficiency even in humid environments or after being washed with water. The above experiments demonstrate that Nomex nanofibers have intrinsic high molecular dipole moments. In other words, Nomex nanofibers can have high filtration efficiency even when external charges are eliminated. To corroborate the long-term efficiency stability of the Nomex nanofibrous membranes for PM0.3, the filtration efficiency of two membranes with areal densities of 1.929 and 4.618 g m−2 was tested for 15 consecutive days. The test results show that the filtration efficiency of the Nomex nanofibrous membrane with an areal density of 1.929 g m−2 fluctuates between 96 and 98% over the 15 days, while the filtration efficiency of the Nomex nanofibrous membrane with an areal density of 4.618 g m−2 decreases only from 99.92 to 99.87% (Fig. 4k).
Practical High-Temperature Filtration
To test the high-temperature filtration performance of the Nomex nanofibrous membranes, we built a high-temperature filtration device to simulate practical high-temperature filtration scenarios. The schematic diagram of the device is shown in Fig. 5a, and the details of its working mechanism can be found in the Experimental Section. We generated a large amount of PM by burning incense, which releases various air pollutants, including CO, SO2, NO2, and volatile organic compounds (VOCs). This approach is commonly used to simulate actual PM generation sources [53, 73]. Next, we tested the filtration efficiency of the Nomex nanofibrous membranes for PM0.3–10 at a high temperature of 250 °C and airflow velocity of 5.33 cm s−1 using the high-temperature filtration device. The test results show that the Nomex nanofibrous membrane with an areal density of 4.631 g m−2 has a relatively high filtration efficiency (greater than 99.50%) for PM0.3–10, meeting the required standard of high-efficiency filters (Fig. 5b). Figures 5c and S24 show the SEM images of the windward and leeward sides of the Nomex nanofibrous membrane after filtration at 250 °C for 10 min, respectively. The results show that the membrane successfully captured almost all PM at high temperature.Fig. 5 Filtration performance of the Nomex nanofibrous membranes at high temperature. a Schematic diagram of the high-temperature filtration test device. b Filtration efficiency of the Nomex nanofibrous membranes for PM0.3–10 at 250 °C via high-temperature filtration test device. c SEM image of the windward side of a Nomex nanofibrous membrane after polluted air filtration for 10 min at 250 °C. d SEM images of the Nomex nanofibrous membranes after heating at 150 °C, 200 °C, 250 °C, and 300 °C for 12 h. e Thermal shrinkage test images of the Nomex, PTFE, PAN, and PP membranes after heating at 250 °C for 12 h. f PM0.3 removal efficiency of air filters made of different materials in the temperature range of 40–300 °C, “Com.” stands for commercial. g Filtration efficiency of the Nomex nanofibrous membrane with an areal density of 4.618 g m−2 for PM0.3 at 180–280 °C. h Images of the field filtration test for vehicle exhausts. i The filtration stability test results after long-term heating of the Nomex nanofibrous filter at 250 °C. j Radar chart of fibrous membrane comparing areal density, filtration efficiency, pressure drop, working temperature, and cost of Nomex nanofibrous membranes, commercial PTFE membranes, commercial ceramic nanofibrous membranes, commercial PP membranes, and PI nanofibrous membranes
To investigate the dimensional stability of the Nomex nanofibrous membranes, in high temperatures, Nomex nanofibers, were observed by SEM, in a specific position, after heating at 150 °C, 200 °C, 250 °C, and 300 °C for 12 h (Fig. 5d). The SEM images show that the Nomex nanofibers retain their original microscopic morphology and position after long-term heating at 250 °C. We also placed the Nomex nanofibrous membranes in a muffle furnace for long-term heating. Commercial PTFE membranes, PAN, and PP nanofibrous membranes were also placed in the muffle furnace for comparison (Fig. 5e). After being heated at 150 °C, 200 °C, and 250 °C for 12 h, the Nomex nanofibrous membranes did not substantially shrink in size. However, the commercial PTFE membranes were severely deformed after being treated at 250 °C. As the heating temperature increased to 250 °C, the PAN nanofibrous filter shrank significantly and turned black. The PP nanofibrous membranes were severely deformed after treatment at only 150 °C and even melted at 200 °C (Fig. S25). These phenomena demonstrate the advantages of the Nomex nanofibrous membranes in terms of high-temperature dimensional stability.
To investigate the advantages of the Nomex nanofibrous membranes in high-temperature filtration, we compared their high-temperature filtration performance with that of other ordinary filters, such as PAN nanofibrous membranes and commercial filters (PP and PTFE) (Fig. 5f). To obtain these results, the following procedure was carried out: we placed these filters (size 25 cm (length) × 20 cm (width)) in a muffle furnace and heated them at a temperature ranging from 40 to 300 °C for 12 h, and then tested their filtration performance for PM0.3. At an airflow velocity of 5.33 cm s−1, as the temperature increased from 40 to 260 °C, the filtration efficiency of the Nomex nanofibrous membrane with an areal density of 4.618 g m−2 for PM0.3 remained stable between 99.93 and 99.95%, which indicates the better filtration stability of this membrane compared with those of the commercial filters. Figure 5g shows the filtration efficiency of the Nomex nanofibrous membranes for PM0.3 after being heated in a temperature range of 180–280 °C for 12 h. Even after being heated for 12 h at 280 °C, the Nomex nanofibrous membranes retain a filtration efficiency for PM0.3 of 99.363%. We also used a Nomex nanofibrous membrane with an areal density of 4.212 g m−2 to filter vehicle exhausts (~ 70 °C) [13, 51]. The exhaust gas disappeared upon installing the Nomex nanofibrous filter, and the vehicle could normally run (Fig. 5h, Video S4). When the operating speed of the vehicle engine is 3000 rpm, the Nomex nanofibrous membrane could capture more than 97% of PM0.3–10 emitted from the vehicle exhausts (Fig. S26).
To confirm that the filtration efficiency of the Nomex nanofibrous membranes for PM0.3 remains stable for a long time at high temperature, we heated two Nomex nanofibrous membranes with areal densities of 2.525 and 4.631 g m−2 in the muffle furnace at 250 °C for 15 days. The filtration efficiency of these Nomex nanofibrous membranes for PM0.3 over the 15–day period was tested using the TSI 8130A tester. Because of its ultra-fine diameter of ~ 100 nm and high intrinsic dipole moment of 4.87 D, the Nomex nanofibrous membrane has sustained high filtration efficiency and low air resistance after high-temperature treatment (Fig. 5i). For example, when a Nomex nanofibrous membrane with an areal density of 4.631 g m−2 was heated at 250 °C for 15 days, the PM0.3 filtration efficiency was consistent between 99.92 and 99.94%. Overall, the Nomex nanofibrous membrane exhibits an array of excellent behaviors that are highly desirable for practical air filtration but generally difficult to achieve. Figure 5j compares the filtration efficiency, air resistance, cost, areal density, and working temperature of the Nomex nanofiber membrane with those of commercial PTFE filters, commercial ceramic nanofibrous filters, commercial PP filters, and reported PI fibrous membranes. Although the working temperature and air resistance perform slightly worse than PI nanofibrous membranes [51], other indexes are much superior to commercial PTFE, ceramic, and PP filters and PI fibrous membranes (Fig. 5j). It is worth noting that the Nomex nanofibrous membrane used at high temperature and room temperature can be washed with water or alcohol and reused for filtration applications, and can also be redissolved by the LiCl/DMAc solution system, reflecting the recyclability and renewability of the membrane (Fig. S27). The Nomex nanofibrous membrane exhibits the unprecedented integration of high filtration efficiency, high working temperature, low areal density, low air resistance, and low cost, combing with inherently excellent flame retardancy, chemical inertness, and mechanical properties, making them highly attractive for next generation advanced air filters.
Conclusions
In summary, we successfully developed hard-to-dissolve Nomex nanofibrous filters using a cost-effective and scalable ionic SBS method. The hard-to-dissolve Nomex microfibers were successfully dissolved into the precursor solution of the LiCl/DMAc system, and Nomex nanofibers with a diameter of about 100 nm were readily and stably prepared. The Nomex nanofibrous membrane with an areal density of only 4.618 g m−2 can filter up to 99.92% of NaCl aerosols with a diameter of 0.3 μm and with ΔP = 189.47 Pa. The membrane can retain η = 99.36% for PM0.3 after being heated at 280 °C for 12 h. Owing to their ultra-low weight, low cost, excellent high-temperature resistance, flame retardancy, acid corrosion resistance, stable filtration efficiency, and outstanding mechanical properties, Nomex nanofibrous membranes can be used in various fields that require PM-free air, such as precision electronics manufacturing, hospitals, and the aerospace industry. Most importantly, Nomex nanofibrous material is promising for high-temperature gas filtration in several industrial-grade fields, such as gas boilers, coal furnaces, glass factories, vehicle exhausts, and the chemical industry.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary data related to this article can be found in the online version. Materials and methods of the preparation for other hard-to-dissolve polymetric precursor solution; characterization method of the hard-to-dissolve Nomex nanofibrous membranes; FTIR analysis of the Nomex nanofibrous precursor solution and Nomex nanofibers; evidence that electrospinning is challenging to prepare hard-to-dissolve polymeric nanofibers; the device of ionic solution blow-spinning method; images of Nomex nanofibrous membranes, sponges and vehicle exhaust filter; evidence that ionic solution blow-spinning method is suitable and stable to prepare hard-to-dissolve nanofibers; XRD image of Nomex nanofibers; the comparison of raw material cost, areal density, thermal stability of Nomex nanofibrous membrane with other air filters; High-speed camera display of forming nanofibers via ionic solution blow-spinning method; TGA, DSC, LOI, MCC test results of Nomex nanofibers; the test results and demonstration of mechanical stability, flame retardancy, acidic corrosive resistance, and efficient filtration of Nomex nanofibers; the field test results of Nomex nanofibrous vehicle exhaust filter (PDF 1553 KB)
High-speed video of the ionic blow-spinning process. Burning test of Nomex nanofibrous membrane. Mechanical property demonstration of Nomex nanofibrous membrane. Vehicle exhaust filtration (RAR 17483 KB)
Acknowledgements
We appropriate the financial support of the Basic Science Center Program of the National Natural Science Foundation of China (NSFC) under Grant no. 51788104 and Beijing Natural Science Foundation under Grant no. JQ19005, and China Postdoctoral Science Foundation Grant no. 2021M691713.
Author contributions
CJ, LL, and HW conceived the idea and supervised the research. ZKC, HYW, and LL designed the experiments. ZKC, CJ, and LL designed and constructed the experimental system. ZKC, CJ, ZWL, CY, BPZ, YQZ, YXW, LL, and HW synthesized the specimens and analyzed different characterizations. ZKC, HYW, CJ, LL, and HW contributed to writing the manuscript.
Declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735215 | NO-CC CODE | 2022-12-14 23:29:53 | no | Adv Fiber Mater. 2022 Dec 8;:1-17 | utf-8 | Adv Fiber Mater | 2,022 | 10.1007/s42765-022-00231-x | oa_other |
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Int J Clin Pharm
Int J Clin Pharm
International Journal of Clinical Pharmacy
2210-7703
2210-7711
Springer International Publishing Cham
36469215
1515
10.1007/s11096-022-01515-3
Research Article
Prioritizing patients for medication review by emergency department pharmacists: a multi-method study
http://orcid.org/0000-0002-5354-2976
Almarsdóttir Anna Birna [email protected]
1
Haq Romana 1
Nørgaard Josefine Dalgaard Scheel Vandel 2
1 grid.5254.6 0000 0001 0674 042X Department of Pharmacy, Social and Clinical Pharmacy Research Group, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark
2 grid.511100.4 Capital Region Hospital Pharmacy, Region Copenhagen, Denmark
5 12 2022
110
14 3 2022
28 10 2022
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Background
Little is known about how pharmacists think and act in the situation when they need to prioritize patients without prioritization tools.
Aim
To understand how Emergency Department (ED) pharmacists prioritize patients for medication review.
Method
A multi-method study with pharmacists working in one ED in Denmark. At the start of the study, non-clinical prioritization rules had been implemented at the ED to ensure that medication histories were available quickly. Qualitative participant observations of all seven pharmacists who work at the ED were carried out. Semi-structured interviews with six of the pharmacists were held near in time to the observations. Observations for each pharmacists’ patients were analysed inductively looking for patterns and themes. The interviews were audiotaped, transcribed verbatim and analysed inductively.
Results
The interviews shed light on the kinds of considerations pharmacists processed when prioritizing patients and how they used the ground rules (as set out in the PDSA process). The observations supplemented these data by showing some notable differences between pharmacists’ prioritization procedures that linked to their clinical experience. The interviews highlighted the importance of collaboration with physicians and how pharmacists could be better integrated in the ward team.
Conclusion
Although the ward-established rules increased efficiency, they were handled differently by the pharmacists according to experience, and were not deemed helpful in detecting the clinically meaningful ED patients. A prioritization tool and sitting near to the physicians at the ward would enable pharmacists to become further integrated into patient care and improve prioritization of patients for medication reviews.
Keywords
Clinical pharmacists
Medication reviews
Pharmaceutical care
Prioritization tools
Qualitative methods
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pmcImpact statements
A clinical prioritization tool is needed to help the Emergency Department select the most relevant patients for medication reviews.
Situating pharmacists closer to the medical team would facilitate effective selection of patients for medication reviews at the Emergency Department.
Clinical experience plays an important role when pharmacists prioritize patients without the help of tools, although it is unknown whether a clinical prioritization tool would eliminate differences in how pharmacists select according to clinical experience.
Introduction
Medication reviews performed by clinical pharmacists’ help detect and prevent medication errors, and have been shown to increase patient safety and reduce the risk of medication errors by up to 50% [1, 2]. Clinical pharmacists have limited time to use their competencies within the field of patient safety and pharmaceuticals to optimize the patient's medication [3, 4]. Currently there is great interest in implementing clinical prioritization tools for medication reviews by pharmacists [5–7]. These tools are prognostic models that target patients most in need of pharmacists’ input based on their risk of medication related problems [8]. Various such tools have been developed and already in use. For example, in the UK 70 out of 130 hospitals reported using such tools [9]. The prioritization tools often include indicators such as high-risk medicines, acute organ failure, age over 75, and polypharmacy. There are both paper-based, electronic and combined paper and electronic tools [10–12]. Most of the tools are designed for a specific setting and it is therefore uncertain whether they can be directly put to use in another setting. Factors such as patient’s age, polypharmacy, certain drugs classified as risky, and kidney function should be considered when prioritizing patients for medication review without using specific tools [8, 13–16]. Moreover, some professional and authority bodies provide official general guidance regarding certain medications [17].
This qualitative multi method study was situated at an Emergency Department (ED) at a hospital in Denmark with a catchment of 323,000 citizens and yearly emergency visits of 130,000. Medication reviews are performed every day year round by a pharmacist who is on duty 9 h each day. These are clinical medication reviews as defined by Blenkinsopp et al. [18], although tailored to the setting of ED to solve drug related problems that can be dealt with there.
The study explored how pharmacists, without the benefits of clinical algorithms, prioritize patients for medication review. However, prior to initiating the study, the ED leadership laid out non-clinical ground rules to increase work efficiency. Therefore, the study was refocused on documenting how prioritization was carried out using these new ground rules in the ED. Although studies have asked pharmacists to name criteria they use to prioritize patients [18, 19] to the best of our knowledge this study is the first to study how ED pharmacists prioritize patients for medication review in a setting where no clinical prioritization tools are in use [20].
Aim
To understand how ED pharmacists prioritize patients for medication review.
Ethics approval
Written informed consent was given by all pharmacists for participant observations and interviews. No ethics approval was required according to Danish law [21], however, ethical considerations were met and the pharmacists signed an informed consent form. All interviewees are anonymous and all materials are stored confidentially. All data collection and processing were carried out in compliance with European General Data Protection regulation (GDPR).
Method
Design
A multi-method study was conducted using two qualitative methods. One of the authors (RH) a student in her last semester prior to graduating as a pharmacist, observed each pharmacist while working at the ED for one whole day. RH then followed up the observation with a semi-structured interview with each of the observed pharmacists.
Setting
The ED in this study is situated at a hospital which is served by the Capital Region Hospital Pharmacy in Denmark. It includes triage, acute medical department, emergency room, and the medical specialities cardiology, lung and infectious disease medicine, nephrology, endocrinology, neurology and surgery. A pharmacist is present every day of the year during 8 am–5 pm, aiding with obtaining a medication history, performing medication reviews and making sure the patient’s medication list is up to date in the hospital electronic health record (EHR) system. At the time of this study, seven pharmacists were employed by the hospital pharmacy to consult the ED on a regular rotation.
Seven high-risk situation medication categories that require extra attention by all healthcare workers have been identified by the Danish authorities [17]. These include warfarin, digoxin, insulin, potassium, gentamicin, methotrexate, and opioids. Although tools to aid in medication reviews exist, such as a national interaction database, national deprescribing guidelines and overviews, no algorithm or guideline for prioritizing patients for medication review exists.
In early February 2021, a set of non-clinical rules was implemented at the ED. The ward leadership wished to ensure that medication histories were available quickly, which resulted in a Plan-Do-Study-Act process (PDSA). Patients were to be selected according to three prioritization criteria. The pharmacists should (1) ensure that all patients had their medication entered in the EHR; (2) next prioritize patients according to length of stay. When all patients had their medication entered, the pharmacist could turn their attention to other patients where it was believed a medication review would be beneficial. (3) Regardless of these two criteria, referrals from a physician for a medication review were to be prioritized first.
The PDSA went through two rounds during the observation period (Fig. 1). During the first round, all patients were to undergo a medication history assessment and medication review. However, since only one pharmacist was on call, it was not always possible to assess medicines of all admitted patients. During the second round, several exclusion criteria were added to further aid in selecting patients.Fig. 1 The normal PDSA flow with an added description of the PDSA cycles relevant for this study’s case at Capital Region of Denmark's Pharmacy
Participant recruitment
The study focused on one ED and seven pharmacists working there who were invited to participate in order to fully cover the ways of working and their views on the process of patient selection for medication reviews.
Data collection
The observations were participant observations which followed a pre-constructed observation guide. The observation guide focused on each potential patient that could be chosen by the pharmacist to receive a medication review. The guide collected clinical data on the patient, observations on which approaches, and parameters the pharmacist used in prioritizing the patients for medication review; and which activities or steps the pharmacist took in the process. In addition, the observer recorded data on how and why the pharmacist prioritized or did not prioritize each patient admitted to the ward (Fig. 2).Fig. 2 Observation guide used for studying the pharmacists at the ED
The interview followed an interview guide constructed by RH to collect the pharmacists’ views on the current and past work processes at the ward, how the pharmacist prioritizes patients for medication review and suggestions for improvement of the workflow (Fig. 3). The interview guide consisted mostly of open-ended questions in order to provide a deeper understanding of the pharmacists’ thoughts while prioritizing. Some closed-ended questions were also used to specify the considerations made by the pharmacist while prioritizing patients for medication review. The guide was reviewed and critiqued by one of the authors (JN) with insight into the ED’s work processes.Fig. 3 interview guide used for studying the pharmacists at the ED
For the most part the interviews were held on the same day as each pharmacist was observed. One pharmacist was interviewed the following day. One pharmacist was not available for interviewing during the study period.
Data analysis
The observations were noted in writing on the observation guide. Written open-ended observations were collected for each pharmacists’ patients and analysed inductively looking for patterns and themes. The interviews were audiotaped and transcribed verbatim. Conventional content analysis was conducted where researchers avoid using preconceived categories by inductive approach [22]. The interviews were repeatedly read looking for themes, marking representative quotes and condensing the meaning of each theme and its relevance for the study objective. The initial coding scheme was devised by one of the authors (RH). Codes were then grouped into meaningful clusters and validated using three interviews by another author (ABA). Any discrepancies or uncertainties were resolved among all authors.
Results
All seven pharmacists who work at the ED (all female, mean age 35.4 years (range 29–42)) were observed and six of them were interviewed (F1-6). Three of the pharmacists had less than 2 years’ experience working in the hospital (F1, F5 and F7). Six of them worked one day per week at the ED and every eighth weekend, whereas one worked there on a less regular basis. The interviews and observations were carried out on nine separate whole days from March 29 to May 5, 2021. The observations lasted at least one whole workday for each of the seven pharmacists.
The interviews shed light on the kinds of considerations pharmacists processed when prioritizing patients and how they used the ground rules (as set out in the PDSA process). The observations supplemented these data by showing some notable differences between pharmacists’ prioritization procedures that linked to their clinical experience. The interviews also highlighted the importance of collaboration with physicians and how pharmacists could be better integrated in the ward team.
Factors to focus on when prioritizing patients
Pharmacists have complex considerations when prioritizing patients during their workday at the ED. They all agreed that not all medications are important when scanning a patient’s medication list. Missing a few regular doses of some preventive medications for patients during their stay at the ward could for instance, be viewed lightly as the patients would soon be discharged.Whether it is a simvastatin or losartan or something like that, I am a bit more, like oh well (…) I am a bit more laid back about that. But of course, they need their medication, however [for these drugs], they won’t die from missing a single dose. (F2)
The seven risk-situation medications were mentioned, but pharmacists did not find them very helpful. Conversely, the entire medication list, looking for interactions, and evaluating the appropriateness of dosages were more important to consider. The age of the patient was not always relevant, but the number of medications and the reason for admittance could be important factors.They [elderly patients] use more medications than the younger patients. But sometimes the younger patients are also important since a few might also be using a lot of medications, even though they are young. (F3)
It could also be a decreased kidney function where we need to look at the dosages. Or that there is some medication that actually caused the admission or the general diagnosis. Is there some sort of a [prescribing] cascade? (F5)
Views on the implemented guidelines (PDSA)
The interviews also shed light on how the pharmacists viewed the guidelines implemented during the observation period and how they chose to work with these or around them. They reported both positive and negative aspects. On the positive side, they felt that they became more efficient due to the PDSA process; that they reviewed a larger number of patient charts per shift and identified a higher number of appropriate patients.I feel like I am covering more, which means that I am getting more done. Which also means that there might be a higher percentage [of patients reviewed] who aren’t important, but I also think that I am catching more relevant [cases], where I might [before] have said “Well, we’ll wait and see” [before performing a review]. (F2)
The negative aspects were that pharmacists feared that the focus on the longest stays and entering medicines into the EHR made for a more haphazard selection of patients. This could make them miss patients in great need of pharmaceutical care.But I think it’s a bit due to chance that I catch them [patients in need of a medication review]. So it all comes down to when you [the patient] enter [the ED]. It is left up to the time factor [to prioritize]. (F5)
In principle we just have to note if they [the patients] have had their medication entered [into the EHR] and [if they have] you aren’t supposed to look any more at the patient. (…) I can’t help it, because sometimes I think there is something problematic, that I spot right away. (F6)
When the pharmacists talked about the PDSA and guidelines, it was clear that they felt that their clinical experience and use of pharmaceutical competencies were undervalued. Most of the pharmacists stated that this process did not optimally utilize the competencies of the pharmacists and that, as professionals, they would be more valuable in direct patient care.I just don’t think that our focus with the doctors should be that we can enter the medication [into the EHR]. I think we need to show that “We are pharmacists. We are specialists within the pharmaceutical treatment”. So we are able to do something else than this. (F6)
This indicated that the pharmacists felt that they were viewed more as technical staff than professionals who have clinical skills.
Pharmacists’ prioritization methods as observed
When the pharmacists were observed, a pattern emerged in the qualitative notes. A notable difference was seen in the workflow and prioritization of patients according to the pharmacists’ clinical experience, where there was a clear distinction between those who had worked more than 2 years in the department and those with less experience. However, this pattern did not emerge in the interviews regarding which factors to focus on when working with patients, nor in their views on the non-clinical guidelines.
Pharmacists with less experience (less than 2 years of clinical hospital experience) worked in the following way: they sorted patients by length of stay, and selected those where medications had not been entered into the EHR. In contrast, experienced pharmacists (two or more years of clinical hospital experience) worked in the following way: the patients' length of stay was noted and used to prioritize the patients. The reason for admission was noted for each patient and whether or not the medications had been added to the EHR. If medications had been added to the EHR, the pharmacist would then critically evaluate if a medication review should be carried out based on the medication list in the EHR and the Shared Medication Record (SMR, a prescription records system covering all of Denmark). With the notes from the morning conference in mind, they decided which patients to prioritize.
In addition, most pharmacists with less clinical experience used the medication list in the EHR and not in the SMR to check whether the usual medication had been added or not. This could potentially be misleading as some patients upon admission were prescribed medication for their acute condition without transferring the usual medication list (as registered in SMR) to the EHR. The observations generally showed that the prioritization guidelines were only used as a rough guide, although less experienced pharmacists followed them more closely than their more experienced colleagues did. The observations supplement the interview findings that pharmacists fear making a haphazard selection. The response to this fear varies between pharmacists who have had substantial experience before implementing the non-clinical ground rules and those who were junior when they were implemented.
Collaboration with physicians
All respondents talked in the interviews about how they see their collaboration with physicians at the ED. Firstly, how being situated near physicians facilitates the collaboration and how they wish to have more referrals from physicians. They spoke of how the Covid-19 pandemic had removed morning briefings and the location of the pharmacists within the department was changed so they did not sit near the physicians anymore.I was used to have a lot more [contact with the physicians] when I was sitting next to them compared to now (…). And I felt more like a part of the team [then] than now (…) Also, during Covid-19 this [contact with the physicians] has been lost, the morning briefing, and then you are a bit lost [with regard to prioritizing patients]. (F6)
Secondly, many pharmacists mentioned how a better collaboration between physicians and pharmacists on prioritization of patients could improve both the workflow and the impact of medication reviews. Referrals from physicians provided the pharmacists with more clinically relevant cases and led to a higher rate of acceptance of recommended changes to the patient’s medications.I wish that we [physicians and pharmacists] were a bit better at prioritizing patients together – what is it we want to look at? So, in the ideal world, the referrals would always be prioritized first. (F5)
Ideas for improvements—using and developing clinical competencies
The pharmacists’ ideas for improving their prioritization and work with patients reflected that, although more efficient, they were still not satisfied with the PDSA criteria at the ED. Especially the longest stay criterion was criticized for not being useful.I don’t think we should prioritize based on the length of stay. I think you need to assess which [individual] patients are important. Thereby obtaining tools to help defining “this is an important patient; this isn’t an important patient. (F6)
Another dissatisfaction among pharmacists was that they felt they were not allocated to the most appropriate patient groups within the ED. Being a department with several specialties, the pharmacists primarily worked with the acute medicine specialty. This specialty has a high turnover rate and patients are often discharged after a short stay. Therefore, the pharmacists’ medication review would not always be ready before the patient was discharged.
Another important improvement they noted was that each pharmacist should work more frequently at the ED. Being there only once a week hampers them in developing a routine and competencies in working with acute patients and becoming a member of the ward team. They stated that it takes time to become professionally strong and experienced in this type of setting and they could benefit from being more than one pharmacist at a time on the ward.… There is so much knowledge and learning potential in each other’s way of working which we don’t really obtain (F5)
Lastly, the pharmacists talked about how the “clinical insight” of the pharmacist needed to come more into play. This would aid them in identifying patients more effectively using the medication lists and the EHR information.So eventually, it’s just experience, it’s just something you know instinctively. “Is there something here [in the medication list]? There is just something strange here”. Or… not that I can remember exactly what it is, but there is just something that tells me that I need to look into this patient. (F3)
The observations reflected these ideas of the pharmacists to their clinical experience. ED pharmacists need a very long time to obtain “clinical insight” because they only work at the department one day a week. Furthermore, the difference observed between experienced and less experienced pharmacists highlights the potential to be overlooked as a valuable member of the ward team.
Discussion
Statement of key findings and interpretation
By observing and interviewing a group of ED pharmacists, this study showed that they have complex considerations about patient factors of importance when selecting them for medication reviews. They see both positive and negative aspects of the newly instated PDSA rules, where the main problem was that the rules focused more on technical rather than clinical input into patient care. Observations of their procedures revealed a pattern which showed that ED experience mattered in how these rules were used and worked around. The pharmacists wished to become more integrated into the ward team and saw physicians as central to boosting the impact of pharmacists’ medication reviews.
Currently, there is no national or international consensus on prioritizing patients for medication reviews, however, screening tools have been developed to guide clinical pharmacists [10–12]. In Denmark there are seven so-called risk situation medications [17], but this list is far from sufficient according to the pharmacists in our study. Research has shown that there is disagreement about what constitutes high-risk medications [16]. This lack of consensus is reflected in the variability in the existing screening tools [10]. The non-clinical rules set at the beginning of the study (through a PDSA process) increased efficiency, although the quality of the medication reviews per se was not measured. Efficiency increases have also been observed when using clinical prioritization tools [23].
Studies have shown that pharmacists with longer experience and more training are more skilled in detecting drug related problems and medication errors [9, 18, 24, 25]. This was evident in the observations, as more experienced pharmacists did not go by the dictated criteria solely to select patients based on whether their medicines had been entered into the EHR and longest stay. They instead employed clinical insight which they gained from experience in the clinic.
The pharmacists in this study found the physician referrals gave more cases for relevant medication reviews. They also stressed the importance of physical proximity to the physicians’ working stations at the ward. Studies from primary care have shown that pharmacists’ personal contact with physicians enables trust and furthers collaboration [26, 27]. However, a study in the hospital setting has shown that even with physical proximity, it is also important that pharmacists engage in proactive communication with physicians [28].
The interviews emphasized that pharmacists felt their clinical knowledge was underutilized which was not surprising and a well-known fact in professional pharmacy circles [29]. This is especially visible as they (and other highly educated health professionals) devote considerable amounts of time to entering medications into the EHR.
Strengths and limitations
This study’s strengths stem from the use of two methods, i.e. of observations followed by qualitative interviews. The interviews provided the opportunity to ask questions closely following the observations. That created a situation for the interviewee to reflect on what she was thinking during her work. Although the observer/interviewer was an outsider to the setting, she was a pharmacy student majoring in clinical pharmacy and had insight into medication reviews. Being an outsider enabled her to observe the setting with a different perspective and improved her understanding of the pharmacists’ work when interviewing and analysing the data. This was also a weakness as the observer/interviewer was not yet a pharmacist and was a novice researcher. The situation could make her unable to catch some nuances of the professional work and its organization. She may therefore not have attended sufficiently to reflexivity and preconceptions while doing field work [30]. Her effect on the environment cannot be ruled out, but pharmacists generally were very busy at the ED, which could mitigate this threat to validity. To counteract these limitations, she held a workshop with the pharmacists where she presented the results and received positive feedback supporting validity. In addition, the other researchers had different expertise and more experience with the subject and methods. They therefore, could question the data material and framework of analysis in support of objectivity [30]. Another limitation is that the study was only carried out in one hospital with a small number of pharmacists who were rather young. This lowers transferability to other settings, although it was possible to observe all pharmacists and interview most. In this way, it was possible to cover the work and views of the entire population in the case studied. A longer time period of observation could have validated and deepened the findings of observation, as well as reduced the influence of the researcher on the environment.
Further research
The clinical pharmacy training that pharmacists receive while in their 5-year pharmacy program in Denmark constitutes a minor part of the program. Due to a high proportion of pharmacy graduates entering the pharmaceutical industry in Denmark, there is less emphasis on clinical pharmacy subjects than in programs in other countries such as the UK or USA. No literature is available describing the on the job training of clinical pharmacists in hospitals in Denmark and there are no national requirements that pharmacists need to meet in order to practice patient care. This study indicates that on the job training could be optimised for new pharmacists prior to working individually at the ED. This makes for future research into the optimisation of clinical skills and knowledge of pharmacists in a Danish hospital setting.
The most important practice improvement is to implement valid and feasible prioritization tools in the clinical pharmacy services. This will firstly, enable pharmacists to focus on which patients need medication reviews from a clinical perspective in particular pharmacists with less experience. Having a more clinical way of prioritizing will give the profession of pharmacy a stronger standing with the physicians with whom they need to collaborate regarding patients.
Conclusion
This study has highlighted that pharmacists according to clinical experience handled the current non-clinical prioritization process differently. Although the process increased efficiency, it was not deemed helpful for detecting the clinically meaningful patients for the pharmacists working at the ED. The study showed that a prioritization tool and being situated more closely to the physicians at the ward would help pharmacists be further integrated into patient care. Future research should focus on documenting how pre- and post-graduate training of pharmacists in Denmark can strengthen the role of clinical pharmacists in the hospital setting.
Acknowledgements
We would like to thank all the pharmacists who made this study possible.
Funding
No funding was obtained for this study.
Conflicts of interest
One of the authors (JN) was employed as clinical pharmacist at the particular hospital at the time of the study and practiced at the ED. The other authors declare that they have no conflict of interest.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36469215 | PMC9735217 | NO-CC CODE | 2022-12-14 23:29:53 | no | Int J Clin Pharm. 2022 Dec 5;:1-10 | utf-8 | Int J Clin Pharm | 2,022 | 10.1007/s11096-022-01515-3 | oa_other |
==== Front
Water Resour
Water Resources
0097-8078
1608-344X
Pleiades Publishing Moscow
8454
10.1134/S0097807822060185
Interaction between Continental Waters and the Environment
A Three-Way Decision Approach for Water Resources System Resilience Evaluation and Its Application
Yang Yafeng 12
Wang Hongrui [email protected]
1
Zhao Yong 3
Gong Shuxin 1
1 grid.20513.35 0000 0004 1789 9964 College of Water Sciences, Beijing Normal University, 100875 Beijing, China
2 grid.440734.0 0000 0001 0707 0296 College of Sciences, North China University of Science and Technology, 063210 Tangshan, China
3 grid.453304.5 0000 0001 0722 2552 State Key Laboratory of Simulation and Regulation of Water Cycle in River Basins, China Institute of Water Resources and Hydropower Research, 100038 Beijing, China
8 12 2022
2022
49 6 10931104
28 11 2021
26 3 2022
3 4 2022
© Pleiades Publishing, Ltd. 2022, ISSN 0097-8078, Water Resources, 2022, Vol. 49, No. 6, pp. 1093–1104. © Pleiades Publishing, Ltd., 2022.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Resilience is a significant uncertainty thought of water resources system security. Compared with risk analysis, resilience pays more attention to the ability of water resources system itself to deal with adverse events. However, a standard system of water resources system resilience’s concept and evaluation have not yet formed. In view of this, this study had attempted to decompose the process of resisting interference of water resources system and analyzed the characteristics and influencing factors of three sub processes of resistance, recovery and adaptation. Furtherly, a new resilience evaluation index system of water resources system was explored and a three-way dicision approach for water resources system resilience analysis based on variable fuzzy sets and partial connection number was developed. Specifically, a multi-grade quantitative evaluation of water resources resilience was carried out based on variable fuzzy sets method, and then the quantitative evaluation results were transformed into qualitative decision-making results using a new three-way decision model based on partial connection number of set pair analysis. Finally, a case study of China’s Yangtze River Economic Belt (YEB) in 2008–2017 was performed and the results show that the resilience of water resources system in the YEB does not show an obvious improvement trend, or even almost stagnant. Of the 110 samples, 83.6% were at the medium level. Only 6.4% are barely at the excellent level, but they are basically in Shanghai.
Keywords:
water resources system
resilience
resistibility-recoverability-adaptability
variable fuzzy sets method
grade eigenvalue
set pair analysis
partial connection number
three-way decision
Yangtze River Economic Belt
issue-copyright-statement© Pleiades Publishing, Ltd. 2022
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pmcINTRODUCTION
A consensus has been reached that water shortages, floods and droughts, and the deteriorationare of water environment becoming increasing serious, which seriously affect the sustainable development of global economy, society, environment and resources [2, 5, 21, 28]. In 2012, the United Nations World Water Assessment Programme pointed out that with the impact of climate change, the amount of water resources available in many regions will be reduced, and the imbalance between water supply and demand and the water shortage will be aggravated [22]. The frequent occurrence of water resources problems has prompted human beings to find more reasonable strategies for sustainable utilization of water resources. Risk analysis is one of the important paths to deal with this problem, which has provided a scientific basis for water resources security [13, 14]. However, it tends to emphasize the probability of adverse events and the degree of loss, and ignores the response capacity of water resources system itself. In fact, the outbreak of COVID-19 has sounded the alarm for us. We have exposed great vulnerability in the face of sudden risks. Water resource is one of the rigid constraints of economic and social development, which is of great significance, but it also presents vulnerability [15]. Therefore, it is particularly urgent to shift from “anti vulnerability” to “resilience” [6, 11, 12, 16].
Resilience origined from “resilio” in Latin, which means “reset to the original state.” It was introduced into ecological field by Holling [7] to describe the extent to which disturbances can be absorbed before the system’s structure was changed. Subsequently, it was gradually extended to many fields, such as human ecology, social ecology, water science, etc. In the application expanding, its core concept is from focusing on the engineering resilience of “single steady state” to “building new steady state” ecological resilience, and then gradually weakening the emphasis on the steady state, while focusing on the learning adaptation process, namely, the improvement of resilience. Resilience has more flexibility than carrying capacity or resistance strategies, which can adapt to various uncertain changes [24].
Resilience emphasizes the system’s resistibility to cope with the disturbance, recoverability after disturbed and adaptive learning ability, which provides a new analytical framework for the sustainable development of water resources system. At present, scholars have paid attention to the water resources system resilience. Alessa et al. established the Arctic water resources vulnerability index to express the resilience [1]. Tanner et al. evaluated the resilience of water resources systems from 5 aspects: decentralization and autonomy, transparency and accountability, responsiveness and flexibility, participation and inclusiveness, and governance experience [20]. Sandoval-Solis et al. established the sustainability index of water resources from three aspects of reliability, recoverability and vulnerability based on “deficit” [17]. Liu et al. established a quantitative evaluation model of water resources system resilience from three aspects of drought, waterlogging and water pollution based on Holling’s resilience thought [10]. Yu et al. considered that water system has the characteristics of resilience [25]. Huang and Ling used GIS spatial analysis and ABM model to study the resilience of urban water resources system [8]. Sun and Meng introduced “soft power” factors such as culture and system into the evaluation index system of regional water system resilience [19], and so on. Obviously, a series of research results on water resources resilience system provide support for the sustainable development of water resources system. However, to the best of our knowledge, no studies have focused on the process decomposition of water resources resilience system, that is, the mechanism and connection of absorbing disturbance, recovering structure and lifting function. In addition, the current evaluation of water resources system resilience is often based on the static index data, and the fuzziness and dynamic of the data are not sufficiently considered. Such questions bear importantly on clarifying the connotation of water resources system resilience, and may shed light on how to formulate better water resources security policies that perform well facing various interference of adverse events.
In view of this, this study firstly referred to the resilience concept, analyzed the characteristics and influencing factors of water resources system resilience from the perspective of process decomposition, and constructed a evaluation index system of resilience; Secondly, focusing on the fuzziness, variable fuzzy sets method was used to describe the unity of opposites of the resilience between adjacent grades, and the grade eigenvalues were used to describe the resilience; Thirdly, considering the dynamics of information, a new three-way decision model was constructed based on partial connection number method to analyze the internal evolution direction of resilience; Finally, the proposed model framework was applied to the multi-level and multi-scale quantitative evaluation of the water resources system resilience of China’s YEB from 2008 to 2017.
METHODS
Firstly, a new evaluation index system of water resources system resilience based on subsystem decomposition was explored. Then, a complete three-way decision approach for resilience evaluation based on variable fuzzy sets and partial connection number was constucted.
Evaluation Index System of Water Resources System Resilience
This study holds that water resources resilience refers to the ability that can maintain stable operation in the disturbed state, recover the original function quickly when impacted, and acquire certain adaptability after one impact process. So, resilience process can be seen as a cycle in which the system improves adaptability and constantly adapts to risks and disturbances. In this process, the system has experienced “be disturbed,” to “maintain system stability after disturbed,” and then to “recovering stability.” In this process, the ability of adaptation and learning has been improved, and then achieve innovative development and enhance resilience (Fig. 1).
Fig. 1. Resilience process of water resources system.
Corresponding to three sub processes: before disturbance, during disturbance and after disturbance, three ability goals of water resources system, that is, resistibility, recoverability and adaptability respectively, and their influencing factors, should be explored.
Influencing factors of resisting process: In disaster science, the impact of disaster process is mainly composed of two parts: external pressure and endogenous pressure. It is caused by the instability and effect accumulation of natural or human activity regional system, including endogenous problems such as population, resources and environment [18]. Similarly, in the water resources system, the main factors affecting the water resources resilience depend on the frequency of external natural disasters and the endogenous factors related to the regional water resources. Therefore, in the water resources system, the greater the potential risk it faces, the more disturbance it will be subjected to, and the weaker its resistibility will be. When there are more exogenous factors such as flood and drought, the impact of water resources system will be greater, the system’s ability to resist risk will be weaker, and the performance of resilience in the resisting process will be worse. In particular, the drought and flood affected area refers to the sowing area where the yield of crops is reduced compared with that in normal years due to flood and drought disasters and it can characterize the frequency and scope of natural disasters closely related to water, that is, the number and range of exogenous factors, and is closely related to the agricultural production system. Correspondingly, endogenous factors such as regional water resources pressure and population pressure will also affect the water resources system to suffer huge impact, leading to the weakening of resistibility.
Influencing factors of recovering process: After the system is disturbed, it will go through a recovering process, and the influencing factors in this process are affected by the stability of the internal factors.The recovering process is affected by internal factors such as water environment, economy and water use structure, which determine the speed of the system recovering process. The recoverability is affected by environment, ecology, economy, society and other aspects: for example, sewage treatment determines the carrying capacity of the water environment; economic structure will affect the water consumption, and industrial and agricultural water consumption will be far greater than that of the tertiary industry; different water use efficiency will also affect the resilience of water resources. For instance, agricultural water consumption includes irrigation of cultivated land and forest land, gardens and pastures, replenishment of fish ponds and livestock water, which in a certain sense reflects the potential ability of the agricultural production system to restore various normal functions after disasters, etc.
Influencing factors of adapting process: After recovering process, the system will learn to adapt to the next disturbance through this disturbance, which is the adaptability in the resilience system. The adapting process of water resources resilience system is mainly affected by regional innovation factors, security factors and so on. Different adaptability levels determine the new initial state level that the system can move to in the next impact.In the water resources system, the impact on adaptability mainly focuses on regional sustainable development and sustainable utilization of water resources. For example, water consumption of ecological environment reflects the water consumption used for ecological environment restoration and construction or maintaining the current ecological environment; the input cost of environmental protection in the region will greatly affect the level of water environment adaptation; high quality R & D platform will promote the efficient use of water resources; the construction level of the region itself can assist the smooth operation of urban water system. These factors do not belong to the water resources endowment, nor in the scope of economic structure and ecological environment, but they have a profound impact on the water resources system and make it change in a better direction.
According to the above analysis, when selecting the evaluation index of water resources resilience, we should pay more attention to the problem orientation and risk pertinence, and consider the diversity of the pressure faced by the water resources system, the complexity of the water resources system and the anti-interference ability [9]. The resilience of water resources system depends on the interaction of various factors such as water resources endowment, ecological environment, economic society, population and system, and different index selection will affect the results of water resources resilience evaluation. In view of this, this study based on the concept of resilience, followed the principles of scientificity, systematicness and operability, screened the corresponding indicators from three aspects of resistibility, recoverability and adaptability. Furtherly, a new evaluation index system of water resources system resilience was constructed, as shown in Table 1.
Table 1. Evaluation index system of water resources system resilience
Subsystem Index Unit Attribute
Resistibility Population 104 –
Drought affected area 103 ha –
Flood affected area 103 ha –
Water consumption per 104 yuan GDP m3 –
Total water supply 108 m3 +
Total water resources 108 m3 +
Recoverability Water resources per capita m3 +
Industrial water consumption 108 m3 –
Agricultural water consumption 108 m3 –
Sewage treatment capacity 108 m3 +
Proportion of tertiary industry % +
Energy consumption per unit output value KWh/104 RMB yuan –
Adaptability Water consumption of ecological environment 108 m3 +
Investment in environmental protection 108 RMB yuan +
Growth rate of fiscal revenue 108 RMB yuan +
R & D investment 108 RMB yuan +
Urban greening rate % +
Forest coverage % +
A New Three-Way Decision Approach Based on Variable Fuzzy Sets and Set Pair Analysis
The proposed three-way decision approach in this study includes three main steps: (1) Calculate the membership degrees of each object relative to each grade by using the variable fuzzy set method, and analysis the time series evolution trend of resilience level based on the grade eigenvalue; (2) Transform the relative membership degree into connection number, and express the uncertain state of each object relative to each resilience grade by a unified mathematical structure; (3) Describing the decision cost by considering dynamic evolution between components by partial connection number, and then construct a new generalized three-way decision model.
Grade Eigenvalue (in Variable Fuzzy Sets Theory)
In 1965, the concept of fuzzy sets was proposed by Professor Zadeh [26], and theory of fuzzy sets was established. This theory promotes the development of the direction and practical application of traditional mathematical theories. However, with the gradual increase in the scope of application fields, this theory fails to consider the dynamic variability of development of objects. To address this shortcoming, Chen [3] established variable fuzzy sets theory based on the principle of mutual transformation of contradictions in natural dialectics, which has been applied to the relative research of water resources system.
The water resources system resilience is also a fuzzy concept, and there is no absolute clear boundary between its adjacent grades. For the resilience level of a specific water resources system, it is difficult to judge it as a certain grade absolutely, because it always maintains a fuzzy unity of opposites between two adjacent grades. The relative membership degree method in variable fuzzy sets theory provides an effective tool to describe this problem.
As stated by Chen [3], U is a fuzzy concept, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$u$$\end{document} is a random element in U, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$u \in U$$\end{document}. A and AC represent attractability and repellency. Then form a pair of continuous number lines expressed by the closed intervals of [1, 0] and [0, 1]. For u in U, µA(u) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{{{A}^{C}}}}}$$\end{document}(u) are the relative membership functions of u to A and AC that respectively express attractability and repellency degree. The mapping is presented as follows:
1 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left\{ \begin{gathered} {{\mu }_{A}},{{\mu }_{{{{A}^{C}}}}}{\kern 1pt} :\,\,\,\,U \to \left[ {0,1} \right] \hfill \\ \left. u \right| \to {{\mu }_{A}}\left( u \right),\,\,{{\mu }_{{{{A}^{C}}}}}\left( u \right) \in \left[ {0,1} \right]. \hfill \\ \end{gathered} \right.$$\end{document}
This mapping is called the relative membership function of A and AC, where \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{A}}\left( u \right) + {{\mu }_{{{{A}^{C}}}}}\left( u \right) = 1$$\end{document}, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0 \leqslant {{\mu }_{A}}\left( u \right) \leqslant 1;0 \leqslant {{\mu }_{{{{A}^{C}}}}}\left( u \right) \leqslant 1$$\end{document}.
If any two adjacent grades constitute an opposite events group, according to variable fuzzy sets, the evaluation object only has relative membership relationship with one group (record as A and AC), and satisfies the unity of opposites.
Let \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$U = \left\{ {{{u}_{j}}} \right\},\left( {j = 1,~2,~ \cdots n} \right)$$\end{document}, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$T = \left\{ {{{t}_{i}}} \right\},\left( {i = 1,~2, \cdots m} \right)$$\end{document} be the indexs set. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{X}_{{ij}}} = \left\{ {{{x}_{{ij}}}} \right\}$$\end{document} refer to the value of uj for ti. ti is divided into s grades, and the corresponding interval matrix is as follows:2 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{I}_{{{{t}_{i}}}}} = \left[ {{{a}_{{ih}}},{{b}_{{ih}}}} \right]\left( {h = 1,2, \cdots ,s} \right),$$\end{document}
where, aih, bih are the upper and lower limits of ti at grade h.
According to the theorem of the unity of opposites of variable fuzzy sets, there must be two gradual change points kih and ki(h + 1) of index ti in the interval of grade h and h + 1 respectively and the relative membership degree meets the conditions in Table 2.
Table 2. Basic conditions of relative membership degree
Conditions Relative membership degree
\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{x}_{{ij}}} \leqslant {{k}_{{jh}}}$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{j\left( {h{\kern 1pt} - {\kern 1pt} 1} \right)}}}\left( {{{O}_{i}}} \right) + {{\mu }_{{jh}}}\left( {{{O}_{i}}} \right) = 1$$\end{document}, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{j\left( {h{+} 1} \right)}}}\left( {{{O}_{i}}} \right) = 0$$\end{document}
\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{x}_{ij}}\ge {{k}_{j(h{\kern 1pt} +{\kern 1pt} 1}}$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{jh}}}\left( {{{O}_{i}}} \right) = 0$$\end{document}, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{j\left( {h{+} 1} \right)}}}\left( {{{O}_{i}}} \right) + {{\mu }_{{j\left( {h{+} 2} \right)}}}\left( {{{O}_{i}}} \right) = 1$$\end{document}
\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{k}_{{jh}}} \leqslant {{x}_{{ij}}} \leqslant {{k}_{{j\left( {h{+} 1} \right)}}}$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{jh}}}\left( {{{O}_{i}}} \right) + {{\mu }_{{j\left( {h{+} 1} \right)}}}\left( {{{O}_{i}}} \right) = 1$$\end{document}
The gradual change points kih, (h = 1, 2, …, s) can be obtained by:3 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{k}_{{ih}}} = \frac{{s - h}}{{s - 1}}{{a}_{{ih}}} + \frac{{h - 1}}{{s - 1}}{{b}_{{ih}}}.$$\end{document}
When \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{k}_{{ih}}} \leqslant {{x}_{{ij}}} \leqslant {{k}_{{i\left( {h{+} 1} \right)}}}$$\end{document}, the relative membership degree of xij to grade h can be calculated as:
4 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{ih}}}\left( {{{u}_{j}}} \right) = 0.5\left( {1 + \frac{{{{b}_{{ih}}} - {{x}_{{ij}}}}}{{{{b}_{{ih}}} - {{k}_{{ih}}}}}} \right)x_{{ij}} \in \left[ {{{k}_{{ih}}},{{b}_{{ih}}}} \right],$$\end{document}
5 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mu }_{{ih}}}\left( {{{u}_{j}}} \right) = 0.5\left( {1 - \frac{{{{b}_{{ih}}} - {{x}_{{ij}}}}}{{{{b}_{{ih}}} - {{k}_{{i\left( {h{+} 1} \right)}}}}}} \right)x_{{ij}} \in \left[ {{{b}_{{ih}}},{{k}_{{i\left( {h{+} 1} \right)}}}} \right].$$\end{document}
Then, the combining relative membership degree of uj to grade h is:6 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{{v}}_{h}}\left( {{{u}_{j}}} \right) = \mathop \sum \limits_{i{\kern 1pt} = {\kern 1pt} 1}^m {{w}_{i}}{{\mu }_{{ih}}}\left( {{{u}_{j}}} \right),$$\end{document}
where: wi is the weight of ti, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sum\nolimits_{i{\kern 1pt} = {\kern 1pt} 1}^m {{{w}_{i}}} = 1$$\end{document}.
The principle of maximum membership is widely used in many fuzzy decision making fields. However, this principle exhibits evident defects when fuzzy concepts are graded. The grade eigenvalue was proposed to address this defect [4].7 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$H\left( {{{u}_{j}}} \right) = \mathop \sum \limits_{h{\kern 1pt} = {\kern 1pt} 1}^s {v}_{h}^{0}\left( {{{u}_{j}}} \right)h,$$\end{document}
is called grade eigenvalue of uj. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${v}_{h}^{0}$$\end{document}(uj) refers to the normalized vector of vh(uj). Grade eigenvalue transforms relative membership degrees into a real number, which can reflect the approximate range of the evaluation object. However, for different relative membership degrees, the same or close grade eigenvalues may appear, which will lead to deviation in the grade determination. Therefore, it is still necessary to consider the size and dynamic evolution of each membership degree for the grade determination. Here, a new three-way decision model is proposed in Section 2.3 to solve this problem.
Connection Number and Partial Connection Numbe in Set Pair Analysis
For the similar problems, set pair analysis (SPA) method proposed by Zhao [31] has another expression, which uses the ternary connection number u = a + bi + cj to express the relationship among the three grades. Where, a, b, c represents the membership degrees (correlation degrees) between the resilience grades (1 to 3) of water resources system. i and j are the marking symbols. Furthermore, the partial connection number was developed to describe the dynamic evolution of information and has been deeply studied and applied [29, 30]. Obviously, for the problem with three grades, we only need to set h (in variable fuzzy sets method of Section 2.2) to 3. Then, the three relative membership degrees can be recorded as each component of the connection number, that is, a, b, and c. In this way, the relationship between relative membership degree of variable fuzzy set and connection number is established, and the evolution characteristics of connection number components are also the evolution characteristics of relative membership degree.
Let a ternary connection number be u = a + bi + cj, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$a,b,c \in \left[ {0,1} \right],a + b + c = 1$$\end{document}, then:8 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{ + }}\mu = {{\partial }^{ + }}a + i{{\partial }^{ + }}b = \frac{a}{{a + b}} + \frac{b}{{b + c}}i,$$\end{document}
is recorded as First-order partial positive connection numbe (FPCN). Where, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{ + }}a$$\end{document} is the positive evolution rate from b to a. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{ + }}b$$\end{document} is the positive evolution rate from c to b.9 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{ - }}\mu = i{{\partial }^{ - }}b + j{{\partial }^{ - }}c = \frac{b}{{a + b}}i + \frac{c}{{b + c}}j,$$\end{document}
is recorded as First-order partial negative connection numbe (FNCN). Where, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{ - }}b$$\end{document} is the negative evolution rate from a to b. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{ - }}c$$\end{document} is the negative evolution rate from b to c.
Furthermore, if the FPCN is calculated again by partial positive evolution, we can get the Second-order partial positive connection number (SPCN) as follow:
10 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{{2 + }}}\mu = \frac{{\frac{a}{{a + b}}}}{{\left( {\frac{a}{{a + b}} + \frac{b}{{b + c}}} \right)}}.$$\end{document}
Similarly, Second-order partial negative connection number (SNCN) is:
11 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\partial }^{{2 - }}}\mu = \left( {\frac{{\frac{c}{{b + c}}}}{{\left( {\frac{b}{{a + b}} + \frac{c}{{b + c}}} \right)}}} \right)j.$$\end{document}
A New Three-Wey Decision Approach Based on Partial Connection Number
Three-way decision (3WD) is a granular computing method developed in recent years to deal with uncertain decision-making [23]. It is a “rule by three” model gradually evolved from decision rough set theory, which is in line with human cognition. The core idea of 3WD is to divide a unified set into three disjoint paired regions, and formulate corresponding decision-making strategies for each region. In fact, due to the fuzziness and limitations of human thinking, most of the affairs we encounter can be understood as 3WD problem in a broad sense [27]. For instance, if the resilience is set to three grades, the problem of resilience evaluation will turn into a 3WD issue. Therefore, we only need to construct the condition set and establish the corresponding decision rules between conditions and resilience grades.
Generally, in the connection nember u = a + bi + cj, the size of a, b, c directly affects the decision results, so it is certainty that the evolution path and degree (based on partial connection number) between them will promote the adjustment of decision results. If the part of b evolving to a is used as the information component of support grade 2, there will be a certain decision cost which can be expressed by \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b{{\partial }^{ - }}b$$\end{document}. Based on the same analysis, the decision cost (DC) of each component for each grade is expressed as follows:
12 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$DC = \left( {\begin{array}{*{20}{c}} 0&{a{{\partial }^{ + }}a}&{a{{\partial }^{{2 + }}}a} \\ {b{{\partial }^{ - }}b}&0&{b{{\partial }^{ + }}b} \\ {c{{\partial }^{{2 - }}}c}&{c{{\partial }^{ - }}c}&0 \end{array}} \right).$$\end{document}
Based on connection number be u = a + bi + cj, the decision cost of each grade are as follows:
13 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$DC\left( {{\text{Grade}}1} \right) = b{{\partial }^{ - }}b + c{{\partial }^{{2 - }}}c,$$\end{document}
14 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$DC\left( {{\text{Grade}}2} \right) = a{{\partial }^{ - }}a + c{{\partial }^{ - }}c,$$\end{document}
15 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$DC\left( {{\text{Grade3}}} \right) = a{{\partial }^{{2 + }}}a + b{{\partial }^{ + }}b.$$\end{document}
In general, decision makers tend to choose the grade with a lowest cost.
Finally, the state of water resources system resilience can be evaluated and analyzed combining with the results of variable fuzzy sets and three-way decision method.
RESULTS
Study Area and Data Sources
YEB refers to the economic belt along the Yangtze River in China, covering 11 provinces (cities), including Shanghai, Jiangsu, Zhejiang, Anhui, Jiangxi, Hubei, Hunan, Chongqing, Guizhou, Sichuan and Yunnan (Fig. 2). It covers a vast area of about 2.05 × 106 km2, accounting for 21.4% of China’s total. YEB’s population and GDP both exceed 40% of China’s total. YEB, spanning the eastern, central and western regions of China, is a key area for developing national productive forces in the new era.
Fig. 2. Location of the administrative division of the YEB.
In this study, 11 provinces (cities) with 10-year water resource data (from 2008 to 2017) were downloaded from the National Bureau of Statistics (http://www.stats.gov.cn/) and government websites of the Water resource Agency in each region. The datasets are available and have been processed with quality control with a missing data rate of less than 0.1%.
Grade Eigenvalue of Resilience
Taking 2017 as an example, this study shows the relative membership degrees and grade eigenvalue in various provinces (cities) in more detail (Table 3). According to the results of grade eigenvalue, the spatial and temporal variation of water resources system resilience in YEB from 2008 to 2017 is visualized by using ArcGIS, as shown in Fig. 3. According to Fig. 3, the distribution of water resources resilience grade in each province of the YEB is uneven. In terms of regional spatial change, the water resources resilience grade of 11 provinces (cities) in the YEB is developing in a balanced way, and the gap between provinces is gradually decreasing.
Table 3. Grade eigenvalue of water resources system resilience in YEB in 2017
Relative membership degree Grade eigenvalue
grade1/E (excellent) grade 2/M (medium) grade 3/P (poor)
Shanghai 0.37 0.16 0.47 2.09
Jiangsu 0.29 0.35 0.35 2.06
Zhejiang 0.45 0.48 0.07 1.62
Anhui 0.33 0.49 0.18 1.85
Jiangxi 0.29 0.56 0.15 1.86
Hubei 0.31 0.58 0.12 1.81
Hunan 0.41 0.47 0.11 1.70
Chongqing 0.26 0.46 0.29 2.03
Sichuan 0.47 0.42 0.11 1.64
Yunnan 0.35 0.49 0.16 1.81
Guizhou 0.17 0.60 0.23 2.06
Fig. 3. Grade eigenvalues of water resources system resilience in YEB from 2008 to 2017.
Three-Way Decision of Resilience Based on Information Evolution
The grade eigenvalue reflects the approximate range of resilience level, but we still need to further consider when judging the grade, because different relative membership degrees may produce similar grade eigenvalues, but in fact they are quite different. For instance, the connection number(transformed from relative membership degrees) of 2008 and 2017 in Shanghai are 0.2389 + 0.4266i + 0.3346 j and 0.3726 + 0.161i + 0.4663j respectively, and the corresponding grade eigenvalues are 2.0958 and 2.0936. Obviously, they are almost the same, but the intuition tells us that they should not have the same grade of resilience. In view of this, we make the three-way decision analysis based on information evolution. The results show that the decision costs of judging 2008 as grade 1, 2 and 3 are 0.608, 0.2328 and 0.4779 respectively. Correspondingly, 0.5149, 0.6068, and 0.414 for 2017. According to the principle of minimum decision cost, it is grade 2 in 2008 and grade 3 in 2017. All results are shown in Table 4.
Table 4. Three-way decision results
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Shanghai M M M E E E E E E P
Jiangsu M M M M M M E M M M
Zhejiang M M M M M M M M M M
Anhui P M M M M M M M M M
Jiangxi M M M M M M M M M M
Hubei P M M M M M M M M M
Hunan M M M M M M M M M M
Chongqing P P P M M M M M M M
Sichuan M M M M M M M M M M
Yunnan M M M M M M M M M M
Guizhou P P P P P M M M M M
DISCUSSIONS
Taking 2017 as an example, the range of resilience grade eigenvalues of 11 provinces (cities) is [1.62, 2.09], accounting for three grade ranges. In the analysis, the resilience level is expressed by higher, medium and lower. Jiangsu, Shanghai and Zhejiang are located in the plain Delta, with high level of coastal economic development, mature and stable industrial structure, and high scientific and technological innovation productivity. However, due to the regional population density, water resources endowment and other factors, the water resources resilience level of Jiangsu and Shanghai is relatively low. Comparatively, Zhejiang benefits from the advantages of better water resource endowment and higher level of science and technology, and its water resource resilienve level is higher. For Anhui, Jiangxi and Hubei, their economic development level is insufficient, their water resources endowment has few advantages, and their water resources resilience is in the medium level; Hubei’s water resource endowment is good, but its adaptability indexes such as environmental governance investment and financial revenue prospect are weak, and its water resource resilience is in the medium level; The resilience of water resources in Chongqing and Guizhou is relatively poor, and the adaptability index level of ecological water use, environmental governance investment and scientific research investment is relatively low; The output value of drought and flood in Sichuan is relatively low, but the water consumption per unit is relatively reasonable; As far as Yunnan is concerned, the sewage treatment capacity, scientific research investment and other indicators in this area are relatively low, the water resource endowment is good, and the water resource resilience is generally at the medium level.
The time series evolution trend of water resources system resilience in the YEB from 2008 to 2017 is shown in Fig. 4.
Fig. 4. The time series evolution of water resources system resilience in YEB from 2008 to 2017.
On the whole, the grade eigenvalues of water resources resilience of all provinces in the YEB are [1.51, 2.52]. In 2008, the eigenvalue interval of 11 provinces in the YEB is [1.90, 2.51], the average value is 2.24, and the eigenvalue interval of 2017 is [1.62, 2.09], the average value is 1.87. The grade eigenvalue decreases, the resilience level increases, and the change trend presents a good trend year by year.
As far as each region is concerned, Shanghai, Zhejiang and Jiangsu are located in the lower reaches of the Yangtze River, belonging to the Yangtze River Delta region, with good economic development, scientific and technological level, and better economic status than other regions. Therefore, their own water resources resilience foundation is good. In 2008, the regional water resources resilience level was significantly better than other regions, and the eigenvalues were about 2.0. However, in recent years, due to the overall development of the YEB showing a gradually balanced trend, the regional water resources resilience advantage has declined, and the resilience level has declined. In the past ten years, the water resources resilience characteristic values of the three provinces or cities are within [1.55, 2.10] as a whole, and the water resources resilience is in a good level range.
Anhui and Jiangxi are located in the middle and lower reaches of the Yangtze River. Compared with the three provinces in the Yangtze River Delta, the regional economic level is slightly weak. In the water resources resilience system, the process of recovery and adaptability is slightly worse than the previous three provinces. In terms of eigenvalue changes, Jiangxi reached 2.23 in 2008, while Anhui reached 2.51, which belong to the degree of poor resilience. In the following 10 years, the resilience level of Anhui province gradually increased, especially the resilience level of water resources and water infrastructure. In 2017, the characteristic value of water resources resilience of the two provinces was about 1.85, which was higher than that of the three provinces in the Yangtze River Delta.
For Hubei, Hunan and Chongqing, the three provinces or cities are located in the middle reaches of the Yangtze River and have good water resources endowment. They are also restricted by the economic structure and the level of scientific research and innovation. In 2008, the resilience level of water resources in the three provinces or cities was poor, with the eigenvalue interval of [2.19, 2.43]. With the change of time, the index level changes of the three provinces or cities mainly come from the restorative indicators, such as environmental governance investment, ecological water consumption, science and technology R & D investment and other indicators have been greatly improved, and the improvement of the restoration ability has improved the resilience of the water resources system. As of 2017, the resilience eigenvalues of Hubei, Hunan and Chongqing were 1.81, 1.70 and 2.03, respectively, indicating that the resilience is stable and there were obvious changes between the two groups.
Sichuan, Yunnan and Guizhou are located in the middle and upper reaches of the Yangtze River, and also in Southwest China. In 2008, the resilience characteristic values of the three provinces were 2.26, 2.12, and 2.44 respectively. Compared with other provinces or cities in the YEB, there is a certain gap in their water resources endowment, and their resilience level is relatively low due to the restrictions of economic development, backward science and technology, and environmental protection investment. With the change of time, the indexes of resistance, resilience and adaptability of the region have improved, which promotes the improvement of resilience level. However, in terms of adaptability, the level of environmental governance investment, scientific research investment, ecological water consumption and other indicators is still poor. In 2017, the resilience characteristic values of Sichuan, Yunnan and Guizhou reached 1.64, 1.81 and 2.06, respectively, and the resilience level improved significantly.
Among the three-way decisions of water resource system resilience in the YEB as shown in Fig. 5. In 2008, Anhui, Hubei, Chongqing and Guizhou have the decision results of grade 3, and their water resource resilience decision-making performance is poor, and the other provinces are all grade 2, and the resilience decision-making of these provinces is medium; in 2011, only Guizhou was decisioned as grade 3, while the results of Shanghai are changed from grade 2 to grade 1, which indicates that the water resource resilience of Shanghai has improved qualitatively compared with 2008. The decision results of other provinces (cities) are all grade 2; in 2014, Jiangsu’s decision-making results were improved to grade 1, Guizhou’s decision-making results were improved to grade 2, and the water resource resilience of both was also improved qualitatively. Except Shanghai and Jiangsu, the three-way decision results of other provinces or cities were all grade 2; in 2017, the decision results are all grade 2 except Shanghai, and the water resources resilience of Shanghai and Jiangsu have decreased compared with 2014, which should be given more attention. Shanghai, in particular, plummeted to grade 3 in 2017. Compared with 2016, although Shanghai has increased investment in science and technology research and development, limited by natural conditions, the amount of water resources has declined seriously, with the per capita water resources decreasing by 39.3%. In addition, the growth rate of fiscal revenue has slowed down, with a year-on-year decrease of 75.9%, which may be the main reason for the sharp decline in the resilience of the water resources system.
Fig. 5. Three-way decision results of water resource system resilience in YEB from 2008–2017.
CONCLUSIONS
Based on the resilience theory, this paper constructs a new index system of water resources system resilience from three aspects: resistibility, recoverability and adaptability. Then, the grade eigenvalues of water resources system resilience of 11 provinces (cities) in the YEB were calculated using variable fuzzy sets and the resilience grades were judged combining the proposed three-way decision model. The main conclusions are as follows: (1) The resilience level of water resources systems in 11 provinces (cities) of the YEB has increased year by year, and the average value of level eigenvalues has changed from [1.90, 2.51] in 2008 to [1.62, 2.09] in 2017, but the effect is not significant. (2) From 2008 to 2017, the three-way decisions results in the YEB showed of the 110 samples, 83.6% were at the medium level. Only 6.4% are barely at the excellent level, but they are basically in Shanghai. This shows that the toughness of the water resources system in the YEB is not satisfactory. With its ultra-high economic and scientific and technological level, Shanghai is at an excellent level, but it also exposes the problems of water shortage and low forest coverage. Therefore, with the east wind of “great protection of the Yangtze River” and “high-quality development of the YEB,” 11 provinces (cities) still need to adjust measures to local conditions, implement accurate policies, and strive to improve the toughness level of water resources system, so as to deal with various uncertain problems that may occur in the future.
FUNDING
This research was supported by National Natural Science Foundation of China (No. 51 879 010) and National Key Research and Development Program of China (No. 2019YFC0408902).
CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest.
==== Refs
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| 0 | PMC9735218 | NO-CC CODE | 2022-12-14 23:29:53 | no | Water Resour. 2022 Dec 8; 49(6):1093-1104 | utf-8 | null | null | null | oa_other |
==== Front
Curr Psychol
Curr Psychol
Current Psychology (New Brunswick, N.j.)
1046-1310
1936-4733
Springer US New York
4041
10.1007/s12144-022-04041-7
Article
Modeling the contributions of EFL university professors’ emotion regulation to self-efficacy, work engagement, and anger
http://orcid.org/0000-0002-8393-2537
Namaziandost Ehsan [email protected]
1
http://orcid.org/0000-0003-0011-9442
Heydarnejad Tahereh [email protected]
2
Rahmani Doqaruni Vahid [email protected]
2
http://orcid.org/0000-0002-7492-1932
Azizi Zeinab [email protected]
3
1 grid.411230.5 0000 0000 9296 6873 Department of General Courses, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 grid.510437.4 0000 0004 7425 0053 Department of English Language, Faculty of Literature and Humanities, University of Gonabad, Gonabad, Iran
3 Teaching English and Linguistics Department, University of Ayatollah, Ozma Borujerdi, Borujerd City, Iran
7 12 2022
115
14 11 2022
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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
As university professors’ emotion regulation (ER) plays a pivotal role in their efficacy, it is essential to explore if it is significantly correlated with work engagement (WE), self-efficacy, and anger at the workplace. To respond to the call, this research inspected the contributions of university professors’ ER to their WE, self-efficacy, and anger. For this purpose, a total of 278 university professors were selected using a convenience sampling method and asked to fill out Language Teacher Emotion Regulation Inventory, Engaged Teacher Scale, Teacher Sense of Efficacy Scale, and Teacher Anger Scale. A structural equation modeling was used to analyze the gathered data. Results disclosed that the participants’ ER significantly contributed to their WE and self-efficacy. Additionally, the findings documented that the participants’ ER was negatively correlated with their anger. The implications of the findings are discussed for pertinent stakeholders.
Keywords
Anger
EFL university professors
Emotion regulation
Self-efficacy
Work engagement
==== Body
pmcIntroduction
To have a true understanding of the role of emotions in second/foreign language (L2) teachers’ work, it is of utmost importance to find out why and how they make use of particular emotions in their classroom context with what intensity and quality. This is called emotion regulation (ER) and refers to “the set of processes whereby people manage all of their emotionally charged states, including specific emotions, affect, mood, and stress” (Koole, 2009, p. 29). ER is of particular importance in L2 classrooms where teachers constantly regulate their emotions due to various irritations and frustrations (Akbari et al., 2017; Morris & King, 2018). It seems that L2 teachers cannot create a friendly and productive learning context in their classrooms unless they can regulate their emotions, specifically the negative ones (Dewaele & Li, 2020). However, despite such an importance, empirical studies of ER are rare within L2 education (Morris & King, 2020). This is unfortunate as L2 teachers take several and various roles and responsibilities in their classrooms (O’Dwyer, 2006) which makes it unavoidable to experience specific subject-related emotions in unfamiliar emotional contexts. To make it even more complicated, it has been shown that some of these roles and responsibilities are culturally-informed (Mesquita et al., 2016).
On the other hand, studying different factors which might affect ER seems necessary due to the fact that it has been shown that emotions function on multi-dynamic levels (Fried et al., 2015; King & Ng, 2018). In other words, it has been proposed that emotions are continually shaped by contexts rather than being intrapersonal phenomena. In this way, different factors which might influence a teacher’s emotions range from personal experiences and relationships with students, colleagues and administrators to the immediate political, cultural and social contexts in which they work (Boiger & Mesquita, 2012). For example, a teacher might feel happy when a weak student eventually understands a difficult concept or gives the correct answer to a difficult question, disappointed when a colleague does not share their teaching experience, discouraged when the school principal does not care about their innovative practices in the classroom, frustrated when they are not allowed to express their ideology due to political restrictions, pleased when they see their teaching affects their students’ cultural awareness, and satisfied when they are respected in their community.
Given the pivotal role played by ER, this research aims to inspect its contributions to psycho-emotional constructs, such as work engagement (WE), self-efficacy, and anger. Put it more exactly, this research aimed to explore if EFL university professors’ ER is significantly correlated with their WE, self-efficacy, and anger. By disclosing such relationships, it is hoped that the findings of this research can be useful to help EFL university professors realize the power of emotions. That is, it is hoped that the findings of this research can further the understanding of EFL university professors regarding the contributions of their emotions to teaching profession and learning how to manage their emotions.
Literature review
Emotion regulation in L2 education
Given that effective educational systems are made by successful teachers, factors contributing to their professional success should be carefully studied. To give an appropriate response to this necessity, different factors, such as personal factors (Derakhshan et al., 2020; Fathi et al., 2021a, b), interpersonal factors (Nayernia et al., 2020; Pishghadam et al., 2021), and emotional factors (Fan & Wang, 2022; Namaziandost et al., 2022) should be studied. Previous research has shown that there is a mutual relationship between teachers’ professional success and well-being (Fan & Wang, 2022; Wong & Zhang, 2014). As put forward by Garg and Rastogi (2009), well-being deals with the status in which teachers are happy and satisfied in the classrooms.
Tamir (2016) posits that individuals regulate their emotions to achieve different goals, such as instrumental goals (i.e., performance and social), epistemic goals (i.e., an individual’s sense of self), and hedonic goals (i.e., psychological health). Previous research has shown that teachers apply ER to achieve the same goals as they manage their classrooms for instrumental purposes (Hosotani & Imai-Matsumura, 2011; Sutton, 2004; Yin & Lee, 2012), take teaching responsibilities for epistemic purposes (Hagenauer & Volet, 2014; Hosotani & Imai-Matsumura, 2011; Sutton, 2004; Yin & Lee, 2012), and show their well-being for hedonic purposes (Han & Wang, 2021; Haeussler, 2013). So, when a teacher decides to show their happiness to students, they are likely to create a positive atmosphere in the classroom (instrumental), or consider it as part of their job to make students feel happy (epistemic), or to feel pleasant emotions (hedonic).
Teachers use different strategies to modify their emotions so that they can actualize the educational purposes. Different taxonomies have been proposed to explain and rationalize these strategies. Gross’s (1998, 2015) ‘Process Model of Emotion Regulation’ is one of the often-cited models which has received considerable attention in recent years (e.g., Haeussler 2013; Jiang et al., 2016; Sutton, 2004). The model’s strength lies in its comprehensiveness as it helps to delve into ER from both external (i.e., environmental) and internal (i.e., cognitive) perspectives. This model proposes that emotions emerge along a timeline. When an individual encounters an emotional situation, their attention is provoked and they try to evaluate the situation. In case the emotional situation is considered important, five different types of strategies, including situation regulation, situation modification, attentional deployment, cognitive change, and response modulation might be used to regulate that particular emotion. The situation selection refers to an individual’s decision to engage in the desirable emotions or avoid undesirable emotions. The situation modification deals with an individual’s attempt to modify the emotional impact of a situation. The attentional deployment is concerned with controlling the amount of attention to alter an emotional response. The cognitive change means an individual’s attempt to change the evaluation of a situation to affect it emotional influence. The response modulation is viewed as an individual’s engagement in a behavior to affect the generated emotion.
A more recent ER model which has specifically been developed and validated for L2 teachers belongs to Heydarnejad et al. (2021). It is called Language Teacher Emotion Regulation Inventory (LTERI) and involves 27 items. According to the Heydarnejad et al. (2021), LTERI “categorizes language teacher emotion regulation strategies into six dimensions, namely, situation selection, situation modification, attention deployment, reappraisal, suppression, and seeking social support” (p. 12). They took the first three dimensions of the model (i.e., situation selection, situation modification, and attention deployment) from Gross’s (1998, 2015) Process Model of Emotion Regulation. Their fundamental meanings were offered above. Reappraisal refers to a teacher’s attempt to redirect attention to more pleasant situations. Suppression deals with a teacher’s attempt to suppress unpleasant emotions. Reappraisal and suppression were taken from the study of Gross and John (2003). Finally, seeking social support deals with a teachers’ intention to share problems with colleagues (Jennings & Greenberg, 2009; Taxer & Gross, 2018).
Self-efficacy in L2 education
One of psycho-emotional constructs receiving huge attention over the last decades is self-efficacy. It is viewed as an individual’s self-perception about their ability in organizing and executing particular tasks to achieve specific goals (Bandura, 1977). Concerning teachers, it refers to “teachers’ beliefs about their personal capabilities to perform their duties in the classroom” (Klassen et al., 2010, p. 466). It seems that teachers with high self-efficacy believe more in themselves and their professional capabilities. The concept of teacher self-efficacy has been characterized by some features in the classroom context. It is related to teacher’s judgment of their ability in handling the classroom, encouraging and involving students, and employing instructional strategies (Sarfo et al., 2015; Tschannen-Moran et al., 1998).
As self-efficacy plays a pivotal role in actualizing educational objectives by teachers, a mass of studies has explored it across the globe (e.g., Atay, 2007; Wyatt & Dikilitas, 2021; Zonoubi et al., 2017). Previous studies fall into two main bodies of research. The first category includes external and internal variables influencing teachers’ self-efficacy. Some of these factors entail teaching experience (e.g., Hoang & Wyatt, 2021), proficiency level (e.g., Choi & Lee, 2016; Wyatt & Dikilitas, 2021), professional development (e.g., Cabaroglu, 2014; Karimi, 2011; Lee & Davis, 2020; Zonoubi et al., 2017), mode of instructional delivery (e.g., Kissau & Algozzine, 2015), and practicum (e.g., Atay, 2007). The second category deals with the correlation between teachers’ self-efficacy and other psycho-emotional constructs, like emotional intelligence (e.g., Kostic-Bobanovic, 2020; Rastegar & Memarpour, 2009), teacher identity (e.g., Moslemi & Habibi, 2019), occupational commitment (e.g., Gilbert et al., 2014), job satisfaction (e.g., Davaribina & Ghobadi Asl, 2021; Safari et al., 2020), and teacher burnout (e.g., Akbari & Tavassoli, 2011; Davaribina & Ghobadi Asl, 2021; Khani & Mirzaee, 2015).
Although previous research has inspected L2 teachers’ self-efficacy from different perspectives, its correlation with ER has been overlooked in this strand of research. This importance arises from the fact that if we have a robust understanding of the correlation between teachers’ ER and their self-efficacy, we can examine if self-efficacious teachers can regulate their emotions when they encounter an emotionally challenging situation. In this way, gaining insight into this relationship will help teacher educators and administrators alike to foster the self-confidence of teachers at a pedagogical level by raising teachers’ awareness of such situations and look for specific patterns at a theoretical level.
Work engagement in L2 education
Despite the fact that teaching is considered a demanding job (McIntyre et al., 2017), many teachers are so passionate about their profession that they have devoted their whole life to the act of teaching. This is termed WE and refers to the “positive, fulfilling and work-related state of mind that is characterized by vigor, dedication and absorption dimensions” (Schaufeli et al., 2002, p. 75; emphasis added). The first dimension, namely vigor, means “high levels of energy and mental resilience while working, the willingness to invest effort in one’s work, and persistence also in the face of difficulties”, while the second dimension, namely dedication, refers to “a sense of significance, enthusiasm, inspiration, pride, and challenge”, and the third dimension, namely absorption, deals with “being fully concentrated and happily engrossed in one’s work, whereby time passes quickly and one has difficulties with detaching oneself from work” (Hakanen et al., 2006, pp. 498–499). Another model considered as the theoretical foundations of this research posits that work-engagement includes four different kinds of engagement, including cognitive, emotional, social, physical (Klassen et al., 2013). Cognitive engagement refers to the level of focused intensity, engrossment, and concentration devoted by teachers to their job duties (Huang et al., 2022; Rothbard, 2001). Emotional engagement deals with the level of joy that teachers experience in doing job duties (Russell & Barrett, 1999). Social engagement points to the time and energy devoted by teachers to establish long-term, meaningful connections with colleagues and students (Klassen et al., 2013). Physical engagement represents the time and energy that teachers put into accomplishing job duties.
Owing to the fact that the teachers who are more engaged with their job duties are more interested in what they do and have a more positive attitude toward their job, recently researchers’ attention has been drawn to the factors which might affect teachers’ WE in L2 education (e.g., Amini Faskhodi & Siyyari, 2018; Bao et al., 2021; Fathi et al., 2021a, b; Han & Wang, 2021). While few studies have inspected the effects of diverse factors on teachers’ WE in L2 education, ER as an important variable has received scant attention. Taking a careful look at the literature reveals that only one empirical study has been conducted on the contributions of ER to predicting L2 teachers’ WE. In a cross-cultural study, Greenier et al. (2021) explored the contributions of ER and psychological well-being to Iranian and British L2 teachers’ WE. Employing a sequential explanatory mixed-methods approach, they first distributed questionnaires among 255 Iranian and 108 British language teachers, and then conducted interviews with 6 Iranian and 5 British language teachers. Their findings disclosed that both the participants’ WE was positively correlated with their ER and psychological well-being. In addition, as the correlation between psychological well-being and WE was stronger among the British teachers, they concluded that the cross-cultural differences should be given enough attention. To increase the credibility of these findings, this research aimed to disclose the contributions of EFL university professors’ ER and WE.
Anger in L2 education
Emotions have recently become a central focus in L2 education (Bigelow, 2019). There are good reasons for this “affective turn” (Pavlenko, 2013) due to the effects of L2 teachers’ emotions on L2 learners’ achievement (Golombek & Doran, 2014), their burnout (Khajavy et al., 2017), and attrition (Wolf & De Costa, 2017). Therefore, a mass of studies has focused on L2 teachers’ emotional experiences by investigating some of the most common emotions, such as anxiety (e.g., Alrabai, 2015; Merc, 2011; Song, 2018), stress (e.g., Bress, 2006), and frustration (e.g., Cowie, 2011; Morris & King, 2018). Those studies have generally investigated the sources of L2 teachers’ emotions and the factors shaping their construction and expression.
Anger is considered as an unpleasant emotion in educational contexts (Keller et al., 2014; Sutton, 2007; Sutton & Wheatley, 2003). It has been of particular interest in L2 education. For example, using an appraisal-theoretical framework, Khajavy et al. (2018) examined the antecedents of EFL teachers’ pleasant and unpleasant emotions, including anger. The results of the semi-structured interviews with 11 teachers evidenced that disciplinary issues, lack of student commitment to their learning, and explaining a topic to students several times were the primary antecedents of the participants’ pleasant and unpleasant emotions. Adopting a critical approach to analyzing teachers’ emotions, Alzaanin (2021) delved into nine female EFL university professors’ emotional experiences. The results revealed that the construction, expression, and communication of teachers’ emotions were largely affected by the kind of relationships in the classroom and the institutional system. Additionally, they found that as the participants felt disempowered during the students’ disruptive behaviors and were constrained by institutional policies, they felt more anger. Despite such attempts to shed more light on anger as an important and common emotion in L2 classrooms, it seems that more studies are needed to gain a deeper insight into this particular emotion. Thus, this research purported to examine if EFL university professors’ ER significantly contributed to relieving their anger.
Related studies in the literature
The contributions of ER to teachers’ well-being have been explored in a range of studies. To pave the ground for the present study, some of them are critically reviewed. In a study, the effects of emotion regulatory strategies on university professors’ frustration were investigated by Morris and King (2018). Their results indicated that using the emotion regulatory strategies was so beneficial to promote their confidence in taking control of the unpleasant situations in their workplace. Moreover, Taxer and Gross (2018) inspected the cause and effect of ER. They found that the participants’ who had instrumental and hedonic emotional regulation purposes could better take control of their students’ emotions and their own one. Furthermore, their findings evidenced that teachers’ views toward emotional display rules in the classroom, their views toward ER strategies and burnout feelings were significantly correlated. They uncovered that the participants’ views toward emotional display rules in the classroom were positively correlated with views toward ER strategies and burnout feelings. Likewise, Fathi and Derakhshan (2019) explored the impact of Iranian EFL teachers’ self-efficacy and ER on teaching stress. They found that the EFL teachers’ self-efficacy and ER significantly affected their teaching stress. Plus, Fathi et al. (2021a, b) used a structural model to disclose the correlations between Iranian EFL teachers’ reflection, self-efficacy, burnout, and ER. Overall, their findings unveiled that ER mediated the correlations between teachers’ reflection, self-efficacy, and burnout. Namaziandost et al. (2022) examined the correlation between Iranian EFL teachers’ reflective teaching, ER, and immunity, as well as the linkage between their ER and immunity. A strong positive correlation was uncovered between the participants’ reflective teaching, ER, and immunity. Additionally, it was found that the participants’ ER was a strong determinant of their immunity. Moreover, the contributions of critical thinking and ER to university professors’ immunity were investigated by Li et al. (2022). Their results revealed that the participants’ ER was highly correlated with their critical thinking. Furthermore, it was found that the participants’ immunity was a strong predictor of their ER. Finally, Deng et al. (2022) conducted a study to reveal if EFL teachers’ ER was significantly correlated with their WE, self-efficacy, and anger. They discovered that the participants’ ER was positively correlated with their WE and self-efficacy and negatively linked with their anger at the workplace.
As it may be implied from the above-alluded studies, the contributions of EFL university professors’ ER to self-efficacy, WE, and anger has been left disregarded in the Iranian higher education context. As the higher education context is quite unique in Iran, it is essential to examine if EFL university professors’ ER significantly contribute to their self-efficacy, WE, and anger. Therefore, this research was to inspect if Iranian EFL university professors’ ER substantially contributed to their self-efficacy, WE, and anger. To shed light on the possible relationships between the above-mentioned teacher attributed constructs (ER, self-efficacy, WE, and anger), a model was proposed in the current research (Fig. 1). Then, this proposed model was tested via Structural Equation Modeling (SEM) employing Linear Structural Relation (LISREL) 8.80. The following research question was put forward to meet these purposes:
RQ. Does EFL university professors’ ER significantly contribute to their self-efficacy, WE, and anger in the Iranian higher education context?
Consistent with the research question above, the null hypothesis below was formulated:
H01. EFL university professors’ ER does not significantly contribute to their self-efficacy, WE, and anger in the Iranian higher education context.
Fig. 1 Theoretical structural equation model
Theoretical model
This research rests on the premise that EFL university teachers’ ER contributes to their self-efficacy, WE, and anger. This is displayed in Fig. 1.
Method
Setting and participants
This research was conducted in Iranian state-run universities. The higher education system in Iran is administered through three kinds of universities: state-run, private (Azad), and distance-learning universities (Payame Noor). To study at state-run universities, candidates have to take a centralized examination (Kunkur) and gain a good rank. Studying at the state-run universities is free of charge for all students and they are directed and supervised by the Ministry of Science, Research and Technology. The university professors should be highly competent in terms of pedagogical and research issues to be accepted in the Iranian run-state universities.
The participants of this research consisted of 278 EFL university professors selected using a convenience sampling method. As stressed by Riazi (2016), it is a kind of non-probability sampling used to select a sample of participants for the population which is easy to reach. They included both males (n = 164) and females (n = 114), aged from 27 to 50 years old (M = 35.039, SD = 7.384), and their teaching experiences varied from 1 to 25 years (M = 9.082, SD = 7.322). They majored in English Teaching (n = 127), English Literature (n = 59), English Translation (n = 67), and also Linguistics (n = 25). To conduct this research, the researchers adopted a web-based platform started in March and ended in October 2021 to collect the required data. The researchers used it to send the questionnaires to the participants through Google Forms. It should be noted that the return rate was 71. 5% and no data were missed. Of particular note is that the electronic questionnaires were started with a written consent form. If they were willing to take part in the research, they had to sign the written consent to be directed to the questionnaires.
Instruments
The researchers used some instruments to gather the needed data. The first instrument included the Language Teacher Emotion Regulation Inventory (LTERI). It was designed and validated by Heydarnejad et al. (2021) and the researchers used it to measure the participants’ ER. The participants had to read a statement picturizing a situation which they may have encountered already at the workplace and rate the statements concerning their intended ER strategies. The instrument entailed 27 items on a five-point Likert scale, ranging from 1 (= never) to 5 (= always). It measures six factors, including situation selection (e.g., “I try to avoid discussing with troublesome parents”.), situation modification (e.g., “If my students make me angry in language classes, I try to advise them”.), attention deployment (e.g., “When I feel anxious in my language classes, I shift my attention to something pleasant”.), reappraisal (e.g., (“When I feel upset in my language classes, I redirect my attention to more pleasant matters”.), suppression (e.g., “If I feel anxious in my language classes, I try to suppress that”.), and seeking social support (e.g., “When I feel frustrated in my language classes, I share my troubles with my colleagues”.).
The second instrument adopted in this research was The Teachers’ Sense of Efficacy Scale (long form). It was designed and validated by Tschannen-Moran and Hoy (1998) and the researchers used it to gauge self-efficacy among the participants. It consists of 24 on a six-point Likert scale, ranging from 1 (= strongly disagree) to 9 (= strongly agree). It measures their kinds of efficacy, namely instructional strategies (“I know how to foster student creativity”.), students’ engagement (e.g., “I know how to craft good questions for my students”.), and classroom management (e.g., “I know how I should establish a classroom management system with each group of students”.).
The third instrument included the Engaged Teacher Scale (ETS). It was designed and validated by Klassen et al. (2013) and the researchers employed it to measure the participants’ WE. It comprises 16 items on a seven-point Likert scale 1 (= strongly disagree) to 7 (= strongly agree). It entails four factors representing the underlying dimensions of teachers’ WE: cognitive engagement (e.g., “While teaching, I get absorbed in my work”.), emotional engagement (e.g., “I really put my heart into teaching”.), social engagement: students (e.g., “I connect well with my students”.), as well as social engagement: colleagues (e.g., “I am accessible to my colleagues”.), and physical engagement (e.g., “I devote a lot of energy to teaching”.).
The last instrument was the Teacher Anger Scale. Designed and validated by Burić and Frenzel (2019), the researchers utilized it to measure the participants’ anger. It contains 16 items on a five-point Likert scale, ranging from 1 (= never) to 5 (= always). It assesses four dimensions, including: students-related (e.g., “The reactions of some students frustrate me so much that I would rather just quit the job”.), parents-related (e.g., “I feel resistance and anger with parents who overestimate their children’s real capabilities”.), colleagues-related (e.g., “I wish to yell when I just think about the improper behaviour of some colleagues”.), and system-related (e.g., “I get annoyed because educational regulations and laws are prescribed by people who have never worked in the school”.).
Prior to the main study, the researchers recruited an expert in translation to translate the questionnaires in the participants’ mother-tongue. Afterward, they administered them to a sample of 30 university professors to measure their reliability. The results of the internal-consistency calculated using Cronbach’s alpha yielded a range from 0.71 to 0.81 for the LTERI, from 0.74 to 0.86 for the TSES, from 0.71 to 0.82 for the ETS, and from 0.71 to 0.86 for the TAS, respectively. Then, using the experts’ judgment strategy, they invited two university professors majoring in Applied Linguistics to measure the validity of the instruments. After examining the instruments in terms of face and content validities, they affirmed that the instruments can be employed in the current study.
Data collection procedures
The researchers took some distinct steps to conduct this study. First, they recruited an expert translator to translate the questionnaires into Persian. Second, they administered them to a sample of 30 EFL university professors who were similar to the participants in the main study in terms of gender, major, and teaching experience to measure their reliability. Then, they invited two university professors at Applied Linguistics to check out if the instruments had the required validity. They offered some comments regarding the language and the content of the instruments. After applying the given comments by the researchers, the university professors approved that they enjoyed a high level of validity. Third, the researchers sent the questionnaires to the participants via Google Forms. The researchers were available on phone to respond to the participants’ questions concerning the content of the questionnaires. The participants’ responses were stored in a database.
Data analysis procedures
The researchers used different statistical procedures to analyze the collected data. They measured the reliability of the scales through Cronbach’s alpha formula. Furthermore, they assessed the normality distribution of the collected data via a Kolmogorov Smirnov Test. Having been assured of the normality assumption of the collected data, they analyzed them using a Confirmatory Factor Analysis (CFA) and a SEM using LISREL 8.80. An SEM model is built of sub-models, namely the measurement model and the structural model. The researchers used the measurement model to measure the correlations between the observed variables and latent variables. And, they used the structural model to gauge the correlations between the latent variables. Of particular note that the researchers validated the all latent variables using CFA prior to testing the structural model (Hair et al., 1998).
Results
In this section, the gained results are presented. Table 1 presents the calculated descriptive statistics gained for the participants’ emotion regulation, self-efficacy, WE, and anger.
Table 1 Results of descriptive statistics for the Iranian EFL university professors’ ER, self-efficacy, WE, and anger
Inventory Subscale N Min Max Mean Std. Deviation
LTERI Situation Selection 287 1.000 5.000 3.973 0.806
Situation Modification 278 2.000 4.490 3.744 0.746
Attention Deployment 278 2.000 4.560 3.861 0.917
Reappraisal 278 1.000 4.000 3.868 0.728
Suppression 278 2.000 5.000 2.974 0.616
Seeking Social Support 278 2.750 5.000 3.896 0.617
TSES Student Engagement 278 2.750 8.625 6.213 0.727
Instructional Strategies 278 3.875 9.000 6.290 0.962
Classroom Management 278 4.375 9.000 6.272 0.981
ETS Cognitive Engagement 278 3.750 7.000 5.396 0.587
Emotional Engagement 278 3.250 7.000 5.321 0.762
Social Engagement: Students
Social Engagement: Colleagues
278
278
3.500
2.000
7.000
7.000
5.260
4.733
0.657
0.948
TAS Students-Related 278 2.000 4.250 3.339 0.599
Parents-Related 278 1.000 5.000 2.719 0.825
Colleagues-Related 278 1.000 4.250 2.933 0.915
System-Related 278 1.000 4.250 2.538 0.949
As reported in Tables 1, concerning the dimensions of the participants’ ER, the situation selection (M = 3.973, SD = 0.806) and the seeking social support (M = 3.896, SD = 00.617) received the highest mean scores, while the suppression gained the lowest mean score (M = 2.974, SD = 0.616). Moreover, regarding the dimensions of self-efficacy, the instructional strategies gained the highest mean score (M = 6.290, SD = 0.962). Whereas the classroom the student engagement received the lowest mean score (M = 6.213, SD = 0.727). Additionally, considering teacher engagement, the mean score of cognitive engagement (M = 5.396, SD = 0.587) was the highest one among all the components. The mean scores of the subsequent sub-scales were as follows: the emotional engagement (M = 5.321, SD = 0.762), the social engagement: students (M = 5.260, SD = 0.657), and social engagement: colleagues (M = 4.733, SD = 0.948). Besides, regarding teacher anger’ subscales, student-related anger (M = 3.339, SD = 0.599) was the main cause of the EFL university professors’ anger at the workplace. Colleagues-related (M = 2.933, SD = 0.915), system-related (M = 2.538, SD = 2.538), and parents-related anger (M = 2.719, SD = 0.825) were the subsequent triggers of the EFL university professors’ anger at the workplace.
As mentioned above, the researchers used the Kolmogorov-Smirnov Test to examine the normality distribution of the collected data. The obtained results are reported in Table 2.
Table 2 The results of the Kolmogorov-Smirnov Test
Inventory Sub-scales Kolmogorov-Smirnov Z Asymp. Sig. (2-tailed)
LTERI Situation Selection 1.234 0.095
Situation Modification 0.946 0.333
Attention Deployment 0.831 0.495
Reappraisal 0.731 0.660
Suppression 1.352 0.060
Seeking Social Support 1.284 0.074
TSES Student Engagement 0.463 0.983
Instructional Strategies 0.967 0.308
Classroom Management 0.870 0.436
ETS Cognitive Engagement 1.177 0.125
Emotional Engagement 1.339 0.052
Social Engagement: Students 1.216 0.104
Social Engagement: Colleagues 1.275 0.077
TAS Students-related 0.858 0.453
Parents-related 1.181 0.123
Colleagues-related 1.220 0.102
System-related 0.869 0.436
As reported in Table 2, the collected data were normally distributed because the value of the obtained sigs for the different constructs and their sub-components were larger than the significance level (0.05). Thus, parametric methods for data screening can be applied. As the next step, the researchers employed a Pearson product-moment correlation to inspect the correlations among the participants’ ER, self-efficacy, WE, and anger.
Table 3 The correlation coefficients among the EFL university professors’ ER and self-efficacy, WE, and anger
LTERI student engagement instructional strategies classroom management cognitive engagement emotional engagement social engagement: students social engagement: colleagues students-related parents-related colleagues-related system-related
LTERI 1
student engagement 0.657** 1
instructional strategies 0.729** 0.677** 1
classroom management 0.511** 0.335** 0.659** 1
cognitive engagement 0.693** 0.372** 0.657** 0.585** 1
emotional engagement 0.725** 0.471** 0.227** 0.372** 0.449** 1
social engagement: students 0.530** 0.464** 0.368** 0.390** 0.434** 0.322** 1
social engagement: colleagues 0.468** 0.577** 0.475** 0.411** 0.380** 0.340** 0.745** 1
students-related - 0.508** - 0.513** -0.527** -0.491** -0.476* - 0.544** - 0.461** - 0.584** 1
parents-related - 0.427* - 0.485* - 0.383* -0.542** - 0.441** - 0.361** -0.337** -0.645** 0.507** 1
colleagues-related -0.448** - 0.393* -0.411** -0.255** - 0.292* - 0.252** - 0.307** - 0.509** 0.424** 0.562** 1
system-related - 0.361* - 0.378* -0.259* -0.514** - 0.431* - 0.333** -0.487* - 0.669** 0.548** 0.556** 0.425** 1
According to Table 3, the correlations among the LTERI and the student engagement (r = 0.657, p < 0.01), the instructional strategies (r = 0.729, p < 0.01), and the classroom management (r = 0.511, p < 0.01) were significant. Regarding the correlations among the LTERI and the teacher engagement, the results yielded cognitive engagement (r = 0.693, p < 0.01), the emotional engagement (r = 0.725, p < 0.01), the social engagement: students (r = 0.530, p < 0.01), and the social engagement: colleagues (r = 0.468, p < 0.01). Furthermore, the correlations among the LTERI and the sub-scales of the participants’ anger were significantly negative as the findings yielded: the students-related (r = -0.508, p < 0.01), the parents-related (r = -0.427, p < 0.05), the colleagues-related (r = -0.448, p < 0.01), and the system-related (r = -0.361, p < 0.05).
To gauge the structural relations, the researchers used the LISREL 8.80 statistical package to check the suggested model. The following fit indices were utilized to inspect the model fit: the chi-square magnitude, the RMSEA, the GFI, the NFI, and the CFI. As noted by Jöreskog (1990), “the chi-square should be non-significant, the chi-square/df ratio should be lower than 3, and the root mean square error of approximation (RMSEA) should be lower than 0.1” (p. 12). When the cut value is greater than 0.90 for NFI, GFI, and CFI, it indicates a good fit.
As presented in Table 4 (Model 1), the acceptable fit thresholds were reached because the value of chi-square/df ratio was (2.596) and the value of RMSEA was (0.076). Furthermore, as reported, the gained values for GFI (0.932), NFI (0.911), and CFI (0.952) reached the acceptable thresholds.
Table 4 The results of model fit indices (Model 1)
Fitting indexes χ2 df χ2/df RMSEA GFI NFI CFI
Cut value < 3 < 0.1 > 0.9 > 0.9 > 0.9
The first model 301.14 116 2.596 0.076 0.932 0.911 0.952
The researchers used the t-values and standardized estimates to inspect the strengths of the causal correlations among the variables. As displayed in Figs. 2 and 3, the participants’ ER significantly contributed to their self-efficacy (β = 0.58, t = 10.92) and WE (β = 0.71, t = 14.74) because the t-value was larger than 1.96. The participants’ ER was negatively correlated with their anger (β = − 0.44, t = -8.32).
Fig. 2 The schematic representation of path coefficient values for the relationship between LTERS, ETS, TSES, and TAS (Model 1)
Fig. 3 T values for path coefficient significance (Model 1)
Table 5 reports the criteria for fit indices in the model 2. The value of the chi-square/df ratio was (2.622) and the value of RMSEA was (0.076) which were found acceptable. The other three fit indices, GFI (0.934), NFI (0.952), and CFI (0.943) reached the acceptable fit thresholds.
Table 5 The results of model fit indices (Model 2)
Fitting indexes χ2 df χ2/df RMSEA GFI NFI CFI
Cut value < 3 < 0.1 > 0.9 > 0.9 > 0.9
The second model 4767.35 1818 2.622 0.076 0.934 0.952 0.943
As depicted in Figs. 4 and 5 (Model 2), the university professors’ ER significantly contributed to the all-sub-components of teacher self-efficacy as the findings indicated: the student engagement (β = 0.55, t = 10.40), the instructional strategies (β = 0.61, t = 13.19), the classroom management (β = 0.49, t = 10.15). Additionally, the contributions of the university professors’ ER to the sub-components of their WE were significant. The results indicated that the cognitive engagement (β = 0.56, t = 10.65), the emotional engagement (β = 0.69, t = 13.57), the social engagement: students (β = 0.47, t = 8.67), and the social engagement: colleagues (β = 0.36, t = 6.5). Furthermore, the significantly negative contributions of the university professors’ ER on the sub-components of their anger were revealed. The findings evidenced that the students-related (β = -0.42, t = -8.68), the parents-related (β = -0.31, t = -5.76), the colleagues-related (β = -0.34, t = -5.98), and the system-related (β = -0.28, t = -4.57).
Fig. 4 The schematic representation of path coefficient values for the relationship between LTERS and the sub-components of ETS, TSES, and TAS (Model 2)
Fig. 5 T values for path coefficient significance (Model 2)
Discussion
This research purported to disclose the contributions of EFL university professors’ ER to their self-efficacy, WE, and anger in the Iranian higher education context. The obtained results indicated that the participants’ ER could significantly contribute to their self-efficacy and WE. Additionally, the gained findings uncovered that the participants’ ER contributed negatively to their anger. Therefore, considering the gained findings, the null hypothesis of the present study, claiming that EFL university professors’ emotional regulation does not significantly contribute to their self-efficacy, WE, and anger in the Iranian higher education context was rejected. Given the gained findings of this research, it may be argued that the EFL university professors who cloud regulate their emotions might be able to improve their self-efficacy, engage in work duties, and take control of their anger.
A possible explanation for the obtained findings is that as the EFL university professors might use the ER strategies, they might have been able to manage their emotions effectively and take control of the unpleasant situation their classes. Put it in other words, along with the gained findings, it may be argued that the more EFL university professors might practice emotion regulation, the better they might have been able to modify and manage the emotional obligations. This capacity, in turn, might offer the self-measurement and self-evaluation of the EFL university professors’ emotional experiences and it might have given directions to the improvement of their self-efficacy, the increase of their WE, and the decrease of their anger. A part of the findings evidenced that a strong correlation existed between the EFL university professors’ ER and their self-efficacy. These findings lend support to the results of the previous studies disclosing that there was the intertwined relationship between teachers’ ER and their self-efficacy (Burić et al., 2017; Burić et al., 2020; Burić & Macuka, 2017; Chen & Cheng, 2021; Fan & Wang, 2022). Similarly, Burić and Moè (2020) found interrelationships of teachers’ self-efficacy, pleasant emotions, and well-being, which, in turn, affect their enthusiasm. Furthermore, the gained results are consistent with those of Chen (2018), revealing that teachers’ emotion could be predicted based on their self-efficacy.
The gained results also documented that the EFL university professors’ ER can be a strong predictor of their WE. Considering the obtained findings, it may be argued that, the participants might have used emotion-regulatory strategies to establish a balance in their professional lives. This, in turn, might have acted as a strong motive for the EFL university professors to be more enthusiastic and engaged in their job duties. Furthermore, the findings of this research indicated that ER could maximize the EFL university professors’ social engagement to be more in touch with colleagues and students. That is, ER could be a golden key for raising the EFL university professors’ social commitment and enhance their personal and job accomplishments. Put it differently, in line with the gained results, it may be argued that as the EFL university professors manage their emotions in unpleasant situations, they might have engaged in accomplishing their job duties. These results lend credence to those of the previous studies (e.g., Lazarides & Warner 2020; Topchyan & Woehler, 2020; Zeng et al., 2019), indicating that a strong positive correlation existed between teachers’ ER and WE at the workplace.
Moreover, the gained results evidenced the contributions of EFL university professors’ ER to their anger. In other words, the gained findings indicated that the contributions of the participants’ ER was negative. According to the gained findings, this argument can be made that the more the EFL university professors were armed with the emotion regulatory strategies, the better they might have managed their anger at the workplace. In other words, the results can be attributed to this view that the robust ER strategies might have empowered the EFL university professors to control their expressions of anger. Therefore, one of the overriding influences of ER might have been the efficient handling of job duties by the EFL university professors. Furthermore, given the obtained findings, this argument is made that the EFL university professors with high ER might be inclined toward playing safe and relinquish in the face of challenges and difficulties. The attained findings are in line with those of Namaziandost et al. (2022), revealing that the EFL teachers’ reflective teaching and ER and immunity were positively correlated. Additionally, consistent with the obtained findings, they found that the EFL teachers’ ER was a strong determinant of their immunity. Moreover, the gained results lend credence with those of Li et al. (2022), indicating that the participants’ ER was highly correlated with their critical thinking.
To recap the discussion, the EFL university professors might face diverse stimuli that trigger their feeling of anger at the workplace (i.e., students’ inattention or laziness, students’ misbehaviors, parents’ disrespectful behavior, uncooperative colleagues, (non)attainment of educational objectives, teachers’ burnout, lack of commitment, interference of parents, and dissatisfaction from the administrators to name a few) (Burić & Frenzel, 2019). More specifically, it may be argued that the sources of the participants’ anger might mushroom, especially during the COVID-19 pandemic with its extreme disruption of typical daily life and uncertainty for the future. In such a thorny situation, ER might have enhanced the EFL university professors to navigate the contingencies of the workplace and take control of them. At this time, EFL university professors need to heal the maladaptive anger, and aggression and this can be possible by practicing ER strategies (Burić et al., 2017; Chang & Taxer, 2020).
Conclusion
This research inspected the contributions of ER to EFL university professors’ self-efficacy, WE, and anger. The findings evidenced that ER substantially contributed to the participants’ self-efficacy, WE, and anger. The findings of this research indicated that if university professors, in general and EFL university professors, in particular are to be the backbone of the society and make their students ready for the future they will be able to regulate their emotions. In that case, they can improve their self-efficacy, promote their WE, and relieve their anger at the workplace. According to the gained findings, this conclusion can be made that ER should be considered as a crucial factor in the higher education contexts deserving enough attention.
Some stakeholders may benefit from the implications of the gained findings. First, educational officials of universities can be beneficiary of the gained findings to give particular attention to the psycho-emotional constructs, such as ER among university professors. For example, they can administer some tests to determine if university professors can regulate their emotions efficiently, and if not so, they can hold clinical psychological sessions to ameliorate this problem. Second, teacher-educators may benefit from the obtained findings to incorporate ER in their syllabi to make teacher-students familiar with it in their profession. Last but not least, the obtained results may be beneficial for university professors to be aware of the fact that if they aim to improve their self-efficacy, work-derangement, and anger, they have to regulate their emotions at the workplace.
A range of limitations imposed on this research which can be viewed as points of departure for further research in the future. As this research explored the contributions of EFL university teachers’ ER to their self-efficacy, WE, and anger, further experimental studies are needed to disclose how the instruction of ER strategies may affect EFL university professors’ self-efficacy, WE, and anger. Moreover, since a cross-sectional design was used in this research, a longitudinal design can be implemented to unveil the long-term contributions of ER to university professors’ self-efficacy, WE, and anger. Furthermore, because this research selected its participants from EFL university professors, more studies are needed to explore the contributions of ER to school teachers’ self-efficacy, WE, and anger. Finally, because this research adopted a quantitative design, future studies can use qualitative designs, such as observation and interviews to offer deeper insights into the issue.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Declarations
Ethics approval
Not applicable.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Informed consent
Not applicable.
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 0 | PMC9735219 | NO-CC CODE | 2022-12-14 23:29:53 | no | Curr Psychol. 2022 Dec 7;:1-15 | utf-8 | Curr Psychol | 2,022 | 10.1007/s12144-022-04041-7 | oa_other |
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Original Paper
Structural Landscape of nsp Coding Genomic Regions of SARS-CoV-2-ssRNA Genome: A Structural Genomics Approach Toward Identification of Druggable Genome, Ligand-Binding Pockets, and Structure-Based Druggability
http://orcid.org/0000-0002-3958-239X
Chakraborty Chiranjib [email protected]
1
Bhattacharya Manojit 2
Sharma Ashish Ranjan 3
Chatterjee Srijan 1
Agoramoorthy Govindasamy 4
Lee Sang-Soo 3
1 grid.502979.0 0000 0004 6087 8632 Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal 700126 India
2 grid.444315.3 0000 0000 9013 5080 Department of Zoology, Fakir Mohan University, Vyasa Vihar, Balasore, Odisha 756020 India
3 grid.464534.4 0000 0004 0647 1735 Institute for Skeletal Aging & Orthopaedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, Gangwon-do 24252 Republic of Korea
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SARS-CoV-2 has a single-stranded RNA genome (+ssRNA), and synthesizes structural and non-structural proteins (nsps). All 16 nsp are synthesized from the ORF1a, and ORF1b regions associated with different life cycle preprocesses, including replication. The regions of ORF1a synthesizes nsp1 to 11, and ORF1b synthesizes nsp12 to 16. In this paper, we have predicted the secondary structure conformations, entropy & mountain plots, RNA secondary structure in a linear fashion, and 3D structure of nsp coding genes of the SARS-CoV-2 genome. We have also analyzed the A, T, G, C, A+T, and G+C contents, GC-profiling of these genes, showing the range of the GC content from 34.23 to 48.52%. We have observed that the GC-profile value of the nsp coding genomic regions was less (about 0.375) compared to the whole genome (about 0.38). Additionally, druggable pockets were identified from the secondary structure-guided 3D structural conformations. For secondary structure generation of all the nsp coding genes (nsp 1-16), we used a recent algorithm-based tool (deep learning-based) along with the conventional algorithms (centroid and MFE-based) to develop secondary structural conformations, and we found stem-loop, multi-branch loop, pseudoknot, and the bulge structural components, etc. The 3D model shows bound and unbound forms, branched structures, duplex structures, three-way junctions, four-way junctions, etc. Finally, we identified binding pockets of nsp coding genes which will help as a fundamental resource for future researchers to develop RNA-targeted therapeutics using the druggable genome.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12033-022-00605-x.
Keywords
Nsp
RNA secondary structure
3D model
SARS-CoV-2
Drug binding pocket
==== Body
pmcIntroduction
SARS-CoV-2 is an RNA virus of the Coronaviridae family, which is the causative pathogen of the current pandemic. The virus contains a single-stranded RNA (ssRNA) genome [1, 2] with approximately ~30 kb genomes that comprise one of the largest RNA among entire families of RNA viruses. The genome contains positive sense RNA, which includes several significant structural parts of the genome, such as 5′ cap structure and 3′ poly(A) tail [3, 4]. Moreover, the genome structure encodes about twenty-nine proteins [5]. Several researchers have tried to illustrate the genome structure. Manfredonia and Incarnato attempted to provide an insight view of the SARS-CoV-2 genome structure to offer strategies for developing new therapeutics. In this direction, they have illustrated different genome structural elements such as 5′ UTR structure, ribosomal FSE (frameshifting element), 3′ UTR structure [6]. Similarly, several structural elements were projected from the SARS-CoV-2 RNA genome, and in vivo structural characterization was performed for the genome. They have identified that 42 host proteins can interact with the different elements that were projected from the SARS-CoV-2 RNA. It might be helpful in developing new therapeutics against the virus [4]. Similarly, Cao et al. have developed the genome architecture of the SARS-CoV-2 RNA. The researchers have tried to understand the packing of the SARS-CoV-2 genome based on the RNA secondary structure. The study tried to comprehend the framework of the genome for the structure, function, and dynamics of the virus. Finally, they tried to design the siRNA for RNA-based drugs [7].
The large-scale characterization of RNA secondary structure might provide insight into the SARS-CoV-2 genome-wide organization. Simmonds illustrated a SARS-CoV-2 genome organization through RNA secondary structure and compared it with other Coronaviruses [8]. Several studies describe the significance of RNA secondary structures in the light of virus replication and their transcription and translation [9–11]. The genome of SARS-CoV-2 encodes two types of proteins: structural and non-structural proteins (nsps) (Fig. 1a). nsps are significant proteins that help the fundamental process of viruses such as transcription, envelope proteins production, and viral replication [12, 13]. All these NSPs support the RNA-dependent RNA polymerase (RdRp) to perform replication. Therefore, they act as replication machinery [14]. Scientists have used non-structural proteins (nsps) as drug targets [15]. NSP coding genes of SARS-CoV-2 are significant in this point of view. It has been noted that two open reading frames (ORF1a and ORF1b) are associated with the coding of 16 NSPs which are nsp1 to nsp16 (Fig. 1a) [16, 17]. ORF1a codes nsp1 to nsp11, and ORF1b codes nsp12 to nsp16 protein. The main protein includes nsp3 (papain-like proteinase protein), nsp5 (3C-like proteinase), nsp12 (RNA-dependent RNA polymerase, RdRp), nsp13 (helicase, HEL), NSP14 (exoRNAse), nsp15 (endoRNAse), nsp16 (2′-O-Ribose-Methyltransferase), and other non-structural proteins. Other significant nsp are nsp7 (cofactor for RNA-dependent RNA polymerase), nsp8 (cofactor for RdRp, primase, or 3′-terminal adenylyltransferase) [18]. Most of the research work has been performed to illustrate the structural and functional perspective of nsps (nsp1–16). However, less evidence illustrates insight into the nsp coding of genes (ORF1a and ORF1b) and their genomic structural arrangements. Therefore, it is urgent to understand the structural insight of the nsp coding genomic regions (ORF1a and ORF1b) and their structure-based genomic arrangements.Fig. 1 Schematic representation shows the single-stranded RNA (ssRNA) genome of SARS-CoV-2 and methodology flowchart of our study. a SARS-CoV-2 ssRNA genome contains non-structural protein-coding genes (nsp) (nsp1–to 16) and structural protein-coding genes. The nsp coding genes synthesized by ORF1a and ORF1b. ORF1a contains nsp1-to 11 protein-coding genes. ORF1b contains nsp12-to 16 protein-coding genes. b Schematic diagram shows a flowchart of the methodology of our work
RNA structure, both secondary and tertiary, plays critical functional roles in the life cycles of SARS-CoV-2. Using 3D structure, researchers are analyzing components of the structure that can help the structure-based drug discovery for this virus. Very few scientists have tried to illustrate the structure of the RNA genome of SARS-CoV-2. Rangan et al. have assessed RNA sequence conservation of the SARS-CoV-2 genome and found 106 RNA-based conserved regions that act as potential antiviral drug targets [19]. Romano et al. tried to understand the RNA structural-based replication machinery, where they found the interaction between the NSPs [20]. Sun et al. have analyzed RNA secondary structural elements of the SARS-CoV-2 RNA genome that plays a crucial role in viral infection. Their research might help to assess the antisense oligonucleotides targeting using RNA-based structural elements and will help in the therapeutics development against this virus [4]. Some scientists have contributed to identifying the RNA structure-based elements that can help therapeutic development. For example, Manfredonia et al. mapped the RNA structures throughout the SARS-CoV-2 genome. The RNA elements were identified from the genome. The secondary structure patterns have been generated to illustrate the SARS-CoV-2 genome. They have modeled the 3D structure of the RNA, which can help RNA-based therapeutic innovation [21]. However, the secondary and 3D structural RNA conformations of the nsp genes, their druggable genome, and the RNA-based therapeutic target in the virus genome are mostly unexplored. Therefore it is necessary to understand the in-depth analyses of the secondary, 3D RNA structural conformations of the SARS-CoV-2 genomes and the fundamental units of the druggable genome which can initiate the RNA targeting drug discovery against the virus.
In our work, we have tried to evaluate the secondary structure conformations, entropy and mountain plots, RNA secondary structure in a linear fashion, and 3D structure of NSP coding genes of the RNA genome of the SARS-CoV-2. We have predicted recent algorithms-based (deep learning-based) secondary structures, conventional algorithms-based (centroid and MFE-based) secondary structural conformations, entropy & mountain plots based on the secondary structures, single & overlapping structures of arc diagrams in a linear fashion of all the nsp coding genomic regions (nsp1–16). Finally, RNA 3D structural models have been predicted from those secondary structural conformations. Additionally, we have also analyzed the A, T, G, C, and A+T, G+C content, and GC-profiling to understand the GC content of all NSP coding genes. Finally, we have identified the secondary structure-guided druggable pockets (ligand binding sites) in RNA 3D structures conformation.
Method
Our analysis has been divided into three parts: secondary structure conformations analysis, 3D analysis, and the stability of the nsp coding genomic regions (nsp1–16). Several recent methods and current algorithms were used to analyze the RNA secondary structure, 3D structure, and stability of this genomic region.
Retrieval of the Genomic Sequence nsp Coding Genes of the SARS-CoV-2 Genome
We have retrieved the SARS-CoV-2 genome sequence and their nsp coding genes from NCBI (NCBI GenBank Id: MZ054889.1). The nsp coding genes and corresponding sequences’ position have been listed in Table 1. The nsp coding gene sequences (nsp1–16) were used for further analysis.Table 1. Different nsp coding gens and their position (nucleotide in bp) in the SARS-CoV-2-ssRNA genome
Sl. No. Gene Coded protein Position (in bp)
1. nsp1 – 234-773
2. nsp2 – 774-2687
3. nsp3 Papain-like proteinase 2688-8522
4. nsp4 – 8523-10022
5. nsp5 3C-like proteinase 10023-10940
6. nsp6 – 10941-11810
7. nsp7 Cofactor for RNA-dependent RNA polymerase (RdRp) 11811-12059
8. nsp8 Cofactor for RdRp, primase, or 3′-terminal adenylyltransferase 12060-12653
9. nsp9 – 12654-12992
10. nsp10 – 12993-13409
11. nsp11 – 13410-13448
12. nsp12 RNA-dependent RNA polymerase 13410-16204
13. nsp13 Helicase 16205-18007
14. nsp14 3′-to-5′ exonuclease 18008-19588
15. nsp15 EndoRNAse 19589-20626
16. nsp16 2′-O-ribose methyltransferase 20627-21520
Secondary Structure Conformations Analysis
Deep Learning (DL) Based Secondary Structure Conformations Analysis
DL is an emerging approach exploring researchers in structural analysis from nucleic acids to proteins. We have used DL-based UFold server to analyze the DL-based secondary structure of RNA [22]. Using an encoder-decoder architecture, this server uses FCNs (Fully Convolutional Networks) to create fast and efficient RNA secondary structure. It uses the U-Net model for structure generation. The 17×L×L tensor is used as input for the U-Net model. The model predicted a score matrix Y that uses an L×L symmetric score for output through the contact map. In the case of traditional RNA secondary structure prediction methods, algorithms are mainly based on thermodynamic models through free energy minimization, which executes strong prior assumptions and slow speed to run. The UFold server proposes a deep learning-based method for the prediction of RNA secondary structure based directly on annotated data and nucleotide base-pairing rules. This approach might be more acceptable for computationally predicting the secondary structure of RNA [22].
Centroid-Based Secondary Structure Conformations Analysis
Another secondary structure conformation was predicted for the nsp coding genes based on centroid structure, used with minimum base-pair distance. Centroid-based secondary structures were predicted using an RNA sever (Vienna RNA website) [23]. From diverse types of structural RNAs, the centroid structure of RNA ensemble makes a 30.0% lesser prediction error which is measured by the positive predictive value. Moreover, it predicted the unavailable complete model that apparently comprises the unique native structure of studied RNA [24].
MFE-Based Secondary Structure Conformations Analysis
MFE-based secondary structures were generated for the nsp coding genomic regions. This structure was predicted by MFE-based secondary structure, utilizing a minimum of free energy. MFE structure was predicted using the Vienna RNA Website Server [23]. The server uses optimal computer folding employing external bases, the loop-based energy model unique decomposed loops. For predicting the MFE structure, alternatively, the RNA native structure of a given sequence is generated for each admissible base pair (isolated base pairs and stacking base pairs). The energetically best structure contains that base pair in the context of a minimum free energy landscape [25].
Entropy & Mountain Plots Analysis Based on the Secondary Structures
Entropy & mountain plots were generated based on the secondary structures. Entropy plots represent the thermodynamic assembly of a RNA secondary structure and the positional entropy of a RNA secondary structure. Entropy plots were predicted using the Vienna RNA website server [23]. The entropy and mountain plot are exclusively useful for long nucleotide sequences where conventional structure illustrations become a disorder. It is an axis (xy-diagram) oriented plotting, where the number of base pairs circling a sequence position versus the nucleotide position. The sets of computer program transforms a dot plot into the mountain plot coordinates which the graphical user interface can visualize. The resulting plot displays three significant curves, two mountain plots derived from the MFE structure (red), a positional entropy curve (green), and the pairing probabilities (black) [25].
Mountain plots were generated using the same server. It represents the secondary structure through a height and informs us of the positional height of an RNA secondary structure. The height m(k) is allotted by the number of base pairs included in the base at position k.
Arc Diagrams to Understand the Secondary Structure Conformations Linearly Both in a Single Manner, Overlapping Manner, and Trans-RNA–RNA Interactions
The Arc diagrams have been developed through the R-chie server [26]. Arc diagrams were used to describe the secondary structure conformations linearly, both in a single & overlapping manner. To develop the Arc diagrams, the server used the helix prediction method TRANSAT (TRANSAT algorithm), which is visualized through the R package and graphically represented through the line diagram using the package (R4RNA). Finally, the result will help us to understand trans-RNA–RNA interactions. Using the server, we have illustrated the trans-RNA–RNA interactions [27].
3D Structural Conformation Analysis
3D Structural Conformation Based on Line Chain Model And Wire Model
Predicting the 3D structure of RNA and its proper understanding remains a major challenge. The 3D structure can help components of RNA structures and assist in positioning the helical regions of RNA. 3D structure conformation of nsp coding genomic regions (nsp1–16) was developed by RNAComposer [28, 29]. Here we developed two types of 3D models: the line chain 3D model and the wire 3D model. The RNAComposer server is a user-friendly and freely accessible server target for the 3D structure prediction of RNA (up to 500 nucleotides). It employs fully automated fragment assembly-based methods on the RNA secondary structure detailed by the user. Presently, such novel computational methods based on the incorporation of distance restraints resultant strategies are emerging in the field of computational biology [29].
Identification of Druggable Pockets (Ligand Binding Sites) in RNA 3D Structures Conformation and Its Comparison with the Secondary Structure
The identification of druggable pockets is an interesting area of structure-based drug design [30]. Identification of druggable pockets in RNA 3D structural conformation in the nsp coding genes using Voronoia 4-ever server [31]. The server calculates ligand-binding pockets, solvent-free surfaces, packing defects, etc. It also calculates the packing density for every atom packing density is denoted by PD, which is calculated using the following formula:PD = VvdW/VvdW+ Vse
Here, using the Voronoi cell method, VvdW is the volume allocated to each atom, which is just inside the vdW field of the atom. Here, Vse is defined as the remaining volume, and it is excluded from the solvent.
GC Content and GC-Profile Analysis Throughout the nsp Coding Genome
Stability Analysis Through A, T, G, C, and A+T, G+C Content
Scientists have tried to analyze the GC-rich region of the genome of the virus [32]. It can help to understand the GC content bias regions. We used the GC content calculator and calculated A, T, G, C, and A+T, G+C content of the nsp coding genomic regions (nsp1–16) SARS-CoV-2 genome using the retrieved genome sequence.
GC-Profiling to Understand the Content
We have analyzed GC-profiling of the whole genome of SARS-CoV-2 through a GC-profiling plot through the GC-Profile server. We have evaluated GC-profiling of the nsp coding genomic regions of the virus through GC-profiling plot through the GC-Profile server and finally compared the GC-profile of both the regions (the nsp coding genomic regions and whole genome). GC-Profile server uses a segmentation algorithm to estimate the GC-Profile. In the segmentation algorithm, the genome order index is calculated, which is denoted as S. The S is defined as follows:S≡SP= a2+ c2+ g2+ t2
GC-Profile is a web-based, interactive software system mainly used to analyze eukaryotic and prokaryotic genomes. It offers a qualitative as well as a quantitative view of organism genome organization. Server-based results also reproduce the relationships among the G+C content and other significant genomic landscapes, e.g., distributions of CpG islands and genes, which are also analyzed comprehensibly. This proved that GC-profile is an appropriate early point for analyzing the isochore structure of higher eukaryotic genomes and identifying genomic islands in prokaryotic genomes [33].
Finally, the server presented a cumulative GC-profile of the genome or the nsp coding genomic regions.
The entire methodology of our work has been described through a flowchart (Fig. 1b).
Result
Secondary Structure Conformations
Deep Learning (DL)-Based Secondary Structure Conformations
Deep learning (DL)-based secondary structures were developed coding regions of the different nsp (nsp1–16) of the SARS-CoV-2 genome. It illustrated the DL-based secondary structures ORF1a and ORF1b regions. The DL-based secondary structures of ORF1a were illustrated through the coding genomic regions of nsp1-11 (Fig. 2A1–A11). Similarly, DL-based secondary structures of ORF1b were illustrated through the coding genomic regions of nsp12-16 (Fig. 2B1–B5). The nsp1 coding region shows more than 14 internal loops. We also found 2 to 3 larger internal loops (Fig. 2A1). In this region, long stems are found compared to other regions. Similarly, the nsp2 coding region shows more than 14 internal loops (Fig. 2A2). We also found 2 to 3 large internal loops. The bulge loop, multi-branched, stem, hairpin loop, and internal loop were also noticed in this region. Similarly, the nsp3 coding region shows more number of multi-branched loops. We also found the bulge loop, stem, hairpin loop, and internal loop in this region (Fig. 2A3). The nsp4 coding region illustrates three larger multi-branched loops and several small multi-branched loops (Fig. 2A4). Again, the nsp5 coding region illustrates one larger multi-branched loop in conjunction with several small multi-branched loops (Fig. 2A5). nsp6 coding region illustrates one larger multi-branched loop.along with four medium-sized multi-branched loops other several small multi-branched loops (Fig. 2A6). Also, we found one larger multi-branched loop.along with two medium-sized multi-branched loops in the nsp7 coding region (Fig. 2A7). In the nsp8 coding region, a large multi-branched loop along with a bulge loop, stem, hairpin loop, and internal loop was noted (Fig. 2A8). Similarly, in the nsp9 coding region, we found one larger multi-branched loop along with a bulge loop, stem, hairpin loop, and internal loop (Fig. 2A9). In the nsp10 coding region, we found bigger multi-branched loops which the structure complex (Fig. 2A10). However, the nsp11 coding region’s structure is simpler than other regions that show a bulge loop, internal loop, and stem (Fig. 2A11). In the ORF1b regions contain, nsp12 coding region is more complex compared to other regions where we noted three multi-branched loops (Fig. 2B1). Similarly, in the nsp13 coding region, we found several internal loops along with multi-branched loops (Fig. 2B2). Again, the nsp14 coding region shows five multi-branched loops along with a bulge loop, hairpin loop, and internal loop (Fig. 2B3). Similarly, the nsp15 coding region shows three multi-branched loops along with other structures such as the bulge loop, hairpin loop, and internal loop (Fig. 2B4). Finally, we found two multi-branched loops along with other structures, such as the internal loop, hairpin loop, and the bulge in the nsp15 coding region (Fig. 2B5).Fig. 2 RNA secondary structure model predicted by deep learning (DL) of all nsp coding regions (nsp1–nsp16) which shows the different components of the structure such as stem-loop (SL), multi-branch loop, pseudoknot, and bulge etc. A1 Secondary structure conformations of nsp1 coding gene and their components. A2 Secondary structure conformations of nsp2 coding gene and their components. A3 Secondary structure conformations of nsp3 coding gene. A4 Secondary structure conformations of nsp4 coding gene and their components. A5 Secondary structure conformations of nsp5 coding gene and their components. A6 Secondary structure conformations of nsp6 coding gene and their components. A7 Secondary structure conformations of nsp7 coding gene and their components. A8 Secondary structure conformations of nsp8 coding gene and their components. A9 Secondary structure conformations of nsp9 coding gene and their components. A10 Secondary structure conformations of nsp10 coding gene and their components. A11 Secondary structure conformations of nsp11 coding gene and their components. B1 Secondary structure conformations of nsp12 coding gene and their components. B2 Secondary structure conformations of nsp13 coding gene and their components. B3 Secondary structure conformations of nsp14 coding gene and their components. B4 Secondary structure conformations of nsp15 coding gene. B5 Secondary structure conformations of nsp16 coding gene and their components
Centroid-Based Secondary Structure Conformations
Like the DL-based secondary structures, we also developed centroid-based secondary structure conformations of coding regions for the nsps (nsp1–16) of the SARS-CoV-2 genome. We developed centroid-based secondary structures of ORF1a, which were illustrated through the coding genomic regions of nsp1-11 (Fig. S1A1–A11). Similarly, the centroid-based secondary structures of ORF1b were demonstrated through the coding genomic regions of the nsp12-16 (Fig. S1B1–B5). In both cases (ORF1a and ORF1b), the structure of the coding genomic regions of the nsp1-16 are more simple compared to DL-based secondary structures. The nsp1 shows three multi-branched loop structures (Fig. S1A1). Similarly, nsp2 shows three multi-branched loop structures (Fig. S1A2). Likewise, nsp3 shows a linear-type structure, and several stem and loop structures have been generated from the linear structure (Fig. S1A3). Similarly, in the nsp4, three multi-branched loops with a bigger loop structure are noted (Fig. S1A4). In the nsp5, five to six multi-branched loops are observed with a different bulge. We also found hairpin loops and internal loops in the structure (Fig. S1A5). In the nsp6, a major multi-branched loop is observed (Fig. S1A6). Similarly, in the nsp7, two major multi-branched loops are observed (Fig. S1A7). Also, in the nsp8, we noted three major multi-branched loops along with several hairpin loops and internal loops in the entire structure (Fig. S1A8). Likewise, in the nsp9, two major multi-branched loops are noted, and one structure is noted with a bulge (Fig. S1A9). At the same time, several stems, hairpin loops, and internal loops were found in the nsp10 in conjunction with two multi-branched loops (Fig. S1A10). The nsp11 coding region formed a small structure due to its small sequence length (Fig. S1A11). Likewise, in the nsp12, about nine multi-branched loops are noted in the structure of the region. We also found several hairpin loops and internal loops in this region (Fig. S1B1). Similarly, two significant multi-branched loops are noted, which are associated together in the nsp13 (Fig. S1B2). The nsp14 developed a linear-type structure with six multi-branched loops (Fig. S1B3). Likewise, nsp15 contains four multi-branched loops, and the middle multi-branched loop encloses two major bulge structures (Fig. S1B4). Finally, it has been noted that nsp16 formed two multi-branched loops, and the last multi-branched loop encloses one major bulge structure. The first one contains several stems, loops, and hairpin structures (Fig. S1B5).
MFE-Based Secondary Structure Conformations
Like the DL-based and centroid-based secondary structures, we also developed MFE-based conformations of coding regions of the nsps (nsp1–16) of the genome of the virus. We developed MFE-based secondary structures of ORF1a with the coding genomic regions of nsp1-11 (Fig. S2A1–A11). Likewise, the ORF1b was demonstrated through the MFE-based conformations of the coding genomic regions of the nsp12-16 (Fig. S2B1–B5). The nsp1 shows two main multi-branched loops (Fig. S2A1). Similarly, nsp2 shows six multi-branched loop structures (Fig. S2A2). The nsp3 depicts a linear-type structure with several stems and loop structures (Fig. S2A3). This MFE-based secondary of nsp3 is similar to the centroid-based secondary structure. Similarly, It has been noted aboutgenome identifies host proteins vulnerable five multi-branched loops in the nsp4 (Fig. S2A4). Five to six multi-branched loops are observed, a similar type of centroid-based secondary structure (Fig. S2A5). In the nsp6, we have also observed five to six multi-branched loops (Fig. S2A6). Likewise, in the nsp7, one major multi-branched loop is observed. We noted the bulge in the structure (Fig. S2A7). Similarly, in the nsp8, we noted three major multi-branched loops with different components of RNA secondary structure. We noted several structural components (stem, loops, hairpin loop) in the first and last multi-branched structure (Fig S2A8). At the same time, two major multi-branched loops are noted in the nsp9, and the last structure is noted with different structural components (Fig. S2A9). At the same time, we found two multi-branched loops in the nsp10 (Fig. 4A10). Similarly, we found a linear structure that contains about eight multi-branched loops in the structure of the region (Fig. S2B1). In the same way, we found a linear structure of the nsp13 (Fig. S2B2). At the same time, we noted that nsp14 had created a linear-type structure with five multi-branched loops (Fig. S2B3). It has been noted that nsp15 contains about three multi-branched loops, and the middle and last multi-branched loop encloses several stems, loops, and hairpin loop structures (Fig. S2B4). At last, we found that nsp16 formed two multi-branched loops, and the multi-branched loop contained several stems, loops, and hairpin structures (Fig. S2B5).
Entropy and Mountain Plots Based on The Secondary Structures
We depicted the entropy and mountain plots of all nsp coding regions (Fig. S3A1–A11, B1–B5). The nsp1 shows entropy and mountain plots. Maximum entropy exhibited 2.0 (in between 300 and 500 locations), and the height is about 40 in the region of nsp1 (Fig. S3A1). Similarly, nsp2 shows.maximum entropy of 2.0 in between the 1 to 500 location, and the height is about 100 (Fig. S3A2). The nsp3 illustrates a maximum entropy of 2.0 (in between 1 and 1000 locations) and a maximum height of 200 (Fig. S3A3). Similarly, in the nsp12, we noted the energy peaks with a value of 3 (between 1000–1500 and 2000–2500 locations). We noted several energy peaks in those regions. The mountain plot shows a maximum height of about 120, located in the first part (Fig. S3B1). In the region of nsp15, we noted maximum entropy, and it was exhibited at 3.0 (near about 1000 location), and the height of the mountain plots is about 60 to 90 (Fig. S3B4). Again, in the region of nsp16, we noted maximum entropy, and it was exhibited 2.0 to 2.5 (in between 200–400 location, and near about 600) and the height of the mountain plots is about 40 to 60 (Fig. S3B5).
Arc Diagrams of the Secondary Structure Conformations Linearly Both in the Single Manner, Overlapping Manner, and Trans-RNA–RNA Interactions
The arc diagram illustrates the probable base pair of the RNA structure which connects the relevant RNA sequence to the secondary structure. It is depicted as a horizontal line from left to right (5′ to 3′ ends).
We depicted the Arc diagrams of the secondary structure conformations linearly both in the single and overlapping manner for all nsp coding regions (nsp1–16) (Fig. 3A1–A11, B1–B5). Relating to the TRANSAT algorithm, the nsp1 coding region shows a high base paring with a value of [1e-06, 1e-05] in the case of a single line. Similarly, it also shows the high possibility of base pairing in the case of an overlapping manner. More linear arc structures were found in the coding region of nsp1, nsp3, nsp4, nsp7, nsp9, nsp10 in the ORF1a (Fig. 3A1, A3, A4, A7, A9, A10). Similarly, we found more linear arc structures in nsp12 and nsp15 in the ORF1b (Fig. 3B1, B4). It has been noted that the coding region of nsp7 developed denser linear arc structures in both cases of single, overlapping fashion among all of the nsps of ORF1b and ORF1b.Fig. 3 Arc diagrams of the secondary structure conformations linearly both in the single manner, overlapping manner of all nsp coding regions (nsp1–nsp16). A1 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp1 coding gene. A2 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp2 coding gene. A3 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp3 coding gene. A4 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp4 coding gene. A5 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp5 coding gene. A6 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp6 coding gene. A7 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp7 coding gene. A8 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp8 coding gene. A9 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp9 coding gene. A10 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp10 coding gene. A11 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp11 coding gene. B1 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp12 coding gene. B2 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp13 coding gene. B3 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp14 coding gene. B4 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp15 coding gene. B5 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp16 coding gene
3D Structural Conformation Analysis
3D structural Conformation Based on Line Chain Model and Wire Model
We developed the 3D model of the secondary structure to understand the folding for all the nsp coding regions (nsp1–16) (Fig. 4A1–A11, B1–B5). We have understood the proper folding of the RNA structure in 3D structure space. Here we have identified the stem and loop structure in the line chain and wire model for all the nsp coding regions. In the ORF1a region, it has been found that the nsp7 coding region contains more stem structures (Fig. 4A7). At the same time, in ORF1b regions, we found that the nsp13 coding region contains more stem structures (Fig. 4B2).Fig. 4. 3D model of the RNA of nsp coding regions (nsp1–nsp16) shows the different structural components in the line chain model and wire model. A1 3D model (line chain and wire model) of nsp1 coding gene. A2 3D model of nsp2 coding gene. A3 3D model (line chain and wire model) of nsp3 coding gene. A4 3D model (line chain and wire model) of nsp4 coding gene. A5 3D model (line chain and wire model) of nsp5 coding gene. A6 3D model of nsp6 coding gene. A7 3D model (line chain and wire model) of nsp7 coding gene. A8 3D model (line chain and wire model) of nsp8 coding gene. A9 3D model (line chain and wire model) of nsp9 coding gene. A10 3D model (line chain and wire model) of nsp10 coding gene. A11 3D model (line chain and wire model) of nsp11 coding gene. B1 3D model (line chain and wire model) of nsp12 coding gene. B2 3D model (line chain and wire model) of nsp13 coding gene. B3 3D model (line chain and wire model) of nsp14 coding gene. B4 3D model (line chain and wire model) of nsp15 coding gene. B5 3D model of nsp16 coding gene
Presently, understanding the sequence-related RNA helix conformation is an interesting area. Researchers are also trying to understand the RNA helices pattern of the 3D model of RNA structure [34]. Several scientists are trying to assess the bound and unbound form in the RNA 3D model [35]. RNA 3D model of different bound and unbound forms has been shown in the case of base pairing within RNA helices of this conformation. We have also understood the packing of RNA in 3D conformation. Here, we identified the duplex, branched structure, three-way junction, and four-way junction all the nsp coding regions (nsp1–16).
Identification of Druggable Pockets (Ligand Binding Sites) in RNA 3D Structures Conformation and Its Comparison with the Secondary Structure
Finally, we identified the drug-binding pocket of all the nsp coding regions (nsp1–16). Here, we have represented the three nsp coding structures (nsp7, nsp12, and nsp13) (Fig. 5a–c). In all cases, we have shown two drug-binding pockets in each RNA 3D structures conformation. Each drug-binding pocket in each RNA 3D structure has been compared with the secondary structure of RNA predicted from the nsp coding structures.Fig. 5 Identified ligand-binding pocket in RNA 3D structures (nsp coding) conformation guided with the secondary structure. a Identified ligand-binding pocket in nsp7 coding RNA 3D structures conformation guided with the secondary structure. b Identified ligand-binding pocket in nsp12 coding RNA 3D structures conformation guided with the secondary structure. c Identified ligand-binding pocket in nsp13 coding RNA 3D structures conformation guided with the secondary structure. In every case, we have shown two binding pockets
These three nsp regions (nsp7, nsp12, and nsp13) code three significant proteins which are cofactor for RNA-dependent RNA polymerase (nsp7), RNA-dependent RNA polymerase, or RdRp (nsp12), helicase or HEL (nsp13). All these proteins are associated with the viral life cycle. Therefore, druggable pockets (ligand binding sites) will help identify the drug candidates targeting these regions, affecting the viral life cycle. siRNA-based molecules can be predicted using those druggable pockets. Previously, we identified siRNA-based therapeutic candidates targeting RdRp [36].
GC Content and GC-Profile Analysis Throughout the nsp Coding Genome
A, T, G, C, and A+T, G+C Content of the nsp Coding Genomic Regions (nsp1–16)
Here, we have calculated the A, T, G, C, and A+T, G+C content of the nsp coding genomic regions from their sequence space GC-profiling to understand the content of the nsp coding genomic regions (nsp1–16) (Fig. S4A1–A11 and Fig. S4B1–B5). We found that A+T is higher in all the nsp coding regions than G+C content. The G+C content of all the nsps (nsp1 to nsp11) of ORF1a are noted as 48.52%, 39.76%, 35.75%, 36.53%, 38.13%, 36.21%,37.39%, 38.22%, 40.12%, 42.45%, 53.80%. At the same time, G+C content of all the nsps (nsp12 to nsp16) of ORF1b are noted as 37.18%, 38.21%, 38.08%, 34.23%, 35.46%.
GC-Profiling of the nsp Coding Genomic Regions (nsp1–16) and Comparison with the Whole Genome of SARS-CoV-2
We analyzed the GC-profiling of the nsp coding regions of ORF1a and ORF1b. The graph shows the highest peak at 4000 bp and 20,000 bp regions. At the same time, the graph shows the lowest peak, in between 9000 to 12,000 bp regions (Fig. 6a).Fig. 6 GC-profiling of the nsp coding genomic regions a GC-profiling of both the nsp coding regions of ORF1a and ORF1b. It mapped the GC contents in every region of the nsp coding genes of ORF1a and ORF1b regions. b GC-profiling of the whole genome. However, no segmentation in the GC contents was noted in both cases
The GC-profiling of the whole genome shows the highest peak of 4000 bp and 20,000 bp regions, and suddenly, a very high peak was noted in the last part of the genome. At the same time, the graph shows the two lowest peaks, at 9000 to 12,000 bp and around 23,000 bp regions (Fig. 6b).
However, it has been observed that the GC-profile value of the nsp coding genomic regions (nsp1–16) is less (about 0.375) compared to the whole genome (about 0.38).
Discussion
Presently, researchers are trying to understand the architecture of RNA, especially the RNA structure in the genome [7, 37]. RNA structure can be utilized in different other conditions, such as the different significant scientific events (host immunity and the evolution of virus) [38]. At the same time, an understanding of architecture in RNA structures in secondary structural form and 3D structural form is important to illustrate the replication process [14, 39]. Simultaneously, researchers are trying to understand the druggable genome, one of the focus areas for structure-based drug design. Therefore, RNA structure in the genome component will help with RNA-targeted drug design [40]. In this direction, scientists are trying to solve the RNA architecture in the SARS-CoV-2 genome. Understanding the RNA secondary and 3D structure of the SARS-CoV-2-ssRNA genome is significant in this pandemic scenario and will help the RNA-targeted therapeutic design. Manfredonia et al. have tried to evaluate the structural signature of the SARS Cov-2 genome and identified RNA structural components with therapeutic significance [21]. In this direction, we have illustrated the secondary structure, 3D structure rated, and GC-profile of the nsp coding regions of the SARS-CoV-2 genome. Finally, we have identified ligand-binding pockets of the nsp coding regions. Therefore, our study is very significant and will initiate the discovery of RNA-based therapeutics against SARS-CoV-2.
Druggable genome-wide therapeutic siRNA discovery is one of the effective approaches for developing antisense oligonucleotide therapeutics [41–43]. Cao et al. have studied the SARS-CoV-2 RNA genome architecture and siRNA-based therapeutic design. They have identified four observed siRNAs, and no infection was found in the cell after treatment of siRNAs [7]. Sun et al. illustrated the RNA genome architecture of the SARS-CoV-2 and further explored siRNA-based therapeutic design. In this study, researchers have tried to identify the different genomic regions that are potential targets for siRNA. The study will help to develop siRNA-based therapies for SARS-CoV-2 [4]. Previously, we have also identified siRNAs targeting the mRNA of RdRp, an example of the RNA-based therapeutic discovery for SARS-CoV-2. However, we have targeted the mRNA of RdRp of SARS-CoV-2. Several researchers have tried to understand the transcriptomic profile of SARS-CoV-2 [37]. It will help to comprehend the SARS-CoV-2 life cycle and its pathogenicity. At the same time, the study will also help to explore RNA-based therapeutic design.
The druggability characterization within the SARS-CoV-2 proteome is a significant effort for viral drug target-based therapy. Cavasotto et al. [44] measured the functional role of each SARS-CoV-2 protein encoded from the whole RNA genome. Subsequently, they analyzed the main structural landscapes, using the experimental homology models or structural data using in-depth in silico druggability assessment of the viral proteome [45].
Deep learning-based algorithms and tools are important to illustrate the genome structure [46] and are used regularly for RNA secondary structure generation [47]. Sun et al. illustrated the RNA genome architecture of the SARS-CoV-2 using a deep learning tool and developed the RNA secondary structure of this virus. Along with the conventional method, our study used the deep learning-based modern tool to develop the secondary structure of the nsp coding regions of the SARS-CoV-2 RNA genome. The study compared the predicted deep learning-based secondary structures and conventional secondary structures (Centroid and MFE-based) (Table 2).Table 2. A comparative study of our developed deep learning-based secondary structures and conventional secondary structures (Centroid and MFE-based secondary structures)
Sl No Genomic regions nsp coding genes Deep learning-based secondary structures Centroid-based secondary structures MFE-based secondary structures
1 ORF1a nsp1 Approximately 11 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model which is developed by us is conventional Stem-loop, multi-branch loop noted. This structure is conventional
2 nsp2 Approximately 6 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model found as the conventional form Stem-loop, multi-branch loop noted. This secondary structure is conventional
3 nsp3 Approximately 6 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model is conventional Stem-loop, multi-branch loop noted.
The secondary structure model is conventional
4 nsp4 Approximately 6 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. This secondary structure is found as conventional conformation Stem-loop, multi-branch loop noted. It seems to be a conventional
5 nsp5 Approximately 9 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. We found the secondary structure as a conventional model Stem-loop, multi-branch loop noted. We noted as conventional model
6 nsp6 Approximately one complicated is found with pseudoknots Stem-loop, multi-branch loop noted. The model is shown as a conventional model Stem-loop, multi-branch loop noted. We found the structure as a conventional model
7 nsp7 Approximately 2 stem-loop structure are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The structure is the conventional type of structure Stem-loop, multi-branch loop noted. We observed the secondary structure as a conventional model
8 nsp8 Approximately 4 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. This secondary structure looks as conventional Stem-loop, multi-branch loop noted. The secondary structure model is conventional
9 nsp9 Approximately 7 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. Stem-loop, multi-branch loop noted. The secondary structure model found as the conventional form
The secondary structure model is conventional
10 nsp10 Approximately one complicated is found with pseudoknots Stem-loop, multi-branch loop noted. The secondary structure model is conventional Stem-loop, multi-branch loop noted. The secondary structure model found as a conventional form
11 nsp11 One small stem-loop structure is found Stem-loop, multi-branch loop noted. We found the structure as a conventional model Stem-loop, multi-branch loop noted. The secondary structure model found as a conventional form
12 ORF1b nsp12 Approximately 6 stem-loop structure are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model is conventional Stem-loop, multi-branch loop noted. The secondary structure model found as a typical form
13 nsp13 Approximately one complicated is found with pseudoknots Stem-loop, multi-branch loop noted. The secondary structure model is typical Stem-loop, multi-branch loop noted. The secondary structure model found as the typical form
14 nsp14 Approximately 5 stem-loop structure are found and pseudoknots are noted Stem-loop, multi-branch loop noted. This secondary structure looks like a typical model Stem-loop, multi-branch loop noted. This secondary structure is a typical form
15 nsp15 Approximately 4 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model which is developed by us is typical Stem-loop, multi-branch loop noted. This structure found as the typical form
16 nsp16 Approximately 8 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. We found the structure as a conventional model Stem-loop, multi-branch loop noted. The secondary structure model found as a conventional form
Simultaneously, we calculated the GC content of the nsp coding regions. We found that the range of the GC content was 34.23% to 48.52%. Although, we found the nsp11 coding region is about 53.80%. However, the sequence length of this part is too short, so, we have not considered this region. Again, we evaluated the GC-profile of the nsp coding regions and compared to the whole SARS CoV-2 genome. Several other researchers have calculated the GC usage of SARS-CoV-2. Li et al. calculated the GC usage of the genes of SARS-CoV-2 and found lower GC content of the genome. It has been reported that the GC content of the virus coding sequence is around 38%. At the same time, researchers found that the GC content of the vertebrates along with the humans is around 60% [48].
Additionally, our study has identified drug-binding pockets from the RNA genome, and it is a promising approach for the therapeutic development of SARS-CoV-2 or other infective RNA viruses. Therefore, our work has immense value.
Limitations
Several researchers have used the next-generation platform (such as SHAPE-MaP evaluation) to illustrate the architecture of the RNA genome. Due to the lack of resources, we were unable to find the next-generation platform to develop the genome architecture of this RNA virus. However, to fulfill the limitation, we have used modern algorithms (deep learning-based algorithms) to illustrate the secondary structure of the genome structure. We have modeled the 3D structure of all nsp coding genes due to the lack of the crystal or cryo-electron structure. However, we urge researchers to develop crystal or cryo-electron structures of all the nsp coding genes.
The information-centric terminology in biological systems can be considered properly when it is embedded in theoretical biology, and it validates bioinformatics-based analysis. Successive models and experimental validation is exclusively required for any scientific experiment. Many researchers utilizing artificial intelligence are currently exploring new illustrations of information processing systems, often inspired by biological systems, e.g., protein-nucleotide network models and biomolecule pattern recognition. Our study emphasized advanced modeling practices of nsp coding genomic regions of SARS-CoV-2-ssRNA to understand and develop RNA-targeted therapeutics using the druggable genome.
Although all sorts of modeling, structure, and pattern analysis were considered distinct endeavors, we felt that for bioinformatics research, they were both desired and should be united to compare the outcome of such models with “real” data [49, 50].
Future Prospective
Our data illustrated nsp coding regions of the SARS-COV-2 genome. The data of our work act as the fundamental resources to unfold more about the SARS-CoV-2 life cycle, replication, and unknown architecture of the genome. At the same time, understanding the secondary and 3D structure of the genome and its composition is important. However, the secondary structure-guided 3D structure and its identified ligand-binding pocket will shed light on the druggable genome for the researcher to develop multiple therapeutics against the virus.
Conclusion
Our work not only emphasized the secondary and 3D structure development but also identified all the elements of secondary structure, such as stem-loop structure, multi-branch loop, pseudoknot structure, and the bulge structural components in the secondary structure in the nsp coding genes. We also identified the unbound structure, branched structure, duplex structure, three-way junction, four-way junction, etc., in the 3D structure. The study will help to identify the structural elements of the SARS-COV-2 genome.
Our data of binding pocket identification will offer a primary platform for RNA-targeted therapeutic development. It will help identify the druggable genome and unique RNA-based therapeutic target, which will help structure-based drug design against SARS-CoV-2. Finally, the identified binding pocket in the nsp coding regions will help future researchers to multiple small molecule-based ligand discoveries and antisense oligonucleotide therapeutics discoveries targeting those genomic regions to fight against the virus.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (RAR 1691 kb)Fig. S1. RNA secondary structure model based on centroid of all nsp coding regions (nsp1–nsp16) components of the structure such as stem-loop, multi-branch loop etc. (A1) Secondary structure conformations of nsp1 coding gene and it components (A2) Secondary structure conformations of nsp2 coding gene and it components (A3) Secondary structure conformations of nsp3 coding gene and it components (A4) Secondary structure conformations of nsp4 coding gene (A5) Secondary structure conformations of nsp5 coding gene and it components (A6) Secondary structure conformations of nsp6 coding gene and it components (A7) Secondary structure conformations of nsp7 coding gene and it components (A8) Secondary structure conformations of nsp8 coding gene and it components (A9) Secondary structure conformations of nsp9 coding gene and it components (A10) Secondary structure conformations of nsp10 coding gene and it components (A11) Secondary structure conformations of nsp11 coding gene and it components (B1) Secondary structure conformations of nsp12 coding gene and it components (B2) Secondary structure conformations of nsp13 coding gene and it components (B3) Secondary structure conformations of nsp14 coding gene and it components (B4) Secondary structure conformations of nsp15 coding gene and it components (B5) Secondary structure conformations of nsp16 coding gene and it components
Supplementary file2 (RAR 1503 kb)Fig. S2. RNA secondary structure model based on MFE of all nsp coding regions(nsp1–nsp16) (A1) Secondary structure conformations of nsp1 coding gene and it components (A2) Secondary structure conformations of nsp2 coding gene and it components (A3) Secondary structure conformations of nsp3 coding gene and it components (A4) Secondary structure conformations of nsp4 coding gene and it components (A5) Secondary structure conformations of nsp5 coding gene and it components (A6) Secondary structure conformations of nsp6 coding gene and it components (A7) Secondary structure conformations of nsp7 coding gene and it components (A8) Secondary structure conformations of nsp8 coding gene and it components (A9) Secondary structure conformations of nsp9 coding gene and it components (A10) Secondary structure conformations of nsp10 coding gene and it components (A11) Secondary structure conformations of nsp11 coding gene and it components (B1) Secondary structure conformations of nsp12 coding gene and it components (B2) Secondary structure conformations of nsp13 coding gene and it components (B3) Secondary structure conformations of nsp14 coding gene and it components (B4) Secondary structure conformations of nsp15 coding gene and it components (B5) Secondary structure conformations of nsp16 coding gene and it components
Supplementary file3 (RAR 2522 kb)Fig. S3. Entropy and mountain plots based on the secondary structure of all nsp coding regions(nsp1–nsp16) (A1) Entropy and mountain plots of nsp1 coding gene (A2) Entropy and mountain plots of nsp2 coding gene (A3) Entropy and mountain plots of nsp3 coding gene (A4) Entropy and mountain plots of nsp4 coding gene (A5) Entropy and mountain plots of nsp5 coding gene (A6) Entropy and mountain plots of nsp6 coding gene (A7) Entropy and mountain plots of nsp7 coding gene (A8) Entropy and mountain plots of nsp8 coding gene (A9) Entropy and mountain plots of nsp9 coding gene (A10) Entropy and mountain plots of nsp10 coding gene (A11) Entropy and mountain plots of nsp11 coding gene (B1) Entropy and mountain plots of nsp12 coding gene (B2) Entropy and mountain plots of nsp13 coding gene (B3) Entropy and mountain plots of nsp14 coding gene (B4) Entropy and mountain plots of nsp15 coding gene (B5) Entropy and mountain plots of nsp16 coding gene
Supplementary file4 (RAR 1363 kb)Fig. S4. A, T, G, C, A+T, and G+C content of the nsp coding genomic regions (A1) A, T, G, C, A+T, and G+C content of nsp1 coding gene (A2) A, T, G, C, A+T, and G+C content of nsp2 coding gene (A3) A, T, G, C, A+T, and G+C content of nsp3 coding gene (A4) A, T, G, C, A+T, and G+C content of nsp4 coding gene (A5) A, T, G, C, A+T, and G+C content of nsp5 coding gene (A6) A, T, G, C, A+T, and G+C content of nsp6 coding gene (A7) A, T, G, C, A+T, and G+C content of nsp7 coding gene (A8) A, T, G, C, A+T, and G+C content of nsp8 coding gene (A9) A, T, G, C, A+T, and G+C content of nsp9 coding gene (A10) A, T, G, C, A+T, and G+C content of nsp10 coding gene (A11) A, T, G, C, A+T, and G+C content of nsp11 coding gene (B1 A, T, G, C, A+T, and G+C content of nsp12 coding gene (B2) A, T, G, C, A+T, and G+C content of nsp13 coding gene (B3) A, T, G, C, A+T, and G+C content of nsp14 coding gene (B4) A, T, G, C, A+T, and G+C content of nsp15 coding gene (B5) A, T, G, C, A+T, and G+C content of nsp16 coding gene.
Author Contributions
CC conceptualized the study, collected and analyzed the data, wrote the main manuscript. ARS did the validation and editing. MB and SC did formal analysis and developed the figures and tables. GA edited the manuscript. CC and SSL did the overall supervision. All authors read and approved the final manuscript.
Data Availability
The authors confirm that the data supporting the findings of this study are available as Supplementary figures.
Declarations
Conflict of interest
The authors declare no competing interests.
Research Involving Human Participants and/or Animals
Not applicable.
Informed Consent
Not applicable.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Chiranjib Chakraborty and Manojit Bhattacharya contributed equally to this work.
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| 36463562 | PMC9735222 | NO-CC CODE | 2022-12-14 23:29:53 | no | Mol Biotechnol. 2022 Dec 4;:1-22 | utf-8 | Mol Biotechnol | 2,022 | 10.1007/s12033-022-00605-x | oa_other |
==== Front
Mol Biotechnol
Mol Biotechnol
Molecular Biotechnology
1073-6085
1559-0305
Springer US New York
36463562
605
10.1007/s12033-022-00605-x
Original Paper
Structural Landscape of nsp Coding Genomic Regions of SARS-CoV-2-ssRNA Genome: A Structural Genomics Approach Toward Identification of Druggable Genome, Ligand-Binding Pockets, and Structure-Based Druggability
http://orcid.org/0000-0002-3958-239X
Chakraborty Chiranjib [email protected]
1
Bhattacharya Manojit 2
Sharma Ashish Ranjan 3
Chatterjee Srijan 1
Agoramoorthy Govindasamy 4
Lee Sang-Soo 3
1 grid.502979.0 0000 0004 6087 8632 Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal 700126 India
2 grid.444315.3 0000 0000 9013 5080 Department of Zoology, Fakir Mohan University, Vyasa Vihar, Balasore, Odisha 756020 India
3 grid.464534.4 0000 0004 0647 1735 Institute for Skeletal Aging & Orthopaedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, Gangwon-do 24252 Republic of Korea
4 grid.412902.c 0000 0004 0639 0943 College of Pharmacy and Health Care, Tajen University, Yanpu, 907 Pingtung Taiwan
4 12 2022
122
5 5 2022
7 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
SARS-CoV-2 has a single-stranded RNA genome (+ssRNA), and synthesizes structural and non-structural proteins (nsps). All 16 nsp are synthesized from the ORF1a, and ORF1b regions associated with different life cycle preprocesses, including replication. The regions of ORF1a synthesizes nsp1 to 11, and ORF1b synthesizes nsp12 to 16. In this paper, we have predicted the secondary structure conformations, entropy & mountain plots, RNA secondary structure in a linear fashion, and 3D structure of nsp coding genes of the SARS-CoV-2 genome. We have also analyzed the A, T, G, C, A+T, and G+C contents, GC-profiling of these genes, showing the range of the GC content from 34.23 to 48.52%. We have observed that the GC-profile value of the nsp coding genomic regions was less (about 0.375) compared to the whole genome (about 0.38). Additionally, druggable pockets were identified from the secondary structure-guided 3D structural conformations. For secondary structure generation of all the nsp coding genes (nsp 1-16), we used a recent algorithm-based tool (deep learning-based) along with the conventional algorithms (centroid and MFE-based) to develop secondary structural conformations, and we found stem-loop, multi-branch loop, pseudoknot, and the bulge structural components, etc. The 3D model shows bound and unbound forms, branched structures, duplex structures, three-way junctions, four-way junctions, etc. Finally, we identified binding pockets of nsp coding genes which will help as a fundamental resource for future researchers to develop RNA-targeted therapeutics using the druggable genome.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12033-022-00605-x.
Keywords
Nsp
RNA secondary structure
3D model
SARS-CoV-2
Drug binding pocket
==== Body
pmcIntroduction
SARS-CoV-2 is an RNA virus of the Coronaviridae family, which is the causative pathogen of the current pandemic. The virus contains a single-stranded RNA (ssRNA) genome [1, 2] with approximately ~30 kb genomes that comprise one of the largest RNA among entire families of RNA viruses. The genome contains positive sense RNA, which includes several significant structural parts of the genome, such as 5′ cap structure and 3′ poly(A) tail [3, 4]. Moreover, the genome structure encodes about twenty-nine proteins [5]. Several researchers have tried to illustrate the genome structure. Manfredonia and Incarnato attempted to provide an insight view of the SARS-CoV-2 genome structure to offer strategies for developing new therapeutics. In this direction, they have illustrated different genome structural elements such as 5′ UTR structure, ribosomal FSE (frameshifting element), 3′ UTR structure [6]. Similarly, several structural elements were projected from the SARS-CoV-2 RNA genome, and in vivo structural characterization was performed for the genome. They have identified that 42 host proteins can interact with the different elements that were projected from the SARS-CoV-2 RNA. It might be helpful in developing new therapeutics against the virus [4]. Similarly, Cao et al. have developed the genome architecture of the SARS-CoV-2 RNA. The researchers have tried to understand the packing of the SARS-CoV-2 genome based on the RNA secondary structure. The study tried to comprehend the framework of the genome for the structure, function, and dynamics of the virus. Finally, they tried to design the siRNA for RNA-based drugs [7].
The large-scale characterization of RNA secondary structure might provide insight into the SARS-CoV-2 genome-wide organization. Simmonds illustrated a SARS-CoV-2 genome organization through RNA secondary structure and compared it with other Coronaviruses [8]. Several studies describe the significance of RNA secondary structures in the light of virus replication and their transcription and translation [9–11]. The genome of SARS-CoV-2 encodes two types of proteins: structural and non-structural proteins (nsps) (Fig. 1a). nsps are significant proteins that help the fundamental process of viruses such as transcription, envelope proteins production, and viral replication [12, 13]. All these NSPs support the RNA-dependent RNA polymerase (RdRp) to perform replication. Therefore, they act as replication machinery [14]. Scientists have used non-structural proteins (nsps) as drug targets [15]. NSP coding genes of SARS-CoV-2 are significant in this point of view. It has been noted that two open reading frames (ORF1a and ORF1b) are associated with the coding of 16 NSPs which are nsp1 to nsp16 (Fig. 1a) [16, 17]. ORF1a codes nsp1 to nsp11, and ORF1b codes nsp12 to nsp16 protein. The main protein includes nsp3 (papain-like proteinase protein), nsp5 (3C-like proteinase), nsp12 (RNA-dependent RNA polymerase, RdRp), nsp13 (helicase, HEL), NSP14 (exoRNAse), nsp15 (endoRNAse), nsp16 (2′-O-Ribose-Methyltransferase), and other non-structural proteins. Other significant nsp are nsp7 (cofactor for RNA-dependent RNA polymerase), nsp8 (cofactor for RdRp, primase, or 3′-terminal adenylyltransferase) [18]. Most of the research work has been performed to illustrate the structural and functional perspective of nsps (nsp1–16). However, less evidence illustrates insight into the nsp coding of genes (ORF1a and ORF1b) and their genomic structural arrangements. Therefore, it is urgent to understand the structural insight of the nsp coding genomic regions (ORF1a and ORF1b) and their structure-based genomic arrangements.Fig. 1 Schematic representation shows the single-stranded RNA (ssRNA) genome of SARS-CoV-2 and methodology flowchart of our study. a SARS-CoV-2 ssRNA genome contains non-structural protein-coding genes (nsp) (nsp1–to 16) and structural protein-coding genes. The nsp coding genes synthesized by ORF1a and ORF1b. ORF1a contains nsp1-to 11 protein-coding genes. ORF1b contains nsp12-to 16 protein-coding genes. b Schematic diagram shows a flowchart of the methodology of our work
RNA structure, both secondary and tertiary, plays critical functional roles in the life cycles of SARS-CoV-2. Using 3D structure, researchers are analyzing components of the structure that can help the structure-based drug discovery for this virus. Very few scientists have tried to illustrate the structure of the RNA genome of SARS-CoV-2. Rangan et al. have assessed RNA sequence conservation of the SARS-CoV-2 genome and found 106 RNA-based conserved regions that act as potential antiviral drug targets [19]. Romano et al. tried to understand the RNA structural-based replication machinery, where they found the interaction between the NSPs [20]. Sun et al. have analyzed RNA secondary structural elements of the SARS-CoV-2 RNA genome that plays a crucial role in viral infection. Their research might help to assess the antisense oligonucleotides targeting using RNA-based structural elements and will help in the therapeutics development against this virus [4]. Some scientists have contributed to identifying the RNA structure-based elements that can help therapeutic development. For example, Manfredonia et al. mapped the RNA structures throughout the SARS-CoV-2 genome. The RNA elements were identified from the genome. The secondary structure patterns have been generated to illustrate the SARS-CoV-2 genome. They have modeled the 3D structure of the RNA, which can help RNA-based therapeutic innovation [21]. However, the secondary and 3D structural RNA conformations of the nsp genes, their druggable genome, and the RNA-based therapeutic target in the virus genome are mostly unexplored. Therefore it is necessary to understand the in-depth analyses of the secondary, 3D RNA structural conformations of the SARS-CoV-2 genomes and the fundamental units of the druggable genome which can initiate the RNA targeting drug discovery against the virus.
In our work, we have tried to evaluate the secondary structure conformations, entropy and mountain plots, RNA secondary structure in a linear fashion, and 3D structure of NSP coding genes of the RNA genome of the SARS-CoV-2. We have predicted recent algorithms-based (deep learning-based) secondary structures, conventional algorithms-based (centroid and MFE-based) secondary structural conformations, entropy & mountain plots based on the secondary structures, single & overlapping structures of arc diagrams in a linear fashion of all the nsp coding genomic regions (nsp1–16). Finally, RNA 3D structural models have been predicted from those secondary structural conformations. Additionally, we have also analyzed the A, T, G, C, and A+T, G+C content, and GC-profiling to understand the GC content of all NSP coding genes. Finally, we have identified the secondary structure-guided druggable pockets (ligand binding sites) in RNA 3D structures conformation.
Method
Our analysis has been divided into three parts: secondary structure conformations analysis, 3D analysis, and the stability of the nsp coding genomic regions (nsp1–16). Several recent methods and current algorithms were used to analyze the RNA secondary structure, 3D structure, and stability of this genomic region.
Retrieval of the Genomic Sequence nsp Coding Genes of the SARS-CoV-2 Genome
We have retrieved the SARS-CoV-2 genome sequence and their nsp coding genes from NCBI (NCBI GenBank Id: MZ054889.1). The nsp coding genes and corresponding sequences’ position have been listed in Table 1. The nsp coding gene sequences (nsp1–16) were used for further analysis.Table 1. Different nsp coding gens and their position (nucleotide in bp) in the SARS-CoV-2-ssRNA genome
Sl. No. Gene Coded protein Position (in bp)
1. nsp1 – 234-773
2. nsp2 – 774-2687
3. nsp3 Papain-like proteinase 2688-8522
4. nsp4 – 8523-10022
5. nsp5 3C-like proteinase 10023-10940
6. nsp6 – 10941-11810
7. nsp7 Cofactor for RNA-dependent RNA polymerase (RdRp) 11811-12059
8. nsp8 Cofactor for RdRp, primase, or 3′-terminal adenylyltransferase 12060-12653
9. nsp9 – 12654-12992
10. nsp10 – 12993-13409
11. nsp11 – 13410-13448
12. nsp12 RNA-dependent RNA polymerase 13410-16204
13. nsp13 Helicase 16205-18007
14. nsp14 3′-to-5′ exonuclease 18008-19588
15. nsp15 EndoRNAse 19589-20626
16. nsp16 2′-O-ribose methyltransferase 20627-21520
Secondary Structure Conformations Analysis
Deep Learning (DL) Based Secondary Structure Conformations Analysis
DL is an emerging approach exploring researchers in structural analysis from nucleic acids to proteins. We have used DL-based UFold server to analyze the DL-based secondary structure of RNA [22]. Using an encoder-decoder architecture, this server uses FCNs (Fully Convolutional Networks) to create fast and efficient RNA secondary structure. It uses the U-Net model for structure generation. The 17×L×L tensor is used as input for the U-Net model. The model predicted a score matrix Y that uses an L×L symmetric score for output through the contact map. In the case of traditional RNA secondary structure prediction methods, algorithms are mainly based on thermodynamic models through free energy minimization, which executes strong prior assumptions and slow speed to run. The UFold server proposes a deep learning-based method for the prediction of RNA secondary structure based directly on annotated data and nucleotide base-pairing rules. This approach might be more acceptable for computationally predicting the secondary structure of RNA [22].
Centroid-Based Secondary Structure Conformations Analysis
Another secondary structure conformation was predicted for the nsp coding genes based on centroid structure, used with minimum base-pair distance. Centroid-based secondary structures were predicted using an RNA sever (Vienna RNA website) [23]. From diverse types of structural RNAs, the centroid structure of RNA ensemble makes a 30.0% lesser prediction error which is measured by the positive predictive value. Moreover, it predicted the unavailable complete model that apparently comprises the unique native structure of studied RNA [24].
MFE-Based Secondary Structure Conformations Analysis
MFE-based secondary structures were generated for the nsp coding genomic regions. This structure was predicted by MFE-based secondary structure, utilizing a minimum of free energy. MFE structure was predicted using the Vienna RNA Website Server [23]. The server uses optimal computer folding employing external bases, the loop-based energy model unique decomposed loops. For predicting the MFE structure, alternatively, the RNA native structure of a given sequence is generated for each admissible base pair (isolated base pairs and stacking base pairs). The energetically best structure contains that base pair in the context of a minimum free energy landscape [25].
Entropy & Mountain Plots Analysis Based on the Secondary Structures
Entropy & mountain plots were generated based on the secondary structures. Entropy plots represent the thermodynamic assembly of a RNA secondary structure and the positional entropy of a RNA secondary structure. Entropy plots were predicted using the Vienna RNA website server [23]. The entropy and mountain plot are exclusively useful for long nucleotide sequences where conventional structure illustrations become a disorder. It is an axis (xy-diagram) oriented plotting, where the number of base pairs circling a sequence position versus the nucleotide position. The sets of computer program transforms a dot plot into the mountain plot coordinates which the graphical user interface can visualize. The resulting plot displays three significant curves, two mountain plots derived from the MFE structure (red), a positional entropy curve (green), and the pairing probabilities (black) [25].
Mountain plots were generated using the same server. It represents the secondary structure through a height and informs us of the positional height of an RNA secondary structure. The height m(k) is allotted by the number of base pairs included in the base at position k.
Arc Diagrams to Understand the Secondary Structure Conformations Linearly Both in a Single Manner, Overlapping Manner, and Trans-RNA–RNA Interactions
The Arc diagrams have been developed through the R-chie server [26]. Arc diagrams were used to describe the secondary structure conformations linearly, both in a single & overlapping manner. To develop the Arc diagrams, the server used the helix prediction method TRANSAT (TRANSAT algorithm), which is visualized through the R package and graphically represented through the line diagram using the package (R4RNA). Finally, the result will help us to understand trans-RNA–RNA interactions. Using the server, we have illustrated the trans-RNA–RNA interactions [27].
3D Structural Conformation Analysis
3D Structural Conformation Based on Line Chain Model And Wire Model
Predicting the 3D structure of RNA and its proper understanding remains a major challenge. The 3D structure can help components of RNA structures and assist in positioning the helical regions of RNA. 3D structure conformation of nsp coding genomic regions (nsp1–16) was developed by RNAComposer [28, 29]. Here we developed two types of 3D models: the line chain 3D model and the wire 3D model. The RNAComposer server is a user-friendly and freely accessible server target for the 3D structure prediction of RNA (up to 500 nucleotides). It employs fully automated fragment assembly-based methods on the RNA secondary structure detailed by the user. Presently, such novel computational methods based on the incorporation of distance restraints resultant strategies are emerging in the field of computational biology [29].
Identification of Druggable Pockets (Ligand Binding Sites) in RNA 3D Structures Conformation and Its Comparison with the Secondary Structure
The identification of druggable pockets is an interesting area of structure-based drug design [30]. Identification of druggable pockets in RNA 3D structural conformation in the nsp coding genes using Voronoia 4-ever server [31]. The server calculates ligand-binding pockets, solvent-free surfaces, packing defects, etc. It also calculates the packing density for every atom packing density is denoted by PD, which is calculated using the following formula:PD = VvdW/VvdW+ Vse
Here, using the Voronoi cell method, VvdW is the volume allocated to each atom, which is just inside the vdW field of the atom. Here, Vse is defined as the remaining volume, and it is excluded from the solvent.
GC Content and GC-Profile Analysis Throughout the nsp Coding Genome
Stability Analysis Through A, T, G, C, and A+T, G+C Content
Scientists have tried to analyze the GC-rich region of the genome of the virus [32]. It can help to understand the GC content bias regions. We used the GC content calculator and calculated A, T, G, C, and A+T, G+C content of the nsp coding genomic regions (nsp1–16) SARS-CoV-2 genome using the retrieved genome sequence.
GC-Profiling to Understand the Content
We have analyzed GC-profiling of the whole genome of SARS-CoV-2 through a GC-profiling plot through the GC-Profile server. We have evaluated GC-profiling of the nsp coding genomic regions of the virus through GC-profiling plot through the GC-Profile server and finally compared the GC-profile of both the regions (the nsp coding genomic regions and whole genome). GC-Profile server uses a segmentation algorithm to estimate the GC-Profile. In the segmentation algorithm, the genome order index is calculated, which is denoted as S. The S is defined as follows:S≡SP= a2+ c2+ g2+ t2
GC-Profile is a web-based, interactive software system mainly used to analyze eukaryotic and prokaryotic genomes. It offers a qualitative as well as a quantitative view of organism genome organization. Server-based results also reproduce the relationships among the G+C content and other significant genomic landscapes, e.g., distributions of CpG islands and genes, which are also analyzed comprehensibly. This proved that GC-profile is an appropriate early point for analyzing the isochore structure of higher eukaryotic genomes and identifying genomic islands in prokaryotic genomes [33].
Finally, the server presented a cumulative GC-profile of the genome or the nsp coding genomic regions.
The entire methodology of our work has been described through a flowchart (Fig. 1b).
Result
Secondary Structure Conformations
Deep Learning (DL)-Based Secondary Structure Conformations
Deep learning (DL)-based secondary structures were developed coding regions of the different nsp (nsp1–16) of the SARS-CoV-2 genome. It illustrated the DL-based secondary structures ORF1a and ORF1b regions. The DL-based secondary structures of ORF1a were illustrated through the coding genomic regions of nsp1-11 (Fig. 2A1–A11). Similarly, DL-based secondary structures of ORF1b were illustrated through the coding genomic regions of nsp12-16 (Fig. 2B1–B5). The nsp1 coding region shows more than 14 internal loops. We also found 2 to 3 larger internal loops (Fig. 2A1). In this region, long stems are found compared to other regions. Similarly, the nsp2 coding region shows more than 14 internal loops (Fig. 2A2). We also found 2 to 3 large internal loops. The bulge loop, multi-branched, stem, hairpin loop, and internal loop were also noticed in this region. Similarly, the nsp3 coding region shows more number of multi-branched loops. We also found the bulge loop, stem, hairpin loop, and internal loop in this region (Fig. 2A3). The nsp4 coding region illustrates three larger multi-branched loops and several small multi-branched loops (Fig. 2A4). Again, the nsp5 coding region illustrates one larger multi-branched loop in conjunction with several small multi-branched loops (Fig. 2A5). nsp6 coding region illustrates one larger multi-branched loop.along with four medium-sized multi-branched loops other several small multi-branched loops (Fig. 2A6). Also, we found one larger multi-branched loop.along with two medium-sized multi-branched loops in the nsp7 coding region (Fig. 2A7). In the nsp8 coding region, a large multi-branched loop along with a bulge loop, stem, hairpin loop, and internal loop was noted (Fig. 2A8). Similarly, in the nsp9 coding region, we found one larger multi-branched loop along with a bulge loop, stem, hairpin loop, and internal loop (Fig. 2A9). In the nsp10 coding region, we found bigger multi-branched loops which the structure complex (Fig. 2A10). However, the nsp11 coding region’s structure is simpler than other regions that show a bulge loop, internal loop, and stem (Fig. 2A11). In the ORF1b regions contain, nsp12 coding region is more complex compared to other regions where we noted three multi-branched loops (Fig. 2B1). Similarly, in the nsp13 coding region, we found several internal loops along with multi-branched loops (Fig. 2B2). Again, the nsp14 coding region shows five multi-branched loops along with a bulge loop, hairpin loop, and internal loop (Fig. 2B3). Similarly, the nsp15 coding region shows three multi-branched loops along with other structures such as the bulge loop, hairpin loop, and internal loop (Fig. 2B4). Finally, we found two multi-branched loops along with other structures, such as the internal loop, hairpin loop, and the bulge in the nsp15 coding region (Fig. 2B5).Fig. 2 RNA secondary structure model predicted by deep learning (DL) of all nsp coding regions (nsp1–nsp16) which shows the different components of the structure such as stem-loop (SL), multi-branch loop, pseudoknot, and bulge etc. A1 Secondary structure conformations of nsp1 coding gene and their components. A2 Secondary structure conformations of nsp2 coding gene and their components. A3 Secondary structure conformations of nsp3 coding gene. A4 Secondary structure conformations of nsp4 coding gene and their components. A5 Secondary structure conformations of nsp5 coding gene and their components. A6 Secondary structure conformations of nsp6 coding gene and their components. A7 Secondary structure conformations of nsp7 coding gene and their components. A8 Secondary structure conformations of nsp8 coding gene and their components. A9 Secondary structure conformations of nsp9 coding gene and their components. A10 Secondary structure conformations of nsp10 coding gene and their components. A11 Secondary structure conformations of nsp11 coding gene and their components. B1 Secondary structure conformations of nsp12 coding gene and their components. B2 Secondary structure conformations of nsp13 coding gene and their components. B3 Secondary structure conformations of nsp14 coding gene and their components. B4 Secondary structure conformations of nsp15 coding gene. B5 Secondary structure conformations of nsp16 coding gene and their components
Centroid-Based Secondary Structure Conformations
Like the DL-based secondary structures, we also developed centroid-based secondary structure conformations of coding regions for the nsps (nsp1–16) of the SARS-CoV-2 genome. We developed centroid-based secondary structures of ORF1a, which were illustrated through the coding genomic regions of nsp1-11 (Fig. S1A1–A11). Similarly, the centroid-based secondary structures of ORF1b were demonstrated through the coding genomic regions of the nsp12-16 (Fig. S1B1–B5). In both cases (ORF1a and ORF1b), the structure of the coding genomic regions of the nsp1-16 are more simple compared to DL-based secondary structures. The nsp1 shows three multi-branched loop structures (Fig. S1A1). Similarly, nsp2 shows three multi-branched loop structures (Fig. S1A2). Likewise, nsp3 shows a linear-type structure, and several stem and loop structures have been generated from the linear structure (Fig. S1A3). Similarly, in the nsp4, three multi-branched loops with a bigger loop structure are noted (Fig. S1A4). In the nsp5, five to six multi-branched loops are observed with a different bulge. We also found hairpin loops and internal loops in the structure (Fig. S1A5). In the nsp6, a major multi-branched loop is observed (Fig. S1A6). Similarly, in the nsp7, two major multi-branched loops are observed (Fig. S1A7). Also, in the nsp8, we noted three major multi-branched loops along with several hairpin loops and internal loops in the entire structure (Fig. S1A8). Likewise, in the nsp9, two major multi-branched loops are noted, and one structure is noted with a bulge (Fig. S1A9). At the same time, several stems, hairpin loops, and internal loops were found in the nsp10 in conjunction with two multi-branched loops (Fig. S1A10). The nsp11 coding region formed a small structure due to its small sequence length (Fig. S1A11). Likewise, in the nsp12, about nine multi-branched loops are noted in the structure of the region. We also found several hairpin loops and internal loops in this region (Fig. S1B1). Similarly, two significant multi-branched loops are noted, which are associated together in the nsp13 (Fig. S1B2). The nsp14 developed a linear-type structure with six multi-branched loops (Fig. S1B3). Likewise, nsp15 contains four multi-branched loops, and the middle multi-branched loop encloses two major bulge structures (Fig. S1B4). Finally, it has been noted that nsp16 formed two multi-branched loops, and the last multi-branched loop encloses one major bulge structure. The first one contains several stems, loops, and hairpin structures (Fig. S1B5).
MFE-Based Secondary Structure Conformations
Like the DL-based and centroid-based secondary structures, we also developed MFE-based conformations of coding regions of the nsps (nsp1–16) of the genome of the virus. We developed MFE-based secondary structures of ORF1a with the coding genomic regions of nsp1-11 (Fig. S2A1–A11). Likewise, the ORF1b was demonstrated through the MFE-based conformations of the coding genomic regions of the nsp12-16 (Fig. S2B1–B5). The nsp1 shows two main multi-branched loops (Fig. S2A1). Similarly, nsp2 shows six multi-branched loop structures (Fig. S2A2). The nsp3 depicts a linear-type structure with several stems and loop structures (Fig. S2A3). This MFE-based secondary of nsp3 is similar to the centroid-based secondary structure. Similarly, It has been noted aboutgenome identifies host proteins vulnerable five multi-branched loops in the nsp4 (Fig. S2A4). Five to six multi-branched loops are observed, a similar type of centroid-based secondary structure (Fig. S2A5). In the nsp6, we have also observed five to six multi-branched loops (Fig. S2A6). Likewise, in the nsp7, one major multi-branched loop is observed. We noted the bulge in the structure (Fig. S2A7). Similarly, in the nsp8, we noted three major multi-branched loops with different components of RNA secondary structure. We noted several structural components (stem, loops, hairpin loop) in the first and last multi-branched structure (Fig S2A8). At the same time, two major multi-branched loops are noted in the nsp9, and the last structure is noted with different structural components (Fig. S2A9). At the same time, we found two multi-branched loops in the nsp10 (Fig. 4A10). Similarly, we found a linear structure that contains about eight multi-branched loops in the structure of the region (Fig. S2B1). In the same way, we found a linear structure of the nsp13 (Fig. S2B2). At the same time, we noted that nsp14 had created a linear-type structure with five multi-branched loops (Fig. S2B3). It has been noted that nsp15 contains about three multi-branched loops, and the middle and last multi-branched loop encloses several stems, loops, and hairpin loop structures (Fig. S2B4). At last, we found that nsp16 formed two multi-branched loops, and the multi-branched loop contained several stems, loops, and hairpin structures (Fig. S2B5).
Entropy and Mountain Plots Based on The Secondary Structures
We depicted the entropy and mountain plots of all nsp coding regions (Fig. S3A1–A11, B1–B5). The nsp1 shows entropy and mountain plots. Maximum entropy exhibited 2.0 (in between 300 and 500 locations), and the height is about 40 in the region of nsp1 (Fig. S3A1). Similarly, nsp2 shows.maximum entropy of 2.0 in between the 1 to 500 location, and the height is about 100 (Fig. S3A2). The nsp3 illustrates a maximum entropy of 2.0 (in between 1 and 1000 locations) and a maximum height of 200 (Fig. S3A3). Similarly, in the nsp12, we noted the energy peaks with a value of 3 (between 1000–1500 and 2000–2500 locations). We noted several energy peaks in those regions. The mountain plot shows a maximum height of about 120, located in the first part (Fig. S3B1). In the region of nsp15, we noted maximum entropy, and it was exhibited at 3.0 (near about 1000 location), and the height of the mountain plots is about 60 to 90 (Fig. S3B4). Again, in the region of nsp16, we noted maximum entropy, and it was exhibited 2.0 to 2.5 (in between 200–400 location, and near about 600) and the height of the mountain plots is about 40 to 60 (Fig. S3B5).
Arc Diagrams of the Secondary Structure Conformations Linearly Both in the Single Manner, Overlapping Manner, and Trans-RNA–RNA Interactions
The arc diagram illustrates the probable base pair of the RNA structure which connects the relevant RNA sequence to the secondary structure. It is depicted as a horizontal line from left to right (5′ to 3′ ends).
We depicted the Arc diagrams of the secondary structure conformations linearly both in the single and overlapping manner for all nsp coding regions (nsp1–16) (Fig. 3A1–A11, B1–B5). Relating to the TRANSAT algorithm, the nsp1 coding region shows a high base paring with a value of [1e-06, 1e-05] in the case of a single line. Similarly, it also shows the high possibility of base pairing in the case of an overlapping manner. More linear arc structures were found in the coding region of nsp1, nsp3, nsp4, nsp7, nsp9, nsp10 in the ORF1a (Fig. 3A1, A3, A4, A7, A9, A10). Similarly, we found more linear arc structures in nsp12 and nsp15 in the ORF1b (Fig. 3B1, B4). It has been noted that the coding region of nsp7 developed denser linear arc structures in both cases of single, overlapping fashion among all of the nsps of ORF1b and ORF1b.Fig. 3 Arc diagrams of the secondary structure conformations linearly both in the single manner, overlapping manner of all nsp coding regions (nsp1–nsp16). A1 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp1 coding gene. A2 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp2 coding gene. A3 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp3 coding gene. A4 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp4 coding gene. A5 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp5 coding gene. A6 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp6 coding gene. A7 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp7 coding gene. A8 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp8 coding gene. A9 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp9 coding gene. A10 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp10 coding gene. A11 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp11 coding gene. B1 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp12 coding gene. B2 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp13 coding gene. B3 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp14 coding gene. B4 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp15 coding gene. B5 Arc diagrams of the secondary structure conformations in the single manner, overlapping manner of nsp16 coding gene
3D Structural Conformation Analysis
3D structural Conformation Based on Line Chain Model and Wire Model
We developed the 3D model of the secondary structure to understand the folding for all the nsp coding regions (nsp1–16) (Fig. 4A1–A11, B1–B5). We have understood the proper folding of the RNA structure in 3D structure space. Here we have identified the stem and loop structure in the line chain and wire model for all the nsp coding regions. In the ORF1a region, it has been found that the nsp7 coding region contains more stem structures (Fig. 4A7). At the same time, in ORF1b regions, we found that the nsp13 coding region contains more stem structures (Fig. 4B2).Fig. 4. 3D model of the RNA of nsp coding regions (nsp1–nsp16) shows the different structural components in the line chain model and wire model. A1 3D model (line chain and wire model) of nsp1 coding gene. A2 3D model of nsp2 coding gene. A3 3D model (line chain and wire model) of nsp3 coding gene. A4 3D model (line chain and wire model) of nsp4 coding gene. A5 3D model (line chain and wire model) of nsp5 coding gene. A6 3D model of nsp6 coding gene. A7 3D model (line chain and wire model) of nsp7 coding gene. A8 3D model (line chain and wire model) of nsp8 coding gene. A9 3D model (line chain and wire model) of nsp9 coding gene. A10 3D model (line chain and wire model) of nsp10 coding gene. A11 3D model (line chain and wire model) of nsp11 coding gene. B1 3D model (line chain and wire model) of nsp12 coding gene. B2 3D model (line chain and wire model) of nsp13 coding gene. B3 3D model (line chain and wire model) of nsp14 coding gene. B4 3D model (line chain and wire model) of nsp15 coding gene. B5 3D model of nsp16 coding gene
Presently, understanding the sequence-related RNA helix conformation is an interesting area. Researchers are also trying to understand the RNA helices pattern of the 3D model of RNA structure [34]. Several scientists are trying to assess the bound and unbound form in the RNA 3D model [35]. RNA 3D model of different bound and unbound forms has been shown in the case of base pairing within RNA helices of this conformation. We have also understood the packing of RNA in 3D conformation. Here, we identified the duplex, branched structure, three-way junction, and four-way junction all the nsp coding regions (nsp1–16).
Identification of Druggable Pockets (Ligand Binding Sites) in RNA 3D Structures Conformation and Its Comparison with the Secondary Structure
Finally, we identified the drug-binding pocket of all the nsp coding regions (nsp1–16). Here, we have represented the three nsp coding structures (nsp7, nsp12, and nsp13) (Fig. 5a–c). In all cases, we have shown two drug-binding pockets in each RNA 3D structures conformation. Each drug-binding pocket in each RNA 3D structure has been compared with the secondary structure of RNA predicted from the nsp coding structures.Fig. 5 Identified ligand-binding pocket in RNA 3D structures (nsp coding) conformation guided with the secondary structure. a Identified ligand-binding pocket in nsp7 coding RNA 3D structures conformation guided with the secondary structure. b Identified ligand-binding pocket in nsp12 coding RNA 3D structures conformation guided with the secondary structure. c Identified ligand-binding pocket in nsp13 coding RNA 3D structures conformation guided with the secondary structure. In every case, we have shown two binding pockets
These three nsp regions (nsp7, nsp12, and nsp13) code three significant proteins which are cofactor for RNA-dependent RNA polymerase (nsp7), RNA-dependent RNA polymerase, or RdRp (nsp12), helicase or HEL (nsp13). All these proteins are associated with the viral life cycle. Therefore, druggable pockets (ligand binding sites) will help identify the drug candidates targeting these regions, affecting the viral life cycle. siRNA-based molecules can be predicted using those druggable pockets. Previously, we identified siRNA-based therapeutic candidates targeting RdRp [36].
GC Content and GC-Profile Analysis Throughout the nsp Coding Genome
A, T, G, C, and A+T, G+C Content of the nsp Coding Genomic Regions (nsp1–16)
Here, we have calculated the A, T, G, C, and A+T, G+C content of the nsp coding genomic regions from their sequence space GC-profiling to understand the content of the nsp coding genomic regions (nsp1–16) (Fig. S4A1–A11 and Fig. S4B1–B5). We found that A+T is higher in all the nsp coding regions than G+C content. The G+C content of all the nsps (nsp1 to nsp11) of ORF1a are noted as 48.52%, 39.76%, 35.75%, 36.53%, 38.13%, 36.21%,37.39%, 38.22%, 40.12%, 42.45%, 53.80%. At the same time, G+C content of all the nsps (nsp12 to nsp16) of ORF1b are noted as 37.18%, 38.21%, 38.08%, 34.23%, 35.46%.
GC-Profiling of the nsp Coding Genomic Regions (nsp1–16) and Comparison with the Whole Genome of SARS-CoV-2
We analyzed the GC-profiling of the nsp coding regions of ORF1a and ORF1b. The graph shows the highest peak at 4000 bp and 20,000 bp regions. At the same time, the graph shows the lowest peak, in between 9000 to 12,000 bp regions (Fig. 6a).Fig. 6 GC-profiling of the nsp coding genomic regions a GC-profiling of both the nsp coding regions of ORF1a and ORF1b. It mapped the GC contents in every region of the nsp coding genes of ORF1a and ORF1b regions. b GC-profiling of the whole genome. However, no segmentation in the GC contents was noted in both cases
The GC-profiling of the whole genome shows the highest peak of 4000 bp and 20,000 bp regions, and suddenly, a very high peak was noted in the last part of the genome. At the same time, the graph shows the two lowest peaks, at 9000 to 12,000 bp and around 23,000 bp regions (Fig. 6b).
However, it has been observed that the GC-profile value of the nsp coding genomic regions (nsp1–16) is less (about 0.375) compared to the whole genome (about 0.38).
Discussion
Presently, researchers are trying to understand the architecture of RNA, especially the RNA structure in the genome [7, 37]. RNA structure can be utilized in different other conditions, such as the different significant scientific events (host immunity and the evolution of virus) [38]. At the same time, an understanding of architecture in RNA structures in secondary structural form and 3D structural form is important to illustrate the replication process [14, 39]. Simultaneously, researchers are trying to understand the druggable genome, one of the focus areas for structure-based drug design. Therefore, RNA structure in the genome component will help with RNA-targeted drug design [40]. In this direction, scientists are trying to solve the RNA architecture in the SARS-CoV-2 genome. Understanding the RNA secondary and 3D structure of the SARS-CoV-2-ssRNA genome is significant in this pandemic scenario and will help the RNA-targeted therapeutic design. Manfredonia et al. have tried to evaluate the structural signature of the SARS Cov-2 genome and identified RNA structural components with therapeutic significance [21]. In this direction, we have illustrated the secondary structure, 3D structure rated, and GC-profile of the nsp coding regions of the SARS-CoV-2 genome. Finally, we have identified ligand-binding pockets of the nsp coding regions. Therefore, our study is very significant and will initiate the discovery of RNA-based therapeutics against SARS-CoV-2.
Druggable genome-wide therapeutic siRNA discovery is one of the effective approaches for developing antisense oligonucleotide therapeutics [41–43]. Cao et al. have studied the SARS-CoV-2 RNA genome architecture and siRNA-based therapeutic design. They have identified four observed siRNAs, and no infection was found in the cell after treatment of siRNAs [7]. Sun et al. illustrated the RNA genome architecture of the SARS-CoV-2 and further explored siRNA-based therapeutic design. In this study, researchers have tried to identify the different genomic regions that are potential targets for siRNA. The study will help to develop siRNA-based therapies for SARS-CoV-2 [4]. Previously, we have also identified siRNAs targeting the mRNA of RdRp, an example of the RNA-based therapeutic discovery for SARS-CoV-2. However, we have targeted the mRNA of RdRp of SARS-CoV-2. Several researchers have tried to understand the transcriptomic profile of SARS-CoV-2 [37]. It will help to comprehend the SARS-CoV-2 life cycle and its pathogenicity. At the same time, the study will also help to explore RNA-based therapeutic design.
The druggability characterization within the SARS-CoV-2 proteome is a significant effort for viral drug target-based therapy. Cavasotto et al. [44] measured the functional role of each SARS-CoV-2 protein encoded from the whole RNA genome. Subsequently, they analyzed the main structural landscapes, using the experimental homology models or structural data using in-depth in silico druggability assessment of the viral proteome [45].
Deep learning-based algorithms and tools are important to illustrate the genome structure [46] and are used regularly for RNA secondary structure generation [47]. Sun et al. illustrated the RNA genome architecture of the SARS-CoV-2 using a deep learning tool and developed the RNA secondary structure of this virus. Along with the conventional method, our study used the deep learning-based modern tool to develop the secondary structure of the nsp coding regions of the SARS-CoV-2 RNA genome. The study compared the predicted deep learning-based secondary structures and conventional secondary structures (Centroid and MFE-based) (Table 2).Table 2. A comparative study of our developed deep learning-based secondary structures and conventional secondary structures (Centroid and MFE-based secondary structures)
Sl No Genomic regions nsp coding genes Deep learning-based secondary structures Centroid-based secondary structures MFE-based secondary structures
1 ORF1a nsp1 Approximately 11 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model which is developed by us is conventional Stem-loop, multi-branch loop noted. This structure is conventional
2 nsp2 Approximately 6 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model found as the conventional form Stem-loop, multi-branch loop noted. This secondary structure is conventional
3 nsp3 Approximately 6 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model is conventional Stem-loop, multi-branch loop noted.
The secondary structure model is conventional
4 nsp4 Approximately 6 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. This secondary structure is found as conventional conformation Stem-loop, multi-branch loop noted. It seems to be a conventional
5 nsp5 Approximately 9 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. We found the secondary structure as a conventional model Stem-loop, multi-branch loop noted. We noted as conventional model
6 nsp6 Approximately one complicated is found with pseudoknots Stem-loop, multi-branch loop noted. The model is shown as a conventional model Stem-loop, multi-branch loop noted. We found the structure as a conventional model
7 nsp7 Approximately 2 stem-loop structure are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The structure is the conventional type of structure Stem-loop, multi-branch loop noted. We observed the secondary structure as a conventional model
8 nsp8 Approximately 4 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. This secondary structure looks as conventional Stem-loop, multi-branch loop noted. The secondary structure model is conventional
9 nsp9 Approximately 7 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. Stem-loop, multi-branch loop noted. The secondary structure model found as the conventional form
The secondary structure model is conventional
10 nsp10 Approximately one complicated is found with pseudoknots Stem-loop, multi-branch loop noted. The secondary structure model is conventional Stem-loop, multi-branch loop noted. The secondary structure model found as a conventional form
11 nsp11 One small stem-loop structure is found Stem-loop, multi-branch loop noted. We found the structure as a conventional model Stem-loop, multi-branch loop noted. The secondary structure model found as a conventional form
12 ORF1b nsp12 Approximately 6 stem-loop structure are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model is conventional Stem-loop, multi-branch loop noted. The secondary structure model found as a typical form
13 nsp13 Approximately one complicated is found with pseudoknots Stem-loop, multi-branch loop noted. The secondary structure model is typical Stem-loop, multi-branch loop noted. The secondary structure model found as the typical form
14 nsp14 Approximately 5 stem-loop structure are found and pseudoknots are noted Stem-loop, multi-branch loop noted. This secondary structure looks like a typical model Stem-loop, multi-branch loop noted. This secondary structure is a typical form
15 nsp15 Approximately 4 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. The secondary structure model which is developed by us is typical Stem-loop, multi-branch loop noted. This structure found as the typical form
16 nsp16 Approximately 8 stem-loop structures are found and pseudoknots are noted Stem-loop, multi-branch loop noted. We found the structure as a conventional model Stem-loop, multi-branch loop noted. The secondary structure model found as a conventional form
Simultaneously, we calculated the GC content of the nsp coding regions. We found that the range of the GC content was 34.23% to 48.52%. Although, we found the nsp11 coding region is about 53.80%. However, the sequence length of this part is too short, so, we have not considered this region. Again, we evaluated the GC-profile of the nsp coding regions and compared to the whole SARS CoV-2 genome. Several other researchers have calculated the GC usage of SARS-CoV-2. Li et al. calculated the GC usage of the genes of SARS-CoV-2 and found lower GC content of the genome. It has been reported that the GC content of the virus coding sequence is around 38%. At the same time, researchers found that the GC content of the vertebrates along with the humans is around 60% [48].
Additionally, our study has identified drug-binding pockets from the RNA genome, and it is a promising approach for the therapeutic development of SARS-CoV-2 or other infective RNA viruses. Therefore, our work has immense value.
Limitations
Several researchers have used the next-generation platform (such as SHAPE-MaP evaluation) to illustrate the architecture of the RNA genome. Due to the lack of resources, we were unable to find the next-generation platform to develop the genome architecture of this RNA virus. However, to fulfill the limitation, we have used modern algorithms (deep learning-based algorithms) to illustrate the secondary structure of the genome structure. We have modeled the 3D structure of all nsp coding genes due to the lack of the crystal or cryo-electron structure. However, we urge researchers to develop crystal or cryo-electron structures of all the nsp coding genes.
The information-centric terminology in biological systems can be considered properly when it is embedded in theoretical biology, and it validates bioinformatics-based analysis. Successive models and experimental validation is exclusively required for any scientific experiment. Many researchers utilizing artificial intelligence are currently exploring new illustrations of information processing systems, often inspired by biological systems, e.g., protein-nucleotide network models and biomolecule pattern recognition. Our study emphasized advanced modeling practices of nsp coding genomic regions of SARS-CoV-2-ssRNA to understand and develop RNA-targeted therapeutics using the druggable genome.
Although all sorts of modeling, structure, and pattern analysis were considered distinct endeavors, we felt that for bioinformatics research, they were both desired and should be united to compare the outcome of such models with “real” data [49, 50].
Future Prospective
Our data illustrated nsp coding regions of the SARS-COV-2 genome. The data of our work act as the fundamental resources to unfold more about the SARS-CoV-2 life cycle, replication, and unknown architecture of the genome. At the same time, understanding the secondary and 3D structure of the genome and its composition is important. However, the secondary structure-guided 3D structure and its identified ligand-binding pocket will shed light on the druggable genome for the researcher to develop multiple therapeutics against the virus.
Conclusion
Our work not only emphasized the secondary and 3D structure development but also identified all the elements of secondary structure, such as stem-loop structure, multi-branch loop, pseudoknot structure, and the bulge structural components in the secondary structure in the nsp coding genes. We also identified the unbound structure, branched structure, duplex structure, three-way junction, four-way junction, etc., in the 3D structure. The study will help to identify the structural elements of the SARS-COV-2 genome.
Our data of binding pocket identification will offer a primary platform for RNA-targeted therapeutic development. It will help identify the druggable genome and unique RNA-based therapeutic target, which will help structure-based drug design against SARS-CoV-2. Finally, the identified binding pocket in the nsp coding regions will help future researchers to multiple small molecule-based ligand discoveries and antisense oligonucleotide therapeutics discoveries targeting those genomic regions to fight against the virus.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (RAR 1691 kb)Fig. S1. RNA secondary structure model based on centroid of all nsp coding regions (nsp1–nsp16) components of the structure such as stem-loop, multi-branch loop etc. (A1) Secondary structure conformations of nsp1 coding gene and it components (A2) Secondary structure conformations of nsp2 coding gene and it components (A3) Secondary structure conformations of nsp3 coding gene and it components (A4) Secondary structure conformations of nsp4 coding gene (A5) Secondary structure conformations of nsp5 coding gene and it components (A6) Secondary structure conformations of nsp6 coding gene and it components (A7) Secondary structure conformations of nsp7 coding gene and it components (A8) Secondary structure conformations of nsp8 coding gene and it components (A9) Secondary structure conformations of nsp9 coding gene and it components (A10) Secondary structure conformations of nsp10 coding gene and it components (A11) Secondary structure conformations of nsp11 coding gene and it components (B1) Secondary structure conformations of nsp12 coding gene and it components (B2) Secondary structure conformations of nsp13 coding gene and it components (B3) Secondary structure conformations of nsp14 coding gene and it components (B4) Secondary structure conformations of nsp15 coding gene and it components (B5) Secondary structure conformations of nsp16 coding gene and it components
Supplementary file2 (RAR 1503 kb)Fig. S2. RNA secondary structure model based on MFE of all nsp coding regions(nsp1–nsp16) (A1) Secondary structure conformations of nsp1 coding gene and it components (A2) Secondary structure conformations of nsp2 coding gene and it components (A3) Secondary structure conformations of nsp3 coding gene and it components (A4) Secondary structure conformations of nsp4 coding gene and it components (A5) Secondary structure conformations of nsp5 coding gene and it components (A6) Secondary structure conformations of nsp6 coding gene and it components (A7) Secondary structure conformations of nsp7 coding gene and it components (A8) Secondary structure conformations of nsp8 coding gene and it components (A9) Secondary structure conformations of nsp9 coding gene and it components (A10) Secondary structure conformations of nsp10 coding gene and it components (A11) Secondary structure conformations of nsp11 coding gene and it components (B1) Secondary structure conformations of nsp12 coding gene and it components (B2) Secondary structure conformations of nsp13 coding gene and it components (B3) Secondary structure conformations of nsp14 coding gene and it components (B4) Secondary structure conformations of nsp15 coding gene and it components (B5) Secondary structure conformations of nsp16 coding gene and it components
Supplementary file3 (RAR 2522 kb)Fig. S3. Entropy and mountain plots based on the secondary structure of all nsp coding regions(nsp1–nsp16) (A1) Entropy and mountain plots of nsp1 coding gene (A2) Entropy and mountain plots of nsp2 coding gene (A3) Entropy and mountain plots of nsp3 coding gene (A4) Entropy and mountain plots of nsp4 coding gene (A5) Entropy and mountain plots of nsp5 coding gene (A6) Entropy and mountain plots of nsp6 coding gene (A7) Entropy and mountain plots of nsp7 coding gene (A8) Entropy and mountain plots of nsp8 coding gene (A9) Entropy and mountain plots of nsp9 coding gene (A10) Entropy and mountain plots of nsp10 coding gene (A11) Entropy and mountain plots of nsp11 coding gene (B1) Entropy and mountain plots of nsp12 coding gene (B2) Entropy and mountain plots of nsp13 coding gene (B3) Entropy and mountain plots of nsp14 coding gene (B4) Entropy and mountain plots of nsp15 coding gene (B5) Entropy and mountain plots of nsp16 coding gene
Supplementary file4 (RAR 1363 kb)Fig. S4. A, T, G, C, A+T, and G+C content of the nsp coding genomic regions (A1) A, T, G, C, A+T, and G+C content of nsp1 coding gene (A2) A, T, G, C, A+T, and G+C content of nsp2 coding gene (A3) A, T, G, C, A+T, and G+C content of nsp3 coding gene (A4) A, T, G, C, A+T, and G+C content of nsp4 coding gene (A5) A, T, G, C, A+T, and G+C content of nsp5 coding gene (A6) A, T, G, C, A+T, and G+C content of nsp6 coding gene (A7) A, T, G, C, A+T, and G+C content of nsp7 coding gene (A8) A, T, G, C, A+T, and G+C content of nsp8 coding gene (A9) A, T, G, C, A+T, and G+C content of nsp9 coding gene (A10) A, T, G, C, A+T, and G+C content of nsp10 coding gene (A11) A, T, G, C, A+T, and G+C content of nsp11 coding gene (B1 A, T, G, C, A+T, and G+C content of nsp12 coding gene (B2) A, T, G, C, A+T, and G+C content of nsp13 coding gene (B3) A, T, G, C, A+T, and G+C content of nsp14 coding gene (B4) A, T, G, C, A+T, and G+C content of nsp15 coding gene (B5) A, T, G, C, A+T, and G+C content of nsp16 coding gene.
Author Contributions
CC conceptualized the study, collected and analyzed the data, wrote the main manuscript. ARS did the validation and editing. MB and SC did formal analysis and developed the figures and tables. GA edited the manuscript. CC and SSL did the overall supervision. All authors read and approved the final manuscript.
Data Availability
The authors confirm that the data supporting the findings of this study are available as Supplementary figures.
Declarations
Conflict of interest
The authors declare no competing interests.
Research Involving Human Participants and/or Animals
Not applicable.
Informed Consent
Not applicable.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Chiranjib Chakraborty and Manojit Bhattacharya contributed equally to this work.
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Biochem (Mosc) Suppl Ser A Membr Cell Biol
Biochem (Mosc) Suppl Ser A Membr Cell Biol
Biochemistry (Moscow) Supplement. Series A, Membrane and Cell Biology
1990-7478
1990-7494
Pleiades Publishing Moscow
5157
10.1134/S199074782205004X
Article
The Mechanisms of Lipid Vesicle Fusion Inhibition by Extracts of Chaga and Buckthorn Leaves
Efimova S. S. [email protected]
Zlodeeva P. D.
Shekunov E. V.
Ostroumova O. S.
grid.418947.7 0000 0000 9629 3848 Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia
9 12 2022
2022
16 4 311319
16 4 2022
1 6 2022
2 6 2022
© Pleiades Publishing, Ltd. 2022, ISSN 1990-7478, Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2022, Vol. 16, No. 4, pp. 311–319. © Pleiades Publishing, Ltd., 2022.Russian Text © The Author(s), 2022, published in Biologicheskie Membrany, 2022, Vol. 39, No. 5, pp. 355–363.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
The ability of extracts of grapefruit seeds (ESG), sea buckthorn leaves (ESBL), and chaga (EC) to inhibit membrane fusion was evaluated. It was found that ESBL and EC inhibited Ca2+-mediated fusion of phosphatidylglycerol-enriched lipid vesicles; the inhibition indexes were about 90 and 100%, respectively. ESG did not inhibit the fusion of negatively charged liposomes induced by calcium. In addition to calcium-mediated liposome fusion, EC inhibited the fusion of vesicles from a mixture of phosphatidylcholine and cholesterol under the action of polyethylene glycol with a molecular weight of 8000 Da (the inhibition index was 80%). The other two extracts had no effect on polymer-induced fusion of uncharged membranes. The effect of some major components of the tested extracts on the fusion of vesicles was evaluated. It has been shown that flavonols, quercetin and myricetin, which are major components of ESBL, inhibited the fusion of negatively charged membranes under the action of calcium (the inhibition indexes were about 85 and 60%, respectively). Another flavonol of ESBL, the glycoside of quercetin rutin, did not have such an effect. The data obtained made it possible to relate the ESBL suppression of calcium-induced fusion of lipid vesicles with the presence of quercetin and myricetin in its composition. These flavonols had virtually no effect on polyethylene glycol-induced vesicle fusion, which is consistent with the absence of ESBL action on liposome fusion under the action of polymer. The ability of quercetin and myricetin to reduce the melting temperature of phosphatidylglycerol with saturated hydrocarbon chains and to increase the half-width of the peak corresponding to melting has been demonstrated. The observed correlation between the parameters characterizing the thermotropic behavior of the lipid in the presence of quercetin and myricetin and the index of inhibition of calcium-mediated liposome fusion by these compounds may indicate a relationship between the ability of flavonols to influence the packaging of membrane lipids and inhibit vesicle fusion. Pentacyclic triterpenoids, betulin and lupeol, which are part of EC, did not inhibit the fusion of vesicles under the action of both calcium and polyethylene glycol, and their presence in EC cannot be responsible for the antifusogenic activity of EC.
Keywords:
natural extracts
membrane fusion inhibitors
liposomes
flavonols
saponins
issue-copyright-statement© Pleiades Publishing, Ltd. 2022
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pmcINTRODUCTION
Natural extracts are widely used in medicine as independent medications and in combination with other biologically active compounds. In addition, the extracts are actively used as components of cosmetics, since they have pronounced anti-inflammatory and antimicrobial effects.
Published data indicate a high antiviral activity of grapefruit seed extract (EGS). It has been established that EGS has a significant potential for use in poultry farming as a disinfectant, since it significantly reduced the titer of viruses that cause infectious diseases in poultry, in particular, avian influenza and Newcastle disease [1]. The results of recently published studies have shown that a commercially available nasal spray containing EGS can be used as an additional therapy for COVID-19 of mild and moderate severity [2].
It is known that sea buckthorn exhibits antiviral properties against the Dengue virus [3, 4]. Sea buckthorn leaf extract (ESBL) proved to be as effective in maintaining the viability of cells infected with dengue virus as the well-known antiviral drug ribavirin [5]. ESBL has also been shown to exhibit activity comparable to oseltamivir against influenza A and B viruses [6].
Recently, the antiviral activity, including against SARS-CoV-2, of birch fungus, chaga, has been widely discussed [7, 8]. The results of molecular docking showed that the components of the chaga extract (EC) (beta-glucan, galactomannan, and betulinic acid) bind to the C-terminal fragment of the receptor-binding domain of the SARS-CoV-2 S-protein [9]. EC also inhibits the fusion of the type 1 Herpes simplex virus with the cell membrane [10]. It was found that EC exhibits antiviral activity against a large number of viruses that cause diseases in cats: calicivirus, Herpes type 1, H3N2 and H5N6 influenza, panleukopenia, infectious peritonitis and immunodeficiency [11, 12]. A study of the mechanism of antiviral action of EC against feline calicivirus has shown that the inhibitory effect of the extract is associated with blocking the binding/absorption of the virus [11]. The activity of EC against the human immunodeficiency virus has also been demonstrated [13].
It is obvious that the antiviral activity of natural extracts should be due to their specific chemical composition. It is known that the composition of EGS in large quantities includes flavanone glycosides, naringin, hesperidin, and narirutin [14]. Naringin and narirutin are glycosides of naringenin, and hesperidin is a glycoside of a close analogue of naringenin, hesperetin. Analysis of the literature data showed that ESBL are rich in flavonols, quercetin, myricetin, and kaempferol, as well as various quercetin glycosides, in particular, rutin (quercetin-3-rutinoside) [15–17]. To date, about forty lanostane triterpenoids have been identified in the composition of EC, primarily lanosterol and its derivative, inotodiol. Pentacyclic triterpenoids, such as betulin and lupeol, as well as other sterols, in particular ergosterol, were found in several times lower concentrations than tetracyclic triterpenoids in the composition of chaga [18].
In this study, the ability of EGS, ESBL, and EC to inhibit the fusion of negatively charged and uncharged lipid vesicles under the action of calcium and high-molecular polyethylene glycol, respectively, was evaluated. The role of some components of extracts in the liposome fusion inhibition was determined; it was also established which physical and chemical properties of the bilayer are responsible for inhibiting membrane fusion by the components of extracts.
MATERIALS AND METHODS
The following reagents were used in the work: sodium chloride (NaCl), HEPES, NaOH, ethanol, dimethyl sulfoxide (DMSO), Triton X-100, Sephadex G-50, calcein, sorbitol, calcium chloride (CaCl2), polyethylene glycol with a molecular weight of 8000 Da (PEG-8000), quercetin, myricetin, rutin, betulin, lupeol, 1,2-dioleyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG), cholesterol (CHOL), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine) from Sigma (USA).
Grapefruit seed extract (EGS), sea buckthorn leaf extract (ESBL) and chaga extract (EC) were provided by Evalar CJSC. Testing was carried out for three samples of each extract, representing independent extraction series.
Investigation of the ability of the tested extracts and their components to inhibit the fusion of lipid vesicles mediated by various inducers. Monolamellar lipid vesicles from mixtures of DOPC/CHOL (80/20 mol %) and DOPC/DOPG/CHOL (40/40/20 mol %) loaded with a fluorescent marker calcein were formed using a mini extruder from Avanti Polar Lipids (USA). The solutions of lipids in chloroform were placed in a vial and the solvent was removed by a nitrogen stream. The resulting lipid film was hydrated with a buffer (35 mM calcein, 10 mM HEPES-NaOH, pH 7.4) and after five times freezing–thawing the mixture was passed through a polycarbonate membrane (Nucleopore TM, USA) with a pore diameter of 100 nm for 13 times to obtain a homogeneous population of large single-layer liposomes. The calcein that was not entrapped in the vesicles was removed by gel filtration on a column with Sephadex G-50. A calcein-free buffer (150 mM NaCl, 10 mM HEPES-NaOH, pH 7.4) was used as an eluent. Fluorescence of calcein inside liposomes at a concentration of 35 mM was self-quenched. Calcium (40 mM CaCl2) and polyethylene glycol with a molecular weight of 8000 Da (PEG-8000 at a concentration of 20 wt %) were used to induce the fusion of DOPC/DOPG/CHOL and DOPC/CHOL liposomes, respectively [19–22].
The samples of extracts from the initial solutions in water or DMSO were added into a suspension of liposomes up to a concentration of 100 µg/mL.
The fluorescence intensity of calcein outflowing from the liposomes into the solution medium during their fusion was measured with a Fluorat Panorama-02 spectrofluorimeter (at an excitation wavelength of 490 nm and emission of 520 nm). At the end of each experiment, Triton X-100 was introduced into the solution. At a concentration of 10 mM, this detergent destroyed all liposomes in the suspension, releasing the marker trapped by vesicles into the medium.
The index of inhibition of lipid vesicle fusion (II) by the tested extracts was calculated as :1 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$II = \frac{{R{{F}_{{{\text{Ind}}}}} - R{{F}_{{{\text{Inh}}}}}}}{{R{{F}_{{{\text{Ind}}}}}}}\,\, \times \,\,100\% ,$$\end{document}
where RFInd and RFInh represented the average maximum leakage of the fluorescent marker from vesicles induced by the introduction of calcium chloride or PEG-8000 in the absence and in the presence of the tested extracts, respectively.
The values of RF (%) (RFInd and RFInh) were determined by the formula:2 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$RF = \frac{{{\kern 1pt} {{I}_{{\text{i}}}} - {{I}_{0}}}}{{1.1I_{{\max }}^{{}} - {{I}_{0}}}}\,\, \times \,\,100\% ,$$\end{document}
where Ii and I0 were the fluorescence intensities of the solution in the presence and absence of the tested extracts, Imax was the fluorescence intensity of the solution after the addition of Triton X-100 (multiplier 1.1 was introduced to account for dilution of the sample with an aqueous detergent solution). RFInh was evaluated considering a possible intrinsic effect of extracts on the permeability of liposomes for the marker (calcein leakage due to the disordering of lipids under the action of extracts).
The kinetics of marker release under the action of fusion inducers before and after the introduction of the tested extracts was characterized by the time of e-fold increase in relative fluorescence.
For each type of extract, nine independent repetitions were performed with samples from three different batches. The parameters characterizing the effect of individual components of extracts on membrane fusion were determined by calculating the arithmetic mean values obtained in 2–3 independent experiments.
To prove the statistical significance of the detected differences in the average RF values before and after the addition of extracts or their components, the nonparametric Mann–Whitney–Wilcoxon criterion (*p ≤ 0.01) was used.
Confocal fluorescence microscopy of giant liposomes. Visualization of changes in the behavior of vesicles before and after the introduction of PEG-8000 and chaga extract into the suspension was performed using confocal fluorescence microscopy. Giant unilamellar vesicles were prepared from the mixture of DOPC/CHOL (80/20 mol %) and 1 mol % fluorescent lipid probe 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(rhodamine lizzamine) by electroformation (standard protocol, 3 V, 10 Hz, 1 h, 25°C) using a commercially available Nanion vesicle prep pro device (Germany). The resulting suspension of liposomes contained 0.5 mM of lipid in 1 M sorbitol solution. To induce vesicle fusion, PEG-8000 was added into the suspension to a concentration of 10 wt % and incubated for 5–10 min at room temperature (25 ± 1°C). EC (35 µg/mL) and PEG-8000 (10 wt %) were sequentially added into the experimental samples with incubation at each stage for 10 min. Liposomes were observed through a 100×/1.4 HCX PL immersion lens in a Leica TCS SP5 Apo confocal laser system (Leica Microsystems, Germany). The observations were carried out at 25°C. Fluorescence of 1,2‑dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(Rhodamine lizzamine) was excited at 543 nm (Helium–neon laser).
Differential scanning microcalorimetry of lipid vesicles modified with extract components. Giant unilamellar liposomes were formed from DPPG by electroformation using the Nanion vesicle prep pro device (Germany). An alternating voltage with an amplitude of 3 V and a frequency of 10 Hz was applied to the glasses for 1 h at 55°C. The lipid concentration was 3 mM. Quercetin, myricetin, and rutin were added into the experimental samples until the lipid : flavonol ratio reached 10 : 1. Thermograms of liposomal suspensions were obtained using a µDSC7 differential scanning microcalorimeter (Setaram, France). Reproducibility of the temperature dependence of the heat capacity was achieved by reheating the sample immediately after cooling at a constant rate of 0.2°C/min. The peaks on the thermograms were characterized by the maximum temperature of the main phase transition of DPPG (Tm) and the half-width of the main peak (T1/2). The changes in these parameters made it possible to evaluate the effect of flavonols on the packing density of membrane lipids.
The parameters characterizing the effect of flavonols on the thermotropic behavior of lipids were determined by calculating the arithmetic mean of the values obtained for 2 independent series of liposome preparation.
The values of RF, t, II, ΔTm, and ΔT1/2 were presented as mean ± standard error of the mean (mean ± SE).
RESULTS AND DISCUSSION
Figure 1a shows the time dependence of the relative fluorescence intensity of calcein (RF, %) released from DOPC/DOPG/CHOL (40/40/20 mol %) liposomes during vesicle fusion induced by the introduction of 40 mM CaCl2 into the suspension before and after incubation with EGS, ESBL, or EC at a concentration of 100 µg/mL for 30 min at room temperature. Table 1 shows the average values of the maximum calcein leakage (RF) during the fusion of DOPC/DOPG/CHOL vesicles under the action of calcium in the absence and in the presence of various extracts. The average maximum leakage of fluorophore during fusion of lipid vesicles unmodified with extracts upon addition of calcium chloride was about 90%. A decrease or increase in this value indicated the inhibition or activation of calcium-mediated fusion of negatively charged vesicles in the presence of the corresponding extract. As shown in Fig. 1a and Table 1, ESBL and EC significantly inhibited the fusion of DOPC/DOPG/CHOL vesicles caused by the addition of calcium chloride into the suspension: the corresponding RF values were 8 and 2%, respectively. To compare the antifusogenic activity of the extracts, their inhibition indices (II) were calculated based on the RF values according to formula (1) (Table 1). In the case of ESBL, II was about 90%, and in the case of EC it reached almost 100% (Table 1). EGS did not inhibit calcium-mediated fusion of negatively charged liposomes (Fig. 1a and Table 1).
Fig. 1. Time course of the relative fluorescence intensity of calcein (RF, %) leaking upon (a) calcium-mediated fusion of DOPC/DOPG/CHOL (40/40/20 mol %) liposomes and (b) PEG-8000-induced fusion of DOPC/CHOL (80/20 mol %) vesicles in the control conditions (black line) and after incubation with 100 µg/mL of EGS (red line), ESBL (green line), and EC (blue line).
Table 1. Parameters characterizing the effect of the extracts at a concentration of 100 µg/mL on calcein leakage at the fusion of vesicles formed from mixtures of DOPC/DOPG/CHOL (40/40/20 mol %) and DOPC/CHOL (80/20 mol %) upon the action of 40 mM CaCl2 and 20 wt % PEG-8000, respectively
Extract RF, % t, min II, % RF, % t, min II, %
CaCl2 PEG-8000
– 90 ± 6 61 ± 6 – 75 ± 5 46 ± 8 –
EGS 92 ± 5 9 ± 5 –3 ± 2 73 ± 6 33 ± 5 –10 ± 5
ESBL 8 ± 3* –# 90 ± 3 72 ± 7 4 ± 2 –8 ± 9
EC 2 ± 1* –# 97 ± 3 13 ± 5* –# 79 ± 3
RF is the maximum leakage of the fluorescent marker at the fusion of liposomes formed from mixtures of DOPC/DOPG/CHOL (40/40/20 mol %) and DOPC/CHOL (80/20 mol %), upon addition to the suspension of 40 mM CaCl2 and 20 wt % PEG-8000 in the absence (–) and in the presence of the tested extracts at a concentration of 100 µg/mL; t is the time constant characterizing the kinetics of marker release during vesicle fusion (the dependence of marker leakage on time is approximated by a one-exponential function); II is the index of inhibition by extracts of calcium and PEG-8000-mediated fusion of lipid vesicles of different composition. #Evaluation was not carried out due to the smallness of the RF value. *, p ≤ 0.01 (Mann–Whitney–Wilcoxon criterion, comparison of calcium- and PEG-8000-induced dye leakage from the vesicles in the absence and in the presence of extracts).
Figure 1b shows the time dependence of the relative fluorescence intensity of calcein (RF, %) resulting from the fusion of DOPC/CHOL (80/20 mol %) vesicles after addition of 20 wt % PEG-8000 before and after incubation with 100 µg/mL of EGS, ESBL, or EC. The average maximum leakage during fusion of unmodified liposomes extracts upon the introduction of PEG-8000 in the absence of extracts was 75% (Table 1). As is shown in Fig. 1b and Table 1, EGS and ESBL did not suppress PEG-induced fusion of uncharged vesicles: the corresponding RF values (79 and 72%, respectively) were close to the control value. At the same time, as in the case of calcium-induced fusion of negatively charged liposomes, EC suppressed the fusion of uncharged vesicles under the action of PEG-8000: RF was about 10%, and II exceeded 70% (Table 1).
Table 1 also presents the characteristic release times of the marker during liposome fusion in the absence and in the presence of the extracts. It can be seen that the time constant characterizing the kinetics of marker release during the fusion of DOPC/ DOPG/CHOL (40/40/20 mol %) and DOPC/CHOL (80/20 mol %) vesicles under the action of calcium and PEG, was about 60 and 50 min, respectively. Notably, the fusion of DOPC/DOPG/CHOL (40/40/20 mol %) liposomes under the action of calcium in the presence of EGS and the fusion of DOPC/CHOL (80/20 mol %) vesicles under PEG-8000 in the presence of ESBL was accelerated several times. These differences can be explained by the acceleration of adsorption of the corresponding fusion inductors on the membranes modified by the tested extracts.
Confocal fluorescence microscopy of giant unilamellar vesicles formed from the mixture of DOPC/CHOL (80/20 mol %) was performed to visualize the fusion of vesicles under the action of PEG‑8000 and its inhibition by EC. Figure 2 presents fluorescent micrographs of DOPC/CHOL liposomes in the absence of any agent (Fig. 2a), in the presence of 10 wt % PEG-8000 (Fig. 2b), and after the application of 10 wt % PEG-8000 to liposomes, pre-modified with 35 µg/mL of EC (Fig. 2c). PEG-8000 caused an increase in the size of liposomes, their deformation and induced the formation of multilayer and multivesicular liposomes (Fig. 2b); this indicated a high efficiency of fusion of lipid vesicles under the action of the polymer. At the same time, as Fig. 2c shows, PEG‑8000 did not have a similar effect on the lipid vesicles treated with EC: the probability of the appearance of multilamellar structures was low, and single monolamellar vesicles were found in large quantities in the suspension. These data supported the conclusion that EC suppresses PEG-8000-induced fusion of liposomes.
Fig. 2. Examples of fluorescent microphotographs of giant vesicles formed from the mixture of DOPC/CHOL (80/20 mol %) and 1 mol % of fluorescent lipid probe, dipalmitoyl phosphatidylethanolamine-N-(lissamine rhodamine B sulfonyl), in the absence of the agents (a), in the presence of 10 wt % PEG-8000 (b), and after addition of 10 wt % PEG-8000 into the suspension of liposomes pretreated with 35 µg/mL of EC (c). The size of each micrograph is 65 × 65 µm.
To elucidate the mechanisms of inhibition of calcium- and PEG-induced vesicle fusion by ESBL and EC, we evaluated the effect on this process of some major components of extracts: flavonols contained in ESBL; quercetin, rutin and myricetin, as well as pentacyclic triterpenoids found in the composition of EC—betulin and lupeol. The chemical structures of the tested compounds are shown in Fig. 3.
Fig. 3. The chemical structure of some components of ESBL and EC: quercetin, myricetin, rutin, betulin, and lupeol.
Figure 4 and Table 2 summarize the data obtained in the study of the antifusogenic activity of the tested components of ESBL and EC. Figure 4a and Table 2 show that the ESBL flavonols, quercetin and myricetin, inhibited the fusion of negatively charged membranes under the action of calcium (II was about 85 and 60%, respectively). Other component of ESBL—quercetin glycoside rutin—did not cause such an effect. Thus, the suppression of calcium-induced fusion of lipid vesicles under the action of ESBL can be attributed to the presence of quercetin and myricetin in its composition. The inability of flavonols to inhibit the fusion of uncharged liposomes under the action of PEG-8000 (Fig. 4b and Table 2) was in good agreement with the absence of ESBL effect on this process (Table 1).
Fig. 4. Time course of the relative fluorescence intensity (RF, %) of calcein leaking upon (a) calcium-mediated fusion of DOPC/DOPG/CHOL (40/40/20 mol %) liposomes and (b) PEG-8000-induced fusion of DOPC/CHOL (80/20 mol %) vesicles in the control conditions (black line) and after incubation with 20 µM of flavonols, quercetin (red line), myricetin (blue line), or rutin (cyan line) and 10 µM of pentacyclic triterpenoids, betulin (purple line), or lupeol (orange line).
Table 2. Parameters characterizing the effect of the components of the tested extracts on calcein leakage in the course of fusion of the vesicles formed from mixtures of DOPC/DOPG/CHOL (40/40/20 mol %) and DOPC/CHOL (80/20 mol %), upon the action of 40 mM CaCl2 and 20 wt % PEG-8000, respectively
Component, µM RF, % II, % RF, % II, % –ΔTm, °C ΔT1/2, °C
CaCl2 PEG-8000 DPPG
– 90 ± 6 – 75 ± 5 – – –
Quercetin, 20 9 ± 1* 85 ± 2 77 ± 11 –2 ± 5 1.2 ± 0.2 0.8 ± 0.1
Myricetin, 20 31 ± 3* 58 ± 4 76 ± 12 3 ± 10 1.1 ± 0.2 0.6 ± 0.2
Rutin, 20 88 ± 1 –5 ± 2 80 ± 3 –7 ± 6 0 0
Betulin, 10 90 ± 2 1 ± 1 67 ± 5 11 ± 2 0.1 ± 0.1a 0.1 ± 0.1a
Lupeol, 10 82 ± 9 7 ± 8 70 ± 4 8 ± 2 0.1 ± 0.1a 0.2 ± 0.1a
a According to [25]; RF is the maximum leakage of the fluorescent marker at the liposome fusion; II is the index of inhibition by major components of the tested extracts of calcium- and PEG-8000-mediated vesicle fusion; ΔTm and ΔT1/2 are changes in temperature and half-width of the peak of the main phase transition of DPPG ((lipid : flavonol and lipid : triterpenoid ratios were 10 : 1 and 50 : 1, respectively); *, p ≤ 0.01 (Mann–Whitney–Wilcoxon criterion, comparison of calcium- or PEG-8000-induced dye leakage from the vesicles in the absence and in the presence of extract components).
To understand the relationship between the effect of ESBL components on the fusion of negatively charged liposomes enriched with phosphatidylglycerol and their ability to modify the physical properties of phosphatidylglycerol-containing membranes, the thermotropic behavior of DPPG was studied before and after the introduction of quercetin, myricetin, or rutin into the liposomal suspension. In the absence of flavonols, the temperature of the main phase transition of DPPG, Tm, was 41.3°C, the half-width of the main peak, T1/2, was 0.6°C (Fig. 5). The main parameters characterizing the melting of DPPG in the presence of flavonols are presented in Table 2. Quercetin and myricetin at the lipid : flavonol ratio of 10 : 1 lowered Tm to by 1.2 and 1.1°C, respectively. At the same time, quercetin increased T1/2 by 0.8°C, and myricetin increased T1/2 by 0.6°C (Table 2). The introduction of rutin at the same concentration did not change the thermotropic behavior of DPPG (Table 2). The observed correlation between the parameters characterizing the melting of DPPG in the presence of flavonols and their antifusogenic activity in calcium-induced fusion of phosphatidylglycerol-containing vesicles (Table 2) indicated the relationship between their ability to affect the packing density of membrane-forming lipids and inhibit liposome fusion. A similar conclusion was made when the effect of alkaloids on the calcium-mediated fusion of vesicles and the thermotropic behavior of lipids were compared [23].
Fig. 5. The thermograms of DPPG (Cp(T)) in the absence (1) and in the presence of rutin (2), myricetin (3), or quercetin (4). Lipid : flavonol ratio was 10 : 1.
We have previously shown that quercetin and myricetin have a less pronounced effect on the thermotropic behavior of dipalmitoylphosphocholine (DPPC) than DPPG: at the DPPC : flavonol ratio of 10 : 1 quercetin and myricetin caused a drop of Tm by 0.3°C, and an increase in T1/2 by 0.7 and 0.2°C, respectively [24]. As in the case of DPPG, rutin had no effect on the melting of DPPC [24]. The obtained data on the significant suppression of calcium-mediated fusion of phosphatidylglycerol-containing vesicles in the presence of quercetin and myricetin and the absence of the inhibitory ability of these flavonols against PEG-8000-induced fusion of phosphatidylcholine-enriched vesicles (Table 2), the pronounced effect of quercetin and myricetin on DPPG melting (Table 2), and the reduced effect in the case of DPPC [24] suggest that the antifusogenic activity of these flavonols may be due to their ability to disorder phosphatidylglycerol membranes. At the same time, the less pronounced effect of quercetin and myricetin on the packing density of phosphatidylcholine bilayers led to the inability of flavonols to suppress the fusion of phosphatidylcholine-enriched vesicles.
Figure 4 shows that pentacyclic triterpenoids, which are part of EC, betulin and lupeol, practically did not inhibit the fusion of either negatively charged vesicles under the action of calcium (Fig. 4a) or uncharged liposomes in the presence of PEG-8000 (Fig. 4b). Thus, due to the unexpressed antifusogenic activity of these triterpenoids in both systems (Table 2), betulin and lupeol could not be the components responsible for the EC suppression of vesicle fusion under the action of both calcium and PEG-8000 (Table 1). It should be noted that the tested triterpenoids did not affect significantly the thermotropic behavior of DPPG (Tm decreased by less than 0.3°C, and T1/2 increased by 0.1°C (Table 2)) and DPPC [25]. This is in a good agreement with the assumption that the disordering ability of the tested compounds is related to their antifusogenic activity: the weak effect of betulin and lupeol on the melting of DPPG (Table 2) and DPPC [25] manifested in the inability of these triterpenoids to inhibit the fusion of phosphatidylglycerol- and phosphatidylcholine-enriched vesicles (Table 2).
It is unlikely that the antifusogenic ability of EC was due to the presence of sterols in its composition since they are known for their ability to increase the negative spontaneous curvature of lipid monolayers during adsorption [26] and thereby can rather induce membrane fusion. The presence of a hydroxyl group in the side chain of a hydrophilic derivative of lanosterol, inotodiol, could prevent its immersion in the hydrocarbon backbone of the bilayer and change the transmembrane profile of lateral pressure in such a way as to increase the energy of formation of intermediates of fusion and suppress the process of membrane unification. Inhibition of fusion of uncharged lipid vesicles by chaga extract may indicate the antiviral effect of this extract.
FUNDING
The work was partially supported by ZAO Evalar. Studies of the effect of flavonols on membrane fusion and thermotropic behavior of lipids were supported by the Russian Science Foundation (project no. 22-15-00417).
COMPLIANCE WITH ETHICAL STANDARDS
The authors declare that they have no conflict of interest.
This article does not contain any studies involving animals or human participants performed by any of the authors.
Abbreviations: DOPC, 1,2-dioleyl-sn-glycero-3-phosphocholine; DOPG, 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol); CHOL, cholesterol; DPPG, 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol); PEG-8000, polyethylene glycol with a molecular weight of 8000 Da; ESG, extracts of grapefruit seeds; ESBL, extracts of sea buckthorn leaves; EC, extracts of chaga.
Translated by E. Puchkov
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| 0 | PMC9735229 | NO-CC CODE | 2022-12-14 23:29:53 | no | Biochem (Mosc) Suppl Ser A Membr Cell Biol. 2022 Dec 9; 16(4):311-319 | utf-8 | Biochem (Mosc) Suppl Ser A Membr Cell Biol | 2,022 | 10.1134/S199074782205004X | oa_other |
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Mol Biotechnol
Mol Biotechnol
Molecular Biotechnology
1073-6085
1559-0305
Springer US New York
625
10.1007/s12033-022-00625-7
Review Paper
The SHERLOCK Platform: An Insight into Advances in Viral Disease Diagnosis
Zahra Ambreen 1
Shahid Ayesha 1
Shamim Amen 1
Khan Sultan Habibullah 1
http://orcid.org/0000-0003-2218-9054
Arshad Muhammad Imran [email protected]
12
1 grid.413016.1 0000 0004 0607 1563 Center for Advanced Studies (CAS) for Agriculture and Food Security, One Health Lab, University of Agriculture, Faisalabad, 38000 Pakistan
2 grid.413016.1 0000 0004 0607 1563 Institute of Microbiology, University of Agriculture, Faisalabad, 38000 Pakistan
9 12 2022
116
8 10 2022
26 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Persistence and prevalence of microbial diseases (pandemics, epidemics) is the most alarming threats to the human resulting in huge health and economic losses. Rapid detection and understanding of the disease dynamics by molecular biotechnology tools allow for robust reporting, treatment and control of diseases. As per WHO, the optimal diagnostic approach should be quick, specific, sensitive, without a stringed instrument, and low cost. The drawbacks of traditional detection techniques promote the use of CRISPR-mediated nucleic acid detection methods such as SHERLOCK as detection method. It takes advantage of the unexpected in vitro features of CRISPR-Cas system to develop field-deployable sensitive detection tools. Previously, CRISPR-mediated diagnostic methods have extensively been reviewed particularly for SARS-COV-2 detection, but it fails to provide the insight into advances of this technique. This study is the first attempt to review the advances of SHERLOCK approach as diagnostic tool for viral diseases detection. Variations of SHERLOCK mechanism for improved efficiency are discussed. Particularly integrated SHERLOCK approaches in terms of extraction-free assay and Bluetooth-enabled detection are reviewed to access their feasibility for the development of simpler and cost-effective diagnostic toolkits. Insight in to perks and limitations of diagnostic methods indicates its potential as ultimate diagnostic instrument for disease management.
Graphical Abstract
Keywords
COVID-19
Infectious diseases
CRISPR
Robust techniques
Diagnostics
SHERLOCK
http://dx.doi.org/10.13039/100019473 Ministry of Science and Technology, Pakistan DDWP-2021 Khan Sultan Habibullah
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pmcIntroduction
In recent years, the spread of infectious diseases like severe acute respiratory syndrome (SARS), ZIKA, Ebola, Hepatitis, Influenza, Tuberculosis, Human Monkey Pox, Hemorrhagic Fever, Typhoid, etc. has increased, posing a serious threat to public health [1]. The pattern of reoccurrence and resurgence of infectious disease would continue to grow due to increased population, increased number of aged persons, and enhanced inter/intra continental traveling which facilitates the growth, mutation, and spread of novel infectious diseases [2]. In the last 3 decades, the world has witnessed the emergence of more than 30 new infectious diseases. Unfortunately, in most instances, Asia is the epicenter for the emergence and reemergence of these diseases [3]. All these atrocious diseases significantly affected global health, social stability, and the world economy. Authorities in the healthcare system highlighted the importance of screening as many people as possible to detect affected persons and locating their connections as an efficient solution for controlling viral transmission [2].
As per an estimation, until now approximately 39 diagnostic tests have been approved by FDA which mainly rely on laboratory procedures [4]. The current paradigm of clinical disease detection relies on the pathogen culture and detection of specific antibodies, antigens, or nucleic acid of pathogens for which patient samples have to be sent to centralized diagnostic laboratories for analysis [5, 6]. Conventional methods like “Enzyme-Linked Immunosorbent Assay” (ELISA), “Reverse Transcriptase Quantitative PCR” (RT-qPCR), “Next Generation Sequencing” (NGS), and Point of Care (POC) diagnosis are the most common in practice (Table 1) for the microbial identification and nucleic acid testing. However, these methods are time-consuming, rely on laboratory procedures, and require high-cost machines which limit their applicability as on-site diagnostic procedures [5]. It demands the development of robust, efficient, sensitive, accurate, and economical detection methods to enhance the timely disease detection for their intervention.Table 1 Comparative overview of the SHERLOCK with conventional disease diagnostic technologies in terms of its efficiency, merits, and demerits
Diagnostic method Methodology Target molecule Test time (min) Sensitivity
(%) Specificity (%) Signal detection Strength Challenges References
RT-qPCR PCR mRNA 120–140 90–100 100 Fluorescence Widely adopted, real-time assay, quantitative, sensitive, high sensitivity Costly, requires skilled personnel, high chances of false-positive results, turnaround time of 2–5 days [2, 7]
ELISA Immunoassay Antibody 60–180 85–100 90–100 Calorimetric Identification of recovering plasma donors, disease prevalence studies Not suitable for the active cases detection [8, 9]
NGS Sequencing mRNA 1–2 days – – Contact tracing, identifying viral evolution Expensive [2, 10]
Biosensors mRNA, antigen, antibody < 60 – – Robust, cost-effective, real-time detection Low accuracy, not suitable for on-site diagnosis, reduced shelflife [11]
Aptamer-based biosensor Biological interaction ssDNA, ssDNA hairpins – – – – Specific, robust, low cost, and reusable Need improvement in sensitivity & reproducibility [12]
Nanocomposite-sensing platform Hybridization of nucleic acid with nanocomposite ssRNA – – – Electrochemical impedance spectroscopy High sensitivity, biocompatible, & non-toxicity Incompatibility with many agents, single use application [13, 14]
DETECTOR RPA followed by CRISPR-Cas12 detection DNA and RNA 60–120 93 95.5 Fluorescent, lateral flow detection Sensitive, single-copy viral detection, accurate, no need for specialized infrastructure False-positive results, risk of post-amplification contamination [15, 16]
SHERLOCK RPA followed by CRISPR-Cas13a detection RNA 60 100 100 Fluorescence, lateral flow detection Detect low concentrations, Discriminate between single-nucleotide differences, portable deployment Contamination risk due to two-step reaction, weak signals for low template concentration, strong background due to multiple enzymes [17, 18]
Alternatively, “Clustered Regularly Interspaced Short Palindromic Repeats” (CRISPR) has emerged as a potent tool for genome editing since its discovery in 1987. The ability of CRISPR and CRISPR-Associated Proteins (Cas Proteins) to correct genetic defects and prevent disease spread enabled scientists to utilize this technology in therapeutics and molecular diagnostics of infectious diseases. These methods have higher diagnostic accuracy and emerged as a promising tool not only for diagnostic purposes but also to identify antibacterial or antiviral-resistant microbes and for the inactivation of infectious pathogens [19]. Mostly the CRISPR-Cas platforms are developed on Cas-9 protein which transformed the world of genetic manipulation thus, speeding the development of new techniques in fundamental studies and clinical practices. CRISPR-Cas9 techniques were able to detect the Zika virus in 2016 and MRSA in 2017 [20]. However, the recognition and cleavage activity is restricted in specific systems because of the requirement of “Protospacer Adjacent Motif” (PAM) or “Protospacer Flanking Sequence” (PFS) [21]. The discovery of Cas12a (formerly Cpf1) and Cas13a (formerly C2c2) proteins revolutionized nucleic acid detection due to their collateral cleavage activity and the lack of PAM and PFS in some orthologs. Particularly Cas13a is ssRNA-specific single component RNA-guided RNA-targeting effector protein that target and cleaves the desired RNA as well as neighboring non-targeted RNA [22].
The particular activity of Cas13a was considered to develop an effective CRISPR platform known as “Specific High-Sensitivity Enzymatic Reporter Unlocking” (SHERLOCK) in 2017 by Prof. Feng Zhang and his team. Later it was used as a diagnostic platform in 2018 for the speedy detection of infectious diseases such as; ZIKA and COVID-19 [17]. In SHERLOCK, nucleic acid pre-amplification was combined with the collateral activity of Cas13 for specific recognition of desired nucleic acid that allows the ultrasensitive, portable, and multiplexed identification of pathogenic nucleic acid from clinical samples [23]. It emerged as promising diagnostic technology, especially in the recent wave of COVID-19. The sensitivity and accuracy of SHERLOCK are advantageous for the development of the cost-effective off-site diagnostic procedure (Table 1) as compared to PCR-based methods. While previously published plethora of literature reviews the CRISPR as diagnostic and therapeutic tool specially for SARS-COV2, the present study reviews the developments of SHERLOCK (CRISPR-mediated technique) and its use as diagnostic tool for viral disease detection. It is first study where the potential and advances of SHERLOCK has comprehensively been reviewed. The objective of this paper is to explain the features, functions, and possibilities of SHERLOCK as prospective testing equipment for infectious viral disease diagnosis to curb the disease outbreaks. Being progressing technique currently SHERLOCK is facing some challenges/shortcomings that are being addressed by integrating other diagnostic methods with this technique. The highlight of the review is the advancements in the SHERLOCK through integrated approaches particularly focusing on extraction-free assays and Bluetooth-enabled detection. This information paves the way for the development of SHERLOCK-based point-of-care devices for viral disease diagnosis.
Mechanism of SHERLOCK-Mediated Approach
SHERLOCK is the CRISPR-Cas13-based real-time nucleic acid detection method based on the “Recombinase Polymerase Amplification” (RPA) and “Loop-Mediated Isothermal Amplification” (LAMP) amplification of the nucleic acid followed by collateral cleavage of a reported sequence by Cas13a (Fig. 1). Although the original protocol focused on the RPA and LwCas13a, it can be modified for Cas12a, Cas13a, or any other Cas protein variant accordingly. Depending on the choice of reporter molecule, fluorescence detection or lateral flow assay both are compatible with SHERLOCK. Generally, CRISPR-Cas13 system comprises of two components (i) RNA-guided Cas13 RNase with HEPN (higher eukaryotic and prokaryotic nucleotide-binding domain) mediated endonuclease activity, and (ii) pre-CRISPR-RNA (crRNA) that can recognize mature crRNA for targeted activity [24].Fig. 1 Schematic overview of the SHERLOCK-mediated disease diagnostic approach representing the various methods adopted for sample preparation, nucleic acid extraction, and Cas-mediated detection. The figure showed that nucleic acid could be extracted from blood, urine, or nasopharyngeal samples by kit-based extraction, HUDSON method, and magnetic-bead-based extraction. The extracted nucleic acid is then amplified either by LAMP or RPA methods, where amplicons are detected by probe-associated CRISPR-Cas. The results could be obtained on lateral flow strip or through fluorometer
SHERLOCK detection approach consist of three major steps including (i) sample acquisition, (ii) amplification, and (iii) CRISPR-mediated collateral activity and detection. The detection procedure starts from the sample acquisition which could be in the form of blood, urine, and nasal swab or the nucleic acid (either DNA or RNA) extracted from the patient samples. It is followed by the isothermal amplification of the target genome through recombinase polymerase (RPA) or loop-mediated isothermal amplification (LAMP). The target molecules are then subsequently converted to RNA targets by T7 transcription. Binding and collateral cleavage activity of Cas13 is then utilize for the detection. Specificity of this system is ensured by the crRNA-target pairing which is confirmed by designing target-specific Cas13: crRNA complexes according to the target agent to activate and cleave fluorescent RNA sensors. Signal amplification of cleavage activity of LwCas13a protein on RNA reporter (already added in reaction) is done to achieve further sensitivity [17, 25]. The results of collateral activity conferred by detached biotin-fluorescein RNA reporter is then captured. Single-plex colorimetric or lateral flow reactions and single- or multiplex fluorescence-based SHERLOCK reactions are both viable options for detection (Fig. 1). The intensity and existence of fluorescent light indicate the concentration of the target molecule in the clinical samples [25]. Combining Cas13 with Cas12 in the same assay allows for the simultaneous detection of several targets inside the same reaction.
SHERLOCK-Mediated Disease Diagnosis
SHERLOCK has proven as versatile and robust method for the detection of DNA or RNA and has vast applications in rapid disease diagnosis and genotyping. The use of handheld spectrometers or portable electronic fluorescent readers can reduce the instrumentation cost to < 200$ which could be further reduced to 0.61$/test by redesigning the method on paper [25]. In 2017, SHERLOCK v1 was introduced that relies on the Cas13a nuclease originating from Leptotrichia wadei that could detect and cleave RNA molecules unlike the activity of Cas12. Though, SHERLOCK v1 was reliable and able to detect low viral concentrations its applicability was limited by its qualitative nature, dependence on the fluorescent detection instrument for expression readout, and detection of a single target molecule in a single reaction. These limitations were addressed in the SHERLOCK v2 which focused on the (i) combined activity of Cas13 with Csm6 to enhance the sensitivity by 3.5-fold, (ii) 4-channeled multiplexed reaction by Cas enzyme orthologs for the detection of up to four different targets in a single reaction, (iii) quantitative measurement of signals, and (iv) lateral flow readout for instrument-free portable detection. The combination of Cas13 with Csm6 not only improves the sensitivity but also allows the direct detection of most pathogen variants without pre-amplification. These modifications broaden the quantification aspect and the process utility, so it is more visual and sensitive [26]. The validity of SHERLOCK testing for SARS-COV-2 detection on the clinical patient samples from Thailand indicated 100% specificity and sensitivity in the case of fluorescent detection while, lateral flow assay showed 100% specificity with 97% sensitivity [27].
Two-step SHERLOCK testing in combination with LAMP assay was given emergency use authorization by FDA as a portable diagnostic kit for COVID testing thus making it the first-ever FDA-approved CRISPR-Cas diagnostic system. The commercial availability of the kit allows viral detection in one hour with standard laboratory equipment such as a water bath and fluorometer. Testing of the kit on 30 positive and negative nasopharyngeal samples indicated 100% sensitivity and specificity of the test with 6.75 copies/µL of limit-of-detection [28]. However, the cost and the requirement of proper lab setup are the limitations that must be addressed for the economical implementation of such a system in laboratory settings.
Time consumption and higher risks of cross-contamination hinder the applicability of two-step diagnosis. An important variation in this regard enabled the performance of the whole SHERLOCK assay in a single tube which is termed SHERLOCK Testing in One Pot (STOP). It allows for rapid viral detection in femtomolar concentration in 10–15 min and attomolar concentration in less than an hour. It reduces the cross-contamination chances and allows cost-effective offsite disease detection [17]. Recently, a similar type of diagnostic approach is used for detecting SARS-COV 2 (termed STOPCOVID v1). The Nucleic Acid is amplified by LAMP at temperatures 55–70 °C is detected through the specific activity of thermostable Cas12b in the presence of reporter molecule. In STOPCOVID v2, the nucleic acid sample was concentrated by magnetic beads that result in 600 times higher yielding input as compared to the CDC test. Overall, the process can detect 100 copies/sample or 33 copies/mL as compared to 1000 copies/mL detected by the CDC-approved RT-qPCR. Although, this process has the advantage of high sensitivity, unextracted sample processing, and one-fluid handling at a single temperature yet its cost must be reduced. Installation of modular heather will help in streamlining the workflow for a simpler process [29].
Quality assurance of the tested method is challenging due to varying sample collection and preparation methods, incomplete understanding of time course viral dynamics, and lack of standard reference. Integrated approaches based on simpler sample preparation and portable analytical procedures are the future exploratory areas for researchers.
Extraction-Free SHERLOCK Analysis
Replacement of diagnostic gold standard “RT-PCR” with more robust and economical CRISPR-mediated methods would require them to be more scalable, efficient, and sensitive for their easier deployment in low-resource settings. Nucleic acid extraction by commercially available kits is the major hurdle in the field deployment of CRISPR diagnostics due to the multi-step processing, and the requirement of expensive chemicals and trained personnel [30]. Eliminating nucleic acid extraction (Fig. 1) can greatly reduce the time and chemical requirements [5]. The pairing of SHERLOCK with direct sample detection is a must for this technique to excel in any context. Raw nucleic acid extraction through mechanical or chemical forces is suitable but it may contaminate the sample with nucleases or PCR inhibitors which can degrade reporter molecules and cause false-positive signals. Pre-treatment of nucleic acid with RNase inhibitors or HUDSON [inactivation of inhibitors by heat and reducing agents such as Tris (2-carboxyethyl) phosphine hydrochloride (TCEP)] is a viable approach to reduce contamination risk [17]. To develop the field-deployable diagnostic system, HUDSON was integrated with SHERLOCK for the detection of ZIKA and Dengue virus. HUDSDON-treated unextracted saliva or urine samples were directly employed for the RPA while, blood samples need 1:3 dilution with phosphate buffer saline to avoid coagulation during the amplification process [31]. Focusing on this aspect, an extraction-free sensitive SARS-COV-2 detection test known as streamline highlighting of Infections to Navigate Epidemics (SHINE) has been developed. In version 1 of the protocol, patient samples were treated with a mixture of TCEP, EDTA, and murine RNase inhibitors at 40 °C for 5 min followed by incubation at 70 °C for 5 min for sample lysis. The extracted sample was then processed and analyzed by optimized single-step SHERLOCK where visual readouts were monitored through a specially designed smartphone app. The overall process took almost 50 min. Validation of protocol on 50 patients indicates 90% sensitivity and 100% specificity compared with RT-PCR [5]. The process was further simplified in SHINE.v2 by eliminating the need for heating and cold storage of reagents. The modified process took < 90 min and showed 100% specificity and 90.5% of sensitivity as compared to RT-PCR. SHINE.v2 was effectively discriminated between a different variant of the SARS-COV-2. Heat block working at 37 °C and lateral flow sticks were mainly required for the process which enabled its easy use in far reached low-resource areas [32].
Similarly, an RNA-extraction-free CRISPR detection method known as Diagnostics with Coronavirus Enzymatic Reporting (DISCoVER) has been developed for the covid diagnosis. It allows the direct lysis of saliva samples through heating in lysis buffer followed by sample loading in a gravity-driven microfluidic cartridge where samples are amplified by LAMP at 65 °C for 20–30 min. LbuCas13 molecules then identify and cleave the crRNA-specific amplicons at 37 °C and provide fluorescent readouts in 5 min. Unextracted samples are usually at a high risk of degradation due to the presence of RNase in the raw sample as was observed in the present scenario but the treatment of saliva samples with low concentrations of TCEP-EDTA was found to preserve the target RNA. The attomole sensitivity with 100% positive predictive value and 93.7% negative predictive value as seen by automated processes substantially decreases the likelihood of contamination spread. The clinical trial showed 94% sensitivity and 100% specificity of the test [33]. However, the need for specialized equipment is a major limitation of the process in its applicability as a portable diagnostic tool.
Recently, SHERLOCK testing has been optimized with LAMP amplification. Even though, RPA has been in more practice as many CRISPR-based diagnostic methods are developed on it. However, it faces the challenges of cross-contamination due to two-step reactions, weak signals, and long-incubation time. Alternatively, LAMP has a high yield, affordability, and accessibility as it is more specific and speedier [34] but it is limited by false-positive results due to contamination, formation of primer dimers, and sequence similarities [35]. Diseased samples were mixed with proteinase K and heated at 65 °C for 6 min followed by 3 min of treatment at 98 °C. Cooled samples were then processed for the LAMP-based SHERLOCK where amplification was performed at 61 °C for 30 min followed by LwCas13a detection reaction with amplicons at 37 °C. Positive samples were detected by measuring fluorescence for 10 min at 2 min intervals [36].
Integrated Approaches for SHERLOCK Diagnosis
The limitations of the SHERLOCK-mediated diagnosis call for the integration of various methods to enhance the efficiency and efficacy of this technology. Recently, many research groups were able to combine two or more aspects of a process in a single process pipeline to develop efficient methods like SHINE, Sherlock, CARMEN, CREST, etc. which enabled robust disease detection (Fig. 2). Each method has its own set of possibilities and challenges.Fig. 2 Comparative evaluation of SHERLOCK-mediated diagnostic approaches in terms of experimental duration. The figure showed the time required for extraction, amplification, and detection step for various variations of SHERLOCK method. Two-step SHERLOCK took almost 220 min while STOPCovid V2 took almost 60–70 min
In an attempt to develop an economical and self-contained POC diagnostic approach, SHERLOCK was modified to be operated by utilizing minimum instruments (miSHERLOCK). This platform integrated STOP reaction with RNA paper-capture technique for the instrument-free, battery-operated multiplexed detection of SARS-COV-2 and its different variants. The experiment was performed in a specially designed battery-operated heater that could achieve temperatures up to 95 °C. Saliva samples were inactivated at 95 °C and RNA was concentrated onto a column filter which was then automatically plunged into SHERLOCK reaction mixture (consisting of RPA reagents and Cas12a) and processed at 37 °C. Reaction output was monitored visually or through the smartphone app. RNA filtration and concentration through this method not only reduces the chances of cross-contamination but also improves the sensitivity of the assay by 2–20-folds. The cost of miSHERLOCK device is approximately $15 which can further be reduced to $11 by reusing the heater and electronics. The major share of the cost accounts for the commercially obtained reagents and enzymes. Testing of the assay on a small set of saliva samples and the unavailability of test clinical samples were the major limiting factors of the assay [37].
The development of affordable and portable diagnostic facilities is the major goal of the current efforts. Integration of CRISPR with battery-operated, Bluetooth-enabled, field-ready mini thermocyclers allows the deployment of this technology in unconventional environments for viral detection. Based on this aspect, CREST protocol has been developed where the use of mini-PCR mini16 has been suggested as an economical solution for viral target amplification. Whereas for the visualization of results, a battery-powered P51 cardboard fluorescence visualizer has been used instead of lateral flow assay or the fluorometer [38]. Currently, RNA extraction through commercial kits is the limiting factor in the affordable scalability of this technique. An extraction-free protocol precipitation-enhanced analyte retrieval (PEARL) has been combined with CREST to omit the need for commercial RNA extraction kits. PEARL utilize common laboratory reagents such as sodium acetate, TCEP, IGEPAL, polyacrylamide, and HEPES–KOH as lysis solution for nucleic acid or protein extraction. Sample purification was performed by ice-cold precipitation by isopropanol and ethanol. The extracted sample can directly be utilized for detection purposes making the process more streamlined and robust [39].
Routine laboratory diagnostics are sufficient to provide information to patients and healthcare workers to curb the disease’s spread. However, multiplexing of the detection method is essential for robust and inexpensive identification of circulating pathogens [4]. Cas13 approaches are blessed with the advantage of multiplexing which allows the (i) targeting of multiple sites in a single genome, (ii) differentiation between related serotypes and viral species, and (iii) simultaneous detection of multiple mutations within co-circulating SARS-COV-2 variants with high fidelity [24]. Combining the strengths of CRISPR with multiplexing will be ideal for the surveillance of hundreds of samples in one go. For this purpose, the “Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic-acids” (CARMEN) approach was developed where CRISPR-related detecting reagents including Cas13, crRNA, and reporter molecule were combined as fluorescent color-coded nanoliter droplets on the microwell-array system which were then paired with amplified nucleic acid samples in a single-step. Detection reaction monitored by fluorescence microscopy [4].
In general, regardless of the adopted method, there must be some modifications in SHERLOCK or CRISPR-based techniques for their improvement. It includes the (i) development of extraction-free methods with concomitant advances in customized reagents, (ii) improvement in one-pot assays for better control over reaction dynamics, (iii) focus on the portable deployment of the diagnostic methods by improving reagent shelf-life or by employing battery-operated equipment, (iv) identification of novel Cas variants to meet the specific diagnostic needs, (v) per sample reduction in diagnostic cost.
CRISPR Diagnostics and Its Potential Applications
An ideal diagnostic test would have high specificity and low false rates for detecting pathogens, in addition, to be cheap, portable, and capable of differentiating between various types of pathogens. Currently, such test type of diagnostic tolls is very fewer in the market. For the overwhelming infectious as well as noninfectious diseases around the globe, the development of novel instruments that meet the requirements of the WHO’s recommended screening procedures has the potential to profoundly transform epidemiological monitoring and healthcare delivery. Employing a universal “16S rRNA gene V3 RPA” primer set, SHERLOCK can distinguish bacterial strains. SHERLOCK has also been used to uncover antibiotic resistance genes to detect and genotype bacterial or viral infectious disease pathogens. When a critical SNP is known, SHERLOCK can be used to do SNP screening by carefully constructing a crRNA to target the area containing the SNP of interest, which promotes preferential binding of one mutant over another [25].
SHERLOCK has recently been extensively used for the detection of viral diseases such as COVID-19, Dengue, Pneumonia, Hepatitis, Zika, Ebola, and Influenza, etc. (Table 2). In first of its kind study to identify the Zika virus (ZIKV) to determine its genotype, Pardee et al. amplified the viral RNA employing isothermal amplification. The DNA was subsequently cut using CRISPR/Cas9, and this activity was recognized by toehold switch sensors, resulting in a colorimetric display on a test paper. With a single-base precision, this approach can discriminate between the American and African variants of the ZIKA virus [40].Table 2 Diagnostic potential of SHERLOCK for the detection of viral diseases
Disease Causative agent Cas variant Amplification Detection Assay reaction time (min) Specificity (%) Sensitivity References
COVID-19 SARS-COV-2 AapCas12b Loop-mediated isothermal amplification (LAMP) of viral RNA Lateral flow detection 140 100 – [41]
COVID-19 SARS-COV-2 LwaCas13 Direct amplification by real-time-recombinase polymerase amplification (RT-RPA) Fluorometric detection 60 100 2.5 copies/µL (96%) [42]
ZIKA ZIKV LwCas13a RT-RPA of viral sample treated via HUDSON method Fluorescence or calorimetric < 120 100 1–1000 cp/µL [31]
Dengue DENV1 LwCas13a RT-RPA of viral sample treated via HUDSON method Calorimetric (lateral flow) < 60 100 – [31]
Tuberculosis (TB) Mycobacterium tuberculosis Cas12 LAMP of extracted viral nucleic acid Later flow/real-time fluorescence 55–60 100 10 cp/reaction [43]
Pneumonia Pneumocystis jirovecii Cas13a Transcription-mediated amplication of viral RNA Fluorescence plate reader 120 97.7 2 cp/µL
(78.9%)
[44]
Hepatitis Hepatitis B virus Cas13a Recombinase-aided amplification (RAA) Lateral flow detection < 60 – 93.8% [45]
Hemorrhagic fevers (Ebola & Lassa) Ebola virus, Lassa virus Cas13a RT-RPA of samples treated by HUDSON method Fluorescence/lateral flow method < 60 100% 91% [46]
Influenza Avian influenza A H7N9 LwCas13 RT-RPA of extracted viral RNA Fluorescence plate reader 50 min – – [47]
African Swine Flu African swine virus LbuCas13a, AsCas12a RPA of heat-treated samples, detected by AuNP detection < 1 200 copies/µL [48]
The CRISPR/Cas9 driven isothermal exponential amplification reaction (CAS-EXPAR) technique was recently established by Huang and colleagues. The technique is used to detect the sequence of DNA with attomolar (aM) level of sensitivity & single-base specificity. The target DNA fragment left over after CRISPR/Cas9 cleavage primes CAS-EXPAR, which then cycles through the amplification process to produce a huge number of DNA copies that are identified by utilizing a real-time SYBR Green detectable fluorescent signal. The technique successfully shows that it is sensitive enough to detect Listeria monocytogenes RNA and Epigenetic changes [49]. Another team created two techniques called CRISPR-associated reverse PCR (CARP) and CRISPR-typing PCR (ctPCR) for finding DNA [50]. These tests combine PCR amplification of the target sequence with CRISPR-specific cleavage, and the outcome can subsequently be seen using gel electrophoresis or real-time PCR. Human papillomavirus (HPV) HPV16 and HPV18 L1 gene detection was used to validate ctPCR and CARP. CRISPR/Cas9-based lateral flow assay (CASLFA) was developed more recently by Wang et al. This method combines CRISPR/Cas9 with the lateral flow assay. The CASLFA is used to diagnose Listeria monocytogenes [51] as well as the African swine fever with great specificity and within one hour at a LOD of hundreds of copies of genomic samples.
Another tool that has been modified is the nuclease-dead Cas9 (dCas9) that binds DNA without splitting it. The researchers divided luciferase and joined the two halves to dCas9; these two fragments can heterodimerize to rebuild complete protein and emit bioluminescent signal if targeted to neighboring DNA locations. To diagnose Mycobacterium tuberculosis DNA, the bacterial DNA sequence was pre-amplified, and the dual gRNAs targeting the bacterial DNA were added. If the amplified DNA is the predicted pathogen DNA, bioluminescence will result [49]. A similar technique known as the rolling circle amplification (RCA)-CRISPRsplit-HRP system is employed for quickly detecting MicroRNAs [52]. Pretty recently, Kyeonghye Guk and associates offer a CRISPR-based DNA-FISH approach for the straightforward, quick, and highly sensitive detection employing SYBR Green-I acting as fluorescent probe and dCas9 for precise targeting. Methicillin resistant Staphylococcus aureus (MRSA) can be found using this CRISPR-based DNA-FISH in just 30 min [53].
To increase sensitivity, all of the methods mentioned above need the pre-amplification procedure. The CRISPR-Chip, a label-free DNA-testing device, was created by Reza Hajian et al. to find a target DNA sequence. The biosensor makes use of a field-effect transistor based on graphene and immobilized dCas9-gRNA complex, whose output signal may be detected by a straightforward handheld reader. The CRISPR-Chip can identify mutations in DNA in patients of Duchene muscular dystrophy with a sensitivity of 1.7 femto moles in 15 min. The use of CRISPR-Chip technology to detect nucleic acids electrically on a chip broadens the applicability of CRISPR-Cas9 [54]. In future, exploitation of Cas9 as diagnostic agent in SHERLOCK method will be an interesting avenue to explore.
In another attempt, the improved SHERLOCKv2 utilize the multiplexing approach to enhance the process efficiency. In this technique, four different DNA or RNA sequences can be detected in a single reaction by utilizing a combination of four different Cas13 and Cas12 enzymes. Additionally, the detection sensitivity can be increased by approximately 3.5-fold through the utilization of Csm6, a CRISPR-associated enzyme, in order to boost Cas13 activity. The final step involves the incorporation of a reporter molecule for a lateral flow assay, which enables a visible reading on the test strip. Through the use of lateral flow, SHERLOCKv2 is able to identify mutations in clinical samples as well as single-stranded RNA from the Dengue or Zika virus [26].
Cas12-based monitoring system Cas12a, which is also designated as Cpf1, is a Class V CRISPR-Cas protein. It comprises of one RuvC domain and may identify T-rich PAM sequences for target cleavage as mentioned in Table 3. Because of its ability to degrade dsDNA in the presence of an attached dsDNA substrate, this enzyme also exhibits generalized ssDNase activity. In the DETECTR and HOLMES experiments, Isothermal amplification of the target sequence is performed by RPA or RT-RPA, which subsequently bind the Cas12a-crRNA complex and cause the breakdown of a ssDNA fluorophore-quencher reporter, so producing a fluorescent signal. Both DETECTR and HOLMES are capable of detecting DNA segments with a sensitivity that is attomolar and a specificity that is extremely high [55]. The same approach could be adopted with SHERLOCK to enhance its specificity. Cas12b has an activity that is comparable to that of Cas12a and is utilized in HOLMESv2 and CDetection. CDetection has demonstrated the ability to directly detect HPV16 DNAs in patient blood at concentrations as low as 1 attomolar [56]. There have been improvements to Cas12-based nucleic acid identification. To this day, many amplification techniques such as PCR, RPA, and LAMP and single output forms such as fluorescence detectors, naked-eye views, and subsequently flow assays have been combined into the procedures, which has allowed them to become sensitive, accurate, portable, and simple to employ [49].Table 3 Characteristics of CRISPR-associated proteins and their applications
Features Cas9 Cas12 Cas13 Cas14
Class Class II type II Class II type V Class II, Type VI Class II, Type V
Types Deactivated Cas-9 (dCas9), Cas 9 nickase (nCas9): Cas9D10A and Cas9H84 Cas12a, Cas12b, Cas12c, Cas12d, Cas12e Cas13a, Cas13b, Cas13c, Cas13d Cas14a, Cas14b, Cas14c
Description A bacterial enzyme called Cas9 employs base pairing to identify and cleave targeted DNAs that complement the guide RNA A new RNA-directed endonuclease developed as an innovative genome editing tool and is quickly becoming a potent molecular scissor Novel effectors can target viral RNA(s) using rationally designed crRNA(s) Exceptionally compact but small RNA-guided DNA endonucleases
DNA cleavage Cas9 cleaves the DNA strand complementary to the crRNA using the HNH domain and the non-complementary DNA strand using the RuvC domain Indiscriminate ssDNA degradation activity upon activation with an ssDNA complementary to the crRNA guide Cas13 prefers to target and cut RNA rather than DNA, which would have less off-target consequences ssDNA cutting
Suggested use The first choice for genome editing projects is now being used for screening purposes too Pre-crRNA processing makes it a desirable option for multiplex gene regulation
Plant targeted mutagenesis
SARS-CoV-2/related coronavirus strains detection by Cas12
Used to study and perturb RNAs in endogenous microenvironments
And for targeting viral RNA for either RNA-mediated degradation or CRISPR–Cas13-based diagnostics
Cas14 facilitates high-fidelity SNP genotyping
Molecular weight 1000–1600 amino acids (160 kD) 1300 amino acids (130 kD) 800–900 amino acids (130 kD) 400–700 amino acids (40–70 kD)
Type of cut Create blunt ends Create sticky ends Cut ss RNA Cut ssDNA as well as dsDNA
PAM sequence requirement Identifies 3′ G-rich
PAM sequences of 3–5 nt
Identifies 5′ T-rich
PAM sequences of 3–4 nucleotides
Don’t need a PAM sequence No PAM sequence binding
gRNA crRNA as well as tracer RNA required Only crRNA required crRNA as well as tracer RNA required Require gRNA
Picture’s reproduced from the [57] with permission from Royal Society of Chemistry
One of the tiniest Cas proteins, Cas14, contains 24 distinct variants grouped into three distinct families. Proteins belonging to the Cas14 family are able to breakdown the targeted DNA sequence without the need for needing a PAM in order to be activated. Furthermore, target identification by Cas 14 triggers the breakdown of ssDNA molecule that is not specific. Cas14a has been incorporated into the DETECTR platform so that it can create a brand-new system for the detection of ssDNA called Cas14a-DETECTR. It makes possible high-fidelity DNA SNP analysis (detection of single-nucleotide polymorphisms) without being constrained by the PAM. Because of this inspirational study, a number of scientists have proposed analyzing DNA as part of their work. Cas14a-DETECTR is able to detect pathogens, but there has been no documented case of the diagnosis of a pathogen [58]. In future, research on the suitability of Cas14 as diagnostic marker with SHERLOCK method will be an interesting avenue to explore.
Perks and Pitfalls of CRISPR/Cas-Mediated Pathogen Detection Systems
Using CRISPR/Cas-based methods, microbes like SARS-CoV-2, Zika, Ebola, HPV, and Mycobacterium tuberculosis can be detected with greater precision, speed, cost-effectiveness, and ease. CRIPSR-mediated system also has the potential to be used as identification, imaging, and therapeutic tool in addition to its use as disease diagnostic approach (Fig. 3). The procedures are undergoing additional enhancements and modifications in order to render them more adaptable [49].Fig. 3 Potential applications of the CRISPR diagnostics for identification, detection, and therapeutics. The figure showed that SHERLOCK is used for species identification and single-nucleotide polymorphism analysis. Nucleic acid detection could be adopted for mutation analysis or antibiotic resistance gene detection. As diagnostic tool, SHERLOCK is used to detect bacterial, viral, and infectious diseases. CRISPR-mediated nucleic acid imaging is useful for disease genotyping. Nucleic acid editing and gene expression regulation by SHERLOCK are the potential areas for its as therapeutic agent
The ease of use of the CRISPR/Cas-based detection system makes it possible to rapidly develop diagnostic methods in the event of an unexpected outbreak of infectious diseases. This is an extremely important feature. For instance, integrated later flow assay (CRISPR/Cas12a-LFD) and naked-eye detection (CRISPR/Cas-based colorimetric system, fluorescence-based POC system) was developed for rapid Cas12a-mediated on-site detection assays of African swine virus (ASFV), an emerging virus for the international swine industry [41]. These screening tools can identify as few as two copies of RNA and readout on a later flow ribbon in 60 min without the need for complicated instrumentation or visualization by green fluorescent with the naked-eye under 485 nm light. In addition, these diagnostic methods can detect as few as two copies of SARS-CoV-2 RNA. While back, Joung and peers [29] proposed an integrated assay for detecting SARS-CoV-2 called STOPCovid (SHERLOCK Testing in One Pot). This test can return result on the strip in 70 min, with an LOD of 100 copies of viral RNA In saliva or nasopharyngeal swabs. These CRISPR/Cas-based SARS-CoV-2 tests, in contrast to the RT-qPCR-based diagnostic methods, have the advantages of high speed, the absence of a requirement for expensive instrumentation and the assistance of trained technician, and will be a significant help in the COVID-19 epidemic control.
SHERLOCK uses the Cas13 enzyme, which does not require tight sequence partialities at the target location, whereas Cas12 requires a PAM to cleave. As a result, SHERLOCK can tolerate a longer target range as compared to DETECTR [59].
Despite its advantages over existing detection systems, SHERLOCK has some drawbacks that may make it unsuitable in some situations. Currently, SHERLOCK entails the manufacture and testing of reaction components, some of which necessitate knowledge of protein purification as well as RNA biology. Furthermore, pre-designed assays for SHERLOCK, such as reaction mixes and DNA/RNA oligonucleotides, are not presently commercially available. Existing routine detection techniques, such as cancer assays, may be better for applications that do not require the speed or portability of SHERLOCK [17].
The multi-step nucleic acid amplification procedure, which may influence precise target quantification, is another possible restriction of SHERLOCK. Although Kellner et al. recently showed quantitative nucleic acid detection using SHERLOCK, absolute digital quantification, such as in digital droplet PCR, is presently not attainable, and minor differences in target quantity may not be identified. As a result, SHERLOCK may be less useful for determining accurate gene expression profiles [17].
Opportunities for SHERLOCK-Mediated Pathogen Detection Systems
The SHERLOCK reaction mixture can be lyophilized and utilized after long periods of storage without affecting the test's sensitivity and specificity. SHERLOCK can easily identify between viruses like the dengue virus and the Zika virus [25]. SHERLOCKv2 can identify two cancer mutations in simulated cell-free DNA (cfDNA) specimens with single-base mismatch sensitivity under low allelic fraction [60]. In parallel to in vitro RNA target identification, catalytically active LwaCas13 preserves its RNA-binding activity, allowing for live cell RNA tracking using a fluorescent probe. This provides a different way of recognizing and visualizing RNA. SHERLOCK’s single-nucleotide specificity has been used to offer a genotyping profile of cancer victims by exposing cancer-associated mutations in circulating cell-free DNA, even at low attomolar concentrations of 0.1% allelic fraction in serum samples or urine samples. Cas13’s specificity can be enhanced in such circumstances by inserting a synthetic mismatch’ into the crRNA [59].
Bio-SCAN (biotin-coupled-specific CRISPR-based assay for nucleic acid detection) was created as an efficient pathogen detection tool that doesn’t require any special equipment or technical knowledge. From specimen collection to result, Bio-SCAN recognizes the SARS-CoV-2 nucleic acid in less than 1 h. In the first phase, the target sequence is isothermally amplified in 15 min using recombinase polymerase amplification (RPA) then precisely identified on commercially available lateral flow strips using biotin-labeled nuclease-dead SpCas9 (dCas9). Furthermore, Bio-SCAN was able to discriminate between the SARS-CoV-2 variants using variant-specific guide RNAs in the detection reaction. The findings also revealed that the Bio-SCAN assay reagents and chemicals have a long shelf-life and can be constructed locally in non-laboratory and low-resource environments. The Bio-SCAN system can also be used with the nucleic acid rapid extraction methodology. Our findings indicate Bio-potential SCAN’s as a potential point-of-care diagnostic technology for cost-effective mass screening for SARS-CoV-2 [61].
Cas13’s specificity can be improved by inserting a synthetic mismatch’ into the crRNA. The assay’s speed is one of SHERLOCK’s most appealing features. RPA is usually done for 5–10 min as a first reaction, after which a portion of the solution is passed to the Cas13 detection reaction, which can detect the target in 5 min. The inexpensive cost of its components is another perk of the SHERLOCK system over other detection methods (such as TaqMan qPCR). A typical single-plex reaction costs around $0.60.
The point-of-care testing (PoC) may get benefit from nanotechnology in the near future. In addition to lateral flow tests, several additional diagnostic procedures like chest computed tomography, other new variants of Cas proteins, and paper microfluidic device can be integrated with smartphones and artificial intelligence (AI) for point-of-care testing. These advancements will completely change the way diseases are diagnosed by providing a POC testing method that is rapid, accurate, low cost, and user-friendly. These technologies need to be developed further so that they can be quickly put into action in the event of unanticipated medical emergency.
Conclusion
SHERLOCK is recently developed CRISPR-mediated diagnostic technique with high sensitivity and specificity. It allows for the single-molecule detection of DNA and RNA target sequences in as low as 1-µL sample volumes without the need of specialized instruments which makes it suitable for on-site disease diagnostics. SHERLOCK takes advantage of both Cas13 and Cas12 enzyme specificity. Integration of SHERLOCK with extraction-free assays, multiplexing with Cas variants, and Bluetooth-enabled detection had ushered a new era in molecular diagnostics by offering portable, extremely sensitive diagnostic platforms capable of quickly diagnosing emerging infectious & non-infectious viral diseases. Albeit still in its infancy, SHERLOCK assay has proved to be a game-changer which have the potential to revolutionize our capability of detecting infectious disease and pathogens with ultra-sensitive tests which do not involve extensive complicated processing, allowing for mass screening and better control of viral outbreaks as well as widespread distribution of field-deployable diagnostics toolkits at an affordable cost.
Funding
This study was supported by Ministry of Science and Technology, Pakistan (Grant No. DDWP-2021) to PCSIR and University of Agriculture Faisalabad, Pakistan.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36494593 | PMC9735230 | NO-CC CODE | 2022-12-14 23:29:53 | no | Mol Biotechnol. 2022 Dec 9;:1-16 | utf-8 | Mol Biotechnol | 2,022 | 10.1007/s12033-022-00625-7 | oa_other |
==== Front
Polym Bull (Berl)
Polym Bull (Berl)
Polymer Bulletin (Berlin, Germany)
0170-0839
1436-2449
Springer Berlin Heidelberg Berlin/Heidelberg
4565
10.1007/s00289-022-04565-9
Review Paper
A road map on synthetic strategies and applications of biodegradable polymers
Meghana M. C.
Nandhini C.
Benny Libina
George Louis [email protected]
http://orcid.org/0000-0001-7188-8420
Varghese Anitha [email protected]
grid.440672.3 0000 0004 1761 0390 Department of Chemistry, CHRIST (Deemed to be University), Hosur Road, Bengaluru, 560029 India
9 12 2022
150
1 5 2022
28 10 2022
5 11 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Biodegradable polymers have emerged as fascinating materials due to their non-toxicity, environmentally benign nature and good mechanical strength. The toxic effects of non-biodegradable plastics paved way for the development of sustainable and biodegradable polymers. The engineering of biodegradable polymers employing various strategies like radical ring opening polymerization, enzymatic ring opening polymerization, anionic ring opening polymerization, photo-initiated radical polymerization, chemoenzymatic method, enzymatic polymerization, ring opening polymerization and coordinative ring opening polymerization have been discussed in this review. The application of biodegradable polymeric nanoparticles in the biomedical field and cosmetic industry is considered to be an emerging field of interest. However, this review mainly highlights the applications of selected biodegradable polymers like polylactic acid, poly(ε-caprolactone), polyethylene glycol, polyhydroxyalkanoates, poly(lactide-co-glycolide) and polytrimethyl carbonate in various fields like agriculture, biomedical, biosensing, food packaging, automobiles, wastewater treatment, textile and hygiene, cosmetics and electronic devices.
Keywords
Biodegradable polymers
Chemoenzymatic method
Biomedical applications
Polyethylene glycol
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pmcIntroduction
The rise in the global population leads to an increase in the usage of plastics which in turn increased environmental pollution [1, 2] synthetic plastics are usually made from non-renewable petroleum-based resources which are non-biodegradable [3]. The increase in the usage of synthetic non-biodegradable polymers in industries, households and agriculture, causes waste generation and serious issues in the environment [4]. It increased the demand for fossil resources which are depleting resources, and there is a major concern that these resources will get completely exhausted within several hundred years [5]. Industries, researchers and technologists were looking forward to the development of a cleaner and more efficient manufacturing process for biodegradable polymers that produces less waste and avoids the usage of harmful reagents and solvents [6–8]. There is an urgent need to develop renewable, eco-friendly biodegradable polymers to replace the existing synthetic polymers [9]. The current global goal is the development of an efficient and sustainable process for a greener and biopolymer-based future [10–12]. Biopolymers attract remarkable attention of scientists since they are found abundant [12]. The research and development of new biodegradable polymeric materials are gaining momentum [13].
Biodegradable polymers can be synthesized by various methods like ring opening polymerization (ROP) [14], chemoenzymatic methods [8], photo-initiated radical polymerization [15], enzymatic polymerization [16], cationic, anionic, enzymatic, coordinative and radical ring opening polymerization [17]. The definition of biodegradable polymers according to the American Society for Testing and Materials (ASTM) is "they are the polymers that degrade or decompose under chemical, physical and biological interactions with microorganisms from environment, such as bacteria, fungus and algae” [18]. They break down into natural components such as CO2, water and biomass without producing hazardous waste [19, 20] Biodegradable polymers can be classified based on their renewability and biodegradability level. The demand for biodegradable polymers is ever increasing because of their properties like degradability, eco-friendliness, sustainability and non-toxicity [21, 22].
Plastics are mainly used in the packaging field which are disposed of in landfills which results in environmental pollution and also a decrease in the availability of land space. The use of conventional plastic in agriculture increases the risk of non-degradation. The introduction of biodegradable polymers in place of these synthetic plastic materials enhances the rate of degradation since they are broken down by microorganisms present in the soil. The biomedical world is continuously changing, and the materials used in the field are also getting better by the use of these biodegradable polymers. Biodegradable polymers are ideally suited for biomedical, cosmetics and sanitary fields because of their non-toxic nature. In wastewater treatment, the use of conventional chemical methods for the removal of contaminants may sometimes release toxic by-products into water which can be overcome by the use of biodegradable polymers.
Usage of green/biodegradable polymers has increased over the past decade, as these are widely used in many fields like medical, agricultural, automobiles, packaging, electronics, health care, pharmacy and so on [23]. During this period, a large number of biodegradable polymers were developed, which found their applications in new biomedical techniques such as controlled drug delivery, regenerative medicine, biological nanotechnology, therapy and tissue engineering [24]. In this review, we mainly focused on the various methods of synthesis of biodegradable polymers and the application of these biodegradable polymers in different fields (Fig. 1).Fig. 1 Schematic representation of diverse biodegradable polymers and their applications
In this present work, the complete information of biodegradable polymers beginning from their origin, various methods of synthesis, their properties, importance, degradation and applications in various fields is completely discussed. This reviews mainly highlight applications of biodegradable polymers in the field of agriculture, packaging, medical, cosmetics, automobiles, textiles and hygiene, biosensors, wastewater treatment and electronic devices. The polymers that are used in all these applications are non-toxic to environment and safe to use. The biodegradability of each polymers is achieved by various degradation mechanisms which give non-toxic substances.
Strategies in synthesis of biodegradable polymers
Diverse methods for the synthesis of sustainable biodegradable polymers are discussed below (Fig. 2). Some of the methods include radical ring opening polymerization, enzymatic ring opening polymerization, anionic ring opening polymerization, photo-initiated radical polymerization, chemoenzymatic method, enzymatic polymerization, ring opening polymerization and coordinative ring opening polymerization. Ring opening polymerization is considered one of the best methods to synthesize high molecular weight biodegradable polymers. Enzymatic and chemoenzymatic methods are also beneficial because of their regioselectivity and stereospecificity (Fig. 3). Each type of biodegradable polymer can be synthesized by choosing the appropriate method of synthesis.Fig. 2 Strategies involved in the synthesis of biodegradable polymers
Fig. 3 White biodegradable film (WBF). A Black biodegradable film (BBF). B Control polyethylene films (CPF). C After 5 weeks in contact with soil [86]. Reprinted with the permission of Elsevier
Ring opening polymerization (ROP)
Polymerization of cyclic monomers into an acyclic monomeric unit is called ROP. Here a long polymer chain is formed by opening the ring system of cyclic monomers where the terminal end of a polymeric chain behaves as a reactive center. There are three propagating centers, namely radical, anionic and cationic. This method is considered one of the most versatile methods for the synthesis of biopolymers in huge quantities. Polylactic acid is a biodegradable polymer that is synthesized by using ROP as follows.
PLA (polylactic acid) is synthesized by the chain growth ROP of lactide. To carry out the ROP of lactide, various catalysts and initiators are used. Sn(oct)2 is a commonly used robust catalyst/initiator. ROP of lactide and glycolide results in the formation of PLGA. The catalyst used here is Sn(oct)2. The molecular weight of PLGA is high. PDS can be produced by the ROP of p-dioxanone which is a relatively weak and rapidly biodegradable polymer. But it generates degradation products that are less acidic than PLA and PGA [25].
Radical ring opening polymerization
The consecutive addition of free radicals as building blocks formed by various mechanisms which involve separate initiator molecules to produce polymers is called free radical ring opening polymerization (FROP). The initiating free radicals which are generated newly add the monomer units to the polymer chain which results in chain growth. FROP is considered as one of the most versatile forms of polymerization which allows facile reactions of polymeric free radical chain ends with other substrates or chemicals [26]. ε-Caprolactone-based materials are synthesized by using this method. For example, poly(HEMA-g-CLk) NPs are synthesized by using the free radical polymerization synthesis technique. Here, ε-caprolactone is combined with 2-hydroxyethyl methacrylate (HEMA) to produce poly(HEMAg-CLk) NPs [26].
Chemoenzymatic method of polymerization
Chemoenzymatic synthesis is well known for the production of active pharmaceutical ingredients (AAPIs). By using this approach, the scientists have fabricated some polymeric prodrugs which are optically active. These prodrugs are nonsteroidal anti-inflammatory substrates having high molecular weight [25]. This method combines conventional polymerization with an enzymatic approach which is highly efficient. Chemoenzymatic synthesis is coined as an attractive strategy for the synthesis of high molecular weight BPMS. For example, the PLA monomer can be synthesized by a chemoenzymatic approach [8].
Photo-initiated radical polymerization
Photo-initiated ring opening polymerization is an interesting technique because it provides rapid polymerization rates under physiological conditions with spatiotemporal control. It eliminates the use of a toxic cross-linker in the reaction medium. Most of the polymers that are commonly used in biomedical applications are commonly synthesized by using this greener route [15].
Enzymatic polymerization
In recent times, the enzymatic synthesis of biodegradable polymers is considered a novel and green methodology for the production of polymers. Enzymes are biocatalysts that are non-toxic and renewable with high catalytic activities. The use of enzymes for biodegradable polymer synthesis involves low activation energy compared to the conventional methods of synthesis [27]. The enzymatic synthesis of biodegradable polymers takes place even in milder conditions without the use of metal or toxic organic contaminants. This increases its application in various fields, especially in the biomedical field [28]. The enzyme lipase is used as a catalyst for the synthesis of novel biodegradable polymers like polyester by using methyl 12HS (12HS-Me). It is a thermoplastic elastomer that is biobased [29].
Anionic ring opening polymerization
Anionic ring opening polymerization is used as one of the elegant methods to synthesize telechelic polymers in various topologies such as hyper-branched, linear, star, core–shell polymers. Anionic ring opening polymerization is considered one of the most advantageous methods because of controllable polymerization kinetics and no side effects and provides a higher degree of monomer conversion [30].
PCL block–poly(butyrolactone) copolymers were synthesized utilizing anionic ring opening polymerization. PCL was synthesized by anionic ring opening polymerization of CL which is initiated with anhydrous KOH-activated 12-crown-4 cation complexing agent. This reaction is carried out in the presence of tetrahydrofuran solution and argon atmosphere at room temperature. Further, butyrolactone (BL) 16 crown-6 are added to the system which results in PCL-block-PBL copolymer [31].
Coordinative ring opening polymerization
In coordinative ROP, the metal atom will coordinate the molecule of the cyclic ester. Here, the metal atom plays the role of the electrophilic catalytic center. This coordination insertion mechanism results in carbon atom activation of the carbonyl group for cyclic esters or phosphorous atoms for the cyclic phosphates. The initiator like amino, alkoxy, alkyl, etc. is directly bonded or coordinated weakly with the metal. This dual monomer and initiator coordination form a reaction complex [33]. “Coordination–insertion” ROP is often called pseudo-anionic ring opening polymerization. This type of polymerization will yield well-defined polyesters through living polymerization [34].
Enzymatic ring opening polymerization
In this type of polymerization, the enzyme lipase is more commonly used. Some of the lipase enzymes that are used are pseudomonas cepacia lipase PS, porcine pancreatic lipase (PPL), Burkholderia cepacia lipase PS [35]. The enzymatic ring opening polymerization synthesis technique is very sensitive to reaction conditions such as water content, solvents and temperature [36]. For example, high molecular polylactic acid is synthesized through the enzymatic ring opening polymerization route using free enzyme and (CALB) candida Antarctica lipase enzyme [37].
Applications of biodegradable polymers
The applications of biodegradable polymers are vast and diverse. Each biodegradable polymer that is applied in different fields will have different synthetic routes. While designing a biodegradable polymer for specific applications, one should also look into its degradation mechanisms, as the degradation of biodegradable polymer is the most crucial property. Irrespective of any degradation mechanism, it should not produce any toxic by-products after decomposition.
Each biodegradable polymer has different properties which apply to various fields. A tabular representation of the synthesis and their applications have been displayed Table 1. PLA has properties like heat resistance, good stability and visual transparency which can be used for food packaging. PCL is a polyester that can be degraded by ester hydrolysis under physiological conditions, so it is used in injectable implants. PCL also stimulates collagen production; hence, it is used in periodontal regeneration. PHA has good moisture resistance and aroma barrier properties, so it is applicable in pesticide transfer in the field of agriculture. Superabsorbent polymers are biodegradable and have good water absorption properties and retain a large amount of liquid. It also has good antimicrobial properties and is non-toxic, so it is used in sanitary napkins, diapers and other personal hygiene products (Table 2).Table 1 Method of synthesis and application of biodegradable polymers
Biodegradable polymer Structure Method of synthesis Application Ref. No
PLA Ring opening method. Direct condensation Drug delivery, Fertilizer delivery, Tissue engineering and Biosensors [59]
PCL Ring opening polymerization (ROP). Enzymatic ROP Fertilizer transfer, Injectable implants, Periodontal regeneration and Food packaging [60]
PEG Cationic polymerization, anionic polymerization and polymerization Drug delivery and agricultural mulching films [61]
PHA Enzymatic synthesis Release of agricultural pesticides [62]
PLGA ROP glycoside lactide monomers Tissue engineering and Medicinal implants [63]
PTMC Ring opening polymerization Soft tissue engineering [64]
Table 2 Diverse applications of biodegradable polymers
Polymer used Application References
Agriculture Halloysite nanotubes (HNPs) Used as botanical pesticide carrier [69]
Polycaprolactone (PCL) and polylactic acid (PLA Used in fertilizer transfer [70]
Modified starch graft-polyacrylate superabsorbent polymer (MS-g-PA SAP) Improves the moisture content of the soil [76]
Water hyacinth cellulose-graft-poly(ammonium acrylate-co-acrylic acid) polymer hydrogel Formulates the soil conditioning and slow liberation of fertilizers [76]
Semi-interpenetrating polymer network (semi-IPN) hydrogels of cassava starch-g-polyacrylic acid/ natural rubbers/ polyvinyl alcohols blends (CSt-g-PAA/NR/PVA Provides good water absorption and excellent water retention capacity [72]
Poly(butylene adipate-co-terephthalate) (PBAT) and poly butylene terephthalate (PBT) Mulching in agriculture [53]
Hydrolyzed proteins crosslinked with PEG (polyethylene glycol) Used for spray mulching [82]
Polyacrylic acid lignin hydrogel (LBPAA Used for sustainable release of pesticide [83]
Polyhydroxyalkanoates (PHA Used as a material for construction of controlled release system for agricultural pesticides [85]
Polylactic acid (PLA ECOFLEX and wood fibers Manufacturing of biodegradable transplanting pots for nursery and green house industry [86]
Biomedical Tissue engineering Poly (tri-methylene carbonate) (PTMC is used in the Fabrication of non-commercial devices of soft tissue engineering [93]
Polyurethane Scaffolding material for hypopharyngeal tissue engineering [101]
Drug delivery Hyper-branched polyglycerols (hPGOCs) Intradermal drug delivery [104]
Poly lactic acid (PLA thin film composities ad hydroxyapatite (cHAP) Drug delivery systems for bone regeneration [107]
Silk fibroin- poly(sebacic acid) diacetoxy terminated (SF-PSADT) poly,eric composite coating Drug delivery with enhanced stability. olymerized Nano Coatings—As a Biodegradable Solid Carrier for Tu [109]
PCL-co-PEG coating Tunable drug delivery [110]
Polymeric solid implants (PSI) Ultra-long acting (ULA drug delivering of anti-retroviral drugs for HIV [111]
Anticancer drugs Polyphosphazenes Carrier in anticancer drug delivery of Cisplatin [116]
PEG-poly(pentadecalactone-co–N-methyl-diethyleneamine sebacate-co-2,2’- thiodiethylene sebacate(PEG-PMT) micelles Vectors for controlled release of anti-tumor drugs at tumor intracellular site [113]
Polytyrosine nanoparticles Drug delivery of Doxorubicin (DOX) 100
Poly(1,4-phenyleneacetone thioketal) (PPADT) nanoparticles Intracellular drug delivery of anticancer drug agents [119]
Polyamidoamin (PAMAM) Drug delivery for the treat for the treatment of skin cancers [120]
Contraceptive drugs Poly(caprolactone) PCL Controlled dug delivery of contraceptive drug such as levonorgestrel (LNG) [122]
Poly-lactic-co-glycolic acid (PLGA Controlled contraceptive drug release such as Etonogestrol (ENG) [125]
Medical packaging Polypropylene/ poly(lactic acid) blends Medical packaging due to its water barrier and antimicrobial properties [127]
Polylactic acid/ styrene–isoprene-styrene blends (PLA/SIS) Medical packaging SIS enhances strength 111
Orthopedics HA-poly(PEG-co-propylene fuurate-co-ascorbate) Bone graft materials [130]
AZ31 Mg alloy sheets coated with PCL nanofibers Biodegradable Mg – based orthopedic implants [131]
Periodontal regeneration Helixician (HX) immobilized biodegradable chitosan (CS)/ PVA/HA based electrospun films and fibers Periodontal treatment for prolonged drug release [137]
Polylactic acid/ cellulose acetate (PCL/CA Periodontal tissues regeneration [221]
(PCL/CA or PCL incorporated with silver and hydroxyapatite nanoparticles GTR/ GBR applications. Improves periodontal tissues and bone regeneration [221]
Food packaging Mater- Bi Manufacturing of nets for fruits and vegetables [143]
Polyvinyl butyrate (PVB Coating on paperboards to enhance water barrier property and to prevent wetting [154]
Binary blend films of polyvinyl alcohol (PVA with k-carrageenan Packaging material in the food industry [145]
Montmorillonite Limits the penetration of gases during food packaging [146]
Poly(3-hydroxy-butyrate-co-3-hydroxy valerate) Fruits packaging and enhances the shelf life of perishable fruits [147]
Cellulose nanocrystal alginate (CNC/Alg) Food packaging due to their UV and water barrier properties [147]
Polylactic acid (PLA Packaging of fruits, vegetable and salads [151]
Polyglycolic acid Packaging of perishable foods or goods with limited shelf life [150]
Automotives Coconut shell powder reinforced composites Interiors of spacecraft, aircraft, motor cars and other automobiles [155]
Bark cloth reinforced epoxy bio-composites Interiors of automotive panels like dashboards in cars [157]
Epoxymatrix with addition of jute Indoor panels of E- class vehicles of Mercedes benz [125]
Waste water treatments Biodegradable wheat fluor absorbent Removal of cationic Rhodamine B (RB dye from water [131]
Polyacrylonitrile-g-arabic gum- graft polymer Removal of Pb2+, Cd2+, Hg2+, etc. from wastewater [164]
Cellulose-EDTA or Carboxymethyl Removal of heavy metal ions like Pb2+ and Cd2+ [168]
Magnetic carboxy methyl starch (CMS)/ poly(vinyl alcohol) hydrogel mCMS/ PVA Removal of methylene blue dye contamination from water [171]
Magnetic nanoparticles (MNPs)/ starch-g-poly(vinylsulfate) nanocomposite Adsorption of various cationic dyes like methylene blue and malachite green [172]
Crosslink cationic starch Removal of golden yellow dye from water [173]
Kappa-carrageenan/poly(glycidyl methacrylate) (CG/PG) hydrogel Removal of cationic methylene blue dye from waste water [175]
Crosslinked chitosan/ sepiolite composites Removal of organic and inorganic pollutants from water and also for the removal of dyes such as reactive orange-16, acid red-2 and methylene blue [176]
Calcium- alginate based hydrogel beads Removal of mutagens and mitotic poison, methyl violet from wastewater [177]
Textile and hygiene Face mask PLA, PHA, poly(lactic-co-glycolic acid) Manufacturing of face masks [182]
Poly(isoprene) units-(latex free rubber) Manufacturing of ear loops of both N95 and surgical masks [184]
Melt-blown PLA (MBPLA electret membranes Production of face masks due to their excellent air filter capacity [184]
Cellulose acetate polymer nanofibers Production of face masks because of its high efficiency filtration for aerosol nanoparticles [187]
Chitosan nanolowiskers (CSW) and PBS (polybutylene succinate) Manufacturing of biodegradable mask filters [188]
Gluten Manufacturing of face masks and has good viral filtration capacity [189]
Hygiene Superabsorbent polymers (SAPs) Manufacturing of sanitary napkins and disposable diapers [193]
Chitosan, citric acid and urea (CHCAUR) Used in diapers due to high water absorption capacity [196]
Mimosa pudica hydrogel (MPH) Used as SAP in sanitary napkins [193]
Sodium alginate and carboxy methyl cellulose (CMC hydrogels Used as absorbent core for sanitary napkins [198]
Sodium carboxymethyl cellulose (NaCMC and hydroxyethyl cellulose (HEC crosslinked with divinylsulfone (DVS) Used as hydrogel in the manufacturing of sanitary napkins [199]
Electronic devices Poly(1,4-cyclohexylenedimethylene terephthalate-co-1,4-cyclohexylene 2,6-naphthalene dicarboxylate) copolyester (PCITN) Used as smart films for making flexible optical and electronic devices [207]
Cellulose Manufacturing of field-effect transistors (FET), organic light emitting diodes (OLEDs) and also used in solar cells [238]
Poly(caprolactone) PCL Used in manufacturing of solar cells, ion batteries, supercapacitors, electrochemical display devices and fuel cells [192]
Biosensors PLA- based microneedles (MN) Manufacturing of glucose sensors [195]
Poly(3,4-ethylene dioxythiophene): poly (styrene sulfonate) (PEDOT:PSS) Manufacturing of medical biosensors [239]
Three arm-stereo complex PLA (tasc PLA Fabrication of skin-like temperature sensors [197]
Polydimethyl siloxane (PDMS) foil Measurement of electrical activity produced by heat, skeletal muscles and brain [197]
Polyglycerol sebacate (PGS) Temporary health monitoring electronic devices [224]
Electrospun PGS-PCL Manufacturing of elastic temperature sensors, strain guage and heaters for bioresorbable electronics and smart wound dressing technique [224]
Cosmetics Polylactic acid (PLA Used as microencapsulating agent in the production care products [228]
Sodium alginate microbeads Used as abrasive agents in skin exfoliators (peeling products) [193]
Soluble starch Used as an ingredient in skin lotion and hair care products [231]
Chitosan Used in lotions and nail lacquers as a moisturizing agent [232]
Cellulose fibrils Used in face mask [234]
Polyquaternium-10 Used in hair conditioning products [198]
Silk fibroin Used in shampoos [231]
Collagen Used in antiaging and anti-wrinkling products [236]
Glycerol (bio-derived polymer) Used as an additive in cosmetic products such as thickener, demulcent, plasticizer, body lubricating agent, etc [237]
Pullalun (PUL) Used as moisturizing agent in facial packs and cosmetic lotions and protective agent in hair shampoos, hair dressing and tooth powders [235]
Polysaccharides are one of the naturally available biodegradable polymer. It is a kind of monosaccharide or combination of more than one type of monosaccharides. These polysaccharides are most commonly found in living organisms such as animals and plants. The animal origin polysaccharides are chondroitin and chitin. The plant origin polysaccharides are mainly cellulose, hemicellulose, starch, alginate, etc. The slight differences in the microstructures of the polysaccharides gives a significant difference in the properties. For example, cellulose and starch which differ only in stereochemistry play a unique role in nature. These are abundant in functional groups such as carboxyl, hydroxyl, amide and other hydrophilic functional groups that can be used to modify the properties of polymers of polymers that suits the desired applications. These are known as amorphous polymers [38]. Aligiate is most common available polysaccharide in brown seaweed. It is composed of monomeric units of (1,4) linked-D-mannuronic acid and L-gulucronic acid residues which is used in thickening, stabilizing, gel producing, film forming. Polysaccharides are cross-linked with other synthetic biodegradable polymer to gain better desired altered properties such as improved mechanical strength, swelling capacity and intact in shape. These cross-linked polysaccharides such as alginate/polyacrylamide and chitosan/chondroitin sulfate are used in various biomedical applications such as tissue engineering, wound dressing and gene therapy [39].
Polysaccharide degradation is induced by ascorbic acid. A series of changes in the properties of polysaccharides like smoother apparent morphology and lower apparent viscosity will take place on the addition of ascorbic acid to polysaccharides. Based on molecular weight measurement, it was identified that molecular weight of polysaccharide product after the addition of ascorbic acid was lowered. This is because ascorbic acid generates hydroxyl radicals based on Fenton reaction. These hydroxyl radicals will attack polysaccharide molecules which causes a series of reaction such as depolymerization that results in lowering of molecular weight. This degradation of polysaccharides can be inhibited by radical scavengers, but prevented by catalase. Ascorbic acid reduces oxygen to hydrogen and reduces metal ions. The hydroxyl radical is formed by a Fenton reaction between reduced metal ion and hydrogen peroxide or these radicals are produced by oxidation of ascorbic acid by hydrogen peroxide which will produce 2,3-diketogulconic acid (DKG). The generated hydroxyl radicals are very reactive and react with hydrogen atoms of polysaccharide that causes the glycoside bond cleavage [40]. The redox enzymes role in biomass conversion is gaining more interest. These enzymes promote the conversion of recalcitrant polysaccharide. Lytic polysaccharide monooxygenases (LPMOS) are mono-copper enzymes [41]. In the presence of external electron donor. It catalyzes hydroxylation of one of the carbons (C1 or C4) in the scissile glycosidic bond, which leads to bond cleavage by elimination reaction. LPMOS will act on polysaccharide chains that reside in crystalline environment. This leads to the disruption of structure of polysaccharides [42].
Cellulose is a natural biodegradable polymer plays an important role as a raw material for the development of commercial plastics. Cellulose-based resins are used during the molding process in plastic industry. Cellulose films are used for the packaging of mangos instead of PE (polyethyelne). This decreases the diseases, extends the ripening period of fruits and increases color indexes of fruits [43]. Carboxymethyl cellulose (CMC) is a crucial derivative of cellulose. CMC is also used in packaging material as polymeric blends. The degradation of these blends depends on degradation of carbonyl groups and inactivation of side chain [44].
The degradation of cellulose can be carried out by the enzymes called “cellulases” which is responsible for the hydrolysis of beta-1,4-linkages present in the cellulose [45]. Cellulose is hydrolyzed by a variety of simultaneously acting enzymes which interacts each other to bring complete hydrolysis. At least three different type of enzyme activities are essential for the complete hydrolysis of this polymeric substrate into its monomeric unit. Exoglucanase activity (cellodextrinase or cellobiohydrolase), Endoglucanaoe activity and Glucosidase activity. By the cooperation of all these enzyme activities the disruption of cellulose structure will takes place. The mechanism of degradation will take place by the following ways. Endoglucanases produce random internal cuts within the amorphous region in the cellulose molecule which yields cell oligosaccharides of various length and new chain ends are generated. Exoglucanases act progressively on non-reducing/reducing ends producing either cellobiose, glucose or cello-olidosaccharides. These cellodextrins and cellobiose which are soluble are then hydrolyzed by glucosidases to glucose [46].
The degradation of cellulose can be achieved by hydrothermal method and sonication method. By hydrothermal method, cellulose degrades and produces reducing sugar. Sonication pretreatment changes the degradation phenomenon, which occurs faster, increasing the degradation rate. The pressurization of H2 C2 O4–NaCl solution with carbon dioxide has produced a solvent with high solvent power capable of swelling, penetrating and changing the cellulose chain interaction which results in production of reducing sugar. The combination of hydrothermal (at high temperature) sonication process has a greater risk of degradation than hydrothermal process alone [47, 48].
At the molecular level, plastics may be described as a backbone chain built from units (monomers) of mostly carbon. The functional group (or side chain) of the individual monomer is the main contribution to the difference in the chemical and mechanical properties of plastics. These vary from simple carbon chains, for examples polypropylene (PP) and polyvinyl chlorine (PVC), and complex side chains, for example poly(methyl methacrylate) (PMMA). In terms of biodegradation, the functional group is of critical importance, as some chemical groups and bonds are more easily degraded by biological agents. The basic driving force of biodegradation is the use of carbon bound in the polymer as a feedstock for microorganisms to grow under aerobic conditions, and this reaction can be simply written asCpolymer+O2→CO2+H2O+Cbiomass
The rate of biodegradation is usually determined by measuring the amount of CO2 evolved or the amount of Cpolymer that has disappeared over time. The theoretical total amount of CO2 can be determined from the known input of Cpolymer. Biodegradability is based on a percentage of the theoretical CO2 produced over a given time frame. When oxygen is not available, methane gas (CH4) is also produced which can also be measured. Table 3 comprises the rate degradability of various biodegradable polymers. The timescale for biodegradable of place material is dependent on many factors, including the composition of starting material, environment and shape of the material (surface area) [49].Table 3 Rate of degradability of different biodegradable polymers
Biodegradable polymers Environment Rate of degradability Duration (Days) References
PLA Compost 84% 58 [50]
PLA Soil 10% 98 [51]
PHA Soil 48.5% 280 [52]
PHB Compost 79.9% 110 [53]
PHBV Sea water 99% 49 [54]
PCL Compost 38% 6 [55]
PBS Compost 90% 160 [56]
Cellulose Compost 80% 154 [51]
Starch Soil 14.2% 110 [57]
Mater-Bi Compost 26.9% 72 [58]
Application of biodegradable polymers in agriculture
In agriculture, biodegradable polymers are very important because of their degradability. Biodegradable Ecoflex films are used to cover the young plants which are sensitive to frost. As the plant grows, these biodegradable films will break down in the soil and it is degraded by microorganisms [65]. The biodegradable polymers can be developed by cost-effective techniques, and these polymers improve the phytostabilization of heavily contaminated soils by metals [66]. Chemical storage bags and fertilizer bags which are made up of polymers like polyethylene or polypropylene are replaced by biodegradable polymers [65]. Chemical pesticides are greatly affecting public health and the environment because of their toxicity. Nowadays botanical pesticides are in great demand. To deliver these pesticides, a suitable drug carrier is required, so the biodegradable polymer drug carrier like halloysite nanotubes (HNPs) are used [67]. Liquid marbles which are made up of PCL [poly(ε-caprolactone)] and PLA are used in fertilizer transfer. By using this method, urea can be successfully encapsulated inside these liquid marbles for safe fertilizer delivering systems [68]. The polymer-encapsulated formulation is superior to non-encapsulated formulation in extending activity and also in reducing evaporative and degradation loss [69].
The main problem in present-day agriculture is to increase land suitable for cultivation and enhance water productivity without causing any harm to the environment. The superabsorbent polymer hydrogels will influence the soil permeability, structure, texture, evaporation and infiltration rate of water through the soil. To increase the efficiency of herbicides and pesticides, some of the functionalized biodegradable polymers are used. The use of these polymers will reduce pollution and protect the environment [66]. These biodegradable hydrogels are widely used in modern agricultural and horticultural applications [70].
The usage of sprayable biodegradable polymer membrane (SBPM) increases the soil temperature, and in turn, it reduces the water evaporation which results in an improvement in seedling and crop yield. Table 3 The main purpose of SBPM is to increase crop germination, and the use of SBPM reduces seedbed water loss [71]. The biobased superabsorbent polymers (SAP) which are synthesized from modified starch (MS) are used for agricultural applications since it increases the antibacterial properties and biodegradability [72]. These SAPs will also increase the efficiency of water use of soil and also be used for the controlled release of fertilizers [73]. The modified starch-graft-polyacrylate superabsorbent polymer (MS-g-PA SAP) shows excellent reusability and biodegradation property. The (MS-g-PA SAP) will not impose inhibition of growth in mung beans (vigna radiata) and this provides some transient drought relief [72]. The SAPs improve the moisture contents of soil and help in water saving, so it is widely applied in the growth of many horticultural crops like gerbera [74]. There are many advantages of using SAP hydrogels in agriculture such as stabilization of fertilizers in the soil, reduction in the water consumption in irrigation, reduction in the death of plants and crops, and these hydrogels prevent draining out an active ingredient to the groundwater, thereby improving the plant growth [75].
Water hyacinth cellulose-graft-poly(ammonium acrylate-co-acrylic acid) polymer hydrogel is capable of absorption and retention of water in the soil. This also formulates the soil conditioning and slow liberation of fertilizers [76]. The biodegradable semi-interpenetrating polymer network (semi-IPN) hydrogels of cassava starch-g-polyacrylic acid/natural rubbers/polyvinyl alcohols blends (CSt-g-PAA/NR/PVA) are used in agriculture because of their good water absorption and excellent water retention capacity [70]. The polymer hydrogels (PHGs) are used in agriculture as slow release fertilizer (SRF) carriers and soil conditioners due to their water absorption and the retention property [77]. Polymer nanocomposites phosphate fertilizers are synthesized by grafting partially neutralized acrylic acid onto cellulose matrix in the presence of nano-HA (nanohydroxyapatite). This polymer increases phosphorus use efficiency and conditions of the soil due to improved moisture-holding capacity. The use of these polymeric nanocomposites is minimizing the cost of production and reduces environmental contamination [78].
The use of polyethylene (PE) fragments for mulching in agriculture increases soil pollution, since it is non-biodegradable and non-recoverable. So this can be overthrown by biodegradable polymers like poly(butylene adipate-co-terephthalate) (PBAT) and polybutylene terephthalate (PBT). The use of this polymers increases the mulching efficiency [79]. The preformed biodegradable plastic mulch is used in agriculture to improve the crop yield by suppressing the heat and altering the soil thermal environment [80]. The hydrolyzed proteins which are derived from waste products of the leather industry are used as biodegradable polymeric ingredients and are cross-linked with PEG (polyethylene glycol) and used for spray mulching [81].
The polyacrylic acid lignin hydrogel (LBPAA) is prepared by grafting lignin on the surface of the polyacrylic acid network. It is used for the sustainable release of pesticides, so it found its application in CPR (controlled pesticide release) [82]. Avermectin (Av) is extensively used to control weeds, plant diseases and insects. These are the derivatives of pentacyclic 16-membered lactones and a broad spectrum of antiparasitic agents. A controllable avermectin release system triggered by pH and temperature stimuli makes it an environmentally friendly hydrogel for controllable pesticide release [83] PHA (polyhydroxyalkanoates) is used as material for the construction of a controlled release system for agricultural pesticides. The mixture of PHA and pesticides can be designed in different forms like microparticles, granules, films and tablets. By using these strategies, some of the herbicides like metribuzin and tribenuron-methyl were successfully delivered and it showed a positive effect on the crop yield [84]. The biodegradable transplanting pots are designed by using the biobased composites with PLA, Ecoflex and wood fibers. These biodegradable plant pots are widely used in the nursery and greenhouse industry. The main advantage of these pots is that they can be planted along with the growing medium and seedling without causing any damage to the development of roots because these pots will easily break down and degrade fast after that is planted in the soil [85]. Poly(butylene adipate-co-terephthalate) is used for manufacturing agricultural mulching films and these biodegradable films are commonly used in strawberry plantations (Fig. 3) [86].
Biodegradable superabsorbent polymers and polymer hydrogels are playing a major role in agriculture due to their water absorption and retention properties. It also helps in the delivery of fertilizers to the plant. Apart from this, biodegradable pots, mulching films are also widely used. The use of biodegradable polymers in agriculture is environmentally safe. But, still, some advancement in polymer technology is needed in this field.
Application of biodegradable polymers in biomedical applications
Biodegradable polymers are widely used in various biomedical applications. These polymers are sterile and show a smart response toward various physiological stimuli [87]. Some of the biodegradable polymers are used in controlled release drug carriers and they have high water stability and improved pharmacokinetics [88]. The application of biodegradable polymers in surgeries and implantation medical devices reduces the chances of infection, and also, they have antimicrobial properties [89]. Some of the biodegradable polymers like poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and their copolymers like poly(lactide-co-glycolide) (PLGA) are non-toxic to human tissues [90]. These are biodegradable polymers approved by the US Food and Drug Administration (FDA) [91]. Because of their non-toxicity, these polymers are widely used in medical applications like bone fixation devices, surgical sutures, artificial skin, wound dressing, cell scaffolding for tissue engineering and controlled drug delivery systems [90]. This is also used for disposable medical devices such as injection pipes, surgical gloves, pads and syringes. Hence, they have wide commercial applications [92]. Citrate-based biodegradable step index optical fibers were used for drug delivery, photodynamic therapy, optogenetics and tissue/scaffold imaging and monitoring [93].
The biodegradable polyhydroxyalkanoates are a promising biomaterial and extensively used in biomedical applications such as wound dressing, stents, orthopedic pins, nerve guides and bone marrow scaffolds [94]. It is also used in other medical applications like coronary angioplasty, nerve regeneration, bone tissue engineering and cardiac tissue engineering [95]. Biodegradable polymeric nanoparticles are greatly used in various biomedical applications. They show high potential for site-specific targeted drug delivery. It is mainly used for oral administration of peptides and proteins and it is also used in gene therapy. So, these biodegradable polymeric nanoparticles are usually synthesized from preformed polymers by using various technologies like emulsification–solvent evaporation, nanoprecipitation, dialysis and supercritical fluid technology, or these polymeric nanoparticles can be directly prepared by polymerization of monomers by using some of the polymerization techniques like mini-emulsion, microemulsion, surfactant-free emulsion and interfacial polymerization [96].
Application of biodegradable polymers in tissue engineering
Biodegradable electrospun nanofibers have the same size as biomolecules and mimic biological properties. Since electrospinning is a simple and inexpensive technique, these electrospun nanofibers are playing a very important role in biomedical applications like cardiac tissue engineering, skin tissue engineering, bone tissue engineering and nerve tissue engineering [97]. The biodegradable thermoresponsive polymers can be used for 3D printing of hydrogel scaffolds in tissue engineering [98]. These polymers can act as sacrificial materials for bioprinting. By using the freeform reversible embedding of suspended hydrogels (FRESH) technique, the printing of low viscosity and soft hydrogels like collagen can be obtained. Therefore, thermoresponsive biodegradable polymers are used for 3D printing of hydrogels such as collagen and gelatin and notably widening the range of printable materials for tissue regeneration [99].
Poly(tri-methylene carbonate) (PTMC) is used in the fabrication of non-commercial devices of soft tissue engineering [92]. The biodegradable polyurethane (cPU) is produced by cross-linking with hexamethylene diisocyanate (HDI), polyethylene glycol (PGA) and prepolymer PLEG and is used as a scaffolding material for hypopharyngeal tissue engineering. This has excellent hydrophilicity and relatively quick degradation. It can support the growth of human hypopharyngeal fibroblasts [72].
Application of biodegradable polymers in drug delivery
Biodegradable polymers have vast applications in the areas of drug design, development and therapy [101]. To obtain steady drug release, the two prominent groups of polymeric materials, i.e., degradable polymeric and porous polymers, are used. These polymers are used to encapsulate the drug compounds [102]. The biodegradable hyper-branched polyglycerols consisting of oligo caprolactone segments in the backbone (hPGOCs) are used as intradermal drug delivery. This polymer penetrates the skin and transports the hydrophobic guest molecules through the stratum corneum into deeper skin layers [103]. These hPGOCs may degrade into lighter fragments in the presence of the enzymes' skin lysate [104]. Because of this property, there will be a facilitated release of drugs and less accumulation inside the tissues without causing any serious effect on the viable dermal layers [103]. The biodegradable silk fibroin (SF)/alginate blend films are used in the controlled release delivery system for water-soluble drugs. It is used in the controlled release of an antimicrobial model drug called tetracycline hydrochloride [105].
The biodegradable PLA thin-film composites which are developed by using polylactic acid and microspheres of hydrothermally converted coralline hydroxyapatite (cHAp) are used in drug delivery systems for regeneration [106]. In this system, PLA provides flexibility and biodegradability to the drug delivery system [107]. On the other hand, coralline hydroxyapatite supplies a sufficient amount of phosphate and calcium ions for bone regeneration [106].
Electrospun nanofibers have a high surface area–volume ratio and these fibers possess interconnected pores which enhance dissolution rate and therapeutics index because this property is more likely used in drug delivery [97]. Biodegradable thermoresponsive polymers like collagen, gelatin, cellulose, poly(N-vinyl caprolactam) is used for drug delivery system [98]. Silk fibroin–poly(sebacic acid) diacetoxy terminated (SF-PSADT) polymeric composite coatings are used in drug delivery. This polymer prevents drug denaturation and also enhances drug stability. Here, the SF matrix can be degraded by enzymes and get excretes without any side effects from the body [108].
Plasma co-polymerized nanocoatings like biodegradable PCL-co-PEG coating are used for tunable drug delivery applications which reduces nephrotoxicity and myelosuppression [109]. The biodegradable polymeric solid implants (PSIs) are used for ultra-long-acting (ULA) drug delivery of antiretroviral drugs for HIV PrEP/ART (HIV preexposure profile access/antiretroviral therapy) and delivering the other drugs [110]. The biodegradable phosphazene–tannic acid nanospheres are antioxidants and have good drug-holding capacity with a drug release rate linked to pH. They act as nanocarriers to transport drugs in the treatment of diseases like stomach, uterus, esophageal and colon cancer [111].
Application of biodegradable polymers in anticancer drug delivery
Cancer or tumor is a growth of abnormal mass of tissue that has a distinct tumor microenvironment and complex structure [112]. Anticancer drugs are usually toxic or lethal and it also shows serious side effects. The risk of these side effects can be reduced by delivering the drugs to the tumor site without leaking into other sites. This can be done by developing a suitable drug delivery system that can ensure the encapsulation of suitable drugs before reaching the targeted tumor site without any leakage, but can be able to discharge the drug after entering the tumor tissues [113]. Biodegradable polymer conjugates are used as anticancer agents in cancer therapy, these anticancer polymer conjugates are effective in delivering the drugs and genes [114].
The biodegradable polyphosphazenes are used as a carrier in anticancer drug delivery of platinum-based anticancer agents like cisplatin. Poly(organo) phosphazenes are also used in various biomedical applications like polyelectrolytes which are used as vaccine immunoadjuvants and polyplexes for gene delivery [115]. The biodegradable PEG–poly(pentadecalactone-co-N-methyl-diethyleneamine sebacate-co-2,2’-thiodiethylene sebacate) (PEG-PMT) micelles are used as eminent vectors for controlled release of antitumor drugs at their tumor intracellular site. The PEG-PMT nanoparticles show non-toxicity toward the normal organs like kidneys and liver [112]. The hydrophobic anticancer drugs such as paclitaxel (PTX) and doxorubicin (DOX) are successfully delivered to the targeted site by using biodegradable polymeric micelle. The use of these micelles has numerous advantages such as enhancement of water solubility of anticancer drugs, passive targeting tumor tissue via the enhanced permeability and retention (EPR), prolonged drug circulation time, improved drug bioavailability and excellent biocompatibility [2].
The biodegradable polymeric nanoparticles are also used in the treatment of colorectal cancer [116]. The polytyrosine nanoparticles are multifunctional biodegradable nanovehicles that have high encapsulation of doxorubicin (DOX) and it exhibits superstability, prolonged blood circulation time and stimulated drug release inside the cancer cells. It shows high specificity toward HCT-116 colorectal cancer cells and notably improves tumor accumulation [117]. The biodegradable poly(1,4-phenyleneacetone dimethylene thioketal) (PPADT) nanoparticles are used as intracellular drug delivery of anticancer drug agents [118]. PLA or PAMAM (polyamidoamin)-based polymers are used as topical delivery of drugs and also as carrier systems for the treatment of different types of skin tumors or skin cancers [119].
The major side effects observed in conventional cancer therapeutics could be reduced with a targeted polymeric system. Drug delivery systems based on biodegradable polymers have a significantly high potential to deliver the payload to the targeted site and can improve drug availability at the targeted site (Fig. 4) [120].Fig. 4 Schematic representation of biodegradable polymers as facile tools for targeted anticancer drug delivery: a carriers for systemic drug delivery: micelles, nanoparticles, polymer lipid hybrid nanoparticles, polymersome, dendrimers, polyplexes, polymer–drug conjugates loaded with chemotherapeutic agents. b Carriers for local drug delivery: in situ gels, wafers, meshes, millirods. c Polymeric products used for cancer treatment in clinic. d Clinical trials on biodegradable polymer-based drug delivery [99]. Reprinted with the permission of Taylor and Francis
Application of biodegradable polymers as contraceptive Drugs
Hormonal contraceptives are used to prevent or delay pregnancy. There are many contraceptive methods, some of the most common ones are combined oral contraceptives (COC) or progestogen-only pill (POP) which contains combined progestogen and estrogen, and only progestogen hormone. But they are not much effective and also require daily oral intake of pills [121]. There are other contraceptive methods such as the use of male and female condoms, subdermal implants, vaginal rings, intrauterine devices (IUDs) [122]. But the use of these conventional contraceptive implants and injectables has shown less effectiveness. The use of IUDs is not economically efficient and also it should be inserted and removed through surgical procedures every few months. Certain IUDs can be used greater than one-year providing contraceptive therapy, but they are extremely costly, also lead to discomfort to patients and irregularities in menstrual bleeding [123].
PCL [poly(ε-caprolactone)] is a biodegradable polymer which is FDA-approved and it is extensively used as an implantable biomaterial and injectable implants for controlled release drug delivery system. PCL microsphere is fabricated with two loading concentrations of levonorgestrel (LNG) for long-term contraceptive drug delivery. LNG is an FDA-approved progestin hormone that prevents ovulation by eliciting changes in the uterine lining. PCL–LNG system has many advantages compared to many other commercially available products. This ensures prolonged contraceptive therapy combined with steady degradation for therapy and also overcomes the need for secondary surgery [121]. PLGA (polylactic-co-glycolic acid) microsphere fabricated with etonogestrel (ENG) which is also a progestin hormone used as a controlled contraceptive drug delivery system and releases the drug ENG [124].
The biodegradable passive implants which are made up of polymers or block copolymers can be degraded and eliminated or absorbed by the body. Polymers such as PCL, PLA PLGA are used in these implants. The mechanism of drug delivery in these implants is a combination of diffusion dependent drug release with matrix degradation. The matrix degradation is a major driving force. The use of these biodegradable polymer implants over non-degradable implants is more advantageous. They do not need any procedure for extraction after their intended course of use [125].
Application of biodegradable polymers in medical packaging
A blend of polypropylene/poly(lactic acid) is used in medical packaging because of its water barrier property, contamination reduction, prevention of bacterial growth and antimicrobial properties. It is extensively used in medical fields and hospitals [126]. The development of biodegradable polymeric material in pharmaceutical packaging is a complex task. In this case biodegradable polymers should have certain characteristics and properties as follows: biodegradable polymeric material should not allow penetration into production; it should not change the formulation of medicine and should not react within or change medicinal ingredients; it should be consistent and able to withstand external influencing factors like moisture, heat, oxygen, light, mechanical and biological contamination, etc. [127]. The PLA/SIS blends (polylactic acid/styrene–isoprene–styrene) are also used in medical packaging applications. The presence of SIS enhances the oxidation strength, so it has a wide range of applications in the field of medical packaging [128].
Application of biodegradable polymers as Orthopedics
Nowadays biodegradable polymers are used in orthopedics applications. The bioceramics like Hydroxyapatite (HA) as excellent biocompatibility, bioactivity and osteoconductivity properties. The hybrid polymer products that are based on HA–poly(PEG-co-propylene fumarate-co-ascorbate) hybrid macromers are used in bone graft materials because of their excellent mechanical properties and osteointegration ability and promote albumin adsorption and osteoconduction [129].
The biodegradable implants which contain magnesium-based materials are used for temporary orthopedic and cardiovascular stent applications. The use of magnesium-based biodegradable implants avoids second surgical procedures and reduces the stress-shielding effect. So, it is more advantageous than compared to other metallic implants such as 316L steel, titanium alloys and Co–Cr alloys. Nowadays AZ31Mg alloy sheets that are coated with PCL nanofibers are used in designing biodegradable Mg-based implants and it has shown excellent corrosion resistance, wettability, bioactivity and degradation properties [130].
Most of the materials that are commonly used for bone fracture fixation are 316L stainless steel, cobalt–chromium-based alloys, pure titanium and its alloys, but all these are non-biodegradable. One of the important characteristics of an implant is its ability to degrade after the healing of bone. Since the implant is metallic, it is a foreign body to the tissue due to which local inflammation may take place, and in some cases, a second surgery may be required for the removal of that implant. To avoid such risks, biodegradable metallic implants came into use. One of the most commonly used degradable metallic materials is magnesium and its alloys. But again, there is an issue of corrosion and also it degrades rapidly with the release of hydrogen gas on degradation. To overcome this issue, several strategies like alloying, various surface treatments were tried to enhance the corrosion resistance of magnesium. To alter its original mechanical properties some of the rare earth metals like Zr, Ce is added into the Mg substrate, but they are toxic to the human cells and also the cytocompatibility of these elements is not known. To overcome all these drawbacks, the biodegradable polymeric membrane fabricated by dichloromethane and PCL onto Mg alloys is developed. By coating this controllable polymeric membrane on Mg alloy, the corrosion and degradation rate is reduced and also it provides good cytocompatibility of eGFP and SaOS-2 osteoblasts. The cell toxicity is also not observed. Now, these biodegradable polymeric membrane implants are extensively used in clinical use for orthopedic applications [131].
Some of the important parameters of ideal biodegradable implants are lower rates of biodegradability, to provide sufficient mechanical support until the healing process gets completed. Another parameter is biocompatibility which can be controlled by using bioinert elements, nutrients, etc. [132]. The organ which undergoes the most transplants/grafts every year is bone. Bone fracture is a common problem everywhere due to the increased rate of accidents/diseases. It is also estimated that every year over 3 million bone surgeries are performed worldwide. For this reason, the quality and efficiency of bone fracture treatments are more important for patients as well as for doctors [133].
The biodegradable cortical screws with porous interconnections were recently developed. The porous biodegradable screws have interconnected pores similar to that of native bone tissue (~ 300 μm) and have similar mechanical strength so that the stress-shielding effect has been prevented. These biodegradable porous screws showed enhanced mineralization over 4 weeks and the pores act as nucleation sites for the deposition of salt which was confirmed by the invitro degradation test [134]. There are a lot of biomaterials that have been developed by researchers for various orthopedic applications like stents, scaffolds, hard tissue replacements and spinal degeneration disease [135].
Application of biodegradable polymers in periodontal regeneration
Periodontal disease is one of the inflammatory diseases in the tooth which leads to the destruction of periodontal tissues and is also associated with severe pain. The biodegradable polymers like Helixician (HX) immobilized biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA)-based electrospun films and fibers are used in this periodontal treatment. These systems were tailored to achieve prolonged drug release. These biodegradable scaffolds are used for periodontal tissues regeneration, because of anti-inflammatory and antimicrobial properties these polymers are greatly used [136]. Nanofibrous scaffolds prepared from PCL or PCL/CA (polylactic acid/cellulose acetate) are used for periodontal tissue regeneration and also in bone regeneration with antibacterial activity [137].
A drug delivery system consisting of ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6] incorporated and chitosan modified polymeric nanoparticles by using the base materials like poly(DL lactide-co-glycolide) (PLGA) and polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft polymer is used for the prevention and early treatment of periodontal disease. These polymeric nanoparticles have high tissue affinity and antimicrobial activity [138]121. Periodontitis is mainly caused due to bacterial infection. Because of this, antibacterial agents are commonly added to GTR/GBR scaffolds. Silver nanoparticles can also be used because it belongs to broad spectrum antibacterial activity. Electrospun nanofibrous scaffolds are used for GTR/GBR applications. The nanofibers are synthesized either by the combination of polylactic acid and cellulose acetate (PLA/CA) or poly(caprolactone) (PCL) polymers. In addition to this, silver nanoparticles (AgNPs) and hydroxyapatite nanoparticles (HANPs) which are green synthesized are incorporated into the scaffolds to improve their antibacterial and bone regeneration activity. These GTR/GBR scaffolds (Fig. 5) are biodegradable, antibacterial, Osteoconductive and provide optimal mechanical strength, so it helps in periodontal tissue and bone regeneration [137].Fig. 5 Development of a new series of electrospun nanoparticles-in-nanofibrous scaffolds for GTR/GBR applications with enhanced antibacterial and bone regeneration activity [137]. Reprinted with the permission of Elsevier
Application of biodegradable polymers in food packaging
Biodegradable polymers are biocompatible, non-toxic and highly selective [139]. In the packaging industry, they are replacing conventional petroleum-based polymers [140]. In the plastic industry packaging field is one of the largest sectors. Nowadays these biodegradable polymers are in great demand for packaging [141].
A commercial biodegradable polymer named Mater-Bi is based on biodegradable polyesters has numerous applications in the packaging industry because of its interesting thermal stability, processability, mechanical property and biodegradability. It is used as one of the polymers in the manufacturing of nets for fruits and vegetables [112].
Polyvinyl alcohol (PVA) is blended with some biodegradable polymers like sodium alginate, gelatin, carboxymethyl cellulose and K-carrageenan, but particularly PVA is blended with K-carrageenan to form a strong binary blend film which exhibits high resistance and water barrier property. So, it is used as a packing material in the food industry [144].
To improve the water vapor barrier property, biodegradable polymers like PCL are more favorable because of their flexibility. The polar groups which are present on the side chains of biodegradable polymers tend to decrease the water vapor barrier property. Biodegradable PCL/C18 blends are used in packaging materials due to their high oxygen and water vapor barrier property even at high humidity. The biodegradable polymers which are having the polar groups –OH at their molecular side chains show less water vapor barrier property. To improve the water vapor barrier property, biodegradable polymers like PCL are mixed with glycerol tris stearate (C18) which in turn increases the hydrophobicity. This is an extensively used biopolymer over polyethylene due to its better biostability and mechanical strength [140].
The conventional thermoplastic materials used in food packaging can be replaced by biodegradable cellulose esters. Cellulose esters such as cellulose triacetate and cellulose diacetate can be prepared by the addition of additives. Montmorillonite is a biodegradable nanoclay biocomposite and it is hydrated alumina silicate layered clay. The specialty of this is to limit the penetration of gases during food packaging. Biodegradable films like whey protein isolate films are strengthened by the addition of nanoparticles like TiO2 and SiO2 and these films are effectively used as a packaging material that favors food quality and safety [145].
The biodegradable polymer films like poly(3-hydroxybutyrate-co-3-ydroxyl valerate) which is developed from the Ceiba pentandra. These biocomposite films are specially designed for fruits packaging. This extends the shelf life of perishable fruits and also shows antimicrobial activity [141]. The bionanocomposite films are prepared by blending cellulose nanocrystals with silver alginate from cellulose nanocrystal alginate (CNC/Alg). These are used in food packaging due to their UV and water barrier properties [146].
Biodegradable TiO2 NPs embedded cellulose acetate (CA) films which have photo-catalytic activity, high transparency and antimicrobial property are packing materials in the food packaging industry [147]. The polypyrrole silver-coated layered double hydroxide (LDH/Ppy-Ag) embedded into a biodegradable polymer matrix, i.e., LDH/Ppy-Ag/PCL nanocomposites are used widely in the packaging industry. These biodegradable polymer nanocomposites possess excellent gas barrier and mechanical properties; in addition to this, they also show good antibacterial activity [148].
Biodegradable polyglycolic acid is used as a packaging material to enclose perishable foods or goods with limited shelf life. This packing film contains two layers with a reactive chemical layer that is interposed between two layers. If one layer degrades, the synthetic layer is exposed to air and it causes the change of color in the remnant layer which indicates the expiry of the shelf life of the package [149]. PLA is used as packaging material and it is considered a “Green” food packaging polymer as it possesses good microbial activity. It is used in the retail market for packaging vegetables, fruits and salads [150]. Natural biodegradable polymer-based silane cross-linked blended films are also used in the food packing industry because of their antioxidant activity, biodegradability, water vapor permeability, lower water vapor transmission rate has shown better shelf life. Hence, these biodegradable films have good potential for food and packaging [151].
Active packaging is essential to extend the shelf life of the goods and to keep the product fresh. It should also maintain the quality of the product and should ensure the safety of the environment [143]. The direct disposal of plastic bags brought many serious concerns, so this led to the use of biodegradable polymers in the food packing industry and also in other packaging materials. This resulted in a decrease in the ecological impacts due to synthetic packaging materials [151].
The starch-based biodegradable polymer is used as thermoplastic. They are prepared by plasticization through destructuration with water or plasticizers and by heating. So thermoplastic starch blended with other biodegradable polymers or additives shows good mechanical strength and resistance to water. So, this is widely used in the food packaging field. Protein-based biodegradable polymers are also widely used in food packaging and other non-food packaging applications. The protein polymers like whey protein, milk protein, zein, wheat gluten, corn, soy protein, etc. are used in food packaging. These protein-based biodegradable polymers can be consumed along with the food. These edible films in food packaging with barrier and mechanical properties are very much useful in food packaging [152].
Packaging is mainly dealt with polymers. But synthetic polymers are extensively used in packaging because of their low cost of production. But there are many disadvantages of using synthetic polymers. The use of biodegradable polymers in place of synthetic polymer had become a greater and greener alternative. However, the cost of production is high compared to that of conventional polymers. But there are many advantages of using biodegradable polymers. It is user-friendly as well as eco-friendly. In this review, we discussed the majority of biodegradable polymers that are applied in the packaging field. Most of the biopolymers that are obtained from nature are used as food packaging materials.
Application of biodegradable polymers in making paper boards
Paper boards are one of the extensively used polymers which are used in industries. Since paper boards are highly water-soluble, they are coated with some biodegradable polymers like polyurethane, paraffin wax, polyamides, polyesters and polyvinyl copolymers. This, in turn, increases the physical and mechanical strength of the paper board, since they are hydrophobic; the surface of the paper board is prevented from wetting, and the water barrier property is enhanced. Paraffin waxes are not preferentially used as coating copolymer because of their instability and less durability at high temperatures. So other copolymers like PVB (polyvinyl butyral) which is water-insoluble are used for coating on paper boards because of which it exhibits excellent commercial applications [153].
Application of biodegradable polymers in automobiles
In recent times, biodegradable polymers are extensively used in automobile industries because of their good mechanical properties, high specific strength and eco-friendly nature. It is now replacing conventional fiber like glass, aramid and carbon. Nowadays industrial and agricultural waste materials are used for making biodegradable polymers. For example, the coconut shell powder-reinforced composite is used in the interiors of spacecraft, ships, aircraft, motor cars and automobiles instead of conventional plastic materials [154].
The biodegradable polymers can be used for both exterior and interior components of automobiles, but because of present materials properties constraints, these biobased materials are only used in the manufacturing of interior components of automobiles [155]. The biodegradable bark cloth-reinforced epoxy biocomposites are used in making the interior automotive panels because of their mechanical property and high tensile strength. It is used in the manufacturing of interior panels in cars like dashboards (Fig. 6) [156]. Henry Ford has used biopolymers in the manufacturing of his own Ford cars [157]. The epoxy matrix with the addition of jute is used indoor panels of E-class vehicles of Mercedes Benz. The ecoplastic developed which is made from sugarcane is developed by TOYOTA and it is used as the interior lining of cars [154]. The application of biodegradable polymers in automobiles is considered to be interesting and challenging. Most of the high-branded automotive companies have switched to biodegradable polymers to manufacture various parts of the vehicle.Fig. 6 Biocomposite processing: a bark cloth fabrics, b fabricated composite mold [156]. Reprinted with the permission of Elsevier
Application of biodegradabe polymers in wastewater treatment
The natural biodegradable polymeric absorbents can be used to remove toxic dyes [158]. Dye contamination is found to be one of the serious issues which are occurring in water bodies which also affects human health. The amount of freshwater availability decreases as the amount of wastewater production [129]. To solve this problem, biodegradable polymeric materials were designed to clean up the dye-contaminated water. These polymeric absorbents have high dye removal efficiency with vast sensitivity. The biodegradable wheat flour absorbent which is a carbohydrate absorbent is used for the removal of cationic Rhodamine B (RB) dye from water. This polymer shows high sensitivity and selectivity toward this particular dye. RB dye is a cationic organic dye compound and it is applied for various industrial purposes like dying in textiles, paints, leathers, paper and printing. There are many metals for organic dye removal like coagulation–flocculation, degradation, adsorption, oxidation, etc. Since these techniques are effective and show low selectivity, the bioadsorbents are widely used [160]. Several pollutants are causing pollution in water and other harmful health issues to humans and other living organisms. But among them, the presence of heavy metals in water is a major concern. This heavy metal contamination leads to death of living beings [161].
As the result of rapid industrialization, there are many toxic heavy metals, released into water. This leads to damaging the aquatic ecosystem as well as human health [162]. Many methods like precipitation, reverse osmosis and electrolysis were developed for the removal of heavy metals from industrial wastewater. But these techniques are so expensive and also inefficient in the removal of toxic heavy metal ions. Sometimes, the application of these methods produces toxic waste. This can be overcome by using natural biodegradable polymers. Even superabsorbent polymers are also used to remove these ions, but due to their high cost this is not much encouraged. The chemically modified graft product, polyacrylonitrile-g-Arabic gum were used which is very effective in removing Pb2+, Cd2+, Hg2+, etc. from the wastewater. So, this method is cheap and easily accessible [133].
The removal of heavy metals from wastewater is a major concern [164]. They are carcinogenic and is mainly discharged from industries [165]. Heavy metals cannot be destroyed like other organic pollutants. Once these heavy metals are released into the ecosystem they can be easily absorbed and accumulated in the tissues of an organism which leads to several serious health issues [164]. One of the widely used methods for the removal of heavy metals from wastewater is adsorption techniques [166]. Cell EDTA (cellulose-EDTA) or cell CM (carboxymethyl) are the two modified cellulose that is used as bioadsorbent for the removal of heavy metal ions like Pb2+ and Cd2+. The cellulose fiber is obtained from pineapple leaves or modified as bioadsorbent for heavy metals removal from wastewater [167]. Most of the biopolymers are applied in offshore oil and gas pipelines since it is biodegradable and also prevents the gas hydrates from the gas pipelines [168].
Cross-linked porous starch is prepared by cross-linking of corn starch with the epichlorohydrin followed by treatment of hydrolyzation with α-amylase. This novel biopolymer-based sorbent is very much useful in removing methylene blue dye from water [169]. Magnetic carboxy methyl starch (CMS)/poly(vinyl alcohol) hydrogel (mCMS/PVA) is also used in the effective removal of methylene blue dye contamination from the water [170].
Magnetic nanoparticles (MNPs)/starch-g-poly(vinylsulfate) nanocomposite is used in the adsorption of various cationic dyes like methylene blue and malachite green which are present in the wastewater [171]. The cross-linked cationic starch is used for the removal of golden yellow dye from the water samples [172]. Toxic metals and other harmful organic compounds are also removed from water by using this cross-linked starch [169]. Cellulose-based nanomaterials are also used in the removal of various hazardous chemicals and other contaminants from the water, because of their non-toxicity, biodegradability and availability [173]. Kappa-carrageenan/poly(glycidyl methacrylate) (CG/PG) hydrogel is an environmental-friendly adsorbent which contains many functional groups. These are used in the removal of cationic methylene blue dye during wastewater treatment [174]. Cross-linked chitosan/sepiolite composites are also used to remove the organic and inorganic pollutants from water. They are very selective in the removal of dyes like reactive orange 16, acid red-2 and methylene blue when epichlorohydrin is added as an additive [175]. Calcium alginate-based hydrogel beads are a low-cost biomaterial used to remove the mutagen and mitotic poison, methyl Violet from wastewater [176]. Endocrine-disrupting chemicals (EDCs) present in the wastewater can be removed by using biodegradable polymers. Pharmaceuticals, personal care products, industrial compounds, pesticides, dyes and heavy metals which are present in wastewater are considered as EDCs. These chemicals have a severe impact on humans and animals [177].
Applications of biodegradable polymers in textiles and hygiene products
In recent times, the usage of personal protective equipment like face masks, gloves, gowns, aprons, hoods, eye shields and shoe covers has increased across the globe due to the COVID-19 pandemic [178]. Majorly the usage of face masks has increased to a great extent. Since most of the face masks are made up of petroleum-based non-biodegradable polymers, the amount of waste generated is high which leads to severe environmental pollution [179]. Generally, there are three different types of masks consisting of different layers, namely N95 mask (four layers), surgical mask (three layers) and cloth mask (one layer) [180]. These masks can be replaced by biodegradable polymers, but complete replacement of biodegradable polymers in face masks production is not possible. So any one of the layers in the mask can be replaced by biodegradable like PLA, PHA, poly(lactic-co-glycolic acid), cellulose acetate, polycaprolactone, etc. [181]. In particular, the layer which is in contact with skin is replaced by using biodegradable polymers. In addition to air filtration, these masks are antimicrobial, antifungal, UV protective and skin-friendly [182]. The ear loops of both N95 and surgical masks are made up of biodegradable polymers called poly(isoprene) units (latex-free rubber) [183].
Biodegradable polymers like PLA and cellulose are used in the manufacturing of face masks. These polymers are lightweight, low cost, safely disposable and comfortable to use. In addition to this, it provides adequate filtering performance and readily degrades after discarding [184]. Melt-blown PLA (MBPLA) electret membranes are used as interesting material for the production of face masks due to their excellent air filter capacity. These PLA melt-blown nonwoven fabrics can form electrets by corona charging technology [185]. The biodegradable cellulose acetate polymer nanofibers provide high-efficiency filtration for aerosol nanoparticles and also provide antibacterial properties, so it majorly used in the production of masks [186]. The biodegradable mask filters manufactured by using CsW (chitosan nanowhiskers) and PBS (polybutylene succinate) are highly efficient sustainable and fully biodegradable within a month in the soil [187]. The gluten-based biodegradable face masks are also being manufactured and it has good viral filtration capacity. Its antiviral properties can be enhanced by using natural products like turmeric, basil, neem oil, moringa seeds, etc. The nanofiber membrane in this mask can be produced by the electrospinning method and gluten sheets are produced by the hot-press method (Fig. 7)[188].Fig. 7 Production of gluten-based biodegradable polymers [189]. Reprinted with the permission of Elsevier
In this review, we mainly focus on the applications of biodegradable polymers in tissue engineering, drug delivery, anticancer drugs, contraceptive drugs, orthopedics and medical packaging. Biodegradable polymeric electrospun nanofibers are also used particularly in tissue engineering and drug delivery. The use of biodegradable polymers in the biomedical field is extremely safe for the human body as well as for the environment.
The use of personal hygiene disposable products is increased 50% more due to COVID-19 outbreak [190]. The presence of non-biodegradable polymers in personal hygiene products like diapers and sanitary napkins leads to the emission of methane after disposal into landfills which in turn increases global warming issues [191]. Superabsorbent polymers (SAP) are hydrogels that are cross-linked 3D hydrophilic polymers, these can absorb, swell and retain a large quantity of water or any biological fluids. Because of these properties, it is widely used in most commercial products such as sanitary napkins, disposable diapers and also used in some other areas [192]. The SAPs absorb and retain the fluids under mild mechanical pressure and this swollen gel retains the fluids in a solid, rubbery state and prevents the leaking of fluid onto the baby's skin and clothing [193]. The physiological fluids are retained within a gel structure and are not even released under pressure of baby weight. As the result, these SAPs are greatly used in the personal hygiene products and healthcare industries [194].
The disposable baby diapers are made up of multiple layers consisting of different materials. The top layer consists of polypropylene sheets which are hydrophilic nonwoven and allow the urine to pass through it. The middle layer is made up of superabsorbent polymer which helps in holding the urine. The bottom layer is made up of hydrophobic nonwoven films which consist of polypropylene fibers. Since polypropylene is toxic and non-degradable, it can be replaced by biodegradable viscous nonwoven which is made up of cellulose. The advantages of using this cellulose provide physiological safety, skin tolerance, better moisture absorbance, easily degradable and being eco-friendly [193]. Chitosan, citric acid and urea (CHCAUR) is biodegradable polymer which has excellent water absorption property. It has maximum saline water-absorbing capacity and it is also used as an alternative for SAPs in diapers due to its superior water absorption characteristics [195].
The use of synthetic SAPs like polyacrylate-based sap in sanitary napkins is toxic and carcinogenic. They are non-biodegradable and lead to environmental pollution, so to overcome these drawbacks some of the greener alternative SAPs are used in sanitary napkins. For example, the natural polysaccharides-based SAPs which are made from chia seeds (salvia histanica), chia flour and mimosa pudica hydrogel (MPH) are used as the absorbent core of sanitary napkins. These are biodegradable, biocompatible, renewable and non-toxic. The chia seeds have the highest swelling capacity, but MPH has the highest absorbing capacity compared to chia seeds and chia flour. Because of its high absorbing capacity, low re-wet value, good antibacterial property, biodegradability. This MPH is used as SAP in sanitary napkins [196].
Synthetic sanitary napkins have poor fluid retention capacity and because the use of these synthetic materials, blocks moisture and temperature that further leads to yeast and bacterial infection in vagina which causes toxic shock syndrome. The use of plasticizers in sanitary pads leads to multiple organ failures. In order to overcome these problems, the biodegradable polymer-based sanitary napkins came into existence. Sodium alginate and carboxy methyl cellulose (CMC)-based hydrogels are used as an absorbent core for sanitary napkins and these napkins are non-infectious, biodegradable and non-toxic [197].
Since the use of non-biodegradable polymers in sanitary napkins increases the risk of the health of tissues, it can be replaced by biodegradable polymers which are obtained from natural and sustainable raw materials like bamboo fiber, banana fibers, jute fiber and coconut fiber. In order to increase the absorbance of sanitary napkins, cellulose-based hydrogels were used. For example, sodium carboxymethylcellulose (NaCMC) and hydroxyethyl cellulose (HEC) cross-linked with divinyl sulfone (DVS) are used as a hydrogel [198]. It has better fluid retention property and antimicrobial property is improved by treating the absorbent core with 70% halogen extract. The cellulose-based hydrogels are biodegradable and environment-friendly, and possess excellent biocompatibility. The use of natural fibers in sanitary napkins will reduce the cost of production and also prevents waste generation [199, 200]. The superabsorbent polymers can be obtained from recycled carboxymethyl cellulose material by using it as a precursor. These biobased SAPs are very much used in diaper applications [201].
The application of biodegradable polymer in sanitary needs like sanitary napkins and diapers is extremely beneficial. Majorly SAPs are used in sanitary napkins and diapers. Since the biodegradable polymers possess antibacterial and antifungal properties, it will be an added advantage. The use of biodegradable SAPs in sanitary needs is considered to be safer. The use of biodegradable polymers in sanitary needs had also controlled many health-related issues and also environment-related issues.
Application of biodegradable polymers in electronic devices
In the present era, the generation of E-waste is ever increasing. To overcome this, biodegradable polymers are used in the manufacturing of various electronic devices [202]. The biomaterial-based organic electronics or “green” electronics are having good potential and create a positive impact in the future [203]. The utilization of biodegradable and organic electronic materials can contribute to minimizing the environmental impact in the electronic industry [204]. Silk is an enzymatically degradable biomaterial which is widely used [205].
Poly(1,4-cyclohexylenedimethylene terephthalate-co 1,4 cyclohexylene dimethylene 2,6-naphthalene dicarboxylate) copolyester (PCITN) is a biobased polymer used as smart films for making flexible optical devices and electronic devices. It has high thermal, mechanical, optical and water barrier property compared to other conventional polymers, so it is used as a smart film in various industrial applications [206]. Cellulose is used as a substrate material in different electronic applications like in the manufacturing of field-effect transistors (FET), organic light-emitting diodes (OLEDs) and also solar cells (Fig. 8) [207]. The ultra-thin cellulose film which is chemically and thermally stable is used as a biodegradable substrate for the development of charge transport, transient and biodegradable electronics [208].Fig. 8 Application of biopolymers in the flexible display: a structure and flexibility of biodegradable devices on chitin transparent paper. b Schematic representation of the fabrication of luminescent CNC-PGM-RG composites with white light generation [207]. Reprinted with the permission of Elsevier
A common strategy, to develop biodegradable dielectrics is by incorporating high-dielectric-constant (K) fillers into a matrix of the degradable polymer. Some of the general high (K) metal oxides are SiO2 (K = 3.9), HfO2 (K = 25) and Al2O3(K = 9). Dielectronic substrates are insulators that are used to fabricate capacitors [189]. Semiconducting polymers possess good biocompatibility which is one of the essential requirements for the manufacturing of implantable medical devices or sensory devices that can directly contact living tissues [208]. Semiconducting polymers are used in the development of organic FET devices for prosthetic skins and biosensors [190]. The biodegradable polymer electrolytes in particularly polycaprolactone (PCL)-based electrolytes have electrochemical stability, high ionic conductivity, high thermal stability, ease of molding into desired shapes and sizes. So, they are used in different electronic devices like ion batteries, solar cells, supercapacitors, electrochemical display devices and fuel cells [191].
Cellulose nanocrystals (CNC) are used in the modification of internal photonic crystal structure of cellulose-based liquid crystals (LC). Because of its low-cost sustainability, non-toxicity, easy availability of raw ingredients simple manufacturing methods and low energy consumption. This innovative type of liquid crystals materials as the potential for commercial large-scale use [212].
Since biodegradable polymers conduct electricity, they had found their application even in the manufacturing of electronic devices. Various strategies are used for the applications of biodegradable polymers in electronic devices. The biopolymers like cellulose Silk and biodegradable polymer like PCL is majorly used in electronic devices. Till now, we have only limited use of biodegradable polymers in electronic devices. Still, research is needed for the efficient use of biodegradable polymers in various electronic devices. The work done in biosensors with the use of biodegradable polymers is more beneficial, especially in the biomedical field.
Application of biodegradable polymers in biosensors
Nowadays eco-friendly biodegradable polymeric materials which are having good mechanical and thermal properties were developed and used in biosensors [192]. Among the biodegradable polymers, the bioblends of poly(ethylene oxide) (PEO), polylactic acid and CNT were used. The PLA and PEO are easily degradable and biocompatible. Bioblends and conductive nanocomposites are used in biomedical biosensors [193]. The biodegradable PLA-based microneedles (MN) are used in glucose sensing for diabetes patients. The PLA-based MNs are coated with gold nanoparticles to enhance their conductivity. So, these MN-based glucose sensors can easily penetrate the skin without causing any pain and also avoid invasions that are caused by some of the commercial glucometer blood samplings from fingers. So, these biodegradable MN-based glucose sensors are used in the continuous monitoring of glucose in diabetic-based patients in a minimally invasive way [215]. Polyacrylamide–poly(ethylene glycol) hydrogen are polyacrylamide-15-crown-h Hydrogen with pendent phenylboronic acid groups are used in manufacturing of photonic crystals in glucose in glucose sensors. In this, boronic acid and PEG functional groups are prepositioned in the photonic crystals hydrogen such that glucose cells assemble these functional groups into a supramolecular complex. This complex results in an increase in the hydrogel cross-linking, which for physiologically relevant glucose concentration blue shift the photonic crystals diffractions. These materials response too glucose at physiological ionic strengths and pH values, and they are selective in their mode of response for glucose over fructose, mannose and galactose [216].
Flexible biosensors need various methodologies to tune materials for different biomedical applications; poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is fabricated on biodegradable and flexible silk fibroin matrix by photolithographic technique (Fig. 9). So, these biosensors are mechanically flexible, electroactive, optically transparent, cytocompatible and biodegradable. By this technique, inexpensive biosensors can be developed with better degradability [217].Fig. 9 Formation of the complex microstructure of PEDOT:PSS via photolithography a Large area micropatterns of PEDOT:PSS formed on flexible and conformable silk fibroin sheets, b optical micrographs. c SEM images of PEDOT:PSS micropatterns on glass [217]. Reprinted with the permission of Elsevier
The recent advancements of the biodegradable polymers in public healthcare technologies has offered various opportunities by enabling sensors that degrade naturally after use. The biodegradable polymeric implantable electronic systems which are made from these materials avoid the need for reoperation or extraction and reduce chronic inflammatory responses. This also helps to minimize some of the serious environmental problems by reducing the medical waste production or several electronic productions. Hence, biodegradable polymers are used in different biodegradable bioresorbable electronic devices such as body monitoring, medical therapeutics and diagnostic devices. These implantable devices in turn provide wireless data power transfer. The use of biodegradable natural polymers in implants or other electronic devices can elicit an immune response in the body [196]. Biodegradable electrospun nanofibers are used to detect blood glucose levels. It is widely used in glucometers. Biodegradable electrospun nanofibers are used in immunoassay techniques to detect specific antigen-antibodies. For example, biodegradable nanofibers are used in ELISA. The conventional ELISA technique has few drawbacks. These drawbacks can be overcome by coupling with electrospun silica nanofiber membrane [97].
The biodegradable PLA is a commercially attractive polymer due to its similarities with non-biodegradable and traditional hydrocarbon polymers like polyethylene (PP), polyethylene terephthalate (PET) and polystyrene (PS). PLA is a biodegradable synthetic polymer that can be synthesized by direct polycondensation of lactic acid or by ring opening polymerization of lactide monomers [150]. FDA has approved the usage of PLA in specific clinical applications. The application of PLLA [poly-L-lactide] and PLGA [poly(lactic-co-glycolic acid)] with PLA are used in the manufacturing of many biodegradable disposal products like scaffolds, bioresorbable biomaterials, drug delivery systems and medical implants. Three arm-stereo complex PLA (tascPLA) is used as a dielectric and substrate material for the skin-like temperature sensors fabrication which is thermally stable and flexible organic field-effect transistor (OFET). Flexible wearable transient ensures the sensor acts as an electronic skin (e-skin) which is used for mapping tactile stimuli and to monitor the patient’s health conditions [196]. These sensors are developed by inserting the porous MXene-impregnated (two-dimensional material) tissue paper between the two thin sheets of PLA, where one sheet is coated with the interdigitated electrode [197]. The sensor degrades after 14 days with NaOH solution due to the degradability of Mxene paper and PLA [196].
PVA (polyvinyl alcohol) is also used for developing biodegradable and biocompatible organic electronic devices [220]. PVA is used as substrate in the manufacturing of sensors, LEDs, photodetectors, transistors, radiofrequency inductors, oscillators, wireless coils, capacitors, on thin PDMS foil (polydimethyl siloxane) for the measurement of electrical activity that is produced by the heart, skeletal muscles and brain [196]. PVA polymer matrix has enough film strength and transience required for glucose levels by using the electrochemical test strips [221]. These PVA films maintain their strength and shape during electrochemical analysis. PVA–gelatin substrate in the deionized water can easily degrade after 7 days at room temperature. Hence, this is used in the manufacturing of sensors to monitor human activity and transient wearable sensors for healthcare diagnosis. PVA-LMP-based sensor is a hydrogel stabilized liquid–metal particle with PVA which demonstrates the dissolving features for transient electronics [222]. It dissolves easily at pH5 in HCl solution at room temperature after 3 days [196]. PGS (polyglycerol sebacate) is a biodegradable elastomer used in temporary health monitoring electronic devices. Electrospun PGS-PCL substrate is used to develop biodegradable and stretchable electronics to serve as biocompatible and elastic temperature sensors, strain gauges and heaters for bioresorbable electronics and smart wound dressing techniques [223]. This completely degrades after 30 days [196]. Recently, polyethylene glycols (PEG) are used in manufacturing of photonic crystals in humidity sensors. Fe3O4@SiO2/PEG acrayte photonic crystal humidity sensor has been fabricated by combination of magnetic assembly and photo-polymerization. These sensors self-displays brilliant colors as humidity changes. These photonic crystal sensors have great potential as energy efficient devices since no electric power is required for their operation [224].
Application of biodegradable polymers in cosmetics
Nowadays biodegradable polymers are finding applications in the cosmetic industry. Natural and synthetic biodegradable polymers are extensively used in cosmetics and personal care materials [225]. The major benefit of using biodegradable polymers in the cosmetic industry is that they are usually non-reactive when in contact with the human skin and body. It can be easily broken down or metabolized and eliminated from the body through normal metabolic pathways [226].
The microencapsulation technique is extensively used during cosmetic production because of the controlled release of several active agents. One of the commonly used agents is PLA which is a biodegradable polymer that encapsulates thyme oil, because of which it protects fragments and also other active agents from oxidation caused by light, moisture and heat [226]. Most of the personal products that we use for skin, hair or body contain many biologically active compounds such as vitamins. So, encapsulation is required to increase the stability of biologically active materials [226]. This microencapsulation process protects the evaporation of volatile compounds present in cosmetics [226].
Microparticles are based on natural and synthetic polymers in cosmetics. Biodegradable materials used as abrasive agents is most of the skin exfoliators (peeling products). Usually, synthetic microbeads are used as abrasive agents in these exfoliations, but due to their non-biodegradable nature, they showed an adverse impact on the aquatic ecosystem and also irritation on human skin [227]. To replace these synthetic microbeads, biodegradable polymeric microbeads like sodium alginate and sodium alginate with starch beads are used in these peeling products. This does not cause any irritation or dryness or itching to the skin. The use of these sodium alginate microparticles did not show any impact on the aquatic ecosystem because of their biodegradability [228].
Starch is a biodegradable polysaccharide that is utilized in various forms such as soluble starch and granule starch. The soluble starch is extracted and heated, so it becomes humidity-resistant which results in smooth hair and skin. So, it is mostly used as an ingredient in skin lotion and hair care products [229]. Chitosan is used in lotion and nail lacquers which is a good moisturizing agent and used to moisturize the lips and skin [230]. It is also used in sunscreens which have good antimicrobial and water resistance. It is also used in acne treatment [229, 231]. Cellulose fibrils are non-irritant to the skin, have better ability to spread and adherence to the skin. The cationic hydroxyethyl cellulose polymer called polyquaternium-10 is used in hair conditioning products because of the antistatic and moisturizing properties it keeps the hair smooth and shiny. Cellulose is combined with carrageenan and is used as a thickener [231].
Silk fibroin is used in shampoos and also used in the product which is used to prevent brittleness of nail [232]. Collagen is used in antiaging and antiwrinkling products [229, 233]. Glycerol is a bioderived polymer that is used in the cosmetic industry because of its skin-nourishing and smoothening properties [234]. So, it is used as an additive in cosmetic products such as thickener, demulcent, plasticizer, bodying agent and lubricant [237]. Pullalun (PUL) is a biopolymer that has found numerous applications in the cosmetics field. PUL is non-toxic, non-irritant, biodegradable, skin and environmentally friendly. It also exhibits good adhesive and binder properties. It has good water retention and film-forming properties. So, it is widely used as a moisturizing and protecting ingredient for facial packs cosmetic lotion and powders. In hair shampoos, hairdressing and tooth powders, it is used as a protective agent. Additionally, PUL has good antimicrobial activity, it stimulates the immune response and lowers cholesterol and triglycerides [232].
There are several different types of biodegradable polymer-based DDS (drug delivery systems) that have been tested for drug delivery agents in dermatology. When it is applied to the skin, the biodegradable polymeric material will undergo degradation which results in a non-toxic product and controlled release of the drug into the targeted site in dermatology treatment. The degraded polymer should not interfere with the releasing drug or accelerate or inhibit or degrade the drug. The degradation of biodegradable polymers depends on the nature of the polymer. The polymer may undergo degradation by chemical or enzymatic methods [119]. Most biopolymers like silk fibroin, collagen, glycerol and starch are commonly used in the cosmetic industry. Most of the biodegradable polymeric microparticles and nanoparticles are used in cosmetics, especially in skin-related products. The use of biodegradable polymers in cosmetic products is considered to be safe and efficient.
Conclusion and future perspectives
The progress made in the area of eco-friendly biodegradable polymers has been impressive. Many companies across the globe are involved in this field of producing a wide variety of products. However, the cost of biodegradable polymers is comparatively high compared to conventional plastic. To overcome this issue, much advanced research has grown as per consumer demand for biodegradable polymer products. With the use of biodegradable polymers, most of the ecological issues like water pollution, global warming, greenhouse effect, etc. can be controlled to some extent. Most of the biodegradable polymers exhibit antibacterial and antifungal properties. The biodegradable polymers exhibiting antiviral properties will be comparatively better and also find a lot of application in the field of biomedical, pharmaceutical and cosmetics. The biodegradable polymers possessing antiviral properties will be extremely safe. In this COVID-19 pandemic situation, the materials possessing antiviral properties are of extremely high in demand. Even today the awareness of biodegradable polymers is not fully known to the common public, so they are preferring non-degradable plastics over biodegradable ones. Industrialists should take a step to increase the use of biodegradable polymers in their operations. Biodegradable polymers have received much more attention in the last decades due their potential applications in the fields related to environmental protection and the maintenance of physical health. The future outlook for development the field of biopolymers materials is promising. At present, only a few biodegradable polymers are gaining marketing importance. The future of each biodegradable polymer mainly depends not only on its competitiveness but also on society's acceptance and capacity to pay for it.
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Umbrello Michele a⁎
Brena Nicola b
Vercelli Ruggero c
Foa Riccardo Alessandro c
Femia Marco c
Rossi Umberto d
Podda Gian Marco e
Cortellaro Francesca b
Muttini Stefano a
a SC Anestesia e Rianimazione II, Ospedale San Carlo Borromeo, ASST Santi Paolo e Carlo – Polo Universitario, Milano, Italy
b SC Pronto Soccorso e Degenza Breve, Ospedale San Carlo Borromeo, ASST Santi Paolo e Carlo – Polo Universitario, Milano, Italy
c SC Radiologia I, Ospedale San Carlo Borromeo, ASST Santi Paolo e Carlo – Polo Universitario, Milano, Italy
d SSD UO a Direzione Universitaria di Radiologia Vascolare ed Interventistica, Ospedale Galliera, Genova, Italy
e SC Medicina Generale II, Ospedale Paolo, ASST Santi Paolo e Carlo – Polo Universitario, Milano, Italy
⁎ Corresponding author at: U.O. Anestesia e Rianimazione II, Ospedale San Carlo Borromeo, ASST Santi Paolo e Carlo – Polo Universitario, Via Pio II, 3, 20153 Milano, Italy.
4 6 2021
10 2021
4 6 2021
65 7275
© 2021 Elsevier Inc. All rights reserved.
2021
Elsevier Inc.
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Several cases of deep venous thrombosis in people who had recently received Vaxzevria (previously known as COVID-19 Vaccine AstraZeneca) have recently been reported, mainly presenting as cerebral vein/cerebral venous sinus thrombosis. This syndrome has been termed “vaccine-induced immune thrombotic thrombocytopenia (VITT)”. Acute spleno-porto-mesenteric vein thrombosis is an uncommon but serious condition with potential sequelae, such as small-bowel gangrene and end-stage liver failure. We describe a case of concomitant thrombosis of portal, superior mesenteric and splenic veins in a young female patient with no other risk factors who received Vaxzevria (previously ChAdOx1 nCoV-19 vaccine, AstraZeneca) 17 days before. The diagnostic workup and the successful endovascular treatment and systemic anticoagulation management is reported.
Keywords
COVID-19 vaccine
Splanchnic thrombosis
Thrombocytopenia
Ultrasound-enhanced thrombolysis
VITT
==== Body
pmc1 Background
Vaccination is considered as the critical weapon in the battle against COVID-19. In March 2021, several cases of deep venous thrombosis in people who had recently received Vaxzevria (previously known as COVID-19 Vaccine AstraZeneca) have been reported, mainly presenting as cerebral vein/cerebral venous sinus thrombosis. This syndrome has been termed vaccine-induced immune thrombotic thrombocytopenia (VITT). We present a case of a 36-year-old woman who developed a spleno-porto-mesenteric vein thrombosis few days after vaccination with Vaxzevria.
2 Case presentation
A previously healthy, Caucasian Italian 36-year-old female patient presented to the Emergency Departement with a 10-day history of upper abdominal pain. 17 days before she received her first dose of Vaxzevria COVID-19 Vaccine. A few days after the vaccination she suffered from a short course of fever, asthenia and diffuse ostheoarticular pain. She was not taking oral contraceptives, nor did she report a personal or familiar history of venous thromboembolism or thrombophilia.
On admission she was normotensive, vital parameters and physical examination were normal. Bloods showed a mild thrombocytopenia (133 * 103/μL, normal values 150–350), while the remaining tests were normal. The nasopharingeal swab ruled out SARS-COV-2 infection. Chest X-ray was negative, her electrocardiogram showed sinus rhythm 98 b/min. Emergency US and a subsequent abdominal CT with contrast showed complete thrombosis of spleno-mesenteric-portal axis (Fig. 1 ), with abdominal and pelvic free fluid. A continuous infusion of unfractioned heparin was started and the patient was admitted to the ICU for close monitoring of her disease course and adverse events.Fig. 1 Contrast-enhanced MDCT scan of the abdomen.
Coronal MIP reconstruction that demonstrates splenic, portal and superior mesenteric veins massive thrombosis (arrowheads).
Fig. 1
Considering the thrombotic burden, on the following day the patient underwent trans-hepatic portal vein venography via right internal jugular vein access that confirmed the complete thrombosis of splenic, superior mesenteric and portal vein (Fig. 2 A). Thrombus aspiration with a Penumbra catheter was performed (Fig. 2B). A porto-systemic shunt was performed between the right suprahepatic and the right portal vein. Venous pressure measures are reported in Table 1 . Ultrasound-accelerated thrombolysis was performed with two EkoSonic ultrasound-enhanced infusion catheters inserted through the right internal jugular vein. A 1 mg/h rtPA infusion was started and continued for 24 h. The results of coagulation tests are reported in Table 2 .Fig. 2 Venography of the splanchnic veins during the first angiography.
Panel A: Venography of the splenic vein that confirms portal, splenic and superior mesenteric veins massive thrombosis. Panel B: Venography of the portal and superior mesenteric vein during thrombus aspiration manoeuvres with partially restoration of blood flow into these vessels.
Fig. 2
Table 1 Values of venous pressures (in mmHg) in the different sites involved in the thrombosis, during the first and the second angiography (performed one week after the first).
Table 1Site of measurement 1st angiography 2nd angiography
Right atrium 15 18
Portal vein n.a. 21
Portal vein (TIPS occluded) n.a. 31.5
Splenic vein 26 22
Superior mesenteric vein 24 22
TIPS 17 20.5
TIPS: Transjugular Intrahepatic Porto-systemic Shunt; n.a. not available.
Table 2 Results of the coagulation tests performed.
Table 2Test Unit of measure Normal values Result
Prothrombin time sec 13
INR INR 0.8–1.2 1.08
Activated partial thromboplastin time ratio 0.8–1.2 0.96
Fibrinogen mg/dl 150–450 501
Protein C % 72–142 78
Protein S % 65–128 44
Antithrombin III % 70–120 68
IgG/IgM Anti-cardiolipin Antibodies U/ml <20 <2.6
IgG/IgM Anti-b2 glycoprotein Antibodies U/ml <20 7
Lupus anticoagulant Negative Negative
Paroxysmal nocturnal hemoglobinuria clone Negative Negative
Factor V Leiden mutation Absent Absent
Factor II mutation Absent Absent
Anti-heparin PF4 antibodies OD 0.4 2.503
INR: International normalized ratio. PF4: platelet factor 4. OD: Optical density.
Anti-PF4/heparin immunoglobulins G were measured by an enzyme-linked immunosorbent assay (ELISA, PF4 Enhanced test, Immucor, Norcross, Georgia, US); the cut-off for normal values is <0.4 Optical Density.
Serum and urine protein electrophoresis excluded a myeloproliferative disorder. Given the findings of anti-heparin PF4 antibodies, the continuous infusion of heparin was discontinued and a continuous infusion of argatroban 2 μg/kg/min, with a target aPTT of 45″, was started. A diagnosis of an autoimmune HIT was suggested, and a 5-day course of 0.4 g/kg intravenous Immunoglobulin was started.
During the second day of ICU stay, the patient developed melena and the haemoglobin levels dropped to 5.6 g/dl; her BP dropped to 90/60 mmHg and heart rate rose to 130 b/min. Three units of packed red blood cells were transfused, with normalisation of blood pressure and heart rate. Urgent esophagogastroduodenoscopy was performed and several vascular lesions at greater curvature and gastric fundus were found, which were treated with local epinephrine injection with no further evidence of bleeding.
The patient stayed in the ICU for 6 further days. Her clinical conditions remained stable. A mesenteric angiography was repeated on the 7th day. The superior mesenteric, portal and splenic veins were patent, and a partial reperfusion right intrahepatic portal vein branches (Fig. 3 ). Venous pressures are reported in Table 1. The patient was then eventually discharged from the ICU and transferred to a gastroenterology unit in good conditions. Long-term anticoagulation with apixaban was started. At 5 weeks of follow up no relapse had occurred.Fig. 3 Venography of the splanchnic veins during the second angiography.
Venography of the superior mesenteric (Panel A) and splenic-portal veins (Panel B) 7 days after the first endovascular procedure demonstrates good recanalization of the whole venous system (arrowheads) and good patency of the TIPS (arrow).
Fig. 3
3 Discussion
We report the case of a young, healthy, female patient in whom total spleno-porto-mesenteric thrombosis developed few days after Vaxzevria (previously COVID-19 Vaccine AstraZeneca), associated with thrombocytopenia and antiPF4 antibodies with no prior history of heparin exposure.
As of late March 2021, >20 million people in Europe and the UK had received the Vaxzevria vaccine. Cases of thrombosis and thrombocytopenia, mainly presenting as cerebral vein/cerebral venous sinus thrombosis, have been reported in persons who had recently received the vaccine, mostly within 14 days after vaccination. In some of these cases, mainly in women under 55, a combination of thrombosis and thrombocytopenia and bleeding, was described and attributed to an autoimmune form of Heparin-induced thrombocytopenia (HIT), which was termed vaccine-induced immune thrombotic thrombocytopenia (VITT) [1].
During the review process of this report, several other papers [[2], [3], [4], [5], [6], [7]] described cases of a new syndrome characterized by thrombocytopenia and deep thrombosis, which developed 5 to 24 days after administration of ChAdOx1 nCoV-19, a recombinant chimpanzee adenoviral-vector COVID-19 vaccine. Most of the patients were young (<50 years), healthy women, and a remarkably high percentage of them had thromboses at unusual sites, i.e. cerebral venous sinus or splanchnic thrombosis. All patients presented with concomitant thrombocytopenia; notably, none of them had received any form of heparin before onset of symptoms, and they all tested positive for the PF4-heparin antibodies. In total, the case-series describe the course of 43 patients; of these, 8 (18.6%) had splanchnic vein thrombosis. The European Medicines Agency estimated the incidence of this condition to be about 1 in 100,000 vaccinated people, with cerebral vein thrombosis being about three times more common than splanchnic vein thrombosis [8].
HIT is a prothrombotic condition caused by antibodies targeting platelet factor 4, which form PF4/heparin/IgG immune complexes and further activating platelets in a heparin-dependent fashion. Autoimmune HIT (aHIT) refers to a specific form of HIT in which of antiPF4 antibodies cause platelet activation despite not having previously received heparin [9]. We found antibodies against PF4, which induce massive platelet activation via the Fc receptor in analogy to heparin-induced thrombocytopenia (HIT mimicry), possibly as part of the inflammatory reaction and immune stimulation subsequent to the vaccine administration [10]; this lead to a treatment with a 5-day course of intravenous Immunoglobulin. Given the autoimmune process, steroids were also considered steroids for treating VITT. However, we didn't want to prevent the immune response to vaccine and platelet response to intravenous Immunoglobulin was complete. For the same reason plasma exchange, albeit potentially indicated in case of treatment failure, was not considered.
Acute thrombosis of the splanchnic venous circulation is a rare condition in the general population, accounting for about 5% of all abdominal ischaemic events [11]. Nevertheless, it is of vital importance to the clinician, given it clinical non-specific and highly variable presentation [12]. Clinical expression varies from asymptomatic cases to abdominal cramps, nausea, anorexia, vomiting, diarrhoea, and/or melaena [13]; potentially life-threatening severe manifestations include mesenteric ischaemia and variceal bleeding and progressive liver failure [14]. Improved imaging techniques have led to an increased recognition of this condition [15], allowing clinicians to treat the thrombosis conservatively, in an effort to avoid bowel resection and its associated complications [16].
Our case presented significant management challenges because the three major veins comprising the portal circulation were all acutely occluded. Moreover, since this was categorized as an unprovoked deep vein thrombosis event in a young patient, thrombophilia testing was performed as suggested [17]. While we were waiting for the blood test results, anti-coagulation therapy was started with an unfractioned heparin continuous infusion. Blood tests excluded other forms of thrombophilia, such as protein C or protein S deficiency, antithrombin III deficiency, disseminated intravascular coagulation, antiphospholipid syndrome or the presence of lupus anticoagulant. The finding of antiPF4 antibodies suggested a possible diagnosis of aHIT or the newly described VITT [1].
Intravenous immunoglobulin and aggressive anticoagulation with argatroban was started as suggested [9], with the aim of interrupting HIT antibody-induced platelet activation, leading to rapid platelet count recovery. Although the role of heparin in the pathogenesis of VITT is uncertain, to date there is no evidence that heparin dislodges PF4 bound to endothelium and other cellular surfaces also in VITT, thus increasing anti-PF4/heparin antibodies. Thus, according to ISTH recommendations [18] non-heparin anticoagulants are recommended. We chose argatroban for its short half-life in a patient with high bleeding risk.
As far as the specific treatment for the spleno-porto-mesenteric vein thrombosis is concerned, there is not a universally accepted protocol for management and treatment [13]. Systemic anticoagulation has shown a six-month recanalization rate of about 50%, as well as a failure rate of 10% [19]. Local infusion of thrombolytic therapy, given via a transjugular route, was shown effective to provide recanalization [12]. Adjunctive endovascular techniques have recently been developed to reduce thrombolytic drug exposure, and improve efficacy compared with standard thrombolysis [20,21], which include balloon angioplasty, thrombectomy devices, ultrasound–accelerated thrombolysis, aspiration thrombectomy and TIPS creation. Ultrasound–accelerated thrombolysis involves the simultaneous endovascular delivery of low-intensity ultrasounds and thrombolytic agent. In in vitro studies, this technique proved effective in accelerating clot lysis by increasing clot permeability and penetration of the thrombolytic agent, exposing additional plasminogen receptor sites to the thrombolytic agent [22]. In a multicentre, retrospective report, this technique was shown to be associated to a reduced drug infusion time, with a greater incidence of complete lysis and a reduction in bleeding rates [23]. In the case reported, effective venous recanalization was achieved; however, a major haemorrhagic complication occurred. Gastric bleeding, despite potentially associated with splenic vein thrombosis [24], is most likely a major complication of the systemic anticoagulation and the regional thrombolysis. In our centre, the EkoSonic ultrasound-enhanced thrombolysis system is routinely used in cases of intermediate-high risk pulmonary embolism. The decision to use the device in this case of splanchnic thrombosis, as well as the prolonged duration of the rtPA infusion, was empiric and based on our previous experience, as well as on the significant thrombotic burden. Given the only recent description of VITT, no data are available for the risk of recurrence. Hence, long-term duration of anticoagulant therapy is still an open issue.
4 Conclusion
While the vaccination campaign to progress, further studies will be required to allow for a better understanding of the real incidence and the exact pathogenesis, as well as the optimal treatment of this condition. In the meantime, we suggest that to (1) consider spleno-porto-mesenteric thrombosis in the differential diagnosis of epigastric abdominal pain, (2) perform a complete thrombotic work-up to elucidate abnormalities that could be contributing to a pro-thrombotic state and (3) initiate aggressive endovascular and systemic measures in order to avoid decompensation and a significant adverse outcome.
Declarations of interest
None.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
==== Refs
References
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2 Greinacher A. Thiele T. Warkentin T.E. Weisser K. Kyrle P.A. Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination N Engl J Med 2021 10.1056/NEJMoa2104840
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5 Scully M. Singh D. Lown R. Poles A. Solomon T. Levi M. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination N Engl J Med 2021 10.1056/NEJMoa2105385
6 Thaler J. Ay C. Gleixner K.V. Hauswirth A.W. Cacioppo F. Grafeneder J. Successful treatment of vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) J Thromb Haemost 2021 10.1111/jth.15346
7 Wolf M.E. Luz B. Niehaus L. Bhogal P. Bazner H. Henkes H. Thrombocytopenia and intracranial venous sinus thrombosis after “COVID-19 Vaccine AstraZeneca” exposure J Clin Med 10 8 2021 10.3390/jcm10081599
8 Agency E.M. AstraZeneca's COVID-19 vaccine: benefits and risks in context https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-benefits-risks-context; (accessed April 23rd 2021)
9 Greinacher A. Selleng K. Warkentin T.E. Autoimmune heparin-induced thrombocytopenia J Thromb Haemost 15 11 2017 2099 2114 10.1111/jth.13813 28846826
10 Oldenburg J. Klamroth R. Langer F. Albisetti M. von Auer C. Ay C. Diagnosis and management of vaccine-related thrombosis following AstraZeneca COVID-19 vaccination: guidance statement from the GTH Hamostaseologie 2021 10.1055/a-1469-7481
11 Battistelli S. Coratti F. Gori T. Porto-spleno-mesenteric venous thrombosis Int Angiol 30 1 2011 1 11 21248667
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13 Russell C.E. Wadhera R.K. Piazza G. Mesenteric venous thrombosis Circulation 131 18 2015 1599 1603 10.1161/CIRCULATIONAHA.114.012871 25940967
14 Liu F.Y. Wang M.Q. Fan Q.S. Duan F. Wang Z.J. Song P. Interventional treatment for symptomatic acute-subacute portal and superior mesenteric vein thrombosis World J Gastroenterol 15 40 2009 5028 5034 10.3748/wjg.15.5028 19859995
15 Rajesh S. Mukund A. Arora A. Imaging diagnosis of splanchnic venous thrombosis Gastroenterol Res Pract 2015 2015 101029 10.1155/2015/101029 26600801
16 Emile S.H. Predictive factors for intestinal transmural necrosis in patients with acute mesenteric ischemia World J Surg 42 8 2018 2364 2372 10.1007/s00268-018-4503-3 29387956
17 Connors J.M. Thrombophilia testing and venous thrombosis N Engl J Med 377 12 2017 1177 1187 10.1056/NEJMra1700365 28930509
18 Haemostasis ISoTa Statement from the ISTH on reports indicating blood clots associated with the Astrazeneca vaccine https://www.isth.org/news/559981/; 2021 (accessed April 9th 2021)
19 Parikh S. Shah R. Kapoor P. Portal vein thrombosis Am J Med 123 2 2010 111 119 10.1016/j.amjmed.2009.05.023 20103016
20 Ferro C. Rossi U.G. Bovio G. Dahamane M. Centanaro M. Transjugular intrahepatic portosystemic shunt, mechanical aspiration thrombectomy, and direct thrombolysis in the treatment of acute portal and superior mesenteric vein thrombosis Cardiovasc Intervent Radiol 30 5 2007 1070 1074 10.1007/s00270-007-9137-z 17687601
21 Rossi U.G. Rollandi G.A. Dallatana R. Cariati M. Mechanical aspiration thrombectomy in the treatment of acute intrastent renal artery thrombosis Cardiovasc Revasc Med 20 4 2019 344 346 10.1016/j.carrev.2018.04.009 29786531
22 Braaten J.V. Goss R.A. Francis C.W. Ultrasound reversibly disaggregates fibrin fibers Thromb Haemost 78 3 1997 1063 1068 9308755
23 Parikh S. Motarjeme A. McNamara T. Raabe R. Hagspiel K. Benenati J.F. Ultrasound-accelerated thrombolysis for the treatment of deep vein thrombosis: initial clinical experience J Vasc Interv Radiol 19 4 2008 521 528 10.1016/j.jvir.2007.11.023 18375296
24 Paramythiotis D. Papavramidis T.S. Giavroglou K. Potsi S. Girtovitis F. Michalopoulos A. Massive variceal bleeding secondary to splenic vein thrombosis successfully treated with splenic artery embolization: a case report J Med Case Reports 4 2010 139 10.1186/1752-1947-4-139
| 34111682 | PMC9735233 | NO-CC CODE | 2022-12-14 23:29:53 | no | J Crit Care. 2021 Oct 4; 65:72-75 | utf-8 | J Crit Care | 2,021 | 10.1016/j.jcrc.2021.05.021 | oa_other |
==== Front
Biomed Signal Process Control
Biomed Signal Process Control
Biomedical Signal Processing and Control
1746-8094
1746-8094
Elsevier Ltd.
S1746-8094(22)00941-7
10.1016/j.bspc.2022.104487
104487
Article
Contactless blood oxygen estimation from face videos: A multi-model fusion method based on deep learning
Hu Min a
Wu Xia a
Wang Xiaohua a⁎
Xing Yan b
An Ning ac
Shi Piao a
a Key Laboratory of Knowledge Engineering with Big Data, Ministry of Education,Anhui Province Key Laboratory of Affective Computing and Advanced Intelligent Machine, Hefei University of Technology, Hefei, Anhui 230601, China
b School of Mathematics, Hefei University of Technology, Hefei, Anhui 230601, China
c National Smart Eldercare International S&T Cooperation Base, Hefei University of Technology, Hefei, Anhui 230601, China
⁎ Corresponding author.
10 12 2022
3 2023
10 12 2022
81 104487104487
30 7 2022
13 11 2022
1 12 2022
© 2022 Elsevier Ltd. All rights reserved.
2022
Elsevier Ltd
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Blood Oxygen (SpO2), a key indicator of respiratory function, has received increasing attention during the COVID-19 pandemic. Clinical results show that patients with COVID-19 likely have distinct lower SpO2 before the onset of significant symptoms. Aiming at the shortcomings of current methods for monitoring SpO2 by face videos, this paper proposes a novel multi-model fusion method based on deep learning for SpO2 estimation. The method includes the feature extraction network named Residuals and Coordinate Attention (RCA) and the multi-model fusion SpO2 estimation module. The RCA network uses the residual block cascade and coordinate attention mechanism to focus on the correlation between feature channels and the location information of feature space. The multi-model fusion module includes the Color Channel Model (CCM) and the Network-Based Model(NBM). To fully use the color feature information in face videos, an image generator is constructed in the CCM to calculate SpO2 by reconstructing the red and blue channel signals. Besides, to reduce the disturbance of other physiological signals, a novel two-part loss function is designed in the NBM. Given the complementarity of the features and models that CCM and NBM focus on, a Multi-Model Fusion Model(MMFM) is constructed. The experimental results on the PURE and VIPL-HR datasets show that three models meet the clinical requirement(the mean absolute error ⩽ 2%) and demonstrate that the multi-model fusion can fully exploit the SpO2 features of face videos and improve the SpO2 estimation performance. Our research achievements will facilitate applications in remote medicine and home health.
Keywords
Estimation
Remote photo-plethysmography
Deep learning
Residual network
Coordinate attention
Multi-model fusion
==== Body
pmc1 Introduction
SpO2 saturation reflects the function of the cardiopulmonary and respiratory system and is an essential physiological indicator for clinical medical monitoring [1]. Many lung diseases can be detected by detecting abnormal values of SpO2, such as SARS coronavirus in 2003, MERS, the Middle East respiratory syndrome coronavirus in 2012, and COVID-19 which spread uncontrollably in the current period. The literature [2] stated that patients with pulmonary infections did not feel shortness of breath in the early stages, but their SpO2 levels were decreasing. Therefore, monitoring SpO2, an important physiological parameter, is essential to avoid disease deterioration. In addition, regarding blood vessel detection, anomaly and blood glucose disease can be determined from the data collected from blood glucose meter [3].
Traditional contact pulse SpO2 meters [4] are widely used in routine and critical scenarios, but they are challenging to perform in particular scenarios, such as possible injury to burn patients and inaccurate SpO2 monitoring in patients with hand and foot tremors. In addition, pulmonary diseases are highly contagious in general, and incomplete disinfection of healthcare workers and healthcare tools may lead to the secondary transmission of pathogens. In these scenarios, contactless measurement of physiological parameters becomes an effective method for estimating SpO2. Several scholars have already studied the implementation of contactless monitoring of vital characteristics [5], for example, Remote Photo-plethysmography (rPPG), Image Photo-plethysmography (iPPG), contactless pulse SpO2 measurement, and others. To our best knowledge, a few articles studied contactless SpO2 estimation methods based on videos. Among them, most of the rPPG-based SpO2 estimation methods use traditional signal processing methods, such as filtering [6], signal interpolation [7], and fast Fourier transform [8].
However, with the rapid growth of deep learning techniques, an increasing number of scholars have applied them to biomedical scenarios and daily health monitoring and achieved desirable results, such as detecting COVID-19 by chest X-ray images [9] and physiological indicator estimation [10]. In particular, deep learning techniques regarding heart rate estimation have matured in physiological indicator estimation. However, the application of deep learning to contactless SpO2 estimation is still at an early stage of development, and the literature [11] provided a systematic review of them. Last year, J. Mathew et al. proposed a study combining deep learning with contactless SpO2 estimation in hands by their self-built dataset and achieved the clinical requirement [12]. Apart from the literature [12], no other literature uses deep learning techniques for non-contact SpO2 estimation tasks. However, considering the maturity and convenience of facial estimation and inspired by the previous studies of rPPG-based heart rate estimation literature [13] and the contactless blood oxygen estimation literature [14], a contactless SpO2 estimation method combined with deep learning based on face videos is proposed in this paper. Experimental results show that the SpO2 estimation values of this paper's method are comparable to those values obtained by the commercial pulse SpO2 meter, and the SpO2 measurement error in this paper is within an acceptable range according to the literature [15].
The main contributions of the work in this paper are as follows.1) To fully extract SpO2 features from face videos by deep learning, a network named Residuals and Coordinate Attention(RCA) for feature extraction is constructed. It is a combination of residual block cascade and coordinate attention mechanism. Thus, the RCA network not only learns the high-dimensional features of the image, but also focuses on the correlation relationship between feature channels and the location information in the feature space. In this way, the RCA network has a stronger feature representation capability.
2) To use the classical color channel ratio algorithm to calculate SpO2, a SpO2 estimation model named Color Channel Model(CCM) for face videos is constructed, which is based on an image generator. CCM firstly uses residual blocks and transposed convolution to reconstruct feature maps learned by the RCA network into RGB images. Then, CCM calculates SpO2 using the red/blue color channel ratio method.
3) To facilitate the network to focus on learning SpO2 features in many aspects, a SpO2 estimation model named Network-Based Model(NBM) is constructed. The NBM is based on a network and a two-part loss function. Then, it is fused with the CCM model into a multi-model fusion SpO2 estimation model named Multi-Model Fusion Model(MMFM), which constructs a loss function that takes full advantage of the features that CCM and NBM focus on as well as the complementarity between them. The CCM, RBM and MMFM perform SpO2 estimation experiments on the public datasets (PURE [16] and VIPL-HR [17], [18]) to achieve accurate SpO2 estimation.
2 Related work
SpO2 is the oxygen concentration in the blood and represents the ratio of oxygenated hemoglobin to total hemoglobin, with a normal range of 95 % to 100 %. The medical device commonly used to measure arterial SpO2 is the pulse SpO2 meter, which is based on the use of photo-plethysmography (PPG) to assess changes in blood volume in the human tissue microcirculation [19]. However, the pulse SpO2 meter has many limitations, such as possible injury to burn patients and inaccurate SpO2 monitoring in patients with hand and foot tremors [20]. In addition, there is a risk of virus infection when using contact oximeter to check the physiological health of patients with infectious diseases. So researchers proposed the remote photo-plethysmography (rPPG) which is a contactless method for estimating pulse waves generated by the heart through peripheral blood perfusion measurements, using a video camera to capture video of body parts, and a series of processing of the video to obtain the desired physiological information, such as heart rate [21], respiration rate [22] and heart rate variability [23].
In recent years, many scholars have started to use videos to investigate contactless measurements of SpO2, but most of these studies have used conventional signal processing equipment and methods. The literature [14] used a CMOS camera to record PPG signals for SpO2 estimation, with the light source alternating between orange light at 611 nm and near-infrared light at 880 nm. SpO2 was derived from the pulsatile component(AC) and the nonpulsatile component(DC) component analysis of the tracked PPG signals. The literature [24] proposed a method using iris tissue irradiated by two light wavelengths (630 nm and 940 nm) for reflectance images to assess SpO2 levels. The literature [25] developed a contactless skin SpO2 imaging system that uses reflected images of superficial tissue skin to create a map of SpO2 distribution across the measurement area to assess SpO2, heart rate(HR) and blood flow velocity(BFV). The literature [26] used two orthogonal vectors in RGB color space to extract the PPG signal and used a denoising algorithm based on a double-tree composite wavelet transform to reduce illumination and motion artifacts.
With the continuous development of deep learning techniques, there are a proliferation of studies using them for video-based physiological metrics estimation with excellent results, such as heart rate and respiration rate. The literature [17] proposed an end-to-end convolutional attention network to detect blood volume pulses in face videos, which in turn performs frequency analysis of the detected pulse signal to track heart rate and respiration rate. The literature [27] designed a DeepPhys model based on a two-stream approach based on a skin reflection model, which used the appearance module to provide attention to guide the learning of the motion module and thus recovered a more robust rPPG signal. The literature [13] divided the input videos into segments and applied a time-domain segment subnet to extract spatial and temporal information. The literature [28] was built on deep learning to construct temporal signals and used Action Units (AUs) for signal denoising to improve HR estimation.
However, the research on deep learning algorithms for SpO2 estimation by videos is still in its early stages. The literature [29] proposed a convolutional neural network architecture for contact SpO2 monitoring from smartphone cameras. Although they performed better than traditional ratio methods, they still had the drawbacks associated with contact measurements. In July 2021, J. Mathew et al. proposed a study combining deep learning with contactless SpO2 estimation in hands [12]. Experiments were conducted to collect 14 volunteers' hand videos to estimate SpO2, containing both normal breathing and breath-holding states, with a MAE of around 2 %, which aligns with clinical indications. However, the dataset collected in this literature is not public, and no relevant experiments have been performed on public datasets.
Inspired by the above articles, this paper proposes a contactless SpO2 estimation method based on deep learning with multi-model fusion, and conducts rich experiments on the public datasets (PURE and VIPL-HR). PURE and VIPL-HR contain face videos and physiological signal recordings of faces in rich scenes, such as stillness, brightness, darkness, head movement and physical post-exercise state. In PURE dataset, the ground truth value of SpO2 have been captured using a finger clip pulse oximeter (pulox CMS50E). In VIPL-HR dataset, the ground truth value of SpO2 have been captured using the CONTEC CMS60C BVP sensor. There are more than one hundred volunteers involved in the dataset construction work. Rich experiments verify that the RCA network can adequately extract SpO2 features from face videos, and the fusion model can achieve better SpO2 estimation. These also confirm that deep learning techniques can estimate SpO2 effectively and be applied to health screening and remote health assessment.
3 Material and methods
The proposed multi-model fused SpO2 estimation model based on deep learning is shown in Fig. 1 , which consists of two parts: the RCA network and the multi-model SpO2 estimation module. RCA network mainly consists of the residual network module and the coordinate attention module, which is used to extract physiological features from the facial image sequences. The multi-model SpO2 estimation module includes Color Channel Model, the Network-Based Model, and the Multi-Model Fused Model. SpO2 is calculated by feeding the features extracted by the RCA network into the SpO2 estimation module.Fig. 1 Structure of SpO2 estimation network model based on deep learning.
3.1 RCA network
This section introduces an RCA network to extract feature signals with physiological information from face videos and use them to calculate the SpO2. Fig. 1 shows the structure of this RCA network. In terms of logical structure, RCA network and the conventional deep CNN [30] are similar. Both of them mainly consist of these types of layers: input layer, convolutional layer, activation function layer, pooling layer and fully connected layer. However, the difference is that the RCA network has residual blocks and attention composition. Residual blocks can alleviate the gradient disappearance problem in the conventional deep CNN by using jump connections. In addition, residual blocks can protect the integrity of the information. Besides, by using attention, more representative feature information can be extracted and result in a higher computational accuracy.
The input image sequence is denoted as V and the pixel size of images is 3 * 224 * 224. Firstly, V is fed into a convolution layer with the kernel size of 7,7 to downsample, namely, Conv7×7. Then, batch normalization(BN) and ReLu activation function(δ) are performed to accelerate the convergence of the network, and finally, global average pooling(GAP) output F′:(1) F′=GAP(δ(BN(Conv7×7(V))))
3.1.1 Residual module
To extract the high-dimensional features from F′, F′ is fed into the Residual Block (RB) cascade, and the features F¯ are obtained. The residual module in this paper is constructed based on ideas from the literature [31]. It alleviates the gradient disappearance problem by using jump connections. In addition, the residual block protects the integrity of the information by passing the input information directly to the output in a bypass, reducing information loss and attrition and improving the learning capability of the network. Besides, to improve network performance and obtain a larger perceptual field to help capture the features that need to be learned and attended to, the network depth is increased by cascading two residual blocks. The structure is shown in Fig. 2 .Fig. 2 Residual block cascade structure.
The formula for a single residual module is shown in Equation (2). δ is the ReLu activation function. Conv3×3 is a convolution layer with the kernel size of 3,3, and Conv1×1 is a convolution layer with the kernel size of 1,1. ⊕ represents the Element-wise Sum.(2) RB(F′)=δ(Conv3×3(δ(Conv3×3(F′)))⊕Conv1×1(F′))
The output of the cascade of the two residual blocks is F¯ as Equation (3):(3) F¯=RB2(RB1(F′))
3.1.2 Coordinate attention module
Large-amplitude head movements and changes in lighting conditions during the recovery of the rPPG signal cycle can interfere with signal estimation, resulting in excessive fluctuations in feature information changes, which can interfere with the signal periodicity [13]. However, the coordinate attention module [32] can focus on the relationship between feature channels and the location information in the feature space. Therefore, we add it after extracting the acquired high-dimensional features to enhance the feature representation.
Coordinate attention refers to embedding location information into channel attention and decomposing channel attention into two parallel 1D feature encoding processes, i.e., pooling, convolution and activation operations for feature information in the X (horizontal) and Y (vertical) directions respectively, to effectively integrate spatial coordinate information into the generated attention graph and construct a coordinate aware attention graph. In this paper, the coordinate attention idea is embedded into the RCA network, and the network structure is shown in Fig. 1. First, the high-dimensional features F¯=f¯1,f¯2,...,f¯C are used as input. Each channel is encoded along the horizontal and vertical directions using pooling layers of size H,1 and 1,W respectively to enable the attention module to capture the precise position information of the features. Thus, the output of the c-th channel at height h can be formulated as Equation (4). ∑ stands for summation.(4) zch(h)=1W∑f¯c(j,w)f¯c(h,i)
Similarly, the output of the c-th channel at width w can be written as Equation (5):(5) zcw(w)=1H∑0⩽i<Hf¯c(j,w)
f¯c represents the c-th channel of F¯. The above transformations perform feature aggregation along two spatial directions to obtain a pair of direction-aware feature maps [zh,zw]. They also enable the attention module to capture long-term dependencies along one spatial direction and preserve precise location information along with the other, which helps the network locate the target of interest more accurately.
Then, results of the two transformations are concatenated and transform operations are performed on them using the 1×1 convolutional transform function F1 as shown in Equation (6).(6) fc=δ(F1([zch,zcw]))
Here, δ is ReLu activation function. fc is the intermediate feature mapping result of encoding the spatial information of the c-th channel in the horizontal and vertical directions. Decompose fc into two separate tensors fch∈RC/r×H and fcw∈RC/r×W along the spatial dimensions. fch and fcw are transformed into tensors with the same number of channels by using two 1×1 convolution transforms Fh and Fw respectively to obtain gch and gcw as shown in Equation (7).(7) gch=σ(Fh(fch)),gcw=σ(Fw(fcw)).
Here, σ is Sigmoid activation function. Subsequently, gch and gcw are expanded using the function named expand_as so that both of them are of the same size as the input feature F¯ so as to serve as the attentional weights of F¯. The output of the coordinate attentive module is F″=f1″,f2″,...,fC″, in which the component of the c-th channel of F″ is:(8) fc″(i,j)=fc(i,j)×gch(i)×gcw(j)
3.2 Multi-Model fusion for SpO2 estimation
Existing research results show that the color channel ratio method based on videos has achieved certain results, such as the literature [26]. In order to combine the advantages of the Color Channel Model and the Network-Based Model, the features that both models focus on and the complementarity between the models are fully utilized. In this paper, a multi-model fusion SpO2 estimation module is constructed, as shown in Fig. 1. The Color Channel Model reconstructs RGB images from feature maps by the image generator, and then calculates the SpO2 value using the red and blue color channel AC/DC ratio analysis. The Network-Based Model is a simple network model based on deep learning techniques, and SpO2 is estimated directly from the feature maps output of the RCA network.
3.2.1 Color channel model
The structure of the Color Channel Model is shown in Fig. 1. The module consists of the image generator and the SpO2 Estimator1. In order to calculate the SpO2 using the signals from the red and blue color channels, the features F″ learned by the RCA network are first reconstructed into the RGB feature map feat by the image generator, and then fed into the SpO2 Estimator1 to obtain SpO2CCM. In addition, the loss functions Lossimg and LossCCM_S are constructed for the feature map SpO2CCM and the estimation value SpO2CCM respectively to improve the SpO2 estimation accuracy.
The feature F″ is first fed into the image generator to reconstruct the RGB image. The structure of the image generator is shown in Fig. 3 . This means that F″ is first fed into the residual block. Then, send the result to a transposed convolution kernel of size [3,3] which named ConvT3×3 for upsampling. Next, send it into normalization and non-linear activation to obtain I′. Finally, I′ is fed into a convolution kernel of size [7,7] named Conv7×7 to obtain the RGB feature map feat which pixel size is 3 * 224 * 224.Fig. 3 Structure of Image Generator.
Then, the reconstructed feat is fed into SpO2 Estimator1. Here, the signals of the red and blue channels are calculated by conversion to obtain cardiovascular pulse wave signals that can replace two different wavelengths (660 nm and 940 nm) in the pulse SpO2 meter [4], thus using the AC/DC ratio estimation, whose mathematical equation for the conversion calculation is shown in Equation (9):(9) SpO2CCM=A-BACRED/DCREDACBLUE/DCBLUE
Here, ACRED and ACBLUE represent the standard deviation of the red and blue channels respectively. DCRED and DCBLUE represent the mean of the red and blue channels respectively, with fixed coefficients A = 125 and B = 26 based on the empirical evaluation [4].
In this section, loss functions are designed for feat and SpO2CCM respectively. In order to learn more SpO2-related information and preserve original image features as much as possible during the RCA network learning and feature map reconstruction, the L1Loss function is used to evaluate the loss between the reconstructed RGB feature map feat and the original map img to obtain Lossimg. H, W, and C represent the image height, width, and number of channels respectively.(10) Lossimg(img,feat)=1H×W×C∑i=1H∑j=1W∑c=1Cimgi,j,c-feati,j,c
Besides, for guiding the Color Channel Model learning to obtain more accurate SpO2 estimation values, the Smooth L1 loss function is used to evaluate the loss between SpO2CCM and the ground truth SpO2gt to obtain LossCCM_S:(11) LossCCM_S(x,y)=1L∑i=1L0.5∗(yi-xi)2,ifyi-xi<1yi-xi-0.5,otherwise
Here, L represents the length of the input video frame, x and y represent the estimated value SpO2CCM and the ground truth SpO2gt respectively. When the absolute value of the difference between x and y is less than 1, L2 Loss is used. When the difference is larger, the translation of L1 Loss is used. The Smooth L1 loss function has a constant gradient when the difference between x and y is large solves the problem of large gradients destroying the training parameters in L2 loss. When the difference is small, the gradient decreases dynamically, solving the problem of difficult convergence in L1 loss.
By designing λimg and λCCM_S as balancing parameters to adjust the importance of Lossimg and LossCCM- S, the total loss of the Color Channel Model is denoted to estimate the SpO2 value as LossCCM:(12) LossCCM=λimg×Lossimg+λCCM_S×LossCCM_S
3.2.2 Network-based model
The structure of the Network-Based Model is shown in Fig. 1. F″ learned by the RCA network is fed into the SpO2 Estimator2 to calculate the SpO2 value SpO2NBM. The two-part loss functions including Losslabel and LossNBM_S between SpO2NBM and the SpO2 ground truth SpO2gt monitored by the pulse oximeter are constructed to optimize the model, so that the model can focus on more SpO2 information and improve the accuracy of SpO2 estimation.
The structure of SpO2 Estimator2 is shown in Fig. 4 . Firstly, the high-dimensional features F″ generated by the RCA network are globally averaged and pooled to replace the fully connected operation to reduce the network parameters and overfitting. Then, feed it into a convolution named Conv1×1 with the kernel of size [1,1] to compress the number of channels, increase the nonlinearity of the network and obtain the feature map with 100 channels. Then, activate it by the SoftMax function to obtain Fpre. Since SpO2 can take values from 1 % to 100 %, the sequential vector S=1,2,...,100 is constructed and multiplied with Fpre to obtain the estimated value SpO2NBM.(13) Fpre=δ(Conv1×1(GAP(F″)))
(14) SpO2NBM=∑i=1100Si×Fipre
Fig. 4 Structure of SpO2 Estimator2.
Since the face videos contain not only SpO2-related signals, but also some other physiological signals. To motivate the network to learn more SpO2 signals than other signals, a two-part loss function is designed for Fpre and SpO2NBM in this section. First, the SpO2 ground truth SpO2gt is processed by the label distribution learning technique [33] to obtain a matrix label l of the same size as Fpre. The Kullback-Leibler Dispersion [34] (KLD) loss Losslabel between Fpre and l is constructed so that the real label l is used to direct Fpre to focus on more SpO2 information. The rule for calculating Losslabel is shown in Equation (15).(15) Losslabel(l‖Fpre)=∑i=1T∑j=1100[lijloglij-lijlogFijpre]
Besides, to guide the Color Channel Model learning to obtain more accurate SpO2 estimation values, the Smooth L1 loss function is used to evaluate the loss between SpO2NBM and the ground truth SpO2gt to obtain LossNBM_S. It follows the same rules as Equation (11).(16) LossNBM_S(x,y)=1L∑i=1L0.5∗(yi-xi)2,ifyi-xi<1yi-xi-0.5,otherwise
Here, x and y represent the estimated value SpO2NBM and the ground truth SpO2gt respectively.
By designing λlabel and λNBM_S as balancing parameters to adjust the importance of Losslabel and LossNBM_S, the total loss of the Network-Based Model is denoted to estimate the SpO2 value as LossNBM:(17) LossNBM=λlabel×Losslabel+λNBM_S×LossNBM
3.2.3 Multi-Model fusion model
To facilitate the network to focus on and learn SpO2 features in many aspects and to improve the accuracy of SpO2 estimation, the Color Channel Model is combined with the Network-Based Model to construct a Multi-Model Fusion Model (MMFM). Using the SmoothL1Loss loss function, a new loss named LossMMFM is constructed for the estimation values SpO2CCM and SpO2NBM of the two models, allowing the two models bootstrap each other, making full use of the features of interest to both and the complementarity between them.(18) LossMMFM(x,y)=1L∑i=1L0.5∗(yi-xi)2,ifyi-xi<1yi-xi-0.5,otherwise
Here, x and y represent SpO2CCM and SpO2NBM respectively. It follows the same calculation rules as Equation(11) and Equation(16). The importance of LossNBM, LossCCM and LossMMFM is adjusted by designing equilibrium parameters λNBM, λCCM and λMMFM, respectively.Losstotal=λNBM×LossNBM+λCCM×LossCCM+λMMFM×LossMMFM
4 Implementation processes
This section introduces the implementation processes of the remote multi-model fusion SpO2 estimation model based on deep learning proposed in this paper. The model is divided into three parts: facial video preprocessing, the RCA network model training and SpO2 estimation.
4.1 Video preprocessing
In this paper, the PURE and VIPL-HR datasets are chosen for experiments, which contain face video sequences, timestamped text and SpO2-valued text corresponding to video frames. All video sequences need to be processed by face detection, localization (Fig. 5 ) and normalization. The specific steps are as follows.Fig. 5 Facial cutting process.
Step 1. Face detection. Firstly, the images are input to a multi-task convolutional neural network (MTCNN) [35] for face detection and localization.
Step 2. Key landmark localization. During the key landmark localization process, we pre-downloaded an open-source file containing the 81 landmarks [36] of the face. Subsequently, we take the file as an argument and call the method named shape_predictor of the Dlib library to achieve the localization of the key landmarks.
Step 3.The selection of regions of interest(ROI). The facial landmarks obtained in the previous stage are processed to locate the ROI region: the maximum and minimum values of the ×, y axes of 81 points are combined to form the four corner coordinates of the ROI and cropped.
Step 4. The facial image sequence normalization. All the facial images in this paper are normalized to 224 × 224 pixel RGB images.
4.2 RCA network model training
The processed facial image sequence V∈RC×L×H×W is fed into the RCA network for feature extraction, where C, L, H and W represent the number of channels, length, height and width of the input video respectively.
V is firstly subjected to 7×7 convolutional transform and pooling, and then high-dimensional features with strong representation ability are extracted by residual block cascade and coordinate attention module. The image information is learned and SpO2 values are estimated from them by three SpO2 estimation models respectively. The model convergence speed is accelerated by adjusting the optimizer, learning rate, loss function, and other hyperparameters to obtain the best results.
4.3 SpO2 estimation
The high-dimensional features are extracted from the RCA network, and the SpO2 values are estimated by Color Channel Model, Network-Based Model, and Multi-Model Fusion Model respectively. It should be mentioned that the estimated values of both models and the corresponding errors are obtained in the fusion estimation model. The estimated value with the smallest error is taken as the result of the fusion estimation model. The effect is compared with the other two models to select the best model.
In addition, to avoid frame redundancy, the frame number is selected according to the setting of batch_size. In other words, the median of SpO2 ground truth in T frames is used as SpO2gt. The estimated values are obtained by averaging the T frames of SpO2 values output from the three models. It also reduces the error caused by single-frame computation without considering time characteristics and noise.
5 Experimental results
5.1 Experimental datasets
Most of the datasets used in the existing SpO2 research literature were taken by the authors themselves and are not public, and most of them had fewer subjects and scenes. Our experiments are conducted on the public datasets of PURE [16] and VIPL-HR [17], [18] for easier comparison. Both contain sufficient study subjects and rich scenarios to verify the robustness of the model. In addition, using the public dataset can facilitate method comparisons for subsequent studies. In the experiments, two datasets are divided 6:4 between the training and test datasets, and the information about them is shown in Table 1 .Table 1 Information of PURE and VIPL-HR.
Dataset Num Scenes Acquisition equipment Frame rate
PURE 10 • Steady
• Speck
• Slow translate
• Fast translate
• Small rotate
• Medium rotate
• eco274CVGE Camera
30fps
VIPL-HR 107 • Steady
• Head-move
• Speck
• Dark
• Bright
• Remote
• After skipping
• RealSense F200 color camera
30fps
Fig. 6 (a) and (b) show histograms of the distribution of SpO2 values collected from the PURE and VIPL-HR datasets respectively. The range of SpO2 collected from the PURE dataset is 89–99 and the range from VIPL-HR is 86–99.Fig. 6 Histogram of the distribution of SpO2 values.
5.2 Experimental settings
In this paper, MTCNN [35] model is used to detect and locate the face region of the original video, select the ROI and crop it, and normalize the face images to 224 × 224 pixels. We conduct experiments on the PURE dataset using the CCM model as a benchmark. The PURE dataset is small according to Table 1. Small dataset is more likely to show uncontrollable performance during the training process due to parameter changes. Therefore, experiments on the PURE dataset are more representative. Table 2 shows the experimental results for different image sizes. In all tables, the bold values indicate minimal errors.Table 2 Comparative experimentation of image sizes.
Dataset/Image size PURE
MAE (%) RMSE (%)
3 * 32 * 32 1.02 1.48
3 * 112 * 112 0.83 1.07
3 * 196 * 196 0.72 0.97
3 * 224 * 224 0.65 0.85
3 * 304 * 304 0.76 0.99
3 * 352 * 352 0.78 1.05
3 * 448 * 448 0.88 1.22
According to Table2, increasing the pixel size of images, the images contain more texture and contextual information, which capture better features. In addition, it is easier to obtain discriminative features when images become larger. However, when the size becomes larger to a certain extent, the model complexity is too large, which tends to lead to overfitting and the experimental performance decreases instead. In addition, the computational overhead also becomes much larger accordingly. From experiments, the input image size is set to 3 * 224 * 224, which is more suitable.
Then, the image sequences are fed into RCA network model to extract features, and SpO2 values are calculated using each of the three methods. In order to select the optimal optimizer and learning rate, rich ablation experiments are implemented. Four optimizers (RMSProp, Adagrad, Adam, AdamW) with different learning rates are used for model training and testing. Fig. 7 shows the comparative experimentation of different learning rates and optimizers.Fig. 7 Comparative experimentation of different learning rates and optimizers.
From Fig. 7, when the RMSProp optimizer is used and the learning rate is 0.02 or 0.05, the situation arises where the model is difficult to converge. When the Adam or AdamW optimizer are used and the learning rate is 0.05, our model is also difficult to converge. As a whole, it is optimal to set the learning rate to 0.01. During the training process, the Adam optimizer is used to continuously adjust the learning rate to achieve the best results.
In general, the optimal experimental setup is determined with rich experiments. The Losstotal in Section 3.2.3 is used as the loss function. The Adam optimizer with a weight decay of 1e−4 is employed. The learning rate is set to 0.01. The ReduceLROnPlateau scheduler with a patience of 20 and factor of 0.1 is employed. The maximal epoch number and early stopping counter are set to 100 and 20, respectively. The batch_size is set to 50 frames on the PURE dataset. Extensive experiments verify that the above choice of parameters is optimal. Then, the converged model is migrated to the VIPL-HR dataset, and some hyperparameters are fine-tuned. The model network frameworks are all implemented based on PyTorch, and the graphics card used for the experiments is NVIDIA GTX1080TI.
5.3 Evaluation metrics
In order to verify the validity of the model, the mean absolute error (MAE) and root mean square error (RMSE) are used to present the experimental results, and the MAE and RMSE are calculated as shown in Equation (20), (21):(20) MAE=∑i=1LSpO2pre(i)-SpO2gt(i)L
(21) RMSE=∑i=1LSpO2pre(i)-SpO2gt(i)2L
Here, L represents the length of the input video frame, SpO2pre represents the estimated value of SpO2, and SpO2gt represents the SpO2 ground truth.
5.4 Experiment and discussion
As none of the studies on contactless estimation of SpO2 have published its datasets and algorithms, this paper will use medical indicators to measure the model's validity. If MAE between the estimated SpO2 value of the model and the SpO2 ground truth is within 2 %, SpO2 is valid and the model is reliable [15].
5.4.1 Max-min coordinate face image cropping
In this paper, the maximum and minimum values of the × and y coordinates of 81 key points of the face are combined into the four corner point coordinates of ROI. The face is cropped by the coordinates, which preserves the most effective area of the face and reduces the effect of some areas of the face being occluded. In order to verify this conclusion, this paper does a comparison experiment between full face cropping and maximum-minimum boundary cropping (m_face), and here the Color Channel Model is used for verification. The results are shown in Table 3 . SpO2 values are given in %. Therefore, MAE and RMSE are also in %. We mark it in all of the experimental tables accordingly.Table 3 Comparative experimentation of facial cutting methods.
Dataset/Crop Type PURE VIPL-HR
MAE (%) RMSE (%) MAE (%) RMSE (%)
all_face 0.86 1.18 1.15 1.61
m_face 0.65 0.85 1.04 1.48
The proposed image cropping method calculates the SpO2 values for the PURE and VIPL-HR datasets respectively. Fig. 8 and Fig. 9 show the comparison of the SpO2 estimation values and the reference values for the two datasets respectively. The horizontal label in Fig. 8 and Fig. 9 is “Batch”. It means the SpO2 value calculated for the nth batch of the image sequences. In order to closely reflect the true human SpO2 status, the estimated SpO2 are retained to two decimal places. The retention of these two decimals gives rise to reasonable fluctuations in Fig. 8 and Fig. 9.Fig. 8 Experimental effect of PURE dataset.
Fig. 9 Experimental effect of VIPL-HR dataset.
It is of interest to note the abrupt changes in Fig. 8 and Fig. 9 that the model failed to detect, such as the point around 80 in Fig. 8. By analysing the details of the original dataset, the reason for the problem has been found. In fact, during the construction of the dataset, there are discontinuities and interruptions when shooting different scenes of the same object. Therefore, during this interval, the SpO2 status may change, and naturally the data within the corresponding dataset may also change abruptly. As datasets are feed as a whole continuously into the model for training and testing, the model does not immediately capture the sudden changes in SpO2 values due to scene switching, yet it is relatively seldom the case in general. In addition, undetectable abrupt changes are within 1 % and return to pre-change SpO2 status rapidly. In practice, in the actual scenario, the permissible error range is 2 %. It indicates that the estimation error due to the switching of detection objects and scenes is still acceptable. But whether or not it is these reasons that brought about the changes, when the magnitude exceeds 1 %, our model is still able to capture the change relatively quickly and estimate close SpO2 values. For example, the drop in SpO2 values at point around 120 in Fig. 8 and the rise at point around 160 in Fig. 9. It indicates that our model is effective and has application values.
Besides, since the normal range of SpO2 values in the human body are 95 %–100 %, values below 95 % are considered to be low SpO2 values. The proportion of low SpO2 values is relatively small. The PURE dataset captures SpO2 values once per frame at a frame rate of 30 fps and the percentage of the low SpO2 value is 4.9 %. In contrast, the VIPL-HR dataset collects SpO2 values once every second and the percentage of the low SpO2 value is 5.8 %. However, in clinical scenarios, low SpO2 samples need to be given more attention. Therefore, in addition to giving the overall SpO2 estimation errors for PURE and VIPL-HR dataset, low SpO2 values (<95) have been purposefully extracted for error calculations with the SpO2 values calculated by the Color Channel Model. The MAE in PURE dataset is 1.28 %, and the MAE in VIPL-HR dataset is 1.57 %. From the experimental results, even with the low SpO2 scenarios, the MAEs are still below 2 % and meeting the clinical target. It demonstrates that our model is valid for the low SpO2 situations as well.
5.4.2 RCA network
In this section, rich ablation experiments are conducted for the RCA network model, and each module and parameter inside the model, and the effectiveness of the model and each module is verified on the PURE and VIPL-HR datasets using the Color Channel Model.
First, the setting of batch_size affects the experimental results and reasonableness. Each batch will get the corresponding SpO2 estimation value and the average of the corresponding batch_size SpO2 ground truth, from which the overall MAE and RMSE of the test sets of PURE and VIPL-HR are calculated. Due to the limitations of the hardware device, a too large batch_size will result in insufficient memory to allow for training. A too small bitch_size will result in too little data being trained in a single batch. It may lead to large experimental errors and unstable experimental results. At this point, it is difficult to extract more global features. Therefore, we try to choose a multiple of 10 in the appropriate region for the ablation experiments. Besides, due to the experimental setup, the minimum value of batch_size is 15. Fig. 10 shows the comparison experiments of different batch_size.Fig. 10 Plot of batch_size comparison experiments.
From Table 1 and Fig. 10, the PURE dataset is small and it is significantly affected by batch_size. In the process of randomly selecting a small batch_size and training, some uncontrollable factors are generated, resulting in fluctuations in the curve. Nevertheless, as the batch_size increases, PURE as a whole also produces the effect within the expectation, which is consistent with the training effect of large dataset. Finally, we choose 50 as batch_size after several experimental comparisons. Combined with the frame rate of the dataset, it can be considered reasonable to do the estimation and error calculation every less than 2 s with this setting. Subsequent experiments were set to a batch size of 50 frames.
Afterward, to verify the effectiveness of the RCA network and the internal modules for extracting SpO2 features, the RCA network is replaced by the feature extraction modules of classical deep neural networks (ResNet-50[31] and Inception v3[37]). The FLOPs and Params are used to measure the time complexity and memory complexity of the model respectively. FLOPs refer to floating point operations which is understood as the amount of computation. It can be used to measure the complexity of an algorithm or a model. Params refers to the number of parameters which represents the amount of memory used. Then, ablation experiments for residual blocks (RB) and the coordinate attention (CA) in the RCA are conducted. The above experiments are based on the Color Channel Model. According to Table 4 , the RCA network outperforms the other networks in terms of feature extraction capability. In addition, RCA networks have a lower time complexity and space complexity. It means that RCA network is more efficient and uses less memory. Our proposed model do not require much capturing equipment and calculation environment. Besides, both RB and CA can effectively improve the accuracy of SpO2 estimation and reduce MAE and RMSE. RB reduces information attrition and improves the learning capability. Besides, CA can focuses on feature channels and the location information, and enhances the feature representation.Table 4 Ablation experiments with RCA network.
Dataset/Model FLOPs (GMac) Params (M) PURE VIPL-HR
MAE (%) RMSE (%) MAE (%) RMSE (%)
ResNet-50 [31] 5.12 24.05 1.02 1.49 1.50 1.77
Inception v3 [37] 3.67 22.68 1.04 1.47 1.14 1.51
RCA w/o CA 2.048 1.077 0.74 1.05 1.11 1.50
RCA w/o RB 0.94 0.11 1.02 1.44 1.15 1.53
RCA 2.05 1.08 0.65 0.85 1.04 1.48
Next, the selection experiment of the number of cascades for the cascaded residual network is conducted. According to Table 5 , the best results were obtained when two residual blocks were used for cascading, extracting the most effective high-dimensional features. Besides, using two residual blocks does not unduly increase FLOPs and Params.Table 5 Cascade number selection experiment for cascade residual blocks.
Dataset/RB num FLOPs (GMac) Params (M) PURE VIPL-HR
MAE (%) RMSE (%) MAE (%) RMSE (%)
1 1.4 0.26 0.79 1.02 1.12 1.54
2 2.05 1.08 0.65 0.85 1.04 1.48
3 2.69 4.36 0.89 1.15 1.10 1.50
4 3.33 17.47 1.02 1.44 1.15 1.52
After determining the experimental setup and the structure of the RCA model, visualisations were used to show the facial regions that the RCA model learned and focused on.
First, a set of images of faces wearing glasses and hair coverings and their attention graphs are as shown in Fig. 11 . As can be seen from them, the RCA network focuses more on the cheek and forehead regions. Meanwhile, the model reduces the attention to the eyes, eyeglasses, hair, lips and chin.Fig. 11 Visualisation of scenes with eyeglasses.
In addition, the visual scenes of facial rotation and movement and specking are as shown in Fig. 12 . As can be seen from them, the RCA network also reduces the focus on teeth and male beards. In non-stationary scenes, the RCA network still accurately focuses on the cheek and forehead regions.Fig. 12 Visualisation of non-stationary scenes.
In general, SpO2 needs to be estimated from bare skin. Not focusing on disruptions such as beards, teeth, hair, eyes and eyeglasses helps to improve the accuracy of the model in detecting SpO2.
Besides, to explore the effectiveness of deep learning in greater depth, a SpO2 estimation experiment with traditional color channel segmentation is designed for comparison. The red and blue channel of the original image sequence are separated and fed into the RCA network separately to extract the signal features. The corresponding standard deviation and mean values were calculated respectively, and the SpO2 values were calculated by substituting into the SpO2 calculation Equation (9). Table 6 shows the experimental results, which demonstrate the effectiveness of deep learning in terms of the SpO2 estimation accuracy.Table 6 Red and blue color channel method selection experiment.
Dataset/Channel Method PURE VIPL-HR
MAE (%) RMSE (%) MAE (%) RMSE (%)
Tradition Color Model 0.92 1.17 1.18 1.60
CCM 0.65 0.85 1.04 1.48
5.4.3 Comparative study of three SpO2 estimation models
After the experiments in the previous section, the RCA network structure is determined, and then the three SpO2 estimation models are trained and tested separately, the results are shown in Table 7 .Table 7 SpO2 estimation model comparison experiment.
Dataset/Estimate Model FLOPs (GMac) Params (M) PURE VIPL-HR
MAE (%) RMSE (%) MAE (%) RMSE (%)
CCM 2.05 1.08 0.65 0.85 1.04 1.48
NBM 1.00 0.70 0.86 1.04 1.10 1.50
MMFM 3.05 1.77 0.63 0.80 1.00 1.43
As can be seen from the results, the MMFM has the lowest error in SpO2 estimation, the conventional CCM has the middle error, and the NBM has the highest error, but all of them are within 2 % of the clinical target. The MMFM effectively combines the advantages of the NBM and the CCM, making full use of the characteristics and complementarity between the two models to achieve relatively better estimation results. The complexity of MMFM is the sum of the complexity of CCM and NBN.
Besides, to evaluate the real-time property and the latency property, extensive experiments are done. Specifically, the time required to load the pre-trained model, and the time required to load the batch_size (50) frames and feed them into the models to estimate the SpO2 are calculated. Separate experiments are conducted on the PURE and VIPL-HR datasets. Both of them have similar loading and estimating times, so their average time are chosen as the result. In Color Channel Model, the loading time is about 1.1 s, and the estimating time is about 0.5 s. In Network-Based Model, the loading time is about 0.4 s, and the estimating time is about 0.5 s. In Multi-Model Fusion Model, the loading time is about1.6 s, and the estimating time is about 0.5 s. Overall, the CCM, NBM and MMFM all take around 0.5 s to estimate SpO2 after the pre-trained models are loaded. The delay of 0.5 s is acceptable in terms of timeliness.
In addition, ablation experiments on the loss functions are conducted to verify the effectiveness of Lossimg and Losslabel for CCM, NBM and MMFM respectively. The experimental results are shown in Table 8 , which can confirm that the reduced image loss and KLD loss help to improve the model estimation accuracy and reduce its error.Table 8 Loss function ablation experiments.
Lossimg Losslabel PURE VIPL-HR
MAE (%) RMSE (%) MAE (%) RMSE (%)
CCM ✗ — 0.81 1.05 1.15 1.55
✓ — 0.65 0.85 1.04 1.48
NBM — ✗ 0.89 1.13 1.19 1.56
— ✓ 0.86 1.04 1.10 1.50
MMFM ✗ ✗ 0.87 1.06 1.18 1.59
✓ ✗ 0.77 1.01 1.08 1.46
✗ ✓ 0.82 0.99 1.14 1.48
✓ ✓ 0.63 0.80 1.00 1.43
5.4.4 Sub-scene verification
To analyze whether the RCA model still maintains better performance under head motion states and different lighting conditions, three SpO2 estimation models will be individually trained and validated for several unstable scenes in the PURE and VIPL-HR datasets respectively to improve the robustness of the model. The experimental results are shown in Fig. 13 and Fig. 14 .Fig. 13 Comparison of experimental results of the three models in PURE by scene.
Fig. 14 Comparison of experimental results of the three models in VIPL-HR by scene.
According to Fig. 13, the estimation errors of MMFM are lower than those of NBM and CCM in different scenes of the PURE dataset. NBM outperforms CCM only in the steady scenes and performs worse than CCM in the rest of the unstable scenes.
According to Fig. 14, each of the three estimation models has advantages and disadvantages in different scenarios in the VIPL-HR dataset, but all of them are relatively small in difference. Based on the presentation of the dataset in Table 1, it can be seen that VIPL-HR is large compared to PURE. In the smaller PURE dataset, the results of the three estimation models differ significantly and the Color Channel Model significantly outperforms the Network-Based Model. In the larger VIPL-HR dataset, the difference between the three models is tiny. Through these experiments, this paper concludes that when the experimental samples are large enough and the learning objects are large enough, the features extracted from the RCA network can gradually be detected by the network model with comparable accuracy to that of the Color Channel Model. In addition, MMFM takes into account the advantages of CCM and NBM to achieve a more accurate result.
5.4.5 Comparison with other models
We summarise articles on contactless SpO2 estimation over the years. From these, representative articles are selected to compare the experimental results with MMFM. Since the code and dataset of them are not public, the MAEs in these articles are extracted for comparison as shown in Table 9 . The Num denotes the number of volunteers involved in the construction of these datasets. DL denotes Deep Learning. Area denotes the area of the body to be photographed.Table 9 Comparison of different contactless SpO2 estimation methods.
Method Dataset Num MAE (%) DL Area
[25] 2016 Self-built 9 1.00 ✗ hands
[38] 2020 Self-built 9 0.85 ✗ face
[39] 2020 Self-built 21 0.83 ✗ face
[40] 2021 Self-built 25 1.7 ✗ face
[12] 2021 Self-built 14 1.81 ✓ hands
[41] 2022 BIDMC PPG [42] 52 1.45 ✗ PPG signal
*[38] 2020 PURE 10 1.51 ✗ face
VIPL-HR 107 2.32
*[39] 2020 PURE 10 1.30 ✗ face
VIPL-HR 107 2.02
Ours-MMFM PURE 10 0.63 ✓ face
VIPL-HR 107 1.00
The literature [38] presented a SpO2 monitoring method without physical contact with the patient using imaging photoplethysmography (iPPG). Firstly, the authors used a camera to capture videos and extracted the forehead area as an ROI. Then, they performed Eulerian video magnification (EVM) [43] on the facial videos to amplify the changes in skin color due to the heart cycle. Lastly, the red and blue channel ratio method is used to calculate SpO2 values.
The literature [39] presented a SpO2 monitoring method by using a video camera. The authors used the face detector provided by the Dlib library to detect faces in the images. Then, they select the forehead and left and right cheeks as three ROIs. To track the ROIs in the videos, they used the Kanade-Lucas-Tomasi (KLT) [44] tracking method. The next step was the analysis of the RGB signals coming from the ROIs marked in each video frame of a short sequence. To avoid noise, the signals are improved through a preprocessing phase. Next, they used Power Spectral Density (PSD) through Welch’s method [45] to select the most informative ROI. Finally, they used the chosen ROI to calculate SpO2 values by the red and blue channel ratio method.
As the source code of the literature [38], [39] is not publicly available, we reproduce the model based on details from the literature and do comparative experiments on the PURE and VIPL-HR datasets. Therefore, we mark them with * in Table 9. By reproducing the models from the literature [38], [39] and conducting comparative experiments on the PURE and VIPL-HR datasets, the RCA network and the MMFM model are proven to be more effective in extracting SpO2-related feature from facial image sequences. Besides, it demonstrates the effectiveness of deep learning in the field of contactless SpO2 measurement as well.
In addition, we conduct an experimental comparison with the literature [41] published in August 2022. It is an extremely new literature. It utilizes PPG signals and machine learning technology to extract SpO2 and achieve clinical indicators. But in general, MMFM can adapt better to the SpO2 estimation task. Furthermore, it confirms the effectiveness of deep learning in the area of contactless SpO2 detection.
Since there is no method based on deep learning for Sp02 estimation by face videos, it is important to compare our model with a simple deep neural network trained with a regression loss. Therefore, we experiment with SpO2 estimation task on Classical network models(ResNet-18[31] and VGG16[46]) with L1 Loss and compare these results. According to Table 10 , the MMFM has a slightly higher time complexity than ResNet-18, but the lowest spatial complexity of the three models. The MMFM has the lowest detection error and highest accuracy. Overall, the estimation model of this paper is more applicable to the SpO2 estimation task.Table 10 Deep learning model comparison experiments.
Dataset/Model FLOPs (GMac) Params (M) PURE VIPL-HR
MAE (%) RMSE (%) MAE (%) RMSE (%)
VGG16 [46] 15.38 72.34 2.00 2.66 2.94 3.21
RestNet-18 [31] 1.82 11.18 1.16 1.37 1.98 2.23
Ours-MMFM 3.05 1.77 0.63 0.80 1.00 1.43
6 Conclusion
In contactless estimating of SpO2, traditional contactless methods require elaborate and detailed signal processing techniques to meet medical specifications. How to develop deep learning techniques for contactless SpO2 estimation for better accuracy is the focus of our research. The multi-model fusion method based on deep learning is proposed in this paper. Firstly, the maximum and minimum corner cropping of faces is proposed. It can preserve the most effective information about faces and reduce the impact of facial occlusion. Next, we combine the residual network module and the coordinate attention module as the RCA network to obtain a high-dimensional feature map with greater representation. Finally, the SpO2 values are calculated by three SpO2 estimation models(CCM, NBM and MMFM). Their advantages and disadvantages are compared. From the experimental results on the PURE and VIPL-HR datasets, the MAEs of three models are less than 2 % and all of them meet the clinical requirement. It confirms the effectiveness of deep learning for contactless SpO2 estimation from face videos. Additionally, the MMFM combines the advantages of CCM and NBM effectively. It fully uses the features of interest and complementarity between the two models to achieve more accurate estimation results.
In future research, we will focus on how to construct deep learning models to obtain a more accurate SpO2 estimation. For example, we can design our network models based on large pre-trained models for migration learning, and use the latest relevant variants based on Transformer instead of the traditional convolution. Beisides, we will focus on improving the ability to deal with small, transient changes in SpO2 status for more valuable applications. Furthermore, how to minimize the redundancy of videos and how to achieve real-time monitoring to achieve practical value are also directions for our future research. We will continue to improve model accuracy and performance and apply it to telemedicine and home health.
CRediT authorship contribution statement
Min Hu: Conceptualization, Methodology, Software, Formal analysis, Investigation, Writing – original draft, Writing – review & editing, Visualization. Xia Wu: Conceptualization, Methodology, Software, Writing – original draft, Investigation, Data curation, Formal analysis, Writing – review & editing, Visualization. Xiaohua Wang: Conceptualization, Validation, Writing – review & editing, Supervision. Yan Xing: Conceptualization, Investigation, Validation, Resources, Supervision. Ning An: Conceptualization, Writing – review & editing, Resources, Supervision. Piao Shi: Validation, Resources, Writing – review & editing, Supervision.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data availability
Data will be made available on request.
Acknowledgment
This work was supported in part by 10.13039/501100001809 National Natural Science Foundation of China under Grant 62176084, and Grant 62176083, and in part by the 10.13039/501100012226 Fundamental Research Funds for the Central Universities of China under Grant PA2021GDSK0092 and PA2022GDSK0066.
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| 0 | PMC9735266 | NO-CC CODE | 2022-12-14 23:29:53 | no | Biomed Signal Process Control. 2023 Mar 10; 81:104487 | utf-8 | Biomed Signal Process Control | 2,022 | 10.1016/j.bspc.2022.104487 | oa_other |
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Child Adolesc Social Work J
Child Adolesc Social Work J
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Article
Meeting the Mental Health Needs of College Students with a Background in Foster Care
Lietz Cynthia A. [email protected]
http://orcid.org/0000-0002-2038-9813
Cheung Justine R. [email protected]
grid.215654.1 0000 0001 2151 2636 School of Social Work, Watts College of Public Service and Community Solutions, Arizona State University, 411 N. Central Ave, Phoenix, AZ 85004 USA
10 12 2022
114
1 11 2022
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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Many colleges and universities are creating campus-based programs to support students with a background in foster care. When considering the histories of trauma experienced by these young people, meeting mental health needs is an important part of a portfolio of services. ASuPIRE is a strengths-based, trauma-informed counseling program that was designed to respond to the unique needs of college students who aged-out and/or experienced foster care at any point across their development. This program can stand alone or can be used to supplement campus-based support programs. This approach, including its theoretical framework and related interventions, will be described. A case study is also provided to illustrate the model for other post-secondary institutions interested in adopting this approach.
Keywords
Foster Care Alumni (FCA)
Mental health and wellbeing
College persistence and attainment
College counseling
==== Body
pmcColleges and universities are grappling to determine how best to address the increased mental health needs presented by students as they pursue their undergraduate or graduate degrees (Brown, 2020). Emotional and behavioral symptoms associated with anxiety and depression have only increased since the introduction of the COVID-19 pandemic in 2020 (Hoyt et al., 2021; Santomauro et al., 2021; Seitz et al., 2021). Based on our own observations, this is particularly true for students who enter post-secondary education with a history of trauma. There are aspects of college that can mirror and trigger post-traumatic stress symptoms, an experience that is even more common for students who come to college with a background in foster care. White et al. (2005) found that one of the most common explanations given by students who have experienced foster care for leaving university was emotional and behavioral challenges. Meeting the mental health needs of students who have foster care experience, which includes both those young people who age-out of foster care and those who have a prior history of foster care but may have achieved permanency before turning 18, offers a unique opportunity to address trauma and activate the process of resilience.
Over the past decade, the number of campus-based support programs that seek to increase the recruitment and retention of young people with a background in foster care in post-secondary education has substantially increased (Fostering Success Michigan, 2022; Geiger et al., 2018). A recent review of college websites suggests there are now over 100 programs that were designed to improve the educational outcomes for this population. Similar to other institutions, in response to state legislation that was passed offering a tuition waiver or scholarships to young people who experienced the foster care system after age 14 in this state, a group of faculty and staff created Bridging Success, Arizona State University’s campus-based support program for students who have foster care experience (Arizona State University Bridging Success, 2022; Lietz, 2021). The Bridging Success program offers services to support the transition of young people to Arizona State University while also providing coaching throughout a student’s academic journey to degree completion. Although this program has been an important part of the strategy for increasing the recruitment, retention, and persistence of these undergraduate students, it became clear that more was needed to meet the mental health needs of this population. As a result, ASuPIRE, a strengths-based, trauma-informed counseling program was created and implemented in 2020. This article will provide a brief overview of student support programs and research recognizing the need for more campus-based mental health interventions. It will further summarize ASuPIRE program elements allowing other colleges and universities to consider adopting this model to supplement campus-based support programs for students who have foster care experience that are being created or are already in existence. Initial feedback from students regarding this program is promising, however, more research is needed to evaluate the effectiveness of this program overtime and across multiple universities.
The latter half of this article will use a case study example to better illustrate how a program like ASuPIRE can support students who have foster care experience as they pursue their undergraduate degree. Case studies are often used in social work to encourage critical thinking and the application of intervention tools in a practice setting. The case study provided draws upon observations and interactions of both the ASuPIRE clinician and Bridging Success staff working with students who have foster care experience, integrating common scenarios involving the social-emotional challenges they may face, as well as ways a practitioner can activate and/or cultivate the protective factors of resiliency.
Educational Outcomes for Students with Foster Care Experience
When a young person reaches the age of majority while remaining in foster care, they “age-out” of the system. Research suggests the outcomes for young people who age-out of foster care are concerning, citing higher levels of emotional and behavioral symptomatology such as anxiety, depression, PTSD, and suicidality (Courtney et al., 2005; Landsverk et al., 2006; McMillen et al., 2005; Okpych & Courtney, 2018). Students who have foster care experience are more likely than their peers to end up homeless, incarcerated, or to become involved in the child welfare system as a parent (Courtney & Heuring, 2005; Courtney et al., 2011, 2012; Hernandez & Lee, 2020). Although there are a variety of explanations that range from systemic discrimination to micro-level experiences, what is clear is that young people with a background in foster care, whether they aged-out of care or achieved permanency prior to turning 18, have experienced trauma (Engler et al., 2022; Hallett et al., 2018; Hambrick et al., 2016; Morton, 2018; Okpych & Courtney, 2018).
A recent systematic review by Engler et al. (2022) stated that trauma associated with events that led to placement in foster care and the foster care experience itself can contribute to poor mental health outcomes, with children who experience foster care having a 3–4 times higher likelihood of a mental health diagnosis than their non-foster counterparts (Engler et al., 2022). Copeland et al., (2018) demonstrated that, in general, higher rates of traumatic events prior to age 16 were associated with statistically significant higher rates of adult mental health diagnosis and poor functioning such as holding a job or building a social support network. An additional systematic review concluded that early life stress, such as physical abuse, sexual abuse, or emotional abuse and/or neglect are predictors of mental health diagnosis in adulthood (Carr et al., 2013). Considering the occurrence of traumatic events among children and youth in foster care, it is understandable that this population would have poorer, mental health outcomes than the general population.
Maltreatment by the hands of a caregiver is one of the most devasting examples of trauma a human being can experience. Children and youth in foster care also experience removal from their family of origin, the potential of leaving not just family, but also friends and a sense of belonging to a community. They may also face multiple placements, and a series of emotional ups and downs and losses that are associated with every transition. This level of trauma can impact a young person’s emotional wellbeing, and it can also affect academic achievement. According to a study by Okpych and Courtney (2018), these factors can negatively impact a child or youth’s ability to experience positive attachment with others, which in turn may limit their help seeking behaviors while attending school and adversely impact their educational progress.
The educational outcomes for children and youth in K-12 education are concerning, as are the outcomes for students who have foster care experience in post-secondary education. Children and youth in foster care face more school changes than their peers and are more likely to repeat classes and/or grades (Allen & Vacca, 2010; Clemens et al., 2018; O’Higgins et al., 2017; Okpych & Courtney, 2017; Pears et al., 2015; Ryan et al., 2018), and their education can be impacted by trauma as it is more difficult to pay attention and retain concepts when facing loss and fear about one’s future (Daly et al., 2017; Mothes et al., 2015; Shonkoff & Garner, 2012). Many young people in care may continue to experience abuse while in foster care which can further impair academic success (Morton, 2015a).
These concerns are of particular significance in racial/ethnic or sexual minority communities. Racial/ethnic minorities are disproportionately represented in the foster care system and are more likely to be placed in foster care than their white peers (Children’s Bureau, 2016; O’Higgins et al., 2017; Puzzanchera & Taylor, 2020; Watt & Kim, 2019). This disproportionality can be attributed to several factors, with low socioeconomic status, lack of social supports, and racial bias of child welfare workers often cited (Dettlaff et al., 2011; Ward & Booth, 2021). Black children and youth are more likely to attend low performing schools that lack needed resources and are more likely to face disciplinary action (United States Government Accountability Office, 2018; Ward & Booth, 2021). LGBTQ youth in foster care face additional challenges as they are three to five times more likely to experience depression, twice as likely to have significant behavioral problems, three times more likely to have a substance use disorder, and six times more likely to have experienced clinically significant trauma than their non-sexual minority peers (Dettlaff & Washburn., 2021; Grooms, 2020; Ward & Booth, 2021).
When this constellation of factors is considered, achievement in K-12 for students with foster care experience is hindered and far fewer of these young people are prepared for or consider college than their non-foster care peers (Day et al., 2011; Kirk et al., 2011; Morton, 2015b; Okpych & Courtney, 2017; Rios & Rocco, 2014). For those who do consider college, their outcomes remain a concern (Day et al., 2011). Current research suggests that roughly 3–11% of students who have foster care experience will earn an undergraduate degree (Courtney et al., 2011; Davis, 2006; Pecora, 2012; Wolanin, 2005). Attainment of a college degree is correlated with several outcomes including initial and lifelong earning potential, level of civic engagement as it relates to voting and volunteerism, and availability to support children should they chose to become parents (Ma et al., 2020). Improving the educational outcomes of students who have foster care experience offers real potential to change not just the life of a student, but also the trajectory of their future and that of their future family.
When young people age-out of foster care in the U.S., that means the state is no longer their legal guardian upon turning 18. We see the ability to influence educational outcomes as not just practical but also ethical, in that taking responsibility for the development of a young person should not cease at 18, instead, ongoing support is needed for this population similar to what is typically available to their peers. This argument has supported the passing of federal and state legislation extending the period of time young people can remain in care (The Fostering Connections to Success & Increasing Adoptions Act, 2008; The Annie E. Casey Foundation, 2021) providing ongoing access to services, and local legislation now available in 35 states offering a tuition waiver or other type of scholarship program (University of Washington, 2022). We also agree with the idea that all college students with a background in foster care should be supported throughout their post-secondary experience. Supporting both those who aged-out and those who were in care but may have achieved permanency is important.
As mentioned earlier, a number of programs have been created to increase access to and persistence at institutions of higher education. However, researchers and practitioners are still identifying best practices to understand which aspects of a program impact student success and increase graduation rates. Geiger et al. (2018) identified key services offered by a variety of 2-year and 4-year institutions, but these authors acknowledge that each campus-based support program for students who have foster care experience is different. A consistent theme in the literature points to the need for programing beyond academics that includes a strong element of mental health support (Geenen et al., 2018; Geiger et al., 2018; Hallett et al., 2018; Miller et al., 2020; Morton, 2018; Okpych & Courtney, 2018; Salazar, 2012).
Although efforts associated with implementing campus-based, support programs are leading to improved educational outcomes for some, it is our contention that they remain insufficient as many of these programs are not meeting the mental health needs of this population overall. Without appropriate access to trauma-informed counseling, some students with a background in foster care will not be able to persist in college despite the presence of important services provided by campus-based support programs.
Mental Health Needs of Students with Foster Care Experience
Young people with a background in foster care are more likely to experience mental health symptoms (Barnett et al., 2016; Courtney & Dworsky, 2006; Garcia et al., 2015; Zlotnick et al., 2012). A study of recently emancipated ethnic-racial minority foster youth by Tyrell et al. (2019) showed strong associations between trauma, placement disruption, and ethic-racial identity (ERI) and mental health outcomes such as depression, anxiety, and low self-esteem. Trauma theory suggests emotional and behavioral challenges are a direct result of one incident or ongoing experience with disturbing events in which one’s safety and wellbeing is threatened (Alisic et al., 2011; Substance Abuse & Mental Health Services Administration, 2014). The Adverse Childhood Experiences (ACEs) research offers an assessment regarding the type and severity of traumatic events, and how these experiences are related to long-term negative impacts on one’s health (Centers for Disease Control and Prevention [CDC], 2021). Considering children and youth in foster care often experience ongoing trauma during their development, research suggests their physical and mental health are impacted (Leslie et al., 2005; Morton, 2018; Okpych & Courtney, 2018; Rebbe et al., 2017).
Coming to college creates an opportunity for students who have foster care experience to achieve an undergraduate degree prompting the potential for positive life outcomes. Salazar (2013) found that students with foster care experience who have graduated, when compared to general population graduates, had similar individual income and employment rates. These findings were supported by additional research conducted by Okpych and Courtney (2014) which found that as higher levels of education were achieved, students who have foster care experience and the young adult general population employment and earnings were comparable. Salazar and Schelbe (2021) demonstrated that campus-based support programs that used the It’s My Life (Casey Family Programs, 2001) framework could have a positive impact on post-graduation success. The most significantly impactful domains were supportive relationships and community connections, life skills, and physical and mental health were strong predictors of post-graduation life outcomes.
However, after many years of supporting students who have a foster care history at our institution, we noticed that several aspects of college can indeed trigger traumatic events experienced as a child or youth when they were in foster care. For example, while moving into residential halls is a highlight for many college students, for a young person who grew up in foster care, it may remind them of moving into a group home if congregate care was a part of their foster care journey. The misuse of alcohol and other substances is more common on college campuses as some students experiment with risky behaviors. For these students, seeing other students return to their resident halls intoxicated can bring back memories of observing addiction of a parent. As other students return home for holiday breaks, some students who have foster care experience find themselves left behind, igniting feelings of loss and loneliness experienced as a child. Finally, having to navigate a college or university system can be overwhelming considering children and youth in foster care are, at times, not empowered to make decisions on their own behalf or develop skills to do so, leaving many to feel unprepared to navigate the child welfare and juvenile justice systems effectively. Being in college is an exciting time, but it is also stressful even for students without a trauma history. For college students with a background in foster care, the experiences can trigger thoughts and behaviors associated with their trauma. These direct experiences with students who have a history of foster care, coupled with prior research of these students in higher education, motived us to prioritize the development of a mental health intervention model that can better meet the mental health needs of this student population.
Developing a Strengths-Based, Trauma-Informed Counseling Program for Students with Foster Care Experience
ASuPIRE is a mental health counseling program that was created at Arizona State University specifically for college students with a background in foster care (Lietz, 2021). Pronounced aspire, the acronym comes from its four primary objectives. First, to prepare (P) for the expectations associated with attaining an undergraduate degree. Second, to imagine (I) one’s potential and combat negative internalized beliefs that can hinder academic success. Recognizing the difficult history that young people experienced while in foster care, the third objective is to help students recover (R) from the trauma they experienced that may be retriggered by the college experience. Finally, the program seeks to help students excel (E) in their academic program by activating the process of resilience. The program consists of three components: (a) time-limited individual counseling that is embedded within the university’s counseling services program, (b) a set of four one-credit student success courses, and (c) an 11-week text-based intervention.
The program is grounded in five theories that are integrated to meet the program objectives. Having a theoretical basis to this work is important, because theories offer an explanation to the causes of problems in human behavior while describing a potential mechanism for change. As a result, theories can be used to inform both the assessment and intervention that is provided in the counseling, student success courses, and text-based intervention. In ASuPIRE, underpinnings from attachment theory, cognitive theory, trans-theoretical stages of change theory, self-authorship, and trauma theory provide the foundation for everything included in the model. In addition to these theories, ASuPIRE is strengths-based and framed in resilience research that describes a process of coping and adaptation that can be activated and cultivated through the presence of ten protective factors that are provided (Cheung et al., 2019; Lietz et al., 2016; Lietz et al., 2011).
Resilience is a process of coping and adaptation. This construct builds upon a risk perspective that indicates the presence of a high-level of risk factors increases one’s likelihood of negative outcomes, often related to one’s physical, emotional, and behavioral wellbeing (Luthar et al., 2000). Understanding the factors that predict negative outcomes is important, because this risk-focused research provides important opportunities for prevention (Werner & Smith, 2001). If social services can prevent loss, trauma, and adversity, these programs can positively impact social-emotional wellbeing. However, many people experience high levels of loss, trauma, or other adversity that has already occurred or remains unpreventable such as the sudden and unexpected death of a parent. Only focusing on risk factors fails to provide intervention options for the situations that are not preventable.
The construct of resilience is important, because it involves examining the times at which people were at-risk for negative outcomes, and maintained healthy functioning anyway (Luthar et al., 2000; Nunez et al., 2022; Werner & Smith, 2001). By uncovering these examples of resilience, a set of protective factors has been identified that can help to activate the process of coping and adaptation when risk is present (Lietz, ). Resilience research helps to uncover the ways protective factors or strengths can moderate the negative outcomes associated with risk which is particularly important for people who have already experienced a high level of adversity. Building up the protective factors can help to hinder the potential negative effects of risk, something that is particularly relevant for young people in foster care (Cheung et al., 2019 ; Hass et al., 2014; Hines et al., 2005; Neal, 2017).
The combination of being self-reliant, needing to find support/seek help, addressing mental and social-emotional needs, and balancing the demands of transitioning to adulthood and college can prove overwhelming and negatively impact a young person with a foster care background’s ability to successfully complete their post-secondary education (Dumais & Spence, 2020; Jones & Dean, 2020; Miller et al., 2020; Morton, 2017; Samuels & Pryce, 2008). A recent qualitative study by Jones and Dean (2020) explored the experiences of students who have a history of foster care as they transitioned to college. Findings indicate that students who had experienced foster care believed their trauma and foster care background both helped and hindered their transition to college. Although participants felt more prepared for higher education, citing their higher level of maturity, self-awareness, and ability to address challenges independent of others, they also described feeling disconnected and different from their non-foster peers. Similar findings were reported by Hines et al. (2005), with participants describing their sense of being different because of their family dynamic, history of abuse and neglect, and involvement in foster care. The participants further acknowledged difficulty with their mental and emotional health, impacting their ability to form relationships, cope with the pressures of attending college, and manage life as an adult. However, they also stated that their background required that they adapt and build personal resilience (Hines et al., 2005). These findings acknowledge both the resiliency of these young people who have faced adversity but found coping skills to help them overcome challenges, but also reinforces the need of programs that support mental and emotional wellbeing through cultivating and activating additional resiliency protective factors.
Activating protective factors involves labeling and drawing out current strengths a student presents with at the onset of counseling. Cultivating resilience involves building up new protective factors, to increase the strengths students can draw from as they face challenges during their academic programs. The ten specific protective factors ASuPIRE is seeking to activate or cultivate are provided in Table 1. In summary, ASuPIRE is a strengths-based, trauma-informed counseling program created to address the mental health needs of students with a background in foster care as they pursue post-secondary education.Table 1 Strengths/protective factors
Social support Giving and receiving practical and emotional care and concern during challenging times
Communication Expressing thoughts and feelings about a trauma or loss through verbal and non-verbal forms of expression
Insight/empathy Gaining understanding into oneself and others as it relates to the difficulties faced by a person, family, community, or organization
Boundary setting Creating space or separating from influences that are unhealthy
Initiative/self-efficacy Taking action and maintaining a belief that one is capable of accomplishing that goal
Creativity/flexibility Finding multiple solutions to a problem and being willing
to try new solutions
Humor Remaining light-hearted even in the face of difficulty
Commitment Setting a goal and sticking with it
Morality/spirituality Having a belief system that provides direction and strength as one faces trauma, loss or other difficulties
Appraisal Attaching a positive meaning to a difficulty one faces or has faced
(Cheung, 2019; Lietz et al., 2011, 2016)
ASuPIRE’s Theoretical Framework
As seen in Fig. 1, ASuPIRE integrates fives theories and ten protective factors to accomplish its four primary objectives. These theories were chosen, because they are particularly relevant for students with a background in foster care and for use in a postsecondary education setting. The resilience framework is important, because it helps to describe the change process, meaning, the theoretically-informed and/or evidence-based interventions are intentionally designed to activate and cultivate the process of resilience.Fig. 1 ASuPIRE theoretical framework
Attachment Theory was created by John Bowlby (1977) and contends an infant’s strong attachment to a primary caregiver as a fundamental human need. The theory explains that a lack of safety and security in infancy and early childhood caused by a poor attachment can lead to psychological and relationship problems that extend into adulthood. The ideas were further developed by Ainsworth (1985) who categorized attachments as: secure, ambivalent, avoidant, or disorganized. For some young people who grew up in foster care, their capacity for a secure attachment was hindered as a result of neglect and/or physical, emotional, or sexual abuse. Social skill training is a key component of the program in recognition that attachment concerns can lead to problems in one’s professional and personal relationships potentially undermining their success in college. Content regarding healthy relationships and concepts such as hierarchy, equality, boundaries, connection, and communication are integrated throughout the counseling services and included in one of the four student success courses. Attachment theory serves as a foundation to ASuPIRE leading to interventions that are designed specifically to enhance relationship skills for students with a background in foster care.
Research in the field of students who have foster care experience in higher education supports the use of attachment theory in the development of ASuPIRE. A recent study by Okpych and Courtney (2018) found that for 17/18-year old foster youth, there was a strong association between maltreatment and relational instability with avoidant attachment (an adaptive self-protective response to previous maltreatment and abuse), which in turn decreased the likelihood of these students to persist and complete their postsecondary education. Bederian-Gardner et al. (2018) further found that residential and school instability contributed significantly to a young person’s ability to form attachments.
Cognitive Theory suggests that negative and unrealistic interpretations can drive emotions and behavior. First developed by Albert Ellis (1962), the ABC triangle demonstrated how an initial event would be interpreted based on one’s beliefs or thoughts about the event, then leading to a person’s emotional and behavioral response. This theory created the foundation for cognitive restructuring, an evidence-based intervention that changes emotions and behavior by recognizing automatic thoughts and then uncovering and reframing deeply held schemas (Beck, 1976). Overtime, behavioral theory was integrated with cognitive theory leading to the development of Cognitive and Behavioral Therapy (CBT) which offers evidence-based treatments that have been found to effectively reduce symptoms associated with depression, anxiety and other mental health symptoms (Beck, 2021). CBT is an important component of ASuPIRE, because it introduces important interventions such as thought records, cognitive restructuring, emotional regulation, activity scheduling, and imagery based-exposure into the treatment program. CBT can be effective in short-term, time-limited counseling making it another important fit for this program (Beck, 2021).
Motivational Interviewing (MI) is a client-centered, evidence-based intervention developed by Miller and Rollnick (2013). The process involves assessing a student’s level of motivation based on the Transtheoretical Stages of Change Theory (Prochasca & DiClimente, 1983). This model suggests the change process involves the following five phases: pre-contemplation; contemplation; preparation; action; and maintenance. Assessing one’s placement on this continuum of motivation according to this theory allows an ASuPIRE counselor to tailor interventions to meet students where they are as they begin the counseling program. Once their level of motivation is assessed, ASuPIRE counselors can use the intervention of MI to: identify students’ goals, recognize any inherent resistance to the change process, and then help to overcome ambivalence so that students are empowered to meet their own self-determined objective. Integrating MI into ASuPIRE offers another evidence-based intervention and seems particularly relevant regarding this setting considering motivation is so important to academic achievement.
Another important theory integrated into the ASuPIRE program model is self-authorship, a student development theory that is centered on the early works of Robert Kegan and self- evolution (Kegan, 1982). Baxter Magolda elaborated on Kegan’s work and developed the theory of self-authorship, a seminal theory in higher education (Baxter Magolda, 2001). It was important to include a student development theory such as this one considering higher education is the context for this counseling program. Self-authorship is focused on recognizing how young people develop their individual identity during and after post-secondary education. It defines a set of developmental tasks which include: determining what knowledge, relationships, and identity they want to create for themselves (Baxter Magolda, 2001, 2009). This theory sets up the use of narrative interventions that help students think about what it means to be the author of their own stories by valuing exploration, making sense of the world, determining one’s personal path or goals, and taking steps to move that path forward. Narrative interventions, grounded in social construction, also acknowledge how macro influences can lead to internalized negative self-image and beliefs (White & Epston, 1992), something particularly relevant for young people with a background in foster care. Creating space for students to tell their own stories, externalize negative influences, and be empowered to appraise and attach meaning to their experiences is an important contribution stemming from self-authorship theory.
Finally, as mentioned earlier, trauma theory suggests that exposure to ongoing trauma increases the likelihood of experiencing anxiety, depression and other emotional or behavioral disturbances (Barnett et al., 2016; Courtney & Dworsky, 2006; Garcia et al., 2015; Zlotnik et al., 2012). Ongoing exposure to events that threaten one’s safety, security, or wellbeing can lead to long-term negative implications for health and mental health functioning (CDC, 2021; Rebbe et al., 2017; Leslie et al., 2005). Taking a trauma-informed approach means that ASuPIRE counselors recognize that presenting symptoms are often a result of past trauma. As a result, trauma is validated and a safe space is created for students to share their experiences without judgement. Special attention is also given to self-determination ensuring students are the drivers of their own treatment. To address the trauma, mindfulness interventions are incorporated into ASuPIRE to help students recognize their emotional, physical and behavioral reactions to the past and current events. This increased awareness and capacity for emotion regulation can help students to cope with the implications of their past trauma. It is our contention that integrating a trauma-informed approach with a strengths-based, resiliency approach is essential. Focusing only on trauma, while validating, can give students the message that growth is not possible. We find this a short-sighted view of what is possible and potentially dangerous for young people who are emerging adults in the process of developing their identity. Validating past trauma and its consequences while concurrently presenting the process of resilience is fundamental to ASuPIRE.
Case Study
The following is a hypothetical case study of what engagement with ASuPIRE might look like for students who have foster care experience. It is meant to provide an example of how various campus-based supports for students who have foster care experience work together to address mental health needs. It also helps practitioners, evaluators, and policy decision makers explore a complex idea in the real-life setting of a student with a foster care history engaged in higher education.
Jesse Valenzuela is a 20-year-old undergraduate student studying business who transferred from community college after earning his associate’s degree. Jesse is a bright young man who demonstrated a high level of success in community college. Prior to community college, Jesse attended five different high schools as he was moved from a relative foster care placement at his grandfather’s home to four different group homes during his adolescence after the unexpected death of his “papa”. He underperformed in high school, and his academic achievement in community college surprised not only his high school counselors, but even himself. Jesse came to a large university hopeful about his ability to continue this positive trajectory. However, within the first semester, he was placed on academic probation, because Jesse failed four of his five courses. Jesse informed his Bridging Success coach, Teresa, about his academic standing. He expressed his desire to leave college but said that he did not have any place to live if he were to move out of the residence hall.
Teresa talked to Jesse about how his choices were impacting his academic standing, but he said he was too overwhelmed and depressed to focus on his studies at this time. Teresa worked with Jesse to address some of his immediate financial needs, and she made connections with the tutoring center. Recognizing that meeting his immediate needs was insufficient considering his presentation of mental health symptoms, she also referred Jesse to ASuPIRE.
Jesse told Teresa that he would follow-up, but he missed the first two appointments that were scheduled over winter break. When classes resumed in the spring semester, Jesse again continued a pattern of not attending his classes. This prompted a referral to the Dean of Student’s Office who connected with the Office of Student Housing to see if Jesse had vacated his room. His lack of attendance caused university officials to believe he had left college. When the resident assistant knocked on his door, Jesse reluctantly opened it. He was informed that he needed to attend class and participate in university activities if he was to maintain his residence on campus.
Jesse called his Bridging Success coach in a panic, and she again encouraged him to follow-through on the referral to ASuPIRE. This time, he did. During the first session, Jesse completed the intake documentation and assessment process. During the assessment, Jesse explained that he was not “cut-out” for college, but that he needed to stay in college to maintain his housing. His ASuPIRE counselor, Jake, asked Jesse about his goals. Jesse said he wanted to work in accounting, because he felt that would provide him a good income and stability, but he felt this was unlikely because he “was incapable of being successful at a university.” Very quickly, the ambivalence regarding his goals became clear when considering the stages of change theory. Jesse wanted to remain in housing. Yet, his housing was dependent on his status as a student.
The counselor asked about his past academic experience and while he acknowledged his challenges in high school, Jesse spoke with great pride about his success in community college. The counselor was curious to know what was different now, and Jesse explained that he knew he “wasn’t college material,” a direct contradiction to his recent achievements, potentially illustrating a cognitive distortion. Digging deeper, Jesse talked about being a first-generation student and not having any family members who attended college. This provided further evidence to him that he did not belong in a college environment. He also talked about messages he received from a high school advisor and one particular group home staff member who reinforced the idea that he “should get a job,” because he likely “would not be successful in college.”
Jake decided to continue to explore this thought process with Jesse. After further exploration, it became clear that Jesse’s academic status was not a result of his performance on assignments and tests, but instead, a result of him not turning in assignments and skipping exams. His counselor assessed that the comments were internalized and created automatic negative beliefs stemming from a deeply held schema that caused Jesse to feel insecure about his academic potential, thereby leading to avoidance. His insecurity was driving his behavior, which resulted in poor academic performance. This assessment suggested CBT might be helpful to restructure the negative cognitions. Some narrative interventions might also be helpful in externalizing negative experiences and empowering Jesse to author a new story.
Taking a trauma-informed approach, Jake also recognized the importance of respecting Jesse’s agency regarding goal-setting. It was clear that initially, his goal was housing, not academic achievement. At the same time, Jesse presented as an insightful, intelligent young person. He understood that the two things were inextricably linked. Focusing on Jesse’s goals, Jake asked, “Would you be willing to commit to attending classes over the next few weeks while we start your counseling program to ensure there is no disruption to your housing? This is the best way to ensure you have housing as you make decisions about your next steps.” Jesse agreed.
As counseling continued, the counselor was able to learn more about Jesse. He was working two jobs and visited his younger brother who was placed at a group home over an hour from campus. Not having other transportation, Jesse had to transfer three times on public transportation to visit his brother each week, a commitment he was not willing to miss, illustrating an important protective factor. Although Jesse aged-out of child welfare, he maintained relationships with his mother, uncle, and three cousins. His mother would ask Jesse for financial help from time to time, and Jesse, at one point, gave a large portion of his student loan to his mother as she was facing eviction. What became clear is that Jesse is a caring, committed person who has taken on a great deal of responsibility. He demonstrates the protective factors of commitment and initiative but may need increased capacity in the protective factor, boundary setting.
As time went on, Jesse described the domestic violence that occurred between his parents and at times, involved other family members, that was serious enough to lead to his father’s long-term incarceration. His mother struggled with drug addiction and came in and out of Jesse’s life. Although Jesse was committed to supporting his brother and would at times financially support his mother, his social support was not reciprocal. He was giving far more support than he was receiving, an important thing for Jake to address in counseling considering social support is such an important protective factor. At one point, Jesse was quite tearful when talking about the incident that involved witnessing his father shoot and injure a family member leading to his incarceration. Taking a trauma-informed approach, Jake created a safe space for Jesse to recall details of this very difficult event. Later, Jesse said that he had never recounted this experienced to anyone since after the trial. Jake closed this session by teaching Jesse how to engage in mindful breathing, and they discussed ways to settle his thoughts as the retelling of this experience brought a flood of emotions. To ensure safety, Jake asked Jesse to call the counseling center anytime between sessions if he noticed emotions he could not contain through these exercises. Jesse thanked him and acknowledged a sense of relief at the end of this session.
When Jesse returned the next week, Jake talked to him about enrolling in one of the student success courses that was starting in March. At this point, Jesse had consistently been attending classes for five weeks and only missed turning in one assignment. Jake integrated open questioning, affirmations, reflective listening and summary reflections (OARS) from motivational interviewing as he revisited Jesse’s goals regarding his academic program. His mid-term reports were positive, but Jesse still questioned whether he “was college material.” Jesse started attending the student success course that was focused on healthy relationships. This ended up being another important turning point in his counseling, because Jesse was able to bring content about boundaries, connection, and power into his counseling sessions with Jake. He also connected with one of the other students in the course. Their shared experience not only created a friendship, it helped both young men to find another person with a similar background. Jesse said it was the first time he felt that “he belonged.” Jake asked, “The first time you feel that you belong in college?” Jesse said, “No, the first time I feel I belong anywhere.”
By the end of the semester, Jesse’s 15 sessions for this academic year were completed. He also completed one student success course, and the text-based intervention that focused on the protective factors. Jake reminded him that the weekly tips are still available and that he can enroll in any of the three additional courses. He is also eligible to sign-up for counseling again in a new academic year. Jesse agreed and thanked him. It was a hard good-bye. Termination of services and letting go of professional relationships like the one developed between Jake and Jesse is not easy, particularly for young people with a background in foster care for whom previous endings felt more like a rejection, than a planned ending.
Over the next three years, Jesse engaged in services intermittently. Like many students who have foster care experience, he continued to experience challenges both in his personal life and in college. At one point, Jesse’s mother was arrested for drug possession, and he found himself spiraling back into a depression. He missed a week of class, but this time, demonstrating insight developed through ASuPIRE, he quickly re-engaged with counseling services to get back on track. He also reached out to his friend who provided a listening ear, illustrating not just the giving, but also the receiving of social support. It took him a bit longer to graduate considering the challenges of his first semester, but he did complete his undergraduate degree in business, although he ended up changing his major from accounting to human resources, as he had become very interested in human behavior as a result of all he had faced. When asked about his greatest accomplishment, surprisingly, it was not his own graduation that he cited. Instead, he noted the fact that his younger brother was starting college next fall as the thing that brought him the most pride.
Jesse experienced lots of ups and downs throughout his time in college. College is not easy nor is emerging as an adult when someone carries the level of responsibility Jesse did along with the pain and loss he experienced during his adolescence. With that said, Jesse did not just graduate from college. He gained new life skills. He developed stronger interpersonal skills. He learned to look to his strengths when facing a problem. He worked through negative thought patterns, even though these cognitions would come up again time and again. And, most importantly, he set bigger goals for himself. His initial goal of maintaining housing changed to a goal of graduating and finding employment that would provide him security and choice for his future that he felt he lacked as a child. By creating a safe space to reframe negative cognitions, work through resistance by focusing on change talk, acknowledge trauma and build new coping skills, enhance social skills, and help Jesse author a new story, these interventions provided the support needed so that Jesse could accomplish his goals.
Implications and Conclusions
Creating campus-based programs that support young people with a background in foster care as they transition to and persist in college remains an important opportunity to impact their long-term academic success. With that said, these goals may be undermined without specific attention to meeting the mental health needs of students who have foster care experience. As universities consider this, designing evidence-based, theoretically-informed interventions remains essential. Additionally, universities/colleges, counseling services, and campus-based programs for students who have foster care experience may also need to consider the creation or adaptation of policies that impact the delivery of mental health services.
Implementing a program such as ASuPIRE may be challenging given that many campus-based support programs for students who have foster care experience have limited resources such as personnel, funding, and capacity to provide expanded services. Considering the ASuPIRE intervention model is made up of three components: (a) time-limited individual counseling that is embedded within the university’s counseling services program, (b) a set of four one-credit student success courses, and (c) a 12-week text-based intervention, leaders at institutions can think creatively about what might be possible given their unique circumstances. Choosing one, two, or all three elements of ASuPIRE moves the needle forward in meeting the mental health needs of students with foster care experience.
Providing individual counseling is optimal, as many students who have foster care experience may have receiving past mental health services that were not positive and did not understand the connection between being a college student and their symptomology. Bridging Success was fortunate in that we had an existing positive relationship with the leaders overseeing counseling services. We were able to leverage our shared interest in meeting the mental health needs of students at the university, while explaining the unique needs of students who have foster care experience. We also shared ownership of ASuPIRE with counseling services and worked through this process as a shared partnership. For example, counseling services provided the ASuPIRE service provider with office space and administrative support, Bridging Success secured philanthropic funding to cover the salary and benefits-related expenses associated with hiring a full-time counselor. An alternative approach might be to identify someone within an institution’s counseling services that can be a designated therapist for students who have foster care experience and provide specialized training to build their knowledge base of the student population.
The design of the one-credit student success courses was based on a pre-existing model used by the university to support incoming students and/or students on academic probation. Most colleges and universities use similar first year success classes that can be easily adapted to meet the needs of students who have foster care experience. We were able to integrate topics that students have expressed interest in such as developing personal wellness habits, skills for authoring and redefining personal narratives, developing a growth mindset, and how to navigate and build healthy/helpful relationships. It was beneficial to reach out to experts in the topics that were employed at the university. We found that once we explained the need to faculty and staff, they were more than happy to help us build the curriculum. It is important to note that we offered contributors financial compensation for their efforts.
Lastly, and maybe the most manageable element of ASuPIRE that an institution can implement, is the creation of a weekly text-based mental health intervention. Because most young people are comfortable with technology and use it as a primary source of information, creating a text-based intervention was a natural extension of ASuPIRE. It was important to us to find contributors with lived foster care experience. Seeing and hearing other students share personal, and at times vulnerable stories, of facing challenges and overcoming them by intentionally activating their resilience skills brings this important content to life. The creation of the actual text/videos required us to collaborate with the university’s marketing and website design teams because our staff did not have the technological skills needed to produce them ourselves. Students who have foster care experience wishing to receive the ASuPIRE text messages can sign up to receive them through the foster youth section of the university’s website.
The authors acknowledge that it may be challenging to implement all or parts of the ASuPIRE program due to limited resources, financial supports, and institutional capacity to provide such services. Many institutions of higher education may offer only limited counseling services and could require policy changes that provide for more robust mental health interventions. Additional funding would also be needed to fulfill such a policy change. Campus support program for students who have a foster care background can advocate for such policy changes.
Formal evaluation of ASuPIRE is anticipated in the next year and will likely examine the usefulness/impact of program elements on improvement of mental health outcomes using validated tools that measure symptomology over time. These findings will be viewed in conjunction with retention and persistence rates of participants. We acknowledge this scope of evaluation will be limited, because graduation rates are based on a six-year timeframe, and it would not be possible to evaluate the impact of ASuPIRE on graduation outcomes for several years.
Although formal evaluation is pending, the initial group of students who participated in ASuPIRE offer positive feedback about the experience. For example, on an anonymous feedback survey, one student stated, “Counseling offered me a safe-space to share my feelings with a supportive figure. I never realized the benefits of this until now. It has been a perspective-shifting experience and one that I will never forget,” and another shared that from counseling, he would remember, “to continually practice self-care and to promote my overall wellbeing. I will remember that it is not a weakness to ask for help. My counseling experience helped me to solidify that my thoughts and feelings are valid and should be listened to.” Students also appreciated the student success courses. For example, one concluded:Growing up, I did not have healthy boundaries. And you know it is hard to determine what exactly is a healthy relationship or not, because that has never been modeled for me. When [the instructor] modeled healthy relationships, and all their different forms, it really stood out to me.
Although the early feedback is promising, more research is needed to implement the program with high fidelity at multiple sites to adequately evaluate its effectiveness in improving wellbeing and increased college persistence and graduation rates. The opportunity is larger than graduation – providing these services at this particular point in a young person’s development can offer skill building that, when coupled with a college education, can go a long way in preparing students who have foster care experience for their next steps beyond college.
We are working on publishing a manual that describes the program elements in great detail about how to implement our campus-based, support program for students who have foster care experience which includes ASuPIRE. Once this manual is available, these programs can easily be translated to other colleges and universities. As colleges and universities consider how best to support students with a background in foster care, implementing increased services through a holistic campus-based support program is the first step. Being intentional about having part of the programming focus on meeting the mental health needs of students who have foster care experience is also beneficial.
When considering implementation of programs such as ASuPIRE on a college or university campus, advocates can investigate existing policies and practices for addressing mental health concerns for students. At the local level, health centers located at colleges and universities can consider accepting Medicaid so that the cost of counseling can be covered under the insurance system often used by students with a history of foster care. At the state level, there are still many states that do not offer a tuition waiver for these students. Considering legislation that will not just require the waiver, but also appropriate resources to fund these programs can ensure colleges and universities are incentivized to offer services that can assist this population. At the federal level, legislation that allows young people to extend their time in foster care has been influential in providing ongoing support for these emerging adults. Including funding for mental health services as part of federal legislation could reduce the likelihood childhood trauma being left untreated. More research is needed to evaluate the effectiveness of this program. Those findings will offer implications for policy and practice as best practices are more fully informed through evidence.
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The authors of this manuscript do not have any potential conflicts of interest.
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The manuscript is a theoretical article and informed consent was not required since no research was conducted.
Research Involving Human and Animals Rights
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| 0 | PMC9735276 | NO-CC CODE | 2022-12-14 23:29:53 | no | Child Adolesc Social Work J. 2022 Dec 10;:1-14 | utf-8 | Child Adolesc Social Work J | 2,022 | 10.1007/s10560-022-00905-w | oa_other |
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Lancet Reg Health Eur
Lancet Reg Health Eur
The Lancet Regional Health - Europe
2666-7762
The Authors. Published by Elsevier Ltd.
S2666-7762(22)00260-5
10.1016/j.lanepe.2022.100564
100564
Correspondence
Rapid emergence of omicron sublineages expressing spike protein R346T
Groenheit Ramona a
Galanis Ilias a
Sondén Klara ab
Sperk Maike a
Movert Elin a
Bacchus Philip cd
Efimova Tatiana a
Petersson Lina a
Rapp Marie a
Sahlén Viktoria a
Söderholm Sandra a
Valentin Asin Karin a
Zanetti Sarah a
Lind Karlberg Maria a
Bråve Andreas a
Klingström Jonas aef∗
Blom Kim a
a Public Health Agency of Sweden, Solna, Sweden
b Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
c Swedish Armed Forces, Umeå, Sweden
d Department of Laboratory Medicine, Lund University, Lund, Sweden
e Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
f Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden
∗ Corresponding author. Public Health Agency of Sweden, Solna, Sweden.
10 12 2022
1 2023
10 12 2022
24 100564100564
17 10 2022
20 11 2022
24 11 2022
© 2022 The Authors
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Keywords
SARS-CoV-2
Point prevalence
National survey
Omicron
Spike protein
Receptor binding domain
Convergent evolution
COVID-19
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pmcText
Although vaccinations and SARS-CoV-2 infections have resulted in a high level of antibody-positive individuals SARS-CoV-2 omicron variants continue to spread, including with high infection rates in triple-vaccinated individuals.1 The first waves of SARS-CoV-2 infections were caused by distinct variants of concern (VOC), each dominating until being replaced by a novel VOC. Since the emergence of omicron in late 2021, new subvariants exhibiting increased capacity for immune escape have emerged.2 , 3 Currently, various BA.2/4/5 sublineages circulate in the population, strongly dominated by BA.5.
Recently, sequencing data has revealed the emergence of new circulating omicron variants in e.g. the United Kingdom,4 with indication of accelerated convergent evolution4 , 5 resulting in shared phenotypes between variants. This marks a possible shift in the transmission landscape; rather than one specific sublineage dominating, several distinct subvariants with a specific phenotype may together form a dominating cluster. One of such important mutations is R346X, in particular R346T, situated in the receptor binding domain (RBD) of the spike protein, with an enhanced capacity to escape neutralizing antibodies.5 Current sequencing data is largely generated from group-specific testing, possibly delaying detection of novel variants and transmission patterns in society.4
To estimate the prevalence of SARS-CoV-2 infection and to identify variants causing them, we invited individuals being part of a Swedish nationwide probability-based web panel to participate in a survey taking place September 26–29, 2022. Enrolled participants (n = 1774) received material for self-sampling of upper respiratory tract for PCR-analysis for presence of SARS-CoV-2 and of blood for serological analysis (Fig. 1 A, Supplementary Appendix for methods).Fig. 1 High frequency of circulating R346X mutated omicron-variants in circulation late September, 2022, Sweden. (A) Overview of enrolled study participants, collected and analyzed samples. (B) Variants detected (pangolin classification) in the PCR-screening. Of the 31 PCR-positive samples, 30 could be sequenced. In total 13 different omicron sublineages was detected. Variants with R346X-mutations are marked with an asterix.
In total, 1524 of 1554 participants were positive for anti-spike IgG. Ongoing SARS-CoV-2-infection was detected in 31 out of 1687 participants, resulting in an age-, sex- and region-adjusted estimated overall point-prevalence of 1·5% (95% CI: 0·9–2·5%). Of the 31 positive samples, 30 were successfully sequenced. In total, 13 different omicron sublineages were identified, among which BA.5.2 (n = 7) and BF.7 (n = 7) were the most common ones (Fig. 1B, Table S1). Strikingly, 40% of infections were caused by R346X-mutated variants represented by six different sublineages. Moreover, five of these sublineages showed an identical pattern of RBD mutations (Table S2).
To conclude, these results show a rapid emergence of several R346T expressing sublineages with identical or very similar RBD, indicating that the next wave of SARS-CoV-2 infections may be caused by a group of sublineages sharing a phenotype, rather than by one specific sublineage.
Contributors
Literature search: R.G., I.G., J.K., K.B.
Figures: R.G., I.G., J.K., K.B.
Study design: R.G., I.G., P.B., M.R., A.B., J.K., K.B.
Data collection: R.G., I.G., K.S., M.S., E.M., P.B., T.E., L.P., M.R., V.S., S.S., K.V.A., S.Z., M.L.K., J.K., K.B.
Data analysis: R.G., I.G., K.V.A, J.K., K.B.
Data interpretation R.G., I.G., J.K., K.B.
Writing – original draft: R.G., I.G., J.K., K.B.
Writing – review & editing: All authors.
Data sharing statement
The datasets that support the findings of this study are not publicly available, but are available from the corresponding author upon reasonable request.
Declaration of interests
All authors have no conflicts of interest related to this work.
Appendix A Supplementary data
Supplementary Material
Appendix A Supplementary data related to this article can be found at https://doi.org/10.1016/j.lanepe.2022.100564.
==== Refs
References
1 Blom K. Havervall S. Marking S. Infection rate of SARS-CoV-2 in asymptomatic healthcare workers, Sweden, June 2022 Emerg Infect Dis 28 2022 2119 2121 35997692
2 Viana R. Moyo S. Amoako D.G. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa Nature 603 2022 679 686 35042229
3 Hachmann N.P. Miller J. Collier A.-R.Y. Neutralization escape by SARS-CoV-2 omicron subvariants BA.2.12.1, BA.4, and BA.5 N Engl J Med 387 2022 86 88 35731894
4 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1109820/Technical-Briefing-46.pdf. 2022.
5 Cao Y. Jian F. Wang J. Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution bioRxiv 2022 10.1101/2022.09.15.507787 [preprint]
| 0 | PMC9735319 | NO-CC CODE | 2022-12-14 23:29:53 | no | Lancet Reg Health Eur. 2023 Jan 10; 24:100564 | utf-8 | Lancet Reg Health Eur | 2,022 | 10.1016/j.lanepe.2022.100564 | oa_other |
==== Front
Clin Microbiol Infect
Clin Microbiol Infect
Clinical Microbiology and Infection
1198-743X
1469-0691
European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd.
S1198-743X(22)00604-8
10.1016/j.cmi.2022.12.001
Research Note
Myocarditis in monkeypox-infected patients: a case series
Dumont Maëlle MD 12
Guilhou Thomas MD 3
Gerin Magdalena MD 1
Frémont-Goudot Guillemette MD 12
Nivose Pierre-Louis MD 1
Koubbi Arnaud MD 4
Joly Véronique 3
Bouadma Lila PHD 5
Yazdanpanah Yazdan PHD 3
André Marie-Hélène MD 1
de La Porte des Vaux Clémentine MD 3∗
1 Department of Internal Medicine and Infectious Diseases, André Grégoire Hospital Center, Montreuil, France
2 Department of Dermatology, AP-HP, Saint-Louis University Hospital, Paris, France
3 Department of Infectious Diseases, AP-HP, Bichat Claude-Bernard University Hospital, Paris, France
4 Cardiology Department, André Grégoire Hospital Center, Montreuil, France
5 Intensive Care Unit, AP-HP, Bichat Claude-Bernard University Hospital, Paris, France
∗ corresponding author: Service de Maladies Infectieuses et Tropicales, Centre Hospitalo-Universitaire Bichat Claude-Bernard, AP-HP, 46 rue Henri Huchard, 75018, Paris, France ; , +33684045327.
9 12 2022
9 12 2022
10 11 2022
28 11 2022
1 12 2022
© 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
2022
Elsevier has created a Monkeypox Information Center (https://www.elsevier.com/connect/monkeypox-information-center) in response to the declared public health emergency of international concern, with free information in English on the monkeypox virus. The Monkeypox Information Center is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its monkeypox related research that is available on the Monkeypox Information Center - including this research content - immediately available in publicly funded repositories, with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the Monkeypox Information Center remains active.
Objectives
Monkeypox, a zoonotic orthopoxvirus, has spread to many countries in recent months, involving mostly men who have sex with men (MSM) with multiple partners. Clinical presentation includes skin lesions, systemic signs, and less frequently skin superinfections, or ano-rectal and ophthalmic involvements. We aim to detail cases of myocarditis attributable to monkeypox, an entity that has been poorly described.
Methods
This is a descriptive case series reporting three cases of myocarditis that occurred in monkeypox-infected patients in France in 2022.
Results
Patients were adult men with no medical history who had skin lesions with positive polymerase-chain-reaction for monkeypox virus. A few days after onset of cutaneous signs, patients developed acute chest pain, elevated cardiac markers, and biological inflammatory syndrome compatible with myocarditis. Two patients presented electrocardiogram abnormalities and decreased ejection fraction associated with kinetic disturbances on transthoracic electrocardiography. The last patient had normal transthoracic electrocardiography and normal electrocardiogram, but cardiac magnetic resonance imaging showed segmental inferolateral acute myocarditis. Patients were hospitalized and received cardioprotective treatment. One received antiviral treatment with teicovirimat. Symptoms and laboratory abnormalities rapidly resolved in all patients.
Conclusions
These cases suggest an association between monkeypox infections and cardiac inflammatory complications. The development of chest pain in an infected patient should not be underestimated and should lead to prompt investigations for myocarditis. Monkeypox infection should also be included in the differential diagnosis of myocarditis, particularly in at-risk patients such as MSM with multiple partners in whom complete examination for skin or mucosal lesions should thus be performed.
Editor: Professor L Leibovici
==== Body
pmcIntroduction
Monkeypox, a zoonotic orthopoxvirus, has spread to many countries outside the known endemic areas in recent months (1). The current epidemic has mainly involved men who have sex with men (MSM) with multiple partners. Clinical presentation includes skin lesions, systemic signs, and less frequently skin superinfections, or severe and painful ano-rectal or ophthalmic involvements (2, 3, 4). Myocarditis is a focal or diffuse inflammation of the myocardium that can result in acute arrhythmia, dilated cardiomyopathy, and heart failure (5, 6). Viruses such as adenovirus, parvovirus B19, HIV, or enterovirus are known to cause myocarditis. Only five cases of myocarditis attributed to monkeypox have been described, all in 2022 during the current epidemic, with possible differential causes of myocarditis (3; 7, 8). We describe here three new cases of acute myocarditis attributable to monkeypox.
Methods
This is a case series describing three cases of myocarditis attributable to monkeypox in France in 2022. Cases were identified during a call for observations in a national meeting for coordination of epidemiological risks. Diagnostic criteria for myocarditis were not predefined and remained at the discretion of clinicians. A review of medical records was conducted to detail the cases retrospectively. Each patient had been previously informed that clinico-biological information could be used for research, without oral opposition.
Results
Patient 1, a 21-year-old man, developed fever with anal pain four days after the last unprotected homosexual intercourse, with several sexual intercourses with at-risk partners during the previous month. Monkeypox polymerase-chain-reaction (PCR) on swab from anal pustules was positive. Two days later, acute chest pain radiating into the arms and jaw appeared. Electrocardiogram revealed ST elevation in inferior leads. High-sensitivity troponin T reached 4040 pg/mL (N<58.9), Creatine Kinase (CK) 418 U/L (N 39-308) and C-Reactive-Protein (CRP) 27 mg/L (N<6). Contrast chest-CT scan excluded pulmonary embolism. Transthoracic echocardiography (TTE) showed a non-dilated, non-hypertrophied left ventricle with segmental hypokinesis of inferior and inferolateral walls, left ventricular ejection fraction (LVEF) was estimated at 56%. Cardioprotective treatment with bisoprolol and ramipril was initiated. There was no recurrence of pain and high sensitivity troponin T decreased to 2200 pg/mL on day 1. No other STI or other cause of myocarditis were found (normal serum protein electrophoresis, no declared toxic consumption, negative HIV and syphilis serologies, negative PCRs for EBV, CMV and parvovirus B19, negative nasopharyngeal SARS-COV2 PCR). Coronary explorations were not performed given the patient’s young age, the absence of comorbidity or family history of cardio-vascular disease and the rapidly favorable outcome. Cardiac magnetic resonance imaging was performed four weeks later and demonstrated no evidence of cardiac inflammation.
Patient 2, a 25-year-old man with no medical history, developed pustules on the face and penis a few days after an unprotected sexual intercourse. Five days later, he reported constant chest pain and palpitations. Monkeypox PCR on skin lesions was positive. Electrocardiogram showed discrete ST elevation in the inferior and the anterior territories, with possible under-shift of the PQ segment (Figure 1 ). Blood analyses showed increased high sensitivity troponin T (700 pg/mL; N<58.9), CK (318 U/L; N 39-308) and CRP (39 mg/L; N<6) levels. TTE showed impaired LVEF (45%) with inferolateral akinesia. The evolution was rapidly favorable under bisoprolol and ramipril. No other STI or other cause of myocarditis was found after medical examination and biological assessment (identical to patient 1). For the same reasons as in the first case, coronary explorations were not performed.Figure 1 electrocardiogram of patient 2.
Figure 1
Patient 3, a 32-year-old man with no medical history, developed erosive cutaneous lesions on the penis approximately one week after an unprotected heterosexual intercourse. Three days later, he presented retrosternal chest pain and fever. Monkeypox PCR on skin lesions and pharynx were positive, and was negative in serum. Laboratory analyses showed increased high-sensitivity troponin T (2035 pg/mL; N<58.9), CK (2295 U/L; N 39-308) and CRP (115 mg/l; N<6) levels. Electrocardiogram and TTE were normal. Cardioprotective treatment with bisoprolol, anti-aggregation and antiviral treatment with teicovirimat were initiated. No other STI or other etiology of myocarditis was found (negative blood PCRs for HIV, HSV, CMV, VZV, parvovirus B19, HHV6 and HHV8, slightly detectable EBV DNA in blood < 500 copies/mL, negative nasopharyngeal multiplex PCR, negative serologies for intracellular bacteria, negative screening for toxics consumption, isolated anti-nuclear antibodies with low titer 1/80, normal angiotensin converting enzyme, unconsumed complement, normal serum protein electrophoresis). Chest pain stopped on day 2 and high-sensitivity troponin T levels normalized on day 4. Cardiac-CT scanner showed normal coronary arteries but reflected acute myocarditis. Cardiac magnetic resonance imaging, performed 11 days after the onset of chest pain, showed segmental myocarditis involving the inferolateral segment (Figure 2 ).Figure 2 key pictures of cardiac magnetic resonance imaging of patient 3.
Figure 2
Discussion
In these three cases, the history began with typical monkeypox lesions confirmed by PCR. A few days later, patients presented acute chest pain, fever, elevated cardiac markers and biological inflammatory syndrome, without other systemic signs. Typical electrocardiogram and TTE abnormalities associated with myocarditis were identified in two patients. Cardiac magnetic resonance imaging showed segmental myocarditis in the third patient. Myocarditis was attributed to monkeypox in all: no differential diagnosis was found. Outcome was rapidly favorable in all after cardioprotective treatment, regardless of the use of antiviral treatment.
Only five cases of myocarditis attributed to monkeypox had been previously described. Two were described in a series of 528 human monkeypox infections diagnosed in 16 countries in 2022 (3). One occurred in a HIV-infected patient with 780 CD4 cells per cubic millimeter, the second patient had no medical history. Their symptoms lasted less than 7 days. Recently, three other case reports of myocarditis attributed to monkeypox were reported (7, 8). Patients were immunocompetent and presented with clinical presentation compatible with myocarditis and recently confirmed monkeypox infections. Two patients had ventricular repolarization abnormalities on electrocardiogram with normal TTE, including one in whom cardiac magnetic resonance imaging confirmed the myocarditis. The third patient had normal electrocardiogram and TTE. One patient was treated with teicovirimat. Outcome was rapidly favorable in all. However, differential causes of myocarditis were not discussed in two of these five patients, one had no additional investigation for other causes of elevated cardiac markers although he had family history of coronary disease, one had a concomitant active syphilitic infection, and the last one had had a paucisymptomatic SARS-COV2 infection two months before.
In summary, findings from our present case series suggest the possibility of an association between monkeypox and acute myocarditis, as previously suggested. However, our cases were important to describe because differential diagnoses were explored and deemed unlikely, whereas the presence of other possible causes of myocarditis in previously reported cases (or the deferral of explorations for differential diagnoses) made the suggestion of a causality between monkeypox and myocarditis questionable.
Thus, this series highlights the importance of not underestimating chest pain in monkeypox-infected patients. We should not be completely reassured by the favorable outcome of myocarditis in these patients, given the low number of cases reported: larger studies with appropriate designs are needed to confirm an association between monkeypox infections and myocarditis and to assess the risk of progression towards complications (such as arrhythmia or long-term cardiomyopathy). In the meantime, monkeypox-infected patients should be advised to consult rapidly if they experience chest pain. Furthermore, monkeypox should be considered if myocarditis is diagnosed in at-risk patients in countries experiencing epidemics.
Transparency declaration
Each of the authors declare no conflict of interest regarding this study. No external funding was received for this research.
CRediT authorship contribution statement
Maëlle Dumont: Conceptualization, Data curation, Methodology, Validation, Visualization, Writing - original draft, review & editing. Thomas Guilhou: Conceptualization, Writing - original draft, Review & Editing. Magdalena Gerin: Data curation, Writing - original draft, Review & Editing. Guillemette Frémont-Goudot: Writing - original draft, Review & Editing. Pierre-Louis Nivose: Writing - original draft, Review & Editing. Arnaud Koubbi: Writing - original draft, Review & Editing. Véronique Joly: Writing - original draft, Review & Editing. Lila Bouadma: Writing - original draft, Review & Editing. Yazdan Yazdanpanah: Writing - original draft, Review & Editing. Marie-Hélène André: Clémentine de La Porte des Vaux: Conceptualization, Data curation, Methodology, Validation, Visualization, Writing - original draft, Review & Editing.
==== Refs
References
1 World Health Organization, 2022. https://www.who.int/emergencies/situations/monkeypox-oubreak-2022
2 Mailhe M. Beaumont A.L. Thy M. Le Pluart D. Perrineau S. Houhou-Fidouh N. Deconinck L. Bertin C. Ferré V.M. Cortier M. De La Porte Des Vaux C. Phung B.C. Mollo B. Cresta M. Bouscarat F. Choquet C. Descamps D. Ghosn J. Lescure F.X. Yazdanpanah Y. Joly V. Peiffer-Smadja N. Clinical characteristics of ambulatory and hospitalised patients with monkeypox virus infection: an observational cohort study Clin Microbiol Infect 2022
3 Thornhill J.P. Barkati S. Walmsley S. Rockstroh J. Antinori A. Harrison L.B. Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022 N Engl J Med 2022
4 Bryer J. Freeman E.E. Rosenbach M. Monkeypox emerges on a global scale: A historical review and dermatologic primer J Am Acad Dermatol 2022
5 Temi Lampejo, Simon M Durkin, Naman Bhatt, and Oliver Guttmann. Acute myocarditis: aetiology, diagnosis and management. Clin Med Lond Engl. sept 2021
6 Sozzi F.B. Gherbesi E. Faggiano A. Gnan E. Maruccio A. Schiavone M. Viral Myocarditis: Classification, Diagnosis, and Clinical Implications Front Cardiovasc Med 9 2022 908663
7 Rodriguez-Nava G. Kadlecik P. Filardo T.D. Ain D.L. Cooper J.D. McCormick D.W. Webber B.J. O'Laughlin K. Petersen B.W. Narasimhan S. Sahni H.K. Myocarditis Attributable to Monkeypox Virus Infection in 2 Patients, United States, 2022 Emerg Infect Dis 2022
8 Pinho A.I. Braga M. Vasconcelos M. Oliveira C. Santos L.D. Guimarães A.R. Martins A. Chen-Xu J. Silva S. Macedo F. Acute Myocarditis - a new manifestation of Monkeypox infection? JACC Case Rep 2022
| 36509373 | PMC9735378 | NO-CC CODE | 2022-12-15 23:21:52 | no | Clin Microbiol Infect. 2022 Dec 9; doi: 10.1016/j.cmi.2022.12.001 | utf-8 | Clin Microbiol Infect | 2,022 | 10.1016/j.cmi.2022.12.001 | oa_other |
==== Front
J Infect
J Infect
The Journal of Infection
0163-4453
1532-2742
The British Infection Association. Published by Elsevier Ltd.
S0163-4453(22)00689-2
10.1016/j.jinf.2022.11.028
Letter to the Editor
Changes of Acinetobacter baumannii infections in children before and after the COVID-19 pandemic in Zhengzhou, China
Li Lifeng ⁎
Yu Zengyuan
Li Mingchao
Sun Huiqing ⁎
Henan International Joint Laboratory of Children's Infectious Diseases, Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
⁎ Corresponding author.
5 12 2022
5 12 2022
29 11 2022
© 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
2022
The British Infection Association
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
==== Body
pmcDear Editor,
We read with interest the research results of Li et al.1 and Zhou et al.2 published on this journal, which reported the decline of Streptococcus pneumoniae and Haemophilus influenzae infection in children under the impact of COVID-19 pandemic. Li et al.3 compared the effect of COVID-19 on the incidence of Escherichia coli infections in respiratory system and digestive system in children, the results indicated larger effect on the respiratory system infection. However, no data were available on the prevalence of Acinetobacter baumannii causing lower respiratory infections especially in the bronchoalveolar lavage fluid (BALF) samples of children before and after the COVID-19 pandemic.
Pneumonia is a leading cause of death among children under five years old globally, which accounted for 12.8% causing about 920,000 deaths every year.4 The pathogens causing pneumonia varied, hence identification of pneumonia etiology is critical for the management and treatment of the disease. Multiple samples were used to detect the pathogens, whereas BALF is the ideal specimen for detecting the causative pathogen apart from lung tissue or aspirate.5 A. baumannii is a Gram negative opportunistic human pathogen, which could cause a wide spectrum of illness including bloodstream infection, pneumonia, and endocarditis.6 It has a remarkable capacity to develop antimicrobial resistance, and multidrug resistant strains may account for ∼45% of all isolates, which made them a serious health threat.7 The outbreak of COVID-19 pandemic has changed the lifestyles of human beings, and the measures to control the transmission of SARS-CoV-2 may also affect the prevalence of other respiratory pathogens.1, 2, 3 , 8 Hence, analysis of the pathogen distributions in the BALF cultures and the prevalence trend of A.baumannii infection in children before and after the COVID-19 pandemic is critical for hospital infection prevention and control.
In this study, we firstly compared the total numbers of BALF cultures and the total positive numbers to analyze the impact of COVID-19 pandemic on the pathogen prevalence of children in Henan Children's hospital between January 2018 and November 2022. A total of 5737 children were included (n = 1043 in 2018, n = 1211 in 2019, n = 712 in 2020, n = 1148 in 2021 and n = 1623 in 2022) (Fig. 1 A). The total positive numbers with reported pathogen were 1203 (n = 266 in 2018, n = 208 in 2019, n = 163 in 2020, n = 261 in 2021 and n = 305 in 2022). A significant decrease in the total numbers and positive numbers was found in 2020, the first year of COVID-19 pandemic. However, the total positive rates were not following the decreasing trend.Fig. 1 The total numbers of BALF cultures and the total positive numbers (A) and the total number and the positive rates of A. baumannii infection (B) in children from 2018 to 2022.
Fig 1
Further, the pathogen distributions were analyzed with positive culture results before and after the COVID-19 pandemic. Among the positive BALF cultures, the most common pathogens included A. baumannii, S. pneumoniae, Klebsiella pneumoniae, Burkholderia cepacia complex, Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa and E. coli (Table 1 ), which accounted for over 75% of the total pathogens detected. Among the most common pathogens, a decrease in A. baumannii infections was indicated by the data from 2018 to 2022 (Fig. 1B). The positive rates of S. pneumoniae decreased from 2018 to 2020, while increased in 2021 and 2022. S. pneumoniae was not detected in 2020, whereas a very high rate (40.66%) was detected in 2022. P. aeruginosa increased from 2018 to 2020, while decreased in 2021 and 2022. Other pathogens kept a relatively stable state. Hence, our data indicated significant effect of COVID-19 on the prevalence of A. baumannii infections, which accounted for a high proportion among the positive BALF pathogens before COVID-19 pandemic.Table 1 The pathogen distribution of BAFL cultures in children from 2018 to 2022.
Table 1Pathogen 2018 (n = 266) 2019 (n = 208) 2020 (n = 163) 2021 (n = 261) 2022 (n = 305)
Acinetobacter baumannii 66 (24.81%) 45 (21.63%) 26 (15.95%) 27 (10.34%) 29 (9.51%)
Streptococcus pneumoniae 65 (24.43%) 20 (9.62%) 0 (0%) 37 (14.18%) 124 (40.66%)
Klebsiella pneumoniae 28 (10.53%) 21 (10.10%) 26 (15.95%) 43 (16.48%) 14 (4.59%)
Burkholderia cepacia complex 25 (9.40%) 20 (9.62%) 19 (11.66%) 28 (10.73%) 24 (7.87%)
Staphylococcus aureus 16 (6.02%) 16 (7.69%) 11 (6.75%) 16 (6.13%) 33 (10.82%)
Candida albicans 17 (6.40%) 29 (13.94%) 17 (10.43%) 30 (11.49%) 25 (8.20%)
Pseudomonas aeruginosa 14 (5.26%) 16 (7.69%) 16 (9.82%) 12 (4.60%) 14 (4.59%)
E. coli 8 (3.01%) 8 (3.85%) 7 (4.29%) 12 (4.60%) 6 (1.97%)
Other pathogens 27 (10.15%) 33 (15.87%) 41 (25.15%) 56 (21.46%) 36 (11.80%)
In conclusion, our data indicated that the distribution of the pathogens may vary in different regions and for different pathogens. Among the pathogens detected, A. baumannii decreased gradually in the COVID-19 pandemic. Hence, continuous observations are required to reveal the epidemiology information to provide clues for the prevention and control of related diseases.
Declaration of Competing Interest
The authors declare no conflict of interests.
Acknowledgments
This work was supported by grants from the 10.13039/501100001809 National Natural Science Foundation of China (31900116) and the Medical Science and Technology Projects of Henan Province (LHGJ20190955).
==== Refs
References
1 Li Y. Guo Y. Duan Y. Changes in Streptococcus pneumoniae infection in children before and after the COVID-19 pandemic in Zhengzhou, China J Infect 85 3 2022 e80 e81 35659542
2 Zhou J. Zhao P. Nie M. Gao K. Yang J. Sun J. Changes of Haemophilus influenzae infection in children before and after the COVID-19 pandemic, Henan, China J Infect 2022
3 Li Liping Song Chunlan Li Peng Li Y. Changes of Escherichia coli infection in children before and after the COVID-19 pandemic in Zhengzhou, China J Infect 2022
4 Liu L. Oza S. Hogan D. Chu Y. Perin J. Zhu J. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals The Lancet 388 10063 2016 3027 3035
5 Zhang R. Wu Y. Deng G. Deng J. Value of sputum Gram stain, sputum culture, and bronchoalveolar lavage fluid Gram stain in predicting single bacterial pathogen among children with community-acquired pneumonia BMC Pulm Med 22 1 2022 427 36402959
6 Jalal D. Elzayat M.G. Diab A.A. El-Shqanqery H.E. Samir O. Bakry U. Deciphering Multidrug-Resistant Acinetobacter baumannii from a Pediatric Cancer Hospital in Egypt mSphere 6 6 2021 e0072521
7 Harding C.M. Hennon S.W. Feldman M.F. Uncovering the mechanisms of Acinetobacter baumannii virulence Nat Rev Microbiol 16 2 2018 91 102 29249812
8 Meyer Sauteur P.M. Beeton M.L. Uldum S.A. Bossuyt N. Vermeulen M. Loens K. Mycoplasma pneumoniae detections before and during the COVID-19 pandemic: results of a global survey, 2017 to 2021 Euro Surveill 27 19 2022
| 36470411 | PMC9735382 | NO-CC CODE | 2022-12-14 23:29:53 | no | J Infect. 2022 Dec 5; doi: 10.1016/j.jinf.2022.11.028 | utf-8 | J Infect | 2,022 | 10.1016/j.jinf.2022.11.028 | oa_other |
==== Front
Therapie
Therapie
Therapie
0040-5957
1958-5578
Published by Elsevier Masson SAS
S0040-5957(22)00184-6
10.1016/j.therap.2022.10.015
Co5
Impact des confinements sur les hospitalisations survenues dans un contexte d’usage de substances psycho-actives en France selon l’âge pendant la pandémie de COVID-19
Perino Justine 1⁎
Ramaroson Hanta 2
Ong Nathalie 2
Bezin Julien 1
Gilleron Véronique 23
Daveluy Amélie 14
Tournier Marie 1
1 University Bordeaux ; Inserm U1219, Bph, Univ, 33000 Bordeaux, France
2 Unité de coordination et d’analyse de l’information médicale–département d’information médicale (Ucaim-DIM), service d’information médicale, CHU de Bordeaux, 33000 Bordeaux, France
3 Population Health trAnslational Research (PHARes), University of Bordeaux–Université de Bordeaux, 33000 Bordeaux, France
4 Centre d’addictovigilance, service de pharmacologie médicale, Inserm, Bph, U1219, CHU de Bordeaux, université de Bordeaux, 33000 Bordeaux, France
⁎ Auteur correspondant.
10 12 2022
November-December 2022
10 12 2022
77 6 760760
Copyright © 2022 Published by Elsevier Masson SAS.
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Contexte
L’étude de l’incidence des hospitalisations survenues dans un contexte d’usage de substance psycho-active (SPA) pendant la pandémie de COVID-19 apparaît comme une opportunité unique d’évaluer le poids habituel de l’usage récréatif sur ces hospitalisations. Cette étude avait pour objectif d’évaluer l’impact des confinements sur l’incidence de ces hospitalisations en France selon l’âge des patients, puis de décrire leurs caractéristiques et les SPA impliquées.
Méthode
Cette étude nationale a été réalisée sur les données de la base nationale ATIH du Programme de médicalisation des systèmes d’information entre le 1er janvier 2014 et le 31 décembre 2020. Une analyse de série chronologique a été réalisée chez les adultes âgés ≥ 30 ans et les jeunes adultes âgés.
Résultats
Parmi les 1 358 007 séjours inclus, 215 430 étaient des jeunes adultes et 1 142 577 des adultes âgés de plus de 30 ans. Les deux confinements étaient associés à une forte diminution du nombre de séjours associés à une consommation de SPA, en particulier chez les moins de 30 ans avec une baisse maximale de −39 % pendant le 1er confinement (1566 vs. 2 576 ; IC95 % : 2285–2868), contre −20 % chez les plus de 30 ans. La plus importante baisse des séjours concernait la région Nouvelle Aquitaine pendant le 1er confinement (301 vs. 175). Chez les adultes jeunes et par rapport aux plus de 30 ans, on observait une forte baisse de l’implication de l’alcool tout au long de la pandémie et particulièrement pendant le 2eme confinement, tandis que les benzodiazépines étaient très impliquées pendant le 1er confinement (23,4 et 17,4/7 jours 1000 patients hospitalisés dans un contexte d’usage de SPA, respectivement) et le 2e confinement (39,1 et 26,3, respectivement). Le cannabis était beaucoup plus impliqué chez les moins de 30 ans tout au long de la pandémie.
Conclusion
Les confinements ont réduit l’usage récréatif des SPA et les hospitalisations associées chez les jeunes adultes. L’usage récréatif pourrait être un important levier de prévention.
Mots clés
Substance psychoactive
Pandémie
Confinement
==== Body
pmcDéclaration de liens d’intérêts
Les auteurs déclarent ne pas avoir de liens d’intérêts.
| 0 | PMC9735428 | NO-CC CODE | 2022-12-14 23:29:53 | no | Therapie. 2022 Dec 10 November-December; 77(6):760 | utf-8 | Therapie | 2,022 | 10.1016/j.therap.2022.10.015 | oa_other |
==== Front
Financ Mark Portf Mang
Financ Mark Portf Mang
Financial Markets and Portfolio Management
1934-4554
2373-8529
Springer US New York
423
10.1007/s11408-022-00423-w
Book Review
The palgrave handbook of FinTech and blockchain
Liebi Luca J. [email protected]
grid.15775.31 0000 0001 2156 6618 Swiss Institute of Banking and Finance, University of St. Gallen, Unterer Graben 21, CH-9000 St. Gallen, Switzerland
10 12 2022
13
© The Author(s) under exclusive licence to Swiss Society for Financial Market Research 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
JEL Classification
O32
O39
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pmcThe rapid development of new technologies applied to the finance industry has coined the term Financial Technology (FinTech). Thereby, FinTech is multidisciplinary in its nature and significantly affects nearly every field of our society. Startups are continuously striving to find a compelling use case for distributed ledger technology. The fascination for FinTech and how it may revolutionize traditional databases of institutions is one reason why Maurizio Pompella and Roman Matousek edited the book The Palgrave Handbook of FinTech and Blockchain. The handbook is grouped into five parts and contains 22 research articles on FinTech, blockchain technology, cyber risk, and digital currencies. In total, 37 researchers have contributed to this book. Overall, the reader profits enormously from the author’s extensive knowledge and research experience.
The Palgrave Handbook of FinTech and Blockchain offers an ideal starting point for researchers and practitioners seeking in-depth information on FinTech, blockchain and digital currencies. Part 1 contains two chapters. Chapter 1 provides an overview of the handbook. In Chapter 2, Paul David Richard Griffiths describes the history of FinTech. The author emphasizes that banks overlooked the rapid technological breakthroughs due to regulatory changes following the Global Financial Crisis in 2007-2008.
Part 2 focuses on FinTech and blockchain technology from an international perspective and includes six articles. In Chapter 3, Rupesh Regmi and Zhuo Zhang investigate financial engineering and communication technology. Interestingly, this article describes the historical evolution of information and communication technology over the last three centuries. Chapter 4 argues that blockchain technology revolutionizes the financial landscape due to omitting financial intermediaries. Notably, the use cases of blockchain technology range beyond bitcoin. In short, blockchain technology has numerous advantages, including security, privacy, traceability, and original data provenance. Chapter 5 describes the opportunities and regulatory challenges of FinTech companies. Chapter 6 focuses on FinTech Unicorns. A unicorn is a privately held startup with a valuation above $1 billion. The authors show that 12.2% (7.8%) of the 255 investigated unicorns belong to the FinTech (Big data) industry. A case study of FinTech in India and Africa is provided in Chapter 7. Chapter 8 deals with which policy mix fosters digital transformation and financial inclusion in the Middle East, North Africa, Afghanistan, and Pakistan.
Part 3 investigates blockchain technology and cyber risks. Chapter 9, on alternative data in FinTech and business intelligence, is written by Lin William Cong, Beibei Li, and Qingquan Tony Zhang. This chapter introduces the reader to recent research utilizing unstructured data such as textual analysis, image processing, social media, and mobile data. The authors conclude that the general trend of using alternative data in academic research will continue. Chapter 10 focuses on the central mechanism, governance, and decentralization of bitcoin. The research focus in Chapter 11 is on digital structured products. Chapter 12 provides a nuanced categorization of crypto-tokens and discusses the role of tokens within a digital ecosystem. Overall, the authors define four categories of crypto-tokens. These categories include payment, platform, product, and security tokens. Chapter 13 argues that cyber resilience strengthens the stability of financial markets. Initial coin offerings and potential risks during the platform’s early development are described in Chapter 14. Chapter 15 investigates the risks of blockchain technology. The authors interviewed 80 individuals from 60 firms to identify these risks. In the next step, the authors develop a practical framework to improve the security decisions of firms.
The next part of the book deals with how blockchain technology affects traditional financial services. Chapter 16 assesses the impact of FinTech on the banking industry and financial intermediation. The currently observed financial disintermediation due to innovations in technology is discussed in chapter 17. Chapter 18 examines to what extent the COVID-19 pandemic affected FinTech. Chapter 19 describes digital currencies and payments. Specifically, the author investigates the mechanism and role of central bank digital currencies and provides insights into how China enforces its currency. Chapter 20 gives a broad overview of cryptocurrencies and other digital assets. The author describes the most prominent cryptocurrencies and the critical differences between them. Additionally, Andria van der Merwe compares the characteristics of cryptocurrencies with fiat money. The author describes the network value to transactions metric to detect cryptocurrency bubbles. Finally, stylized facts about cryptocurrencies are discussed. Chapter 21 investigates the effect of FinTech from a customer’s perspective. The author argues that FinTech can significantly improve customer experience and customer journey.
The final part of the book includes one article. Chapter 22: From Disruption to post-Pandemic Scenario is written by Maurizio Pompella and Lorenzo Constantino. Generally, the COVID-19 pandemic has affected multiple aspects of our society. However, the article exclusively focuses on how COVID-19 affected FinTech. The authors conclude that the COVID-19 pandemic deflated the blockchain and FinTech bubble.
The Palgrave Handbook of FinTech and Blockchain ties together research on FinTech and Blockchain from various perspectives, including 22 articles from 37 researchers. The authors combine their FinTech knowledge to make this highly interdisciplinary topic accessible to readers without prior knowledge. Importantly, the authors constantly provide a link to the current academic literature. Each article investigates FinTech from a different perspective. The handbook includes case studies, practical frameworks as well as academic research. Thus, the book is an excellent starting point due to its multifaceted content and moderately technical focus. The book presupposes no prior knowledge of FinTech, blockchain technology, and bitcoin. Therefore, the handbook is targeted toward interested readers and academics who want to delve deeper into the topic of FinTech. Since FinTech is a rapidly evolving field of research, this handbook provides an excellent overview of the current state. Overall, the authors offer valuable insights and demystify FinTech, blockchain technology and digital currencies
In summary, The Palgrave Handbook of FinTech and Blockchain is a must-have for market practitioners, scientific researchers, and experienced finance students interested in FinTech, blockchain technology and cryptocurrencies.
About the author: Luca Liebi is currently a Ph.D. candidate and research assistant at the School of Finance of the University of St.Gallen, Switzerland. His research interests are empirical asset pricing and risk management with a special focus on cryptoassets.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
Reference
Pompella, M., Matousek, R. (eds.): The Palgrave Handbook of FinTech and Blockchain. Springer (2021)
| 0 | PMC9736698 | NO-CC CODE | 2022-12-14 23:29:53 | no | Financ Mark Portf Mang. 2022 Dec 10;:1-3 | utf-8 | Financ Mark Portf Mang | 2,022 | 10.1007/s11408-022-00423-w | oa_other |
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Indian J Otolaryngol Head Neck Surg
Indian J Otolaryngol Head Neck Surg
Indian Journal of Otolaryngology and Head & Neck Surgery
2231-3796
0973-7707
Springer India New Delhi
3303
10.1007/s12070-022-03303-x
Clinical Report
Covid 19 Associated Idiopathic Intracranial Hypertension and Acute Vision loss
Thakur Sheetal
Mahajan Manisha
Azad Ramesh K
http://orcid.org/0000-0003-2311-0571
Thakur Jagdeep S [email protected]
grid.414489.4 0000 0004 1768 2079 Department of Otolaryngology-Head and Neck Surgery (ENT), Indira Gandhi Medical College, 171001 Shimla, HP India
10 12 2022
14
16 2 2022
21 11 2022
© Association of Otolaryngologists of India 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Headache is a frequent complaint in COVID-19 while intracranial hypertension leading to acute vision loss is unusual. A 49-years-old female presented with persistent headache and vision loss and was found Covid 19 positive. Investigations suggested Covid 19 associated intracranial hypertension. She improved with medical management but again presented with acute vision loss. The visual loss was managed by endoscopic optic nerve fenestration surgery. She had significant recovery in vision during follow up period. Persistent headache in Covid 19 should have a high index of suspicion for idiopathic intracranial hypertension to avoid irreversible vision loss.
Keywords
Covid 19
Idiopathic intracranial hypertension
vision loss
==== Body
pmcBackground
Covid − 19 is the current health problem all over the world. Commonly, it manifests with respiratory symptoms but neuro-ophthalmic presentations have also been found. [1] Headache is one of the important clinical feature of Covid 19 however; persistent headache is also the main feature of idiopathic intracranial hypertension. Advance stage of Idiopathic intracranial hypertension causes vision loss and requires surgical intervention. Covid 19 induced intracranial hypertension and vision loss is rare. [2] We present the second case report of Covid 19 induced Idiopathic intracranial hypertension leading to vision loss and review the literature on this rare but important clinical entity.
Case Presentation
A 49-year-old lady presented in emergency medicine with persistent headache and progressive vision loss in both eyes for last 5 days. This vison loss started one day after the headache and was progressive. There was no other significant contributory history of fever, vomiting, convulsion or trauma. She turned out to be Rapid Antigen test positive and admitted in isolation ward. She had single dose of Covid 19 vaccine (Covishield) about four months back.
Patient had body mass index of 23 with normal physical examination. ENT examination didn’t find any abnormality. Ophthalmic examination found 6/36 visual acuity in both eyes with normal pupillary reactions. Retinoscopy found Frisen grade 3 papilloedema in both optic discs.
Neurology examination was also found normal. CSF tap was done for biochemical and microbiological examination. This CSF puncture for analysis improved her vision and pressure was found more than 25 cm H2O. A possibility of intracranial hypertension was kept and managed accordingly.
Magnetic resonance imaging of brain (Fig. 1) found empty sella turcica without any other significant vascular or meningeal abnormality. Bilateral optic nerves showed tortuosity, increased thickness and ballooning. Cerebrospinal fluid pressure was more than 25cmH2O while biochemical analysis was normal. D-dimers levels were less than 1.0ug/ml FEU while serum ferritin levels were 171.0ng/ml. The clinical history and examination, and radiology didn’t find any other cause of intracranial hypertension. Keeping this in view, diagnosis of Covid-19 induced intracranial hypertension was made. She underwent supportive management of mild Covid-19 and mannitol infusion and oral acetazolamide 250 mg twice daily. Patient showed improvement in headache and vision, and became Covid-19 RTPCR negative on fourth day of admission. She was discharged on oral medication. However; on tenth day of discharge, patient presented again with deterioration of vision. Ophthalmic examination found perception of hand movement close to face in both eyes. Fundus examination and MRI brain also had similar findings as earlier. A multidisciplinary decision for trans-nasal endoscope B/L optic nerve decompression was taken and performed under general anaesthesia. Bilateral optic canals were opened as per the standard surgical protocol. However, optic sheath fenestration led to further vision loss in the immediate post operative period. The urgent MRI scan showed edematous optic nerves bilaterally with no other abnormality (Fig. 2 and 3). Parental methyl prednisolone was started and showed progressive improvement in vision. Follow up after four weeks found favourable outcome with visual acuity of 6/12 on left side and 6/36 on right side. Patient has been kept on regular follow up. The visual acuity was 6/6 in left eye and 6/36 in right eye at the time of final follow up.
Fig. 1 MRI showing tortuous optic nerves bilaterally
Fig. 2 MRI in immediate post-operative period showing thickened optic sheaths right more than left
Fig. 3 MRI in immediate postoperative period showing empty sella and normal dural sinuses
Discussion
The pathogenesis of idiopathic intracranial hypertension remains elusive although various vascular, hormonal and metabolic factors have been implicated. [3–5] It is predominantly found in young, obese, females in child bearing age.[5] Clinically presentation includes (in order of decreasing incidence) headache that increases on coughing or Valsalva manoeuvre, transient visual disturbances on bending or standing, pulsatile tinnitus, back pain, dizziness, neck pain, visual loss, cognitive disturbances, radicular pain and horizontal diplopia.[5] Fundus examination shows papilledema that warrants neuroimaging (CT/MRI with angiography) to excludes tumour or other causes of increased intracranial pressure. Neuroimaging may show empty sella, flattening of posterior aspect of orbital globe, distension of perioptic subarchnoid space, tortuous optic nerve, attenuation of cerberovenous sinuses and stenosis of transverse sinus. Normal cerebrospinal analysis with pressure more that 25 cm H2O makes the diagnosis of idiopathic intracranial hypertension. Abducen nerve palsy is also found in IIH without papilledema. Treatment include reduction of BMI and life modification. Acetazolamide is drug of choice. Lumbar drain is required in refractory cases while acute and progressive vision loss required optic sheath fenestration although optic decompression is also sufficient as observed in our case.[6, 7] Unilateral optic nerve fenestration also lead to visual improvement in contralateral eye.
Covid 19 has challenged every speciality of the medical science. Covid 19 cause viral neurotropism, immunologic upregulation, vasodilation and vascular permeability, endothelial dysfunction, coagulopathy. These pathological mechanisms lead to neuro-opththalmic complications like causes optic neuritis, papillophlebitis, papilledema, visual disturbance associated with posterior reversible encephalopathy syndrome, and vision loss caused by stroke. [1] Covid 19 associated intracranial hypertension is unusual while just one case report on associated acute vision loss.[2, 8, 9] This is the second case report of Covid 19 induced idiopathic intracranial hypertension leading to acute vision loss. This case report emphasises on keeping a high index of suspicion of idiopathic intracranial hypertension in Covid 19 positive patients as vision loss is inevitable. Intervention without any delay leads to complete recovery of vision as observed in present case although immediate postoperative surgical complication put up some glitches in the case.
Conclusion
Persistent headache in Covid 19 shouldn’t be ignored as it may be symptom of Idiopathic intracranial hypertension which is an unusual complication of Covid 19. Early diagnosis and prompt management in such cases gives best visual outcome.
Funding Sources
None.
Declarations
Conflict of Interest
The authors have no conflicts of interest to declare.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References
1. Tisdale AK Dinkin M Chwalisz BK Afferent and Efferent Neuro-Ophthalmic Complications of Coronavirus Disease 19 J Neuroophthalmol 2021 41 154 165 10.1097/WNO.0000000000001276 33935220
2. Ilhan B Cokal BG Mungan Y Intracranial hypertension and visual loss following COVID-19: a case report Indian J Ophthalmol 2021 69 1625 1627 10.4103/ijo.IJO_342_21 34011757
3. Markey KA Mollan SP Jensen RH Sinclair AJ Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions Lancet Neurol 2016 15 78 91 10.1016/S1474-4422(15)00298-7 26700907
4. Eftekhari S Westgate CSJ Uldall MS Jensen RH Preclinical update on regulation of intracranial pressure in relation to idiopathic intracranial hypertension Fluids Barriers CNS 2019 16 35 10.1186/s12987-019-0155-4 31767019
5. Wakerley BR Mollan SP Sinclair AJ Idiopathic intracranial hypertension: update on diagnosis and management Clin Med (Lond) 2020 20 384 388 10.7861/clinmed.2020-0232 32675143
6. Thakar A Aggarwal K Nasal endoscopic transsphenoidal optic nerve sheath fenestration for intractable intracranial hypertension with papilloedema-optimism with caution Neurol India 2020 68 61 62 10.4103/0028-3886.279661 32129245
7. Tarrats L Hernández G Busquets JM Outcomes of endoscopic optic nerve decompression in patients with idiopathic intracranial hypertension Int Forum Allergy Rhinol 2017 7 615 623 10.1002/alr.21927 28383199
8. Silva MTT Lima MA Torezani G Isolated intracranial hypertension associated with COVID-19 Cephalalgia 2020 40 1452 1458 10.1177/0333102420965963 33146040
9. Noro F Cardoso FM Marchiori E COVID-19 and benign intracranial hypertension: a case report Rev Soc Bras Med Trop 2020 53 e20200325 10.1590/0037-8682-0325-2020 32520086
| 0 | PMC9736703 | NO-CC CODE | 2022-12-14 23:29:53 | no | Indian J Otolaryngol Head Neck Surg. 2022 Dec 10;:1-4 | utf-8 | Indian J Otolaryngol Head Neck Surg | 2,022 | 10.1007/s12070-022-03303-x | oa_other |
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SN Bus Econ
SN Bus Econ
Sn Business & Economics
2662-9399
Springer International Publishing Cham
381
10.1007/s43546-022-00381-5
Original Article
Microfinance and women entrepreneurship development: evidence from Tunisia
Bel Hadj Miled Kamel [email protected]
12
1 grid.449644.f 0000 0004 0441 5692 College of Sciences and Arts Sajir, Shaqra University, Riyadh, Saudi Arabia
2 grid.7900.e 0000 0001 2114 4570 Laboratory of Management of Innovation and Sustainable Development (LAMIDED), University of Sousse, Sousse, Tunisia
10 12 2022
2023
3 1 1219 12 2021
22 11 2022
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
The main objective of this paper is to investigate the effects of microfinance on women’s entrepreneurship and empowerment, using national household data from Tunisia. We have employed Logistic Regressions and Fuzzy-set qualitative comparative analysis (fsQCA) to study the consequences of microfinance use.We find positive and significant effects of access to credit on women’s work, attitudes toward income increase, execution of the micro-projects, and schooling attendance. The results confirm the potential of micro-finance in women’s empowerment and Entrepreneurship Development in Tunisia, especially during COVID-19 pandemic.
JEL Classification
G21
L26
B54
Keywords
Micro-finance
Entrepreneurship
Women’s empowerment
issue-copyright-statement© Springer Nature Switzerland AG 2023
==== Body
pmcIntroduction
The coronavirus pandemic imposes not only a global health threat but also an economic shutdown in many countries especially in developing countries like Tunisia.Microfinance has since a long time ago assumed a basic part in destitution easing. It surrenders individuals a hand, engaging them to assist themselves for the way out of poverty. However, the role of microfinance within COVID-19 recovery efforts is even more prominent (Onwuka 2021). The award in 2006 of the Nobel Peace Prize to Muhammad Yunus has made it possible to widely publicize micro-credit as one of the effective tools for the fight against poverty, and even the empowerment of the poor and especially of poor women (Elizabeth 2007). Financing of women’s micro-enterprises is a priority of the microfinance financial system, simply because it is reported that women are the priority target of micro-credit institutions (Guérin and Servet 2003). Women entrepreneurs in developing countries, however, face several additional barriers to enterprise such as lack of access to capital, land, and business premises because asset ownership is male-dominated (Roomi 2005), and they usually require small loans for business start-ups (S. Mahmood 2011).
The basic measures of women’s empowerment are constructed mainly to capture the multidimensional nature of the situation of women (Mason 1986) concerning the main indicators, such as mobility, decision-making, and independence. It is part of the “gender and development” approach, which has taken over from the “integration of women in development.” Hashemi et al. (1996) argue that the most challenging task in conducting female empowerment assessments is to develop a valid and reliable measurement index, as accountability can be viewed from different angles.
Microfinance is a sector which concerns the arrangements for allocating small amounts of credit to low-income people, who are excluded from the banking system, and to positively influence their living conditions through the granting of loans that boost the activity of economic units. Women, who belong to a vulnerable social category, are the most affected by this phenomenon. They were often excluded from development programs. International circles then became aware of the need to reduce inequalities between men and women while considering their role in development plans and projects. This awareness will also promote a series of measures to improve their status in society. It was then that the concept of “integrating women into development” was launched (Hoffmann and Marius-Gnanou 2002).
During the 1970s, it was recognized that most development programs tended to ignore women’s specific problems. The concept of “women’s inclusion in development” gained recognition as the international community became more aware of the need to reduce gender inequalities and the importance of women in reproductive function and agricultural production. Empowerment may seem like an obvious solution. Microfinance institutions encourage women in developing countries to start micro-enterprises to overcome economic and social barriers. To integrate with development and combat poverty and exclusion, poor women have used the informal sector to create a source of income. In Tunisia, as in developing countries, tackling poverty, exclusion and inequality are critical objectives, and the informal sector plays a significant role in achieving these goals. However, this sector has grown with the emergence of microfinance or micro-credit. However, micro-finance appears to be a tool for emancipation and promotion of the status of women, with multiple objectives:
- Create a source of income for women and facilitate their financial independence.
- stabilize and professionalize their entrepreneurial activities.
- improve their status within the family.
- Increase self-esteem.
The impact of microfinance on women entrepreneurs and their micro-enterprises remains under-explored; however, the focus of the larger ongoing research project from which these initial findings are reported.
Very few studies have justified the relation between microfinance and entrepreneurship development in developing countries. Therefore, the question of whether microfinance improves or worsens entrepreneurship still merits further research. In short, there are significant gaps in the relevant literature on developing countries, including Tunisia, remains to be studied further.
A study by Chowdhury and Jahangir (2008) found that the microfinance program does not promote women’s entrepreneurship at the household level in Bangladesh, but it helps to increase the capital of already established businesses. However, Neeti et al. (2021) found that microfinance implementation tools— micro-credit, micro-savings, skill development, business assistance have the significant relationship with entrepreneurship development.
This study makes two main contributions in the existing literature. First, it extends previous studies by providing new empirical evidence of the effect of microfinance on Women Entrepreneurship development in Tunisia during COVID-19 pandemic. Second, to better understand this relationship, this study builds on complexity theory based on fsQCA. This approach has been widely used in recent years in various domains, because fsQCA controls correctly for endogeneity, noisy data and collinearity between independent variables (Ragin 2008; Woodside 2014). Using this approach, researchers have the opportunity to gain a deeper and richer perspective on the data.
The micro-finance or micro-credit system has emerged as the most appropriate instrument for financing the needs of low-income populations, particularly women. Since the Washington summit in 1997, micro-credit has had two main objectives: to reduce poverty or exclusion and contribute to promoting women's entrepreneurship. And this dual objective gives a new approach to microfinance institutions.
In Tunisia, the micro-credit system was implemented in March 1999 to promote national solidarity. Similarly, these micro-credit programs aim at the economic and social integration of the poor, creating sources of income, and improving the living conditions of the poorest.
The participation of Tunisian women in these programs is remarkable, and the rate of her participation rises from one year to another from 38% in 2005 to 57% in 2019 (African Development Bank 2019).1 This shows the Tunisian woman's awareness of creating financial autonomy to improve her living conditions and integrate economically and socially through the creation of productive projects.
Context of micro-credit in Tunisia
Despite the diversity of funding programs, a segment of the population remains away from the various funding instruments. This population could not turn to commercial banks because of the lack of guarantees and qualifications. In addition, it was necessary to create a financing instrument that would allow the poorest to take charge of themselves and have a source of income while settling on the land of their ancestors. This is how the micro-credit system was born in Tunisia, which enabled the poorest social stratum to fight against poverty and banish the assisted mentality.
Inter-Arab Enda
Founded in 1990, the NGO Enda Inter-arabe began its activity by supporting ecological and development projects. It introduced micro-credit in 1995 to reach people excluded from adequate financing. In 2015, after serving 500,000 clients, Enda evolved and decided to transfer its micro-credit activities to Enda Tamweel, the NGO focusing on supporting entrepreneurship. Over the years, it has become a reference institution in Tunisia and the Arab world in microfinance. Today, the two structures combine a tailor-made offer to contribute to the financial empowerment of marginalized populations, including women and youth and farmers and ranchers.
The non-governmental organization (NGO) Enda Inter-Arabe, has been awarded the rating «Alpha» by the rating agency "Micro Rate" for its financial performance and «Excellent» for its social performance. With the awarding of the "alpha" rating ("alpha + " being the maximum rating), Enda progressed and obtained one of the best ratings issued by the agency, among more than 450 ratings made on MFIs from Latin America Eastern Europe and Africa. The result of the study, dating from May 2010, confirms a continuous annual increase since the first rating in 2005.
It should be noted that, in the interest of transparency and improvement of its services, Enda has used rating agencies to evaluate its social and financial activities since 2005. With 130,000 active customers, a total of 358 million Tunisian dinars granted, and 630,000 loans awarded since 1995 (figures for May 2010), Enda called on the credit risk rating agency MicroRate, to perform the MFI's fourth rating to assess and optimize activities.
Thus, the rating obtained by Enda, qualified as excellent by the rating agency, is explained by the work undertaken on three axes: the diversification of the proposed products, the consolidation of the structure of Enda Inter-Arabe, and the reorganization of its portfolio. The rating agency explained that this result was justified by the particular effort made on sound management, securing diversified funds, and maintaining a relatively low-interest rate (compared to others rated by the agency).
Micro-rate also described Enda Inter-Arabe’s social outcomes as excellent. The agency based its assessment on the efforts made to protect clients and improve their services. Other factors were taken into account: sound financial management, which helped to support social activities in favor of clients but also of staff, the decentralization project, the development of new products that have effectively affected the target populations of micro-credit, and a strong culture of social engagement.
Tunisian solidarity bank (BTS)
The Tunisian Solidarity Bank (BTS) was created in 1997 on the initiative of the Tunisian State to finance young graduates of higher education and vocational training. She specializes in microfinance for the promotion of tiny enterprises (TPE). It has a capital of 60 million dinars (54% public and 46% private) with a shareholder base (more than 220,000 shareholders).
The BTS thus appears as a microfinance institution but borrows several characteristics of solidarity finance. Moreover, it is an independent institution. In fact, there is no intermediary between the bank and the entrepreneur. The BTS is an institution inspired by the Grameen Bank. This is one of the first experiences of implementing micro-credit practices (Manaï 2005). For this, BTS is the crucial experiment that can be studied. It finances projects not eligible for credit under the traditional banking system. The major innovation is its most extensive geographical and sectoral intervention. The target population is most widespread, with a particular interest for higher education graduates. The BTS is the first experiment that allows the poor to obtain small loans (without guarantees) that facilitates the exercise of an independent and income-generating activity (Benarous 2004). The question remains whether this institution respects the missions assigned to it to meet the objectives of its creation. To answer this question, we can rely on the analysis of the creative texts and internal documents of the BTS.
Moreover, the population sought by the BTS is mainly made up of young graduates and qualified professionals, inhabited by the idea of a profitable project and wishing to establish themselves for their own account but who have neither the means nor sufficient collateral to request credit from another bank.
Micro-credits granted by associations
Micro-credit is any credit aimed at helping economic and social integration. These micro-credits are granted to finance the acquisition of small inputs necessary for production or in the form of working capital. These credits may also be given to financing needs to improve living conditions." The associations do not have the right to distribute profits, and the reimbursement by the beneficiaries is made to the associations which keep the proceeds of interest and return the principal to the BTS. However, these associations are under the control of the Department of Finance and must maintain regular accounting. They shall also be subject to external audit if deemed necessary. If an association fails to fulfill its obligations, it may be subject to the withdrawal of its authorization to register loan contracts and value-added tax.
A maximum of 4000 dinars characterizes the micro-credit system in Tunisia for productive activities and 700 dinars for improving living conditions, a maximum interest rate of 5% per annum, and a maximum repayment period of 3 years with the possibility of deductibility. In addition, the amounts used for each association for granting micro-credit must be at least 95% of the resources allocated to the micro-credit credit, and the total amount of credit granted by each association for the financing of needs for the improvement of living conditions must not exceed 20% of the resources. Also, micro-credits are eligible for the FNG National Guarantee Fund (90% taken over by the FNG and 10% by the association).
Finally, the association receives an installation fee of 15,000 Dinars and an operating fee of 20 Dinars per file with a ceiling of 10,000 Dinars per year.
On this basis, we propose in the framework of this paper to identify the contribution of micro-credit to the capacity building of women in Tunisia. The literature review on the various works established on the relationship between microfinance and female entrepreneurship will be examined in the second section. The third section will report the empirical methodology adopted (sample presentation, test and comments). The conclusion, which is the subject of the fourth section, will take up the main lessons learned from the empirical study carried out in this paper.
Objectives of the study
The objective of this study is to examine the impact of microfinance on women's entrepreneurship and empowerment in Tunisia.i. To examine the role of microfinance on women's entrepreneurship development and empowerment in Tunisia.
ii. To examine the relationship between micro-credit, micro-savings, Payment deadline, Business sector, skills development programs, age and women entrepreneurship using microfinance services in Tunisia.
Hypothesis
The following null hypotheses were constructed and tested.
Hypothesis 01: There is a significant relationship between micro-credit and women entrepreneurial development in using microfinance services in Tunisia.
Hypothesis 02: There is a significant relationship between micro-savings and women entrepreneurial development using microfinance services in Tunisia.
Hypothesis 03: There is a significant relationship between age and women entrepreneurship using microfinance services in Tunisia.
Hypothesis 04: There is a significant relationship between skills development and entrepreneurship using microfinance services in Tunisia.
Hypothesis 05: There is a significant relationship between Business sector and entrepreneurship using microfinance services in Tunisia.
Literature review
Studies of Women's entrepreneurship and empowerment have been the subject of several studies. These studies were done either at the request of funding agencies or as academic work or to better target the use of funds to achieve specific social and economic objectives. Chatterjee et al. (2018) show that group-based financial services to micro-enterprises empower women borrowers and translate into economic upliftment. Neeti Mathur et al. (2021) found that microfinance implementation tools— micro-credit, micro-savings, skill development, business assistance have the significant link with entrepreneurship development. Attention has been paid to microfinance as one of the contributors to poverty reduction, women's empowerment, health, education, democratization, and environmental improvement (Mayoux 2001a; Chandrasekar and Prakash, 2010).
Existing studies on the impact of micro-finance on women's empowerment vary considerably in terms of the findings of these studies and the measures and indicators of women's empowerment used. In the existing literature, it is clear that there is no consistent measure of female empowerment; however, some indicators have always been seen as the most critical determinants of empowerment in most studies.
Some of these critical indicators used include mobility, political and legal awareness, economic security (Hashemi et al. 1996, Steele et al. 1998), decision-making capacity (Mizan 1993; Pitt et al. 2006, Steele et al. 1998), and increasing assets and controlling those assets (Goetz and Gupta 1996; Montgomery 2005). It is intended that targeting micro-finance programs toward women can empower them in various aspects of their lives. In addition, women are considered reasonable credit risks (Garikipati 2008) and are therefore less likely to abuse the credit they receive. While some studies show that micro-finance has developed at the confidence level of women by helping them increase their income opportunities (Hashemi et al. 1996; Pitt et al. 2006), others suggest that loans given to women in most cases end up with their husbands or under their control, which in the long run makes women even more vulnerable (Garikipati 2012; Rahman et al. 2009).
Women's empowerment was also associated with the length of time. Women were considered clients of MFIs. Above all, women's solidarity groups confirm that women's participation in micro-credit programs helps develop social networks while improving levels of access to the economy and financial resources. The establishment of these social networks allows women to know each other. It also increases the level of awareness and political and social inclusion among women (Bali et al. 2014).
In addition, with the support of IMFs (which includes micro-credit and training), women can gain better control over their financial assets, including their savings and income (Li et al. 2011a). This, in the long term, affects their participation in household decision-making (Hashemi et al. 1996; Pitt et al. 2006). Most MFIs aim to help women achieve financial independence. For example, it is said that women can become economically self-sufficient when they begin to take control of their financial assets (Li et al. 2011a). Anderson and Eswaran (2009) point out that with economic emancipation, there is an increase in female empowerment, usually highlighted in purchasing decision-making. In addition, Armendariz de Aghion and Morduch (2005) argue that micro-finance affects women's bargaining power and the level of resources available. Steele et al. (1998) often find that micro-finance has not significantly impacted women's decision-making capacity. Rahman et al. (2009) also found no significant impact of micro-finance on women's empowerment.
In this respect, although micro-finance positively affects women's empowerment and the accumulation of resources, existence, however, various dimensions of empowerment, some of which are hampered by the presence of social and cultural constraints. For example, Montgomery et al. (1996) argue that micro-credit programs exacerbate discrimination against women and reinforce gender inequality. In some cases, men are excluded from micro-credit programs, which reinforces inequalities, generating friction between men and women in the family. This is because men feel threatened. After all, they are convinced that they may be less favorable to women (see, for example, Mayoux 1999; Armendariz de Aghion and Morduch 2005).
Most studies are either examining the context of the environment in which microfinance operates or investigating the potential effect on macroeconomic variables, such as gross domestic product or inequality. There is some evidence to suggest that microfinance is indeed effective and beneficial to clients (Imai et al. 2010; Imai and Azam 2012), while other wide-ranging literatures suggest the opposite (Hulme and Mosley 1996; Hulme 2000; Copestake 2002; Hoque 2005; Shaw 2004; Nghiem et al. 2012). This study's interest is to clarify a theme that has not been much discussed, namely the direct link between microfinance and women's entrepreneurship and empowerment.
Research methodology
The data source
The population studied is the total number of women receiving micro-credit during 2021, 450 women from development associations in the Monastir and Sousse regions. It was based on the records of the requests for micro-credits made by these women to associations belonging to the Governorate of Monastir and Sousse.
For the research study, 450 respondents were selected. These respondents were beneficiaries of micro-credit associations and engaged in their own business, such as artisans, retailers, small-scale manufacturers, producers of agricultural products. The data used are based on 450 loan application files issued within these associations.
These data are qualitative and quantitative concerning socio-demographic characteristics and the borrowing of women.
Data processing is on the basis of basic statistics (number and percentage), logistic regression and Qualitative comparative analysis (QCA).
Our objective is to study the role of micro-credit granted by development associations of women entrepreneurship development in Tunisia.
Modeling methods
Binary logit model
The logistic function used is defined as:Zi=logpi1-pi
where "p" is the probability of entrepreneurship development, from the previous relation, we can have the probability p, that is:pi=Exp(Zi)1+Exp(Zi)
where Zi is the dependent variable. It represents the Development (or not) of the Entrepreneurship.
Entrepreneurship Development: Judged on the basis of the questions like increase in assets of business, family income, turnover of the business, number of buyers, and loan repayment capacity (Neeti Mathur et al. 2021). Table 1 presents all the independent variables of the model.Table 1 Independent variables
Variables Type Descriptor Concept
Socio-demographic variables
Age Numerical AGE Customer’s age
Education Dichotomous PRIMARY SCHOOL It takes the value of 1 if the beneficiary studied at only primary school and 0 otherwise
SECONDARY SCHOOL It takes the value of 1 if the beneficiary studied at secondary school and 0 otherwise
HIGH SCHOOL It takes the value of 1 if the beneficiary studied at High school and 0 otherwise
Marital status Dichotomous MARITAL It takes the value of 1 if the beneficiary is Marrie and 0 otherwise
Business sector Categorical ARTISAN 1 if the beneficiary is artisan
SERVICE 2 if the beneficiary is service sector
TRADE 3 if the beneficiary is trade sector
Micro savings Dichotomous MSAVING It takes the value 1 if there is an improvement of beneficiary’s saving level and 0 if not
Skill development Dichotomous SKILL.D It takes the value 1 if there is useful in improving the earning capacity of beneficiary’s and 0 if not
Loan variables
Amount of micro-credit Numerical AMOUNT Amount of loan (TND)
Payment deadline Numerical DURATION micro-credit payment deadline
TND is the currency of Tunisia
FsQCA
Qualitative comparative analysis (QCA) is a technique that is capable of bridging the gap between qualitative and quantitative analyses (Rihoux and Ragin 2009). This method has attracted significant attention on various domains, such as marking (Capatina et al. 2017; Meneses et al. 2016); tourism (Olya and Mehran 2017; Olya and Al-ansi 2018), finance (Isaksson and Woodside 2016; Vizcaíno and Chousa 2016) and economics (Arts and Koning 2017; Aloysius and Zhang 2019). The fsQCA (fuzzy-set Qualitative Comparative Analysis, or AQC) method, developed in political science by Ragin (1987) then democratized in management by Fiss (2009) and (2011). It allows both to take into account the specificities of the cases while adopting a holistic and rigorous approach, thus combining the advantages of qualitative and quantitative methods. The fsQCA method thus makes it possible to highlight the causal complexity underlying many phenomena in social sciences, i.e., phenomena subject to three sources of complexity (Vergne and Depeyre 2016; Ragin 2008). In our study, we used the fsQCA method to examine the robustness of the results found previously.
The fsQCA technique requires that all the variables be calibrated in fuzzy logic with values ranging from 0 to 1. Thus, all the variables will be transformed into continuous variables from 0 to 1, which define their membership level.
The formula for calculation of consistency and coverage can be calculated as follows:
Consistency (Xj≤Yj)=∑minXj,Yj/∑Xj
Coverage Xj≤Yj=∑minXj,Yj/∑Yj
Xj is the membership score in the set of causal conditions, and Yj is the membership score in the outcome condition.
Results and discussion
Results of binomial logit model
As we specified previously, the use of a logistic regression for the modeling of a binary variable is the most appropriate because of the nature of the studied endogenous variable. This technique makes it possible to predict the values taken by a discrete variable from a series of continuous or binary explanatory variables (Trabelsi M and Chichti J 2011).
This paper aims to study the induced effects of the participation of women entrepreneurs in micro-loan programs and test the impact of these micro-credits on entrepreneurship development. Table 2 summarizes the model estimation results using the STATA 14 software.Table 2 Results of binomial Logit model
Coefficients Standard error Student
AGE −0.067 0.042 0.10***
PRIMARY SCHOOL −0.469 0.681 0.491
SECONDARY SCHOOL 0.287 1.082 0.791
MARITAL −3.146 1.707 0.065*
TRADE −1.346 1.719 0.434
SERVICE 3.758 2.447 0.125
MSAVING 0.154 0.070 0.027**
SKILL.D 2.059 1.118 0.065*
DURATION −1.457 1.097 0.184**
AMOUNT 0.006 0.003 0.023**
Cost 10.622 4.458 0.017**
Entrepreneurship development
*Significant at 10% level
**Significant at 5% level
***Significant at 1% level
This result indicates that the variables Amount of Micro-credit (AMOUNT) and "Skill development" are positive and statistically significant. This result is evident since the more significant the benefit, the better the situation. On the other hand, we find that the age variable is negative and statistically significant, indicating that micro-credit has a better effect for young women entrepreneurs for creators in the realization of their projects.
The second variable, "DURATION," is significant at the 5% threshold, but its coefficient is negative, implying that the higher the monthly payment, the more the tendency toward the probability of project defeat. So, to ensure that the situation of an entrepreneur (woman), who has just applied for a micro-credit, will be improved after indebtedness, we must think about reducing the monthly payments or tolerating more in the amounts granted. Based on the data collected, it was noted that there is a difference between the amount requested and the amount awarded in most cases. So, if the concern of those in charge is to improve the situation of a person living in precarious situations, we must tolerate the amounts granted, and why not consider going further to the ceiling. At the 10% threshold, the only family status variable determines the characteristics of women and, more particularly, the variable "MARITAL." The single woman does not have much charge by comparing her with a married woman who has children. So the credit obtained improves the situation of a single. The reason for indebtedness variable for « MSAVING» is also significant at the 10% threshold, which implies that the micro-credit obtained improves the beneficiary's standard of living.
For the department, variable for "Education" is not significant. This comes back, perhaps, to the follow-up carried out with the women beneficiaries. The amount obtained may not result in a period of one year. Therefore, it is not possible to know if the women beneficiaries, for reasons of education, are satisfied. Moreover, and for greater relevance, follow-up should normally be done after loan payment and not within one year. This represents a limit to our empirical study. Another limitation in our research is that observing situations after indebtedness is not a direct observation on the ground. It was a telephone report in which the women concerned could hide the truth and may not give accurate information.
In conclusion, and from what we have obtained from the results, it must be deduced that the micro-credit policy has given the funded women an opportunity to get out of precarity and enable them to improve their business.
Results of fsQCA
Table 3 presents the causal configuration in predicting low and high scores of women entrepreneurship development in Tunisia.Table 3 Causal recipes of entrepreneurship development
Models for predicting high and low score of entrepreneurship development Raw coverage Unique coverage Consistency
Entrepreneurship development = f(SKILL.D, AMOUNT, DURATION, MSAVING, SERVICE, AGE)
M1: ~ SKILL.D * ~ AMOUNT * ~ DURATION * MSAVING * SERVICE * ~ AGE 0.131 0.131 0.773
Solution coverage: 0.131
Solution consistency: 0.773
~ Entrepreneurship development = f(SKILL.D, AMOUNT, DURATION, MSAVING, SERVICE, AGE)
M1 * ~ SKILL.D * ~ AMOUNT * ~ DURATION * MSAVING * SERVICE * ~ AGE 0.228 0.053 0.782
M2: * ~ AMOUNT * ~ SKILL.D * ~ DURATION * MSAVING * SERVICE* ~ AGE 0.527 0.196 0.818
M3: ~ SKILL.D * ~ DURATION * MSAVING * SERVICE* ~ AGE 0.355 0.027 0.756
M4: * ~ AMOUNT * ~ DURATION *MSAVING * SERVICE * ~ AGE 0.228 0.07 0.779
Solution coverage: 0.646
Solution consistency: 0.754
Complex solution, * represents “and”, and ~ represents “negation”
The main objective of this estimate is to examine the relationship between micro-credit, Micro-saving, skills development programs, micro-credit payment deadline, Business sector and age of beneficiaries of micro-credit allocated by MFIs (microfinance institutions) in Tunisia.
One consistent and sufficient causal recipe explained the Entrepreneurship Development (coverage: 0.131, consistency: 0.773). The model (M1) suggests that females with high amounts of micro-credit, low repayment period (DURATION), and working in service sector have a high score of Entrepreneurship Development. These factors have a positive effect on opportunity for entrepreneurial activity. These results are in line with Karlan and Valdivia (2011) and Neeti Mathur et al. (2021), who concluded that microfinance has had a positive impact on entrepreneurship development.
The second model (M2) suggests that young married female working in service activity which low amount of micro-credit and high micro-savings, lead to have a high score of Entrepreneurship Development.
The third model indicates that older, less-educated female working in service sector, who benefited from low amount of micro-credit and useful in improving the earning capacity, results in increase in assets of business and loan repayment capacity.
Model 4 advises that female working in service benefited from low amount of micro-credit and less deadline of repayment lead to the improvement of the assets of business which confirms the significant relationship between micro-credit and entrepreneurial development in using microfinance services in Tunisia.
Conclusion and policy implications
Throughout this chapter, an attempt was made to provide an overview of the Tunisian experience with micro-credit. The evolution of microfinance and Women’s entrepreneurship in Tunisia was the subject of two first sections.The last section relates to an empirical investigation: the study of the results of a small survey carried out among certain women receiving micro-credit from these development associations. The main objective of this study is to investigate the effects of microfinance on women's entrepreneurship and empowerment in Tunisia It has been found that microfinance implementation tools— micro-credit, micro-savings, skill development, Business sector have the significant relationship with entrepreneurship development. Micro-finance has spread remarkably, thanks to the proliferation of agencies that help and finance people with low income. Its emergence has been fostered by information from informal finance and the desire to institutionalize everyday practices, by the need to integrate the financial excluded, and by broadening the concepts of sustainable development relating to decent living conditions and the participation of women. Tunisia's microfinance experience is rich and has benefited from the arrival of new players in the 1990s. Micro-credit policy is the main step in this development process. In collaboration with other organizations, such as NGOs and specialized financing funds, the Tunisian Solidarity Bank plays a crucial role in applying for micro-finance projects, entrepreneurship development and improve the living conditions of households. The credits are effectively accessible to the people or the gatherings to begin the business, which prompts new employment opportunities, which address the joblessness issue. Microfinance works at a fundamental level by providing support, it works without loan collateral and provides skills development assistance to marginalized rural people.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Ethical approval
Ethics approval was not required for such study.
Informed consent
Informed consent was obtained from all individual participants included in the study.
1 AFRICAN DEVELOPMENT BANK, 2021. FINANCIAL SECTOR MODERNISATION SUPPORT PROGRAMME II—(PAMSFI II). TUNISIA.
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| 0 | PMC9736707 | NO-CC CODE | 2022-12-14 23:29:53 | no | SN Bus Econ. 2023 Dec 10; 3(1):12 | utf-8 | SN Bus Econ | 2,022 | 10.1007/s43546-022-00381-5 | oa_other |
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J Community Genet
J Community Genet
Journal of Community Genetics
1868-310X
1868-6001
Springer Berlin Heidelberg Berlin/Heidelberg
624
10.1007/s12687-022-00624-w
Research
Identification of psychoeducation needs and an intervention response for pre-symptomatic Huntington’s disease
http://orcid.org/0000-0002-5592-7730
Gluyas Cathy [email protected]
1
Mottram Lisa 1
Gibb Rosanne 1
http://orcid.org/0000-0001-9637-8590
Stout Julie 2
1 grid.477004.0 0000 0000 9035 8882 Statewide Progressive Neurological Disease Service, Calvary Health Care Bethlehem, 152 Como Parade West, Parkdale, Victoria 3195 Australia
2 grid.1002.3 0000 0004 1936 7857 Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Clayton, Victoria 3168 Australia
10 12 2022
19
7 7 2022
30 11 2022
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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
People who are aware that they are gene-positive for Huntington’s disease (HD) may face an array of personal, relationship, social, financial and employment challenges prior to the onset of the disease. These challenges have been associated with increased psychological problems such as anxiety and depression. Information and support for people with pre-symptomatic HD is indicated, but there is a scarcity of research and service models to inform psychological interventions. We trialled an intervention strategy involving psychoeducation forums designed specifically for pre-symptomatic HD. In phase I of the study, we asked people with pre-symptomatic HD to identify their uppermost needs for information. Phase II involved the delivery of this information via a series of forums. The forums also provided an opportunity for interaction among the participants. Three forums were attended by 88 people with pre-symptomatic HD and significant others. Analysis of post-forum feedback questionnaires indicated high levels of satisfaction with the forums’ structure, content and relevance, and notably, the pre-symptomatic specificity of focus. Additional qualitative data from recordings of forum discussion groups revealed that participants greatly valued the opportunity to meet similar others, and share their concerns and strategies for addressing these concerns. There was an abundance of requests for more forums on a wide range of relevant topics. It is recommended that this model of intervention may be of value for implementation in other HD services or community groups.
Keywords
Huntington’s disease
Premanifest
Pre-symptomatic
Psychological
Psychoeducation
Intervention
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pmcIntroduction
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease, characterised by a triad of cognitive, psychiatric and motor symptoms that progress over time (Reiner et al. 2011). Pre-symptomatic HD is the period of time prior to the development of HD symptoms in HD gene-positive individuals (Duff et al. 2008). With predictive testing available at age 18 (CGE 2017), and an average disease age onset of 40 (Myers 2004), a gene-positive individual could spend a significant portion of their life in the pre-symptomatic period. The name ‘pre-symptomatic’ can give a false impression of a time untroubled by the disease. While the actual disease symptoms may not yet have manifested, this period may in fact pose significant personal, social, psychological, work and familial HD-related challenges. These may develop even prior to having a gene test and can include a sense of hopelessness, powerlessness and self-restriction of life choices, and then further adverse psychological effects may develop subsequent to the gene test, regardless of the test result being positive or negative (Tilleras et al. 2020). For those who are gene-positive, they then face living with uncertainty about the timing of illness onset and a foreshortened lifespan; hypervigilance for early signs of the disease; the impact of being gene positive on personal identity, relationships and reproductive choices; the burden of care of a parent with HD; the widespread lack of understanding about HD and societal barriers to openness in discussing these issues (Ho and Hocaoglu 2011; Timman et al. 2004). Research has documented an increased risk of psychological difficulties in the pre-symptomatic period, including anxiety, hostility, interpersonal sensitivity, obsessive-compulsiveness, irritability, depression and suicide risk, with indications of intensified symptoms prior to the onset of manifest disease (Duff et al. 2007; Honrath et al. 2018).
Despite the breadth and depth of these challenges, there has been minimal research into the range of support needs specific to people with pre-symptomatic HD. One significant exception is a large international study by Braisch et al. (2016) that surveyed 683 young adults from HD families, of whom 54% were at risk of HD but not tested, and 28% were confirmed as gene positive. The findings showed that aside from general information about HD and predictive testing, the majority of participants lacked vital information about and support with multiple important issues. These issues pertained to legal concerns, lifestyle recommendations (exercise, diet, stress management), caregiving, relationship issues and knowing how to talk with their children about HD. This lack of information and support suggests a need for intervention programs specific to pre-symptomatic HD, and these also appear lacking in the literature.
Only three intervention studies were identified in a literature search focussed on pre-symptomatic HD needs (A’Campo et al. 2012; Eccles et al. 2020; Stopford et al. 2020). A’Campo et al. (2012) conducted an 8-week psychoeducation and cognitive behaviour therapy program to improve coping skills in HD and created a separate group for pre-symptomatic individuals. Unfortunately, there was a large drop-out rate and limited evidence of positive impact. In a second study, Eccles et al. (2020) explored the feasibility of an 8-week mindfulness-based cognitive therapy group program. Participants found the program helpful, with reductions in stress and improvements in some elements of mindfulness noted. A third study assessed group narrative therapy for a small sample (n = 6) of people with pre-symptomatic HD, with results indicating that participants found the experience normalising and de-isolating (Stopford et al. 2020). Recently, Zarotti et al. (2020) have made a ‘call to arms’ encouraging further psychological intervention research for people across the clinical trajectory of HD. They highlighted that the mental health benefits of psychological interventions are likely to be greatest for those in the pre-symptomatic, prodromal and early stages.
The present study aimed to address the identified need for improved access to information and support for individuals with pre-symptomatic HD. A consumer-informed approach was adopted in developing the psychoeducational intervention, in line with the Australian health-care policy impetus to partner with consumers in the planning, design and evaluation of health initiatives (ACSQHC 2017). The benefits of consumer-driven research include improvements to the patient-centredness of research design and outcomes, better recruitment and retention rates, greater relevance of the research and greater accountability to and empowerment of the consumer group (Harrison et al. 2019). We aimed to maximise the relevance for people with pre-symptomatic HD, so began with a survey of the information and support needs that are specific to this consumer group. Based on the survey results, we then developed and delivered a psychoeducational intervention that targeted the top consumer-identified needs. Participant experiences and feedback about the intervention were documented in order to evaluate the program.
Methods
The study comprised two phases. In the first phase, we surveyed people with pre-symptomatic HD about their perceived needs for information and support relevant to HD. In the second phase, we responded to the survey data by developing and delivering a series of three targeted psychoeducation and support forums (Fig. 1). Fig. 1 Study design
Phase I: Psychoeducation needs identification
Potential participants for this study phase included individuals with pre-symptomatic HD who consecutively attended routine consultations with an HD nurse (LM, second author) over a one-month period at the Statewide Progressive Neurological Diseases Service (SPNDS), Calvary Healthcare Bethlehem. The SPNDS provides assessment and treatment for a range of progressive neurological diseases including HD, using the skills of a multidisciplinary team comprising neurologists, psychiatrists, nurses and allied health clinicians. Information about the study was provided at the HD nurse consultation, and those who agreed to participate provided written informed consent. Twenty-two individuals agreed to participate and were sent an online survey.
The survey was developed by the authors. It requested that respondents indicate their preferences for information about a range of possible topics, including many that are frequent subjects of inquiry and interest during phone and clinic consultations, such as HD research updates, anxiety about symptom onset, and disclosure obligations. The survey also provided scope for respondents to add their own additional topics of interest. Respondents were invited to nominate their top three information preferences. We also asked four scoping questions exploring participants’ perceived level of knowledge about HD, their frequency of communication with family and friends about HD and their interest in meeting others with pre-symptomatic HD. They were asked to respond to these four questions on a 4-point Likert rating scale (low/minimal/moderate/high). A final question asked participants whether they would be interested in attending information and support forums.
Phase II: Psychoeducation intervention
Topics that were rated as of greatest interest to consumers in Phase I were chosen for the intervention phase (Phase II). Phase II provided a series of information forums, addressing these top topics of interest and inviting those with pre-symptomatic HD that attend the SPNDS. Experts in the identified specialist topics were sourced from within and outside our service and were invited to present at the relevant forum by the research team. The first two forums occurred bi-monthly over the subsequent months. The final forum was delayed due to the onset of COVID-19 pandemic restrictions and was ultimately delivered via videoconference.
For each of the forums, we sent an initial email invitation to people with pre-symptomatic HD who attend our clinic. Those who replied with an ‘expression-of-interest’ response were sent additional information, including consent details and advice that the forums would be audio recorded. Further to requests from respondents, attendance was opened to significant others including family members or partners. For each forum, a completed consent form was necessary for the provision of an entry ticket.
The structure of the forums included a 40-min presentation on the selected topic, followed by a 10-min refreshment break, small discussion groups for 30 min and finally re-joining the larger group for closure and completion of the Forum Feedback Questionnaire. The written questionnaire used in the first two forums was translated into an online version for the third (videoconference) forum. The alteration to videoconference delivery for the third forum meant that while no small discussion groups occurred, participants were still able to ask questions and make comments. These were communicated verbally (via a moderator) and in writing (via chat box) during and after the course of the presentation.
The Forum Feedback Questionnaire consisted of two sections. In the first section, we asked the participants to rate their satisfaction (low/mild/moderate/high) with five aspects of the forum. Specifically, ratings were sought in relation to (1) the quality of the speaker’s presentation, (2) the speaker’s responses to comments and questions, (3) the opportunity to meet others in a similar situation (first two forums only), (4) their perceived increase in knowledge of HD and (5) the relevance of the content to their needs. We analysed and summarised these results using descriptive statistics.
The second section of the Forum Feedback Questionnaire inquired about participants’ experience of the forum and included questions about the following: the choice to restrict the focus to pre-symptomatic HD, the timing and length of the forum, the best aspect of the forum, barriers to attendance and additional topics of interest for potential future forums. We obtained further qualitative data from the audio recordings of the small discussion groups that occurred in the first two forums. Each small discussion group was facilitated by a member of the SPNDS HD team. They were semi-structured, with guiding questions that were derived from the presentation. Participants were invited to reflect these questions and how the topic related to their lived experience. The audio recordings were transcribed and subjected to thematic analysis by the first author. A modified phenomenological approach was followed, which involved reflecting on the meaning of the transcribed text responses, paying attention to the similarities and differences in experiences, summarising descriptions of the text in a table, identifying core themes and providing examples of the themes (Smith 2003).
This project received ethics approval from the Calvary Health Care Bethlehem Research Ethics and Ethics Committee (HREC number 19041801).
Results
Phase I: Psychoeducation needs identification
Fifteen individuals responded to the online survey out of the twenty-two that had agreed to participate (response rate: 68%). The issues that were nominated as of greatest interest included (1) HD research (67%); (2) preparing for financial and legal issues such as superannuation, insurance and employment discrimination (53%); (3) the value of exercise (47%); (4) managing fears of future HD (47%); (5) family care pressures (33%); (6) an update of HD knowledge (27%) and (7) dealing with disclosure and stigma (20%). Other topics raised by respondents included reproductive choices, differentiating normal ageing from HD progression, HD treatments, access to assisted dying, impact of diet and alcohol, how to delay disease onset and quality of life at the different stages of HD. The top four topics were selected to be covered in the three planned forums.
In relation to the four scoping questions about HD knowledge and communication, the modal response for each issue was as follows: ‘moderate’ for their current level of knowledge about HD (n = 10), ‘minimal’ for their likelihood of discussing HD with friends (n = 8), ‘moderate’ for their likelihood of discussing HD with family (n = 9) and ‘minimal’ for the importance to them of meeting others with HD (n = 6). Ninety two per cent indicated interest in attending the forums.
Phase II: Psychoeducation intervention
The top four topics identified in phase I were chosen as the focus of three psychoeducational forums. Topics and presenters were:Forum 1— The Value of Physical Activity and Managing HD Future Fears: senior clinicians in physiotherapy and clinical psychology from SPNDS
Forum 2— HD Research: an international specialist in the cognitive neuroscience of HD
Forum 3— Preparing for Financial and Legal Issues: a lawyer and specialist in financial issues pertaining to genetic and terminal illness, together with a senior consultant nurse from the HD service at the SPNDS.
Eighty-eight people participated in at least one of the three forums: n = 20 (15 HD, 5 significant others) at forum 1, n = 31 (21 HD, 10 significant others) at forum 2 and n = 37 (32 HD, 5 significant others) at forum 3. Eight additional people provided prior consent but did not attend forums, with reasons provided including work or child-care demands. Of the 88 attendees, 72 (82%) completed the Forum Feedback Questionnaire relating to the forum that they attended. In summarising ratings across all three forums, responses indicated predominantly moderate or high satisfaction with the content of the speakers’ presentations (90% participants) and with their responses to questions posed by participants (95% of participants). Satisfaction with meeting similar others was rated as moderate or high by 88% of participants. Satisfaction that the forum increased HD knowledge was rated as moderate to high by 57% of participants. The relevance of the presentation to their individual needs was reported as moderate or high by 87% of participants.
Regarding logistical aspects of the forum, the majority of participants (80%) indicated support for the 1.5-hour length of the forum, with a minority (16%) of those attending the first two ‘in-person’ forums commenting that they would have preferred a longer time allocation for the small group discussion. There was overall endorsement for conducting the forums after business hours to allow participants to attend after work. The venue of the SPNDS for the first two forums was generally supported, although a minority of participants indicated that the distance from their home was a disincentive. The videoconference format of the final forum was identified as beneficial for many, due to the convenience of not needing to travel to attend. Participants from rural or regional Victoria noted that they were only able to attend the final forum due to its availability via videoconference. Some participants stated that they missed the opportunity for ‘in-person’ interactions in the third forum. In the final forum, participants were asked to indicate their preference for forum delivery format, and two-thirds stated a preference for the videoconference over the in-person format. In addition to travel, some other barriers to attendance were identified, including securing child-minding and anxiety about meeting others with pre-symptomatic HD for the first time.
A wide range of topics were suggested by participants for future forums including peer support, support for partners, strategies for disclosing about HD with friends, risks of disclosure at work, family planning and reproductive technologies, HD treatments, how meditation might help, diet and gut health, how to delay onset, how to prepare for becoming symptomatic, couple relationship issues, caregiving for HD relatives, discussing HD with children, dispelling myths about HD, how to identify early symptoms and creating ways of connecting with other pre-symptomatic people (e.g. Facebook groups, camps).
The text responses from the Forum Feedback Questionnaires and the transcribed audio recordings of small group discussions were collated and classified into two general categories: the first involved comments specific to the structure and content of the forums, and the second involved comments pertaining to participants’ experience of pre-symptomatic HD. Thematic analysis of these two categories of comments can be seen in Tables 1 and 2.Table 1 Forum structure and content: themes and exemplar quotes
Theme Quotes
Context conducive to comfort - friendly and comfortable environment to discuss tough issues
- it flowed easily and was good to just chat
- I felt very comfortable
- I could be as interactive or as private as needed
Value of clear, current and accurate information - info provided seemed very relevant and up to date
- knowledge is key
- having the most up-to-date information
- very informative…educated me in ways I didn’t foresee
- knowledge is power
- gives me a clear idea of what to expect in the future
Availability and accessibility of research and clinical specialists - (Forum information is) …better than to research it on the internet and being depressed by it
- informed of the latest research developments
- having those presenters address us, with all their knowledge
- having an expert available to speak with us about relevant information
- presenter was eager and happy to answer questions without notice
- very helpful and empowering, especially for people unfamiliar with navigating health and financial bureaucracy
- access to people in the industry is very important to me
Positive energy infusing the Forums - the general atmosphere and discussions were positive and reassuring
- beneficial with respect to hopefulness
- just getting another dose of positive energy from the speakers
- encouraging and targeted in its proactive approach
- gave people hope
- gives me hope and confidence
- (research) is really positive…fantastic!
Forum specificity for pre-symptomatic HD - I’ve never seen a forum specifically for pre-symptomatic HD before
- people with pre-symptomatic HD probably don’t get a lot of airtime and support, so it’s a rare opportunity to share with those in the same boat
- it was better than attending forums that include symptomatic people as it removes some of the stress that dealing with symptoms brings
- it allows a franker discussion
- very useful going through the ‘more-relevant-to-my-situation’ type (of) questions
- great to hear how others manage the pre-symptomatic stage
Confronting to attend - a bit nervous at first
- scary, but nice
- it makes my HD more real
- I find it hard talking in front of other people
- it’s much easier not to think about it
Table 2 Pre-symptomatic HD experience: themes and exemplar quotes
Theme Sub-theme Quotes
The isolation of secrecy, and the value connecting with similar others Keeping HD secret and not talking about it with others - (my family do) … the whole ‘head-in-the-sand’ thing
- it was this dirty secret
- even within my own family, relatives didn’t talk with relatives…it seemed like such a shame thing
- there is still this ‘hush-hush’
- it can be quite lonely…(with)…no other family members to talk about it
- on the train…people…don’t know what’s going on genetically inside us
- I just can’t wait for the day that it is completely out there
Meeting others who are pre-symptomatic provided a sense of community - great to meet others going through the same experience
- beneficial to mix with people who are going through similar life experiences
- prefer these type of group sessions…you feel a part of a community, not alone
- a wonderful chance to talk with other HD people and share the journey
- we are visible, and we have hope
- we’re not alone on this journey
- seeing that I am not alone, but that is kind of sad too
- I had never met anyone with HD before
- it was really important to see that there were people just like me
- good to hear from others in the same situation without being family members
Sharing concerns specific to pre-symptomatic HD Attribution of normal behaviours to HD symptoms - they are watching everything they do…. If a cup drops …or anything…. that happens to normal people, they apply this to (HD)
- I can’t remember something … (so) I’m like mum (with HD)
Uncertainty how HD will manifest - a lot of unknowns… when it kicks in, what symptoms might you get?
Reproductive and family planning considerations - I’m going through IVF. I had PDG testing on my…7 embryos and…5 had HD; we were so unlucky
- do you just take the risk that there is going to be a cure for your child?
- IVF is an emotional rollercoaster anyway and then you factor in that whole other (HD PGD) level
- our government should be supporting us as PGD is really expensive
Worry re children - is she going to get it?
Hope research identifies an effective treatment - I was a bit disappointed…. expecting to hear more progress
- just how far away is (an effective treatment) though?
- research update was reassuring
- helpful staying informed of the latest research developments
Variability in approaches to and experiences of gene testing - I just found it liberating, even though I didn’t get the result I wanted
- such a relief I don’t have to worry anymore because I knew the answer
- I found mine (gene test result) devastating
- I immediately…felt this lift; OK, you can move on
- not knowing was 100 times worse than knowing for me
- wanted to know if it is, then my path is this way, and if it is not, there is another way
- my children don’t want to get tested… (and have not told their children) …but some are in relationships…and you never know what is going to happen
Sharing helpful strategies Ideas for increasing physical activity - I started walking an extra train stop…I do it in the morning, as in the evening I just want to get home and have a wine
- suggested 5 times a week for 30 min
- take the stairs instead of the lift
Telling children - there are booklets available…for adults to be able to talk to children
Ways of coping with the emotional challenges - reinforce how to maintain a healthy attitude to HD
- it was a lot of denial… being scared of the unknown
- counselling… helped a lot
- important not to over-think
- (with a CAG repeat of 39) don’t catastrophize what may or may not occur
- I (avoid) the ‘should’ word
Preparing for future financial issues when unable to work - make sure we are going to be OK when the time comes, to retire in a comfortable way
- has got me thinking about my super and if I need to look over it or change it
- learning new things about future economic pathways … giving us options
- gave me a clear idea of what to expect in the future
The themes shown in Table 1 were derived from participants’ comments about the structure and content of the forums. Themes included the forums’ positive, hopeful energy; the comfortable setting; the security of knowing that information was current and reliable, sourced from HD specialists and focussed singularly on their needs, as a pre-symptomatic group. Some comments pointed to confronting aspects of attending a forum.
Table 2 highlights themes that were significant to the lived experience of people with pre-symptomatic HD, derived from their questionnaire and discussion comments. These themes include their sense of isolation and stigma, their overwhelming gratification in meeting similar others, feeling able to discuss significant shared challenges and their adaptations and strategies for living with these challenges.
Discussion
In this two-phase consumer-focused research, information forums that met key areas of identified need were found to be strongly valued by people with pre-symptomatic HD. In phase 1, the information needs identified by those with pre-symptomatic HD related to how to prepare now for a future that is likely to be affected by HD (e.g. financial and legal preparation), factors that may delay or mitigate HD onset (e.g. pharmacological research, impact of physical activity) and strategies to deal with their current emotional challenges (e.g. managing fears, stigma, caring for HD family members). As in the study by Braisch et al. (2016), basic knowledge of the disease and predictive testing were not paramount. Participants may have felt sufficiently well-informed about these areas.
In phase 2, forums based on topics of greatest interest (identified in phase 1) were delivered. These forums attracted strong attendance and were positively evaluated in participant feedback data. The structure of the forums, the selection of speakers with specific HD professional or research experience, the actual content of the presentations and the quality of speakers’ responses to participant questions were all rated highly. Forum acceptability was increased by its familiar location, being timed in a way that minimised interference with participants’ work or family lives, and the availability of small group facilitated interactions with people who faced similar issues. Participants expressed great appreciation of the rare opportunity for sharing their experiences, their common HD challenges and strategies they used to deal with these issues. Indeed, this specificity of the forums to pre-symptomatic HD was frequently highlighted and valued in the written and audio-recorded responses.
The forum feedback in phase 2 provided an opportunity for participants to expand on the topics of interest already identified in phase 1. These ranged from more information about reproductive choices, to ways of improving physical and mental health factors that may impact HD onset or course (diet, alcohol and other drugs, stress management), assisted dying legislation, strategies for communication with family and significant others about HD, caregiving for HD relatives, ways to get support with maintaining intimate relationships, preparing for becoming symptomatic, identifying early symptoms and increasing peer support connections, including via social media. These topics align with, and further develop, the information and support needs identified in two other studies. Ho and Hocaoglu (2011) found a predominance of social (stigma, family), emotional (future anxiety) and legal issues were most significant to those in the pre-symptomatic stage of HD. Stigma and genetic discrimination in the domains of insurance, employment and relationships were pinpointed as a concern by 46% people at risk for HD in the large international RESPOND-HD study (Erwin et al. 2010). These extensive needs for support and information in a wide range of topics present worthy directions for future forums for people with pre-symptomatic HD.
Valuable insights into the lived experience of people with pre-symptomatic HD were revealed during the forums. Meeting similar others and sharing their lived experiences appeared to facilitate a normalising and supportive process. Participants spoke of a longstanding familial and social imperative to maintain secrecy about their gene-positive status, commonly associated with a sense of shame and stigma. The forums’ unique opportunities for disclosure in a safe space that was specific to their needs seemed to generate a powerful and welcome sense of connection and positive identification, facilitating a potential community antidote to broader societal stigma. They shared some of their on-going concerns, such as uncertainty about when and how symptoms will manifest, an anxious tendency to attribute normal cognitive or motor errors (such as forgetting or dropping something) to HD early symptoms, concerns about whether their children might be affected and a yearning for research to discover effective treatments. Great variability was seen in their emotional response to learning of their gene-positive status, ranging from devastation to relief (from previous uncertainty). Strategies for dealing with their shared concerns were also discussed by participants, including approaches to maintaining their emotional health, regular physical activity, use of online resources and preparing for future financial security. That these coping strategies were recommended by people with authentic lived experiences was likely to be quite compelling for participants. The range of significant psychological challenges and potential coping strategies described by participants with pre-symptomatic HD certainly warrants further research attention.
Participant descriptions of the sense of unity and hope generated within the forum discussion groups provide an initial indication of the potential for such interventions to have positive psychological effects. This contrasts with a pervasive belief that psychological symptoms associated with HD are solely biologically determined, even in pre-symptomatic stage (Theed et al. 2018). It is likely that this longstanding belief has been a disincentive to research exploring psychological interventions. A recent article by Zarotti et al. (2020) has challenged the belief. They have strongly encouraged both individual and group-based psychological intervention research into anxiety, depression, improving coping strategies and quality of life, especially amongst those who are pre-symptomatic. Future research is needed to explore whether regular access to the type of group-based information and support sessions described in this paper may have a positive impact on psychological problems associated with pre-symptomatic HD.
Another important aspect of this study to consider is the degree to which it was guided by consumer involvement. The identification of topics relevant to those with pre-symptomatic HD informed the intervention, and this consumer group provided feedback about their experience of the intervention. That 87% of participants regarded the forum intervention as closely aligned with their individual needs affirmed the value of consumer involvement in developing the project. Our approach adhered to the guidelines for consumer involvement in health research (NHMRC 2016). Consumer involvement is vital for increasing the relevance of research for pre-symptomatic HD consumers, as well as instilling greater confidence in and engagement with the resulting interventions. This project has provided consumer-generated recommendations for future topics and consumer feedback that can inform the structure and delivery of future forums. There are multiple opportunities for even more extensive consumer involvement to be developed, including more collaboration between people with pre-symptomatic HD and the research team in improving the design and running of future forums, in evaluating their efficacy and in disseminating the research results, possibly through social media that is developed by the consumer group.
In addition to increasing the input of consumers, the participants had suggestions for other improvements to the forums. A number of participants in the first two forums noted that they would have preferred more time in the small discussion groups. Some described anxiety about attending the forums. These individuals may require some extra targeted support to facilitate their well-being during forums. Participants recommended that accessing the forums via videoconference should be routinely offered, allowing the involvement of those who live at geographic distance or who have other care responsibilities. A comparison of the experience of in-person versus videoconference delivery of forums would be of future interest. Developing options for break-out discussion groups within videoconference forums may increase the possibility of peer support in that modality. Independent analysis of the experience of the pre-symptomatic individuals compared with their significant others would also be valuable. The study was restricted to those who were pre-symptomatic and aware of their gene status and did not include those who are at risk of developing HD but have not yet had predictive testing. This is an important group that also have unique needs for information and support and should not be overlooked. Understanding the reasons for not attending forums is also important: Are non-attenders fearful, disinterested, avoidant, unavailable or not see forums as relevant? What features distinguish those who attend information and support forums from those who do not? Finally, the present study drew on the experience of pre-symptomatic individuals who attended a single, large, government-funded clinic. Their experience may differ from those who attend, for instance, private-health practitioners, and as such, the results may be limited in their generalisability.
In summary, a consumer-driven research focus allowed the issues and information needs of greatest significance for pre-symptomatic HD to be addressed in a series of forums. This enabled a stigmatized and silenced group to discover a sense of community, shared concerns, helpful strategies and support and reduce their sense of isolation. They received up-to-date information that potentially empowered them with knowledge that is relevant to current and future decision-making and quality of life. Opportunities for this model to be developed should be encouraged, with many more key issues — already identified in this study — to be addressed to meet the needs of the pre-symptomatic HD group.
Acknowledgements
Nicholas Jackson and Roxanne Maule provided invaluable support with the logistics involved in conducting the forums. Dr. Fiona Fisher, Marie-Claire Davis and Dr Sarah Velissaris assisted with the preparation of the manuscript.
Author contribution
The study’s conception and design involved Cathy Gluyas, Lisa Mottram and Rosie Gibb. Cathy Gluyas collated the data and completed the qualitative analysis. The first draft of the manuscript was written by Cathy Gluyas, and all the authors commented on subsequent versions of the manuscript. All the authors approved the final manuscript.
Funding
Prof Julie Stout of Monash University kindly provided funding for this project that enabled it to be conducted outside of business hours.
Data availability
The authors confirm that the non-patient-identifying raw data supporting the findings of this study are available from the corresponding author.
Declarations
Ethics approval
All work was conducted in accordance with the Declaration of Helsinki (1975). This research received ethics approval from the Calvary Health Care Bethlehem Ethics Committee (HREEC number 19041801).
Conflict of interest
The authors declare no competing interests.
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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| 36495385 | PMC9736709 | NO-CC CODE | 2022-12-14 23:29:53 | no | J Community Genet. 2022 Dec 10;:1-9 | utf-8 | J Community Genet | 2,022 | 10.1007/s12687-022-00624-w | oa_other |
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16
22 11 2022
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Background and Objective
The rapid rate at which the current mpox virus outbreak has spread across the globe has led the World Health Organization to declare it a Public Health Emergency of International Concern. Polymerase chain reaction-based methods are one of the cornerstones for effective molecular detection of viruses including mpox virus. Genetic variants in primer binding sites are known to impact the efficiency of polymerase chain reaction and therefore diagnosis. Here we have analyzed the genetic variants and their impact on efficient binding of oligonucleotides used in diagnostics.
Methods
In this study, we have systematically collected primers and probes used in the detection of mpox virus from published literature and public resources, and assessed the impact of primer binding region genetic variants in the detection of mpox virus by analysing the thermodynamic parameters, Gibbs free energy and melting temperature. These were calculated using the nearest neighbour method for variants in mpox virus genomes available and the deviation in parameters was computed with respect to the reference genome sequence.
Results
We have identified 170 genetic variations that fall within the oligo binding region in 1176 mpox virus genomes out of which five oligos showed at least a 2 °C decrease in melting temperature, which could potentially affect the diagnostic efficacy.
Conclusions
Our analysis shows the importance of continuous monitoring of mpox virus detection primer efficacy and provides the list of oligos with potentially reduced detection efficiency in the current mpox virus outbreak.
Supplementary Information
The online version contains supplementary material available at 10.1007/s40291-022-00629-8.
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pmcKey Points
Genomic variant analysis of mpox virus suggests a large number of variants located within the diagnostic primer binding region.
Thermodynamic analysis of a mismatch sequence provides a list of potentially affected primers/probes by genomic variation.
Introduction
According to the Centers for Disease Control and Prevention [1], as of 2 September, 2022, the current mpox virus (MPXV) outbreak has affected 53,027 individuals across the world in 100 different countries. Of the total cases, 52,516 cases have been reported in locations that have historically never reported MPXV infections before, thereby highlighting the fact that rapid and accurate detection of pathogens is necessary for effective surveillance and reducing the impact of the disease outbreak. Since the detection of the first case of MPXV infection in a human in 1970 [2], several primers and probes have been studied and published. The rapid spread of the current outbreak has also led to the creation and availability of several commercial kits as well as Centers for Disease Control and Prevention-recommended primer sequences [3].
Mpox virus is a double-stranded DNA virus with a previously established low mutation frequency. However, a recent study has identified 46 common mutations among the strains observed in the current outbreak [4]. Other studies focusing on the virus strains that have been reported since 2017 have found the virus to have a mutation rate of around ten times higher than its standard mutation rate [5]. As the virus can evolve at rapid rates through the accumulation of such genetic variants, these genetic variants can also directly affect the efficacy of the primers and probes used in polymerase chain reaction assays. In this study, we have systematically analysed the genetic variants of the MPXV genomes and our analysis suggests that some genetic variations that correspond to the target sites for the probes/primers may have an impact on the efficiency of detection/diagnosis.
Materials and Methods
Genome Sequences
The MPXV genomes that were deposited in the Global Initiative on Sharing Avian Influenza Data database [6] from 27-05-2022 to 23-08-2022 were downloaded. In total, 1176 genomes were used for the analysis of a primer mismatch out of which 15 were of lineage A and the remaining 1158 sequences were of lineage B.1.
Primers and Probes Used in Molecular Assays
A list of primers and probes used across molecular assays to detect the MPXV was curated using PubMed and Google Scholar. All primers reported in PubMed were collected using the search term “monkey pox primer sequence”, while Google Scholar was queried to include all preprints reported in 2022 using the search terms “biorxiv”, “monkeypox” and “primer” as well as “medrxiv”, “monkeypox” and “primer” [7–36]. Additionally, primers recommended by the Centers for Disease Control and Prevention, World Health Organization and the US Food and Drug Administration were also collected, along with those reported in commercially available kits for MPXV detection. In addition, multiplexed amplicon-based whole genome sequencing primers mentioned in protocols.io [37] were also included for the analysis.
All primers/probes were processed and were given unique IDs. A compiled collection of primers/probes was mapped against the reference genome [38] (NC_063383.1) using BLASTN [39], and the start and end positions of the primer binding sites in the genome were extracted. Further, 163 multiplexed primer pairs described in protocols.io for amplicon sequencing of MPXV were also independently analysed for their efficiency in covering the complete genome.
Variant Calling and Thermodynamic Parameter Calculation
Genetic variants in the MPXV genomes were called using Nextclade [40] against the reference genome. Substitutions, deletions and insertions that fell under the primer/probe binding regions were identified, and the frequency of each genetic variant at the primer binding region was calculated for 1176 genomes downloaded from the Global Initiative on Sharing Avian Influenza Data database.
For the calculation of thermodynamic parameters such as Gibbs free energy (ΔG) and melting temperature (Tm), first the 1176 MPXV genomes were aligned against the reference genome using nextalign [40]. Upon multiple sequence alignment, 1083 MPXV genomes were found aligned whereas the remaining 93 genomes failed to align because of multiple insertion/deletion events. Primer binding sequences were then extracted from the 1083 aligned genomes and were used for further analysis. The ΔG of primers and MPXV sequences/reference were calculated by the nearest neighbour method using the following equation:
ΔG037(DNAduplex)=ΔG037(initiation)+ΔG037(symmetry)+∑ΔG037(stack)+ΔG0AT(terminal),where ΔG0 37 (initiation) =1.96 kcal/mol, ΔG0 AT (terminal) = 0.05 kcal/mol, ΔG0 37 (symmetry) = 0.43 kcal/mol penalty is applied on self-complementary sequences and ∑ΔG0 37 (stack) is the summation of the ΔG0 37 of the adjacent bases.
Next, the percentage change in ΔG for each primer/probe was calculated from the ΔG of primer/probe binding to the reference genome. The frequency of MPXV genome with at least a 2% increase in ΔG from the reference genome was calculated to assess the usability of the oligos in the current outbreak.
For the calculation of the Tm difference, Tm_NN function from the R package TmCalculator [41] was used. The difference was estimated by subtracting the Tm of the extracted primers/probes sequences from that of the reference sequence for each oligo.
Results and Discussion
We compiled a total of 207 oligos through our literature survey, and upon the removal of duplicate primer sets we were left with 180 oligos. Further, upon mapping to the reference genome, 12 primers mapped to two regions as they were falling within the variable region in left/right of the MPXV genome, and hence both mapping positions were included in the analysis. Seventy-six out of 180 oligos did not map to the reference genome and upon blasting against all nucleotide databases of the National Center for Biotechnology Information, these oligos aligned mostly to MPXV complete genomes of West African and Congo basin sequences. The 114 oligos that had a perfect match on the reference genome were taken for further analysis. To obtain an overview of how many genetic variants fell within the oligo binding region, we combined the number of substitutions, deletions and insertions in the MPXV genome: in total, 170 genetic variants were present in 1176 MPXV genome sequences that fell within the 114 oligos that were analysed, with the variant frequency range from 0.0008 to 0.9719 (median 0.0008). Two out of the 170 genetic variants were present in at least 1% of the compared genomes, namely G2591A was present in 1143/1176 (97.19%) of genomes followed by G159277A, which was present in 12/1176 (1.02%) of genomes (Fig. 1). Similarly, genetic variants falling within 326 primers of multiplexed whole genome amplification primers from protocol.io were analysed in which 362 genetic variants were present within the primer binding regions, with the frequency range from 0.0008 to 0.9821 (median 0.0008) [Fig. 1 of the Electronic Supplementary Material [ESM]). Four of 362 genetic variants were observed in at least 1% of the genome namely C121320T (98.21%), G2591A (97.19%), G161296A (1.53%) and C38937T (1.10%).Fig. 1 Variant frequency in mpox virus genome sequences from the Global Initiative on Sharing Avian Influenza Data database. Red dots indicate variants within the detection primer/probe binding region
As a significant number of genetic variants were found within the oligo binding regions that are used in the detection or whole genome amplification of MPXV, we further analysed whether these genetic variants brought about changes in ΔG and Tm due to mismatches in genetic variants of MPXV genome and oligos as compared with the reference genome, as these thermodynamic parameters are good indicators of binding stability. An increase in ΔG and/or reduction in Tm by at least 2 °C as compared with the reference can lead to reduced binding stability and ultimately affect the PCR efficiency. Seventeen oligos that were used in Loop-mediated isothermal amplification assays were removed from this analysis and the ΔG for MPXV genome was calculated for the remaining 97 oligos. Interestingly, an increase of 2% ΔG was observed in 20/97 oligos. Of the 20, five oligos were observed in at least 1% of the 1083 MPXV genomes analysed. The same five oligos also had at least a 2 °C decrease in Tm as compared with the reference genome, out of which four had a more than a 5 °C deviation (Fig. 2). The frequency of genomes with reduced stability for each oligo is provided in Table 1 of the ESM. Similarly, 5/326 primers that were used for multiplex whole genome amplification displayed a 2% increase in ΔG in at least 1% of the genomes while four primers had at least a 5 °C decrease in Tm as compared with the reference genome (Fig. 2 of the ESM). These analyses indicate the requirement for constant monitoring of detection-evading MPXV variants for efficient surveillance of the disease. The frequency of genomes with reduced stability for each oligo used in whole genome amplification is provided in Table 2 of the ESM.Fig. 2 Frequency heat map of oligos with destabilised thermodynamic parameters with both a minimum 2% Δ Gibbs free energy increase and melting temperature differences in the mpox virus (MPXV) genome where MPXV lineage A, lineage B.1 and all sequences were described as MPX_A, MPX_B.1 and MPX_All, respectively
Conclusions
The recent severe acute respiratory syndrome coronavirus 2 pandemic has shown us the importance of efficient detection and genomic surveillance of outbreak potential pathogens in mitigating the effect of damage. In this short report, we examined all available oligos that were used for the detection or whole genome amplification of MPXV and analysed their detection efficiency using whole genome sequences available on the Global Initiative on Sharing Avian Influenza Data platform. Our analysis shows the importance of continuous monitoring of MXPV detection oligos that could be impacted by genetic variants. We also provide a list of frequencies of genomes with reduced stability for all analysed oligos for healthcare workers to make an informed decision in the choice of using oligos in PCR-based detection of MPXV in the current outbreak. While an exhaustive search of published oligos was performed for the analysis, our study is limited by the fact that available sequence data are not uniform across all affected countries/regions. This might lead to an unintentional bias towards data from countries/regions that perform extensive sequencing, and an under-representation of data from countries/regions that have not participated in extensive genomic surveillance of MPXV.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (PDF 2339 KB)
Supplementary file2 (XLSX 48 KB)
Acknowledgements
The authors acknowledge the contribution of Mercy Rophina in proofreading and correction of the manuscript. Arvinden VR acknowledges a fellowship from the Council of Scientific and Industrial Research, India.
Declarations
Funding
No funding has been acquired for this study.
Conflicts of interest/competing interests
Aastha Vatsyayan, Arvinden VR and Vinod Scaria have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Ethics approval
Not applicable.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Availability of data and material
Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. All data analysed during this study are included in this published article (and its supplementary information files).
Code availability
Not applicable.
Authors’ contributions
VS conceptualised, designed and supervised the study. AV collected the compendium of primers and probes. AVR performed the analysis and data visualisation. Both AV and AVR contributed towards compiling the manuscript.
Aastha Vatsyayan and V. R. Arvinden contributed equally to the article and would like to be known as joint first authors.
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| 36495397 | PMC9736716 | NO-CC CODE | 2022-12-14 23:45:41 | no | Mol Diagn Ther. 2022 Dec 10;:1-6 | utf-8 | Mol Diagn Ther | 2,022 | 10.1007/s40291-022-00629-8 | oa_other |
==== Front
Asia Pacific Educ. Rev.
Asia Pacific Education Review
1598-1037
1876-407X
Springer Netherlands Dordrecht
9815
10.1007/s12564-022-09815-z
Article
Discrimination against private-school students under a special quota for the underprivileged: a case in India
Kumar Atul 1
Brar Vinaydeep 2
Chaudhari Chetan 3
http://orcid.org/0000-0002-8017-7740
Raibagkar Shirish S. [email protected]
4
1 Dr. D. Y. Patil B-School, Pune, India
2 S.N.G. Institute of Management & Research, Pune, Maharashtra India
3 Global Business School and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra India
4 Institute of Cost Accountants of India, Ahmednagar, India
10 12 2022
110
29 4 2022
24 11 2022
1 12 2022
© Education Research Institute, Seoul National University 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
The Indian government enacted the Right to Education Act (RTE) to provide free and compulsory elementary education to all economically underprivileged children between ages 6 and 14. All schools, including private schools, are required to reserve 25% of their enrollment slots for such students, with the government shouldering their fees. While student enrollment has increased, some challenges have emerged in the schooling of RTE students. We surveyed the parents of 400 RTE students and interviewed five private-school principals. Findings showed that private schools practice discrimination against RTE students, who are susceptible to various risks. Private schools argue that for the past several years, the government has not paid the fees for these students. Based on the social equity theory of education, we suggest that the fees of underprivileged students be charged to the majority of upper- and middle-class students.
Keywords
Social equity theory
School students
Private schools
Discrimination
Financial problem
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pmcIntroduction
In a landmark decision, the Indian government passed the Right to Education Act (RTE) in 2009 to provide children between ages 6 and 14 free and compulsory elementary education, fulfilling the requirement set in Article 21a of its constitution. With the RTE Act coming into force on April 1, 2010, India became one of 135 countries to declare education a fundamental right of every child (RightToEducation.In, 2013). The law makes education a basic right for every child between 6 and 14 years old and clarifies basic requirements for primary schools. According to the RTE Act, all private schools must reserve 25% of their enrollment seats for children (with the government reimbursing fees as part of a public–private partnership program). In India, private schools are not under government management and control and are classified into two: aided and unaided (Gandhi-Kingdon, 2017). Aided private schools receive grant-in-aid for salaries and/or other items of expenditures, while unaided private schools receive no funding support from the government and, except for the fees, manage their finances independently. Private schools enroll children based on their economic status or category-based reservations. This prevents unrecognized schools from operating, facilitates non-donation or capitation funding, and eliminates the practice of child or parent interviews. The RTE Act also provides that no child should be turned away, expelled, or required to pass a board examination until they complete their elementary school education. Specialized training is also offered to students who drop out of school to fit in with students of the same age. Following the implementation of the RTE Act, the gross enrollment ratio increased from 109.101 in 2010 to a high of 114.538 in 2016 (World Bank, 2022).
Currently, however, all is not well with economically backward students enrolled through the 25% quota. Sarasvati (2020) cited the case of a laborer who was treated like a second-class citizen when he tried to register his daughter in a neighboring private-school and was also asked to pay for the cost of books, which was to be paid by the government: “The barriers Kale (laborer) faced are critical reasons why the RTE reservation system in Maharashtra is struggling to reach its objective: to provide free, inclusive education while incentivizing private schools by reimbursing their costs for educating poor, disadvantaged children, we found. If the Andheri School had followed RTE rules, Kale would not be forced to pay for his daughter’s books nor would he be made to feel humiliated and unwelcome.” Sarasvati added that private schools force RTE students to sit in separate classrooms. These unfair practices hinder RTE students’ academic development.
Joshi (2021) reported that 1267 English-medium schools from Maharashtra, which are private schools, decided to boycott the RTE admissions for the academic year 2021–2022 because of the government’s failure to pay several years of fees for these students. Meanwhile, the government has threatened these schools with strict actions if they do not comply with the provisions of the RTE Act. The association of these schools is seeking the intervention of the high court. This shows that the government and private schools are at a standstill, threatening the future of thousands of underprivileged students.
One way to examine this phenomenon is from the perspective of the social responsibility of private schools. Lightstone (2008) stated that scant research has been done to investigate private schools’ social responsibility. Ojha and Chakravarty (2012) criticized private schools for being operated for profit and non-inclusive, while in India, most private schools are established as charitable trusts and not-for-profit organizations. Therefore, no income tax is imposed on their profits since Indian tax laws designate surpluses from charitable activities as tax-exempt (Income Tax Department, 2022). However, private schools are found to discriminate against children admitted under the RTE quota. The term “discrimination” has changed with a broad spectrum of social exclusion, which has widened. For instance, the India Exclusion Report 2013–2014 (Centre for Equity Studies, 2014) discussed exclusions for girls, Dalits, Adivasis, Muslims, and children with disabilities. However, discrimination has been observed against the 25% RTE quota.
As a result of the 25% admission quota impasse, the underprivileged faced discrimination in terms of social equity and equality. Hence, the purpose of the RTE Act is being defeated because of private schools’ refusal to cooperate with the government.
Additionally, situations such as the COVID-19 pandemic have only worsened this scenario. One can imagine the plight of RTE quota students who have been deprived of school during the pandemic period because they lack access to digital resources for attending online classes. School authorities have not done much to overcome this digital divide, and RTE quota students have continued to suffer.
Mohalik and Sethy (2021) found abysmally low attendance among students in government schools in tribal areas such as Jharkhand state. In these areas, most students regularly skip school because they perform domestic chores and take care of their siblings during school hours. The children also work to earn a livelihood, which disrupts their school attendance. Such schools would need to be shut down, which only aggravates the problem.
Other measures have been implemented, such as the Mid-day Meal Scheme, which provides free lunch to students in government-run schools but has been criticized for the poor quality of food (The Economic Times, 2014). A revamp of the scheme has been demanded.
The Indian government recently announced its National Education Policy (NEP) 2020. According to Kakumanu (2022), the NEP strengthens the RTE by addressing three important dimensions of education delivery: students, teachers, and parents. The NEP aims to enhance the educational infrastructure in small towns and rural areas. When these places become self-sufficient in providing education to their inhabitants, the equitable provision of education as envisioned in the RTE will become a more achievable goal. If this happens, RTE provisions could be revamped as the NEP aims for robust systemic changes especially for small towns and rural areas.
Sabale (2017) observed that despite the Indian government’s adoption of an inclusive education strategy, underprivileged students continue to lag in academic development. Sharma and Subramanyam (2020) found that Indian underprivileged students faced discrimination, which led to poor academic performance, low self-esteem, and weak motivation.
Based on reports such as that of Sarasvati (2020) and literature by Sabale (2017) and Sharma and Subramanyam (2020), we set the first objective of our study: to find out whether students enrolled in the RTE quota in private schools are facing discrimination. We propose to achieve this goal by surveying a sizable number of parents of RTE students. For balance, our second objective is to understand the problems faced by private schools in dealing with RTE students. We propose to meet this objective by interviewing five principals of private schools.
Our study is grounded on the social equity theory of education, examines the situation through the lens of this theory, and draws important implications.
The definition of “discrimination” adopted by this study is consistent with the one in the Protection of Child Rights Act 2005, which shields children from discrimination based on race, color, sex, language, religion, political or other opinions, national ethnic or social origin, property, disability, birth, or other status. The act is enforced by the National Commission for the Protection of Child Rights.
The remainder of the paper is organized into four sections: literature review, methods, data analysis and results, and conclusion.
Literature review
We begin the review by examining studies on the social equity theory of education to provide the theoretical framework for our study. We also review literature related to discrimination against students, highlighting the normative nature of the social equity theory of education.
Social equity theory of education
In an influential study, Gonski et al. (2011) argued that equity implies that children must have equal access to schooling and opportunities to succeed regardless of their socioeconomic status, language, or ethnic background. Drawing on Field et al.’s (2007) definition, Gonski et al. stated that their definition of equity focuses on two constructs: fairness and inclusivity. Fairness means that social and personal circumstances are not impediments to reaching one’s academic potential, while inclusivity ensures a minimum level of education for all. Caldwell and Spinks (2008) observed that given the right support and circumstances, all children can learn and achieve at school. McKown (2013) suggested that the racial–ethnic achievement gap be studied based on an understanding of its origins from social equity theory. Kamat (2008) examined two educationally disadvantaged groups from India and recommended an inclusive strategy based on social equity theory. She highlighted that the two groups—scheduled castes and scheduled tribes—should have access to education on the grounds of inclusivity. Rizvi and Lingard (2011) asserted that the notion of social equity cannot be fully understood in a generalized abstract manner and can instead be better viewed as a collection of several competing and contrasting views. Fowler and Brown (2018) stated that viewing equity theory through the lens of social justice can provide data that can help marginalized students improve their educational achievements. Rosenbloom (2005), discussing the limitations of a symposium on social equity in public affairs education, emphasized the need to define social equity. Espinoza (2007) reviewed the literature on the “equity–equality” conceptual dilemma (in education) and suggested concepts such as “equity for equal needs,” “equity for equal potential,” “equity for equal achievement,” “equality of opportunity,” and “equality for all.”
The Indian government’s legislative intent, the RTE Act, can be correlated with the social equity theory of education since it is based on the principles of fairness and inclusivity, among others (Field et al., 2007; Gonski et al., 2011). It seeks to provide compulsory and free education to underprivileged children. However, it has encountered a crisis, challenging the ideologies of fairness and inclusivity. These are discussed in the conclusion section.
Discrimination faced by students
Moran (2002), examining gender and race-based discrimination, highlighted diverse views on the nature and incidence of discrimination at schools. Welply (2018) found that race-based discrimination at schools is tacit and cumulative and that Muslim children are positioned as the “bad other.” Losen and Welner (2001) described the systemic nature of discrimination practiced in U.S. public schools. Regarding racial discrimination, Reskin (2012) stated that discrimination is a meta-level phenomenon that shapes culture, cognition, and institutions.
Hanassab (2006) found that international students in U.S. higher-learning institutions face varying degrees of discrimination. Tran et al. (2020) discussed the worldwide escalation of racism and discrimination against Asian students since the COVID-19 outbreak. Dehadray (2019) found that discrimination is practiced in the punishment of students; those from socially disadvantaged classes are penalized more than other students. Feagin (1992) found that black students face discrimination in enrollment and graduation rates in colleges run by white officials. Poyrazil and Lopez (2007), in a U.S.-based study, found that international students faced higher discrimination and therefore experienced more homesickness compared with U.S. students. Among international students, those from Europe encountered less discrimination and were less homesick than those from other parts of the world. Thorat and Neuman (2012) investigated the discrimination faced by Dalits (socially backward) and minority students, which leads to inequalities in various aspects of their life. Siraj et al. (2021) reported gender-based discrimination faced by female medical students in Georgia, while Evivie (2009) found that African students face discrimination in the United States. Beemyn (2003) examined discrimination against transgender students, and Thomson (2013) investigated general ethnic discrimination faced by Native American postsecondary students. Brown and Tylka (2011) observed that racial discrimination places African Americans at risk for psychological distress, in which they experience low levels of well-being. D’augelli (1992) discussed the discrimination faced by lesbian and gay undergraduate students. Channar et al. (2017) highlighted the discrimination against female postgraduate students at Jamshoro University in Pakistan. Usher et al. (2005) found that undergraduate nursing students across Australia experience discrimination. Schmitt et al. (2003) observed that the discrimination faced by international students diminishes their self-esteem. Shaukat and Pell (2015) found that female students from the arts faculty in the Lahore district of Pakistan faced discrimination. Starovoytova and Namango (2016) found that female engineering students experienced gender-based discrimination, while Arora (2021) observed students who have migrated to Delhi, the capital of India, from other parts of the country encountered discrimination based on race, gender, and caste. Matsheka and Garutsa (2022) focused on the discrimination faced by racial minority students in Germany and South Africa, and Creighton (2007) discussed the discrimination faced by African American students in the United States, resulting in lower graduation rates. Yoo et al. (2010) pointed out the discrimination faced by Asian students studying in the United States, while Huang (2012) specifically discussed discrimination against Chinese international students, also in the United States. Sanders (1997) examined racial discrimination experienced by African American students and its negative consequences. John et al. (2018) focused on the case of male nursing students in the minority (25%), who also faced discrimination. Ressa et al. (2021) discussed the discrimination that students face for having speech and visual disabilities. Ahn et al. (2021) investigated discrimination encountered by Asian American medical students. Vedhavalli (2021) examined gender-based discrimination against female students in Turkey. Okech et al. (2020) studied the discrimination faced by students with special needs. Letsoalo et al. (2020) discussed a case of discrimination against gay and lesbian students from a semirural university in South Africa. Konur (2006) observed the discrimination encountered by disabled students in higher education. Melikan et al. (2020) highlighted the discrimination experienced by women studying medicine in two U.S. colleges. Amiri (2019) focused on religion-based discrimination. Wolanin and Steele (2004) examined the discrimination faced by students with disabilities. Chen (2022) discussed a case of gender-based discrimination against English learners from China. Azra (2014) observed that female students from Pakistan’s Sindh province experience discrimination.
The literature shows that students worldwide experience discrimination based on gender, social status, race, nationality, caste, religion, faculty membership, disability, and sexuality and that such discrimination has an adverse effect on these students. Indeed, recent studies imply that student discrimination remains a reality. However, scholars have not focused on discrimination in private schools based on a government-mandated quota for underprivileged students, who constitute a significant portion of the student population in India. Therefore, understanding the implications of such discrimination on the public–private partnership model, which the government has adopted to educate its vast population, would be beneficial. This study is expected to clarify some practical dynamics of the social equity theory of education.
Based on the two sections of the literature review, we construct the following hypotheses:
Ho: RTE students face no discrimination at private schools (normative theory).
Ha: RTE students face discrimination at private schools (practical situation).
Methods
Two research methods were adopted in the study. First, a quantitative survey was conducted to ascertain if discrimination against RTE students is indeed practiced at private schools. This survey did not include the parents of students from government-owned public schools and exclusively involved private schools. Second, to understand the problems of the private schools, a qualitative method was used.
Given the large population of RTE students, the survey used a sample size of 400. References to standard sample size tables such as Krejcie and Morgan (1970) indicate a sample size of 370 for a population of 10,000 at a 95% confidence level and a 5% confidence interval. We rounded this off to 400 to address sampling errors. We then performed convenience and snowball sampling to gather responses from parents of RTE students from all over India. The World Health Organization lists two Indian national ethics committees for the ethical approval of medical or biotechnology research: the Indian Council of Medical Research and the National Bioethics Committee of the Department of Biotechnology of the Ministry of Science and Technology (World Health Organization, 2015). Since our study is outside the purview of clinical or biotechnological research, local ethics committee approval is not applicable.
We distributed about 500 questionnaires and closed the survey upon receipt of the 400th response. The survey was administered through Google Forms and conducted during the second week of March 2022. The questionnaire contained a single section with 10 statements to ascertain if RTE students experienced discrimination. These statements were prepared based on secondary data (e.g., Sarasvati, 2020: RTE students made to sit in a separate class; Dehadray, 2019: Disadvantaged students are punished more) and informal discussions with some parents of RTE students. The 10 statements are as follows:The RTE students are made to sit in a separate classroom.
Teachers are less attentive to RTE students.
RTE students are never allowed to sit on front benches.
RTE students are given fewer marks.
Other evaluation of RTE students is done with reluctance.
RTE students are given more punishment.
RTE students are given fewer opportunities to participate in extracurricular activities.
RTE students never get an opportunity to represent or lead the class.
As parents, we receive discriminatory treatment at the parent–teacher meetings.
RTE students are seldom encouraged to participate in interschool competitions.
Menold and Bogner (2016) recommended providing a “do not know” filter in the response options to provide for an early exit option in case the respondent did not know or wish to answer. The responses used a five-point Likert agree/disagree scale (Cannot say, Somewhat agree, Strongly agree, Somewhat disagree, and Strongly disagree). The survey questionnaire underwent a validation checklist as suggested by Brown et al. (2015), with satisfactory results. A reliability test produced a Cronbach’s alpha score of 0.77.
We performed the following steps to test the hypotheses:The responses for the section were aggregated under two opposite groups of agreeing and disagreeing.
While doing so for each extreme response, a weight of 2 was assigned to “Strongly agree” and “Strongly disagree” to distinguish them from “Somewhat agree” and “Somewhat disagree,” respectively.
The “Cannot say” responses were ignored in the calculations by assigning a weight of zero.
For each subquestion, an average score was calculated for the two opposite opinions of agreeing and disagreeing.
A comparison was made to determine which of the two groups, agree or disagree, had a higher score.
The higher average score percentage for the Likert scale section (Brown, 2011) was then compared with a hypothesized mean of the population of 50% score, connoting an event by chance and not due to statistical significance using a t-test, which is usually the case when the standard deviation of the population is unknown.
p-value was calculated and the null hypothesis checked for rejection or nonrejection. The calculation was performed at a 99% confidence level.
Statistical functions including standard deviation and MS Excel formulae such as t-dist were deployed for the calculations.
To understand the issues of private schools, a qualitative method was preferred since it involves some deeper probing, which might not be possible with a quantitative method. For the interviews, a sample size of five private-school principals was established. This sample size was based on the opinion of expert researcher Dworkin (2012), who said, “While some experts in qualitative research avoid the topic of ‘how many’ interviews are ‘enough,’ there is indeed variability in what is suggested as a minimum. Many articles, chapters, and books recommend guidance and suggest that anywhere from 5 to 50 participants are adequate” (p. 1319). The five private-school principals selected were senior men and women from different parts of the country, and all of them had rich experience in the field of school education of more than 20 years. They agreed to respond on conditions of strict anonymity. The responses received were carefully read and common themes identified. They were asked the following three questions:Is it the case that RTE students face discrimination at private schools? If yes, why?
What are the problems faced by the private schools concerning RTE students?
What do you think should be done to overcome the problems?
Data analysis and results
Survey data analysis
Table 1 presents the profile characteristics of the sample, which was a good representation of all four zones of India. All ages of RTE students (from 6 to 14 years) were well-represented as well.Table 1 Profile characteristics of the sample
Variable Category Respondents Percentage
Zone North 94 24%
East 107 27%
West 109 27%
South 90 23%
Gender Male 204 51%
Female 196 49%
Age of wards 6 years 39 10%
7 years 41 10%
8 years 33 8%
9 years 52 13%
10 years 47 12%
11 years 46 12%
12 years 52 13%
13 years 50 13%
14 years 40 10%
Source Primary data
Table 2 shows a plain count of the responses to the 10 statements. Table 3 displays a weighted summary of agreement and disagreement. Table 4 provides the statistical outcomes for the 10 statements and their averages.Table 2 Summary of responses to the 10 statements
Responses 1 2 3 4 5 6 7 8 9 10
Cannot say 6 6 6 2 9 4 10 11 10 12
Somewhat agree 91 127 127 134 143 127 123 120 118 115
Strongly agree 85 138 138 167 144 157 139 149 152 161
Somewhat disagree 82 72 73 64 60 41 44 47 48 48
Strongly disagree 136 57 56 33 44 71 84 73 72 64
Total 400 400 400 400 400 400 400 400 400 400
Source Primary data
Table 3 Weighted agreement/disagreement summary
Statement 1 2 3 4 5 6 7 8 9 10 Average
Agree (%) 42 68 69 78 74 71 65 68 69 71 68
Disagree (%) 58 32 31 22 26 29 35 32 31 29 32
Source Primary data calculations
Table 4 Statistical outcomes for the 10 statements
Statement Agree (%) t-value p-value
1 42 − 1.25 0.10593
2 68 3.49 0.00027**
3 69 3.52 0.00024**
4 78 6.14 0.00000**
5 74 4.80 0.00000**
6 71 3.84 0.00007**
7 65 2.67 0.00392**
8 68 3.30 0.00052**
9 69 3.39 0.00038**
10 71 3.95 0.00005**
Average 68 3.11 0.00101**
**Significant at the 99% confidence level
The average agreement of 68% was compared with the hypothesized population mean of 50%, connoting an agreement by chance and not due to statistical significance. Table 5 shows the results of the hypothesis testing.Table 5 Testing of the hypotheses
Parameter Value
Ho (Sample mean) 68%
SD (Standard deviation) 1.14
H1 (Hypothesized mean of population) 50%
n (Sample Size) 400
t-value 3.11
p-value 0.001
Decision Reject null
Source Primary data calculations
The aggregate (average) result of agreement of 68% is statistically significant at the 99% confidence level; since the average agreement is significantly higher than 50% (p = 0.001), the null hypothesis (RTE students face no discrimination at private schools) was rejected in favor of the alternate hypothesis (RTE students face discrimination at private schools).
It is important to note that the analysis relies on the principles of Likert scales rather than those of Likert items (Brown, 2011). In our analysis, the 10 statements are Likert items, which together constitute a Likert scale. Therefore, we tested the hypotheses based on the average of the 10 statements. All 10 statements were linked to a common underlying construct: discrimination against RTE students at private schools. Out of these 10, the first statement (the RTE students are made to sit in a separate classroom) was the only one where the average disagreement (58%) was higher than the average agreement (42%). For the rest of the statements, the average agreement was higher than the average disagreement. The highest agreement was recorded for the fourth statement (RTE students are given fewer marks). Agreement regarding other discriminatory practices ranged from 60 to 70%.
Interview data analysis
All five private-school principals interviewed as a part of the qualitative study agreed that RTE students face discrimination at private schools. The principals also expressed general agreement regarding our 10-statement list, which was shared with them along with the three questions. They further found that discrimination was quite rampant at English-medium private schools and were unanimous in saying that this was due to a significant cultural clash. Teachers experience difficulty in dealing with two groups of students—one that is raw, lacks manners and etiquette, and exhibits low intelligence and emotional quotient, and another with the exact opposite characteristics. One principal said, “Dealing with such a heterogeneous mix is stressful for the teachers. It affects their teaching and performance. They are always in a dilemma. If they pay more attention to the RTE students, they leave the 75% majority unattended who get disengaged. If they ignore the RTE students, they are the ones who suffer. So, eventually, they prefer to go with the majority; as a result, the RTE students face discrimination.” All five principals stated that teachers were aware that the government does not pay the fees for the RTE students on time, which in turn affects their salary. Thus, teachers may subconsciously blame RTE students for their delayed salaries, leading to negative attitudes and discriminatory practices.
In response to the second question, all five principals identified the state government’s failure to reimburse the fees for the RTE students as a major problem. According to one principal, “We are private unaided organizations. Our only source of income of ours is student fees. How will we function if 25% of the fees remain unpaid for years together? From where will we pay the salaries and other operating costs?” At least four principals stated that more than three years of their RTE fees have been pending with the state government. “If we follow up with the state government,” according to another principal, “they reply that they do not have funds and will pay when they receive funds from the central government.” Thus, the state government has been avoiding its responsibility of reimbursing the fees for the RTE students. According to the RTE Act, the government is responsible for providing free education, but instead, the government is imposing this responsibility on the schools. This may be acceptable with government schools to some extent but not so with private schools. The principals unanimously pointed out that this was a major departure by the government from the basic tenets of the RTE Act, which has created serious operational problems for private schools. The principal from Maharashtra said, “Situation now has gone out of control. This year (2021/22), we have decided to boycott the RTE admissions. Unless the government clears the previous outstanding fees of the RTE students, we are not going to admit fresh RTE students.”
Regarding the third question, the principals thought that the 25% reservation quota was extremely high. Two of them thought it should be lowered to 10%, while the other three felt that the quota should be 5%. The fact is that the government does not have the resources to fund the RTE program; hence, instead of being too ambitious, the government should be more practical and realistic. The central and the state government should convene and make a clear decision about sharing the burden of the fees for the RTE students. They should be reasonable in their approach and think pragmatically. Overambitious decisions have proven counterproductive.
With regard to discrimination, they argued that the divide between the two classes is so wide that practicing inclusivity in such a situation is extremely challenging; it is ideal and wishful thinking that there should be no discrimination. In practice, however, when a teacher must address a class with a majority of students from elite backgrounds and a minority from ordinary circumstances, they are bound to be tilted more toward the majority. These are some ground realities of teaching a heterogeneous group of students. One of the principals clarified, “It is not that they are doing this intentionally. But the situation is such that it happens on its own. After all, the teachers have their key performance indicators and responsibilities. So obviously they are bound to focus more on the 75% majority students.”
Conclusion
Both analyses confirmed that RTE students experience discrimination at private schools. The survey results showed that discrimination is practiced in various forms, while the interviews revealed that such practices are more prevalent in English-medium schools, where sociocultural diversity is extremely high. Such discrimination puts students at high risk of loss of self-esteem (Schmitt et al., 2003; Shaukat & Pell, 2015; Sharma and Subramanyam, 2020), poor academic performance (Sharma and Subramanyam, 2020; Creighton, 2007), and other psychological problems (Brown & Tylka, 2011).
The main problem of private schools in terms of compliance is that the government has not been paying the fees for the RTE students; because of this, they have been facing operational problems and delays in staff salary payments. The private schools had agreed, in good faith, to support the government’s vision of providing free and compulsory education to all children aged 6 to 14. While the schools have played their part, the government has failed to keep its promise of paying the fees, implying that the government wants the schools to teach 100 students for the cost of teaching 75, which is also not possible because of restrictions on fees charged by schools put forth by other legislation. For example, the state of Maharashtra enforces a regulation called the Maharashtra Educational Institutions (Regulation of Fee) Act 2011 (Government of Maharashtra, 2014), which places limits on fees charged to students.
This creates a paradoxical situation. The government has taken the major responsibility of providing free and compulsory education for children between ages 6 and 14. To do so, it has sought the partnership of private schools on the condition that it will pay them the fees for these students since they are private institutions. However, because of a lack of funds, the government has been unable to pay these fees for several years, so the schools refused to cooperate further. In response, the government has threatened to close the schools if they do not comply with the law. The paradox is that because of the issue involving underprivileged students from the 25% quota, the remaining 75% of students might lose the opportunity to learn if the schools are closed. This is the impact of neoliberalism and the failure of the PPP model of inclusive education policy.
Examining the situation from the lens of the social equity theory of education, we found that the intentions of the Indian government are well placed on the principles of fairness and inclusivity (Field et al., 2007; Gonski et al., 2011). However, it does not have the financial resources to fulfill its obligations. In Gonski et al.’s (2011) report submitted to the Australian government titled “Review of Funding for Schooling,” we found that the expert panel had recommended that the government continue to fund socially and economically disadvantaged students in private schools through more simple schemes. However, since the problem in India is that the government does not have the money, how theory will be put into practice remains a big question. We ask a basic question here: is the social equity theory of education applicable only to the government, or is it also applicable to society? We believe that the theory has universal applicability. Hence, along with the government, private schools and parents of privileged students must also play their part in the implementation. Theories and ideologies become a reality through collaborative efforts. Private schools should stop discriminatory practices and realize and accept that they are equally committed to the core values of fairness and inclusivity, which are the two main pillars of the theory of equity in education.
To overcome the financial impasse, the solution would be to pass the burden of the RTE students to the parents of the upper- and middle-class students from the remaining 75%. The fees that should be charged to them should be calculated by dividing the total expenditure for 100 students by 75 students. In other words, each upper- and middle-class student from the 75% should contribute a little bit to the expenditures for the RTE students. This must be done since the government does not have the money to finance the fees for these students. At the same time, underprivileged students should have a right to education. Rightfully, therefore, on the principles of fairness and inclusivity, the majority should help and care for the minority. These principles are often seen in taxation policies where the rich are taxed at a higher rate, and the tax collected is spent for the welfare of the economically weaker population. It is illogical on the part of the government to burden private schools with this responsibility. This is because if they are asked to manage the expenditures for 100 students from income generated from 75, expenses would be limited, which will have repercussions on the quality. Instead, the idea should be to increase the income to 100. Only then will private schools have adequate income to pay their teachers’ salaries, and at least to some extent, discrimination will be reduced. They will not hold grudges as a result of delays in their salaries because of RTE students.
India faces two major challenges: a massive population of school-going children to serve and a scarcity of resources. Against this backdrop, a natural change is seen in the approach to welfarism in terms of education as a public good and the entitlement of basic rights as enshrined in Articles 14, 15, 16, and 21 of the Constitution of India. The government is seeking more participation from the private sector, which must do so given the challenges faced by the government. The private sector should not look at education as a “commodity” and try to profit from it and instead genuinely take responsibility for helping the government ensure the efficient and effective delivery of public goods to all those who are entitled to them.
An implication of our study is for the government to implement a change in the formula for calculating the fees for the upper- and middle-class students from the 75%. Another is for private schools to design special training programs to help teachers work with heterogeneous groups of children and practice inclusivity. Most importantly, we suggest that the parents of upper- and middle-class students uphold the principles of social equity theory as theories are implemented through the support and cooperation of all corners of society. Each should make it their responsibility to ensure fairness and inclusivity in education. They must be socially responsible citizens. Urgent action is required to help thousands of RTE students, who are facing denial of admission to private schools.
We invite research into the practical dynamics of the social equity theory of education, especially in situations where financial resources are a major constraint. Realistic solutions for implementation are required; otherwise, the theory would be labeled as another purely normative concept.
Acknowledgements
The authors would like to thank the Editor, the two anonymous reviewers, and the APER Editorial team for their support in making this work more worthy of publication.
Funding
No external funding was used for this paper.
Data availability
Data set associated with this study has been deposited with a repository and can be accessed from https://www.openicpsr.org/openicpsr/project/166021/version/V1/view
Declarations
Conflict of interest
The authors declare that they do not have any conflicting/competing interest arising out of this paper.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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==== Front
Ann Oper Res
Ann Oper Res
Annals of Operations Research
0254-5330
1572-9338
Springer US New York
5116
10.1007/s10479-022-05116-1
Original Research
A mathematical model to investigate the interactive effects of important economic factors on the behaviors of retailers
Khakbaz Amir [email protected]
1
http://orcid.org/0000-0003-1664-9210
Tirkolaee Erfan Babaee [email protected]
2
1 grid.411973.9 0000 0004 0611 8472 Department of Industrial Engineering, School of Engineering, Damghan University, Damghan, Iran
2 grid.508740.e 0000 0004 5936 1556 Department of Industrial Engineering, Istinye University, Istanbul, Turkey
10 12 2022
125
28 11 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
Cost management is a key step to the success of any logistics system and supply chain management. Inventory costs are an important part of logistics costs which are highly affected by economic factors such as demand growth rate (DGR), interest rate (ir), and inflation rate (e). Analyzing the interactive effects of these economic factors plays a key role in preventing failures of logistics systems This study aims to develop a novel mathematical model and investigate the interactive effects of these factors on the behavior of retailers in Iran. To the best of our knowledge, this is the first time that the sale price is defined as a function of time and inflation rate where the demand rate is built up with a linear function of time. Different scenarios and sub-scenarios are then taken into consideration based on different combinations of factors and assumptions. As the main findings of the study, it is revealed that if e≤18% or ir≥40.52%, holding costs are much higher than buying costs, and retailers are reluctant to invest in inventories. Given that DGR is independent of the inflation rate, and also if e≥20.45% or ir≤31.9%, then DGR fluctuations have no impact on the total cost. Hence, in this case, buying costs are much higher than holding costs, and retailers are eager to invest in inventories instead of bank deposits. Furthermore, it is concluded that decision-makers can use the interest rate as leverage to set the probability of shortages and hoardings. Finally, some useful future research directions are discussed based on the main limitations of the study.
Keywords
Logistic system
Cost management
Mathematical model
Interest rate
Inflation rate
Demand growth rate
==== Body
pmcIntroduction
Logistics system as the main part or activity of supply chains plays a key role in achieving maximum competitiveness and profitability. Supply Chain Management (SCM) with the utilization of efficient logistics helps to guarantee an invariably high level of customer service with significant savings in the cost of extracting raw materials, production, storing, distributing and transporting, and selling final products/services to end-customers (Mondal & Roy, 2021).
Cost management within transportation and logistics systems is known as the most important internal obstacle to succeed in today’s competitive environment (Cichosz et al., 2020). Many factors can influence logistics cost, so it is essential to specify which are the most sensitive components on this issue, to utilize control and analytical measures. Logistics cost management have engage the attention of companies and also appeared as a focal point in academia recently (Santos et al., 2016).
Among different cost terms of a logistics system; i.e., transportation, warehousing, inventory and administrative, inventory costs are known as the second significant element (Dobos & Vörösmarty, 2019; Pervin et al., 2018). Inventory levels should be smoothed to form the economic cycles. Economic factors are the key components to estimate inventory costs. To this end, it is critical to identify and analyze the interactive effects of economic factors in order to prevent failures of logistics systems (Ghadge et al., 2021; Ghoreishi et al., 2015). Demand Growth Rate (DGR), interest rate and inflation rate are taken into account as the main factors. Interest and inflation rates respectively affect the holding and buying costs, and consequently, their impacts on the total cost are to be evaluated. Furthermore, DGR as the key factor drives the total cost directly.
On the other hand, among different supply chain actors (e.g., suppliers, manufacturers, distributors or retailers), retailers are highly subject to losses of a mismanaged inventory management (Sridhar et al., 2021). In today’s business competitive environment, it is clearly observed that suppliers or manufacturers provide the same products to their downstream retailers or distributors which then sell those products to consumers. Due to the same product characteristics, the retailers have to continuously compete with each other in the market (Cai et al., 2020). The retailers act as decision-makers for the order quantity and the suppliers/manufacturer simply supply and provide the required quantity as demanded by the retailers (Choi, 2018; Wu et al., 2022). They are more plausible to have sufficient inventory to grab every possible sale while minimizing overall logistics costs or maximizing total profit along with avoiding overstock (Arcelus et al., 2006; Wu et al., 2022). In this regard, some input parameters should be directly taken into account such as annual demand rate, holding cost, ordering cost, price and inflation and interest rates in order to analyze the output variables including the number of annual orders, quantity of orders, cycle time and inventory level. Besides, retailers are working more closely with logistics systems and especially, inventory control systems in which this collaboration is both a cost decrement initiative driven by the market and a customer expectation initiative.
The main questions of the research are given as follows:i. How can we develop a mathematical model to investigate the interactive effects of the economic factors on the behavior of retailers?
ii. How can we treat different combinations of economic factors in the model to find the optimal policy?
iii. Is a linear function effective enough to address all possible trends of demand?
iv. What are the main factors affecting the sale price?
To maintain the risk level under control, retailers lean toward possessing a risk-averse behavior in making their inventory decisions. This study tries to develop a novel mathematical model to study the behavior of retailers with respect to such inputs and outputs where the optimal inventory policy can be determined for a given time horizon. Furthermore, the dynamicity of interest rate and inflation rate is investigated in different scenarios in order to simulate practical conditions. The sale price is considered as a function of time and inflation rate to make the model closer to the real-world condition, while it was treated as a decision variable in previous studies. On the other hand, the demand rate is taken into account as a linear function of time whose slope can either be zero, positive or negative. All possible trends of demand can be incorporated into the model accordingly. To the best of our knowledge, these options have not been addressed in the literature.
We analytically obtain significant theoretical insights regarding the retailer’s optimal decisions. Therefore, our main contributions can be summarized as follows:I. Developing a novel non-linear mathematical model to concurrently analyze the effects of three economic factors of DGR, interest rate and inflation rate on the behaviors of retailers for minimizing the total inventory cost,
II. Considering the sale price as a function of time and inflation rate,
III. Addressing all possible trends of demand using a linear function of time with zero, positive or negative slopes,
IV. Determining the retailer’s optimal policy under different scenarios and sub-scenarios to address unstable real-world situations,
V. Validating the proposed model using a real case study in Iran,
VI. Performing a set of sensitivity analyses in order to evolve useful managerial insights.
The rest of the manuscript is organized as follows. Section 2 reviews the background following three main economic factors. The proposed mathematical model is described in Section 3. Section 4 represents the empirical study of the proposed methodology. The numerical analysis of different scenarios and sub-scenarios is presented in Section 5. Finally, the conclusion and future research directions are provided in Section 6.
Literature review
In this section, the attempts done by researchers in the field of inventory cost management for logistics and supply chain systems are reviewed considering the effects of DGR, interest rate and inflation rate, respectively. To do so, three subsections are given as follows:
DGR and demand uncertainty
Here, the main research studies addressing DGR and demand uncertainty as the main factors are reviewed. Alamri (2011) offered a general reverse logistics inventory model in order to minimize the total cost per unit time of a unified inventory system during a given cycle. They approximated the DGR using a linear demand function of time. The proposed model coordinated joint production and remanufacturing options and was validated using illustrative examples. The impact of credit financing, demand variation and inventory storage system on investment for deteriorating items was studied by Jaggi et al. (2019) through a mathematical model in order to minimize the present worth of the total cost. DGR was considered as a constant increase at the initial stage and stabilized at the maturity stage of products in the marketplace.
In two studies performed by Manna and Chauhduri (2006) and Skouri et al. (2011), two inventory models with ramp type demand rate were proposed in which shortages were allowed and not allowed, respectively. Skouri et al. (2011) extended the models suggested by Manna and Chauhduri (2006) where the demand rate is stabilized after the production stopping/restarting time. They also assumed a general time-oriented function for the variable term of the demand rate to make it more practical. Shi et al. (2019) offered a single-product inventory model with ramp type demand and permissible payment delay in order to minimize the average total cost. Two scenarios were considered and analyzed based on the relations between changing points from linear demand to the constant demand and replenishment cycle time. A case study of Liquefied Petroleum Gas (LPG) cylinders within a reverse logistics system was examined by Lopes et al. (2020) using three inventory models. As the third inventory model, they took into account stochastic demand and returns along with discrete replenishment from the supplier which was not considered in the first two models. It was concluded that the third would better suit the company’s challenges.
Recently, Derhami et al. (2021) proposed a model to assess product availability in a closed-form expression considering on-demand inventory transshipment and customer substitution for an omnichannel retail network. They modeled the problem from the perspective of customers and retail centers and examined their different behaviors under probabilistic demand shares. In the case of recreational vehicles, they demonstrated that their model leads to a significant increase in total sale by controlling the inventory cost. DGR was evaluated in a three-echelon supply chain was evaluated by Sebatjane and Adetunji (2021) and defined as a function of inventory level and expiration date. They developed a mathematical model in order to deal with optimal lot-sizing and shipment decisions for growing items such as crops and livestock. They also took into account the perspective of customers and retailers and revealed that their suggested model can provide more profitability in comparison with the traditional zero-ending inventory policy. Song et al. (2021) suggested a model to investigate three inventory strategies (push, pull, and prebook + at-once) to mitigate the risk arising from demand uncertainty for two participants (suppliers and manufacturers) in a supply chain. As the main outcome of the model, a particular strategy was considered to be preferred by both supplier and manufacturer. Recently, price-sensitive demand was taken into account by Khan et al. (2022) to find the optimal lot-size decision for perishable products where the retailer buys an item from a supplier. They also considered linearly time-dependent holding costs with all-units discount policy to maximize the total profit of the inventory system. A heuristic algorithm was developed to tackle the complexity of the problem using two numerical examples. Sweeney et al. (2022) applied the log-linear function for regression analysis of operational performance variables to address product variety in retail. They evaluated how demand variability influences product category inventory levels and stockout rates of retail firms. They conducted the proposed methodology for 78 individual retail stores in China and it was demonstrated that product variety and demand variability negatively affect product category inventory levels and stockout rates.
Interest rate
In this subsection, the main research works, concentrating on the interest rate as the main factor, are reviewed.
Teunter et al. (2000) proposed a mathematical model based on continuous interest rate, DGR, recovery rate and backorder cost rate to set the holding cost rates in Average Cost (AC) inventory models for reverse logistics systems. They compared different methods to calculate the holding cost rates of manufactured and remanufactured items and returned non-serviceable. They also showed that the traditional way (multiplication of interest/discount rate by marginal production/ordering cost) is not straightforward for inventory systems with reverse logistics. A non-linear model was offered by Jin et al. (2009) to optimally design a logistics network under stochastic demand and inventory control. They just considered the discount rate based on interest rate in order to convert fixed-cost into day-cost in the calculation of total logistics cost. It was proved that inventory cost plays a key role to control the total cost.
Akan et al. (2021) introduced a single-product dynamic pricing problem of a retailer with time-dependent interest rate. They also treated the demand as a deterministic and dependent parameter on the decay with time and price. Different initial inventory levels were investigated using an optimal-control-theoretic technique. Banomyong et al. (2022) conducted a study in order to calculate the national logistics cost in Thailand per gross domestic product considering inventory-carrying cost as one of the most effective factors. The interest rate was incorporated into the model as the main factor influencing the inventory-carrying cost. Havenga et al. (2022) demonstrated that inventory-carrying costs take into consideration the repo rate (interest rate announced by the central bank) as well as the average storage time per commodity, and accordingly, national logistics cost is measured in an emerging economy context for South Africa.
Inflation rate
Here, the main studies focusing on the inflation rate as the main factor are reviewed. Lo et al. (2007) offered an integrated production-inventory model under inflation from the perspective of the manufacturer and retailer. They regarded variable deterioration rate, partial backordering, multiple deliveries and imperfect production processes along with inflation in order to find the optimal joint cost of manufacturer and retailer in comparison with independent cost. The Discounted Cash Flow (DCF) and some classical optimization methods were utilized to optimize the problem. Sarkar et al. (2014) dealt with an economic manufacturing quantity model in an imperfect production process under inflation in order to address selling price, time-dependent demand and machine breakdown (reliability). The aim was to maximize the total profit using Euler–Lagrange model.
An extended inventory lot-size model was suggested by Chern et al. (2008) to incorporate general partial backlogging and inflation rate which were not given in the traditional models. They developed a model for deteriorating items with fluctuating demand and designed a heuristic algorithm to solve several numerical examples. Pal et al. (2014) proposed a production-inventory model for deteriorating items in order to minimize total cost under fuzziness. They also considered ramp type demand and examined the effect of inflation using a numerical example. In another study, Pal et al. (2015) extended their previous work where shortages of items were allowed. A dynamic inventory model was developed by Mahata et al. (2019) for deteriorating items considering price inflation and permissible payment delay. They defined the demand function to be iso-elastic and selling price dependent. A heuristic algorithm based on dynamic programming approaches was then applied in order to maximize net profit and optimize retail price, number of replenishments and cycle time. The effects of the inflation rate and time value of money were evaluated within a production-repairing inventory model with fuzzy rough coefficients by Mondal et al. (2013). The stock-dependent demand was defined for items in order to maximize the total profit within a finite planning horizon. A gradient-based non-linear optimization technique was implemented to solve several numerical examples. Alikar et al. (2017) examined the combination of the time value of money and inflation in a bi-objective multi-component multi-period series–parallel inventory-redundancy allocation problem. The optimal order quantity was found for each subsystem by minimizing inventory costs and maximizing reliability simultaneously. They applied multiple multi-objective meta-heuristic algorithms to find the Pareto optimal solutions. In another study, Huang et al. (2021) tried to formulate a food supply chain design problem considering the time value of money, DGR and inflation rate. The optimal pricing and replenishment policy of the inventory system were simultaneously developed to maximize total profit using the DCF model.
Yadav et al. (2021) examined the economic impact of the medicine industry inventory system during the recent COVID-19 pandemic considering ramp type demand with inflation effects. They took into account the application of block-chain and developed an inventory model including ordering cost, holding cost, deterioration cost, shortage cost, opportunity cost, etc. Particle Swarm Optimization (PSO) algorithm was utilized to solve the problem using a numerical example. Barman et al. (2021) introduced a back-ordered inventory model for deteriorating items under inflation and time-dependent demand. They studied the uncertain nature of the problem under a cloudy-fuzzy environment and defuzzified the total inventory cost using Ranking Index Method (RIM). Finally, a numerical example was investigated to validate the performance of the proposed model. A hybrid payment inventory model was introduced by Mashud et al. (2021) in order to cope with post COVID-19 conditions considering inflation, price-sensitive demand, cash discount and preservation technology investment for non-instantaneous deteriorating items. LINGO software was employed to optimize the proposed non-linear model in terms of total profit maximization. It was demonstrated that the total profit is highly sensitive to the inflation rate.
To the best of our knowledge, there are not enough research works in the literature examining the interactive effects of economic factors on the behavior of retailers, particularly for evaluating inventory costs. As of the last decade, researchers have gradually started addressing the criticality of the issue in logistics and supply chains. Table 1 summarizes the survey based on different criteria in order to highlight the contributions of the study.Table 1 Comparison between the most relevant studies and our work
References Economic factors Case study Objective(s) Methodology/Software
DGR/uncertain demand/dependent demand Interest rate Inflation rate
Alamri (2011) ✓ ✓ Total cost minimization Mathematical model
Sarkar et al. (2014) ✓ ✓ Total profit maximization Mathematical model/Mathematica 7
Jaggi et al. (2019) ✓ ✓ Total cost minimization Mathematical model
Mahata et al. (2019) ✓ ✓ ✓ Total profit maximization Mathematical model and heuristic algorithm based on dynamic programming/Lingo software
Lopes et al. (2020) ✓ ✓ Total cost minimization Mathematical model
Sebatjane and Adetunji (2021) ✓ ✓ Total profit maximization Mathematical model
Yadav et al. (2021) ✓ ✓ Total cost minimization Particle swarm optimization (PSO)
Mashud et al. (2021) ✓ ✓ ✓ Total cost minimization Mathematical model /Lingo software
Sweeney et al. (2022) ✓ ✓ Estimating Inventory levels and stockout rates Three-stage least squares regression model
Banomyong et al. (2022) ✓ ✓ Total cost minimization Cargo account settlement systems (CASS) model
Havenga et al. (2022) ✓ ✓ Total cost minimization South Africa's freight demand model (FDM)
Khan et al. (2022) ✓ Total profit maximization Mathematical model and heuristic algorithm
Current study ✓ ✓ ✓ ✓ Total cost minimization Mathematical model /MATLAB
In most of the previous studies, only one or two of the above-mentioned factors, i.e., inflation rate, interest rate, and DGR, have been investigated. A few of them, such as Mahata et al. (2019) and Mashud et al. (2021), have considered these factors simultaneously. In these studies, the sale price was considered as a decision variable, however, in the present study, it is considered as a function of time and inflation rate, which will be closer to the real-world condition. Moreover, in previous studies, the demand rate has usually been introduced as a linear function whose slope can only have one positive or negative sign. In the present study, the demand rate is considered as a linear function of time whose slope can either be zero, positive or negative. In fact, the present study considers all possible trends of demand which were ignored in the literature. Furthermore, in previous studies, the objective function has often been analyzed by considering the effects of just one of the threefold factors. For example, Mashud et al. (2021) analyzed the effects of different values of the inflation rate, i.e., 0.14, 0.18, 0.2, 0.22, and 0.24, on the optimal values of the total profit. In the present study, the total cost is analyzed by considering the combined effects of inflation and interest rates, which were not seen in the literature.
Mathematical model
As discussed in the previous section, the developed model aims to find the optimal replenishment policy by considering the interactive effects of interest and inflationary rates. Here, holding and buying costs are respectively defined as a function of interest and inflation rates, which are highly dependent on time (Paul et al., 2022). As interest rate increases, holding cost increases and consequently total cost increases. Furthermore, as the inflation rate increases, buying cost increases and consequently total cost increases. Moreover, the effects of DGR on total cost are investigated. However, the definitions of parameters, variables, and assumptions are as follows:
Parameters
ft Annual demand rate at time t,
Ft Cumulative demand at time t,
ht Holding cost per unit at time t,
A Ordering cost per order,
ct Unit price at time t,
ir Annual interest rate
Here ht=irct.d0 Annual demand rate at the start of the year,
d1 Annual demand rate at the end of the year,
e Annual inflation rate (e>-100%)
Variables
n Number of annual orders,
Qi Order quantity in period i (i=1,2,3,…,n),
Ti Cycle time of period i (i=1,2,3,…,n),
Iit Inventory level at time t in period i (i=1,2,3,…,n)
Assumptions
The replenishment occurs instantaneously at an infinite rate.
The ordering cost, A, is constant.
Shortages are not allowed.
Quantity discounts are not available.
The demand rate, ft, is considered as a linear function of time, which is defined as:ft=at+d0,0≤t≤1,
where a can either be zero, positive or negative (see Fig. 1), and d0 is the annual demand rate at the start of the year, i.e., f0=d0. Moreover, d1 is the annual demand rate at the end of the year, i.e., f1=a+d0=d1. Therefore, we have a=d1-d0.
Unit price, ct, is also considered as a linear function of time, which is defined as (Barman et al., 2021):ct=bt+c0,0≤t≤1,
where b can either be zero, positive or negative, and c0 is the unit price at the start of the year, i.e., c0=c0. Moreover, the unit price is equal to b+c0 at the end of the year, i.e., c1=b+c0. By considering e as the annual inflation rate, it is clear that c1=e+1c0. Therefore, we have b+c0=e+1c0, and consequently b=c0e.
The same fixed order cycle time is considered. Hence, we have Ti=T;i=1,2,3,…,n.
The ending inventory level is zero for each order cycle.
Fig. 1 Demand rate at time t
As said previously, the present study differs from the previous ones in several ways. First, as mentioned in assumption 5, the demand rate is introduced as a linear function of time whose slope can either be zero, positive or negative. This enables the model to consider all possible trends of demand, which were ignored in the literature. In addition, as mentioned in assumption 6, the unit price is defined as a function of time and inflation rate whose slope can either be zero, positive or negative. It helps the decision-makers to analyze the effects of the inflation rate in different conditions, i.e., constant inflation, rising inflation, and decreasing inflation, which is new to the literature.
As given above, ft=at+d0. Therefore, we have:1 Ft=∫0tftdt=at22+d0t0≤t≤1.
Accordingly, F1=a2+d0. In other words, the total demand over the year is equal to a2+d0. Since shortages are not allowed and ending inventory must be zero, the total order quantity over the year is equal to the total demand over the year. Thus2 ∑i=1nQi=a2+d0.
It is clear that, inventory level at time t in period i = Cumulative demand at the end of ith period – Cumulative demand at time t. Therefore3 Iit=FiT-Fti=1,2,…,n;i-1T≤t≤iT,
where FiT indicates the Cumulative demand at the end of ith period (see Fig. 2). In this figure, dashed lines are not included in the computations and are just used to identify the values of FiT. According to Fig. 2, the inventory level is equal to Q1 at the start of the first period and then it decreases gradually until it reaches zero at the end of the first period. In other words,I10=Q1 and I1T=0. These equations indicate that4 FT=Q1=aT22+d0T.
Fig. 2 Changes in the inventory level during the planning horizon
However for period i, it can be seen easily that Iii-1T=Qi and IiiT=0. Therefore5 Qi=2i-1aT22+d0Ti=1,2,3,…,n.
As mentioned previously, the aim is to determine the optimal number of orders in the developed model it is aimed so that the total inventory cost is minimized. The total cost consists of ordering cost (OC), buying cost (BC), and holding cost (HC). Hence, we have6 TC=OC+BC+HC.
In the following, the three-fold costs are formulated by use of the pre-determined parameters and variables. The ordering cost is written as7 OC=nA
Here, it is assumed that Qi is received instantaneously at the start of period i, i.e., t=i-1T. Because of that, the unit price in period i is equal to ci-1T. Hence, buying cost is calculated as:BC=∑i=1nctQi=∑i=1ni-1bT+c0Qi=∑i=1ni-1bT+c02i-1aT22+d0T=∑i=1ni-12i-1abT32+∑i=1ni-1bd0T2+∑i=1n2i-1ac0T22+∑i=1nc0d0T.
By considering ∑i=1ni=n2+n2, ∑i=1ni2=2n3+3n2+n6, and T=1n, we have:8 BC=ab3+bd02+ac02+c0d0-ab4+bd02n-1-ab12n-2.
Furthermore, the holding cost is presented as:HC=∫01htItdt=ir∫01ctItdt=ir∑i=1n∫i-1TiTctIitdt=ir∑i=1n∫i-1TiTbt+c0aT2i22+d0Ti-at22-d0tdt.
Since ∑i=1ni=n2+n2, ∑i=1ni2=2n3+3n2+n6, ∑i=1ni3=n4+2n3+n24, and T=1n, HC is simplified as:9 HC=ir2ab+3bd0+3ac0+6c0d012n-1+ac0-bd012n-2-ab24n-3.
Based on Eqs. (7)–(9), TC is stated as10 TC=m1n-1+m2n-2+m3n-3+m4+nA,
where m1=ir122ab+3bd0+3ac0+6c0d0-ab4+bd02, m2=ir12ac0-bd0-ab12, m3=-irab24, and m4=ab3+bd02+ac02+c0d0. The first and second derivatives of TC in terms of n are11 ∂TC∂n=-m1n-2-2m2n-3-3m3n-4+A,
12 ∂2TC∂n2=2m1n-3+6m2n-4+12m3n-5.
By considering b=c0e, the above coefficients are rewritten as follows13 m1=c0air2e+3-3e12+d0ir3e+6-6e12,
14 m2=c0air-e12-d0ire12,
15 m3=-c0aire24,
16 m4=c0a2e+36+d03e+66.
Sincea=d1-d0, thenad0=d1-d0d0. In other words, ad0=Annual demand rate at the end of the year - Annual demand rate at the end of the yearAnnualdemandrateattheendoftheyear that can be referred to as DGR. Since d0 andd1≥0, ad0 is always greater than or equal to − 1. Here, ad0>0 means that the level of annual demand has increased throughout the year. This increase can be due to several reasons, such as population growth and increasing purchasing power (increasing income). Moreover, ad0=0 states that the level of annual demand has remained relatively constant throughout the year. This situation can be due to population stabilization or price stability. At last, -1≤ad0<0 means that the level of annual demand has decreased throughout the year. This reduction can be due to several reasons, such as population decline and decreasing purchasing power (decreasing income). By consideringad0=DGR, Eqs. (13)–(16) can be rewritten as Eqs. (17)–(20).17 m1=c0d0DGRir2e+3-3e12+ir3e+6-6e12,
18 m2=c0d0DGRir-e12-ire12,
19 m3=-c0d0DGRire24,
20 m4=c0d0DGR2e+36+3e+66.
Data extracted from the Statistical Center of Iran (2021) revealed that between 01.06.2020 and 01.06.2021, the monthly inflation rate ranged from a low of 22.5% (2020–06) to a record high of 49.5% (2021–05), averaging out at 40.52%. In the same interval, the annual interest rate has been reported as 18%. By considering ir=18% and e=40.52%, the pre-defined coefficients i.e., m1, m2, m3, and m4 can be rewritten as follows.21 m1=-c00.04414a+0.09437d0,
22 m2=-c00.01877a+0.00608d0,
23 m3=-0.00304c0a,
24 m4=c00.63508a+1.202624d0.
By solving mi=0, we have DGR=αi. Based on Eqs. (25)–(28), if ir=18% and e=40.52% then α1, α2, α3, and α4 are equal to − 2.13769, − 0.32387, 0, and − 1.89366, respectively. If DGR≥0 then m1<0, m2<0, m3≤0, and m4>0, and consequently ∂TC∂n>0. In this case, n∗=1. If -0.32387≤DGR<0 then m1<0, m2≤0, m3>0, and m4>0, and consequently ∂TC∂n>0. Moreover, in this case, n∗=1. If -1.89366≤DGR<-0.32387 then m1<0, m2>0, m3>0, and m4≥0, and consequently ∂TC∂n>0. In this case, similar to the previous cases, n∗=1. As mentioned before, DGR is always greater than or equal to − 1. Therefore, it is concluded that n∗=1 in all previous cases. However, the sign of m1, m2, m3, and m4 are defined in Table 2. Summarily, for all three cases of DGR (positive, zero, and negative), the total cost function is strictly increasing, and consequently, n∗=1.25 α1=6e-ir3e+6ir2e+3-3e,
26 α2=ireir-e,
27 α3=0,
28 α4=-3e-62e+3.
Table 2 Sign of m1, m2, m3, and m4 (for ir=18% and e=40.52%)
DGR
− 1 − 0.32387 0
m1 NA* − − −
m2 NA + − −
m3 NA + + −
m4 NA + + +
*NA, Not applicable
Due to the economic conditions of Iran, it is the best replenishment policy to order all needed items at once at the start of the year. This policy, in turn, leads to the hoarding of goods. In the next section, two scenarios are determined to analyze the developed model. In the first scenario, the interest rate is assumed constant, and changes in the inflation rate are investigated. In the second scenario, the inflation rate is assumed constant, and changes in the interest rate are studied. These scenarios enable the decision-maker to select the best inventory policy by considering important factors, including interest rate, inflation rate, and DGR.
Empirical study
In this section, different scenarios and sub-scenarios for DGR, interest rate and inflation rate are defined in order to investigate the behavior of the system. The simulation is coded in MATLAB software on a laptop with Intel Core i5 8250U 3.4 GHz (two cores) and 8 GB RAM running Windows 10.
Scenario 1
As discussed before, in this scenario, the interest rate is assumed constant, i.e., ir=18%, and the changes in the inflation rate are investigated with respect to 0%≤e≤10000%. Based on Eqs. (25)–(28), if ir=18% then we have:29 α1=5.46e-1.08-2.64e+0.54,
30 α2=0.18e-e+0.18,
31 α3=0
32 α4=-3e-62e+3.
In Eq. (29), -2.64e+0.54≠0, and consequently e≠20.45%. Moreover, if e=19.78% then α1=0. It is clear that if 19.78%<e<20.45% then α1>0. In addition, if e<19.78% or e>20.45% then α1<0. In Eq. (30), -e+0.18≠0, and consequently e≠18%. Moreover, if e=0% then α2=0. It is clear that if 0%<e<18% then α2>0. Moreover, if -100%<e<0% or e>18% then α2<0. Based on Eq. (31), for any value of e, we have α3=0. In Eq. (32), 2e+3≠0, and consequently e≠-150%. Since e is always greater than − 100%, e≠-150% is an additional constraint. Furthermore, since -100%<e<+∞ then -3<α4<-1.5. By solving αi=αj (i<j;i,j=1,2,3,4), e is computed as equal to 0%, 19.78%, and 19.84%. Hence, 0%, 18%, 19.78%, 19.84%, and 20.45% are defined as key values of the inflation rate.
However, five intervals are determined to investigate the effects of the inflation rate, i.e., [0%,18%], [18%,19.78%], [19.78%,19.84%], [19.84%,20.45%], and [20.45%,100%]. In addition, e=10000% is determined as mega inflation. Here, the borders and the averages of intervals are used to perform sensitivity analysis. In summary, twelve different sub-scenarios are introduced including e=0%, e=9%, e=18%, e=18.89%, e=19.78%, e=19.81%, e=19.84%, e=20.145%, e=20.45%, e=60.225%, e=100%, and e=10000%. To analyze the above-mentioned sub-scenarios, DGR∈-1,10 and n∈1,2,…,1000 are considered. Table 3 shows the changes in ∂TC∂n according to different sub-scenarios.Table 3 Sign of ∂TC∂n in Scenario 1
Sub-scenarios
1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12
ir (%) 18 18 18 18 18 18 18 18 18 18 18 18
e (%) 0 9 18 18.89 19.78 19.81 19.84 20.145 20.45 60.225 100 10,000
∂TC/∂n − − − ± ± ± ± ± + + + +
Based on Table 3, for Sub-scenarios 1.1, 1.2, and 1.3, ∂TC∂n is lower than zero. This means that if ir=18% and e∈0%,18% then it is the best inventory policy for retailers to hold no inventory and send customer orders directly to the suppliers. For Sub-scenarios 1.4, 1.5, 1.6, 1.7, and 1.8, ∂TC∂n may have different signs depending on the values of DGR and n. Moreover, for Sub-scenarios 1.9, 1.10, 1.11, and 1.12, ∂TC∂n is greater than zero. This means that if ir=18% and e∈20.45%,+∞ then it is the best inventory policy for retailers to order all needed items at once at the start of the year, which in turn, leads to hoarding of goods. In the following, Sub-scenarios 1.4, 1.5, 1.6, 1.7, and 1.8 are investigated to evaluate the effects of DGR on the optimal inventory policies.
Sub-scenario 1.4: (ir=18%, e=18.89%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as − 1.17679, − 3.82045, 0, and − 1.94408, respectively. Table 4 represents the changes of ∂TC∂n in terms of DGR. As shown in this table, for DGR∈[-1,10], TC is not a strictly increasing or decreasing function. Hence, for finding n∗, we should find all extremum points by solving ∂TC∂n=0.Table 4 Sign of ∂TC∂n in Sub-scenario 1.4
DGR
− 1 0 10
∂TC/∂n NA ± ± NA
Sub-scenario 1.5: (ir=18%, e=19.78%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 0, − 2, 0, and − 1.94175, respectively. As shown in Table 5, for DGR∈[-1,0], we have ∂TC∂n>0, and consequently n∗=1. Moreover, for DGR∈[0,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 5 Sign of ∂TC∂n in Sub-scenario 1.5
DGR
− 1 0 10
∂TC/∂n NA + ± NA
Sub-scenario 1.6: (ir=18%, e=19.81%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 0.09556, − 1.97006, 0, and − 1.94167, respectively. As shown in Table 6, for DGR∈[-1,0.09556], ∂TC∂n>0, and consequently n∗=1. Moreover, for DGR∈[0.09556,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 6 Sign of ∂TC∂n in Sub-scenario 1.6
DGR
− 1 0 0.09556 10
∂TC/∂n NA + + ± NA
Sub-scenario 1.7: (ir=18%, e=19.84%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 0.19839, − 1.94159, 0, and − 1.94159, respectively. As shown in Table 7, for DGR∈[-1,0.19839], ∂TC∂n>0, and consequently n∗=1. Moreover, for DGR∈[0.19839,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 7 Sign of ∂TC∂n in Sub-scenario 1.7
DGR
− 1 0 0.19839 10
∂TC/∂n NA + + ± NA
Sub-scenario 1.8: (ir=18%, e=20.145%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 2.43722, − 1.69049, 0, and − 1.9408, respectively. As shown in Table 8, for DGR∈[-1,2.43722], ∂TC∂n>0, and consequently n∗=1. Moreover, for DGR∈[2.43722,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 8 Sign of ∂TC∂n in Sub-scenario 1.8
DGR
− 1 0 2.43722 10
∂TC/∂n NA + + ± NA
Scenario 2
As mentioned previously, in this scenario, the inflation rate is assumed constant, i.e., e=40.52%, and the changes in the interest rate are investigated with respect to 0%≤ir≤100%. Based on Eqs. (25)–(28), if e=40.52% then we have33 α1=18039ir-6078-9526ir+3039,
34 α2=1013ir2500ir-1013,
35 α3=0.
36 α4=-1.89366.
In Eq. (33), -9526ir+3039≠0, and consequently ir≠31.9%. Moreover, if ir=33.69% then α1=0. It is clear that if 31.9%<ir<33.69% then α1>0. Furthermore, if ir<31.9% or ir>33.69% then α1<0. In Eq. (34), 2500ir-1013≠0, and consequently ir≠40.52%. Moreover, if ir=0% then α2=0. It is clear that if 0%<ir<40.52% then α2<0. In addition, if ir>40.52% then α2>0. Based on Eqs. (35) and (36), for any value of ir, we have α3=0 and α4=-1.89366. By solving αi=αj (i<ji,j=1,2,3,4), ir is computed as equal to 0%, 33.38%, and 33.69%. Hence, 0%, 31.9%, 33.378%, 33.69%, and 40.52% are defined as key values of interest rate.
However, five intervals are determined to investigate the effects of interest rate, i.e., [0%, 31.9%], [31.9%, 33.378%], [33.378%, 33.69%], [33.69%, 40.52%], and [40.52%, 100%]. Here, the borders and the averages of intervals are used to perform sensitivity analysis. In summary, eleven different sub-scenarios are introduced including ir=0%, ir=15.95%, ir=31.9%, ir=32.639%, ir=33.378%, ir=33.534%, ir=33.69%, ir=37.105%, ir=40.52%, ir=70.26%, and ir=100%. To analyze the above-mentioned sub-scenarios, DGR∈[-1,10] and n∈{1,2,⋯,1000} are considered. Table 9 represents the changes in ∂TC∂n according to different sub-scenarios.Table 9 Sign of ∂TC∂n in Scenario 2
Sub-scenarios
2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 2.10 2.11
ir (%) 0 15.95 31.9 32.639 33.378 33.534 33.69 37.105 40.52 70.26 100
e (%) 40.52 40.52 40.52 40.52 40.52 40.52 40.52 40.52 40.52 40.52 40.52
∂TC/∂n + + + ± ± ± ± ± − − −
According to Table 9, for Sub-scenarios 2.1, 2.2, and 2.3, ∂TC∂n is greater than zero. This means that if e=40.52% and ir∈0%,31.9% then it is the best inventory policy for retailers to order all needed items at once at the start of the year, which in turn, leads to the hoarding of goods. For Sub-scenarios 2.4, 2.5, 2.6, 2.7, and 2.8, ∂TC∂n may have different signs depending on the values of DGR and n. Moreover, for Sub-scenarios 2.9, 2.10, and 2.11, ∂TC∂n is lower than zero. This means that if e=40.52% and ir∈40.52%,100% then it is the best inventory policy for retailers to hold no inventory and send customer orders directly to the suppliers. In the following, Sub-scenarios 2.4, 2.5, 2.6, 2.7, and 2.8 are investigated to evaluate the effects of DGR on the optimal inventory policies.
Sub-scenario 2.4: (ir=32.639%, e=40.52%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 2.71047, − 1.67813, 0, and − 1.89366, respectively. As shown in Table 10, for DGR∈[-1,2.71047], ∂TC∂n>0, and consequently n∗=1. Moreover, for DGR∈[2.71047,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 10 Sign of ∂TC∂n in Sub-scenario 2.4
DGR
− 1 0 2.71047 10
∂TC/∂n NA + + ± NA
Sub-scenario 2.5: (ir=33.378%, e=40.52%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 0.4052, − 1.89366, 0, and − 1.89366, respectively. As shown in Table 11, for DGR∈[-1,0.4052], ∂TC∂n>0, and consequently n∗=1. Moreover, for DGR∈[0.4052,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 11 Sign of ∂TC∂n in Sub-scenario 2.5
DGR
− 1 0 0.4052 10
∂TC/∂n NA + + ± NA
Sub-scenario 2.6: (ir=33.534%, e=40.52%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 0.18528, − 1.94503, 0, and − 1.89366, respectively. As shown in Table 12, for DGR∈[-1,0.18528], ∂TC∂n>0, and consequently n∗=1. Moreover, for DGR∈[0.18528,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 12 Sign of ∂TC∂n in Sub-scenario 2.6
DGR
− 1 0 0.18528 10
∂TC/∂n NA + + ± NA
Sub-scenario 2.7: (ir=33.69%, e=40.52%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as 0, − 2, 0, and − 1.89366, respectively. As shown in Table 13, for DGR∈[-1,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 13 Sign of ∂TC∂n in Sub-scenario 2.7
DGR
− 1 0 10
∂TC/∂n NA ± ± NA
Sub-scenario 2.8: (ir=37.105%, e=40.52%)
Based on Eqs. (25)–(28), α1, α2, α3, and α4 are computed as − 1.24161, − 4.40262, 0, and − 1.89366, respectively. As shown in Table 14, for DGR∈[-1,10], TC is not a strictly increasing or decreasing function and n∗ is obtained by seeking the extremum points.Table 14 Sign of ∂TC∂n in Sub-scenario 2.8
DGR
− 1 0 10
∂TC/∂n NA ± ± NA
In the following, three of the most important macroeconomic factors, i.e., inflation rate, interest rate, and DGR, are considered in a thorough analysis. In general, interest rate is a primary tool used by government banks to manage the inflation rate. In other words, government banks tend to increase the interest rate in response to the rising inflation rate. When the interest rate increases, people are more willing to save in banks, which in turn leads to a lower amount of purchases and consequently reduces the inflation rate. In contrast, when the interest rate decreases, people are reluctant to save in banks which leads to a higher amount of purchases. In this case, the probability of shortage increases and consequently increases the inflation rate.
Discussion
In the previous section, changes in interest and inflation rates have been investigated under two different scenarios. Based on the obtained results, each scenario is divided into three sections. In the first section of Scenario 1, which includes Sub-scenarios 1.1, 1.2, and 1.3, the inflation rate is lower than or equal to the interest rate, e∈[0%,18%]. In this section, it is the best inventory policy for retailers to hold no inventory and send customer orders directly to the suppliers. In other words, due to the high costs of inventory holding, retailers are reluctant to invest in inventory. Because of that, the probability of shortages increases but the potential of hoardings decreases.
The second section of Scenario 1, i.e., e∈[18%,20.45%], includes Sub-scenarios 1.4, 1.5, 1.6, 1.7, and 1.8. However, ∂TC∂n shows a non-uniform behavior in this section. In Sub-scenario 1.4, for DGR∈[-1,10], TC is not a strictly increasing or decreasing function, and its behavior depends on the values of DGR and n. At first, all extremum points are extracted from TC. Among them, the point with the minimum total cost is introduced as the optimal inventory policy. Similarly, for DGR∈[0,10] of Sub-scenario 1.5, DGR∈[0.09556,10] of Sub-scenario 1.6, DGR∈[0.19839,10] of Sub-scenario 1.7, and DGR∈[2.43722,10] of Sub-scenario 1.8, the optimal inventory policy is obtained by seeking the extremum points. In addition, for DGR∈[-1,0] of Sub-scenario 1.5, DGR∈[-1,0.09556] of Sub-scenario 1.6, DGR∈[-1,0.19839] of Sub-scenario 1.7, and DGR∈[-1,2.43722] of Sub-scenario 1.8, the optimal inventory policy is n∗=1. Each above-mentioned sub-scenario can be analyzed based on the changes in DGR. For example, in Sub-scenario 1.7, if DGR is lower than or equal to 0.19839, holding costs are less than buying costs. In this case, retailers prefer to invest in inventories (instead of investing in bank deposits), which in turn increases the hoardings of goods. Moreover, for DGR>0.19839, holding costs increases gradually when DGR increases, and consequently, retailers prefer to reduce the size of orders. The comparison of Sub-scenarios 1.4, 1.5, 1.6, 1.7, and 1.8 indicates that when e-ir increases, buying costs increase more rapidly than holding costs, and consequently, retailers are more eager to invest in inventories.
The third section of Scenario 1, i.e., e∈20.45%,+∞, includes Sub-scenarios 1.9, 1.10, 1.11, and 1.12. For all these sub-scenarios, we have ∂TC∂n>0. It means that total inventory cost increases when increasing the number of orders. In other words, total inventory cost is minimized at n=1, i.e., n∗=1. In this section, the inflation rate is much greater than the interest rate, and consequently, holding costs are much smaller than buying costs. In this situation, due to the low costs of inventory holding, it is the best replenishment policy for retailers to place a single order at the start of the year and use the on-hand inventory to satisfy the annual demand. Because of that, the probability of shortages decreases but the potential of hoardings increases.
Similar to Scenario 1, Scenario 2 is divided into three sections. The first section of Scenario 2, i.e., ir∈0%,31.9%, includes Sub-scenarios 2.1, 2.2, and 2.3. Since ∂TC∂n is greater than zero for all DGR levels, the optimal replenishment policy is n∗=1. In other words, in this section, holding costs are much smaller than buying costs which is a strong incentive for retailers to order all needed items at the start of the planning horizon leading to the hoarding of goods.
The second section of Scenario 2, i.e., ir∈[32.639%,37.105%], includes Sub-scenarios 2.4, 2.5, 2.6, 2.7, and 2.8. Since ∂TC∂n has different signs for each sub-scenario, TC is analyzed based on the values of DGR. In Sub-scenario 2.4, if DGR is lower than or equal to 2.71047, holding costs are less than buying costs. In this case, retailers prefer to invest in inventories which in turn increases hoardings of goods. Moreover, for DGR>2.71047, TC is not a strictly increasing or decreasing function, and its behavior depends on the values of DGR and n. Here, the optimal inventory policy is obtained by extracting the local extremum points. Similarly, for DGR∈[0.4052,10] of Sub-scenario 2.5, DGR∈[0.18528,10] of Sub-scenario 2.6, DGR∈[-1,10] of Sub-scenario 2.7, and DGR∈[-1,10] of Sub-scenario 2.8, the optimal inventory policy is obtained by seeking the extremum points. In addition, for DGR∈[-1,0.4052] of Sub-scenario 2.5 and DGR∈[-1,0.18528] of Sub-scenario 1.6, the optimal inventory policy is n∗=1. The comparison of Sub-scenarios 2.4, 2.5, 2.6, 2.7, and 2.8 indicates that when e-ir decreases, holding costs increase more rapidly than buying costs, and consequently, retailers are more reluctant to invest in inventories.
In the third section of Scenario 2, which includes Sub-scenarios 2.9, 2.10, and 2.11, the interest rate is grower than or equal to the inflation rate, ir∈[40.52%,100%]. In this section, it is the best inventory policy for retailers to hold no inventory and send customer orders directly to the suppliers. In other words, due to the high costs of inventory holding, retailers are reluctant to invest in inventory. Because of that, the probability of shortages increases but the potential of hoardings decreases.
Conclusions
In this study, a novel mathematical model was developed to investigate the interactive of three main economic factors on the behaviors of retailers in Iran. The impact of DGR on the optimal replenishment policy was studied. In the developed model, the annual inflation and interest rates were assumed constant over time. Furthermore, DGR was considered to be independent of the inflation rate. According to different scenarios and sub-scenarios, we obtained the following results: (1) if e≤18% or ir≥40.52%, ∂TC∂n is lower than zero for all DGR levels. In other words, changes in DGR have no impact on the behavior of TC. In this case, holding costs are much higher than buying costs, and retailers are reluctant to invest in inventories, (2) if e≥20.45% or ir≤31.9%, ∂TC∂n is greater than zero for all DGR levels. In other words, changes in DGR have no impact on the behavior of TC. In this case, buying costs are much higher than holding costs, and retailers are eager to invest in inventories instead of bank deposits, and (3) if 18%<e<20.45% or 31.9%<ir<40.52%, ∂TC∂n has different signs depending on the values of DGR. In this case, the first step is to find all extremum points, then among them, the point with the minimum cost is chosen as the optimal replenishment policy.
In summary, the present study analyzed the effects of the most important macroeconomic factors, i.e., inflation rate, interest rate, and DGR, on the behavior of retailers in Iran. From one point of view, the proposed methodology enables the decision-makers to predict the behavior of retailers based on the values of the inflation rate, interest rate, and DGR. Form the other point of view, the decision-makers can use the interest rate as leverage to set the probability of shortages and hoardings.
Besides the benefits of the proposed methodology, there are several options to develop the present study. First of all, the developed model can be used to analyze the behavior of retailers in other countries, especially the ones which suffer high fluctuations in the inflation rate, such as Argentina, Venezuela, and Turkey. However, considering stochastic interest and inflation rates, and studying DGR as a function of the inflation rate, are some of the possible directions of future research. Sustainable development of the problem is another interesting direction to study the impacts of environmental factors. Moreover, the entire supply chain of a specific product can be taken into account in order to minimize/maximize the total cost/profit according to the proposed model.
Declarations
Conflict of interest
The authors declare no conflict of interest.
Human or animals rights
This article does not contain any studies with human participants performed by any of the authors.
Informed consent
Informed consent was obtained from all individual participants included in the study.
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| 0 | PMC9736725 | NO-CC CODE | 2022-12-14 23:29:53 | no | Ann Oper Res. 2022 Dec 10;:1-25 | utf-8 | Ann Oper Res | 2,022 | 10.1007/s10479-022-05116-1 | oa_other |
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Int J Pediatr Otorhinolaryngol
Int J Pediatr Otorhinolaryngol
International Journal of Pediatric Otorhinolaryngology
0165-5876
1872-8464
Elsevier B.V.
S0165-5876(22)00367-6
10.1016/j.ijporl.2022.111406
111406
Article
The short-term effect of COVID-19 on the cochleovestibular system in pediatric patients
Demir Ismail a
Aydin Sukru b∗
Cengiz Deniz Ugur a
a , Department of Audiology, Inonu University Faculty of Health Sciences, Malatya, Turkey
b , Department of Otolaryngology Head and Neck Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
∗ Corresponding author.
10 12 2022
1 2023
10 12 2022
164 111406111406
1 10 2022
14 11 2022
8 12 2022
© 2022 Elsevier B.V. All rights reserved.
2022
Elsevier B.V.
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Objectives
The audio-vestibular equivalent of neurological symptoms secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been discussed; however, it has not been fully clarified. Although it has been reported that the vestibulocochlear system is affected in adult coronavirus disease-2019 (COVID-19) patients, there is no study in the literature in which the pediatric patient group with COVID-19 was evaluated comprehensively with auditory and vestibular tests. In this study, the short-term damage caused by SARS-CoV-2 in the vestibulocochlear system in pediatric patients was examined.
Methods
This study aimed to evaluate the vestibulocochlear system of pediatric patients (aged 9–15 years) with a recent history of COVID-19. The study included 35 individuals with a recent history of COVID-19 and 35 age-gender-matched healthy individuals (control group). Pure tone audiometry, suppressed otoacoustic emission (OAE), video head impulse test (VHIT), and cervical and ocular vestibular evoked myogenic potentials (c/o-VEMP) tests were administered to all participants following their otoscopic examinations, and the obtained data were compared between the two groups.
Results
When the data obtained with pure tone audiometry were compared, statistically significant differences were found between the groups at four different frequencies (1000, 2000, 4000, and 8000 Hz) in favor of the control group. There was a statistically significant difference between the groups in the signal-to-noise ratio (SNR) values obtained before noise at 2800 Hz and before and after noise at 4000 Hz. VHIT lateral gain, LARP gain, and RALP gain were statistically significantly lower in the COVID-19 group than in the control group (p < 0.05). VHIT lateral asymmetry parameter was measured higher in the COVID-19 group than in the control group, and this difference was statistically significant (p < 0.05). In the VHIT test, the asymmetry parameter was significantly higher in the COVID-19 group (p < 0.05). In the o-VEMP test, n10 latency, p15 latency, n10-p15 interlatency, n10-p15 interpeak amplitude, and asymmetry parameters were measured, and no statistically significant difference was found between the COVID-19 group and the control group (p > 0.05).
Conclusion
Evidence was obtained that the cochleovestibular system was damaged in pediatric patients in the early post-COVID-19 period.
Keywords
Cochleovestibular system
COVID-19
Pediatric
Vertigo
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pmc1 Introduction
A new type of coronavirus emerged in the city of Wuhan in China in 2019, spreading worldwide and creating a pandemic. This new type of coronavirus was defined as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and named coronavirus disease-2019 (COVID-19) by the World Health Organization [1].
COVID-19 may be asymptomatic or present with a wide range of clinical complaints such as respiratory distress, fever, myalgia, sore throat, cough, and smell and taste disorders. In addition to these classical complaints, other symptoms such as facial paralysis, sudden hearing loss, and dizziness and tinnitus, which alert otolaryngologists, were frequently observed during the pandemic process.
In studies, it has been shown that many viral pathogens (Rubella, measles, mumps, herpes simplex virus, human immunodeficiency virus, varicella zoster virus), especially cytomegalovirus (CMV), cause congenital or acquired hearing loss by damaging labyrinth structures [2]. Viral pathogens are thought to damage the labyrinth structures directly (stria vascularis, organ of Corti, Reissner's membrane, cochlear and central neuronal structures) or indirectly (decreased immunity and secondary infection, host immune response to viral antigen) [2]. In temporal bone studies, it has been shown histopathologically that viruses pass through the stria vascularis and endolymph, cause cochlear duct and saccule hydrops, can be cultured from the perilymph fluid, and cause viral antigen production in spiral ganglion cells in the organ of Corti [[3], [4], [5]]. Since the neurotropic and neuroinvasive characteristics of SARS-CoV-2 were defined, its neurological effects have been discussed [6]. In studies published so far, it has been reported that SARS-CoV-2 causes neurological symptoms in approximately 30% of the patients [7]. It is discussed whether the neurological symptoms secondary to SARS-CoV-2 are the direct or indirect effects of the virus. Various authors have reported that the vestibulocochlear system is affected in patients with COVID-19 [8,9]; however, there is no study in the literature in which pediatric COVID-19 patients were evaluated comprehensively with auditory and vestibular tests. As this is the first study in the literature to examine the audio-vestibular findings in this group, it is of great importance.
Numerous subjective and objective tests have been described to evaluate the vestibulocochlear system. An otoacoustic emission (OAE) is used for measuring outer hair cells and the function of the cochlea [10]. It gives precious information to evaluate the early damage in the cochlea and outer hair cells that cannot be assessed in pure tone audiometry [11]. Suppressed OAE is used to evaluate whether the efferents originating from the Medial Olivary Complex (MOC) are functioning. Vestibular-evoked myogenic potentials (VEMP) is an objective test defined to measure saccule and utricle functions [12]. The video head impulse test (VHIT) is an objective test battery that assesses the semicircular canals and the superior and inferior vestibular nerves via the vestibule-ocular reflex.
Studies evaluating the cochleovestibular system in the literature are mostly on adult patients. Studies examining the vestibulocochlear system in detail in pediatric patients are scarce and have a narrow scope [13]. In this study, the vestibulocochlear system was discussed with objective and subjective tests in pediatric patients in the early-post-COVID-19 period, and it was investigated whether SARS-CoV-2 damaged the vestibulocochlear system in this period.
2 Materials end methods
In this study, we aimed to evaluate the vestibulocochlear involvement of pediatric patients (aged 9–15 years) in the early period of post-COVID-19. The research was carried out in the Audiology Unit and Otolaryngology Clinic of the Inonu University Turgut Ozal Medical Center between December 2021 and March 2022. Thirty-five patients in the early post-COVID-19 period (COVID-19 group) and 35 age- and gender-matched healthy individuals (control group) were included in the study. All patients in the COVID-19 group were evaluated after their first COVID-19 infection and none of them had been vaccinated before. In the COVID-19 group, patients who survived the COVID-19 disease as an outpatient and did not need oxygen support during the recovery period were included (which can be classified as a mild disease). The diagnosis of COVID-19 was made in all patients by real-time Polymerase Chain Reaction (PCR) via the oro-nasopharyngeal swab sample. Those who had complaints of dizziness and imbalance, conductive hearing loss, and otologic and neurological diseases in both control group and COVID-19 group (before COVID-19) were excluded from the study. Ethical approval was obtained from the Inonu University Health Sciences Institute Non-Interventional Clinical Research Ethics Committee (Decision number: 2021/2558), and written and verbal informed consent was obtained from the parents of all children participating in the study. While conducting the research, all principles of the Declaration of Helsinki were adhered to and followed. Pure tone audiometry, suppressed OAE, VHIT, and c/o-VEMP tests were applied to all participants included in the study after their otoscopic examinations.
2.1 Sociodemographic data form
The parents filled out a form containing information such as age, gender, symptoms during the disease process, date of diagnosis, and duration of disease.
2.2 Otoacoustic emission (OAE) and pure tone audiometry
Audiological evaluations were made by the same audiologist, accompanied by an otolaryngologist. Pure tone audiometry consisting of 8 frequencies (125, 250, 500, 1000, 2000, 4000, 6000, and 8000 Hz) was performed in all patients with the Interacoustics-Clinical Audiometer AC40 (Middelfart, Denmark) device in a quiet cabin. During the statistical analysis, each frequency was compared between the two groups.
Transient evoked OAE (TE-OAE) tests and contralateral suppression (CLS) application were performed using an Otodynamics-ILO 292 USB II (Herts, United Kingdom) device. A test probe was placed in both ears and 260 linear instantaneous stimuli with 80 ± 3 dB sound-pressure level (dB SPL) intensity were recorded in the ipsilateral ear, and a 60 dB wideband noise was sent to the contralateral ear in linear stimulus mode, then TEOAE measurements were made in the ipsilateral ear with and without noise [14]. Immediate evoked otoacoustic emission responses were recorded at frequencies of 1000, 1400, 2000, 2800, and 4000 Hz. Signal-to-noise ratio (SNR) values of both tests were analyzed as operating parameters.
2.3 Video head impulse test (VHIT)
The Video Head Impulse Test (VHIT) is a vestibular test battery used to evaluate the functions of the semicircular canals (SCC). This test battery provides information about the vestibulo-ocular reflex (VOR) at high frequencies by evaluating the harmony between rapid head movement and eye movement. The test was performed with a Micromedical Technologies-EyeSeeCam (Illınois, US) device. At the end of the test, the VOR gain graph was obtained according to the head and eye movement speeds. The speed ratio of head and eye movement should be 1.0 in healthy individuals. In our clinic, the standard deviations of this value were calculated and evaluated between 0.8 and 1.1. A VOR gain of less than 0.8 and a percentage of asymmetry greater than 6.9 were considered a pathological VHIT response [15].
2.4 Vestibular evoked myogenic potentials test (c-VEMP/o-VEMP)
c-VEMP and o-VEMP tests were performed with the Neurosoft Neuro-Audio (Ivanovo-Russia) device. When myogenic potentials could not be obtained, it was considered a pathological finding. The proportion of patients in whom myogenic potentials could not be obtained in both the o-VEMP test and the c-VEMP test were statistically compared between groups. The electromyographic signals were amplified and bandpass-filtered between 30 and 2000 Hz. Short-tone burst stimulations (105 dB HL, 500 Hz, each with a 2-ms rise fall time and a 0-ms plateau time) were delivered to each ear. The peak latencies of waves p13 and n23, p13-n23 interpeak latencies, and peak-to-peak amplitudes (p13–n23) were recorded for each ear. The asymmetry ratio was calculated to compare the right and left ears using the formula described by Murofushi et al. [16].
The Ocular VEMP (o-VEMP) test was performed while the participants were in a sitting position. The peaks of the first waveform formed after the stimulus were determined as n10 and p15. The electromyographic signals were amplified and bandpass-filtered between 1 and 1000 Hz. Sound stimuli were delivered to the contralateral side of the active electrode with an intensity of 105 dB HL. The peak latencies of waves n10 and p15 and peak-to-peak amplitudes (n10–p15) were recorded for each ear. The asymmetry ratio was calculated to compare the right and left ears using the formula described by Murofushi et al. [16].
2.5 Statistical analysis
Data analysis was carried out with the SPSS 25 (New York, US) program. Whether the data included in the study conformed to the normal distribution was checked with the Kolmogorov-Smirnov Test [17]. The significance level (p) for comparison tests was taken as 0.05.
Since the variables did not have a normal distribution (p > 0.05), the analysis was continued with non-parametric test methods. Comparisons in independent pairs were made with the Mann-Whitney U test because the assumption of normality was not provided. In the analysis of categorical data, cross tables were created and the Chi-square (ꭓ2) analysis was performed.
3 Results
Demographic data are presented in Table 1 . The mean age of the participants included in the study was 12.66 ± 2.11 years (min: 9-max: 15) in the COVID-19 group and 11.71 ± 2.23 years (min: 9-max: 15) in the control group. There was no statistically significant difference between the groups in terms of mean age (p = 0.070). The gender distribution of the groups was similar and there was no statistically significant difference (p = 0.810).Table 1 Comparison of demographic data between groups.
Table 1 Groups p-value
COVID-19 Group Control Group
Mean ± SD Min-Max Mean ± SD Min-Max
Age 12,66 ± 2,11 9–15 11,71 ± 2,23 9–15 0,070b
Count Percent (%) Count Percent (%)
Gender Female 15 42,9% 16 45,7% 0,810a
Male 20 57,1% 19 54,3%
SD; standard deviation pa; Chi-square test value (ꭓ2), pb; Mann Whitney U test value, *p-values in bold indicate statistically significance.
The parameters related to the disease process of COVID-19 were analyzed, and none of the patients with COVID-19 were hospitalized and received oxygen therapy. The most common symptom was evaluated as fever (68.6%). Apart from fever, the symptoms recorded in the patients were shortness of breath, arthralgia, weakness, headache, dizziness and vertigo, and loss of taste and loss of smell, in order of frequency. When patients were retrospectively screened for audiovestibular complaints during the COVID-19 period, six patients had complaints of vertigo/dizziness, fullness in the ear, and tinnitus. There were only vertigo/dizziness and hearing loss in three patients, only tinnitus in two patients, and fullness in the ear only in two patients. Tinnitus and vertiginous complaints were present in only two patients at time of study. In the further examinations of these two patients, mild sensorineural hearing loss affecting advanced frequencies (4000 Hz and above) was observed in both, and vestibular tests were considered normal. The mean duration of COVID-19 was 11.31 ± 2.79 days. The mean time from one negative COVID-19 PCR test to audio-vestibular evaluation was 51.75 ± 18.82 days.
Pure tone audiometry was measured at eight different frequencies. When the groups were compared, statistically significant differences were noted between the groups at four different frequencies (1000, 2000, 4000, and 8000 Hz). The hearing thresholds of the control group were determined better than the COVID-19 group in all four frequencies. In Table 2 , mean values of 8 frequencies and comparisons of both groups are presented.Table 2 Comparisons of pure tone averages between groups.
Table 2Frequency Control COVID-19 p value
Mean ± SD Median (Min-Max) Mean ± SD Median (Min-Max)
125 Hz 5,36 ± 2,46 5 (0–10) 5,29 ± 2,68 5 (0–10) 0,884
250 Hz 6,71 ± 3,8 5 (0–15) 7,64 ± 3,97 5 (0–20) 0,291
500 Hz 7,07 ± 3,76 5 (0–15) 7,5 ± 3,48 5 (5–20) 0,821
1000 Hz 5,29 ± 3,98 5 (0–15) 7,71 ± 3,48 10 (0–15) <0,001*
2000 Hz 5,14 ± 4,08 5 (0–15) 7,29 ± 3,68 5 (0–15) 0,001*
4000 Hz 5,5 ± 4,67 5 (0–20) 7,71 ± 3,58 5 (0–20) 0,001*
6000 Hz 9,36 ± 6,19 10 (0–30) 7,57 ± 3,78 5 (0–20) 0,078
8000 Hz 8,79 ± 8,53 5 (0–50) 7,43 ± 3,38 7,5 (0–15) 0,945
SD; standard deviation, Hz; Hertz, *p-values in bold indicate statistically significance.
Statistical analysis of whether suppression occurred in suppressed transient otoacoustic emission is presented in Table 3 . Suppression at five different frequencies was obtained almost completely in the control group (not observed in 1 participant at 1000 Hz and 2 participants at 1400 Hz). In contrast, there were patients in whom suppression was not obtained at every frequency in the COVID-19 group. The inability to obtain suppression in the COVID-19 group at all frequencies was higher and statistically significant compared to the control group.Table 3 Comparison of the presence of suppression in the otoacoustic emission test between groups.
Table 3Frequencies Suppression (dB SPL) Groups p value
COVID-19 Control
1000 Hz <1 14 (20,0%) 1 (1,4%) 0,001*
>1 56 (80,0%) 69 (98,6%)
1400 Hz <1 14 (20,0%) 2 (2,9%) 0,003*
>1 56 (80,0%) 68 (97,1%)
2000 Hz <1 5 (7,1%) 0 (0,0%) 0,008*
>1 65 (92,9%) 70 (100,0%)
2800 Hz <1 16 (22,9%) 0 (0,0%) 0,001*
>1 54 (77,1%) 70 (100,0%)
4000 Hz <1 17 (24,3%) 0 (0,0%) 0,001*
>1 53 (75,7%) 70 (100,0%)
dB SPL: decibel Sound Pressure Level, *p-values in bold indicate statistically significance.
Suppressed otoacoustic emission data were analyzed by comparing the signal-noise ratio (SNR) values obtained from the ipsilateral ear before and after the noise was introduced into the contralateral ear (Table 4 ). There was a statistically significant difference between the groups in terms of the SNR values obtained before the noise at 2800 Hz and before and after the noise at 4000 Hz.Table 4 Comparison of SNR values obtained during OAE and Suppressed OAE between groups.
Table 4Frequency Groups p-value*
COVID-19 Group Control Group
Mean ± SD Median (Min-Max) Mean ± SD Median (Min-Max)
1 kHz 14,39 ± 5,16 13,65 (5,2–25,20) 14,24 ± 4,65 13,90 (7,5–25,6) 0,833
1 kHz with suppression 11,17 ± 5,23 10,15 (3,1–24,8) 9,86 ± 4,02 9,1 (5,1–20,9) 0,212
1.4 kHz 14,13 ± 5,01 12,65 (7,1–27,1) 13,82 ± 4,91 14,35 (6,3–25)9 0,698
1.4 kHz with suppression 11,45 ± 5,08 11,1 (5,1–26,4) 10,36 ± 4,67 10,15 (4,2–23)9 0,157
2 kHz 14,35 ± 4,49 14,55 (6,8–25,9) 15,36 ± 5,65 15 (6,2–27,1) 0,498
2 kHz with suppression 11,19 ± 4,07 11,45 (5,1–23,7) 10,97 ± 4,98 10,5 (4,5–22,9) 0,486
2.8 kHz 13,12 ± 4,51 12,2 (7,1–25,5) 15,39 ± 6,1 14,55 (6,1–28,6) 0,042*
2.8 kHz with suppression 10,59 ± 4,51 10,75 (3,7–25,4) 11,59 ± 5,28 10,95 (4,5–22,9) 0,381
4 kHz 11,63 ± 4,24 10,1 (4,2–21,5) 15,36 ± 5,34 15,45 (6,1–27,5) <0,001*
4 kHz with suppression 9,22 ± 4,08 7,85 (4,1–19,8) 11,44 ± 4,46 11,35 (5–21,8) 0,003*
SNR: The signal-to-noise ratio, OAE: otoacoustic emission, kHz: kilohertz, SD: Standard deviation, *p-values in bold indicate statistically significance.
The VHIT lateral gain, left anterior right posterior (LARP) gain, right anterior left posterior (RALP) gain, lateral asymmetry, LARP asymmetry, and RALP asymmetry values of the participants included in the study were compared between the groups, and the data are presented in Table 5 . VHIT lateral gain, LARP gain, and RALP gain were statistically significantly lower in the COVID-19 group than in the control group (p < 0.001, p = 0.049, p = 0.044, respectively). The VHIT lateral asymmetry parameter was statistically higher in the COVID-19 group than in the control group (p = 0.036). In addition, there was no statistically significant difference between patients with and without COVID-19 according to LARP asymmetry and RALP asymmetry values (p > 0.05, Table 5).Table 5 Comparison of the v-HIT parameters between groups.
Table 5 Groups p-value*
COVID-19 Group Control Group
Mean ± SD Median (Min-Max) Mean ± SD Median (Min-Max)
v-HIT lateral gain 0,91 ± 0,07 0,9 (0,76–1,12) 0,97 ± 0,06 0,98 (0,8–1,08) <0,001*
v-HIT LARP gain 0,84 ± 0,1 0,85 (0,62–1,06) 0,88 ± 0,12 0,9 (0,63–1,07) 0,049*
v-HIT RALP gain 0,84 ± 0,12 0,85 (0,6–1,03) 0,88 ± 0,11 0,9 (0,67–1,08) 0,044*
v-HIT lateral asymmetry 3,14 ± 1,54 3,1 (0,8–6,7) 2,39 ± 1,59 2 (0,4–7) 0,036*
v-HIT LARP asymmetry 4,49 ± 2,94 3,3 (0,9–12,7) 3,93 ± 2,84 3 (0,5–10,5) 0,344
v-HIT RALP asymmetry 4,51 ± 3 3,6 (0,1–15,2) 3,55 ± 2,36 2,5 (1–9,7) 0,075
v-HIT: Video Head Impulse Test, LARP: Left Anterior, Right Posterior, RALP: Right Anterior, Left Posterior SD: Standard deviation, *p-values in bold indicate statistically significance.
The participants also received the c-VEMP and o-VEMP tests. In the c-VEMP test, p13 latency, n23 latency, p13-n23 interlatency, and p13-n23 interpeak amplitude and asymmetry parameters were measured and compared between groups. Except for the asymmetry value, there was no statistically significant difference between the groups (p > 0.05). The asymmetry parameter was statistically higher in the COVID-19 group (p = 0.008). In the o-VEMP test, n10 latency, p15 latency, n10-p15 interlatency, and n10-p15 interpeak amplitude and asymmetry parameters were measured and no statistically significant difference was found between the groups (p > 0.05, Table 6 ). The presence of waves in the c-VEMP and o-VEMP tests were compared between the groups. In the COVID-19 group, c-VEMP could not be obtained in 10 patients, whereas it could not be obtained in 4 patients in the control group. In the COVID-19 group, the o-VEMP test could not be obtained in 6 patients, whereas it could not be obtained in 4 patients in the control group. When the number of patients in whom waves could not be obtained in both o-VEMP and c-VEMP were compared, there was no statistical difference (p > 0.05).Table 6 Comparison of the c-VEMP and o-VEMP parameters between groups.
Table 6 Groups p-value*
COVID-19 Group Control Group
Mean ± SD Median (Min-Max) Mean ± SD Median (Min-Max)
c-VEMP p13 (ms) 13,11 ± 1,47 13,1 (10,5–17,2) 13,16 ± 1,35 13 (10,5–16,2) 0,904
c-VEMP n23 (ms) 21,23 ± 1,61 21,6 (17,1–24,5) 20,95 ± 1,61 20,95 (17,8–24,5) 0,213
p13-n23 interlatency (ms) 8,09 ± 1,93 8,1 (4,2–11,5) 7,72 ± 1,12 7,9 (5,1–9,9) 0,234
p13-n23amplitude (mV) 86,6 ± 38,42 84,15 (24,3–176,9) 90,81 ± 51 78,4 (35,3–267,1) 0,880
c-VEMP asymmetry 13,91 ± 6,69 13,9 (1,8–26,8) 10,08 ± 5,2 10 (0,6–27,3) 0,008
o-VEMP n10 (ms) 10,21 ± 1,37 10,05 (8,4–15,7) 10,26 ± 1,08 10 (8,4–12,8) 0,513
o-VEMP p15 (ms) 15,73 ± 1,56 15,3 (13,4–19,5) 15,91 ± 1,64 15,95 (12,7–19,1) 0,449
n10-p15 interlatency (ms) 5,53 ± 1 5,65 (3,2–7,4) 5,66 ± 1,09 5,45 (3,6–8,4) 0,462
n10-p15 amplitude (mV) 8,5 ± 5,6 7,3 (3,1–28,3) 9,82 ± 5,95 7,95 (2,8–29,5) 0,746
o-VEMP asymmetry 15,88 ± 10 15,9 (0,7–35,6) 10,95 ± 6,39 11,2 (0,4–24,4) 0,067
c-VEMP: Cervical vestibular-evoked myogenic potential, o-VMEP: Ocular vestibular-evoked myogenic potential, SD: Standard deviation,ms:millisecond, mV:millivolt, *p-values in bold indicate statistically significance.
4 Discussion
The effects of SARS-CoV-2 on the cochleovestibular system have been widely discussed in adult patients, and most studies show that it damages the system [8,18,19]. On the other hand, some studies claim that SARS-CoV-2 does not cause any damage to the cochleovestibular system [20]. Although there are a few studies that evaluate cochlear functions in the pediatric patient group, no study evaluating the vestibular system has been reported [13,21,22]. It has been reported that not only SARS-CoV-2 but also other viral infections can damage the cochleovestibular system by causing inflammation directly or through mediators [23,24]. Since the neurotropic and neuroinvasive characteristic of SARS-CoV-2 has been described [6], its effects on the vestibulocochlear system in pediatric patients are intriguing. In this study, it was aimed to evaluate the cochleovestibular system with objective and subjective test batteries in pediatric patients with COVID-19.
In our study, hearing thresholds obtained at 1000, 2000, 4000, and 8000 Hz in pure tone audiometry were statistically significantly worse in the COVID-19 group (p < 0.001, p = 0.001, p = 0.001, p = 0.014, respectively) compared to the control group. In studies conducted with pure tone audiometry in adult patients, it was stated that SARS-CoV-2 might play a role in the etiopathogenesis of hearing loss [18]. Swain et al. conducted a study in which they evaluated 192 cases of COVID-19, and reported hearing loss in 24 (12.5%) patients [25]. COVID-19 patients presenting with sudden hearing loss have also been reported. In our study, similar to the literature, hearing thresholds in pediatric patients with COVID-19 were worse at 4 frequencies, which may indicate a possible cochlear damage. Viral infections can adversely affect the auditory system. This involvement is usually intracochlear. Organ of Corti, stria vascularis, or spiral ganglion may be affected in peripheral involvement [26]. The negative impact of hearing thresholds in pediatric patients with COVID-19 in our study supports this relationship. The data were obtained in the early period after COVID-19. Although there were statistically significant data, the clinical effect on patients was minimal. It seems very likely that they will improve over time.
Efferents from the MOC originate from the medial part of the Superior Olivary Complex and terminate in the outer hair cells. The activation of MOC efferents causes a decrease in signals from outer hair cells (as obtained via OAE), which is called suppression [[27], [28], [29]]. MOC efferents have critical functions in hearing. They support auditory perception in noisy environments through anti-masking, and this mechanism maintains enhanced tone and intensity determination and speech discrimination. They regulate selective attention by regulating the functions of outer hair cells in the ear where the stimulus is targeted. In addition, MOC protects the inner ear from acoustic damage [30]. In a study conducted by Koca et al. MOC functions of pediatric COVID-19 patients were measured with suppressed OAE and they reported that some frequencies of patients with COVID-19 were affected [21]. In this study, SNR measurements were performed in the suppressed OAE test to evaluate the efferent pathways. In all frequencies (1000, 1400, 2000, 2800, and 4000 Hz), suppression was obtained in more patients in the control group than in the COVID-19 group (p < 0.001, p = 0.003, p = 0.008, p < 0.001, p < 0.001 for each frequency, respectively). The SNR values obtained without suppression at 2800 Hz and the SNR values with and without suppression obtained at 4000 Hz were statistically significantly lower in the COVID-19 group (p = 0.042, p < 0.001, p = 0.003, respectively). Data from our study and previously reported studies suggest that the MOC efferent system may be damaged in patients with COVID-19. The clinical response of this damage shown by the data in the MOC system is not fully known. It should be noted that it may be temporary and these data may become similar to the data from the control group over time. In the future, it will be possible to clarify whether a problem will occur later in critical tasks such as speech discrimination and tonal discrimination with studies examining the longer period.
The v-HIT is an objective test developed to evaluate the functions of the semicircular canals and superior/inferior vestibular nerves via the vestibulo-ocular reflex [31,32]. In a study conducted by Bozdemir et al. in adult patients, caloric and v-HIT tests were performed in patients with COVID-19, and they found a decrease in lateral canal gains compared to the control group [33]. In the data obtained in our study, lateral gains and RALP and LARP gains were lower in the COVID-19 group. In addition, lateral asymmetry was higher in the COVID-19 group than in the control group. These results show that the vestibular systems of pediatric patients may be more affected by COVID-19 than adult patients.
c-VEMP measures the functions of the inferior vestibular nerve and saccule over the vestibulo-collic reflex, and o-VEMP is an objective test battery that can measure the functions of the superior vestibular nerve and utricle. Longer latency of VEMP waves, longer interpeak latency, lower amplitude of the waves, or no waves are considered pathological in the VEMP test [12]. In our previous study with VEMP in patients with COVID-19, the amplitude of p13-n23 was significantly lower in adult patients with COVID-19, and longer latency of n23 was detected [9]. In this study, only the c-VEMP asymmetry value was higher in the COVID-19 group than that in the control group. When the patients in whom c-VEMP and o-VEMP waves could not be obtained were compared between the groups, no significant difference was observed. Based on the data obtained with the VEMP test battery, it can be said that COVID-19 does not cause a possible sequela in the c-VEMP and o-VEMP arc in pediatric patients.
The lack of caloric testing in this study can be considered a limitation. Another limitation is the lack of pre-study patient data. The data obtained are short-term data after COVID-19. Long-term follow-ups are required to reach a conclusion more clearly. Since no imaging was performed on the temporal bones of the patients included in the study, middle and inner ear anomalies could not be excluded.
In conclusion, the effects of COVID-19 on the cochleovestibular system are still a topic of research interest. Studies on pediatric patients are limited and this is the first study in terms of vestibular assessment. Evidence was obtained that COVID-19 causes damage to the cochlea-vestibular system in pediatric patients in the early post-COVID-19 period; however, it is certain that prospective studies with longer follow-up of these patients are needed.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
==== Refs
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| 36521194 | PMC9737457 | NO-CC CODE | 2022-12-14 23:45:33 | no | Int J Pediatr Otorhinolaryngol. 2023 Jan 10; 164:111406 | utf-8 | Int J Pediatr Otorhinolaryngol | 2,022 | 10.1016/j.ijporl.2022.111406 | oa_other |
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
The Author(s). Published by Elsevier Ltd.
S2405-8440(22)03583-6
10.1016/j.heliyon.2022.e12295
e12295
Research Article
Hand hygiene products and adverse skin reactions: A cross-sectional comparison between healthcare and non-healthcare workers of Bangladesh during COVID-19 pandemic
Roy Simanta abc
Iktidar Mohammad Azmain abcd∗
Saha Aishik Dipta e
Chowdhury Sreshtha abc
Tabassum Hridi Syeda Tasnim f
Sayeem Tanvir Syed Md. abc
Hossain Hawlader Mohammad Delwer a
a Department of Public Health, North South University, Dhaka 1229, Bangladesh
b Public Health Professional Development Society (PPDS), Dhaka 1215, Bangladesh
c School of Research, Chittagong 4203, Bangladesh
d Directorate General of Health Services, Dhaka 1212, Bangladesh
e Chattogram Medical College, 57 K.B. Fazlul Kader Rd, Chattogram 4203, Bangladesh
f North East Medical College, South Surma, Sylhet 3100, Bangladesh
∗ Corresponding author.
10 12 2022
12 2022
10 12 2022
8 12 e12295e12295
24 6 2022
21 10 2022
5 12 2022
© 2022 The Author(s)
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Background
The deadly COVID-19 pandemic has swept the globe since December 2019. Due to the significant risk of infection, frontline health workers had to use Personal Protective Equipment and hand hygiene products, to help prevent transmission of infection. The present study aims to compare the adverse skin responses between healthcare workers (HCW) and non-healthcare workers (NHCW).
Materials and methods
A descriptive, cross-sectional study of HCW and NHCW throughout the country wa executed. A self-structured questionnaire was utilized to gather data from 404 HCWs and 826 NHCWs during a two-month period using multistage sampling. STATA (v16) was used to analyse the data.
Results
41.87% of the study participants experienced adverse skin reactions, which were more prevalent amongs HCW (65.10%) than NHCW (30.51%). The most frequently reported skin condition was skin dryness (34.39%), followed by skin peeling (11.71%). Users of alcohol-based hand sanitizers (ABHS) were more likely to get itch (8.13%), whereas soap water users were more likely to suffer from skin peeling (35.74%) and rash (7.46%). There was a significant (p < 0.001) association between occupation and adverse skin responses, with HCW being 3.5 times more likely to have adverse skin manifestations than NHCW.
Conclusion
The research showed that healthcare workers were at a greater risk to developing skin reactions than the overall population with frequent use of hand hygiene measures being a significant risk factor.
Hand wash, Hand Hygiene, Skin problem, Skin Reaction, Sanitizer.
Keywords
Hand wash
Hand hygiene
Skin problem
Skin reaction
Sanitizer
==== Body
pmc1 Introduction
COVID-19 was declared a global pandemic by the World Health Organization on March 11, 2020, signifying the spread of a major global infectious disease [1]. As of this writing, the total number of confirmed cases worldwide has climbed to 250, 154, 972 [2] and claimed about 5,054,267 lives despite intensive public health precautions [2]. As the disease spread, governments began to recognize the pressure it had on the economy and health care sector. Accelerated public health campaigns were thus put into motion in all forms of mass media. With social distancing, facial masks, immaculate hand hygiene, and vaccinations forming the pillars of the preventive strategy.
Hand hygiene is of utmost importance after facial masks as a measure of infection control to prevent contamination of hands directly via 'respiratory droplets from coughs and sneezes or indirectly via touching infected fomites. The CDC recommends hand hygiene by either using soap and water or ABHS (Alcohol Based Hand Sanitizer) [3]. Hand sanitizers with an alcohol concentration of at least 60% ethanol or 70% isopropyl alcohol can be used in place of soap and water to inactivate SARS-CoV-2 [3].
As healthcare and non-healthcare professionals, began to adopt strict hygiene protocols with frequent hand washing with soap and water or ABHS, a series of adverse effects linked to the use of cleansing agents began to emerge. Numerous individual studies looking into the healthcare and general population separately revealed an increase in the incidence of adverse skin reactions in both groups [4, 5, 6, 7, 8, 9, 10]. In Wuhan (China), 74.5% of health professionals developed hand eczema, with an increased frequency of handwashing as a significant predictor [4]. Similar studies in Germany [5], Turkey [6], and India [7] also revealed a rise in hand eczema reported by healthcare workers at 90.4%, 50.5%, and 65.5% respectively. Studies into the non-healthcare population group also saw a rise in hand hygiene reactions due to increased hand washing and the use of sanitisers. 24 new cases of hand eczema were diagnosed in urgent care in a study in Milan [8], 16 new cases were reported in 10 days in a survey India [9] and nearly half the participants in a study in Saudi Arabia experienced skin reactions, particularly people those with a history of eczema [10]. But very limited research was carried out to compare the risks in both the groups side by side [11, 12].This study aims to explore these adverse effects within both the groups identify potential risk factors and propose appropriate changes in an attempt to prevent or reduce these effects.
2 Materials and Methods
2.1 Study participants and study site
This cross-sectional study surveyed healthcare workers (HCW) and non-healthcare workers (NHCW) across Bangladesh in a period of two months (May and June 2021).
Sample size estimation was done using the formula: n = (Zα/2+Zβ)2p1(1−p1)+p2(1−p2)(p1−p2)2, where Zα/2 = critical value of the normal distribution at α/2 (for a confidence level of 95%, α is 0.05 and the critical value is 1.96), Zβ = critical value of the normal distribution at β (for a power of 80%, β is 0.2 and the critical value is 0.84), p1 = assumed prevalence of adverse skin reactions among HCW = 0.55 [12], and p2 = assumed prevalence of adverse skin reactions among NHCW = 0.45 [12]. The calculated sample size was 389 in each group. However, we recruited 404 HCW and 826 NHCW (a total of 1230 participants) to ensure adequate power for the study (see Figure 1).
Initially, one government hospital, one private hospital, and one dental clinic were picked at random from a list of hospitals and dental clinics in each of the eight divisions (Dhaka, Chittagong, Rajshahi, Barisal, Mymensingh, Rangpur, Khulna, and Sylhet). A similar list was used to pick a military health-care institution. If any institution refused to participate that institution was excluded from the sampling frame and another institution was chosen randomly according to the inclusion criteria. Later, using the convenient sampling approach, 404 HCW were chosen from these institutions.
Secondly, 826 consenting general citizens (NHCW) were interviewed at public locations across the eight divisions using a fixed-step approach on a random route sample (every fifth person). To establish a representative sample of the general population per city, a quota sampling approach based on gender was applied (using data from the Bangladesh Bureau of Statistics). If a male subject is needed to fulfil the quota, every fifth person is contacted until a male is found.
2.2 Data collection
Volunteers were recruited and trained at each of the research locations. After informed written consent, volunteers conducted face-to-face interviews with subjects. A telephone interview was considered for health care personnel on COVID duty or who were isolated at home and informed verbal consent was taken from them. The HCW included registered physicians, nurses, technicians, and assistants whereas NHCW were included in the general population. Due to the genetic and cultural diversity, foreign nationals were excluded.
2.3 Study instrument
The researchers developed an initial questionnaire based on their review of existing studies. It was then pretested on 30 respondents, and the final version was accepted based on their recommendations. The final questionnaire retrieved information regarding respondents' sociodemographic characteristics (age, sex, occupation, place of employment, average work hours in the previous month), hand hygiene product type, and frequency of usage (1–4, 5–10, 11–15, 16–20, >20). Additionally, the questionnaire included questions about the history of COVID-19 infection and vaccinations. Moreover, respondents were asked about any new skin problems associated with the usage of hand hygiene products. The researchers compiled a list of frequent and relevant dermatological problems from the responses. All the reporting was done according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [13].
2.4 Ethical consideration
The Institutional Review Board of North South University approved (Approval no 2021/OR-NSU/IRB/1001) the research protocol. Wherever feasible, the 1964 Declaration of Helsinki and later modifications and comparable ethical standards were followed. Data collection was voluntary, and no incentive was offered to participants. Data were only accessible to the authors and were not disclosed anywhere.
2.5 Statistical analysis
We used Stata (version 16; StataCorp, College Station, TX, USA) for data analysis. A histogram, a normal Q-Q plot, and the Kolmogorov-Smirnov test were used to check for normality in continuous data. Arithmetic mean was used for quantitative data as a measure of center, and standard deviation was used as measure of dispersion. Two independent sample t-test (for continuous variables) and Pearson's chi-square (χ2) test (for categorical variables) were used to explore the bivariate relationship between outcome and predictor variables. Finally, variables with a p-value of ≤0.2 in the bivariate analysis were imputed into a binary logistic regression model to investigate the factors associated with adverse skin reactions among hand hygiene product users. All p-values were considered statistically significant if < 0.05.
3 Results
3.1 Baseline characteristics of study participants
Table 1 depicts the background characteristics of the study population. Out of the entire study cohort, 826 (67.17%) were non-healthcare workers (NHCW) & 404 (32.83%) were healthcare workers (HCW). 56.83% of the respondents were male and 51.79% were literate up to graduate level. 38% of the NHCW worked for more than 32 h a week which mainly included private job holders (39%) and labourers (21%) but in the other hand, the 59.65% of the HCW worked greater than 32 h a week. 75.53% of the entire study cohort used ABHS, while 69.35% used soap water. When asked about daily use frequency, 30.81% of the cohort reported that they had cleansed their hands 1 to 4 times a day, while 35.01 % reported that they had used hand hygiene products 5 to 10 times a day. 19.95% of the HCW cleansed their hands greater than 20 times a day, while only 4.68% of the NHCW did the same. 31.22% of the entire cohort had a prior history of COVID-19 infection. Among HCW, 65.84% were infected and among NHCW, only 14.29% were infected. 60.89% of the study cohort was fully vaccinated.Table 1 Background characteristics of study population.
Table 1Characteristics Entire study cohort (n = 1230) NHCW (n = 826) HCW (n = 404)
Age, years (mean ± SD) 29.45 ± 11.53 29.45 ± 13.18 29.46 ± 7.06
Gender
Male 699 (56.83%) 417 (50.48%) 282 (69.8%)
Female 531 (43.17%) 409 (49.52%) 122 (30.2%)
Educational Status
Illiterate 23 (1.87%) 23 (2.78%) -
Primary 73 (5.93%) 69 (8.35%) 4 (0.99%)
Secondary 116 (9.43%) 88 (10.65%) 28 (6.93%)
Higher Secondary 205 (16.67%) 157 (19.01%) 48 (11.88%)
Graduate 637 (51.79%) 377 (45.64%) 260 (64.36%)
Post-graduate 176 (14.31%) 112 (13.56%) 64 (15.84%)
Marital Status
Unmarried 655 (53.3%) 514 (62.23%) 141 (34.99%)
Married 552 (44.91%) 299 (36.2%) 253 (62.78%)
Widow∖Divorced∖Separated 22 (1.79%) 13 (1.57%) 9 (2.23%)
Religion
Islam 891 (72.44%) 560 (67.8%) 331 (81.93%)
Hindu 289 (23.5%) 230 (27.85%) 59 (14.6%)
Buddhism 41 (3.33%) 28 (3.39%) 13 (3.22%)
Other 9 (0.73%) 8 (0.97%) 1 (0.25%)
Occupation
Business 59 (4.8%) 59 (7.14%) -
Government Job 30 (2.44%) 30 (3.63%) -
Private Job 123 (10%) 123 (14.89%) -
Labourer 52 (4.23%) 52 (6.3%) -
Medical Student 46 (3.74%) 46 (5.57%) -
Non-medical Student 411 (33.41%) 411 (49.76%) -
Unemployed 103 (8.37%) 103 (12.47%) -
Other 2 (0.16%) 2 (0.24%) -
Doctor 301 (24.47%) - 301 (74.5%)
Nurse 35 (2.85%) - 35 (8.66%)
Medical Technologist 31 (2.52%) - 31 (7.67%)
Other Healthcare Worker 37 (3.01%) - 37 (9.16%)
Work hour (hours/week)
<8 249 (26.32%) 190 (35.06%) 59 (14.6%)
8 to 16 141 (14.9%) 84 (15.5%) 57 (14.11%)
16 to 24 40 (4.23%) 24 (4.43%) 16 (3.96%)
24 to 32 70 (7.4%) 39 (7.2%) 31 (7.67%)
32 to 48 151 (15.96%) 72 (13.28%) 79 (19.55%)
48 to 56 197 (20.82%) 133 (24.54%) 64 (15.84%)
>56 98 (10.36%) - 98 (24.26%)
Hand hygiene product
Alcohol based sanitizer 929 (75.53%) 572 (69.25%) 357 (88.37%)
Soap water 853 (69.35%) 592 (71.67%) 261 (64.6%)
Detergent solution/Savlon solution/Bleaching powder solution 15 (1.22%) 9 (1.09%) 6 (1.49%)
Daily use frequency (times/day)
1 to 4 367 (30.81%) 306 (38.73%) 61 (15.21%)
5 to 10 417 (35.01%) 279 (35.32%) 138 (34.41%)
11 to 15 214 (17.97%) 135 (17.09%) 79 (19.7%)
16 to 20 76 (6.38%) 33 (4.18%) 43 (10.72%)
>20 117 (9.82%) 37 (4.68%) 80 (19.95%)
H/O COVID-19 infection 384 (31.22%) 118 (14.29%) 266 (65.84%)
Vaccination Status
Not vaccinated 347 (28.21%) 316 (38.26%) 31 (7.67%)
Received first dose 134 (10.89%) 99 (11.99%) 35 (8.66%)
Fully vaccinated 749 (60.89%) 411 (49.76%) 338 (83.66%)
SD, standard deviation; NHCW, non-healthcare workers; HCW, healthcare workers; Data are presented as n (%) unless otherwise indicated.
Figure 1 STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) flow chart of study participants. A total of 1288 individuals (438 HCW & 850 NHCW) were assessed for eligibility. 58 individuals (34 HCW & 24 NHCW) were excluded for not meeting the inclusion criteria leaving a final sample of 1230 (404 HCW & 826 NHCW).
Figure 1
3.2 Prevalence of adverse skin reactions
Overall prevalence of adverse skin reactions in our study population was 41.9% (Table 2 ). Figure 2 depicts that healthcare workers (65.10%) had a higher prevalence of adverse skin reactions compared to non-healthcare workers (30.51%). Among the HCW, nurses (77%) had the highest prevalence of adverse skin reactions, followed by doctors (66%) and other health care professionals (62%). On the other hand, among the NHCW, private job holders (39%) had the highest prevalence of adverse skin reactions, followed by labourers (35%) and medical students (33%).Table 2 Factors associated with adverse skin reactions among the hand sanitizer users.
Table 2Factors Adverse skin reactions (n = 515, 41.9%)a Bivariate analysis Multivariate analysis
Crude OR (95% CI) p-valueb Adjusted OR (95% CI) p-valueb
Age, years
≤21 110 (21.36%) Reference <0.001 Reference 0.004
22-26 159 (30.87%) 2.14 (1.56─2.93) 0.63 (0.36─1.1)
27-34 135 (26.21%) 2.42 (1.74─3.38) 0.48 (0.25─0.89)
≥35 111 (21.55%) 1.29 (0.93─1.78) 0.41 (0.23─0.75)
Gender
Male 287 (55.73%) Reference 0.508 Reference
Female 228 (44.27%) 1.08 (0.86─1.36) 1.92 (1.37─2.7) <0.001
Educational Status
Illiterate 7 (1.36%) Reference 0.168 Reference 0.384
Primary 31 (6.02%) 1.69 (0.62─4.6) 1.21 (0.4─3.68)
Secondary 43 (8.35%) 1.35 (0.51─3.53) 0.85 (0.27─2.64)
Higher Secondary 73 (14.17%) 1.26 (0.5─3.21) 0.60 (0.19─1.89)
Graduate 288 (55.92%) 1.89 (0.77─4.65) 0.71 (0.23─2.22)
Post-graduate 73 (14.17%) 1.62 (0.63─4.14) 0.89 (0.28─2.82)
Marital Status
Unmarried 241 (46.89%) Reference <0.001 Reference 0.246
Married 266 (51.75%) 1.60 (1.27─2.1) 1.24 (0.86─1.77)
Widow∖Divorced∖Separated 7 (1.36%) 0.80 (0.32─1.99) 0.59 (0.19─1.83)
Religion
Islam 387 (75.15%) Reference 0.006 Reference 0.020
Hindu 99 (19.22%) 0.68 (0.51─0.89) 1.03 (0.69─1.53)
Buddhism 24 (4.66%) 1.84 (0.97─3.47) 1.71 (0.76─3.88)
Other 5 (0.97%) 1.63 (0.43─6.1) 14.5 (1.52─139.86)
Occupation
NHCW 252 (30.51%) Reference <0.001 Reference <0.001
HCW 263 (65.10%) 4.25 (3.3─5.47) 3.50 (2.23─5.49)
Work hour (hours/week)
<8 85.00 (19.45%) Reference <0.001 Reference <0.001
8 to 16 64.00 (14.65%) 1.60 (1.5─2.45) 1.62 (1─2.64)
16 to 24 17.00 (3.89%) 1.43 (0.72─2.81) 1.30 (0.61─2.75)
24 to 32 37.00 (8.47%) 2.16 (1.26─3.7) 1.88 (1.03─3.43)
32 to 48 66.00 (15.1%) 1.50 (0.99─2.27) 1.24 (0.75─2.04)
48 to 56 97 (22.2%) 1.87 (1.28─2.74) 2.38 (1.46─3.87)
>56 71 (16.25%) 5.07 (3.3─8.49) 2.51 (1.34─4.7)
Hand hygiene products
Alcohol based sanitizer 427 (82.91%) 2.06 (1.56─2.72) <0.001 1.40 (0.93─2.1) 0.107
Soap water 365 (70.87%) 1.13 (0.88─1.45) 0.325 0.97 (0.69─1.37) 0.88
Detergent/Savlon solution/bleaching powder solution 8 (1.55%) 1.59 (0.57─4.42) 0.371 1.21 (0.33─4.43) 0.76
Daily use frequency (times/day)
1 to 4 103 (20%) Reference <0.001 Reference 0.001
5 to 10 205 (39.81%) 2.48 (1.84─3.34) 1.98 (1.33─2.95)
11 to 15 108 (20.97%) 2.61 (1.84─3.71) 1.96 (1.22─3.15)
16 to 20 44 (8.54%) 3.52 (2.12─5.86) 1.84 (0.97─3.5)
>20 55 (10.68%) 2.27 (1.48─3.49) 0.92 (0.53─1.61)
H/O COVID-19 infection 232 (45.05%) 3.04 (2.37─3.9) <0.001 1.83 (1.29─2.61) 0.001
Vaccination Status
Not vaccinated 114 (22.14%) Reference <0.001 Reference 0.590
Received first dose 55 (10.68%) 1.42 (0.94─2.15) 1.16 (0.68─1.99)
Fully vaccinated 346 (67.18%) 1.75 (1.34─2.29) 0.98 (0.64─1.51)
a Data are presented as n (%).
b Significant p-values (<0.05) are in boldOR, odds ratio; CI, confidence interval; NHCW, non-healthcare workers; HCW, healthcare workers.
Figure 2 Adverse skin reactions among Healthcare Workers (HCW) and Non-Healthcare Workers (NHCW) according to profession. Overall prevalence of adverse skin reactions among HCW and NHCW is 65.10% and 30.51%, respectively. The predominant group with the most adverse skin reactions among HCW were nurses and among NHCW were private job holders.
Figure 2
3.3 Types of adverse skin reactions
Figure 3 depicts the types of adverse skin reactions and their frequencies following hand hygiene product use among the study population. Over half of the cohort reported no adverse reactions (56.1%), among which the majority were NHCW (67.55%). Adverse skin reactions were reported by 41.87% of the study population, which were more common among HCW (65.10%) compared to NHCW (30.51%). Skin dryness was the commonest reported skin problem (34.39%) followed by skin peeling (11.71%).Figure 3 Types of adverse skin reactions among Healthcare Workers and Non-Healthcare Workers. Skin dryness was the most prevalent type of adverse skin reaction followed by skin peeling in both HCWs and NHCWs. However, HCWs were significantly more prone to all types of adverse skin reactions compared to NHCWs.
Figure 3
3.4 Hand hygiene product use and adverse skin reactions
Figure 4 reveals study participants using soap water were significantly more protected from developing adverse reactions (55.74%) compared to those using ABHS (53.01%) and detergent/savlon solution/bleaching powder solution (33.33%). Detergent/savlon solution/bleaching powder solution users were significantly more prone to developing skin dryness (46.67%). Prevalence of skin colour change was also higher in detergent/savlon solution/bleaching powder solution users (13.33%). On the other hand, ABHS users were more likely to develop itch (8.13%), and soap water users were susceptible to skin peeling (35.74%) and rash (7.46%).Figure 4 Adverse skin reactions according to hand hygiene product use. Participants using soap water were significantly more protected from developing adverse reactions than two other groups. Skin dryness was significantly higher and skin color change were also more common among detergent/savlon solution/bleaching powder solution users. Skin peeling and itch were more common among soap water and alcohol-based sanitizer users, respectively.
Figure 4
3.5 Factors associated with adverse skin reactions
Unadjusted and adjusted results of binary logistic regression of the study variables are presented in Table 2. Age had a significant association with adverse skin reactions during both bivariate and multivariate analysis.
The multivariate analysis showed HCW were 3.5 times more likely to suffer from adverse skin manifestations than NHCW. Females were 1.92 times more likely to have adverse skin reactions compared to men. When compared to the group that worked fewer than 8 h per week, those who worked between 48 and 56 h and those who worked more than 56 h were 2.38 times and 2.51 times more likely to experience adverse skin reactions, respectively. ABHS use was significantly associated with developing adverse reactions in bivariate analysis (Crude OR: 2.06; 95% CI: 1.56–2.72. p < 0.001). Although it loses significance in the multivariate analysis, ABHS users were 40% more likely to develop adverse skin reactions, whereas soap water users were 3% less likely. The daily use frequency of hand hygiene products had a significant (p < 0.001) association with adverse skin manifestations. The group that used ABHS 5 to 10 times per day had almost two times the risk of having adverse skin responses compared to the group that used ABHS 1 to 4 times per day. Subjects who had a history of COVID-19 infection were nearly two times more likely to develop adverse skin reactions than those who did not (p = 0.001).
4 Discussion
Skin reactions are common adverse effect of hand hygiene product use. With increased hand hygiene measures to prevent COVID-19 transmission, healthcare workers and the general public were at increased risk of adverse skin reactions. The present study explored the prevalence and types of adverse skin reactions that occurred following hand hygiene product use during COVID-19 pandemic and compared the results between HCW and NHCW.
Our current study showed that of the 41.8% of participants reporting skin reactions, HCWs (65.10 %) were recorded to have more frequent adverse responses than NHCWs (30.51 %). There was significant association between occupation and adverse skin reactions, with HCWs being 3.5 times more likely to suffer from adverse skin manifestations than NHCWs. Our findings were consistent with a population-based survey in Saudi Arabia [11] and a prospective cross-sectional study carried out in Thailand [12] which found skin changes to be common during the pandemic in both healthcare workers and the general population with healthcare workers being at a greater risk. This could be due to the higher frequency of cleansing and increased use of alcohol-based products as revealed in previous studies [11, 12]. The long working hours of HCW compared to NHCW could also be an important factor. This has been supported by a multiple logistic regression model, which showed a significant association between work hours (hours/week) and adverse skin reactions.
The increased risk of dermatological problems linked to frequent handwashing has been evidenced in studies even before the current outbreak. During the strict hygiene practices in the 2014 Ebola pandemic, an increase in the diagnosis of hand eczema was also seen in HCW [14]. The randomised trial in Ebola revealed soap to be more triggering than ABHS [14]. This contradicts our study, which showed participants using soap water to be more protected from developing adverse reactions (55.74%) compared to those using ABHS (53.01%) and detergent/savlon solution/bleaching powder solution (33.33%). This could be the result of more frequent use of hand sanitisers in comparison to soap and water which is less easily accessible or portable than sanitiser. This can be further supported by the fact that the study participants who used ABHS 5 to 10 times per day had early twice the risk of developing unfavourable skin reactions than those using ABHS 1 to 4 times daily. ABHS was also associated with an increased risk of hand eczema in the 2020 study in Thailand [12]. ABHS have a low irritating potential and are more tolerable, but they tend to make the skin dry and more susceptible to contact dermatitis [15]. In general, while using ABHS, it is better to avoid ones with allergenic surfactants, preservatives, fragrances, or dyes [16]. ABHS, with added moisturisers, is beneficial in ameliorating hand dryness associated with frequent hand hygiene [16].Moreover, ethanol is preferable for the formulation since it is less irritating than isopropyl alcohol despite equal effectiveness [17]. In our current study, the most typical skin problem was also skin dryness (34.39%), followed by skin peeling (11.71%). Skin dryness was also the most frequently described reaction in the previous studies carried out in Germany [5], Saudi Arabia [11], India [7], and Thailand [12]. The WHO and the American Contact Dermatitis Society also advocate the use moisturisers after hand cleansing to help alleviate the most reported adverse reaction of dry skin [16, 18].
When exploring the association between gender and adverse skin reactions in our study, females were almost twice as likely to have adverse skin reactions than men. It is believed that the incidence of self-reporting in females could be a result of their thinner epidermis [19] and hormonal changes leading to inflammatory sensitivity [20, 21]. There was no statistically significant association between COVID-19 vaccination status and hand hygiene-related adverse skin conditions. Subjects with a history of COVID-19 infection were nearly two times more likely to suffer from undesirable cutaneous manifestations. However, why such an association exists still owes an explanation and demands further studies to explore the matter.
4.1 Limitations
It's essential to note some of our study's limitations as well as the methods we used to solve them. Firstly, while carrying out the study, the hand hygiene technique was not considered. The WHO and American Contact Dermatitis Society recommend cleansing by gentle patting rather than rubbing to minimise mechanical trauma to the skin barrier [16, 18]. The effect of gloves usage and water temperature during handwashing with soap was also not considered in the study [16, 22]. Wearing gloves when hands are still wet can increase the risk of skin irritation due to the increased chance of entrapment of irritants and so effect adverse reaction [23]. Due to our study's cross-sectional nature, we cannot infer causality for the associations that we have presented in this paper. However, by presenting AORs using multiple regression models, we attempted to account for the potential effect of confounders. All the problems presented in this study were self-reported by the respondents, which may have led to self-reporting bias. In order to minimize this, all our data collectors were medical students with adequate training and followed a predefined neutral script. We also acknowledge that the findings of our study may not be generalizable due to our sample size. To make the sample representative and reduce selection bias, the healthcare workers were selected from randomly selected healthcare facilities, and non-healthcare workers were selected by quota sampling across all the divisions of Bangladesh.
5 Conclusion
Our research revealed healthcare workers to be at a significantly higher risk of developing adverse skin reactions from hand hygiene product use than the overall population. Also, a higher frequency of hand hygiene product use was a risk factor for adverse skin reactions. Although limiting the frequency may reduce the incidence of adverse skin reactions but might not always be practically feasible while adhering to strict infection control protocols. It is thus important to educate everyone about rational hand hygiene techniques and the inclusion of protective measures in their hand hygiene practices.
Declaration
Author contribution statement
Simanta Roy: Conceived and designed the experiments; Wrote the paper.
Mohammad Azmain Iktidar: Conceived and designed the experiments; Analyzed and interpreted the data.
Aishik Dipta Saha: Performed the experiments; Wrote the paper.
Sreshtha Chowdhury, Syed Md. Sayeem Tanvir: Contributed reagents, materials, analysis tools or data.
Syeda Tasnim Tabssum Hridi: Analyzed and interpreted the data; Wrote the paper.
Funding statement
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data availability statement
Data will be made available on request.
Declaration of interests statement
The authors declare no conflict of interest.
Additional information
Supplementary content related to this article has been published online at https://doi.org/10.1016/j.heliyon.2022.e12295.
==== Refs
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| 0 | PMC9737459 | NO-CC CODE | 2022-12-15 23:17:52 | no | Heliyon. 2022 Dec 10; 8(12):e12295 | utf-8 | Heliyon | 2,022 | 10.1016/j.heliyon.2022.e12295 | oa_other |
==== Front
Ann Pharm Fr
Ann Pharm Fr
Annales Pharmaceutiques Francaises
0003-4509
0003-4509
Published by Elsevier Masson SAS on behalf of Académie Nationale de Pharmacie.
S0003-4509(22)00160-2
10.1016/j.pharma.2022.12.002
Article
Evaluation of The Effectiveness of Electronic Prescription In Reducing Medical And Medical Errors (Systematic Review Study)
Osmani Freshteh 1⁎
Arab-Zozani Morteza 2
Osmani Mohammad 3
shahali Zahra 4
1 Freshteh Osmani, Assistant Professor of biostatistics, Dentistry Clinical Research Development Center, Birjand University of Medical Sciences, Birjand, Iran
2 Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran
3 Infectious diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
4 National Center for Health Insurance Research, Tehran, Iran
⁎ Corresponding Author: Infection disease Research center, Birjand University of Medical Sciences, Birjand, Iran
10 12 2022
10 12 2022
19 3 2022
7 12 2022
© 2022 Published by Elsevier Masson SAS on behalf of Académie Nationale de Pharmacie.
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Introduction: The use of electronic systems in prescription is considered as the final solution to overcome the many problems of the paper transcription process, especially with the outbreak of Coronavirus needs more attention than before. But despite the many advantages, its implementation faces many challenges and obstacles. Therefore, the present study was conducted to review the effectiveness of computerized physician order entry systems (CPOE) on relative risk reduction on medication error and adverse drug events (ADE).
Method: This study is one of the systematic review studies that was conducted in 2021. In this study, searching for keywords such as E-Electronic Prescription, Patient safety, Medication Errors prescription, Drug Interactions, orginal articles from 2000 to October-2020 in the valid databases such as ISI web of Science PubMed Embase, Scopus and search engines like google was done. The included studies were based on the main objectives of the study and based on the inclusion criteria after several stages of review and quality evaluation. In fact, the main criteria for selecting articles were studies that compared the rate of medication errors with or without assessing the associated harms (real or potential) before and after the implementation of EMS.
Results: Out of 110 selected studies after initial screening, only 16 articles were selected due to their relevance. Among the final studies, there was a significant heterogeneity. Only 6 studies were of good quality. Of the 10 studies prescribing error rates, 9 reported reductions, but variable denominators prevented meta-analysis. Twelve studies provided specific examples of systemic drug errors. 5 cases reported their occurrence slightly. Out of 9 cases that analyzed the effects on drug error rate, 7 cases showed a significant relative reduction between 13 and 99%. Four of the six studies that analyzed the effects on potential ADEs showed a significant relative reduction of between 35 and 98%. Two of the four studies that analyzed the effect of ADEs showed a relative reduction of between 30 and 84%.
Conclusion: Finally, e-prescribing seems to reduce the risk of medication errors and ADE. However, the studies differed significantly in terms of setting, design, quality and results. More randomized controlled trials (RCTs) are needed to further improve the evidence of health informatics information.
Keyword
Electronic Prescription
Medical Error
Prescription error
Electronic Health
Medication Side Effects
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pmc
| 36513154 | PMC9737496 | NO-CC CODE | 2022-12-14 23:29:53 | no | Ann Pharm Fr. 2022 Dec 10; doi: 10.1016/j.pharma.2022.12.002 | utf-8 | Ann Pharm Fr | 2,022 | 10.1016/j.pharma.2022.12.002 | oa_other |
==== Front
World Neurosurg
World Neurosurg
World Neurosurgery
1878-8750
1878-8769
Elsevier Inc.
S1878-8750(22)01732-6
10.1016/j.wneu.2022.12.027
Original Article
Upper Extremity Neuropathies following Severe COVID-19 Infection: A Multicenter Case Series
Li Neill Y. MD a
Murthy Nikhil K. MD bc
Franz Collin K. MD, PhD def
Spinner Robert J. MD g
Bishop Allen T. MD a
Murray Peter M. MD h
Shin Alexander Y. MD a∗
a Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN, USA
b McGaw Medical Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
c Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
d Shirley Ryan Ability Lab, Chicago, IL, USA
e Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
f The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
g Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA
h Department Orthopaedic Surgery, Mayo Clinic, Jacksonville, FL, USA
∗ Corresponding Author: Alexander Y. Shin, MD, Mayo Clinic, 200 1st Street Southwest, Department of Orthopedic Surgery, Rochester, MN 55905.
10 12 2022
10 12 2022
28 10 2022
5 12 2022
6 12 2022
© 2022 Elsevier Inc. All rights reserved.
2022
Elsevier Inc.
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Purpose
The purpose of the study is to examine presentation, injury patterns, and clinical course, for COVID-19-related peripheral nerve injury following mechanical ventilation.
Methods
A multicenter retrospective study of patients with COVID-19 complicated by ARDS that required mechanical ventilation was undertaken. Patient records were reviewed for ICU and intubation characteristics, prone or lateral decubitus positioning, and the onset of neuropathy diagnosis.
Results
Between September 2020 and January 2022, 11 patients were diagnosed with peripheral neuropathy, including 9 with brachial plexopathy following COVID-19 infection. Each patient developed ARDS requiring mechanical ventilation for a median of 39 days. Six patients(54.5%) underwent prone positioning and 1 lateral decubitus. Neuropathies involved 5 brachial pan-plexopathies, 2 incomplete brachial plexopathies, 2 lower trunk plexopathies, 1 radial neuropathy, and 1 bilateral ulnar neuropathy. At a mean follow-up of 10.2 months, patients with brachial pan-plexopathies demonstrated signs of reinnervation proximally, and one resolved to a radial mononeuropathy; however, the majority have demonstrated minimal clinical improvements.
Conclusion
Our series demonstrates that peripheral neuropathies and especially brachial plexopathies have occurred diagnosed following mechanical ventilation for ARDS-related COVID-19 infections. Contrary to prior COVID-19 studies, only 54.5% of these patients underwent prone positioning. Aside from a traumatic disturbance from prone positioning, the increased incidence of neuropathy may involve an atraumatic effect of COVID-19 via direct invasion of nerves, auto-antibody targeting of nervous tissue, or hypercoagulation induced microthrombotic angiopathy.
Keywords
Acute Respiratory Distress Syndrome
Brachial Plexus
COVID-19
Prone Positioning
Upper Extremity Neuropathy
Abbreviations
ARDS, Acute respiratory distress syndrome
BPI, brachial plexus injury
COVID-19, Coronavirus Disease 2019
ICU, intensive care unit
MRI, magnetic resonance imaging
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
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pmcLevel of Evidence: IV
| 36513302 | PMC9737497 | NO-CC CODE | 2022-12-14 23:29:53 | no | World Neurosurg. 2022 Dec 10; doi: 10.1016/j.wneu.2022.12.027 | utf-8 | World Neurosurg | 2,022 | 10.1016/j.wneu.2022.12.027 | oa_other |
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Psychiatry Res
Psychiatry Res
Psychiatry Research
0165-1781
1872-7123
Elsevier B.V.
S0165-1781(22)00589-3
10.1016/j.psychres.2022.114998
114998
Article
The association of social, economic, and health-related variables with suicidal and/or self-harm thoughts in individuals admitted to a psychiatric inpatient unit during the COVID-19 pandemic: an exploratory study.
Holman Sarah a
Steinberg Rosalie ab
Schaffer Ayal ab
Fiksenbaum Lisa c
Sinyor Mark ab⁎
a Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, Canada M4N 3M5
b Department of Psychiatry, University of Toronto, 27 King's College Cir, Toronto, ON, Canada M5S 1A1
c Department of Psychology, York University, 4700 Keele St, Toronto, ON, Canada M3J 1P3
⁎ Corresponding Author: Mark Sinyor, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room FG 22b, Toronto, ON, M4N 3M5, 416-480-4070
10 12 2022
10 12 2022
1149985 5 2022
28 7 2022
2 12 2022
© 2022 Elsevier B.V. All rights reserved.
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Individuals with pre-existing psychiatric diagnoses appear to be vulnerable to worsening mental health symptoms during the coronavirus disease 2019 (COVID-19) pandemic. Furthermore, psychiatric hospitalizations during the pandemic may be complicated by increased risk of SARS-Cov-2 infection and limited social engagement due to changes in hospital policies. The objective of our exploratory study was to determine whether social, economic, and health-related variables were associated with thoughts of suicide and/or self-harm since March 2020 in individuals admitted to a psychiatric inpatient unit during the COVID-19 pandemic. Chi-square tests revealed four variables were significantly associated with thoughts of suicide and/or self-harm: 1) difficulty with cancellation of important events, 2) some form of loneliness, 3) decreased time spent in green spaces 4) increased time spent using devices with screens. The logistic regression model showed a significant association between suicidal and/or self-harm thoughts and cancellation of important events. Further investigation of the loneliness variable components revealed a significant association between suicidal and/or self-harm thoughts and feeling a lack of companionship, feeling isolated and feeling alone. These results suggest that social challenges experienced during the pandemic were associated with negative mental health symptoms of individuals admitted to a psychiatric inpatient unit during the pandemic.
Keywords
hospitalization
loneliness
life event
green space
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pmc1 Introduction
The coronavirus disease 2019 (COVID-19) pandemic has led to mental health impacts of social isolation, lockdowns, fear of infection, and SARS-Cov-2 infection/COVID-19 disease itself. Individuals with pre-existing mental illnesses were more likely to experience a decline in their mental health during the pandemic (O'Connor et al., 2021; Pierce et al., 2021). Socio-demographic, economic and health determinants such as income, housing, social isolation, substance use, and sexual orientation are independent risk factors for suicidal and/or self-harm thoughts (Mulholland et al., 2021; Näher et al., 2020). Before the pandemic, previous studies found that living alone and feelings of loneliness were associated with suicidal outcomes including suicidal ideation in the general adult population (Calati et al., 2019). Other factors, such engaging in physical activity, meditation, and sleep duration and quality, may be protective against experiencing suicidal ideation (Littlewood et al., 2019; Vancampfort et al., 2018; Wu et al., 2021). After the onset of the pandemic, variables such as COVID-19 stress, loneliness, financial strain, alcohol misuse, and testing positive for COVID-19 were associated with suicidal and/or self-harm thoughts in the general adult population (Elbogen et al., 2021). Moreover, a negative perception of social distancing was bidirectionally associated with suicidal ideation (Ammerman et al., 2021). In Ontario, suicide rates increased at the beginning of the pandemic (Pirkis et al., In press). Given this finding, more studies are needed to understand what has driven thoughts of suicide and/or self-harm during the pandemic.
Despite the surge in research related to the COVID-19 pandemic, relatively few studies have examined the effects of the pandemic on psychiatric inpatient populations. At the beginning of the pandemic in March 2020, psychiatric hospitalizations decreased in Canada, Germany, and France (Jollant et al., 2021; Kim et al., 2021; Zielasek et al., 2021). Examining the effects of the COVID-19 pandemic on inpatient populations is important because these patients are potentially the most severely ill, have an increased SARS-Cov-2 exposure risk, and face challenges related to being hospitalized within an acute care setting during a pandemic (Vigo et al., 2020; Xiang et al., 2020; Zhu et al., 2020). At a time when clinical research may have been limited by COVID-19 restrictions, the current study provides insight into a particularly vulnerable group of psychiatric inpatients at risk of suicide and/or self-harm. In this exploratory study, we investigate whether social, economic, and health-related variables were associated with thoughts of suicide and/or self-harm in individuals admitted to a psychiatric inpatient unit during the COVID-19 pandemic.
2 Methods
Participants were recruited from the Sunnybrook Health Sciences Centre Inpatient Psychiatry Unit in Toronto, Canada from August 2020 to May 2021. The average age of participants was 38.4 years (range 19-77 years, standard deviation 13.5), with 50.8% female, 44.3% male and 4.9% other. Race/ethnicity of participants included 59% White, 13.1% Asian, 4.9% Black, 4.9% Indian-Caribbean, 4.9% Middle Eastern and 13% other. Primary psychiatric diagnoses leading to hospitalization included mood disorders (58.9%), substance-use disorders (17.6%), personality disorders (9.8%), psychotic disorders (9.7%), anxiety disorders (1.6%), and stressor-related disorders (1.6%). The majority of participants were single (62.3%), with 18% divorced or separated, 17.9% married or living common law, and 1.6% widowed. The majority of participants identified as heterosexual (73.8%), with 9.8% identifying as bisexual, 4.9% gay, 4.9% lesbian, 1.6% queer, and 4.9% chose not to disclose.
Participants were recruited as a part of a Caring Contacts randomized controlled trial (RCT). Once recruited for the RCT, they were given the option to complete an additional COVID-19-related questionnaire adapted from standardized questions used by the International COVID-19 Suicide Prevention Research Collaboration (ICSPRC) (https://www.iasp.info/research-collaboration-icsprc/). Participants completed this questionnaire prior to receiving any of the RCT treatments. The questionnaire had 60 questions and 14 sections (Box 1).• Physical/Social Space
• Violence
• Family Relationships
• Cancellation of Major Events
• Children in School
• Isolation
• Change in Subjective Financial Status
• Concerned About Future Finances
• Employment Status Changes
• Adverse Financial Outcomes During the Pandemic
• COVID-19 Infection Related Questions, Changes in Health-Related Behaviours
• Subjective Mental Health
• Experience of Care by People in a Suicidal Crisis
The pre-specified aim of this study was to identify associations between thoughts of suicide and/or self-harm in psychiatric inpatients and other variables on the COVID-19-related questionnaire. Given the exploratory nature of this study, we did not generate a priori hypotheses. After data collection, from the COVID-19 related self-reported questionnaire we identified descriptive variables of interest that included employment status, SARS-CoV-2 infection, high risk category for COVID-19 illness severity, COVID-19 information seeking, self-rating of mental health before lockdown, how participants sought help, and rating of mental health care interaction. We then identified a dependent variable that was suicidal and/or self-harm thoughts which was derived from the question ‘Since the official lockdown was announced on March 14 2020, have you had thoughts that you would be better off dead or of hurting yourself in some way?’ The questions on the survey were complex and many had multiple choice answers. Given the modest sample size, both in terms of participants and responses on the questionnaire, and the number of items on the questionnaire, we combined some related questions into a single variable for analysis and all variables were dichotomized. For example, in the questionnaire, there were separate questions about whether participants had experienced psychological harm and physical harm since the start of lockdown. For the purposes of our analyses, we combined the two questions to be a single variable of ‘experience of physical or psychological harm since lockdown’. There was a total of 23 dichotomized variables for analysis (Table 1). We chose the direction of the dichotomization based on the available literature but we did not have sufficient power to test this as a hypothesis. Other examples include the ‘some form of loneliness’ variable that was combined from multiple source questions and dichotomized. The four component questions related to loneliness were do you 1) feel you lack companionship 2) feel left out 3) feel isolated and 4) feel alone? We combined these questions into a single variable of ‘since lockdown some form of loneliness.’ Similarly, the question pertaining to difficulty with cancellation of major events included life events such as weddings, funerals, graduations, and proms. A chi-square test of independence was conducted for each of the 23 variables. We conducted a false discovery rate (FDR; Benjamini & Hochberg, 1995) correction on these 23 variables with the p-values that were generated from the chi-squares. If any variables representing a combination of questions were found to be significant, further post-hoc chi-square tests of independence were conducted on the individual source questions to determine which drove significance. Variables with a p-value less than or equal to 0.10 were included in a backwards stepwise logistic regression that controlled for age and gender. We also compared the demographic data for participants in the RCT who completed the questionnaire compared to participants who chose not to complete the questionnaire using a t-test and chi-squares.
3 Results
Out of 103 eligible inpatient participants who were approached to complete the COVID-19 related questionnaire, a total of 61 participants agreed to do so (59.2%). Forty-nine of the 61 participants (80.3%) indicated that since the lockdown was announced in March 2020, they have had thoughts that they would be better off dead or thoughts of hurting themselves in some way (suicidal and/or self-harm thoughts).
3.1 Variables associated with suicidal and/or self-harm thoughts
The chi-square tests of independence that tested for an association with suicidal and/or self-harm thoughts found four out of 23 variables to have a p-value less than or equal to 0.10, with two of the variables having a p-value less than 0.05. When we ran the FDR correction, the significance level became p = 0.003. The four variables were: (1) difficulty with cancellation of important events in your life (χ2(1, N = 61) = 4.11, p = 0.042, FDR corrected p = 0.007); (2) some form of loneliness since lockdown (χ2 (1, N = 61) = 7.03, p = 0.023, FDR corrected p = 0.003); (3) decreased time spent in green spaces such as parks or gardens (χ2 (1, N = 60) = 3.33, p = 0.068, FDR corrected p = 0.010).; and (4) increased time spent using devices with a screen (χ2 (1, N = 61) = 3.02, p = 0.086, FDR corrected p = 0.0133). With the FDR correction one variable remained significant. Since this was an exploratory study, we chose to include all four variables in the logistic regression analysis.
Fewer than half of participants (42.6%) reported having difficulty with cancellation of important events, while the majority of participants (88.5%) reported experiencing some form of loneliness since lockdown. Despite 68.3% of participants reporting having a safe outdoor space (e.g., a garden or a yard) to exercise or play, most participants (56.7%) indicated that their time spent in green spaces such as parks or gardens decreased, and 70.5% of participants indicated that their time spent using devices with a screen increased.
3.2 Logistic regression model
The logistic regression model controlling for age and gender was statistically significant, (χ2(5) = 18.53, p = 0.002) (Table 2). The model explained 43.2% (Nagelkerke R 2) of the variance in suicidal and/or self-harm thoughts and correctly classified 86% of cases. Individuals who found the cancellation of important events in their life difficult were 13.2 times more likely to experience suicidal and/or self-harm thoughts.
3.3 Post-hoc tests on loneliness variable
Seventy-two percent of participants reported feeling a lack of companionship, 80.3% reported feeling isolated, 82% reported feeling alone, and 60.7% reported feeling left out. Post-hoc chi-square tests of independence conducted on the four component questions of the ‘some form of loneliness’ variable showed a significant association between suicidal and/or self-harm thoughts and feeling a lack of companionship (χ2(1, N = 61) = 6.90, p = 0.026), feeling isolated (χ2(1, N = 61) = 4.57, p = 0.047), and feeling alone (χ2(1, N = 61) = 10.33, p = 0.005). The was no significant association between thoughts of suicide or self-harm and feeling left out (χ2(1, N = 61) = 0.71, p = 0.513).
3.4 Population Characteristics
Before the lockdown in March 2020, 47.5% of participants were employed or self-employed, 19.7% were in educational settings, 9.8% unemployed, 16.4% permanently sick or disabled, 4.9% in an unpaid work/apprenticeship, and 1.6% retired. At the time they completed the survey, 32.8% were unemployed/unable to work/on unpaid leave, 14.8% employed and currently working, 13.2% employed but working reduced hours or on unpaid leave, 16.4% permanently sick or disabled, 13.1% in education, 4.9% retired, and 4.9% in unpaid work/apprenticeship. Only one participant was known to have been previously infected with SARS-CoV-2 and 13.1% of participants were deemed a high risk category for COVID-19 illness severity (e.g., aged 70+, underlying health condition). Most participants sought out COVID-19 related information less than once a day (52.5%), 42.6% sought out COVID-19 information 1-5 times a day, and 4.9% sought out COVID-19 information 5 times a day. Participants rated their mental health before March 2020 as poor (41%), fair (32.8%), and good (26.2%). Of the 49 participants who indicated they had suicidal and/or self-harm thoughts since the start of lockdown 65.5% of people went to a health care professional, 45.9% of people went to family or friends, 27.8% used a crisis hotline, and 14.8% used an online service. Participants rated their mental health care interaction as good (67.2%), fair (21.3%), and poor (1.6%).
In our comparison of the demographic data between participants in the RCT who completed the questionnaire compared to participants who chose not to complete the questionnaire we found that there were no significant differences in age (p = 0.713), gender (p = 0.417), and psychiatric disorder (p = 0.289). There was a significant difference in race (p = 0.042), marital status (p = 0.035), and sexual orientation (p = 0.033). Our sample had a large portion of white, single and divorced/separated/widowed, and gay/lesbian/queer participants.
4 Discussion
Our study adds to the current literature by exploring the relationship between social, economic, and health-related variables and suicidal and/or self-harm thoughts in individuals admitted to a psychiatric inpatient unit during the COVID-19 pandemic. We found that difficulty with cancellation of important events was associated with thoughts of suicide and/or self-harm. There was also an indication that loneliness, and decreased time spent in green spaces may have been associated with suicidal and/or self-harm thoughts, but to a lesser degree.
Although less than half of participants experienced difficulty with cancellation of important events, it was the variable with the strongest association with suicidal and/or self-harm thoughts. Weddings, graduations and funerals are all rituals that mark a significant occasion in life and in the context of the COVID-19 pandemic, all had to be adapted (Imber-Black, 2020). Individuals dealing with the loss of a loved one are negatively affected by the absence of funeral rituals during the COVID-19 pandemic and as a result of an impacted grieving process may even be at risk of developing complicated grief (Cardoso et al., 2020; Mortazavi et al., 2020).
When the components of the loneliness variable were tested individually, feeling a lack of companionship, feeling isolated, and feeling alone were all associated with suicidal and/or self-harm thoughts. This is in line with previous studies that have shown that feelings of loneliness have increased during the COVID-19 pandemic and have been associated with suicidal thoughts (Allan et al., 2021; Elbogen et al., 2021; Killgore, Cloonan, Taylor, & Dailey, 2020; Killgore, Cloonan, Taylor, Lucas, et al., 2020). Our results provide further support for this finding and suggest that an association between loneliness and suicidal thoughts is also present and may be amplified in psychiatric inpatient populations.
There was a weaker association between suicidal and/or self-harm thoughts and decreased time spent in green spaces. Prior studies have identified a relationship between mental health symptoms and access to green spaces during the COVID-19 pandemic (Pouso et al., 2020; Soga et al., 2021), with one study finding that, depending on the strictness of the lockdown, individuals with a nature view and those with access to private outdoor space had fewer symptoms of depression and anxiety (Pouso et al., 2020). Given this finding, we may have expected our variable home with a safe outdoor space to have an inverse association with suicidal and/or self-harm thoughts however it did not. This could be because having a home with a safe outdoor space does not necessarily translate to spending time in that outdoor space. Soga et al. (2021) found that people who use green space frequently during the COVID-19 pandemic reported lower levels of depression and anxiety, and the frequency of green space use was positively related to self-esteem, life satisfaction, and happiness. Our data showed that although 68.3% of participants had a safe outdoor space, more than half of participants indicated that their time spent in green spaces decreased. This supports the notion that time spent outdoors during the COVID-19 pandemic can be associated with mental health symptoms, and adds that a decrease in time spent outdoors may be associated with suicidal and/or self-harm thoughts in individuals who have experienced psychiatric hospitalization during the pandemic.
The finding of 70.5% of our sample reporting increased screen time during the COVID-19 pandemic is in line with previous epidemiological studies (Colley et al., 2020; Wagner et al., 2021). With physical distancing measures in place, the increase in screen time is likely a combination of many aspects of day-to-day life becoming remote including work, virtual health care appointments, and an increase in recreational device use including for the purposes of socializing. While there are many benefits for the use of devices during the COVID-19 pandemic (Riva et al., 2020), studies have shown that greater time spent using devices has been linked to poorer mental health during the COVID-19 pandemic (Colley et al., 2020; Meyer et al., 2020; Smith et al., 2020). Our findings provide further support for the association between increased screen time and worsening mental health in our clinical sample.
Our study has some notable limitations. First, all participants were hospitalized for an acute illness (including a high proportion with a mood disorder). While we believe this is a strength given the paucity of clinical research on severely ill clinical samples during the pandemic, it must also be acknowledged that we do not know the degree to which these findings generalize to others outside of our clinical sample, including clinical populations with different distributions of mental illness. Second, our study has a small sample size, again limiting the available power to identify findings that otherwise may have been significant. Third, participants responded to the study questionnaire during their stay in the hospital when they were experiencing an acute episode of illness which may have impacted the accuracy of recall. Additionally, the dependent variable captured thoughts of suicide and self-harm in a single measure, not separately, so we were not able to differentiate thoughts of suicide from thoughts of self-harm. Furthermore, we did not have a measure for symptom severity or coping ability which may have provided more insight into the participants’ experience and ability. Finally, our finding of a significant difference in race, marital status, and sexual orientation between the participants in the RCT who completed this questionnaire compared to the non-completers, shows that we were not able to capture a fully representative sample.
In sum, our results suggest a few social variables including difficulty with cancellation of important events, feeling a lack of companionship, feeling isolated, and feeling alone, were all associated with suicidal and/or self-harm thoughts in individuals admitted to a psychiatric inpatient unit during the COVID-19 pandemic. These results suggest that the social challenges individuals experienced during the COVID-19 pandemic were substantial and were associated with negative mental health symptoms for individuals admitted to a psychiatric inpatient unit during the pandemic. The variables found to be associated with suicidal and/or self-harm thoughts may be important targets of mitigation strategies in the later stages of the pandemic and in future pandemics.
Funding: This work was supported by the COVID-19 specific Innovation Fund of the Alternative Funding Plan from the Academic Health Sciences Centres of Ontario. The sponsor had no involvement in study design, collection, analysis and interpretation, writing of the report, nor in the decision to submit the article for publication.
Declaration of interest: The authors declare no conflicts of interest. Dr. Steinberg and Dr. Schaffer receive salary support through academic scholars’ awards from the Department of Psychiatry at Sunnybrook Health Sciences Centre. Dr. Sinyor receives salary support through academic scholars’ awards from the Departments of Psychiatry at Sunnybrook Health Sciences Centre and the University of Toronto.
Sarah Holman: Project administration, Investigation, Formal analysis, Visualization, Writing – Original Draft, Writing – Review & Editing. Rosalie Steinberg: Funding acquisition, Conceptualization, Methodology, Supervision, Writing – Review & Editing. Ayal Schaffer: Funding acquisition, Conceptualization, Methodology, Supervision, Writing – Review & Editing. Lisa Fiksenbaum: Conceptualization, Formal analysis, Writing – Review & Editing. Mark Sinyor: Funding acquisition, Conceptualization, Methodology, Supervision, Writing – Review & Editing.
CRediT authorship contribution statement
Sarah Holman: Project administration, Investigation, Formal analysis, Visualization, Writing – original draft, Writing – review & editing. Rosalie Steinberg: Funding acquisition, Conceptualization, Methodology, Supervision, Writing – review & editing. Ayal Schaffer: Funding acquisition, Conceptualization, Methodology, Supervision, Writing – review & editing. Lisa Fiksenbaum: Conceptualization, Formal analysis, Writing – review & editing. Mark Sinyor: Funding acquisition, Conceptualization, Methodology, Supervision, Writing – review & editing.
Conflict of Interest
Declaration of interest: The authors declare no conflicts of interest. Dr. Steinberg and Dr. Schaffer receive salary support through academic scholars’ awards from the Department of Psychiatry at Sunnybrook Health Sciences Centre. Dr. Sinyor receives salary support through academic scholars’ awards from the Departments of Psychiatry at Sunnybrook Health Sciences Centre and the University of Toronto.
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Vigo D. Patten S. Pajer K. Krausz M. Taylor S. Rush B. Raviola G. Saxena S. Thornicroft G. Yatham L.N. Mental Health of Communities during the COVID-19 Pandemic Canadian Journal of Psychiatry 2020 10.1177/0706743720926676
Wagner B.E. Folk A.L. Hahn S.L. Barr-Anderson D.J. Larson N. Neumark-Sztainer D. Recreational screen time behaviors during the COVID-19 pandemic in the U.S.: A mixed-methods study among a diverse population-based sample of emerging adults International Journal of Environmental Research and Public Health 2021 10.3390/ijerph18094613
Wu R. Zhong S.Y. Wang G.H. Wu M.Y. Xu J.F. Zhu H. Liu L.L. Su W.J. Cao Z.Y. Jiang C.L. The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality Archives of Suicide Research 2021 10.1080/13811118.2021.1982800
Xiang Y.T. Zhao Y.J. Liu Z.H. Li X.H. Zhao N. Cheung T. Ng C.H. The COVID-19 outbreak and psychiatric hospitals in China: Managing challenges through mental health service reform International Journal of Biological Sciences 2020 10.7150/ijbs.45072
Zhu Y. Chen L. Ji H. Xi M. Fang Y. Li Y. The Risk and Prevention of Novel Coronavirus Pneumonia Infections Among Inpatients in Psychiatric Hospitals Neuroscience Bulletin 2020 10.1007/s12264-020-00476-9
Zielasek J. Vrinssen J. Gouzoulis-Mayfrank E. Utilization of Inpatient Mental Health Care in the Rhineland During the COVID-19 Pandemic Frontiers in Public Health 2021 10.3389/fpubh.2021.593307
| 0 | PMC9737504 | NO-CC CODE | 2022-12-15 23:16:09 | no | Psychiatry Res. 2023 Jan 10; 319:114998 | utf-8 | Psychiatry Res | 2,022 | 10.1016/j.psychres.2022.114998 | oa_other |
==== Front
Therapie
Therapie
Therapie
0040-5957
1958-5578
Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS.
S0040-5957(22)00283-9
10.1016/j.therap.2022.11.012
Letter To Editor
The need to shed light on potential insidious SARS-CoV-2 post-vaccination pituitary lesions
Taieb Ach abc⁎
El Euch Mounira bd
a Department of Endocrinology, University Hospital of Farhat Hached, 4000 Sousse, Tunisia
b University of Sousse, Faculty of Medicine of Sousse, 4000 Sousse, Tunisia
c Laboratory of Exercice Physiology and Pathophysiology; L.R.19ES09, 1006 Tunis, Tunisia
d Department of Internal Medicine, University Hospital of Charles Nicoles, 1006 Tunis, Tunisia
⁎ Corresponding author: Department of Endocrinology, University Hospital of Farhat Hached, Hamed Karoui street, 4000 Sousse, Tunisia
10 12 2022
10 12 2022
29 10 2022
© 2022 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.
2022
Société française de pharmacologie et de thérapeutique
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Keywords
SARS-CoV-2
COVID-19
Vaccines
Hypophysitis
Apoplexy
==== Body
pmc
| 0 | PMC9737505 | NO-CC CODE | 2022-12-14 23:29:53 | no | Therapie. 2022 Dec 10; doi: 10.1016/j.therap.2022.11.012 | utf-8 | Therapie | 2,022 | 10.1016/j.therap.2022.11.012 | oa_other |
==== Front
Therapie
Therapie
Therapie
0040-5957
1958-5578
Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS.
S0040-5957(22)00282-7
10.1016/j.therap.2022.11.013
Letter To Editor
Central diabetes insipidus, hypophysitis and SARS-CoV-2 vaccine: correspondence
Mungmunpuntipantip Rujittika a⁎
Wiwanitkit Viroj b
a Private Academic Consultant, 10330 Bangkok, Thailand
b Adjunct professor, University Centre for Research & Development Department of Pharmaceutical Sciences, Chandigarh University Gharuan, Mohali, 140413 Punjab, India
⁎ Corresponding author: Private Academic Consultant, 1111 Bangkok 122 Bangkok, 10330 Thailand
10 12 2022
10 12 2022
26 10 2022
© 2022 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.
2022
Société française de pharmacologie et de thérapeutique
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Keywords
COVID
Vaccine
Diabetes insipidus
==== Body
pmc
| 0 | PMC9737508 | NO-CC CODE | 2022-12-14 23:29:53 | no | Therapie. 2022 Dec 10; doi: 10.1016/j.therap.2022.11.013 | utf-8 | Therapie | 2,022 | 10.1016/j.therap.2022.11.013 | oa_other |
==== Front
Phys Ther Sport
Phys Ther Sport
Physical Therapy in Sport
1466-853X
1873-1600
Elsevier Ltd.
S1466-853X(22)00171-7
10.1016/j.ptsp.2022.12.005
Article
Effect of COVID-19 lockdown on injury incidence and burden in amateur rugby union
Tondelli Eduardo a∗
Zabaloy Santiago b
Comyns Thomas M. cde
Kenny Ian C. cde
a Sport Physiotherapy, Faculty of Medical Sciences, Pontificial Catholic University of Argentina, Buenos Aires, Argentina
b Faculty of Physical Activity and Sports, University of Flores, Buenos Aires, Argentina
c Department of Physical Education and Sport Sciences, University of Limerick, Ireland
d Health Research Institute, University of Limerick, Ireland
e Sport and Human Performance Research Centre, University of Limerick, Ireland
∗ Corresponding author.
10 12 2022
1 2023
10 12 2022
59 8591
6 7 2022
7 12 2022
8 12 2022
© 2022 Elsevier Ltd. All rights reserved.
2022
Elsevier Ltd
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Objectives
To analyse match and training injury incidence rates and burden from pre-(2019) and post-COVID-19 (2021) seasons;
To analyse injury related variables as mechanisms, type, body locations, severity and the differences of the most common injuries according to playing positions.
Design
An observational study was performed according to the consensus statement on injury definitions and data collection from World Rugby. Injury variables were collected retrospectively for 2019 season and prospectively during 2021 season.
Setting
Argentinian amateur rugby club.
Participants
Male (n = 110) senior amateur rugby players.
Main outcome measures
Match and training time loss injuries, time of exposures and injury related variables.
Results
Training incidence rate during post-lockdown season (4.2/1000 player-training-hours) was significantly higher (p < 0.001) than the pre-lockdown season (0.9/1000 player match hours). Post-lockdown hamstring strain injury (HSI) and concussions match incidence rates were significantly (p < 0.001; p < 0.05 respectively) higher in comparison with 2019 season. Regarding playing positions, backs showed a significantly increase (p < 0.05) in HSI match incidence rate post lockdown.
Conclusions
After the COVID-19 lockdown, training incidence rate was significantly higher than previous season (2019), showing the impact of the lockdown restrictions. Coaches and medical staff must consider that players probably need more lead-in time for conditioning and more monitoring after periods of no rugby.
Keywords
Injury surveillance
Rugby
Return to sport
Athletic injuries
==== Body
pmc1 Introduction
COVID-19 was declared a global pandemic by the World Health Organization on March 11, 2020. In this regard, to counteract the impact of the disease many countries implemented preventive measures like quarantine, lockdown, or self-isolation (Brooks et al., 2020). This led to sports and recreational activities being suspended, negatively impacting the physical, nutritional and mental health of the athletes worldwide (Dönmez et al., 2021; Myall, Montero-marin, & Kuyken, 2021; Roberts, Gill, & Sims, 2020). Specifically in Rugby Union, hereafter ‘rugby’, competitions were suspended worldwide in March 2020 across all competitive levels, however, international, and professional competitions were gradually restarted during July and August 2020. For example, international tournaments were played during 2020 (i.e., Six Nations, Rugby Championship, Super Rugby) and 2021 (World Rugby, 2021). Conversely, at the amateur level in the Northern Hemisphere countries from Europe, the 2019–2020 season could not be completed (Kenny & Comyns, 2020). Similarly, in the Southern Hemisphere countries like New Zealand, amateur competitions suffered the same consequences regarding restrictions, and were unable to complete the 2020 season (Otago Rugby Football Union, 2020).
In Argentina, the lockdown started on March 19th, 2020, and for six months, all sporting activities were suspended. The cessation of restrictions and a gradual return to the exercise of training and sports competitions, was on November 6th, 2020, after the announcement of the end of lockdown (Gemelli, 2020). However, many teams began with training sessions provided they strictly followed specific care measures and restrictions (e.g., non-contact training, groups of 10 players or less per session, training equipment not allowed to be shared) from August 21st, 2020 onwards. In the following months, contact training sessions became more flexible for the clubs, until full-rugby training was allowed for the 2021 preseason. This part of the season consisted of 8 weeks of preparation and in this study, both preseasons lasted 8 weeks. After a few months of training where procedures gradually returned to normal, an increased number of COVID-19 cases prompted the announcement of another lockdown on April 14th, 2021 (at the end of our southern hemisphere preseason) which lasted until June 2021 (Cereghini & Gemelli, 2021). After this, and provided health and safety of players, staff and spectators was guaranteed, the Buenos Aires Rugby Union (URBA) officially announced the start of the rugby tournament season from July 31st, which left rugby clubs one month to prepare and be ready for the competitive season (Union de Rugby de Buenos Aires, 2021).
During lockdown period, players had to train at home with limited equipment (Washif et al., 2021), whereas when training at clubs, many restrictions were imposed by the government, especially those related to human contact and collision which were suspended. These situations posed a scenario of missing skills training, reducing the chronic load in strength, speed, jumps and other game demands as well as the loss of habitual contact situations and tackles, among other skills. The latter led club coaches and staff to look for the best strategies to counteract the negative impact on physical performance. Recent reviews literature (Halle et al., 2021; Mohr et al., 2022; Stokes et al., 2020) showed the potential changes in sports physical performance, the strategies needed to mitigate those changes, and the estimated time required for players to safely return to a “game ready” status. However, current epidemiological reports (Mannino et al., 2021; Marotta et al., 2022; Platt, Collofello, et al., 2021; Platt, Uhl, et al., 2021) stated a discrepancy regarding injury incidence status after a period of training and competition restrictions. Firstly, many sports at the professional level such as football, national football league and baseball (Marotta et al., 2022; Platt, Collofello, et al., 2021; Platt, Uhl, et al., 2021) reported an increase of injury incidence rates and burden after the lockdown period. On the other hand, in rugby, Starling et al. (2022) reported the influence of an extended period of restrictions in training and matches on injury risk in professional rugby, and showed that there was an increased rate of injury when players first returned to training, but after 10-weeks of preparatory training, when competition resumed, match incidence rate was not higher than pre-suspension (Starling et al., 2022). In that study, authors stated it was likely that well-structured player management and greater player rotation would decrease match injury incidence rates.
COVID-19 lockdown overall presented several problems to players’ health, physical fitness, and mood, impacting negatively in some sports at the professional level (Dönmez et al., 2021; Myall et al., 2021; Roberts et al., 2020). To date, it is unclear how such an irregular season due to different lockdown periods might have affected injury incidence rates and burden at the amateur level in rugby union players where club resources tend to be less than that of professional clubs. Therefore, determining whether there are differences in incidence rates before and after lockdown as well as differences between playing positions would be of interest to club coaches and medical staff to better tailor physical conditioning to player needs. To the best of our knowledge, to date no studies have investigated the influence of an extended period without competitions and structured training practices on the injury epidemiological status of amateur rugby players. Therefore, the aim of the current study was two-fold: i) to analyse match and training injury incidence rates and injury burden from pre and post lockdown seasons (2019–2021) and examine if there may have been any negative effect by the lockdown due to the pandemic; ii) to analyse injury mechanisms, body locations, severity, and the differences of the most common injuries according to playing positions. It was further hypothesized that due to this unusual situation, injury risk would have been increased in the 2021 season compared to pre–lockdown season.
2 Methods
This study was conducted according to the guidelines of the ‘Strengthening the reporting of observational Studies in Epidemiology (STROBE) – Sports injuries and illness surveillance (SIIS) (Bahr et al., 2020). An observational, analytical, study was performed for the period 2019–2021. One-hundred and ten amateur male rugby players volunteered to participate in this study. Participants were members of one rugby club that regularly competes in the Second division of the URBA competition. All players had more than ten years of training and playing experience. The club fielded four male teams, which competed in four grades representing competitive levels of play. Ethical approval for this study was granted by the Institution's Research Ethics Committee in compliance with the Declaration of Helsinki.
2.1 Data collection
The process implied two instances retrospectively analysed. The pre-lockdown period considered for analysis was between March 15th, 2019, to November 25th, 2019, where data were collected retrospectively from medical records, and during the post-lockdown pandemic period from July 31st, 2021, to November 20th, 2021, where data collection was conducted prospectively. Regarding the 2020 season, there was no data collection due to the lockdown and competitions were cancelled without any games played, whereas the 2021 (i.e., 13 matches) season was shorter than the previous (i.e., 26 matches), due to time and schedule constraints. Data collection was performed exclusively in the club facilities by the main author, digitalized through Google Forms (Google Form-Google, Mountain View, CA, USA), and finally exported to a sheet matrix in which match, and training times were recorded. Injury diagnoses were also classified according to the Orchard Sports Injury and Illness Classification System (OSIICS) (Orchard et al., 2020). The consensus statement on injury definitions and data collection procedures for studies of injuries in rugby developed by the Rugby Injury Consensus Group from World Rugby was used for data collection (Fuller et al., 2007). The injury definition used was: “Any physical complaint, which was caused by a transfer of energy that exceeded the body's ability to maintain its structural and/or functional integrity, that was sustained by a player during a rugby match or rugby training, irrespective of the need for medical attention or time-loss from rugby activities. An injury that results in a player receiving medical attention is referred to as a ‘medical-attention’ injury and an injury that results in a player being unable to take a full part in future rugby training/match as a ‘time-loss’ injury” (Fuller et al., 2007). All the data collection were completed when the last player finished the return-to-play process. The demographic characteristics and injury-related variables were collected for each player: match and/or training situation, day of injury occurrence, playing position (backs and forwards), type of injury, injury location, time of the injury (match or training), mechanisms (contact or non-contact), and action during the injury occurrence. Severity was classified according to the International Olympic Committee Consensus (IOCC) based on the days the player was not fully available to participate in training and competition, as follows: (1–7 days lost), (8–28 days lost), (>28 days lost) (Bahr et al., 2020).
2.2 Data analysis
Match and training exposure were reported from the data recorded, whereas daily training player-hours for each team were calculated as the number of team training hours multiplied by the number of players in the team on that day. Every player continued with their individualised training except in some specific cases (e.g., post-surgery, acute phase of an injury, or illness). The total training player-hours were calculated as the sum of all the daily training player-hours for each team. The formula used was (NP·NM·1.33), where N refers to number, P to players and M refers to match. Injury incidence rates (training, match or overall) were reported as the number of injuries/1000 player-hours of exposure (Brooks, Fuller, Kemp, & Reddin, 2005). To calculate match injury incidence according to playing position match exposure for backs and forwards was individually used. Injury burden was defined as the expected loss in a particular situation within a stated period of time and is quantified using the product of the average consequence of all adverse events (injury severity) and the probability that these adverse events will occur within a specified time period (injury incidence): incidence x severity (Bahr et al., 2020). Injury incidence rates and burden were reported per season.
2.3 Statistical analysis
Categorical variables are reported as presentation number and percentage. Continuous variables that assumed a normal distribution were reported as mean and standard deviation (SD). Otherwise, the median and interquartile range (IQR) were used. The Kolmogorov-Smirnov test was used to determine the distribution of continuous variables. For the comparison between incidence rates, the Chi-squared test was used. For the comparison between incidence rates by playing position Fisher exact test and mid-p exact values was used. A p-value <0.05 was considered significant. For data analysis, the IBM SPSS Macintosh software, version 25.0 (IBM Corp., Armonk, NY, USA) was used.
3 Results
3.1 Player's characteristics and exposure
A total of 110 players were included in the study, 44 (40%) backs, and 66 (60%) forwards. The median age of backs was 26 years (IQR 21–29) and 24 years (IQR 22–28) for the forwards. The median BMI for backs players was 25.5 (IQR 24.5–26.9) and 29.2 (IQR 26.6–31.8) for forwards players. Table 1 reports the number of players (overall, forwards, and backs), total exposure, match, and training exposure per season.Table 1 Number of players (all, forwards, backs) and player-hours (all, match, and training) per season.
Table 1Season All Forwards Backs
2019
Number of players 97 55 42
Total player-hours 14496 8149 6347
Training hours 12416 7040 5376
Match hours 2080 1109 971
2020 COVID-19 LOCKDOWN PERIOD
2021
Number of players 77 45 32
Total player-hours 5843 3357 2486
Training hours 4723 2760 1963
Match hours 1120 597 523
A total of 105 injuries were recorded during the period 2019–2021, 54 occurred during 2019 and 51 injuries in 2021. Forwards sustained a total 30 injuries (55.6%) during 2019 season (22 match, 8 training) and 26 (51%) were post-lockdown season (15 match, 11 training); Backs sustained a total of 24 injuries (44.4%) during 2019 season (21 match, 3 training) and 25 (49%) were post-lockdown (16 match, 9 training).
3.2 Incidences rates
Match incidence rate during 2019 period was 20.7/1000 player-match-hours. After the 2020 lockdown due to COVID-19 match incidence rate (27.7/1000 player-match-hours) was higher (p = 0.219) than the pre-lockdown season (20.7/1000 player-match-hours). Training incidence rate post-lockdown season (4.2/1000 player-training-hours) was significantly higher (p < 0.001) than the pre-lockdown season (0.9/1000 player-training-hours). Regarding playing position, backs and forwards training incidence rates post-lockdown season were significantly higher (p < 0.0001) than the pre-lockdown season. Match, training, and overall incidence rates are exposed per season in Table 2 .Table 2 Number of injuries, severities, incidences rates and injury burden per season (2019–2021) separated by overall, match, and training.
Table 2 2019 2020 2021 P value
Overall
Injury count (n) 54 COVID-19 LOCKDOWN 51
Incidence ratea 3.7 8.6 < .001
Incidence rate forwardsa 3.7 7.7 < .007
Incidence rate backsa 0.6 10.1 < .001
Severity (median)b 32 18 .076
Injury Burdenc 78 190
Match
Injury count (n) 43 31
Incidence rated 20.7 27.7 .219
Incidence rate forwardsd 19.8 25.1 .480
Incidence rate backsd 21.62 30.6 .301
Severity (median)b 38 17 .102
Injury Burdenc 786 470.5
Training
Injury count (n) 11 20
Incidence ratee 0.9 4.2 < .001
Incidence rate forwardse 1.1 3.4 < .008
Incidence rate backse 3.8 10.1 < .001
Severity (median)b 21 22 .670
Injury Burdenc 28 75.3
Bolded P values indicate statistically significant difference between seasons.
a Injuries/1000 total exposure (match and training combined).
b Days lost.
c Days absence/1000 player-hours.
d Injuries/1000 player-match-hours.
e Injuries/1000 player-training-hours.
3.3 Severity and injury burden
The median severity and injury burden per season are shown in Table 2. For 2019 severity by days lost was 3949; 3326 by match injury while 636 days lost by training injury. Six (11.1%) injuries resulted in 1–7 days lost [median 6 (IQR 4–6) days], 20 (37%) resulted in 8–28 days lost [median 15 (IQR 12–22)] and 28 (57.1%) required more than 28 days lost [median 89 (IQR 38–334)]. Regarding severity by days lost during 2021, there were 1958 days lost, 1235 by match injury while 723 days were lost by training injury. Three (5.9%) injuries resulted in 1–7 days lost [median 6 (IQR 4–6) days], 28 (54.9%) resulted in 8–28 days lost [median 17 (IQR 12–22)] and 17 (39.2%) required more than 28 days lost [median 60 (IQR 35–180)].
3.4 Injury mechanisms and match situations
From the total of injuries that occurred during 2019, 63% were contact injuries and most of them (57.4%) occurred in matches, while during 2021, 47.1% were contact injuries of which 33.3% were match injuries. In both the 2019 and 2021 seasons, 44.4% and 35.3% of the injuries respectively were caused by tackle actions. Regarding non-contact injuries, during 2019 22.2% occurred during matches and 14.8% during training sessions. After lockdown, 25.5% of the injuries occurred during match days and 27.5% during training sessions. In both the 2019 and 2021 seasons the most common causes of non-contact injury were during running actions (14.8% and 25.5% respectively) and sprints (7.4% and 21.6% respectively).
3.5 Injuries according to body location
Lower limbs were the most affected in both seasons. During 2019, the lower limb accounted for 30 injuries (55.6%) and during 2021, it was 31 injuries (60.8%). During pre-lockdown 2019 season the thigh (25.9%), the knee (18.5%), and the ankle (9.3%) were the most frequently injured location. Post-lockdown in 2021 thigh injuries (45.1%) were significantly (p < 0.05) higher than the 2019 season. In 2021 other lower limb locations (knee and ankle) presented similar rates (7.8%) but lower than the 2019 season. For the upper limb during 2019, there were 14 injuries (25.9%) and during 2021, it was 4 injuries (7.8%). Pre-lockdown 2019 season upper injuries were significantly (p < 0.05) lower than post-lockdown 2021 season. The shoulder/clavicle was the most frequently injured location for upper limb in both seasons. Finally, there were 3 (5.6%) head injuries in 2019 while in 2021 there were 7 (13.7%).
3.6 Most common diagnoses
Table 3 shows the mean severity, match incidence rate and injury burden of the six most common injuries. During 2019, anterior cruciate ligament (ACL) rupture showed the highest burden while hamstring strain injury (HSI) was the injury that showed highest burden in 2021. Regarding match incidence rate HSI showed the highest match incidence rate in both periods, 3.37/1000 player/hours in 2019 and 8.04/1000 player/hours during 2021 season. Post-lockdown HSI match incidence rate was significantly (p < 0.001) higher than 2019 season. With respect to concussions, match incidence rate in 2021 showed a significant increase (p < 0.05) in comparison with the 2019 season. Match injuries diagnoses according to playing position are shown in Fig. 1, Fig. 2 . The most common injury for backs was the HSI in both seasons showing a significant increase (p < 0.05) in match incidence rate post-lockdown, being running (50%) and sprinting (50%), the game actions responsible for these injuries. The most common injury for forwards in 2021 were concussions, showing an increase (p = 0.14) in match incidence rate than pre-lockdown season. All these injuries were, during tackle actions, specifically, while the player was in the role of tackler.Table 3 The six most common injuries with its respective match incidence rate, severity, and injury burden per season.
Table 3Most common diagnoses 2019 2020 2021
n Severity Match IRa IBb n Severity Match IRa IBb
Hamstring strain 9 25.8 3.37 16.0 COVID-19 LOCKDOWN 17 25.7 8.04 74.0
ACL rupture 5 222.6 1.92 76.8 – – – –
Ankle sprain 4 12.0 1.92 3.3 2 43.5 1.79 14.7
MCL sprain 3 58.0 0.96 55.6 2 36.0 1.79 12.2
Rectus femoris strain 3 23.3 0.48 4.8 3 14.0 1.79 7.1
Concussion 1 17.0 0.48 1.1 6 15.7 4.46 16.0
n: number of injuries.
S: severity (mean in days).
IR: Incidence rate.
IB: Injury Burden (Overall).
ACL: Anterior cruciate ligament.
MCL: Medial collateral ligament.
a Injuries/1000 total exposure (match and training combined).
b Days absence/1000 player-hours.
Fig. 1 Match incidence rates of the most common diagnosis in forwards players in 2019 season against season 2021, expressed by injuries/1000 player-match-hours.
Fig. 1
Fig. 2 Match incidence rates of the most common diagnosis in backs players in 2019 season against season 2021, expressed by injuries/1000 player-match-hours. (∗: significant difference between seasons).
Fig. 2
4 Discussion
4.1 Summary of main findings
This study reported differences in injury incidence rates and burden between a pre-lockdown season (2019) and a post-lockdown season (2021). The main findings of this study were as follows: i) post-lockdown training incidence rate were significantly higher than the previous 2019 season before Covid-19 interruptions. In terms of playing positions, forwards sustained a higher number of injuries than backs, whilst for injury location lower limbs were most affected in both seasons (55.6% and 60.8%); ii) post-lockdown severity (median) was lower than 2019; hamstring strain injuries and concussions were significantly higher (p < 0.001 and p < 0.05 respectively) in 2021 compared with the 2019 season; iii) the most common injury presentations post-lockdown differed across both positional groups, with HSI the most common injury within backs and they occurred during running and sprinting actions, while concussions were the most common diagnoses for forwards and occurred mostly during tacking.
4.2 Incidence rates, severity, and burden
In the present study match incidence rate in 2021 after the lockdown (27.7/1000 player-match-hours), was higher than the previous (2019) season (20.7/1000 player-match-hours). The incidence rate for both seasons were below those reported in recent studies in Argentina (Tondelli, Boerio, Andreu, & Antinori, 2021) and in the northern hemisphere countries (Kemp et al., 2020; Kenny & Comyns, 2020). Similar findings with regards to post-lockdown injuries were reported in a study conducted in national football league (Platt, Collofello, et al., 2021). Other studies (Mannino et al., 2021; Marotta et al., 2022) in football showed no differences in match injuries after the lockdown period, but did not report incidence rates. However, a recent study by Starling et al. (2022) analysed the influence of a prolonged restricted period of matches and training on injury risk in professional rugby showing that there was no significant difference in the overall incidence, severity or burden of injuries sustained but there was a significantly higher (p < 0.05) burden of soft tissue injuries (Starling et al., 2022). Nonetheless, in the current study incidence rate for post-lockdown season training sessions (4.2/1000 player-training-hours) was significantly higher (p < 0.001) when compared to pre-lockdown season (0.9/1000 player-training-hours). However, our post-lockdown season was shorter (13 matches) than 2019 season (26 matches), so we cannot compare season lengths. The present investigation is the first to report the effects of the lockdown on injury incidences rates in amateur rugby. Interestingly, Starling et al. (2022) reported similar findings to those presented here, showing that post-lockdown training injuries were increased when compared to the previous seasons. Additionally, in a recent study in professional football (Waldén et al., 2022) the authors reported an increased training incidence and burden following the COVID-19 lockdown in comparison with 2015–2019 seasons. It is worth highlighting, that players’ internal factors that have been shown to impact the return to sport after an injury such as anxiety (Murphy & Sheehan, 2021), concern about return to performance level, lack of readiness, fears, internal pressure among others, could be considered as likely to be responsible for this injury situation due to the lockdown period. However, each club in the URBA with its respective strength and conditioning coaches and medical staff probably adopted many different strategies to face those potential problems. Likewise, post-lockdown, severity was lower than 2019 and although the incidences were higher post-lockdown, there were no high-severity injuries such as ACL tears (Table 3), as occurred in 2019. In this sense, the days lost were fewer, causing a drop in the median of severity. However, overall injury burden was higher than 2019 (78 days lost/1000 player-hours vs 190 days lost/1000 player-hours respectively) showing a negative impact of the injuries. In contrast, post-lockdown match injury burden was lower, which may be explained by the absence of high severity injuries. These type of injuries can impact negatively on player mental welfare (Murphy & Sheehan, 2021).
4.3 Injuries body locations
With regards to injuries body locations, lower limbs were the most affected in both seasons. Post-lockdown, thigh injuries (45.1%) were significantly higher (p < 0.05) than the pre-lockdown season. Previous studies in amateur rugby (Kemp et al., 2020; Yeomans et al., 2018) reported that the knee was one the most common body location to suffer an injury during a regular season, which is in contrast to the current study. Considering that present findings showed that HSI and the Rectus femoris strain were the most incident injuries, perhaps these differences may be explained by the decrease in muscle strength, poor adaptation to sprint actions or scarce time to prepare and cope with game demands. In addition, it could be assumed that upper limb injuries could have been higher than those reported for the pre-lockdown season due to insufficient training regarding contact and collisions situations which may have caused players to be not fully prepared to cope with all game demands, thus, pre-lockdown season upper limb injuries were significantly (p < 0.05) lower than 2021.
4.4 Most common diagnosis and mechanisms between playing positions
Regarding the most common diagnosis and the incidence by playing position, HSI showed the highest match incidence rate in both periods, 3.37/1000 player/hours in 2019 and 8.04/1000 player/hours during 2021 season. Post-lockdown HSI match incidence rate was significantly higher (p < 0.001) than the pre-lockdown season. Although in this study HSI match incidence rates were among the highest for backs and forwards, backs showed a significant increase compared to forwards during 2021. Considering that backs are most commonly involved in sprints (Darrall-Jones, Jones, & Till, 2016), it would have been necessary to perform specific training according to positions aimed at reducing the risk of injury associated with the return to competitions, since it is established that a combination of Nordic curl hamstring exercises and regular exposure to high-speed running appears to be protective against HSI (Stokes et al., 2020). Also, it strengthens even more the efforts that are made to know the risk factors of this injury and what are the best preventive strategies to implement (Attwood, Roberts, Trewartha, England, & Stokes, 2018; John H.M. Brooks, Fuller, Kemp, & Reddin, 2006; Lahti et al., 2020). Secondly, ankle sprains were other of the most common injuries in the post-lockdown season (1.79/1000 player-match-hours). While post-lockdown ankle sprains match incidence rate was lower than 2019, an important aspect to consider is that median severity in 2021 was three times higher, which highlights that players needed more time to recover from this particular injury. Considering, that ankle sprains incidence could be attributed to failure in motor control or previous injuries (De Noronha, França, Haupenthal, & Nunes, 2013; Kobayashi, Tanaka, & Shida, 2016), and this may be specifically due to the lack of specific preparation and the failure to include change of directions, collision and landing within the programs themselves. This has led in recent years to a deeper analysis of the injury etiology to try to reduce the risk as well as the inclusion of preventive strategies. Finally, concussions reported in the current study during both seasons were in the top 3 most common diagnosis, although the 2019 season numbers were well below than previous reports in amateur rugby (Kemp et al., 2020; Kenny & Comyns, 2020; Yeomans et al., 2021). Curiously, the post-lockdown concussion match incidence rate (4.46/1000 player-match-hours) was significantly higher (p < 0.05) when compared to 2019 (0.48/1000 player-match-hours). This difference in the incidence rate between seasons and compared to other countries may be due to the injury identifying process and implementation of concussion detection tools in comparison with 2019 at the URBA tournaments. It is worth mentioning that concussion injury is probably still underdiagnosed due to the complexity of recognizing concussions on the field (Tucker, Falvey, Hislop, & Raftery, 2021). According to playing positions, forwards sustained twice the incidence rates of concussions when compared to backs. This higher concussion incidence rate for forwards could be explained by the fact that these players are more heavily involved in contact events than backs (Paul et al., 2022). In addition, a study of head-injury events conducted in professional rugby, reported that “tacklers” were 2.6 times more likely to be injured compared to the ball carrier (Tucker, 2017). Similarly, Cross et al. (2019) showed that the accelerating player, tackler speed, head contact type and tackle type were the tackle characteristics that represented the greatest likelihood for modifying the risk of concussion. Therefore, it is suggested that strategies aiming to prevent head injuries and concussions must be included. For this reason, World Rugby is involved in expanding knowledge and prevention tools regarding this issue, such as the blue card system which enables referees to show a blue card to a player suspected of sustaining a concussion who are then removed from the game. If rigorously implemented by referees, it could aid the work of medical staff. Rugby Unions and federations should be focused on this situation, educating and auditing healthcare professionals, coaches, players, and referees to promote welfare.
4.4.1 Study limitations
Firstly, the inclusion of a relatively small sample size for epidemiology research, and the use of only one club, precludes that the results may be generalized across the amateur rugby community. Secondly, this study lacks the report of non-time loss injuries or medical attention, which could have revealed more about the reality of amateur rugby injuries. Lastly, post-lockdown (2021) season was shorter than pre-lockdown (2019). Finally, these results are not representative of female or young rugby players.
5 Conclusion
This study adds to the epidemiological understanding of injury in male amateur rugby players, and match and training incidence rates during two competitive seasons. After the COVID-19 lockdown, overall and training incidence rates increased significantly compared to pre-lockdown season, showing the impact of the restrictions period. Forwards players attained a higher number of injuries than backs, whilst HSI was the most common injury within backs while concussions were the most common diagnoses for forwards. More specifically, hamstring strain injuries, and concussions were higher in comparison with 2019 season. The present study is the first to analysed differences between pre- and post-lockdown incidences rates and to analysed match incidence rates in senior male amateur rugby players. This study demonstrates that practitioners may consider implementing preventive measures to increase player welfare and reduce the injury risk and improve load monitoring strategies, planning training sessions according to the demands required after a long period of restrictions in amateur rugby.
Funding
None declared.
Ethical approval
Ethical approval for this study was granted by the University of Flores' Research Ethics Committee in compliance with the Declaration of Helsinki. Subjects gave informed consent to participate.
Declaration of competing interest
None declared.
==== Refs
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Darrall-Jones J.D. Jones B. Till K. Anthropometric, sprint, and high-intensity running profiles of English academy rugby union players by position The Journal of Strength & Conditioning Research 30 5 2016 1348 1358 26466132
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Dönmez G. Özkan Ö. Menderes Y. Torgutalp Ş.Ş. Karaçoban L. Denerel N. The effects of home confinement on physical activity level and mental status in professional football players during COVID-19 outbreak The Physician and SportsmedicinePhysician and Sportsmedicine 2021 1 7 00(00)
Fuller C.W. Molloy M.G. Bagate C. Bahr R. Brooks J.H.M. Donson H. Consensus statement on injury definitions and data collection procedures for studies of injuries in rugby union British Journal of Sports Medicine 41 5 2007 328 331 17452684
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Kemp S. Faull-Brown R. Hood K. Stokes K. McKay C. Roberts S. RFU community rugby injury surveillance and prevention project 2019-2020 Community rugby injury surveillance and prevention (CRISP) project 2020
Kenny I. Comyns T. The Irish rugby injury surveillance (IRIS) project 2020 All-Ireland league club rugby. 2019-20 season report. In IRIS Clubs Season Report 1920 https://www.irishrugby.ie/playing-the-game/medical/research/
Kobayashi T. Tanaka M. Shida M. Intrinsic risk factors of lateral ankle sprain: A systematic review and meta-analysis Sport Health 8 2 2016 190 193
Lahti J. Mendiguchia J. Ahtiainen J. Anula L. Kononen T. Kujala M. Multifactorial individualised programme for hamstring muscle injury risk reduction in professional football: Protocol for a prospective cohort study BMJ Open Sport and Exercise Medicine 6 1 2020
Mannino B.J. Yedikian T. Mojica E.S. Bi A. Alaia M. Gonzalez-Lomas G. The COVID lockdown and its effects on soft tissue injuries in Premier League Athletes The Physician and Sportsmedicine 1–5 2021
Marotta N. de Sire A. Gimigliano A. Demeco A. Moggio L. Vescio A. Impact of COVID-19 lockdown on the epidemiology of soccer muscle injuries in Italian Serie A professional football players The Journal of Sports Medicine and Physical Fitness 62 3 2022 356 360 34546026
Mohr M. Nassis G.P. Brito J. Randers M.B. Castagna C. Parnell D. Return to elite football after the COVID-19 lockdown Managing Sport and Leisure 27 1–2 2022 172 180
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| 0 | PMC9737509 | NO-CC CODE | 2022-12-14 23:54:18 | no | Phys Ther Sport. 2023 Jan 10; 59:85-91 | utf-8 | Phys Ther Sport | 2,022 | 10.1016/j.ptsp.2022.12.005 | oa_other |
==== Front
J Infect
J Infect
The Journal of Infection
0163-4453
1532-2742
The British Infection Association. Published by Elsevier Ltd.
S0163-4453(22)00697-1
10.1016/j.jinf.2022.12.007
Letter to the Editor
Real-life practice of the Egyptian Kelleni's protocol in the current tripledemic: COVID-19, RSV and influenza
Kelleni Mina T. ⁎
Pharmacology Department, College of Medicine, Minia University, Minya 61111, Egypt
⁎ Corresponding author.
10 12 2022
10 12 2022
8 12 2022
© 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
2022
The British Infection Association
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
==== Body
pmcDear Editor
Currently, we are dealing in Africa as elsewhere globally, with a tripledemic of SARS CoV-2 Omicron numerous sub-variants, respiratory syncytial virus (RSV), and several influenza viruses including novel1 and potential reassortment influenza subtypes’ infection 2, 3, 4. The clinical manifestations of these and other respiratory viral infections are mostly similar 5 especially when the patients are seeking an early medical advice as we highly recommended and continue to recommend, to be noted that the vast majority of our African patients can't afford to perform any investigations due to economic reasons and again we had to adjust our practice to best serve all patients.
Interestingly, though the above mentioned viruses might share in sore throat, rhinitis, cough and fever. I suggest that influenza virus infection in adults is more characterized by the sudden onset of severe body ache, marked physical exhaustion (loss of energy as described by many patients), as well as the sudden troublesome nausea, while RSV infection in young children is more common to be associated with otalgia, and conjunctivitis. Similarly, diarrhea was a predominant GIT manifestation that accompanied or even preceded the usual respiratory manifestations and/or complications in an increasing number of patients in this wave of SARS CoV-2 Omicron infection with/without anosmia, ageusia.
Since SARS CoV-2 has been introduced to our medical challenges in November, 2019, physicians in Africa were obliged to take care of COVID-19 patients basing on our best clinical judgment and we can proudly and humbly announce, three years later, that the minimal COVID-19 mortality in Africa has proved us right when we decided to boost our natural immunity with safe, effective and generic drugs as best scientifically revealed in Kelleni's protocol 6 , 7.
From a daily real-life experience in my clinic which is focusing in management of COVID-19 and Post COVID syndrome, I wish to declare that early treatment using Kelleni's COVID-19 protocol is as safe and effective in management of this tripledemic as it was in SARS CoV-2 pre Omicron variants in pediatric, geriatric, immune-compromised and pregnant patients 8. Noteworthy, nitazoxanide, an integral part of Kelleni's COVID-19 protocol, was previously shown to inhibit the in-vitro replication of Paramyxoviridae including RSV and parainfluenza viruses 9 and human influenza viruses 10.
However, as more immune-evasive SARS CoV-2 variants are continuing to emerge, I adjusted my clinical practice and I wish to recommend a full 5-day-course of Kelleni's protocol rather than the usual 3-day-course 8 in all high risk populations especially kids under 5 years, elderly above 75 years and immune-compromised patients to avoid COVID-19 rebound that was seldom encountered in my clinical practice until recently in a young child who did not receive azithromycin in the initial 3-day-course and after 4 days of clinical resolution, runny nose, cough nausea and low grade fever reappeared and was perfectly and promptly controlled by another 3-day-course of nitazoxanide and azithromycin. Notably, bacterial co-infection is suggested to be considered in such clinical scenario; i.e. in virally infected patients who deteriorate after initial improvement 11. I currently use and recommend the full Kelleni's protocol, including azithromycin, for 5 days in all high risk groups as I suggest a favorable risk benefit ratio is obvious considering its high safety and efficacy as well as the additional potential benefits when using azithromycin prophylactically in those populations 12.
Funding/Financial exposure
None
Declaration of Competing Interest
The author declares that there is no conflict of interest.
==== Refs
References
1 Cheng D Dong Y Wen S Shi C. A child with acute respiratory distress syndrome caused by avian influenza H3N8 virus J Infect 85 2022 174 211
2 Li P Niu M Li Y Human infection with H3N8 avian influenza virus: a novel H9N2-original reassortment virus J Infect 85 2022 e187 -e9 36058414
3 Yu Y Wu M Cui X Pathogenicity and transmissibility of current H3N2 swine influenza virus in Southern China: a zoonotic potential Transbound Emerg Dis 69 2022 2052 2064 34132051
4 Liu T Huang Y Xie S A characterization and an evolutionary and a pathogenicity analysis of reassortment H3N2 avian influenza virus in South China in 2019-2020 Viruses 2022 14
5 Treanor J Viral infections of the lung and respiratory tract Grippi MA Antin-Ozerkis DE Dela-Cruz CS Kotloff RM Kotton CN Pack AI Fishman's Pulmonary Diseases and Disorders, 6e 2023 McGraw-Hill Education New York, NY
6 Kelleni MT. NSAIDs and Kelleni's protocol as potential early COVID-19 treatment game changer: could it be the final countdown? Inflammopharmacology 30 2022 343 348 34822026
7 Kelleni MT. NSAIDs/nitazoxanide/azithromycin repurposed for COVID-19: potential mitigation of the cytokine storm interleukin-6 amplifier via immunomodulatory effects Expert Rev Anti Infect Ther 20 2022 17 21 34088250
8 Kelleni MT. NSAIDs/Nitazoxanide/azithromycin immunomodulatory protocol used in adult, geriatric, pediatric, pregnant, and immunocompromised COVID-19 patients: a real-world experience Can J Med 3 2021 121 143
9 Piacentini S La-Frazia S Riccio A Nitazoxanide inhibits paramyxovirus replication by targeting the Fusion protein folding: role of glycoprotein-specific thiol oxidoreductase ERp57. Sci Rep 8 2018 10425 29992955
10 Tilmanis D van Baalen C Oh DY Rossignol JF Hurt AC. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide Antiviral Res 147 2017 142 148 28986103
11 Uyeki TM Bernstein HH Bradley JS Clinical practice guidelines by the infectious diseases society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenzaa Clin Infect Dis: Off Publ Infect Dis Soc Am 68 2019 e1 e47
12 Mosquera RA Gomez-Rubio AM Harris T Anti-inflammatory effect of prophylactic macrolides on children with chronic lung disease: a protocol for a double-blinded randomised controlled trial BMJ Open 6 2016 e012060
| 36513168 | PMC9737510 | NO-CC CODE | 2022-12-16 23:18:14 | no | J Infect. 2022 Dec 10; doi: 10.1016/j.jinf.2022.12.007 | utf-8 | J Infect | 2,022 | 10.1016/j.jinf.2022.12.007 | oa_other |
==== Front
Public Health Pract (Oxf)
Public Health Pract (Oxf)
Public Health in Practice
2666-5352
The Authors. Published by Elsevier Ltd on behalf of The Royal Society for Public Health.
S2666-5352(22)00125-2
10.1016/j.puhip.2022.100349
100349
Article
COVID-19 vaccination acceptance among older adults: A qualitative study in New South Wales, Australia
Bullivant Bianca ab∗
Bolsewicz Katarzyna T. abc
King Catherine abd
Steffens Maryke S. ab
a National Centre for Immunisation Research and Surveillance, Kids Research, Sydney Children's Hospitals Network, Cnr Hawkesbury Rd & Hainsworth St., Westmead, NSW, 2145, Australia
b The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
c Hunter New England Local Health District, Health Protection, Wallsend Hospital Campus, Wallsend, NSW, 2287, Australia
d Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
∗ Corresponding author. National Centre for Immunisation Research and Surveillance, Kids Research, Sydney Children's Hospitals Network, Cnr Hawkesbury Rd & Hainsworth St., Westmead, NSW, 2145, Australia.
10 12 2022
6 2023
10 12 2022
5 100349100349
4 10 2022
22 11 2022
5 12 2022
© 2022 The Authors
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Objectives
The COVID-19 pandemic has had a severe impact on people across the world, particularly older adults who have a higher risk of death and health complications. We aimed to explore older adults’ intention towards COVID-19 vaccination and factors that influenced their motivation to get vaccinated.
Study design
A qualitative study was conducted in New South Wales, Australia (April 2021), involving interviews with older adults (aged 70 years and older).
Methods
In-depth interviews were carried out with 14 older adults on their perceptions around COVID-19 vaccination. The COVID-19 vaccination program had just commenced at the time of data collection. We thematically analysed interviews and organised the themes within the Behavioural and Social Drivers of Vaccination (BeSD) Framework.
Results
We found that most participants were accepting of COVID-19 vaccination. Participants’ motivation to get vaccinated was influenced by the way they thought and felt about COVID-19 disease and vaccination (including perceptions of vaccine safety, effectiveness, benefits, COVID-19 disease risk, and vaccine brand preferences) and social influences (including healthcare provider recommendation, and influential others). The uptake of COVID-19 vaccination was also mediated by practical issues such as access and affordability.
Conclusions
Efforts to increase COVID-19 vaccination acceptance in this population should focus on highlighting the benefits of vaccination. Support should be given to immunisation providers to enhance efforts to discuss and recommend vaccination to this high-risk group.
Keywords
COVID-19
Older adults
Vaccination
Vaccination acceptance
Australia
Qualitative
==== Body
pmc1 Introduction
Coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) in March 2020 [1]. As of late July 2022, there were over 565 million confirmed cases, and 6.3 million confirmed deaths [2]. Protection against severe disease and death caused by COVID-19 and slowing the emergence of new variants will largely depend on people's acceptance and uptake of COVID-19 vaccines [3]. However, uptake is threatened by vaccine hesitancy, access issues and refusal of COVID-19 vaccines [4,5].
Vaccine uptake is driven by vaccination motivation and experiences. According to the Behavioural and Social Drivers (BeSD) of Vaccination Framework, [5] vaccination motivation is influenced by what people think and feel about vaccine preventable diseases and vaccines and by social processes related to vaccines (i.e., recommendation from a health worker). In addition, practical factors (i.e., access to services and information about vaccination) also influence vaccine uptake.
Vaccination uptake in older adults (those aged 70 years and over) was a focus of the Australian Government's rollout of the COVID-19 vaccine program [6]. Older adults were prioritised as a key group as increasing age is the leading risk factor for mortality and complications from COVID-19 infection [7]. The rollout in Australia began in late February 2021, and older adults were included a priority group. This was the second highest priority group after frontline health and aged care workers, disability and aged care residents and quarantine and border workers.
Previous research on vaccination uptake with Australian older adults has shown mixed results. For example, whilst influenza vaccination has previously reached coverage rates of over 70%, [8,9] awareness and uptake of pneumococcal vaccination is suboptimal, ranging from 39% to 69% [10,11]. In terms of COVID-19 vaccination, being older (>65 years old) has been associated with higher acceptance of COVID-19 vaccines, in Australia and internationally [[12], [13], [14]]. However, there is evidence that some older adults continue to remain uncertain and hesitant about getting a COVID-19 vaccine [15,16].
Understanding the specific factors that influence uptake of vaccines by priority groups during a pandemic (such as COVID-19 vaccines) early in a vaccine rollout is critical to achieving vaccine coverage among that priority group. Such information can inform interventions that aim to impact and modify a priority group's willingness to get vaccinated. Further, the BeSD Framework highlights that qualitative investigations into COVID-19 vaccination uptake can provide in-depth insights into local, context and time specific issues [5]. At the time of this study there was limited qualitative information about the specific drivers of COVID-19 vaccination among Australian older adults early on in the vaccine rollout. With these considerations in mind, this study aimed to qualitatively investigate the factors influencing COVID-19 vaccination decisions among adults aged 70 years and overliving in New South Wales (NSW) Australia, the most populous of the eight Australian states and territories.
2 Methods
2.1 Study design
To address the research aims, we used a qualitative methods design involving individual interviews with older adults living in NSW. This study received approval from the University of Sydney Human Research Ethics Committee (2020/277).
2.2 Setting
Interviews were conducted between the 7th and 23rd of April, 2021. Australia commenced the rollout of COVID-19 vaccines (AstraZeneca and Pfizer) in phased stages, beginning on 21 February, 2021 [6]. Australian Government recommendations changed during our data collection period due to thrombosis with thrombocytopenia (TTS) emerging as a rare but serious side effect of the AstraZeneca COVID-19 vaccine, especially in younger adults. As such, the Australian Technical Advisory Group on Immunisation (ATAGI) recommended preferencing the Pfizer COVID-19 vaccine for all people under 50 years of age on 8 April, 2021 [17]. The majority of our interviews took place after this announcement. Australia had low COVID-19 case numbers at this time, due to the pursuit of a near-elimination strategy [18].
2.3 Participant recruitment
Participants were recruited by a professional recruitment agency to meet predefined eligibility criteria (aged 70 years and over; a resident of NSW). The agency used this criteria to find participants through their database of potential respondents. Participants were provided with an information sheet detailing the purpose of the study. Those who provided written consent were scheduled for a 30-min phone or video conference-based interview at a time that was convenient for them. The research team did not have contact with participants prior to the commencement of the study. The interview guide asked participants about their experiences with previous vaccinations, feelings about, and intentions toward COVID-19 vaccination (see Supplementary File 1). Participants were reimbursed AUD60 (USD45) for their time.
2.4 Procedure
Interviews were conducted by BB, MS, and KB and analysed together with CK, all of whom are experienced researchers skilled in qualitative research methods. The research team worked as social scientists at an immunisation research centre at the time of this study. Interviews were audio-recorded and transcribed by an external transcription company. We conducted sampling and data analysis concurrently, stopping recruitment when our analysis of new transcripts no longer produced new categories.
2.5 Data analysis
We used thematic analysis to identify and extract information relevant to the research question [19,20]. Each transcript was read separately by two researchers who then created a combined analysis file. In addition to the pair analysis, we engaged in a group analysis, where the team met regularly to discuss combined analyses, reconcile differences in interpretation and agree on the emerging categories. Informed by the analysis of an initial seven transcripts, BB drafted a framework of key categories and sub-categories.
We used the key categories of the BeSD Framework, which is based on the ‘increasing vaccination model’ (see Fig. 1 ) [5,21]. This framework was utilised because it an evidence-based way to categories findings and has been used in other COVID-19 vaccination research with priority groups [22,23]. This framework was used as a guide for the remaining analysis and interpretation, during which it was expanded with new insights and refined through a group analysis process.Fig. 1 The adapted BeSD Framework showing key themes identified during the interviews.
Fig. 1
In this paper, and consistent with the definition of vaccine hesitancy, [21] we refer to participants who were hesitant and the one participant who rejected COVID-19 vaccination as ‘hesitant’.
3 Results
3.1 Participants
In total, 14 participants aged between 70 and 83 years were interviewed (Table 1 ). At the time of the interviews, one participant had already received their first dose of a COVID-19 vaccine (AstraZeneca COVID-19 vaccine) and another five participants had booked an appointment for their first dose of a COVID-19 vaccine. We assigned participants pseudonyms to ensure anonymity.Table 1 Characteristics of study participants.
Table 1Category Number of Participants
Gender
Female 6
Male 8
Age group
70–79 12
80+ 2
Location
Metro 8
Regional/rural 6
Chronic health conditiona
Yes 9
No 5
COVID-19 vaccination status
Received one dose of a COVID-19 vaccine 1
Booked in to receive a COVID-19 vaccine 5
Not booked in or received a COVID-19 vaccine 8
a Health conditions included heart disease, inflammatory condition, lung disease, neurological condition, and immunocompromised.
3.2 Findings
Nine themes, aligned with each category of the BeSD Framework, were identified (see Fig. 1) and are described below, accompanied by a small number of de-identified quotes to illustrate key points.
3.3 What participants think and feel
3.3.1 Vaccine brand preferences
Participants who were accepting of COVID-19 vaccination often indicated that they had no preference for a particular COVID-19 vaccine brand. Conversely, most hesitant participants preferred Pfizer over the AstraZeneca COVID-19 vaccine, primarily due to concerns about TTS.“If we were able to have the Pfizer vaccine I probably wouldn’t worry as much, but I think the AstraZeneca one has got quite a few question marks over it, and I am a little bit concerned about it.” (Fiona, female, aged 74 years, hesitant)
Other hesitant participants did not want to receive either COVID-19 vaccine brand, saying that neither was appropriate for them.
3.3.2 Perceived safety and effectiveness of vaccines
Most accepting participants expressed confidence and trust in the safety and effectiveness of COVID-19 vaccines. These participants reported gaining confidence from seeing the vaccines rolled out in other countries (e.g., USA, United Kingdom) and the corresponding small number of people who experienced negative side effects. These participants also commented that vaccination had been effective in reducing hospitalisation rates and the spread of COVID-19 infections in these countries.“We follow England and America. Now, if they’re having good results, I mean, I think they had 20 or 40 people have had a few problems, but when you look at the millions that they’re doing, it’s such a small number.” (Paul, male, aged 77 years, accepting)
Hesitant participants expressed a lack of confidence in the safety of COVID-19 vaccines, expressing concerns about the side effects of the vaccines, from short-term side effects (e.g., severe fatigue, feeling unwell) to potentially unknown long-term side effects. The main safety concern was the risk of developing blood clots associated with the AstraZeneca COVID-19 vaccine. These participants reported that seeing this rare side effect emerge after the vaccine was made available to the public reinforced their hesitancy and their decision to “wait and see” about getting vaccinated.
These participants also described concerns with the speed of vaccine development and viewed the blood clotting side effect associated with the AstraZeneca COVID-19 vaccine as evidence that the vaccine was ‘rushed’. One hesitant participant perceived that the elderly, as one of the first groups to receive the vaccines, were being used as “guinea pigs” for the vaccines.“Something that’s been developed in 12 months, we’ve already seen there’s a very, very slight chance of blood clots. We’re worrying about what the future long-term ramification might be. It could be a hell of a lot worse than what COVID does to you.” (Ben, male, aged 70 years, hesitant)
Hesitant participants were also concerned about the effectiveness of COVID-19 vaccines, particularly in preventing people from getting COVID-19 disease or passing it on to others. Some perceived the data supporting high efficacy rates of these vaccines as weak, inconclusive and lacking credibility as it was provided by pharmaceutical companies.
3.3.3 Perceived COVID-19 disease risk
Accepting participants were more likely to perceive their personal risk of getting COVID-19 as high. Most accepting participants also reported feeling that they would be more susceptible to contracting severe COVID-19 disease due to their age or chronic health condition.“I guess your immune system maybe is not as strong as you get older and therefore – and it seemed to be affecting older people much more than it did young people.” (Julia, female, aged 81 years, accepting)
Conversely, many hesitant participants perceived their personal risk of being infected by COVID-19 as low due to the low COVID-19 case numbers in their local area, state, or Australia more broadly. This contributed to the lack of urgency these participants reported about needing to get vaccinated, and expressed most commonly by participants living in regional NSW.
Hesitant participants also reported not feeling susceptible to contracting severe COVID-19 disease despite their age or chronic health condition. Participants that were in their early seventies and with no chronic health conditions were more likely to express this sentiment.“I sort of feel 70 was an arbitrary figure, I live in this sort of delusion I’m still young and old people is anyone that’s older than me, and I’m still young. I didn’t feel susceptible at all.” (Ben, male, aged 70 years, hesitant)
3.3.4 Perceived benefits of vaccination
For accepting participants, the perceived benefits outweighed the potential risks associated with vaccinating. The main stated benefit was protection for themselves, their family and friends and the broader community. These participants reported a sense of responsibility to protect close family and friends and people more vulnerable than them.“The key would be protection – protection for myself, and obviously people around me.” (Sean, male, aged 70 years, accepting)
Other benefits included the ability to travel domestically and internationally, getting life back to normal and less restrictions in visiting friends in aged care.
For some hesitant participants, the potential benefits did not outweigh the risks. Overall, the potential risk of experiencing an adverse effect was seen as higher and with more negative consequences, than the risk of contracting COVID-19.
Hesitant participants outlined two key benefits to vaccination that might convince them to vaccinate. Some hesitant participants said that if case numbers in NSW were higher, they would consider vaccinating for protection; some others indicated they would consider vaccinating to be able to travel.“One of the main reasons is that I do want to do some overseas travel at some stage, and I don’t think that’s going to be on the cards for Australians until we’re all vaccinated.” (Fiona, female, aged 74 years, hesitant)
3.4 Social processes
3.4.1 Influential others
Participants identified family members and friends as important influences on their vaccination decisions. Accepting participants tended to report knowing someone around their age who had already been vaccinated and had had a positive experience or no side effects. This was reassuring to participants, and a motivation to vaccinate.“The key reason for me was my friends- having the injections, and they were saying how simple it was to have it done.” (Petra, female, aged 74 years, accepting)
Some hesitant participants reported placing a high value on forming their own independent decisions about COVID-19 vaccination, rather than listening to others. Participants said that at t times this was a source of tension between themselves and families and/or friends.“There’s been a bit of tension in my life because my children are into the, you know, work in the medical field and they’re in support of the COVID vaccination.” (Aaron, male, aged 71 years, rejecting)
Accepting participants described that they trusted the assurances from health authorities and the government about vaccinating against COVID-19. These participants praised the response from the federal and state governments in protecting people from COVID-19.“We have assurances from the very top of government and from the top of the medical fraternity, both public and private that, yes, this is what we should be doing.” (Connor, male, aged 84 years, accepting)
While some hesitant participants reported trusting government advice on the public health measures implemented to slow the spread of COVID-19, some were disconcerted by the changing advice around who was eligible to receive the AstraZeneca COVID-19 vaccine. These participants perceived this advice as inconsistent and confusing, and evidence that health authorities were uncertain about the guidance they were providing to the public. These participants were particularly concerned that elderly, unwell people were being put at risk unnecessarily, as the side effects of the AstraZeneca COVID-19 vaccine could cause harm and in some rare cases death.
3.4.2 Health worker recommendation
Accepting participants were more likely to report having received an explicit recommendation to vaccinate from their general practitioner (GP). These participants typically described having a long-standing relationship with their GP and trusting their opinion. Elderly participants with underlying health conditions sometimes also received an active recommendation from their medical specialist or were encouraged by chronic disease organisations to book in for vaccination.
Some hesitant participants also reported valuing their GP's advice and stated that it would influence their decision if they received a recommendation to be vaccinated.“Specifically asking my doctor, since he knows my history of varicose veins whether or not I would be at more of a risk of blood clots through the AstraZeneca vaccination, because of my personal medical history.” (Fiona, female, aged 74 years, hesitant)
Some hesitant participants reported not receiving a recommendation from their GP yet, and this contributed to their impression that vaccination was not urgent.
3.5 Motivation
3.5.1 Intention to get a COVID-19 vaccine
Participants reported a range of COVID-19 vaccination intentions, from accepting (8 participants), hesitant (5 participants) and rejecting (1 participant). Accepting participants had either received one dose of a COVID-19 vaccine, were booked in to receive the vaccine or indicated that they intended to receive the vaccine.“I certainly will obviously have it. I’ve always thought that it was a good idea because at least it’s some finality to it all.” (Sean, male, aged 70 years, accepting)
Participants who were hesitant often planned to wait before vaccinating because they had specific concerns about COVID-19 vaccine safety and side effects.“I just think we all have our own ways of thinking and our own ways of dealing with things, and that I want to wait and that I want to see a bit of outcome.” (Georgia, female, aged 70 years, hesitant)
The one participant who had no intention of vaccinating against COVID-19 stated that the health risks posed by the COVID-19 pandemic had been overstated by the Australian government.
3.6 Practical issues
3.6.1 Access
Many accepting participants who had made a booking to receive a COVID-19 vaccine reported finding the process easy and convenient. These participants had all booked through a GP practice, either online or by calling. For these participants, knowing that they were eligible to get vaccinated from government communications had encouraged them to book an appointment with their GP.“Once you’ve had it, as I did yesterday, I’ve got to ask myself, “What’s all the fuss about it? It’s so straight forward. It’s just an easy process.” It’s not hard, and it’s not painful, and it takes no more than about 20 minutes.” (Leo, male, aged 70 years, accepting)
Participants who intended to get vaccinated in the future discussed several practical issues that made vaccination booking difficult. This included their GP practice not having enough stock when they went to make a booking or their local GP practice not offering COVID-19 vaccinations. This was a source of considerable frustration for these participants.
Hesitant participants living in regional areas of NSW perceived that the vaccine rollout in their area was slow. These participants interpreted the accelerated rollout in other areas as a lack of urgency to vaccinate in their area.
3.6.2 Affordability
Several participants who were less accepting of the vaccine reported financial costs associated with going to the GP and consulting about vaccination.“I don’t really want to have to go to my doctor because now I’ve got to pay a consultation fee and I’m on a pension and that’s quite expensive.” (Fiona, female, aged 74 years, hesitant)
Conversely, knowing that there was no charge associated with vaccination consultation and/or vaccinating, as a key facilitator for accepting participants.
4 Discussion
This study contributes to the limited but growing literature on COVID-19 vaccination intentions, perceptions and experiences among older Australian adults. We found that participants’ motivation to vaccinate was influenced by their perceptions of COVID-19 disease risk, vaccine safety, effectiveness, benefits, vaccine brand preferences, and a provider and influential others recommending vaccination. The uptake of COVID-19 vaccine was also mediated by practical issues such as convenience, vaccine availability and affordability.
These findings are consistent with other international and Australian literature among older adults. Qualitative interviews with Swiss and Australian older adults found that those who reported benefits of vaccination, higher level of confidence in the safety and effectiveness of COVID-19 vaccines, and reported that their provider recommended vaccination to them were more likely to accept vaccination [23,24]. Certain barriers to vaccination were also seen in other older adult samples, including a survey among 488 Saudi Arabian older adults conducted in late 2020. This research found that adverse side effects and safety and efficacy concerns were the main reasons for COVID-19 vaccine hesitancy [25]. Qualitative methods among Australian and UK older adults also uncovered similar reasons for hesitancy, including perceived vaccination risks outweighing the benefits and access issues [23,26].
Several other factors have emerged from the literature that were not found in our study. This includes perceptions of the severity of the potential long-term effects, the social influence of misinformation and the severity of previous infection with COVID-19 [23,27,28]. This is unsurprising as the BeSD Framework posits that the factors that influence vaccination uptake are context and time specific [5]. As such, the framework was useful to in the analysis process to categorise the key themes that emerged from this study.
Whilst most participants in this study were accepting of COVID-19 vaccination, a few did express hesitancy. This is consistent with research conducted in Australia, UK, and US [23,25,29]. Several participants in our study identified a few factors that might change their vaccination intention, including receiving a vaccination recommendation from their GP and being able to travel freely once vaccinated. While cautious when generalising findings to the wider Australian older adult population, our findings have a number of implications for COVID-19 vaccination strategies targeting older adults.
First, the central role of a GP or specialist in vaccination intentions and uptake, found in this study, has been reported previously [21]. Recent research suggests that a provider's recommendation is also a driver of vaccine acceptance for COVID-19 vaccines [30,31]. In light of this, we recommend that GPs and other immunisation providers (e.g., Aboriginal Medical Services, pharmacists, nurses) need to be supported to proactively recommend COVID-19 vaccination. This includes supporting providers' outreach to patients for example by calling or messaging eligible patients, and securing adequate remuneration for vaccination consultations.
Second, providers should also be supported with communication training and resources, particularly around how to have supportive and effective conversations with hesitant patients, and recommend vaccination. Providers in Australia reported that it has been challenging to stay up to date with COVID-19 vaccine information and recommendations, and this has impacted their confidence when talking with patients [23]. Providers in Australia have requested clear and simple resources to support their conversations with parents [32]. Conversation guides, decision aids and information sheets that outline the risks and benefits of vaccination could support discussions and informed consent.
Finally, findings from our study suggest that highlighting the benefits of vaccination, including the non-health benefits (i.e., ability to travel freely) may facilitate vaccination uptake among older adults. Previous vaccination messaging research has demonstrated that benefits-framed messaging is more effective than using fear in regards to vaccination [33]. Likewise, recent research demonstrated that messages that focus on the personal benefits of COVID-19 vaccination are effective in reducing vaccine hesitancy [34,35]. Highlighting such non-health benefits could tip people's risk-benefits calculation in favour of COVID-19 vaccination.
4.1 Limitations and future research
Recruiting participants through a recruitment company may have resulted in our study sample not being representative of the full range of perspectives of older adults living in NSW. It's possible that individuals with certain intentions and attitudes, positive or negative towards vaccination, were over-represented among individuals who agreed to participate in this study. Further, our participant's views may not represent those of older adults living outside of NSW and from culturally and linguistically diverse backgrounds. However, the repeated emergence of key themes in the interviews suggests that the most salient ideas were captured. Further research with diverse communities would provide an understanding of their perceptions and experiences with COVID-19 vaccination.
We conducted this study at a particular point in time; participant's intentions, perceptions and experiences will likely have shifted over time, with the changes in vaccine availability and access, COVID-19 case numbers and public health advice. Continuous monitoring of older adults' sentiment towards COVID-19 vaccination is needed within the pandemic context. This may allow identification of variations in vaccination intentions over time and provide timely, accurate information that can be used by policymakers and service coordinators to tailor immunisation program and services.
5 Conclusions
This qualitative study highlights factors influencing older Australian adults' decision making around COVID-19 vaccination, at the start of the vaccine rollout. Encouragingly, most of the older adults were accepting and intended to vaccinate. As older adults are among those most affected by the negative consequences of COVID-19, however, it's important to focus on those who remain hesitant. Strategies to increase acceptance could involve highlighting the medical and non-medical benefits of COVID-19 vaccination, and supporting immunisation providers in their vaccination consultations with older adults. Findings from this study may inform the development of campaigns to promote vaccination acceptance and uptake during the COVID-19 pandemic and future pandemics.
Funding
All authors’ positions are funded by the National Centre for Immunisation Research and Surveillance. The COVID-19 Vaccination Messaging Study is funded via a grant from 10.13039/501100009287 NSW Health .
Statement of ethical approval
This study received approval from the University of Sydney Human Research Ethics Committee (2020/277).
Declaration of competing interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bianca Bullivant reports financial support was provided by 10.13039/501100009287 NSW Health . Maryke Steffens reports financial support was provided by 10.13039/501100009287 NSW Health . Katarzyna Bolsewicz reports financial support was provided by 10.13039/501100009287 NSW Health . Catherine King reports financial support was provided by 10.13039/501100009287 NSW Health .
Appendix A Supplementary data
The following is the Supplementary data to this article:Multimedia component 1
Multimedia component 1
Acknowledgments
The authors would like to thank the participants for sharing their time and insights about COVID-19 vaccination.
Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.puhip.2022.100349.
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| 0 | PMC9737511 | NO-CC CODE | 2022-12-14 23:45:30 | no | Public Health Pract (Oxf). 2023 Jun 10; 5:100349 | utf-8 | Public Health Pract (Oxf) | 2,022 | 10.1016/j.puhip.2022.100349 | oa_other |
==== Front
Microchem J
Microchem J
Microchemical Journal
0026-265X
1095-9149
Elsevier B.V.
S0026-265X(22)01132-8
10.1016/j.microc.2022.108304
108304
Article
Tetrahedral DNA framework assisted rotational paper-based analytical device for differential detection of SARS-CoV-2 and influenza A H1N1 virus
Li Fengling a
Qi Ji c
Ren Zengzheng a
Hu Xiaoli a
Chen Yan b⁎
Li Bowei c⁎
Fu Xiuli a⁎
a School of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China
b School of Resources and Environmental Engineering, Shandong Agriculture and Engineering University, Jinan 250100, China
c CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, The Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China
⁎ Corresponding authors.
10 12 2022
2 2023
10 12 2022
185 108304108304
10 7 2022
6 12 2022
7 12 2022
© 2022 Elsevier B.V. All rights reserved.
2022
Elsevier B.V.
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Graphical abstract
Coronavirus disease 2019 (COVID-19) and influenza A are two respiratory infectious diseases with similar clinical manifestations. Because of the complex global epidemic situation of COVID-19, the distinction and diagnosis of COVID-19 and influenza A infected persons is crucial for epidemic prevention and control. In this study, tetrahedral DNA framework (TDF) was combined with a rotational paper-based analytical device, and the color change generated by the reaction between horseradish peroxidase (HRP) and 3,3′5,5′-tetramethylbenzidine (TMB)–H2O2 was used for grayscale signal analysis by ImageJ software. The quantitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A H1N1 virus were realized simultaneously. Under the optimal conditions, the paper-based analytical device showed a good linear relationship between the two viruses in the range of 10-14-10-8g/mL, and the two viruses were not affected by cross reaction. This sensor provides a convenient and reliable method for clinical rapid differentiation and diagnosis of COVID-19 and influenza A.
Keywords
Tetrahedral DNA framework
Paper-based analytical device
SARS-CoV-2
Influenza A H1N1 virus
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pmc1 Introduction
COVID-19 and influenza A are two respiratory infectious diseases with very similar clinical symptoms, such as fever, dry cough and general fatigue, which are highly contagious and spread mainly through air droplets and close contact [1], [2], [3], [4], [5]. The similarity of these initial symptoms seriously interferes with accurate diagnosis and treatment of patients [6], [7]. Especially for COVID-19 patients, if the disease is not controlled in time, it will lead to dyspnea and further threaten the life of patients [8], [9]. At present, the clinical detection technologies for COVID-19 are mainly reverse-transcription polymerase chain reaction (RT-PCR) and chest computed tomography (CT) scan, while the clinical test techniques for influenza A are mainly enzyme-linked immunosorbent assay (ELISA) and RT-PCR [10], [11], [12], [13]. However, these detection methods are limited in many aspects, including expensive instruments, complicated procedures, and high professional requirements for testing personnel [14]. Therefore, it is an urgent need to develop rapid, low-cost, highly sensitive and easily scalable detection methods for the rapid detection of SARS-CoV-2 and influenza A H1N1 virus.
Microfluidic paper-based device can integrate the whole experiment process into a miniaturized cellulose paper. It has the advantages including low price, easy fabrication, portability, low reagent consumption, and multiplexed analysis [15], [16], [17], [18]. Microfluidic paper chip technology can make a variety of chip channels through chip pattern design, and realize the detection of one or more targets. Based on the above outstanding characteristics, microfluidic paper-based devices have aroused wide attention for detection of viral which posing a grave threat to human health [19], [20]. For example, Lomae et al. developed a paper-based electrochemical sensor using peptide nucleic acid for detection of SARS-CoV-2 [21].
With the rapid development of DNA nanotechnology, various exquisite DNA nanostructures with good biocompatibility, simple synthesis and high stability have been widely used in biosensing analysis [22], [23], [24], [25]. Of note, tetrahedral DNA framework (TDF) has gained considerable research attention owing to its powerful rigid structure which could be precisely adjusted by controlling the base sequence [26], [27], [28], [29], [30]. TDF as surface immobilized substrate can achieve precise regulation of ligands in well-defined orientation and spacing, which could improve the sensitivity of biosensors [31], [32], [33]. For example, Sun et al. designed a framework nucleic acid loaded with ampicillin to raise the drug detection sensitivity of methicillin-resistant Staphylococcus aureus [34]. Ji et al. reported a DNA framework-mediated hyperbranched hybrid chain reaction for the detection of Pb2+ [35].
Herein, a rotational paper-based analytical device (RPAD) using TDF was proposed for rapid detection of SARS-CoV-2 and influenza A H1N1 virus. In this research, to avoid crowding and entanglement between recognition molecular aptamer, biotin-tagged TDF was used for attaching aptamer with consistent orientation and well-defined spacing, which could effectively improve the recognition efficiency and lower nonspecific adsorption of the system. The rotational paper-based analytical device platform confers the strategy to be simple, portability, low cost and high-efficiency. In addition, the selective recognition was ensured by the stronger specific interaction between aptamer and target than that of the base pairs, which led to detach the aptamer from TDF [36], [37], and then facilitated the combination of biotinylated S-detection DNA or H-detection DNA and TDF based on the principle of base complementary pairing. The quantitative analysis was achieved by monitoring the grayscale value on the RPAD generated by the reaction between streptavidin conjugated horseradish peroxidase (s-HRP) and 3,3′5,5′-tetramethylbenzidine (TMB)–H2O2. Taking advantages of microfluidic paper chip plus TDF, this strategy provided a simple, rapid, sensitive and effective platform for diagnosis of the current epidemic disease and related research.
2 Experimental section
2.1 Materials and chemicals
Trizma hydrochloride (Tris-HCl) buffer solution (pH 7.0), chitosan, tween-20, bovine serum albumin (BSA) were obtained from Sigma-Aldrich (St. Louis, MO, USA). Glutaraldehyde was purchased from Sinopharm Chemical Reagent Co., ltd. (Shanghai, China). TMB-H2O2 solution was purchased from Shanghai Beyotime Biotechnology Co., ltd. (Shanghai, China). TM buffer (pH 7.5), streptavidin, biotin, s-HRP and custom DNA oligonucleotides (see Table S1 for detailed DNA sequences) were acquired from Shanghai Sangon Biological Engineering Technology & Services Co., ltd. (Shanghai, China). Whatman No. 1 filter paper (46 cm × 57 cm) was supplied by GE Healthcare Worldwide Company (Shanghai, China). PBST solution (PBS containing 0.05 % Tween-20, pH 7.4) was used as washing buffer. Inactivated influenza A H1N1 virus antigen was purchased from Absin Bioscience Inc. (Shanghai, China). SARS-CoV-2 (2019-nCoV) spike glycoprotein (S protein) was purchased from Sino Biological Inc. (Beijing, China). The swab virus preservation solution was provided by Shandong Shengkang Medical Equipment Co., ltd (Shandong Heze, China). The rest chemicals were of at least analytical reagent grade. All solutions were prepared using double distilled water (18.2 MΩ, Pall Cascada).
2.2 Instrumentation
The designed rotational paper-based analytical device was printed by a solid-wax printer (XEROX Phaser 8560DN). The printed rotational paper-based analytical device was baked using an oven from Shanghai Jing Hong Laboratory Instrument Co., ltd. (Shanghai, China).
2.3 Synthesis of tetrahedral DNA framework (TDF)
The TDF was synthesized following the reported literatures [38], [39], [40]. To form the TDF, 1 μL of T-S-1/T-H-1, T2, T3 and T4 were mixed in TM buffer with equimolar concentration. Afterward, the compound was annealed at 95 ℃ for 7 min and then rapidly cooled down to 4 ℃ for 25 min to yield uniform and stable TDF. The assembled TDF was characterized using 1.5 % gel electrophoresis analysis in 1X TBE buffer (pH 8.4).
2.4 Design and fabrication of the RPAD
The RPAD was designed using Adobe Illustrator software and directly wax-printed onto Whatman No. 1 filter paper by a wax inkjet printer. After printing, the wax-printed filter paper was heated in an oven at 140 ℃ for 60 s to generate the hydrophobic barrier as shown in Fig. S1.
The RPAD consists of two parts including the detection layer and the washing layer, as displayed in Fig. 1 A and Fig. S1B. The detection layer was designed with a diameter of 60 mm, which containing four reaction zones (5 mm in diameter, white color). Two of the reaction zones were used to detect S protein of SARS-CoV-2 and the other two were used to detect H1N1, respectively. The washing layer (90 mm in diameter) contained four circular holes and four washing channels which could connect with the detection zone vertically by rotation the washing layer to realize the washing function, as shown in Fig. 1B.Fig. 1 (A) Schematic diagram of the wax-patterned paper analytical devices. The designed RPAD consisted of detection and washing layers and both of them containing hydrophobic barrier and hydrophilic zone. These two layers were assembled by a rivet which was punched in the center hole of each paper layer. (B) Schematic of the working process of the RPAD. The “detection/washing” state could be conveniently controlled by rotating the washing layer.
Finally, the center holes of the two layers are connected with rivet, and the assembly sequence is from top to bottom for the detection layer and the washing layer. Simultaneously, the two layers can be rotated freely with the center hole to realize the reaction and washing function.
2.5 Preparation of TDF functionalized RPAD
Firstly, chitosan solution (2.5 μL, 2.5 × 10-4 g/mL, chitosan solution was prepared with 1 % acetic acid, pH 2.8) was dropped onto the reaction zone. After drying, glutaraldehyde solution (2.5 μL, 2.5 %, glutaraldehyde solution was prepared using double distilled water, pH 3.2) was added and incubation for 2 h in order to execute aldehyde cross-linking. Then, the reaction zone on the detection layer was aligned with the washing channel on the washing layer by rotating to perform washing function. After washing with PBST, the washing channel of the washing layer was again turned away from the reaction zone of the detection layer (The washing channel was aligned with the reaction zone when washing in subsequent experiments, and the washing channel was turned away from the reaction zone after the washing was completed). After drying, streptavidin (2.5 μL, 5 × 10-5 g/mL, streptavidin was prepared with 0.1 × PBS, pH 7.4) was added and incubated for 10 min at room temperature. Then, BSA (2.5 μL, 0.5 %, BSA was prepared with 0.1 × PBS, pH 7.4) was added to block the nonspecific active site and the unreacted residual was washed thoroughly by PBST. Afterwards, S protein tetrahedral DNA framework (S-TDF) (2.5 μL, 10-6 mol/L, pH 7.4) and H1N1 tetrahedral DNA framework (H-TDF) (2.5 μL, 10-6 mol/L, pH 7.4) were added to the corresponding reaction zones, and incubated for 10 min. After washing, biotin (2.5 μL, 0.1 %, biotin was prepared using double distilled water, pH 3.9) was introduced to block the residual binding site of streptavidin. Subsequently, S-aptamer (2.5 μL, 10-6 mol/L, S-aptamer was prepared with Tris-HCl, pH 7.4) and H-aptamer (2.5 μL, 10-6 mol/L, pH 7.4) were dropped onto the corresponding reaction zones, and further incubated at room temperature for 10 min. Finally, the obtained TDF functionalized paper-based chip was thoroughly washed with PBST to remove unhybridized aptamer, and dried for following use.
2.6 TDF functionalized chip for detection of S protein and H1N1
The detailed detection processes on the RPAD were displayed in Fig. 2 . Briefly, 2.5 μL of S protein solutions and H1N1 solutions with different concentrations were added into the corresponding reaction zones on the detection layer and incubated for 10 min. Then, S-detection DNA (2.5 μL, 10-6 mol/L, pH 7.4) and H-detection DNA (2.5 μL, 10-6 mol/L, pH 7.4) were added separately in the corresponding reaction zones and reacted for 10 min. After washing and drying, s-HRP (2.5 μL, 4 × 10-7 g/mL, pH 7.4) was added to each reaction zone and incubated for 10 min. After washing with PBST buffer, 4 μL of TMB-H2O2 chromogenic reagent was introduced to the reaction zones of the chip to produce color changes. Finally, the color signals were collected by a mobile phone (Redmi note7pro) and the grayscale values were analyzed by ImageJ software.Fig. 2 Scheme of the analytical procedure for the RPAD detection of S protein and H1N1 based on TDF.
2.7 Sample processing
To assess the validity of the TDF functionalized chip for determination of S protein and H1N1 in real samples, different concentrations of S protein solution and H1N1 solution were spiked in swab virus preservation solution to obtain a series of samples. All the swab virus preservation solution with and without spiking were performed according to the above procedure.
3 Results and discussion
3.1 Principle of the designed RPAD for detection of S protein and H1N1
Fig. 1 displayed the structure of the RPAD platform for the detection of S protein and H1N1. The created rotational paper-based device contains two paper layers including detection layer and washing layer. For each layer, the black (detection layer) or green (washing layer) areas are the hydrophobic barriers, and the white areas are the hydrophilic zones. The hydrophilic circular zone array on the detection layer was used as reaction zone. After rotating, the hydrophilic washing channel on the washing layer could be connected with the reaction zone to perform the washing process.
The principle of the designed TDF functionalized RPAD was demonstrated in Fig. 2. Firstly, streptavidin was modified on the reaction zone with the aid of glutaraldehyde and chitosan by means of Schiff base reaction between aldehyde group and amino group. Subsequently, the synthesized TDF with three biotin groups at three vertices was employed to bind with streptavidin and further to fix aptamer in a straightforward direction and well-defined spacing by hybridization with the ssDNA extension of TDF at the other vertex. In the presence of target, the aptamer (S-aptamer or H-aptamer) would preferentially bind to target (S protein or H1N1) which leading to a change in the configuration of the aptamer and detach from TDF. Thus, biotinylated detection DNA (S-detection DNA or H-detection DNA) could bind to the ssDNA extension of TDF through complementary bases. In this case, s-HRP could be anchored in the reaction zones. After introducing TMB-H2O2 solution, s-HRP could catalyse the oxidation of TMB to produce strong color signal. With the increasing of the concentration of target, more and more s-HRP could be bound on the reaction zone, which generated enhanced color signals. In consequence, using the grayscale value of reaction zone as the color signal, the proposed RPAD could achieve quantitative detection of S protein and H1N1.
3.2 Characterization of the S-TDF and H-TDF
The formation of TDF is important for the subsequent specific recognition of S protein and H1N1. Here, agarose gel electrophoresis was used to characterize S-TDF and H-TDF. S-TDF and H-TDF were constructed by self-assembled of four ssDNA (Table S1; S-TDF: T-S-1, T-2, T-3 and T-4; H-TDF: T-H-1, T-2, T-3 and T-4), respectively. T-S-1 and T-H-1 contain 79 bases and 83 bases, respectively. T-2, T-3 and T-4 have 55 bases, respectively. As demonstrated in Fig. S2, S-TDF (lane 5 in Fig. S2A) and H-TDF (lane 5 in Fig. S2B) moved more slowly than single strand or any other DNA combinations. These results confirms that the S-TDF and H-TDF were successfully synthesized.
3.3 Optimization of experimental conditions
The effects of the concentration of streptavidin, the incubation time of target, and the reaction time of s-HRP were systematically investigated to achieve the best performance of the designed RPAD.
The concentration of streptavidin was first optimized because it could directly affect the amount of TDF bound in the RPAD and thus affect the sensitivity of the assay. The grayscale signal values (ΔI = I 0 – I, I 0 and I were the grayscale values in absence and presence of target, respectively) were employed to assess the performance of the RPAD. Fig. S3 A showed that the ΔI went up with the increment of concentration of streptavidin and reached the maximum at 5 × 10-5 g/mL. Therefore, 5 × 10-5 g/mL was chosen as the optimal concentration of streptavidin.Fig. 3 (A) Photographs of paper chips corresponding to different concentrations of S protein. (B) Histogram of grayscale value variation in response to different concentrations of S protein by functionalized paper chips. (C) The corresponding calibration curve of this system for analysis of S protein (10-14-10-8 g/mL). (D) Photographs of paper chips corresponding to different concentrations of H1N1. (E) Histogram of grayscale value variation in response to different concentrations of H1N1 by functionalized paper chips. (F) The corresponding calibration curve of this system for analysis of H1N1 (10-14-10-8 g/mL). Error bars were calculated from five parallel measurements.
Next, the incubation time of target was investigated to ensure the complete combination of aptamer with the target. As illustrated in Fig. S3B, for both S protein and H1N1, the ΔI gradually increased with increasing incubation time in the range of 1–10 min. The reason for this phenomenon was that with the increase of the incubation time of S protein or H1N1, more and more S protein or H1N1 were bound to the corresponding aptamer respectively. In this case, target and aptamer complex were detached from S-TDF or H-TDF, which was beneficial to the combination of S-detection DNA with S-TDF or H-detection DNA with H-TDF. If the incubation time of S protein or H1N1 was further increased, the ΔI was almost the same which means that the target and aptamer were fully combination. Therefore, 10 min was chosen as the optimal incubation time for S protein and H1N1 for subsequent experiments.
Finally, the effect of the reaction time of s-HRP was examined from 1 to 16 min (Fig. S3C), and the maximum ΔI was achieved at 10 min. This may be because of that s-HRP was completely bound to biotinylated S-detection DNA or H-detection DNA at 10 min. Therefore, 10 min was chosen as the optimal reaction time for s-HRP.
3.4 Analytical performance of the strategy
Based on the above obtained optimized conditions, the analytical performance of the paper-based analytical device auxiliary with TDF for S protein and H1N1 detection was validated. Here, HRP was used to catalyze the TMB-H2O2 color-changing system. The generated visible color signal (grayscale signal) of TMB-H2O2 system from nearly colorless to dark blue could be accurately monitored using a smartphone and analysed by ImageJ software. As displayed in Fig. 3A and 3D, the color of the reaction zones gradually darken with increasing concentrations of S protein and H1N1. Correspondingly, the grayscale value of the reaction zone gradually decreased (Fig. 3B and 3E), and the ΔI was proportional to the concentration of S protein or H1N1 (Fig. 3C and 3F). This phenomenon directly attributed to that the stronger binding affinity between aptamer and its target. Taking advantage of this behavior, the biotinylated S-detection DNA or H-detection DNA could bind with S-TDF or H-TDF, which resulting in increasing amount of s-HRP captured on the reaction zone of the paper chip. As demonstrated in Fig. 3C and 3F, the ΔI was linearly correlated with the S protein and H1N1 concentration in the range of 10-14 to 10-8 g/mL, respectively. The lowest detection concentration was 10-14 g/mL for each target. We further compared our designed strategy with recent cutting-edge techniques for detection of SARS-CoV-2 including CRISPR diagnosis, point-of-care testing and smartphones [41], [42], [43], [44], [45], [46]. As shown in Table S2, these advanced techniques have the advantages of simple and high sensitivity. The performance of our strategy was comparable to the reported advanced techniques without or with signal amplification, which manifesting that our strategy could be a promising efficient method for pathogen diagnosis especially in resource-limited settings.
The reproducibility of the designed paper-based analytical device was evaluated by tested 10 different paper chips with two different concentrations for each target. As shown in Fig. S4, for S protein and H1N1 at 0 g/mL and 10-8 g/mL, the relative standard deviation (RSD) of grayscale value of 10 paper chips was less than 3 % demonstrating that the paper-based device has satisfactory reproducibility. To assess the stability of the strategy, we stored the paper-based analytical device paper chips for 20 days with two different concentrations for each target. Fig. 4 showed that the grayscale value remained stable which revealing excellent storage stability.Fig. 4 Stability of the developed paper-based sensor. (A) Grayscale value of the paper chip incubated with 0 g/mL and 10-8 g/mL S protein. (B) Grayscale value of the paper chip incubated with 0 g/mL and 10-8 g/mL H1N1.
3.5 Cross-reactivity of S protein and H1N1
To verify the cross-reactivity between S protein and H1N1, the mixture of S protein and H1N1 was tested. As shown in Fig. 5 ,10-8 g/mL H1N1 was mixed with various concentrations of S protein in the range of 10-13-10-8 g/mL. As expected, the color of the H1N1 reaction zone changed to almost the same grayscale value for 10-8 g/mL H1N1 in all samples. In contrast, the color of the S protein reaction zone gradually darkened and the corresponding grayscale value exactly correlated with the increasing of S protein concentration. Therefore, it is feasible to use the designed RPAD to quantitative analysis of S protein and H1N1.Fig. 5 Photographs (A) and grayscale value (B) variations in the prescence of (Ⅰ) S protein: 10-13 g/mL, H1N1: 10-8 g/mL; (Ⅱ) S protein: 10-12 g/mL, H1N1: 10-8 g/mL; (III) S protein: 10-11 g/mL, H1N1: 10-8 g/mL; (Ⅳ) S protein: 10-10 g/mL, H1N1: 10-8 g/mL; (Ⅴ) S protein: 10-9 g/mL, H1N1: 10-8 g/mL; (Ⅵ) S protein: 10-8 g/mL, H1N1: 10-8 g/mL.
3.6 Practicability study
To explore the practicality of the developed sensor, we measured S protein and H1N1 in swab virus preservation solution. Towards this goal, different concentrations of S protein standard solution and H1N1 standard solution were spiked in swab virus preservation solution. As seen in Fig. S5, remarkable color and grayscale value changes occurred for the spiked swab virus preservation solution with S protein and H1N1. The grayscale values were dependent on the S protein and H1N1 concentrations over the range of 10-14-10-8 g/mL, respectively. These results suggested that our developed paper-based sensing platform possessed satisfactory reliability and had great potential for detection of S protein and H1N1 in complex sample matrix.
4 Conclusion
In this study, we have successfully constructed a paper-based sensing platform coupling TDF for rapid and multiple virus detection. This strategy permitted S protein and H1N1 detection at adequate sensitivity as low as 10-14 g/mL in both buffer and swab virus preservation solution matrix. Compared with the current virus detection methods, the advantages of this method are as follows: (1) The use of cellulose paper as the immobilization matrix effectively reduces the experimental cost and increases the portability of the device. (2) TDF with good specificity can effectively regulate the orientation and distance of aptamer, which improve the sensitivity and selectivity of target detection. (3) Ascribe to available plenty of aptamers, the developed paper chips could realize quantitative detection of various targets by designing with multiple reaction zones. Given the attractive properties of portability, low cost, disposability and high sensitivity, this paper-based platform presented great promise for rapid differentiation and diagnosis of SARS-CoV-2 and influenza A H1N1 virus.
CRediT authorship contribution statement
Fengling Li: Conceptualization, Methodology, Investigation, Formal analysis, Writing – original draft, Data curation. Ji Qi: Funding acquisition, Software, Formal analysis. Zengzheng Ren: Formal analysis, Investigation. Xiaoli Hu: Software, Investigation. Yan Chen: Conceptualization, Funding acquisition, Supervision. Bowei Li: Writing – review & editing, Funding acquisition, Supervision. Xiuli Fu: Conceptualization, Writing – review & editing, Supervision.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Appendix A Supplementary data
The following are the Supplementary data to this article:Supplementary data 1
Data availability
The authors do not have permission to share data.
Acknowledgements
We gratefully appreciate the financial support from Qingchuang Science and Technology Program of Shandong Province in China (grant no. 2019KJF029), National Natural Science Foundation of China (grant no. 61801274, 41776110 and 22106179) and the Shandong Provincial Natural Science Foundation Key Project (ZR2020KB022).
Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.microc.2022.108304.
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29 Lin M.H. Wang J.J. Zhou G.B. Wang J.B. Wu N. Lu J.X. Gao J.M. Chen X.Q. Shi J.Y. Zuo X.L. Fan C.H. Programmable engineering of a biosensing interface with tetrahedral DNA nanostructures for ultrasensitive DNA detection Angew. Chem. Int. Ed. 54 2015 2151 2155 10.1002/anie.201410720
30 Liu C. Huang Z.K. Jiang W. Liu X.J. Li J. Han X.Y. Tu H.J. Qiu L.P. Tan W.H. Programmable pH-responsive DNA nanosensors for imaging exocytosis and retrieval of synaptic vesicles Anal. Chem. 92 2020 3620 3626 10.1021/acs.analchem.9b04493 32013394
31 Kong L.Q. Wang D. Chai Y.Q. Yuan Y.L. Yuan R. Electrocatalytic efficiency regulation between target-induced HRP-mimicking DNAzyme and GOx with low background for ultrasensitive detection of thrombin Anal. Chem. 91 2019 10289 10294 10.1021/acs.analchem.9b02498 31240904
32 Yang F. Jiang X.Y. Liang W.B. Chai Y.Q. Yuan R. Zhuo Y. 3D matrix-arranged AuAg nanoclusters as electrochemiluminescence emitters for click chemistry-driven signal switch bioanalysis Anal. Chem. 92 2020 2566 2572 10.1021/acs.analchem.9b04256 31922394
33 Ma J.H. Xue L. Zhang M.L. Li C. Xiang Y. Liu P. Li G.X. An electrochemical sensor for Oct4 detection in human tissue based on target-induced steric hindrance effect on a tetrahedral DNA nanostructure Biosens. Bioelectron. 127 2019 194 199 10.1016/j.bios.2018.12.029 30611106
34 Sun Y. Li S.H. Zhang Y.X. Li Q.R. Xie X.P. Zhao D. Tian T.R. Shi S.R. Meng L.X. Lin Y.F. Tetrahedral framework nucleic acids loading ampicillin improve the drug susceptibility against methicillin-resistant staphylococcus aureus ACS Appl. Mater. Interfaces 12 2020 36957 36966 10.1021/acsami.0c11249 32814381
35 Ji P.P. Han G.M. Huang Y. Jiang H.X. Zhou Q.W. Liu X.W. Kong D.M. Ultrasensitive ratiometric detection of Pb2+ using DNA tetrahedron-mediated hyperbranched hybridization chain reaction Anal. Chim. Acta 1147 2021 170 177 10.1016/j.aca.2020.12.050 33485576
36 Song Y.L. Song J. Wei X.Y. Huang M.J. Sun M. Zhu L. Lin B.Q. Shen H.C. Zhu Z. Yang C.Y. Discovery of aptamers targeting the receptor-binding domain of the SARS-CoV-2 spike glycoprotein Anal. Chem. 92 2020 9895 9900 10.1021/acs.analchem.0c01394 32551560
37 Bhardwaj J. Chaudhary N. Kim H. Jang J. Subtyping of influenza A H1N1 virus using a label-free electrochemical biosensor based on the DNA aptamer targeting the stem region of HA protein Anal. Chim. Acta 1064 2019 94 103 10.1016/j.aca.2019.03.005 30982523
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| 0 | PMC9737512 | NO-CC CODE | 2022-12-15 23:17:53 | no | Microchem J. 2023 Feb 10; 185:108304 | utf-8 | Microchem J | 2,022 | 10.1016/j.microc.2022.108304 | oa_other |
==== Front
Prev Med
Prev Med
Preventive Medicine
0091-7435
1096-0260
Published by Elsevier Inc.
S0091-7435(22)00446-7
10.1016/j.ypmed.2022.107381
107381
Article
The intersection of internalizing symptoms and alcohol use during the COVID-19 pandemic: A prospective cohort study
Gohari Mahmood R. a⁎
Varatharajan Thepikaa a
Patte Karen A. b
MacKillop James c
Leatherdale Scott T. a
a School of Public Health Sciences, University of Waterloo, 200 University Avenue West, Waterloo N2L 3G1, Ontario, Canada
b Faculty of Applied Health Sciences, Brock University, Niagara Region, 1812 Sir Isaac Brock Way, St. Catharines L2S 3A1, Ontario, Canada
c Peter Boris Chair in Addictions Research, Department of Psychiatry and Behavioural Neurosciences, McMaster University & St. Joseph's Healthcare, 100 West 5th Street, Hamilton L8P 3R2, Ontario, Canada
⁎ Corresponding author at: School of Public Health Sciences, University of Waterloo, 200 University Avenue West, Waterloo N2L 3G1, ON, Canada.
10 12 2022
10 12 2022
10738118 5 2022
16 11 2022
3 12 2022
© 2022 Published by Elsevier Inc.
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Given the well-established relationship between alcohol and internalizing symptoms, potential increases in depression and anxiety during the COVID-19 pandemic may lead to increases in alcohol consumption and binge drinking. This study examines this association from before to during two phases of the pandemic in a cohort of Canadian youth. We used linked data from a sub-sample of 1901 secondary school students who participated in three consecutive school years of the Cannabis use, Obesity, Mental health, Physical activity, Alcohol use, Smoking, and Sedentary behaviour (COMPASS) study between 2018/19 and 2020/21. Separate multilevel logistic regression models examined the association between depression and anxiety symptoms with odds of escalation and reduction (vs. maintenance) and initiation (vs. abstinence) of alcohol consumption. Results show that depression and anxiety symptoms significantly increased over the three years, and these changes were moderated by changes in alcohol consumption and binge drinking. Students with increased depression symptoms were less likely to reduce their alcohol consumption in the early pandemic (Adjust odds ratio [AOR] 0.94, 95% CI:0.90–0.98), more likely to initiate alcohol consumption in the ongoing pandemic period (AOR 1.03, 95% CI: 1.01–1.05), and more likely to initiate binge drinking in both periods. The depression-alcohol use association was stronger among females than males. This study demonstrates a modest association between internalizing symptoms and alcohol use, particularly for depression symptoms and in females. The identified depression-alcohol use association suggests that preventing or treating depression might be beneficial for adolescent alcohol use and vice versa.
Keywords
Depression
Anxiety
Binge drinking
Longitudinal study
COVID-19
==== Body
pmcData availability
The datasets generated and analyzed during this study will not currently be shared because this is an ongoing study; however, access to the data supporting the findings of the study can be requested
| 36513170 | PMC9737513 | NO-CC CODE | 2022-12-14 23:29:53 | no | Prev Med. 2023 Jan 10; 166:107381 | utf-8 | Prev Med | 2,022 | 10.1016/j.ypmed.2022.107381 | oa_other |
==== Front
Complement Ther Med
Complement Ther Med
Complementary Therapies in Medicine
0965-2299
1873-6963
The Author(s). Published by Elsevier Ltd.
S0965-2299(22)00110-8
10.1016/j.ctim.2022.102907
102907
Article
Benefits of ozone on mortality in patients with COVID-19: A systematic review and meta-analysis
Shang Wenli a1
Wang Yan b1
Wang Guizuo a1
Han Dong a⁎2
a Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, China
b Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
⁎ Correspondence to: Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People’s Hospital, No. 256, West Youyi Road, Xi’an, Shaanxi 710068, China.
1 Contributed equally.
2 ORCID: 0000-0003-3775-4028.
10 12 2022
3 2023
10 12 2022
72 102907102907
8 9 2022
5 12 2022
9 12 2022
© 2022 The Authors
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Background
The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. Ozone therapy has long been used in the treatment of a variety of infectious diseases, probably through its antioxidant properties and the supply of oxygen to hypoxic tissues. This systematic review and meta-analysis aimed to determine the efficacy of ozone on mortality in patients with COVID-19.
Methods
A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Prospective controlled trials on treatment of COVID-19 with ozone, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs) and weighted mean differences (WMDs), with 95% confidence intervals (CIs).
Results
Eight trials (enrolling 371 participants) met the inclusion criteria. Ozone therapy showed significant effects on mortality (RR 0.38, 95% CI 0.17–0.85; P = 0.02), length of hospital stay (WMD −1.63 days, 95% CI −3.05 to −0.22 days; P = 0.02), and polymerase chain reaction (PCR) positivity (RR 0.07, 95% CI 0.01–0.34; P = 0.001).
Conclusions
Ozone therapy significantly reduced mortality, PCR positivity, and length of stay in hospitalized patients with COVID-19. Ozone therapy should be considered for COVID-19 patients.
Graphical Abstract
ga1
Keywords
Mortality
Ozone
COVID-19
Meta-analysis
==== Body
pmc1 Introduction
The Coronavirus disease-2019 (COVID-19) pandemic is the worst pandemic in more than 100 years, causing numerous infections and deaths worldwide.1 Despite the use of multiple drugs with different mechanisms, mortality from COVID-19 remains high, especially in older adults.1, 2 The mortality rate increases significantly with age, even up to 30% in patients aged 85 years or older.2 Therefore, there is an urgent need for treatments, pharmacological or otherwise, that can reduce mortality.
Medical ozone therapy is a complementary medical treatment primarily practiced in Europe and is believed to have immunomodulatory and antioxidant effects.3, 4 Ozone therapy has long been used in the treatment of a variety of infectious diseases,5 probably through its antioxidant properties and the supply of oxygen to hypoxic tissues.6, 7 In addition, ozone has shown an inhibitory effect on viral replication, creating great interest in the possibility of using this non-pharmacological adjunct in the treatment of COVID-19.4, 6, 8 Several clinical controlled trials have assessed the effects of ozone in hospitalized COVID-19 patients, and their results differed.
The aim of the present study therefore was to perform a systematic review and meta-analysis of controlled trials in order to determine the efficacy of ozone therapy on mortality in patients with COVID-19.
2 Methods
2.1 Data sources and search strategy
This systematic review and meta-analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.9 The protocol was previously registered in March 2022 in the PROSPERO database (Review register: CRD42022320948). The PubMed, Embase, Cochrane Library, and clinicaltrials.gov were searched for studies up to March 28, 2022.
2.2 Study selection
To be eligible for inclusion in the meta-analysis studies had to meet the following criteria: (a) inclusion of hospitalized COVID-19 patients being 18 years or older; (b) polymerase chain reaction (PCR) positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); and (c) use of a controlled design to make a comparison of ozone therapy with placebo or blank. The search strings used for the databases were (“COVID-19” OR “SARS-CoV-2” OR “SARS-CoV-19” OR “novel coronavirus 2019” OR “novel coronavirus pneumonia”) AND (“ozone” OR “autohemotherapy” OR “ozonization” OR “ozonized”). The reference lists of any relevant review articles were also screened to identify studies that might have been missed in this search. No language restrictions were applied to our study selection process. The full search strategies for all databases are provided in Table S1.
2.3 Data extraction and quality assessment
Two reviewers independently screened articles according to the inclusion criteria. The reviewers compared selected studies and differences were resolved by consensus. Data tables were used to collect all relevant data from texts, tables and figures of each included trial, including author, year of publication or last update posted, patient number and age, body mass index (BMI), types of ozone therapy, and outcomes such as mortality, length of hospital stay, PCR positivity, intensive care unit (ICU) admission, and tracheal intubation. Study quality was assessed using the Detsky Quality Assessment Scale.10, 11, 12, 13 This is a 20-point scale for studies with statistically significant results and a 21-point scale for studies without statistically significant results.
2.4 Risk of bias of included trials
Two reviewers independently assessed the risk of bias using the Cochrane collaboration risk of bias tool for RCTs,14 which considers allocation sequence generation, concealment of allocation, masking of participants and investigators, incomplete outcome reporting, selective outcome reporting, and other sources of bias. The Newcastle-Ottawa Scale15 was used to assess the risk of bias of observational studies, and full details are provided in Table S2. Disagreements were resolved through negotiation.
2.5 Outcomes
The primary outcome of this meta-analysis was mortality. Secondary outcomes were length of hospital stay, PCR positivity after treatment, ICU admission rate, and tracheal intubation rate.
2.6 Data synthesis and statistical analysis
Meta-analyses were conducted where applicable; otherwise, outcomes were presented in narrative form. Data were analyzed using the RevMan Version 5.4.1 (The Cochrane Collaboration). Next, risk ratios (RRs) for discontinuous outcomes, and weighted mean differences (WMDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs) were computed for individual trials. Chi-squared and Higgins I2 tests were used to assess heterogeneity among included trials. If significant heterogeneity (p ≤ 0.10 for Chi-squared test results or I2 ≥ 50%) was obtained, we used a random-effects model, otherwise a fixed-effects model was used. And a P value < 0.05 was taken to indicate statistical significance. The P value of Egger’s linear regression test16, 17 (STATA version 12.0) was used to assess the presence of publication bias in included studies for each outcome.
2.7 Certainty of evidence
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to grade the quality or certainty of the outcomes and the strength of recommendations.18
3 Results
3.1 Study selection and characteristics
Of 875 trials recognized by the initial search, 38 were retrieved for more detailed assessment, and 8 trials5, 19, 20, 21, 22, 23, 24, 25 were included in this meta-analysis ( Fig. 1). Baseline characteristics of trials included in this meta-analysis are shown in Table 1. A total of 371 patients were included: 197 assigned to the ozone treatment groups and 174 to the control groups. The risk of bias results are summarized in Fig. S1 and Table S2.Fig. 1 Flow chart for selection of studies.
Fig. 1
Table 1 Baseline characteristics of trials included in meta-analysis.
Table 1Study
(Ref. #) Year Quality Score Randomization Types of ozone therapy n Age, years (SD) Male, % BMI, kg/m2 (SD)
Araimo19 2021 17 Randomized Autohemotherapy
Blank 14
14 63.3 (12.1)
60.1 (14.4) 64
50 28.2 (4.6)
28.9 (3.2)
Çolak5 2021 14 Non-randomized Autohemotherapy
Blank 37
18 58.0 (16.3)
64.7 (10.4) 51.4
55.6 NR
NR
Dengiz20 2022 16 Randomized Nebulization
Blank 15
15 51.6 (16.9) ^ 60
53 NR
NR
Fernández-Cuadros21 2021 14 Non-randomized Intra-rectal
Blank 14
14 84.4 (9.5)
83.0 (12.6) 86
50 NR
NR
Hernández22 2021 12 Non-randomized Autohemotherapy
Blank 9
9 64 (11)
71 (18) 78
67 26.2 (4.5)
29.5 (7.1)
Shah23 2021 15 Randomized Intra-rectal + Autohemotherapy
Blank 30
30 44.0 (8.7)
43.6 (9.7) 87
73 NR
NR
Sozio24 2021 17 Randomized Autohemotherapy
Blank 48
44 63.5 (12.5)
64.2 (14.1) 64.6
54.5 26.6 (4.5)
27.4 (6.0)
Tascini25 2021 12 Non-randomized Autohemotherapy
Blank 30
30 57 (12)
65 (13) 77
60 NR
NR
Abbreviations: BMI, body mass index; NR, not reported; SD, standard deviation. ^ Average value of both groups.
3.2 Mortality
Data on mortality were available from seven controlled trials (341 patients). Compared with the control conditions, the mortality was significantly lower in the ozone therapy groups (RR 0.38, 95% CI 0.17–0.85; P = 0.02 [ Fig. 2A]), with a rate of 3.85% versus 10.06%. There was no significant heterogeneity (I2 = 0%; P = 0.87). Egger’s test (P = 0.736) did not show evidence of publication bias.Fig. 2 Forest plot assessing the efficacy of ozone therapy on (A) mortality, (B) length of hospital stay, and (C) PCR positivity.
Fig. 2
3.3 Length of hospital stay
Data on length of hospital stay were available from three trials (118 patients). The length of hospital stay was significantly shorter in the ozone groups (WMD −1.63 days, 95% CI −3.05 to −0.22 days; P = 0.02 [Fig. 2B]). There was no significant heterogeneity (I2 = 39%; P = 0.20). Egger’s test (P = 0.335) did not show evidence of publication bias.
3.4 PCR positivity
The number of patients with PCR positivity after treatment were extracted from two studies (90 patients). The PCR positive rate was significantly lower in the ozone therapy groups (RR 0.07, 95% CI 0.01–0.34; P = 0.001 [Fig. 2C]), with a rate of 2.22% versus 46.67%. There was no significant heterogeneity (I2 = 0%; P = 0.79).
3.5 ICU admission
Five controlled trials reported data on ICU admission (295 patients). There was no statistically significant difference in ICU admission rates between the two groups (RR 0.88, 95% CI 0.44–1.75; P = 0.71 [ Fig. 3A]), with a proportion of 9.43% versus 9.56%. There was no significant heterogeneity (I2 = 0%; P = 0.59). Egger’s test (P = 0.453) did not show evidence of publication bias.Fig. 3 Forest plot assessing the efficacy of ozone therapy on (A) ICU admission rates, and (B) tracheal intubation rates.
Fig. 3
3.6 Tracheal intubation
The number of patients with tracheal intubation were extracted from four studies (198 patients). There was no statistically significant difference in the rate of tracheal intubation between the two groups (RR 0.76, 95% CI 0.30–1.90; P = 0.55 [Fig. 3B]), with a proportion of 6.93% versus 9.28%. There was no significant heterogeneity (I2 = 0%; P = 0.80). Egger’s test (P = 0.411) did not show evidence of publication bias.
3.7 Certainty of evidence
The GRADE assessment for the certainty of evidence for primary and secondary outcomes is summarized in Table S3.
4 Discussion
To our knowledge, this meta-analysis is the first designed specifically to evaluate the efficacy of ozone therapy in patients with COVID-19. Based on the present results, we observed that ozone significantly reduced mortality and PCR positivity, and shortened hospital stays.
COVID-19 is caused by SARS-CoV-2 and has caused a global pandemic. Although most patients have mild symptoms, further development of acute respiratory distress syndrome (ARDS) has been reported in approximately 20% of hospitalized patients with a more severe clinical presentation.26 The main causes of COVID-19-related deaths are respiratory failure, excessive inflammation, cytokine storm or multiple organ failure.5 Healthcare systems in most countries are overwhelmed as global COVID-19 surge continues. Therefore, there is an urgent need for safely, effective and accessible treatment to stop disease progression and shorten hospital stays, thereby preventing the collapse of the healthcare system.
Ozone therapy has been extensively researched and used for over a century,27 and its common types include autohemotherapy, nebulization, non-invasive rectal, mucosal, intramuscular/intraarticular/intradiscal/paravertebral injection23. Several studies6, 19 have explored possible anti-COVID-19 mechanisms of ozone therapy: (1) improving oxygen release in hypoxic tissues, (2) modulating antioxidant balance and inflammatory responses to prevent cytokine storm, and (3) inhibiting viral replication. Ozone therapy is very cheap and safe and does not develop resistance28, so it may play an important role in the treatment of COVID-19, especially for patients in low- and middle-income countries.21
The included studies used several different types of ozone therapy, and all studies lacked blinding which may have exaggerated treatment effects. Future large double-blind RCTs are needed to determine which type is more effective.
This study met most of the methodological criteria recommended for systematic reviews and meta-analyses.29 However, some limitations need to be considered when interpreting the results of this study. Firstly, some included trials had small sample sizes, which may have reduced the power of the results. Secondly, some included trials were non-randomized. Finally, this meta-analysis was not patient-level, so the results should be considered provisional.
5 Conclusions
Treatment with ozone reduced mortality, PCR positivity, and length of stay in hospitalized COVID-19 patients. Ozone therapy should be considered for patients with COVID-19.
Funding
No funding was received for this research.
Author contributions
All authors, led by D.H., were involved in the concept and protocol design of the meta-analysis. W.S. and G.W. screened the titles and abstracts and extracted data from the articles. Y.W. was primarily responsible for statistical analyses. D.H. was primarily involved in the interpretation of the quality data. All authors contributed to interpreting the results. G.W. and D.H accessed and verified the data. All authors contributed to the writing of the article and approved its submission. D.H. was responsible for the decision to submit the article.
Conflict of interest
None of the authors has a conflict of interest to declare.
Appendix A Supplementary material
Supplementary material
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Supplementary material
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Supplementary material
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Supplementary material
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Appendix A Supplementary data associated with this article can be found in the online version at doi:10.1016/j.ctim.2022.102907.
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| 36513208 | PMC9737514 | NO-CC CODE | 2022-12-14 23:30:05 | no | Complement Ther Med. 2023 Mar 10; 72:102907 | utf-8 | Complement Ther Med | 2,022 | 10.1016/j.ctim.2022.102907 | oa_other |
==== Front
Psychiatry Res
Psychiatry Res
Psychiatry Research
0165-1781
1872-7123
Elsevier B.V.
S0165-1781(22)00595-9
10.1016/j.psychres.2022.115004
115004
Article
COVID-19 restrictions and visitations to an Israeli psychiatric emergency department: A four-lockdowns retrospective study
Yaniv-Rosenfeld Amit abc
Rosenfeld Ariel b⁎
Hirsch Klein Efrat ac
a Shalvata Mental Health Care Center, Hod Hasharon, Israel
b Bar-Ilan University, Ramat-Gan, Israel
c Tel-Aviv University, Tel-Aviv, Israel
⁎ Corresponding author.
10 12 2022
1 2023
10 12 2022
319 115004115004
13 7 2022
4 12 2022
9 12 2022
© 2022 Elsevier B.V. All rights reserved.
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
We examine the volume and characteristics of psychiatric ED visitations through a perspective of four COVID-19 lockdowns. All adult visitations to the ED of Shalvata Mental Healthcare center (Israel) during 2020–2021 were retrieved and statistically analysed and data from 2017 to 2019 was considered as control. Voluntary and involuntary ED visitations were considered, separately and combined. We find that the significant decrease in the volume of voluntary ED visitations during the 1st lockdown was quickly overturned, roughly returning to the pre-pandemic state following its conclusion. In parallel, the volume of involuntary ED visitations has dramatically increased, with the most striking levels observed during the second and third lockdowns. Elapsed time since the first occurrence of COVID-19 in Israel and the level of governmental restrictions is significantly associated with the increase in the volume of ED visits and admissions, the admission rate and the rate of involuntary visits. The prolonged consequences associated with the pandemic and the measures taken to control it suggest that it is unreasonable to expect a return to normal ED utilization in the near future. As such, alternatives to strict lockdowns should be favored when possible and urgent strengthening of psychiatric care is warranted.
Keywords
Psychiatric emergency department
COVID-19
Governmental restrictions
Involuntary hospitalization
==== Body
pmc1 Introduction
Since the emergence of the Coronavirus disease 2019 (COVID-19) pandemic at the end of 2019, many countries have been intermittently implementing lockdowns and other restrictions in order to reduce transmission rates and virus-associated morbidity. As a result, many determinants of poor mental health were exacerbated, leading to increased depressive, anxious and post-traumatic stress symptoms in the general population (Vindegaard and Benros, 2020; Salari et al., 2020; Xiong et al., 2020; Santomauro et al., 2021; Czeisler et al., 2021; Henssler et al., 2021).
Focusing on severe mental conditions and symptoms, prior work has examined the possible association between lockdowns and the volume and characteristics of patients requiring urgent psychiatric help in either psychiatric or general Emergency Departments (EDs). These studies were conducted in a wide range of countries including the USA (Holland et al., 2021), Germany (Hoyer et al., 2021), France (Pignon et al., 2020), Portugal (Goncalves-Pinho et al., 2021), Switzerland (Ambrosetti et al., 2021b), Italy (Beghi et al., 2021), Spain (Rodriguez-Jimenez et al., 2021) and Australia (Jagadheesan et al., 2022), to name a few. These studies have consistently demonstrated a sharp reduction in the number of psychiatric ED visitations (ED visits, for short) during the first COVID-19 lockdown compared to the pre-pandemic period, which was later overturned during the post-lockdown period with a significant increase in the number of visitations who, according to most studies, present worse mental conditions and symptoms.
Over time, governments have implemented varying levels of restrictions in response to the COVID-19 outbreak, with most countries today avoiding lockdowns altogether (Hale et al., 2020). Unfortunately, little is known to date about the possible association between non-lockdown restrictions and psychiatric ED visitations.
In this work, we set to examine the volume and characteristics of psychiatric ED visits through a perspective of four COVID-19 lockdowns. We provide a longitudinal analysis of all visitations to the psychiatric ED of Shalvata Mental Healthcare center, Israel, between 2017 and 2021 (N = 15,052). Our analysis focuses on the four lockdowns implemented in Israel to date, and most importantly, the fourth one. This lockdown, termed “soft braking” by the government (N12 News, 2021), was significantly different than the former three as major restrictions were imposed on the population yet a complete lockdown was not strictly imposed. In our analysis, we further pay special attention to the issue of voluntary vs involuntary ED visitations (also known as involuntary or compulsory hospitalizations). In Israel, as in most countries, very strict legislative criteria exist for involuntary psychiatric hospitalizations (see Youngmann et al. (2021) for an up-to-date Israeli overview and Saya et al. (2019) for a worldwide perspective). As such, these involuntary ED visitations are indicative of the most severe and urgent mental conditions in the population who pose a danger to themselves or others (Riecher-Ro¨ssler and Ro¨ssler, 1993).
2 Materials and methods
2.1 Study population
All adult visitations to the psychiatric ED of Shalvata Mental Healthcare center, Israel, between January 1st 2017 and December 31st 2021 (N = 15,052) were retrieved from electronic records of the hospital. Shalvata Mental Healthcare center Shalvata was founded in 1956 in central Israel and currently serves a total population of roughly 600,000 people. It is affiliated with Tel-Aviv University and consists of 4 adult in-patients departments, each encompassing the full range of therapeutic modalities, a Department of Child and Adolescent Psychiatry, a day-care department, and a highly developed network of community-based services. In addition to these, it provides specialized services such as electroconvulsive therapy and a 24-hours ED which serves over 3000 adult visits per year.1
This study was approved by Shalvata mental healthcare center's Helsinki board and patient informed consent was waived (approval code 0015–21-SHA). All methods were carried out in accordance with relevant guidelines and regulations.
2.2 Measures
Each ED visit was characterised by the date, the patient's age and sex, referral indicator (voluntary vs involuntary) and admission status (discharged vs admitted). Daily data was aggregated as follows: for each day, the number of visits and admissions were accumulated along with the patients’ age, sex, admission and referral distributions. Accordingly, the daily male rate (i.e., the number of male visits divided by the total number of visits per day), admission rate (i.e., number of admissions divided by the total number of visits per day), and involuntary rate (i.e., number of involuntary visits divided by the total number of visits per day) were calculated.
The lockdown periods in Israel are defined based on an independent report by the Taub Center for Social Policy Studies in Israel (see Taub Center (2022)). Accordingly, we define the following lockdown periods:• First lockdown: March 19, 2020 - April 24, 2020
• Second lockdown: September 18, 2020 - October 18, 2020
• Third lockdown: December 27, 2020 - February 6, 2021
• Fourth lockdown (“soft braking”): July 29, 2021 - November 27, 2021
We further cross-referenced our data with the Oxford Government Response Stringency Index (OxGR, for short), a common measure depicting the severity of countermeasures taken by authorities to contain the pandemic (Hale et al., 2021) in order to estimate the COVID-19 related burden on the public. It is important to note that the OxGR cannot truly attest to the level of stress and anxiety in the general public, but as those are both unavailable and highly individual, these measures are often assumed to roughly approximate the magnitude of external stressors that are associated with ED presentation (Segev et al., 2021).
As mentioned before, the fourth Israeli lockdown was significantly different from the previous ones as major restrictions were imposed on the population but a complete lockdown, as in the first three, was not strictly imposed (see Taub Center (2022) for a complete breakdown of the restrictions by date). In addition, we consider the 27th of November 2021 as the unofficial ending of the fourth lockdown as the first case of the Omicron variant was detected on that date in Israel, an event which could have changed the population's behavior (although governmental restrictions did not changed significantly during that time). Since the Omicron variant and its subvariants are still very prevalent in the Israeli population during the writing of this article, as well as worldwide, its investigation is left for future work.
2.3 Statistical approaches
Descriptive statistics are reported in a standard form with continuous variables presented as mean ± standard deviation (SD) and categorical variables are presented as percentages. Time series data is checked for stationarity using an Augmented Dickey-Fuller (ADF) test. Lockdown and between-lockdown periods, as defined in Section 2.2, are compared to the respective control periods between 2017 and 2019 using comparative χ2 tests for proportion data (e.g., sex) and Mann–Whitney U tests for continuous measures (e.g., age). p values are reported along with the relevant statistic in parentheses. We further preform a regressionbased analysis using Poisson regressions for count data (i.e., daily number of visitations and admissions) and Logistic regression for dichotomous data (e.g. individuals’ admission and referral status).
3 Results
Fig. 1 presents the (7-day smoothed) daily number of visits and admissions over time along with the (raw) OxGR index. Focusing on the time frame between 2017 and 2019 (i.e., the last 3 years prior to Covid19), we find that the daily number of visitations, admissions, admission rate, male rate and involuntary rate are all statistically stationary at p < 0.01. In other words, all measures examined in this study present no significant trends or seasonality in the 3 years prior to the COVID-19 outbreak, thus these should not be accounted for in the following analysis.Fig. 1 Primary Y-Axis: Daily visitations (top, in blue) and admissions (middle, in orange). Both are smoothed using a moving average over 7 days. Secondary Y-Axis: raw OxGR Stringy Index (bottom, in gray). Time periods between dotted horizontal lines (black, green, red and magenta) indicate the lockdown periods as defined in Section 2.2. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig 1:
We begin by comparing each lockdown period to the averaged corresponding pre-pandemic periods between 2017 and 2019 as shown in Table 1 . As was documented in earlier literature, in our data, the first lockdown resulted in a statistically significant reduction in the number of visits (265 vs 308.3) and admissions (110 vs 135.7) compared to the control periods. In addition, visiting patients during that lockdown period were significantly younger, compared to the control periods, by an average of 2.9 years (36.6 vs 39.5 years). Both differences are significant at p < 0.05. No significant differences were recorded for the patients’ admission rate and sex distribution, yet a notable increase in the involuntary rate was observed (9.1% vs 6.7%). When considering the second and third lockdowns, different phenomena arise. First, unlike the first lockdown, the second and third lockdowns demonstrated only very negligible differences in the number of visits during the lockdown periods compared to the control periods (second lockdown: 256 vs 255; third lockdown: 342 vs 332). Nevertheless, during these periods, a significant increase in the number of admissions (second lockdown: 117 vs 98.3; third lockdown: 165 vs 128), the admission rate (second lockdown: 45.7% vs 38.5%; third lockdown: 48.2% vs 38.5%) and the involuntary rate (second lockdown: 13.3% vs 4.5%; third lockdown: 10.6% vs 6%) were recorded, all significant at p < 0.05. No significant differences were recorded for patients’ age and sex distribution. When considering the fourth lockdown, we encounter a significant increase in the number of visitations (1079 vs 979), admissions (435 vs 391.5) and in the involuntary rate (10.1% vs 7%) as compared to the control periods; while the admission rate remained roughly the same as it was in the control period, the former three are significant at p < 0.05. As before, no significant differences were recorded for the patients’ age and sex distribution.Table 1 Lockdown periods compared to the averaged pre-pandemic control periods between 2017 and 2019. Results in bold are significant at p < 0.05.
Table 1: 1st Lockdown (19/3–24/4) 2nd Lockdown (18/9–18/10) 3rd Lockdown (27/12–6/2) 4th Lockdown (29/7–27/11)
Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.)
Visits 265 308.3 256 255 342 332 1079 979
Daily visits 7.1 ± 3.2 8.3 ± 3.6 0.03
(1650) 8.2 ± 3.1 8.2 ± 3.3 0.49
(1439) 8.1 ± 3.1 7.9 ± 3.3 0.43
(2602) 8.8 ± 3.2 8.1 ± 3.2 0.01
(25,493)
Admissions 110 135.7 117 98.3 165 128 435 391.5
Daily Admis. 2.9 ± 2.2 3.7 ± 2.2 0.03
(1643) 3.8 ± 2.2 3.2 ± 1.6 0.05
(1151) 3.9 ± 2.5 3.1 ± 1.9 0.02
(2079) 3.6 ± 2.1 3.2 ± 1.8 0.05
(26,653)
Admis. Rate 41.5% 44% 0.52
(0.42) 45.7% 38.5% 0.05
(3.8) 48.2% 38.5% <0.01
(9.5) 40.3% 40% 0.85
(0.0)
Age 36.6 ± 6.5 39.5 ± 6 0.01
(1543) 40.3 ± 7.1 40.9 ± 6.2 0.34
(1368) 38.6 ± 6.8 39.2 ± 8.1 0.34
(2534) 40.8 ± 6.3 40.5 ± 7.1 0.28
(28,708)
Male 46% 41.6% 0.71
(0.1) 47.7% 46.7% 0.96
(0.0) 48.8% 43.6% 0.15
(2.1) 47.5% 45.1% 0.07
(3.2)
Involuntary 9.1% 6.7% 0.19
(1.7) 13.3% 4.5% <0.01
(20.2) 10.6% 6% <0.01
(16.3) 10.1% 7% <0.01
(12.2)
We now turn to consider the periods between the lockdowns. As before, we compare each period to the averaged corresponding pre-pandemic periods between 2017 and 2019 as shown in Table 2 . Starting with the period between the first and second lockdowns, we see that the number of visits and admissions, as well as the patients’ admission rate and sex distribution, has not changed significantly compared to the control periods. However, as was the case for the first lockdown, visiting patients were significantly younger by an average of 2 years (38.8 vs 40.8 years), at p < 0.01. Turing to the period between the second and third lockdowns, we find no significant differences in any of the examined measurements other than the involuntary rate, which increased significantly (10.1% vs 7.8%) at p < 0.01. The period between the third and fourth lockdowns have demonstrated a significant increase in the number of admissions (645 vs 585.5), in the admission rate (44% vs 40.3%) and in the involuntary rate (12.5% vs 4.5%), all significant at p < 0.01. No significant differences were observed in terms of the number of visits and patients’ age and sex distribution.Table 2 Between-lockdown periods compared to the averaged pre-Covid19 control periods between 2017 and 2019. Results in bold are significant at p < 0.05.
Table 2: Between 1st-2nd Lockdowns
(25/4–17/9) Between 2nd-3rd Lockdowns (19/10- 26/12) Between 3rd-4th Lockdowns (6/2–28/7)
Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.)
Visits 1263 1221.3 570 537.3 1467 1451.8
Daily visits 8.5 ± 3.4 8.3 ± 3.5 0.14
(30,774) 8 ± 3.3 7.6 ± 3 0.09
(6766) 8.4 ± 3.2 8.3 ± 3.5 0.33
(59,230)
Admissions 514 473.7 251 233 645 585.5
Daily Admis. 3.5 ± 2 3.2 ± 1.9 0.07
(30,131) 3.6 ± 1.9 3.4 ± 1.9 0.32
(7278) 3.7 ± 1.8 3.3 ± 2 <0.01 (52,391)
Admis. Rate 40.7% 38.7% 0.24
(1.4) 44% 43.3% 0.11
(2.4) 44% 40.3% 0.01
(6.3)
Age 38.8 ± 6.3 40.8 ± 7 <0.01 (27,271) 41±6.7 39.7 ± 6.8 0.06
(6597) 40.1 ± 6.1 40±6.6 0.37
(59,583)
Male 43.6% 45.6% 0.49
(0.5) 44% 45.8% 0.45
(0.6) 48.5% 44.9% 0.16
(1.9)
Involuntary 8.4% 5.7% <0.01
(12.7) 10.1% 7.8% <0.01
(10.2) 12.2% 4.5% <0.01
(52.9)
In Table 3 we summarize all of the above results across both lockdowns and between lockdown periods. We report the relative change observed in each of these periods compared to the averaged control periods while focusing on the four key measures which have resulted in most of the significant differences in Tables 1 and 2: number of visits, number of admissions, admission rate and involuntary rate. The summarized results indicate that the significant decrease in the number of visits and admissions (−14% and −18.9%, respectively), which was recorded during the first lockdown was quickly overturned with both measures returning to (and even surpassing) their pre-pandemic levels in the period between the first and second lockdowns (+3.4% and +8.5%, respectively). In addition, the elevated admission rate and involuntary rate during the first lockdown (+2.5% and +2.4%, respectively) seems to continue to the period between the first and second lockdowns, with the latter becoming statistically significant (+1.9% and +2.7%, respectively). Similarly, during the second lockdown period, a significant increase in the number of admissions (+19%), in the admission rate (+7.1%) and in the involuntary rate (+8.8%) were recorded while the number of visits remained roughly the same (+0.4%). During the period between the second and third lockdowns we still encounter elevated levels in the number of visits, admissions and in the admission rate measures (+6.1%, +7.7% and +0.7%, respectively), yet the differences are not statistically significant. Nevertheless, the elevated level of the involuntary rate (+2.3%) is, indeed, significant. The third lockdown shows a very sharp and significant increase in the number of admissions (+28.9%), which was accompanied by a non-significant increase in the number of visits (+3%), resulting in a significant increase in the admission rate (+9.7%). During the same period, a significant increase in the involuntary rate is also observed (+4.6%). Similar results are observed during the period between the third and fourth lockdowns where a significant increase in the number of admissions (+10.2%), the admission rate (+3.6%) and involuntary rate (+7.7%) were observed alongside a non-significant increase in the number of visits (+1.1%). Finally, the fourth lockdown presents a significant increase in the number of visits (+10.4%), admissions (+11.1%) and involuntary rate (+3.1%), which resulted in a non-significant yet slightly elevated admission rate (+0.3%).Table 3 Relative changes during each examined lockdown (LD) and between-lockdown periods with respect to the control periods between 2017 and 2019. Results in bold are significant at p < 0.05.
Table 3: LD1 Between
1–2 LDs LD2 Between
2–3 LDs LD3 Between
3–4 LDs LD4
Visitations −14% +3.4% +0.4% +6.1% +3% +1.1% +10.2%
Admissions −18.9% +8.5% +19% +7.7% +28.9% +10.2% +11.1%
Admission Rate +2.5% +1.9% +7.1% +0.7% +9.7% +3.6% +0.3%
Involuntary Rate +2.4% +2.7% +8.8% +2.3% +4.6% +7.7% +3.1%
Given the consistently elevated involuntary rate across all examined periods, we repeated the above analysis by considering the voluntary and involuntary visits separately.
Starting with the voluntary ED visits, which constituted about 84.5% of the visits during the pre-pandemic 2017–2019 period, we observe slightly different patterns compared to the analysis presented above. Starting with Table 4 , as was the case before, we see that during the first lockdown period a significant decrease in the number of visits (240 vs 287.3) and admissions (85 vs 114.7) was recorded. Similarly, visiting patients during the first lockdown were significantly younger by an average of 3.4 years (36.1 vs 39.5 years). Interestingly, during the second, third and fourth lockdowns, no significant differences were encountered other than a single one which was not observed before – during the third lockdown, the rate of male patients was significantly higher (50.6% vs 44.4%). Similarly, when considering the periods between lockdowns (Table 5 ), only two results are significant – during the period between the first and second lockdowns, visiting patients were younger by an average of 2 years (38.9 vs 40.9 years), and during the period between the third and fourth lockdowns the rate of male patient visits was significantly higher (50.6% vs 46.2%).Table 4 Voluntary patient data during lockdown periods compared to the pre-Covid19 control periods between 2017 and 2019.
Table 4: 1st Lockdown
(19/3–24/4) 2nd Lockdown
(18/9–18/10) 3rd Lockdown
(27/12–6/2) 4th Lockdown
(29/7–27/11)
Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.)
Visits 240 287.3 224 244 296 311 969 911.5
Daily visits 7.5 ± 3.1 7.8 ± 3.6 0.02
(1589) 7.2 ± 3 7.9 ± 3.1 0.21
(1257) 7.1 ± 2.3 7.4 ± 3.1 0.21
(2425) 7.9 ± 3 7.5 ± 3.2 0.06
(27,117)
Admissions 85 114.7 85 87.3 119 107.3 325 324
Daily Admis. 2.3 ± 2.2 3.1 ± 2.1 0.01
(1537) 2.7 ± 2.1 2.8 ± 1.5 0.34
(1369) 2.8 ± 1.5 2.6 ± 1.8 0.07
(2263) 2.7 ± 1.8 2.7 ± 1.7 0.43
(29,406)
Admis. Rate 35.4% 39.9% 0.24
(1.4) 37.9% 35.4% 0.65
(0.2) 40% 34.5% 0.09
(2.9) 33.5% 35.5% 0.29
(1.3)
Age 36.1 ± 7.1 39.5 ± 6.4 0.01
(1553) 40±7.3 41±6.4 0.2
(1294) 38.8 ± 7.5 39.1 ± 8.3 0.34
(2535) 40.9 ± 7 40.6 ± 7.4 0.31
(28,825)
Male 47.1% 42.4% 0.66
(0.2) 50.5% 47.6% 0.71
(0.1) 50.6% 44.4% 0.05
(3.9) 48.8% 46.6% 0.14
(2.2)
Table 5 Voluntary patient data between lockdown periods compared to the pre-Covid19 control periods between 2017 and 2019.
Table 5: Between 1st-2nd Lockdowns
(25/4–17/9) Between 2nd-3rd Lockdowns (19/10- 26/12) Between 3rd-4th Lockdowns (6/2–28/7)
Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.)
Visits 1155 1152.3 507 496 1288 1357.3
Daily visits 7.8 ± 3.2 7.8 ± 3.4 0.35
(32,034) 7.5 ± 2.6 7.4 ± 3.2 0.52
(8263) 7.4 ± 3 7.9 ± 3.3 0.1
(56,869)
Admissions 406 405 188 192.3 467 491
Daily Admis. 2.7 ± 1.6 2.7 ± 1.7 0.42
(32,349) 2.5 ± 1.5 2.7 ± 1.8 0.3
(7224) 2.7 ± 1.6 2.8 ± 1.9 0.27
(58,799)
Admis. Rate 35.1% 35.1% 0.97
(0.0) 37.1% 38.8% 0.69
(0.2) 36.3% 36.2% 0.99
(0.0)
Age 38.9 ± 6.8 40.9 ± 7.2 <0.01 (27,379) 41.2 ± 7.1 39.9 ± 7.2 0.06
(6592) 40.4 ± 6.9 40.1 ± 6.9 0.31
(59,049)
Male 45.3% 47% 0.87
(0.0) 46.2% 47.9% 0.47
(0.5) 50.6% 46.2% 0.05
(4.0)
Turning to involuntary ED visits, in Tables 6 and 7 , we provide the same analysis as performed above. Unlike the voluntary visits, during the first lockdown, an increase in the volume of visits and admissions was observed, albeit non-significant compared to the control period. However, that is not the case for the second, third and fourth lockdowns and all periods between the lockdowns. During all of these periods, without exception, we witness a sharp and significant increase in the number of visits and admissions with no significant changes in age, sex distribution, admission rate and involuntary rate. It is important to note that the admission rate of involuntary visits was extremely high even before the COVID19 outbreak (admission rate of more than 99% between 2017 and 2019) and therefore, no significant changes were expected for that measurement.Table 6 Involuntary patient data during lockdown periods compared to the averaged pre-pandemic control periods between 2017 and 2019. Results in bold are significant at p < 0.05.
Table 6: 1st Lockdown
(19/3–24/4) 2nd Lockdown
(18/9–18/10) 3rd Lockdown
(27/12–6/2) 4th Lockdown
(29/7–27/11)
Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.)
Visits 25 21 32 11 46 21 110 68
Daily visits 0.7 ± 0.4 0.6 ± 0.4 0.3
(312) 1 ± 0.4 0.7 ± 0.5 0.02 (185) 1.1 ± 0.7 0.5 ± 0.5 0.04 (355) 0.9 ± 0.8 0.6 ± 0.6 0.05
(5258)
Admissions 25 21 32 11 46 20.7 110 67.5
Daily admis. 0.7 ± 0.4 0.6 ± 0.4 0.3
(312) 1 ± 0.4 0.7 ± 0.5 0.02 (185) 1.1 ± 0.7 0.5 ± 0.5 0.04 (343) 0.9 ± 0.8 0.6 ± 0.6 0.05
(5207)
Admis. Rate 100% 100% 1
(-) 100% 100% 1
(-) 100% 95% 0.87
(0.0) 100% 99% 0.9
(0.0)
Age 39.8 ± 15.7 38.1 ± 11.1 0.45
(332) 42±16.2 41.6 ± 14.6 0.49
(259) 36.9 ± 10.1 38.5 ± 12 0.34
(433) 41.7 ± 13.1 40.1 ± 14.1 0.15
(5939)
Male 33.3% 32.1% 0.93
(0.0) 36.6% 30.8% 0.85
(0.0) 31.8% 26.4% 0.85
(0.0) 35.5% 26.4% 0.21
(1.6)
Table 7 Involuntary patient data between lockdown periods compared to the averaged pre-pandemic control periods between 2017 and 2019. Results in bold are significant at p < 0.05.
Table 7: Between 1st-2nd Lockdowns (25/4–17/9) Between 2nd-3rd Lockdowns (19/10- 26/12) Between 3rd-4th Lockdowns (6/2–28/7)
Covid19 Control p
(stat.) Covid19 Control p
(stat.) Covid19 Control p
(stat.)
Visits 108 69 63 41.3 179 94.5
Daily visits 1.6 ± 0.7 1.4 ± 0.6 0.05
(3665) 1.7 ± 0.8 1.4 ± 0.7 0.05
(1376) 1.7 ± 0.8 1.4 ± 0.6 <0.01 (11,915)
Admissions 108 68.7 63 40.7 178 94
Daily admis. 1.6 ± 0.7 1.4 ± 0.6 0.05
(3645) 1.7 ± 0.8 1.4 ± 0.7 0.05
(1351) 1.7 ± 0.8 1.4 ± 0.6 <0.01 (11,861)
Admis. Rate 100% 100% 1
(-) 100% 100% 1
(-) 100% 100% 1
(-)
Age 38.8 ± 11.7 39.1 ± 13.6 0.42
(4918) 39±14.6 38.7 ± 12.7 0.42
(1594) 39.8 ± 11.6 38.8 ± 12.8 0.16
(12,931)
Male 22.1% 22.7% 0.74
(0.1) 27.2% 21.4% 0.28
(1.1) 34.4% 27.7% 0.17
(1.8)
Table 8 summarizes the above results across lockdowns and between lockdown periods, again, in relative terms to the averaged control periods. The results indicate that the significant decrease in the number of voluntary visits and admissions during the first lockdown (−16.5% and −25.9%, respectively) was accompanied by a non-significant yet non-negligible increase in the number of involuntary visits and admissions (+19%). From the conclusion of the first lockdown, a very consistent pattern has been observed in which the number of involuntary visits has risen significantly and remains significantly higher compared to the control periods (ranging between +54.4% to +190.9%), whereas the voluntary visits present similar measures to those observed in the control periods. The increase in involuntary visits and admissions culminated during the second lockdown (+190.9% in both visits and admissions) and during the third lockdown (+119% in visits and +122.6% in admissions), which is accompanied by a non-significant decrease in the number of voluntary visits during the same lockdown periods (−8.2% and −4.8%, respectively). As such, any decrease in the number of voluntary visits should be carefully interpreted as it could imply that some potentially voluntary visits have resulted in involuntary visits. We discuss this point further in Section 4.Table 8 Relative changes in voluntary and involuntary visits during each examined lockdown (LD) and between lockdown periods with respect to the control periods between 2017 and 2019. Results in bold are significant at p < 0.05.
Table 8: LD1 Between 1–2 LD2 Between 2–3 LD3 Between 3–4 LD4
Voluntary Visitations Admissions −16.5%
−25.9% +0.3%
+0.2% −8.2%
−2.7% −2.2%
−7.6% −4.8% +10.9% −5.1%
−5% +6.3%
+0.3%
Admission Rate −4.4% 0% +2.2% +1.1% +5.7% 0% −2%
Involuntary Visitations Admissions +19%
+19% +56.5%
+57.3% +190.9%
+190.9% +52.4%
+54.9% +119% +122.6% +89.4%
+89.4% +61.8%
+63%
Admission Rate 0% +0.5% 0% +1.6% +1.6% 0% +0.7%
In order to get a more nuanced understanding of the temporal association between governmental COVID-19 restrictions and the examined ED measures, we further perform a regression-based analysis with two independent variables: the OxGR stringy index and the time elapsed since the start of the pandemic in Israel (days elapsed since the first occurrence of COVID-19 in Israel, time for short). As dependent variables we consider the four main metrics which were found to be most significant in the analysis above: daily number of visits, daily number of admissions, admission rate and involuntary rate. For each dependent variable a separate Log-Linear regression model was fitted.
Table 9 summarizes the results of the four fitted models. The results indicate that the level of governmental restrictions, as captured by the OxGR index, is significantly associated with all four measures when time is controlled. Specifically, OxGR is negatively associated with the daily number of visits (a change in OxGR from 0 to 100 is associated with 11.4% less visits), and positively associated with the daily number of admissions (the same change in OxGR is associated with 4.1% more admissions), the admission rate (the same change is associated with an increase by a factor of 1.139) and the involuntary rate (the same change is associated with an increase by a factor of 1.874). The results further indicate that time is significantly associated with three of the four measures. Specifically, it is positively associated with the daily number of visits and admissions (every 100 days that pass since the first occurrence of COVID-19 in Israel are associated with about 1% more visits and admissions) and with the involuntary rate (the same change is associated with an increase by a factor of 1.062). The association between time and the admission rate is not statistically significant, yet all other examined associations are statistically significant at p < 0.05.Table 9 Log-linear regression results with the dependent variables presented in rows and the independent variables presented in columns. Each coefficient represents the expected multiplicative change in the dependent variable given that the independent variable is increased by 1 unit (i.e., 1 point in the OxGR index or 1 day past the first occurrence of COVID-19 in Israel). Results in bold are significant at p < 0.05.
Table 9: OxGR time
coefficient [95% CI] p coefficient [95% CI] p
Visitations 0.9988[0.998,0.9996] 0.04 1.0001[1.0000,1.0001] 0.02
Admissions 1.0004[1.0001,1.0003] 0.04 1.0001[1.0000,1.0001] 0.02
Admission Rate 1.0013[1.0001,1.0025] 0.05 1.0000[1.0000,1.0000] 0.77
Involuntary Rate 1.0063 [1.004,1.009] <0.01 1.0006 [1.0001,1.0011] <0.01
4 Discussion
Prior work has extensively documented the collateral effects of COVID-19 on the public's mental health both within and outside the scope of psychiatric ED visitations (see Robinson et al. (2022) for a recent systematic review and meta-analysis). Focusing on the former, these works have primarily considered the effects of strict lockdowns on the volume and characteristics of psychiatric ED visits. To the best of our knowledge, this study is the first to examine the possible association between both strict lockdowns as well as other, milder, restrictions on psychiatric ED visits over time.
Our results suggest that, while no trend or seasonality existed in the pre-pandemic volume and characteristics of ED visitations, COVID-19 has brought about major changes on both accounts, especially when considering the most acute and urgent psychiatric conditions – i.e., involuntary ED visits, as shown in Table 8.
Starting with the first lockdown, our results are very much aligned with prior work, demonstrating an overall decline in the volume of visits and admissions. This decline is likely due to a confluence of factors, led by the fear of contracting COVID-19, as documented by public pools in Israel (Bitan et al., 2020) and abroad (American College of Emergency Physicians, 2020). Interestingly, this reduction in the volume of ED visits should be attributed solely to voluntary ED visits, whereas the number of involuntary ED visits has not presented any decline and, in fact, increased compared to the control periods, aligning once more with prior literature (Ambrosetti et al., 2021a). From the conclusion of the first lockdown, we see no significant differences in the volume and characteristics of voluntary ED visits, other than a few minor differences in patient age (the first lockdown and the first between-lockdowns period) and sex distribution (last between-lockdowns period). In sharp contrast, since the conclusion of the first lockdown, the volume of involuntary ED visits and admissions has dramatically increased, with the most striking changes observed during the second and third lockdowns. That is not the case for the fourth lockdown, which presented an increase in volume of involuntary ED visits that is similar to that experienced in the between-lockdown periods. Taken jointly, the results seem to suggest that mild restrictions may result in a reduced strain on psychiatric emergency services compared to strict lockdowns, especially considering the most acute and urgent psychiatric conditions and symptoms which require involuntary ED visitations. We find further support for this outcome through a regression analysis, indicating a significant increase in the volume of ED visits, admissions, admission rate and involuntary rate as a result of an increase in restriction levels and the time elapsed since the beginning of the pandemic in Israel. Specifically, as time elapses since the first occurrence of COVID-19 in Israel, the results suggest a significantly higher volume of ED visits, admissions and involuntary visits. While controlling for these temporal changes, we further find a significant positive associated between the level of governmental restrictions (as captured by the OxGR stingy index) and the volume of ED visits and admissions, and the admission and involuntary rates.
The surge in involuntary ED visits and admissions can be explained in a number of complementary ways. First, it is reasonable to assume that at least some patients requiring consented hospitalization were reluctant to visit the ED voluntarily or to adhere to medical advice due to fear of contagion in hospital settings, governmental restrictions and other pandemic-related concerns. Similarly, community-based, outpatient and ambulatory mental health services, which normally should be appropriate for a large portion of patients admitted to adult psychiatric EDs (Costanza et al., 2020), were, in-part, limited and overwhelmed with requests for help (World Health Organization, 2020). As such, some may not have had sufficient access to much needed timely mental health services, resulting in mental deterioration. For example, the Israeli Association for Emotional First Aid has reported that emergency calls more than tripled during the first months of the pandemic (Kleinerman et al., 2022). Indeed, the World Health Organization (WHO) has reported that certain acute psychiatric conditions are more likely to be triggered or significantly exacerbated as a result of the severe psychological reactions to the pandemic and to the measures taken to contain it (World Health Organization, 2022). These conditions, including suicidal thoughts, attempts and self-harming behaviors (Dub´e et al., 2021), first-onset psychosis (Segev et al., 2021) and major affective disorders (Santomauro et al., 2021), to name a few, are likely to result in involuntary ED visits if not appropriately managed. Additionally, there is growing evidence suggesting that individuals are at significantly increased risk of various severe psychiatric sequelae after a COVID-19 diagnosis (Taquet et al., 2021; Coleman et al., 2022). With the increased prevalence of COVID-19 in the general population (Israeli Ministry of Health, 2022), severe mental conditions may also be triggered following COVID-19 contagion.
4.1 A wider Israeli perspective
Existing knowledge on COVID-19 effects on psychiatric ED visitations in Israel is very limited. The most closely related work to ours is Pikkel Igal et al. (2021) and Dvorak et al. (2021), who examined the effects of the first Israeli lockdown on mental health-related ED visits to a general hospital (the former study was conducted at Rambam Health Care Campus and the latter at Sourasky Medical Center). Similarly, Schreiber et al. (2021) have examined the number of psychiatric consultations on a monthly basis during 2020 for the Sourasky Medical Center. In this respect, our work extends the existing knowledge in three major aspects: First, as prior work has relied on data from two general hospitals, it need not necessarily align with that of a designated mental healthcare center. Specifically, as fear of contagion is likely to play a major role in an individual's decision to visit an ED or not, it is possible that approaching a general hospital's ED would be perceived as more risky since individuals with respiratory symptoms or complaints are expected to approach that ED as well. Consequently, our results are roughly aligned with those observed in prior work, at least for the first lockdown. Second, as this work examines the four lockdowns implemented in Israel thus far, we provide a longitudinal, more up-to-date, perspective on the matter in question. Lastly, as both strict lockdowns and other restrictions are considered in this study, we provide a much needed investigation as to the potential association between governmental restriction levels and the volume and characteristics of ED visits.
Focusing on the issue of involuntary ED visitations in Israel, the rate and volume of involuntary ED visitations has varied significantly over the past decades. In the 90′s, a significant upward trend was recorded (Bauer et al., 2007). However, since the 2000′s, a non-consistent pattern has been observed, with the most recent pre-pandemic data presenting an opposite declining trend since 2015 (Youngmann et al., 2021). Against this background, the outstanding increase in involuntary ED visitations and admission observed and analysed in this work is especially remarkable.
4.2 Strengths and limitations
This work has several strengths. Most importantly, it provides a rigorous and detailed analysis of psychiatric visitations and admissions trends over a course of four lockdowns with different degrees of restriction as well as between lockdown periods. It further relies on extensive pre-COVID-19 data as control and provides a large sample size. However, it also has some important limitations which offer additional fruitful avenues of future research. First, our sample is taken from a single mental healthcare center. Official data from the Israeli Ministry of Health (Israeli Ministry of Health, 2019) shows that Shalvata is roughly representative of the Israeli mental healthcare system in almost every examined measure (e.g., patient characteristics, hospitalization outcome, etc.) for at least the last decade. As such, we plan to extend our investigation outside of Israel in the future. Second, we plan to examine the specific diagnostic categories for both voluntary and involuntary ED visits (e.g., substance use, mood disorders, psychosis). Such an investigation, which presumably requires different levels of “grouping” by different diagnosis codes, dealing with multiple diagnoses and special attention to the issue of first on-set vs. relapse, could help reveal which psychiatric conditions are more likely to be triggered, an issue outside the scope of this work. Lastly, while our results do show major changes in the volume and characteristics of ED visits, they need not necessarily indicate that other major changes have occurred during the hospitalization period (e.g., hospitalization duration, treatment plans, violent incidences, mechanical restraint and insulation). We plan to address this issue in future work.
5 Conclusions
In this work, a staggering increase in the volume of involuntary ED visits and admissions is recorded following the conclusion of the first Israeli lockdown, peaking during strict lockdown periods. In parallel, a rather stable volume of voluntary ED visits is documented with no major changes in their characteristics. In addition, a temporal increase in the total number of ED visitations, regardless of governmental restrictions, is identified. Consequently, it is unreasonable to expect the volume of ED visits, especially of involuntary ED visits, to return to its pre-pandemic levels in the near future. On the contrary, with the prospect of reimposed restrictions in the future given new variants of COVID-19 or other extreme eventualities, the strain on psychiatric emergency services may substantially increase.
Above all, our results highlight some of the severe mental health consequences associated with the pandemic over time and, most importantly, with the measures taken to control it. Specifically, optimistic projections suggesting that the general population will “soon learn to live side-by-side with the pandemic” has proven false thus far, at least when considering the acute and urgent mental conditions in the population which have reached unprecedented levels. In order to partially mitigate this phenomena, alternatives to strict restrictions should be favored when possible and mental health services should be strengthened.
CRediT authorship contribution statement
Amit Yaniv-Rosenfeld: Conceptualization, Data curation, Methodology, Software, Validation, Investigation, Formal analysis, Resources, Project administration, Writing – original draft, Writing – review & editing. Ariel Rosenfeld: Conceptualization, Software, Formal analysis, Visualization, Writing – review & editing. Efrat Hirsch Klein: Conceptualization, Methodology, Investigation, Supervision, Project administration, Writing – review & editing.
1 More information can be found on the hospital's official website at https://hospitals.clalit.co.il/shalvata/
==== Refs
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| 0 | PMC9737515 | NO-CC CODE | 2022-12-14 23:45:38 | no | Psychiatry Res. 2023 Jan 10; 319:115004 | utf-8 | Psychiatry Res | 2,022 | 10.1016/j.psychres.2022.115004 | oa_other |
==== Front
Therapie
Therapie
Therapie
0040-5957
1958-5578
Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS.
S0040-5957(22)00281-5
10.1016/j.therap.2022.12.007
Letter To Editor
Chronic spontaneous urticaria following vaccination against SARS-CoV-2
Zaiem Ahmed ab⁎
Mahjoubi Yasmine Salem a
Aouinti Imen ab
Lakhoua Ghozlane ab
Kaabi Widd ab
Kastalli Sarrah ab
Debbiche Sana Rebii a
Charfi Ons ab
Aidli Sihem El ab
a National Center of Pharmacovigilance, 1006 Tunis, Tunisia
b Research unit: UR17ES12, Faculty of Medicine, University of Tunis El Manar, La Rabta, 1007 Tunis, Tunisia
⁎ Corresponding author: National Center of Pharmacovigilance, 9 Avenue du Dr Zouhaier Essafi, 1006 Tunis, Tunisia
10 12 2022
10 12 2022
12 6 2022
© 2022 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.
2022
Société française de pharmacologie et de thérapeutique
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Keywords
Vaccine
COVID19
Chronic spontaneous urticarial
adverse reaction
immunization
==== Body
pmcThe case was notified to the Pharmacovigilance Center of Tunis (Tunisia) on February 9th, 2022 and registered with the reference number 635/2022
| 0 | PMC9737516 | NO-CC CODE | 2022-12-14 23:29:53 | no | Therapie. 2022 Dec 10; doi: 10.1016/j.therap.2022.12.007 | utf-8 | Therapie | 2,022 | 10.1016/j.therap.2022.12.007 | oa_other |
==== Front
J Infect
J Infect
The Journal of Infection
0163-4453
1532-2742
Published by Elsevier Ltd on behalf of The British Infection Association.
S0163-4453(22)00696-X
10.1016/j.jinf.2022.12.009
Letter to the Editor
Changes of pathogen distribution in children with bacterial meningitis before and after the COVID-19 pandemic in Zhengzhou, China
Cheng Ping 12
Li Lifeng 1
Sun Huiqing 1⁎
Zhu Changlian 2⁎
1 Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
2 Department of Neonatology, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
⁎ Corresponding author: Dr. Huiqing Sun, Children's Hospital Affiliated to Zhengzhou University, China, Tel: +86-373-85515912; Fax: +86-373-85515912
10 12 2022
10 12 2022
8 12 2022
© 2022 Published by Elsevier Ltd on behalf of The British Infection Association.
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
==== Body
pmcDear Editor,
In the Journal of infection, Li et al.[ 1 ] and Zhou et al.[ 2 ] reported the changes in Streptococcus pneumoniae and Haemophilus influenzae infections in children before and after the Coronavirus disease 2019 (COVID-19) pandemic, which attracted our intense attention and interest. However, no data is available regarding pathogen distribution of bacterial meningitis. Here, we present the pathogen distribution of children with bacterial meningitis before and after the COVID-19 pandemic in Zhengzhou, China.
Bacterial meningitis is a common infectious disease of the central nervous system in children. In China, the incidences varies between 20 and 80 cases per 100 000 population[ 3 ]. The mortality rate is high, and some survivors have permanent neurological sequelae[ 4 , 5 ]. Bacterial meningitis could be caused by pathogen infection acquired through birth contact, inhalation, nasopharyngeal colonization and blood flow invasion[ 6 ]. Common pathogens include Streptococcus pneumoniae, Group B hemolytic streptococcus, Escherichia coli, Enterococcus, Haemophilus influenzae, Staphylococcus aureus, coagulase negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae and Neisseria meningitidis [ 7 ]. The distribution of pathogens may be different in different regions. Since the outbreak of COVID-19 pandemic in 2019, many countries have implemented strict intervention measures, such as wearing masks, keeping hands clean and keeping social distance, limiting outdoor activities, etc. COVID-19 and related measures have seriously affected people's lifestyle, and may also affect the epidemiology of pathogens. Hence, we assessed the number of children's bacterial meningitis cases and the distribution of pathogens before and after the COVID-19 pandemic, providing a basis for hospital infection prevention and clinical management strategies.
In this study, we compared the number of child cases with bacterial meningitis and the proportion of different pathogens before and after the COVID-19 pandemic in Zhengzhou Children's Hospital to explore the impact of the COVID-19 pandemic on the pathogen distribution of bacterial meningitis in children. The results showed that ( Figure 1 ) the number of bacterial meningitis in children declined significantly in 2020 (n = 622 in 2018, n = 372 in 2019, n = 138 in 2020 and n = 213 in 2021). However, the number decline could be restriction of movement to the city from town or village. The total positive numbers with reported pathogen were 375 (n = 142 in 2018, n = 93 in 2019, n = 71 in 2020 and n = 69 in 2021). The number of positive cerebrospinal fluid cultures decreased in 2020, the first year of COVID-19 pandemic. However, the total positive rates were not following the decreasing trend.Fig. 1 The number of cerebrospinal fluid (CSF) culture samples, positive CSF culture from 2018 to 2021.
Fig 1
In addition, we analyzed the distribution of pathogens in cerebrospinal fluid cultures of children with bacterial meningitis before and after the COVID-19 pandemic (Table 1 , Figure 2 ). The results showed that before and after the COVID-19 pandemic, the pathogenic bacteria in cerebrospinal fluid culture of children with bacterial meningitis were mainly coagulase negative staphylococcus, Enterococcus faecium, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus, accounting for more than 65% of the pathogenic microorganisms. Among these pathogens, the percentage of Enterococcus faecium and Streptococcus pneumoniae decreased from 2018 to 2020, and then increased slightly in 2021. The percentage of Acinetobacter baumannii gradually decreased in 2020. However, the percentage of Escherichia coli gradually increased in 2020. In addition, Haemophilus influenzae and Stenotrophomonas maltophilia were detected in 2018 and 2019, but were not detected in 2020 and 2021. Other pathogens kept a relatively stable state.Table 1 The pathogen distribution of cerebrospinal fluid cultures in children.
Table 1Pathogens 2018 2019 2020 2021
(n = 142) (n = 93) (n = 71) (n = 69)
Coagulase negative staphylococci 54(38.03%) 34(36.56%) 28(39.44%) 25(36.23%)
Enterococcus faecium 23(16.20%) 12(12.90%) 5(7.04%) 10(14.49%)
Streptococcus pneumoniae 14(9.86%) 6(6.45%) 3(4.23%) 6(8.70%)
Escherichia coli 11(7.75%) 5(5.38%) 8(11.27%) 4(5.80%)
Klebsiella pneumoniae 7(4.93%) 3(3.23%) 3(4.23%) 5(7.25%)
Staphylococcus aureus 6(4.23%) 4(4.30%) 3(4.23%) 3(4.35%)
Haemophilus influenzae 3(2.11%) 4(4.30%) 0(0.00%) 0(0.00%)
Acinetobacter baumannii 2(1.41%) 6(6.45%) 2(2.82%) 1(1.45%)
Stenotrophomonas maltophilia 1(0.70%) 2(2.15%) 0(0.00%) 0(0.00%)
Pseudomonas aeruginosa 2(1.41%) 2(2.15%) 1(1.41%) 1(1.45%)
Other pathogens 19(13.38%) 15(16.13%) 18(25.35%) 14(20.29%)
Fig. 2 Percentages of common pathogens in cerebrospinal fluid from 2018 to 2021.
Fig 2
Our data indicated that the COVID-19 pandemic reduced the number of cases of bacterial meningitis in children and changed the distribution of pathogens in cerebrospinal fluid cultures. With the COVID-19 pandemic under control gradually, people's life return to normal, and the distribution of pathogens also changes. For example, the proportion of Enterococcus faecium and Streptococcus pneumoniae decreased during the period of strict control of COVID-19 (2020), while S. maltophilia and H. influenzae were not detected. Therefore, it is necessary to pay attention to the changes of pathogen distribution in children's bacterial meningitis before and after the COVID-19 pandemic.
In conclusion, since the outbreak of COVID-19, the number of children with bacterial meningitis has decreased significantly, and the distribution of pathogens has also changed. Effective and continuous monitoring is of great significance for the prevention and control of bacterial meningitis in children.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgment
This work was supported by grant from the Medical Science and Technology of Henan Province (2018020656)
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References
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2 Zhou J Zhao P Nie M Changes of Haemophilus influenzae infection in children before and after the COVID-19 pandemic, Henan, China J Infect 2022 10.1016/j.jinf.2022.10.019 S0163-4453(22)00615-6
3 van de Beek D Brouwer MC Koedel U Community-acquired bacterial meningitis Lancet 398 10306 2021 1171 1183 10.1016/S0140-6736(21)00883-7 34303412
4 Snoek L Goncalves BP Horvath-Puho E Short-term and long-term risk of mortality and neurodevelopmental impairments after bacterial meningitis during infancy in children in Denmark and the Netherlands: a nationwide matched cohort study Lancet Child Adolesc Health 6 9 2022 633 642 10.1016/S2352-4642(22)00155-9 35798010
5 Horvath-Puho E van Kassel MN Goncalves BP Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study Lancet Child Adolesc Health 5 6 2021 398 407 10.1016/S2352-4642(21)00022-5 33894156
6 Lundbo LF Benfield T Risk factors for community-acquired bacterial meningitis Infect Dis (Lond) 49 6 2017 433 444 10.1080/23744235.2017.1285046 28301990
7 Koelman DLH van Kassel MN Bijlsma MW changing epidemiology of bacterial meningitis since introduction of conjugate vaccines: 3 decades of national meningitis surveillance in the Netherlands Clin Infect Dis 73 5 2021 e1099 e1107 10.1093/cid/ciaa1774 33247582
| 36513167 | PMC9737517 | NO-CC CODE | 2022-12-14 23:29:53 | no | J Infect. 2022 Dec 10; doi: 10.1016/j.jinf.2022.12.009 | utf-8 | J Infect | 2,022 | 10.1016/j.jinf.2022.12.009 | oa_other |
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Heliyon
Heliyon
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2405-8440
The Author(s). Published by Elsevier Ltd.
S2405-8440(22)03588-5
10.1016/j.heliyon.2022.e12300
e12300
Research Article
A meta-analysis of COVID-19 vaccines acceptance among Black /African American
Ripon Rezaul Karim 1∗
Motahara Umma 1
Alam Adiba 1
Ishadi Kifayat Sadmam 1
Sarker Md. Samun 2
1 Department of Public Health and Informatics, Jahangirnagar University, Savar, Dhaka, Bangladesh
2 Animal Health Division, Bangladesh Livestock Research Institute, Savar, Dhaka, Bangladesh
∗ Corresponding Authors:
10 12 2022
10 12 2022
e1230029 7 2022
20 10 2022
5 12 2022
© 2022 The Author(s)
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
The COVID-19 pandemic had harmed Black /African Americans disproportionately. Mortality and morbidity can reduce by increasing vaccination acceptability and availability. We conducted a meta-analysis of 20 studies that show the prevalence of Black /African Americans who embrace COVID-19 vaccination between 2020 and September, 2022. Investigations conducted before and after the availability of COVID-19 vaccines found the vaccinations effective. The heterogeneity was examined using stratified analyses, the meta-regression approach, and sensitivity analysis in R programming language. This meta-analysis showed that the overall COVID-19 vaccine hesitancy among Black/African Americans is 35% (95% CI: 26%-45%). That means 65% of Black African Americans received vaccines without any hesitancy. According to correlation analysis, there was a negative relationship (r=-0.392, P=0.021) between the prevalence of vaccine hesitancy and the survey year. Evidence suggests ethnic health disparities in Black/ African Americans were for lower socioeconomic status. Some initiatives had to address health disparities, while ethnicity had not consistently been a focus. Only vaccines can prevent COVID-19 like infectious diseases. Policy makers and health educators should concern on vaccine acceptance or hesitancy related programs among Black/African American.
Meta-analysis; COVID-19 vaccine acceptance; Black /African American
Keywords
Meta-analysis
COVID-19 vaccine acceptance
Black /African American
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pmcIntroduction:
Coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), created the pandemic condition. The first COVID-19 patient was diagnosed in the United States (US) in January 2020, and by December 2020, it had become the leading cause of mortality in the US [1]. There were almost 1.9 million confirmed cases worldwide on April 14, 2020, with 601,000 infections and 24,129 deaths in the United States alone [2]. The population must be vaccinated against COVID-19 to achieve immunity, and the vaccination should have a high level of acceptance 3, 34. Hesitancy toward the COVID-19 vaccine threatens the potential for population protection against COVID-19. Vaccine reluctance encompasses various actions, including vaccine refusal and delayed acceptance [3]. Vaccine hesitancy is linked to sociodemographic characteristics such as age, sex, race/ethnicity, income, and education 4, 5. Race and ethnicity significantly impact vaccination, including the COVID-19 vaccine [4]. Black African Americans have an excellent standard of vaccine apprehension and a low level of vaccine assurance. The significant amount of vaccine apprehension is problematic in and of itself, but when combined with mounting evidence that COVID-19 disproportionately affects ethnic minorities, it is pretty alarming [5]. Despite having the highest risk of COVID-19 morbidity and mortality in the United States, racial and ethnic minority communities report poorer vaccine confidence and lower COVID-19 vaccination rates 6, 7. Vaccine hesitancy among Black African Americans is more than double that of whites, and this finding is concerning because COVID-19 hospitalizations and deaths are more common among Black/African Americans [8]. Several discrepancies in health facilities based on race and ethnicity have been observed in the United States, and this gap is worrying in the case of COVID-19 vaccine acceptance [9].
This study will demonstrate a pooled prevalence of acceptability of the COVID-19 vaccine acceptance among Black/ African Americans as they have been disproportionately under-vaccinated.
Methods
Study Design
We conducted a meta-analysis to determine the prevalence of COVID-19 vaccination acceptance among black/ African Americans. The studies' papers were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria [10]. Analyses based on publicly available data do not require ethics approval or authorization.
Eligibility Criteria
Studies that reveal the general proportion of Black/ African Americans who embrace COVID-19 vaccination are one of the requirements for admission. COVID-19 vaccines were confirmed to be efficacious in tests conducted before and after they became available. This study looked into COVID-19 vaccines in all forms. The researchers looked for publications that employed cross-sectional, case-control, and cohort designs published in English between 2020 and September, 2022. Case studies, conference papers, proceedings, abstract-only publications, editorial reviews, letters of communication, comments, systematic reviews, and qualitative research were all excluded from consideration. In addition, articles are written in a language other than English excluded. The studies that satisfy the following requirements were included in our analysis [1] Only Black/ African Americans with COVID-19 vaccine acceptancy or hesitancy were included in the studies, [2] which also studies included the prevalence of vaccine hesitancy or acceptance and [3] clear indication of sample size. According to those studies, only odd ratios/ risk ratios/relative risks/mean differences was left out of the analysis (means there is no indication of prevalence on vaccine hesitancy or acceptance prevalence).
Information Sources Search Strategy
For publications published between 2020 and September, 2022, a thorough search of the PubMed, Google Scholar, Scopus, ISI, and Web of Knowledge databases was conducted. The generic free-text search phrases "COVID-19" AND "vaccine" AND "acceptance" OR "hesitancy" AND "Black/ African American" were used in the search. The search was limited to full-text articles written in English. Cross-checking the reference lists of the listed citations yielded additional potentially relevant studies.
Data Collection Process and Data Items
As a result of our search approach, all items were exported to the EndNote program. Duplicated articles were removed from the database. One neutral reviewer (AA) examined the titles and abstracts of the discovered papers. The whole texts of qualifying papers were obtained and appropriately evaluated for eligibility. The records were examined for legitimacy by the second examiner (KSI). In the event of a disagreement between the two reviewers (AA & KSI), the reviewer was then consulted by RKR. Then the articles information was included by two reviewers (SS & UM). And Final checked by one reviewer (RKR). And statistical analysis was performed by RKR and UM. The search strategy was depicted in a PRISMA flow chart, which showed which studies were included and which were excluded and the reasons for exclusion (Figure: 01).
Reporting Bias Assessment
Data quality was assessed according to the Joanna Briggs Institute 11, 12. Appropriate sample frame, study participants sampled, sample size, description of study subjects and setting, sample size justification, power description, or variance and effect estimates, valid methods for condition identification, a standard and reliable condition measured appropriate statistical analysis, and adequate response rate were among the nine factors used to assess the risk of bias. The phrases "yes," "no," "unclear," and "not available" were used to convey the risk assessment criteria. They received a one-point score, while the others received a zero. The total score was 0 to 9. The likelihood of bias was considered low when the overall score was greater than 70% (a score of 6 or higher), moderate when it was 50–69%, and high when it was 0–49% 11, 12.
Statistical Analysis
After reviewing the entire article for quality, the authors independently extracted data using purpose-built forms that specified the pertinent factors. Disagreements were settled by debating the articles and coming to an agreement. The significant dependent variable was a binary categorization of study results based on whether the article supported the prevalence of vaccine acceptance/hesitancy of Black/ African Americans or not. The proportion for the study based on the standardized effect size was the dependent variable in the meta-analysis. The statistical analysis was carried out with the help of the R programming language. The metafor and metareg package in the R programming language was used to determine the pooled prevalence after excluding low methodological quality articles 40, 41, 42. Metafor uses inverse-variance weights from a random-effects model to pool proportions and offers a weighted sub-group and overall pooled estimate 41, 42. It entailed a meta-analysis of the prevalence values of each publication, weighted by sample size and allowing for potential heterogeneity across studies in this context [42]. Before random-effects model, Freeman-Tukey transformation was used to produce a proportional meta-analysis 40, 41, 42. Utilizing a random-effects meta-analysis to account for between-study heterogeneity, prevalence estimates were merged 39, 41, 42. The statistical heterogeneity was assessed using the chi-square test and on the Q statistic (H & I2), which was quantified by the I-square values, under the assumption that I-square values of 25, 50, and 75% were nominally assigned as low, moderate, and high estimates, respectively 39, 40, 41, 42. To examine potential sources of heterogeneity, the following grouping variables were employed in stratified analyses and meta-regression: sample size, sample type, data collection date, research quality, and sampling technique 39, 41, 42. In order to establish whether one or more studies had an impact on the outcomes by being excluded one at a time, a sensitivity analysis was also performed 41, 42. The distribution of the observed studies was visually inspected on a funnel plot in order to determine publication bias 39, 40, 41, 42. Egger's test was then used to measure the level of bias and then correlation test also conducted 40, 41, 42. The significance threshold was kept at <0.05.
Results
PRISMA was used to outline the specific steps of the systematic review and meta-analysis method, and Fig. 01 outlined the process of selecting relevant papers. We identified 663 of new studies via databases PubMed, Google Scholar, Scopus, ISI, and Web of Knowledge. Due to duplicate records, ineligible by automation tools and other reasons 628 articles are removed. 7 studies were removed for not indicating prevalence and not peer reviewed. Then we include 28 articles in this study and 8 articles also removed for low methodological quality. Then 20 studies were included in the final analysis. The study included 20 studies with a total of 7384 participants (Table 01 ). Every study subject is Black /African American (general population and health care workers). The articles were released in the years 2020 through 2022. Eight studies received a score of 9, three got an 8, five got a 7, four got a 6, and eight got a 4, according to the quality assessment standards. The studies are generally deemed to be of acceptable quality, according to the quality scores. Only three of the twenty studies used probability sampling, out of all the nonprobability sample techniques.Figure 01 PRISMA flow diagram for this study
Figure 01
Table 01 Systematic Review Information
Table 01Study Total Events Sample Quality score Sampling Technique
Matthew C. Sullivan, 2022 109 52 Black 9 Nonprobability
Anna Maria Napoles, 2021 1197 379 Black 9 Nonprobability
Manoj Sharma, 2021 428 208 Black 9 Nonprobability
Olihe Okoro, 2021 183 47 Black 9 Nonprobability
Laura M.Bogart, 2021 101 55 Black 8 probability
Jana Shaw, 2022 263 87 Health Care worker 9 Nonprobability
Marc F. Stern, 2021 1390 775 Black 7 Nonprobability
Mara Eyllon, 2022 342 82 Black 6 Nonprobability
Jeanette B. Ruiz, 2022 87 35 Black 7 probability
Julia H.Rogers, 2022 289 104 Black 8 Nonprobability
Ramey Moore, 2021 85 55 Black 9 Nonprobability
Michael Daly, 2022 917 682 Black 7 probability
Casey L. Daniel, 2022 198 54 Black 7 Nonprobability
Yingjie weng, 2021 116 69 Black 8 Nonprobability
Kiefer et al., 2022 456 80 Black 7 Nonprobability
Carroll et al., 2022 325 41 Black 9 Nonprobability
M. Purnell et al., 2022 210 21 Black 8 Nonprobability
Cepeda et al., 2022 346 64 Black 7 Nonprobability
Johnson et al., 2021 248 46 Black 9 Nonprobability
Jones et al., 2021 94 26 Black 6 Nonprobability
Don E. Willis, 2021 1475 39 Black 4 Nonprobability
Amyn A. Malik, 2020 672 40 Black 4 Nonprobability
Don E. Willis, 2021 1205 50 Black 4 Nonprobability
Germann et al., 2022 456 28 Black 4 Nonprobability
Ruiz & Bell 2021 804 52 Black 4 Nonprobability
Bass et al., 2021 501 38 Black 4 Nonprobability
Benis, Seidmann 2021 1644 17 Black 4 Nonprobability
Fontenot et al., 2021 772 10 Black 4 Nonprobability
We included 20 studies in this meta-analysis. This analysis of show that the overall COVID-19 vaccine hesitancy among Black/ African American was 35% (2962/7384 individuals, 95% CI: 26%-45%), with significant evidence of between study heterogeneity (chi square=1278.25, P<0.001, I2=99%) [Figure 02 ]. That means 65% of Black African Americans received COVID-19 vaccines without any hesitancy. Sensitivity analysis was carried out by calculating pooled vaccination hesitancy prevalence once more when any single study was eliminated in order to verify the stability and liability of the meta-analysis. The related pooled vaccine hesitancy prevalence was shown range from 33.2% (30.0%-38.5%) to 43.8% (37.0% -51.6%) without significantly changing (Fig. 4 ). The statistically identical findings indicated that no single study had an impact on the stability of the overall estimate of the prevalence of vaccine reluctance in this meta-analysis. Even though the funnel plot's visual inspection exhibited asymmetry (Fig. 3 ), Egger's test demonstrated substantial value (p =.654), and there was no chance of publication bias.Figure 02 A forest plot of meta-analysis among Black African American.
Figure 02
Figure 4 Sensitivity analysis for individual studies.
Figure 4
Figure 03 A funnel plot of bias
Figure 03
There was considerable variation between studies. In order to investigate potential sources of heterogeneity, meta-regression (univariate) was used. The meta-regression method was used to examine the sample size, sample type, study period, study quality, and sampling strategy as potential sources of heterogeneity. Table 02 contains the meta-finding on regressions. None of the aforementioned factors were found to be substantially correlated with the identified heterogeneity through the regression model, with the exception of research study time (P=0.004). Therefore, we conducted additional research to examine the relationship between vaccine reluctance prevalence and probable causes. The prevalence of vaccine reluctance was found to be negative correlated with the research study period (r=-0.392, P=0.021) (Table 3 ). That mean vaccine hesitancy may reduce after a time period.Table 02 Result of Meta Regression.
Table 02Covariate Beta (β) (95%CI) P value R2 (%)
Sample size 0.0001 (-0.0001- 0.0004) 0.3539 12.02%
Sample Technique 0.0001 (-0.0001-0.0005) 0.3453 Nill
Study Quality 0.0436 (-0.2328 - 0.3200) 0.7571 Nill
Study period 0.1433(0.0406- -0.459) 0.0039 34.14%
Sample Type 0.0429 (-0.2236 -0.3094) 0.7523 1.73%%
Table 3 The correlation between the vaccine hesitancy prevalence and potential sources.
Table 3Covariate Sample size Sample Type Study period Quality score Sampling Technique
p .513 .123 0.021 .093 .073
r .632 .432 0.392 .534 .645
Discussions
Identifying and reducing vaccination hesitancy in COVID-19 is crucial for public health and health disparities, and the pandemic highlights these issues [28]. Low-risk insight is associated with vaccine acceptance [29]. Vaccine receptivity is linked to the trepidation of infection and broad distrust of immunizations [5]. Initiatives must address the history of racism that has eroded credibility in health and medical science organizations among traditionally marginalized communities shattered faith in COVID-19 vaccines and fostered grossly unequal healthcare coverage 23, 30. COVID-19 vaccination apprehension was higher among racial and ethnic minorities, and Black individuals in the United States were more unlikely than White respondents to take the vaccine [30]. A study reported in the state of Arkansas, where the incidence of COVID-19 vaccination reluctance was most significant among Black/African Americans (50 %), and the odds of COVID-19 vaccine unwillingness were 2.42 times higher for Black/African American respondents assimilated to white respondents (p-0.001) [5]. Another study showed that even though Blacks are disproportionately affected by the virus, they are 40% less interested in seeking a vaccine. Once immunization begins, this could worsen current health disparities [24]. Although Black/ African American women are less vaccinated than other races [35]. One study on Black found that women are 72% more likely to avoid vaccination, implying that measures to increase vaccination attitudes in this group should be a significant focus [31]. Immunization endorsement and acceptability by social referents and health practitioners were linked to women's intention to take the vaccine in seven studies [16]. In another study, 11% of women with negative aspirations expressed embarrassment regarding obtaining a vaccine connected with a sexually transmitted disease [16]. The vulnerable group of Black /African American (Children, pregnant women etc) are vaccinated on few days later [38]. The most widespread refusal causes were a lack of evidence about COVID-19 vaccine safety in pregnant populations and the likelihood of injury to the fetus. Pregnant women had greater acceptance of COVID-19 vaccination in the first trimester than in the second and third trimesters [32].
This proportion meta-analysis shows that the overall COVID-19 vaccine hesitancy among Black African Americans was 35% (95% CI: 26%-45%). More than half of Black African Americans received vaccines without hesitancy [Figure 2]. A study in 2016 on Black indicates social determinants are improving [36]. Social determinants are linked to vaccine acceptance [5]. Whereas another Global Rapid Systematic Meta-Analysis indicated that the overall COVID-19 vaccination acceptance rate in the African region was 42.46% (95% CI: 23.10-61.82) among the general population, while it was 27.70% among healthcare workers (95% CI: 24.16-31.24) and Cameroon had the poorest approval rate at 15.40% (95% CI: 13.99-16.81) [32]. In contrast, the general acceptability rate of the COVID-19 vaccination was determined to be in European and American regions was 67.04% (95% CI: 60.58-73.50) and 64.77% (95% CI: 57.23-72.32). Regarding the precise explanations for apprehension, the most common concerns of people of all races and ethnicities were long-term adverse effects (50-57 %) and unpleasant reactions (45-54 %). Furthermore, Black and Hispanic people were more likely than White people (37-42%) to say they did not know enough regards the vaccine (45-51%) [30].
Another finding of our study was to negative correlation of vaccine hesitancy and study period. Vaccine hesitancy is reducing among black African American after a time period but it is higher than others races [36]. Our study also indicates there was higher heterogeneity for time period among Black /African American vaccine hesitancy. Vaccine hesitancy can be reduced in a defined time period. But for that, the Government should take some initiative early to reduce the severity of diseases. By that Black people who had hesitancy to get vaccines can trust in vaccines, delivery methods, and health care [37]. Nevertheless, there are cogent reasons why Black people in the United States would be skeptical of a COVID-19 vaccination, and these causes are racist. Subconscious biases within healthcare systems and healthcare professionals have been linked to decreased quality of care and even worse medical outcomes among Black people in the United States [33]. To delay the pandemic, tailored health communication techniques that successfully meet the subpopulations most prone to oppose COVID-19 vaccination and work to alleviate the vaccine-core hesitant fears using scientific evidence would be required [24].
Vaccine hesitancy poses dangers to both the individual and his or her community, since exposure to a contagious disease places the person at risk, and individuals are far more likely to spread the disease to others if they do not get vaccinated [43].Even though inventing a vaccine which is secure, effective, and affordable is extremely hard, vaccine hesitancy presents a distinct obstacle for academics, professionals in the medical field, as well as members of the public administration and local communities [43]. Many experts have recommended strategies to address vaccine hesitancy at the population level, which include accountability in decision-making regarding vaccination policies, educating the general public and health care professionals about the sophisticated procedure that ultimately resulted in the approval of new vaccines, and diversified post-marketing surveillance of vaccine-related events [44]. Naturally, those who want to undermine public trust in vaccinations will always find methods to disseminate misleading information. However, if given the right guarantees, a substantially larger section of the population could be inclined to get vaccinations, and when their worries are disregarded, they frequently turn to others for support [45].
The main strength of this articles was the pooled prevalence of COVID-19 vaccine hesitancy/ acceptance among Black/ African American. We solely refer to the Black/ African American subgroup. There was the only one study specifically mentions Black /African Americans with social determinants. Because of this, it was not possible to include any other subgroup (based on demographic information) in this study. We looked through numerous databases and websites to discover all relevant and gray publications in order to eliminate database bias but there may be massing some databases or websites. The limitations mentioned above, as well as publication bias and heterogeneity for some of the pooled results, must all be taken into account when interpreting the results.
Conclusions
Establishing intervention and preventative techniques that focus on changing people's perceptions of vaccination's benefits while simultaneously removing existing barriers is crucial. Governments and policy makers should ensure that people have enough information, a positive attitude, and favourable perceptions about COVID-19 vaccines. Although the vaccine hesitancy less than 50%, the healthcare institutions should implement urgent health promotion programs and disseminate more reliable data on vaccine production process, efficacy and effectiveness. With these activities, vaccine hesitancy may more reduce. In future to increase acceptance, vaccine have available may without any cost.
Declarations
Author contribution statement
LineNoBookmarkStart:ID:104==Name:Line_as2tud_51]
Rezaul karim Ripon: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper. </p>
Umma Motahara: Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper. </p>
Kifayat Sadmam Ishadi, Adiba Alam: Contributed reagents, materials, analysis tools or data; Wrote the paper. </p>
Md Samun Sarker: Contributed reagents, materials, analysis tools or data. </p>
Funding statement:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data availability statement:
Data will be made available on request.
Declaration of interest’s statement:
The authors declare no conflict of interest.
Additional information:
No additional information is available for this paper.
Uncited reference
13., 14., 15., 17., 18., 19., 20., 21., 22., 25., 26., 27..
Acknowledgements:
We are thanked to Md Sojib Bhuyan, Government Bangla College for his technical support.
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| 0 | PMC9737518 | NO-CC CODE | 2022-12-14 23:29:53 | no | Heliyon. 2022 Dec 10;:e12300 | utf-8 | Heliyon | 2,022 | 10.1016/j.heliyon.2022.e12300 | oa_other |
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
The Author(s). Published by Elsevier Ltd.
S2405-8440(22)03621-0
10.1016/j.heliyon.2022.e12333
e12333
Research Article
Model exploration for discovering COVID-19 targeted Traditional Chinese medicine
Sun Yuting 1#
An Xuedong 1#
Jin De 2
Duan Liyun 1
Zhang Yuehong 1
Yang Cunqing 1
Duan Yingying 1
Zhou Rongrong 1
Zhao Yiru 1
Zhang Yuqing 1
Kang Xiaomin 1
Jiang Linlin 1
Lian Fengmei 1∗
1 Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing 100053, China
2 Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
∗ Corresponding author:
# Yuting Sun and Xuedong An contributed equally to this work.
10 12 2022
10 12 2022
e1233330 5 2022
15 8 2022
6 12 2022
© 2022 The Author(s)
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
In terms of treatment, a particularly targeted drug is needed to combat the COVID-19 pandemic. Although there are currently no specific drugs for COVID-19, traditional Chinese medicine(TCM) is clearly effective. It is recommended that through data analysis and mining of TCM cases (expert experience) and population evidence (RCT and cohort studies), core prescriptions for various efficacy can be obtained. Starting from a multidimensional model of regulating immunity, improving inflammation, and protecting multiple organs, this paper constructs a multidimensional model of targeted drug discovery, integrating molecular, cellular, and animal efficacy evaluation. Through functional activity testing, biophysical detection of compound binding to target proteins, multidimensional pharmacodynamic evaluation systems of cells (Vero E6, Vero, Vero81, Huh7, and caca2) and animals (mice infected with the new coronavirus, rhesus macaques, and hamsters), the effectiveness of effective preparations was evaluated, and various efficacy effects including lung moisturizing, dehumidification and detoxification were obtained. Using modern technology, it is now possible to understand how the immune system is controlled, how inflammation is reduced, and how various organs are protected. Complete early drug characterization and finally obtain effective targeted TCM. This article provides a demonstration resource for the development of new drugs specifically for TCM.
COVID-19; targeted Traditional Chinese Medicine; model exploration; effective prescriptions; modern technology; pharmacodynamic evaluation
Keywords
COVID-19
targeted Traditional Chinese Medicine
model exploration
effective prescriptions
modern technology
pharmacodynamic evaluation
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pmc1 Introduction
Globally, COVID-19 has become a pandemic 1, 2. A novel coronavirus (SARS-CoV-2) was reported in January 2020; the World Health Organization (WHO) later designated it as COVID-19 [3]. 526 million confirmed cases and more than 6 million fatalities had been reported globally as of 29 May 2022 [4]. There are currently three new coronavirus epidemics in humans, including COVID-19, Severe Acute Respiratory Distress Syndrome (SARS), and Middle East Respiratory Disease (MERS). SARS-genome SARS-CoV-2 has 80% of its similarities with the original SARS-CoV, which first appeared in humans more than ten years ago, and roughly 97% of its similarities with the bat coronavirus (CoV RaTG13), indicating that it likely evolved from bat viruses [5]. The positive genome of the single-stranded RNA virus SARS-CoV-2 has 29,903 nucleotides (NCBI reference sequence: NC-045512) [5]. The coronavirus needs the S protein to enter the host cell, creating the necessary circumstances [6]. The S protein of SARS-CoV-2 has a greater affinity for the ACE2 receptor than SARS-CoV [7], which may be the key factor for COVID-19 to spread so quickly (which is more infectious). COVID-19 has been curtailed in some ways by the emergence of vaccines. WHO declared the COVID-19 vaccines to be on its "emergency list" for China in June 2021. It is, however, characterized by rapid transmission, high infectivity, and general population susceptibility, and there are currently no specific targeted drugs available. New drugs that are specifically targeted are required to address this problem on a therapeutic level. There is growing evidence that COVID-19 can be effective using traditional Chinese medicine (TCM). The benefits of TCM in the treatment of COVID-19 have been shown in a review of 40 representative clinical trials [8]. TCM can reduce the time of symptom recovery, delay the development of severe disease, protect multiple organs damage; improve lung characteristics; and improve laboratory indicators, including CD4+T, CD8+T, CRP, IL-6, TNF-A, ESR, and thrombogenic-associated pulmonary embolism levels [8]. TCM can also delay the onset of severe disease and protect against damage to multiple organs. The outcomes demonstrate that TCM is effective in treating COVID-19. For COVID-19, there are more specialized, effective, and targeted TCM treatments available. This article explores new targeted TCM treatments for COVID-19 using a multi-dimensional efficacy evaluation system. Firstly, the core medications with strong efficacy evidence are combined in accordance with the various efficacy and pharmacological effects of TCM. Secondly, pharmacodynamic evaluation is performed using the pharmacodynamic evaluation method from the perspectives of immunity, inflammation, and organ protection based on the features of viruses and medications. Thirdly, explain the mechanism. Finally, complete the evaluation of the medicinal properties.
2 Current methods of targeted drug exploration and potential therapeutic drugs
2.1 Current research methods of targeted drugs
The development of targeted drugs based on protein structure has been studied. Spike protein (S), membrane (M), envelope (E), nucleocapsid (N), and Nsp15 protein are the four structural proteins found in coronaviruses. It has been suggested to use virtual screening to investigate potential drugs. Paritaprevir and Elbasvir have some of the lowest free binding energies when compared using molecular docking techniques to identify potential Nsp15 inhibitors for COVID-19 [9]. Through molecular modeling, docking, and kinetic simulations, the study created a model of the viral protein RNA-dependent RNA polymerase (RdRp) and assessed the drug affinities. SARS-CoV-2 RdRp was combined with Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine [10]. Several well-characterized diacylpyrimidine analogs have been computationally identified as inhibitors that may disrupt hACE2 surface spike protein (S) interactions. The pyrimidine derivative AP-NP may be a powerful inhibitor of the hace2-S complex, as was later discovered using molecular docking, molecular dynamics (MD) simulations, and confinement-free energy calculations [11]. Target drug studies are also being conducted using molecular simulation approaches. Based on network pharmacology, a chemical-target network is built to forecast core medications and identify Lianqiao-Jinyinhua core drugs [12]. There have been reports of potential drugs for COVID-19 being found using molecular docking, molecular dynamics (MD), and structure-activity relationship (SAR) simulations. At the same time, some studies combine molecular docking with molecular dynamics. Ramipril, Delapril, and Lisinopril were screened to bind with ACE2 receptor and [SARS-CoV-2/ACE2] complex more effectively [13]. To calculate suitability scores, some studies use molecular dynamics software and machine learning algorithms. In addition, suture algorithms have been used to predict network pharmacology involving multiple active drug candidate pathways, suggesting that cordycepin can be reused in COVID-19 [14].
In some studies, compounds are screened first, followed by in vitro enzyme-inhibition activity screening of SARS-CoV-2 clinical isolates and in vitro culture assays using Vero cells. Finally, two compounds with dual activity were screened, which showed good application prospects by verifying the computational model and toxicity of the compounds. In a study using an integrated approach to identify more drug molecules targeting SARS-CoV-2 proteins, molecular interactions determined by molecular dynamics simulations revealed the role of catechins during the virtual screening of 75 drugs, and the binding of catechins made it easier to participate in key molecular interactions, in addition, catechins and package, stability was mainly achieved through hydrophobic interactions, indicating that catechins have the potential to be developed as multi-target drugs against COVID-19 [15]. Currently, targeted drugs are derived from viral proteins or computer simulations, which lack a basic description of their therapeutic effects. Multidimensional validation at the molecular, cellular, and animal levels is necessary to make targeted drugs more effective in clinical treatment. Based on this, we propose a targeted drug exploration model. Therefore, this paper constructs a multi-dimensional comprehensive efficacy evaluation system of molecules, cells, and animals to improve inflammation, regulate immunity, protect organs, and explore and discover targeted TCM for the treatment of COVID-19. Table 1 summarizes current approaches to exploring targeted drugs, mainly based on computer simulations and protein structure(Table 1).Table 1 summarizes the current methods of exploring targeted drugs, which are mainly based on computer simulation and protein structure.
Table 1basic method research methods result reference
protein structure docking techniques to identify
potential Nsp15 inhibitors Paritaprevir and Elbasvir [9]
protein structure establish a viral protein RNA-dependent RNA
polymerase (RdRp) model through molecular
modeling, docking, and kinetic simulations Sofosbuvir,Ribavirin,Galidesivir,Remdesivir,
Favipiravir,Cefuroxime, Tenofovir, and Hydroxychloroquine [10]
protein structure identify inhibitors that may disrupt hACE2
surface spike protein (S) interface interactions
and through molecular docking, molecular
dynamics (MD) simulation pyrimidine derivative AP-NP [11]
molecular simulation
techniques construct a chemical-target network based
on network pharmacology Lianqiao-Jinyinhua [12]
molecular simulation
techniques molecular docking with molecular dynamics Ramipril, Delapril, and Lisinopril [13]
molecular simulation
techniques molecular dynamics and machine learning
algorithms to calculate suitability scores cordycepin [14]
comprehensive method compounds were firstly screened out, and then
SARS-CoV-2 clinical isolates were screened for their in vitro enzyme inhibitory activity, and vero
cells were used for in vitro culture detection catechins [15]
2.2 potential therapeutic drugs
Antivirals, antibiotics, antimalarials, and immunomodulatory drugs may be effective in combating COVID-19 with the onset of the epidemic. Monoclonal antibody drugs include Bamlanivimab (LY-CoV555), which acts against the SARS-CoV-2 spike protein and may prevent and treat COVID-19 16,17. Etesevimab (also known as JS016 or LY-CoV016) can specifically bind to the receptor binding domain (RBD) of the SARS-CoV-2 surface protein [16], and many studies have shown that Etesevimab has positive significance for the treatment of COVID-19 18,19. Sotrovimab (Xevudy, GlaxoSmithKline and Vir Biotechnology, Inc.) binds to a highly conserved epitope on the RBD of the SARS-CoV-2 S protein and can delay the clinical progression of COVID-19 [20]. Casirivimab (IgG1-κ) and imdevimab (IgG1-λ) bind to non-overlapping epitopes of the SARS-CoV-2 spike protein RBD [21], and clinical trials have shown that REGN-CoV can reduce viral load 22, 23. Tocilizumab (RoActemra, Roche Pharma AG) specifically binds to soluble and membrane-bound receptors (sIL-6R and mIL-6R) of IL-6 [24]. A meta-analysis by Malgie et al showed that the use of tocilizumab was associated with reduced mortality [25]. Remdesivir can inhibit viral replication [26], effectively achieve early clinical improvement and reduce early mortality [27]. Baricitinib can reduce the expression of IL-6 [28] and reduce the mortality of COVID-19 [29]. Application of autophagy and UPR in SARS-CoV-2 infection, Paxlovid and the SARS-CoV-2 covalent 3CL protease inhibitor PF-07,321,332 [30] can reduce mortality compared with placebo [31]. Molnupiravir (Lagevrio) can neutralize pathogens and exert antiviral effects [32], which has a positive significance for the treatment of COVID-19 [33]. Regdanvimab (Regkirona), which blocks cell invasion and SARS-CoV-2 infection [34], is used to treat COVID-19 in adults who do not require supplemental oxygen and those at increased risk of severe disease [35]. Anakinra (Kineret) inhibits the biological activity of interleukin 1. A meta-analysis by Kyriazopoulou et al. showed a significant improvement in survival with Anakinra [36]. Sotrovimab (Xevudy, also known as VIR-7831 and GSK4182136), which can adsorb the S protein of SARS-CoV-2, is an active monoclonal antibody against COVID-19 [37], which can delay disease progression [38]. Tixagevimab and cilgavimab (Evusheld) were designed to attach to different sites of SARS-CoV-2 spike protein 2, reducing the risk of disease progression and mortality [39]. Other drugs with potential efficacy against COVID-19 infection, such as hydroxychloroquine (HCQ) 40, 41, 42, 43, 44, 45, 46, Colchicine 47, 48, 49, convalescent plasma 50, 51, 52, 53, 54, Amantadine 55, 56, 57, 58, 59, Ivermectin 60, 61, 62, 63, 64, 65, 66, Niclosamide (NIC) 63, 67, 68, 69, Sarilumab (Kevzara) [70].
3 Search for targeted drugs
3.1 Find core prescriptions based on data mining
Clinical experience can be accumulated, and valuable experience can be provided for follow-up treatment to improve the accuracy of COVID-19 treatment by digging out core prescriptions for COVID-19 treatment from case experiences (expert experiences) and group evidence (RCTs and cohort studies) and applying the mined prescriptions to follow-up evaluation and exploration, which has an important role.
Through the analysis and mining of expert treatment experiences and whole case data, the core prescriptions with different efficacy sets were obtained. First, electronic medical records (EMR) can be mined [71]. The data processing process of EMR generally includes five processes: data acquisition, data preprocessing, data mining, evaluation, and knowledge application 72, 73, 74. Text mining mainly includes four steps: information retrieval, information extraction, knowledge discovery, and knowledge application [6]. There are three main data mining algorithms: classification, clustering, and association [75]. Core drugs for COVID-19 treatment by experts were searched based on literature collection, and COVID-19 treatment plans issued by the authorities of provinces, municipalities, and autonomous regions were collected. Meanwhile, core prescriptions were retrieved according to COVID-19 diagnosis and treatment protocols released by The National Health Commission of China. Novel Coronavirus Protocol for Diagnosis and Treatment of Pneumonia (Trial) was released on 16 January 2020, followed by Novel Coronavirus Protocol for Diagnosis and Treatment of Pneumonia (Trial Second Edition). The Novel Coronavirus Diagnosis and Treatment Protocol for Pneumonia (Trial Version 3) were released on 22 January 2020. Novel Coronavirus Diagnosis and Treatment protocol for Pneumonia (Trial Edition 4) was released on 27 January 2020. Novel Coronavirus Diagnosis and Treatment protocol for Pneumonia (Trial Edition 5) was released on 5 February 2020. COVID-19 Diagnosis and Treatment Protocol (Revised Trial Fifth Edition) was released on 8 February 2020. Novel Coronavirus Diagnosis and Treatment protocol for Pneumonia (Trial Version 6) was released on 18 February 2020. Novel Coronavirus Diagnosis and Treatment protocol for Pneumonia (Trial Version 7) was released on 4 March 2020. Novel Coronavirus Protocol for diagnosis and Treatment of Pneumonia (Trial Version 8) was released on 18 August 2020. Novel Coronavirus Diagnosis and Treatment Protocol for Pneumonia (Revised Trial Edition 8) was published on 14 April 2021.
According to the recommendation of the eighth edition, the disease stage was divided into the medical observation stage and the clinical treatment stage. Huo Xiang Zhengqi capsule, Jinhua Qinggan granule, Lianhua Qingwen capsule, and Shufeng Jiedu capsule are recommended during the medical observation period. Qingfei Paidu decoction is recommended for clinical treatment. Mild cold and dampness syndrome of stagnation of the lung is Maxing Shigan decoction and damp-heat syndrome of lung storage is Houpo Wenzhong decoction. The common type of dampness and dampness syndromes of lung stagnation are Xuanfei Baidu decoction, and cold dampness and lung obstruction syndromes are Cangzhu, Chenpi, Houpo, HuoXiang, Caoguo, shengMahuang, Qianghuo, Shengjiang, and Binglang. The severe epidemic virus closed lung syndrome for Huashi Baidu decoction, Qi and yin deficiency pattem for Qingwen Baidu decoction. For severe cases of internal closure and external withdrawal, Renshen, Heishun pian, and Shanzhuyu should be taken the Suhexiang pill or Angong Niuhuang pill [76].
3.2 Evaluate core prescriptions
3.2.1 Evaluate the efficacy of core prescriptions at the molecular level
According to the functional activity mechanism and substrate binding characteristics of each protein, in silico virtual screening methods such as molecular docking (molecular docking can predict ligand-target interactions at the molecular level and can determine the therapeutic value of drugs) [77], molecular modeling, molecular dynamics (MD) simulation and binding free energy calculation, structure-activity relationship (SAR). Functional activity detection methods, such as enzyme activity detection methods based on fluorescence resonance energy transfer [78] (the energy of fluorescence resonance energy transfer is transferred from the excited state of the donor fluorophore to the adjacent ground state biophysical method by dipole-dipole coupling to detect the binding of compounds to target proteins, such as protein thermal stability tests). The main methods include isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), time-resolved energy transfer (TR-FRET), and enzyme-linked immunosorbent assay (ELISA). High throughput screening (HTS) technology is based on molecular or cellular-level experimental methods, using microplates as experimental tool carriers, supporting the overall operation of the technical system through program control, sample detection, and corresponding database systems [79]. HTS, such as fluorescence polarization, is usually linearly proportional to the percentage of a conjugate, from which the IC50 value is quantified. Mainly studying protein-molecule (ligand) interactions, protein-protein interactions, nucleic acid hybridization, etc., almost all types of proteins can be studied [80]. ELISA can detect and quantify proteins and other substances [81]. Among other methods used, are surface plasmon resonance, nuclear magnetic resonance, and acoustic fog ionization-mass spectrometry [82]. Biophysical assays were performed, including surface plasmon resonance (SPR), biofilm interferometry interaction (BLI), tri-dependent fluorescence intensity change method (TRIC), fluorescence thermal drift experiment (TSA), and isothermal titration calorimetry (ITC). Based on the P2/P3/P4 laboratory, the Homo-Trimeric spike glycoprotein (S protein), the Nucleocapsid (N) protein, of the SARS-CoV-2 virus, is the first anchor of the virus in the host cell [83], enveloping the viral RNA into a helical ribonucleic capsid (RNP) and interacting with other structural proteins as the virus assembles, resulting in the genome being encased 81, 82, 83. Helicase, RdRp (Multi-subunit RNA-dependent RNA polymerase), 3CLpro (3C-like protease, named after the 3C protease of the Picornaviridae), and Stimulator of Interferon Genes (Sting) are used as protease targets in the Picornaviridae, combining effective prescriptions and their effective compounds, monomers, determine antiviral, immunomodulatory, and anti-inflammatory effects, evaluate effective prescriptions and their effective compounds, antiviral, modulative, anti-inflammatory activity, and other pharmacological effects of monomers. Through preliminary screening, various cold and temperature properties and efficacy groups were obtained.
3.2.2 Evaluate the efficacy of core prescriptions at the cell level
The monkey kidney cell lines Vero E6, Vero and Vero81 are frequently used to culture viruses lacking interferon (itf) secretion. Human lung adenocarcinoma cell Calu3. This cell is readily available and reproducible, differentiates into polarized monocytes with different phenotypes, expresses airway mucus secretion, tight junctions, and microvilli, and can transport proteins and metabolic functions [84], human liver cells Huh7, a permanent cell line [85]. Cancers of colorectal adenoma Caco2 can spontaneously differentiate into single cells, which can form between adjacent cells and are closely related [86]. RAW264.7 cells are typically selected from macrophage cell lines to induce bone marrow-derived macrophages. Thus, during SARS-CoV-2 infection, cell death is induced by stimulating the release of pro-inflammatory cytokines [87]. Using the cell model of fluorescently labeled immune activation pathway as a screening platform, the immune activation characteristics of antiviral, immunomodulatory, and anti-inflammatory activities of different TCM prescriptions were compared. Different outbreak mutants were tested for antiviral, immunomodulatory, and anti-inflammatory effects, and IC50/IC90 values were used to evaluate antiviral effects. In macrophages and other cell lines, differences in the expression of inflammatory factors such as IL-6 and IL-10 within and between groups were tested, and the anti-inflammatory activity of TCM was evaluated. High Content screening (HCS) models are mainly established at the cellular level by observing the various functional effects of samples on the morphology, growth, differentiation, migration, apoptosis, metabolism, and signaling of fixed or dynamic cells. Targets involved include cell membrane receptors, intracellular components, and organelles [88]. Cell-level experiments can be performed to screen COVID-19-targeted drugs by inhibiting cell proliferation, inducing cell differentiation, inducing cell apoptosis, reversing drug resistance, and inducing autophagy. The biological activity test methods at the cellular level mainly include MTT, Cell Counting Kit-8 (CCK-8), and Sulforhodamine B (SRB). Combined with the pharmacodynamic evaluation and screening results at the molecular level, different cold-temperature drug properties and pharmacodynamic groups were determined.
3.2.3 Evaluate the efficacy of core prescriptions at the animal level
In HFH4-hACE2 transgenic mice, K18hACE2 transgenic mice, and hACE2-transgenic mice, the release of inflammatory cytokines such as interferon caused by SARS-CoV-2 can increase ACE2 expression and enhance infection 89, 90. ACE2 can be released from cells into circulation. In addition, the mouse genome is highly homologous to the human genome, and the mouse genome modification method has matured. Rhesus monkeys and rhesus monkeys are genetically and physiologically similar to humans, and the golden hamster infection model is used to test the efficacy evaluation indicators of each component, including anti-inflammatory, immunomodulatory, antiviral, and visceral protection. SARS-CoV-2, lipopolysac-charides (LPS), Toll-like receptors (TLRs) agonists, and superantigens (SAgs) can be used to induce novel coronavirus models. The effectiveness of this active formula and monomer in the prevention and treatment of immune, viral, and inflammatory abnormalities caused by COVID-19 virus infection was further validated in hACE2 transgenic mice and other models. It was determined that the treatment was efficacious when administered pre-infection and post-infection. The protective effect of the drug was confirmed by detecting changes in body weight, death protection status, changes in lung viral titers, pathological changes, inflammatory cell infiltration, and levels of inflammatory factors in animal models. Infection models have also been established, including in gold hamsters. Golden hamsters are also known to experience weight loss, lung pathological damage, and viral replication after infection, which can be used to evaluate antiviral drugs. Animal models of COVID-19 were constructed and administered in animal models (drug administration group and drug administration methods were set). Animal models were used for pharmacodynamic evaluation, and animal models reflecting pharmacological effects were selected. The clinically recommended dosing method was used for reasonable grouping, and the main pharmacodynamic indexes and secondary pharmacodynamic indexes were detected. Combined molecular and cellular pharmacodynamic evaluation, different cold and temperature characteristics were screened and obtained, and the efficacy was grouped.
According to the pathological processes of COVID-19 virus recognition of host cells, virus replication, and host immune inflammation regulation, the existing efficacy evaluation system was improved in multiple dimensions, and the simulation of different pathological types and the selection of pharmacodynamic evaluation models were strengthened (Table 2 ). Recombinant protein expression and purification platforms for COVID-19 virus recognition of host cell receptors to S proteins, key hydrolases 3CLpro and PLpro, cGAS and Sting, and key target proteins in other native immunomodulatory pathways were proposed. Many high-quality protein samples with high purity, high activity, and uniform morphology were obtained for viability testing and complex structural analysis. Furthermore, according to the physiological characteristics and functional modules of the cell model, and according to the species categories and associations of Vero E6, human lung adenocarcinoma cell Calu3, human colorectal adenocarcinoma cell Caco2 and other cell lines, immune cell unit, virus-cell unit and inflammatory cell unit were added through cell line database screening and in vitro experiments. Based on existing animal models such as mice, hamsters, rhesus macaques, and targeted ACE2 genes, animal species and targeted genotyping were further expanded by host global and local selective gene knockout technology. Multi-dimensional analysis of antiviral active ingredients and immunomodulators in TCM prescriptions. To clarify the material basis and mechanism of action of TCM formulas in the treatment of COVID-19, comprehensively use modern biology, immunology, laboratory zoology, and other multidisciplinary technologies to analyze key scientific issues such as antiviral active ingredients and immune function components of TCM formulas from molecular, cellular, animal, and other dimensions. The molecular mechanisms of the interaction between active ingredients in TCM prescriptions and antiviral proteins and host immune pathways were analyzed, and their effectiveness was verified at the cellular and animal levels. To provide the material basis and mechanism of action for the treatment of COVID-19, guide the better application and optimization of TCM formulas, and make emergency reserves for dealing with new infectious diseases.Table 2 shows the model and methodology for evaluating core prescriptions.
Table 2Evaluate core prescriptions Models Methods
molecular level Homo-Trimeric spike glycoprotein (S protein) ,
Nucleocapsid (N) protein ,RdRp (Multi-subunit RNA-dependent RNA polymerase) ,3CLpro (3C-like protease, named after the 3C proteases of the Picornaviridae) ,Stimulator of Interferon Genes (Sting) molecular docking , molecular modeling molecular dynamics (MD) , structure-activity relationship (SAR) , enzyme activity detection method , protein thermal stability tests , isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), time-resolved energy transfer (TR-FRET) , enzyme-linked immunosorbent assay (ELISA)
cell level The monkey kidney cell lines Vero E6, Vero and Vero81,human lung adenocarcinoma cell Calu3 , human liver cells Huh7 , colorectal adenomas Caco2 High Content screening (HCS) ，inhibition of cell proliferation, induction of cell differentiation, induction of apoptosis, drug resistance reversal, induction of autophagy
animal level HFH4-hACE2 transgenic mice ，K18hACE2 transgenic mice ，hACE2 transgenic mice ，rhesus monkey models SARS-CoV-2, lipopolysac-charides(LPS), Toll-like receptors (TLRs) agonists, and superantigens (SAgs) can be used to induce the novel coronavirus model . animal models of COVID-19----drug administration was performed in animal models---pharmacodynamic evaluation
3.3 Mechanism interpretation
3.3.1 Study on the mechanism of core prescription regulating host immunity
Patients with COVID-19 exhibit an abnormal immune response, causing a cytokine storm that leads to acute respiratory distress syndrome (ARDS) and ultimately death [91] . Taking NK cells, macrophages, T cells, plasma cells, and other immune cells as in vitro research objects, innate immune cells include granulocytes (neutrophils, eosinophils, basophils, mast cells), monocytes/macrophages, dendritic cells (DC), natural killer cells (NK), T lymphocytes and innate lymphocytes (ILCs) [92]. Il-6, TNF-α, macrophage inflammatory protein 1-α (MIP-1α), MCP3, GM-CSF, IL-2, IP-10, and chemokines (IP-10, CCL/MCP1, CXCL1, CXCL5) are also elevated in SARS-CoV-2 [93, 94, 95, 96]. Patients with severe COVID-19 had significantly fewer CD4+, CD8+, B cells, and NK cells, and fewer monocytes, eosinophils, and basophils. The total number of T cells, including helper and suppressor T cells, in COVID-19 patients, was significantly reduced [97]. In vitro studies, ACE2 series transgenic mice, COVID-19-infected monkeys, and golden hamster infection models were used to find effective formulations to modulate host immunity. Using multidisciplinary technologies such as single-cell sequencing, flow cytometry, immunofluorescent labeling, protein imprinting, immunohistochemistry, etc., the culture system, immune cell activity, lethality rate, protein genes in immune factors, immune-related genes, etc. were quantified, and stereotyped, and the effectiveness and critical path of monomer components and the intrinsic mechanism of host immunomodulation was verified by preventing and treating the most drugs.
3.3.2 Study on anti-inflammatory mechanism of core prescription
The inflammatory response of infected cells may further induce immune cell infiltration into the lungs, leading to the overproduction of pro-inflammatory cytokines and severe lung damage, and multiorgan dysfunction [98]. After SARS-CoV-2 infection, the expression of p38 MAPK, NF-kB, IL-6, IL-8, and other inflammatory factors changes [99]. Patients with severe COVID-19 have many activated pro-inflammatory cytokines and chemokines, including IL-2, IL-6, IL-10, TNF-α, GSCF, and MCP-1 [100]. Spike proteins promote the 1-mediated signaling cascade by activating MAPK and increasing IL-6 release, inducing transcriptional regulatory molecules NF-KB and AP-1/C-FOS [101]. To study the anti-inflammatory effect of effective prescription, lipopolysac-charides-induced RAW 264.7 cells, BV2 cells, and other cell lines were used as in vitro research objects, and lipopolysac-charides -induced inflammation was taken as animal models such as Wistar and SD rats as in vivo research objects, through effective prescription, preventive administration, and therapeutic administration. In each group, HE staining was used to observe the thickness of the alveolar and bronchial walls, inflammation, hyperlipidemia, and edema. Enzyme-linked immunosorbent assay, western blot, and flow cytometry were used. Expression of IL-6, IL-10, TNF-α, IL-1 β, and other inflammatory factors, as well as expression of key targets of genes, proteins, and related pathways suggested by various omics results, as well as molecular mechanisms of inflammation.
3.3.3 Mechanism of core prescription protecting multiple organs
Multi-organ failure is the leading cause of death in people with COVID-19. Pathologic examination of biopsy specimens from patients with COVID-19 suggests that inflammatory cell infiltration is common in the lungs, heart, kidneys, liver, and other organs [102]. The impact of the COVID-19 lung injury model suggests that ACE2 experimental cells (respiratory epithelial cilia and type 2 alveolar cells) are lost and ACE2 is under-vascular, resulting in endothelial cell damage, vasoconstriction, thrombosis, and interstitial edema, affecting multiple organs of the body 103. In this study, a mouse model of lipopolysac-charide-induced inflammation, a mouse model of bleomycin-induced pulmonary fibrosis, an animal model of humanized ACE2, a novel coronavirus-infected monkey, and a golden hamster infection model were used in vivo to study the effective prescription mechanism of multi-organ protection. Histopathology, imaging, molecular biology, and other methods were used to test the efficacy of TCM. Multiple organs were stained by pulmonary function tests (resting ventilation, airway resistance, lung volume), liver and kidney function tests, blood-brain barrier, visceral ultrasound, internal microcirculation, etc. Cellular edema, cell degeneration injury, organ fibrosis, edema, and other tissue damage were evaluated. Combining inflammatory factors and immune factors, the results of multi-recombination suggested the key targets of the expression of genes, proteins, and related pathways, and interpreted the molecular mechanism of organ damage caused by effective protective agents of COVID-19 from multiple levels and angles.
The multilayered mechanisms of COVID-19, including pathogenic mechanisms, evolution, and organ damage, are still being studied. Quantification and high-throughput detection of multiple omics can further clarify the mechanism of occurrence and evolution of COVID-19, as well as the mechanism of action of TCM from planar to stereological, from static to dynamic, and from morphological to functional. Animal models such as ACE2 transgenic mice, COVID-19 virus-infected monkeys, and golden hamsters were selected for studies. An effective formulation was used as an intervention, and the concentration of the intervention drug was determined by the equivalent dose conversion between animals and humans. High-throughput proteomics, transcriptomics, genomics, and other omics tests were performed on serum, feces, and lung tissues. After clarifying the host associated with COVID-19 virus infection, the differential expression of proteins, lipids, and genes in the baseline, middle, and post-Liao groups expanded the mechanism spectrum from different levels, laying a biological foundation for in-depth interpretation of the mechanism of TCM(Fig.1 ).Fig.1 presents a multi-dimensional comprehensive therapeutic system based on molecules, cells and animals, exploring targeted TCM that can improve inflammation, regulate immunity, and protect organs for the treatment of COVID-19.
Fig.1
3.4 Evaluation of drug properties
By establishing a multi-dimensional drug evaluation system that integrates molecular, cellular, and animal characteristics of core formulas, effective formulas were evaluated, different drug characteristics and efficacy groups were obtained, and specific and targeted innovative TCM formulas were us the treatment of COVID-19 were determined. Explain its mechanism with modern technology and complete early drug evaluation. The evaluation of medicinal properties includes five points, (1) Molecular structure characteristics, hydrogen bond binding, PSA, lipophilicity, SHAPE, molecular weight, pKa. (2) Physical and chemical properties, solubility, permeability, and chemical stability. （3）ADME. (4) PK characteristics, clearance, half-life, bioavailability. (5) Toxicity, LD50, DDI, hERG, genotoxicity. The basic principles for evaluating the medicinal properties of Chinese medicines in the new target are absolute effectiveness and reasonable safety. For new approaches based on theory or research results, the effectiveness and safety of their use should be emphasized. For traditional formulas that have entered clinical application, such as classical formulas and prescriptions, attention should be paid to their medicinal properties and efficacy verification, because their effectiveness has been clinically verified. Many new techniques and theories can be used for pharmacodynamic evaluation, including high-throughput screening, high-intention screening, proteomics, genomics, metabolomics, epigenetics, epipharmacology, phenotypic screening, computer, and transgenic technologies. In addition, there is computer modeling technology, network pharmacology technology, bioinformatics, systems biology technology, model biotechnology, biochip technology, molecular biotechnology, cell biotechnology, comprehensive target technology, and so on.
Discussion
1 Advantages and disadvantages compared to existing models
Compared with the existing models, this paper constructs a complete COVID-19 targeted drug discovery model and constructs a multi-dimensional comprehensive efficacy evaluation system integrating molecular drugs, cellular drugs, and animal drugs. Mechanisms of effective prescriptions such as protection of organs. Multi-dimensional analysis of antiviral active ingredients and immunomodulatory functional ingredients in TCM prescriptions, clarifying the material basis and mechanism of TCM prescriptions for the treatment of COVID-19, and comprehensively using modern biology, immunology, laboratory animals, and other multidisciplinary technologies. The active and functional components of TCM prescriptions were analyzed from molecular, cellular, and animal perspectives. From the perspective of systems biology, the molecular mechanism of the interaction between the active ingredients in TCM prescriptions and key antiviral proteins and host immune pathways was effectively analyzed and verified from the cellular and animal levels. Through the multi-omics combined detection of effective prescriptions and selected effective monomers, the core mechanisms of effective prescriptions to improve lung inflammation, regulate immunity and protect internal organs were elucidated. Based on multidisciplinary research methods, we conduct drug evaluation and interpret the scientific connotation of effective targeted TCM in blocking mild and severe diseases, improving lung damage, and protecting the lungs. Solve the key issues of TCM in the treatment of COVID-19, such as how to play a multi-link, multi-target, and multi-level network mechanism around the interaction between the virus and the host, to reveal the mechanism of TCM to prevent and treat COVID-19, and discover drug targets to guide the research and development of new TCM, and establish a multi-dimensional technology system for the research and development of new anti-COVID-19 drugs. Complete the early pharmacological toxicity evaluation of the optimized new ingredients and develop new TCM-targeted prescriptions for the treatment of COVID-19 with clear ingredients and clear mechanisms of action. Therefore, compared with the current model, the current targeted drug exploration model mostly comes from viral proteins or computer simulations, lacking effective basic research, and the multi-dimensional drug efficacy evaluation system in this article is exploring the targets for the treatment of COVID-19 from multiple aspects It has certain advantages in terms of drugs.
However, targeted TCM also has certain limitations. There are still many uncertainties about COVID-19, and some of the 29 proteins expressed by SARS-CoV-2 have not yet been identified, so there may be certain limitations in the exploration of targeted TCM. In addition, the COVID-19 virus continues to evolve. Since the emergence of the SARS-CoV-2 virus, it has continued to evolve. WHO has so far designated five variants as SARS-CoV-2 Variants of Concern (VOC) – Alpha, Beta, Gamma, Delta, and Omicron – due to differences in transmission, disease severity, or immunity 103. Therefore, the exploration of targeted Chinese medicine is also difficult and limited. At the same time, it takes a certain amount of time to establish a complete exploration model of COVID-19 targeted drugs and a multi-dimensional comprehensive efficacy evaluation system, and there are also certain requirements for the experimental process. Therefore, it will take longer and more research than the existing model.
2 Summary
Effective formulations are effective in the treatment of COVID-19. To deal with new infectious diseases and discover innovative and effective drugs against COVID-19, it is necessary to establish a pharmacodynamic evaluation system to discover effective molecules, ingredients, and formulations quickly and efficiently. Therefore, a comprehensive pharmacodynamic evaluation system is essential. This article established a complete COVID-19 targeted drug discovery model, and a multi-dimensional integrated effect evaluation system of molecules, cells, and animals was constructed. 19 Targeted TCM treatment provides new ideas and directions based on experiments and lays a good foundation for future clinical work. Prepare for new infectious disease outbreaks while making emergency stockpiles.
Competing interests
The authors declare that they have no competing interests
Contribution to the Field Statement
COVID-19 is a pandemic in the world and needs to be supplemented at the therapeutic level by specific targeted drugs. Traditional Chinese medicine has played an effective role in the fight against COVID-19. If more accurate and effective targeted drugs are found, they can provide a choice for the treatment of COVID-19. Explore the pattern of targeted drugs at present is mainly based on protein structure and computer simulation, but there is still no complete targeted drug screening model, this paper builds a molecule, cell, and animal multi-dimensional integration of efficacy evaluation system, and studies the mechanism of effective agent including improving inflammation, immune regulation, protect organs, discovery targeting Chinese medicine for the treatment of COVID - 19.
No data was used for the research described in the article.
Declaration
Author contribution statement
Yuting Sun, Xuedong An: Conceived and designed the experiments; Analyzed and interpreted the data; Wrote the paper. </p>
Liyun Duan, Yuehong Zhang, Cunqing Yang, De Jin, Yingying Duan, Rongrong Zhou, Yiru Zhao, Yuqing Zhang, Xiaomin Kang, Linlin Jiang: Analyzed and interpreted the data; Wrote the paper. </p>
Fengmei Lian: Conceived and designed the experiments; Contributed reagents, materials, analysis tools or data. </p>
Funding statement
FengMei Lian was supported by 2015 Traditional Chinese Medicine Scientific Research [201507001-11], Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine. [ZYYCXTD-D-202001], The National Key Research and Development Program [2020YFC0845000], TCM Emergency Response Special Project for Novel Coronavirus Infection [2020ZYLCYJ04-1].
Data availability statement
No data was used for the research described in the article.
Declaration of interest’s statement
The authors declare no competing interests.
Additional information
No additional information is available for this paper.
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| 0 | PMC9737519 | NO-CC CODE | 2022-12-14 23:29:54 | no | Heliyon. 2022 Dec 10;:e12333 | utf-8 | Heliyon | 2,022 | 10.1016/j.heliyon.2022.e12333 | oa_other |
==== Front
Array (N Y)
Array (N Y)
Array (New York, N.y.)
2590-0056
The Authors. Published by Elsevier Inc.
S2590-0056(22)00104-7
10.1016/j.array.2022.100271
100271
Article
Combating Covid-19 using machine learning and deep learning: Applications, challenges, and future perspectives
Paul Showmick Guha a
Saha Arpa a
Biswas Al Amin a∗
Zulfiker Md Sabab a
Arefin Mohammad Shamsul ab
Rahman Md Mahfujur a
Reza Ahmed Wasif c
a Department of Computer Science and Engineering, Daffodil International University, Dhaka, Bangladesh
b Department of Computer Science and Engineering, Chittagong University of Engineering and Technology, Chittagong, Bangladesh
c Department of Computer Science and Engineering, East West University, Dhaka, Bangladesh
∗ Corresponding author.
10 12 2022
10 12 2022
10027128 10 2022
5 12 2022
7 12 2022
© 2022 The Authors. Published by Elsevier Inc.
2022
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
COVID-19, a worldwide pandemic that has affected many people and thousands of individuals have died due to COVID-19, during the last two years. Due to the benefits of Artificial Intelligence (AI) in X-ray image interpretation, sound analysis, diagnosis, patient monitoring, and CT image identification, it has been further researched in the area of medical science during the period of COVID-19. This study has assessed the performance and investigated different machine learning (ML), deep learning (DL), and combinations of various ML, DL, and AI approaches that have been employed in recent studies with diverse data formats to combat the problems that have arisen due to the COVID-19 pandemic. Finally, this study shows the comparison among the stand-alone ML and DL-based research works regarding the COVID-19 issues with the combinations of ML, DL, and AI-based research works. After in-depth analysis and comparison, this study responds to the proposed research questions and presents the future research directions in this context. This review work will guide different research groups to develop viable applications based on ML, DL, and AI models, and will also guide healthcare institutes, researchers, and governments by showing them how these techniques can ease the process of tackling the COVID-19.
Keywords
Machine learning
Deep learning
Artificial intelligence
Pandemic
COVID-19
==== Body
pmcNomenclature
SVM Support Vector Machine
BERNOULLI INB Bernoulli Naive Bayes
RF Random Forest
LR Logistic Regression
KNN K-Nearest Neighbor
DT Decision Tree
RBFK-SVM Radial Basis Function SVM
RNN Recurrent Neural Network
ANN Artificial Neural Network
ADB Adaboost
NB Naive Bayes
GB Gradient Boosting
QDA Qualitative Data Analysis
RFE Recursive Feature Elimination
LASSO R Lasso Regression
XGB Xgboost
MLP Multilayer Perceptron
NCA Necessary Condition Analysis
DEREx Differential-Evolution-based Rule Extractor
DAE De-noising Auto Encoder
LASSO Least Absolute Shrinkage and Selection Operator
ConvLSTM Convolutional Long Short Term Memory
IMFCC Improved Multi-frequency Cepstral Coefficients
CRNN Cascaded Recurrent Neural Network
LDA Latent Dirichlet Allocation Model
LDA Linear Discriminant Analysis
GFCC Gamma-tone Frequency Cepstral Coefficients
KW Kruskal-Wallis
EDLN Ensemble Deep Learning Network
DBN Deep Belief Network
BN Bayesian Network
SAE Stacked Auto-Encoder
DCNN Deep Cnn
PK Polynomial Kernel
FM Fusion Model
SWEM Semantic Word Embedding Models
LGBM LightGBM
LK Linear Kernel
ARIMA Autoregressive Integrated Moving Average
RBF Radial Basis Function
OR One Rule
RBF KERNEL Radial Basis Function (Gaussian) Kernel
PCA Principal Component Analysis
GPR Gaussian Process Regression
FR-CNN Faster RCNN
CAPS Net Capsule Neural Network
DTL Duplication Transfer Loss
ET ExtraTrees
GRAD-CAM Gradient Weighted Class Activation Mapping
MFCCs Mel Frequency Cepstral Coefficients
SGAN Semi-Supervised Gan
BD-LSTM Bi-directional LSTM
SHAP Shapley Additive exPlanations
NN Neural Network
SGD Stochastic Gradient Descent
LSTM Long Short-Term Memory
CNN Convolutional Neural Network
MNB Multinomial Naive Bayes
MLIO Machine Intelligence Learning Optimizer
GBDT Gradient Boosted Decision Trees
LDA Latent Dirichlet Allocation
TCN Temporal Convolutional Network
L-SVM Lagrangian Support Vector Machines
LRG Linear Regression
GBM Gradient Boosting Machine
PR Polynomial Regression
ET Extremely Randomized Trees
HHOSVC HHO-Based Support Vector Classifier
HHOLGB HHO-Based Light Gradient Boosting
BSOA Bayesian Search Derived Optimal Architecture
HHORF HHO-Based Random Forest
GNB Gaussian Naive Bayes
BT Bagged Trees
HHOXGB HHO-Based EXtreme Gradient Boosting
MKNN Medium Knn
ANOVA Analysis of Variance
DTL Deep Transfer Learning
HHOCAT HHO-Based Categorical Boosting
GA Genetic Algorithm
TDT Temporal Decision Trees
TRF Temporal Random Forests
FFNN Feed-Forward Networks
DNN Deep Neural Network
PSO Particle Swarm Optimization
JLM Joint Learning Model
WSDL Weakly Supervised Deep Learning Model
IPCNN Iteratively Pruned Ensemble Convolutional Neural Network
DECNN Dense CNN Models
ED-LSTM Encoder-decoder LSTM
PARL Prior-attention Residual Learning
AGGDF Adaptive Feature Selection Guided Deep Forest
GCNN Genetic CNN
GRU Gated Recurrent Unit
TF-IDF Term Frequency–Inverse Document Frequency
SCNN Self-Customized Simple CNN
SIFT Scale-Invariant Feature Transform
BRISK Binary Robust Invariant Scalable Key-Points
CCGA Continuous Conditional Generative Adversarial Network
DLCRD Deep Learning-based Chest Radiograph Diagnosis
ADAM Adaptive Moment Estimation
PK-SVM Polynomial Kernel Support Vector Machines
BAG Bagging
1 Introduction
COVID-19, a new coronavirus, emerged in December 2019 as a cluster of deadly serious illnesses in Wuhan, China, and rapidly expanded as an outbreak [1]. The illness is driven by the virus SARS-CoV-2, referred to as COVID-19. WHO labeled COVID-19 a worldwide epidemic on March 11th, 2020 [2]. Therefore, as an outcome of this pandemic, more than six million people have died throughout the world [3]. The COVID-19 pandemic spread worldwide, infecting millions of people. Fig. 1 depicts a worldwide heat map of COVID-19 epidemic deaths.Fig. 1 Global heat map of the COVID-19 outbreak death per capita [4].
Fig. 1
The most typical signs of the COVID-19 infection include terrible cough, failure of flavor and aroma, migraine, exhaustion, and lung ailments such as breathing problems [5,6]. However, medical images such as Chest X-ray (CXR), ultrasonography, computerized tomography (CT), and other imaging techniques have become significant options for diagnosing COVID-19 infection. Because of the extreme contagiousness of this virus, a rapid and precise diagnosis approach is unquestionably essential for combating this pandemic. Many coronavirus diseases like SARS and MERS can persist in a host species without any symptoms. Contagiousness of this virus, a rapid and precise diagnosis approach is unquestionably essential for combating this pandemic. Many coronavirus diseases like SARS and MERS can persist in a host species without any symptoms. Sometimes these diseases create extremely weak and non-characteristic signs in the infected individuals, sometimes these diseases create extremely weak and non-characteristic signs in the infected individuals, Fig. 2 shows the growth pattern of the COVID-19 spread. It can be found that the growth is exponential. Therefore, it may be possible to predict the upcoming COVID-19 wave and be prepared early for it, saving thousands of lives, making prompt detection and treatment of these infections difficult [7] (see Fig. 3).Fig. 2 Growth curve for cases by region with cases per capita [4].
Fig. 2
Fig. 3 Prisma flow diagram of the selection process of the study based on inclusion and exclusion criteria.
Fig. 3
Since the outbreak of the COVID-19, governments of different countries have implemented strict lockdowns in large cities and urban areas to avoid large gatherings of people and reduce the infection's impact. COVID-19 has various clinical signs in its early stages, including malaise, migraine, headache, difficulty breathing, muscle pain, dry mouth, backache, vomiting, and stomach cramps [8,9]. The most prevalent signs for COVID-19 are lack of flavor and aroma [10]. Governments and regulatory organizations throughout the world have implemented a no-compromise lockdown to preserve social isolation and so limit the epidemic as daily notifications of new breakouts have been flooding in at an unprecedented rate. The most impacted nations have closed their borders to transit and travel to stop the spread of COVID-19. In this global health emergency, the health sector is actively searching for new technology and strategies to monitor and manage the spread of the coronavirus epidemic. AI is currently one of the most effective uses of technology since it can monitor the spread of the Coronavirus, assess its danger and severity, and measure its development rate.
AI is a vast field with several sub-fields that may be used to address difficult issues in our daily lives. Learning, planning, representing information, and seeking are some of these sub-areas. The RT-PCR is currently most widely utilized approaches for COVID-19 detection. Using various data types with different AI-based methods, multiple applications have been developed that can now be used as a replacement for traditional RT-PCR tests. Utilizing different AI-based applications, patient management is becoming more effective, as these applications can efficiently predict patients' conditions and needs for hospitalization. The identifying and detecting COVID-19 by AI using CXR can early detect the disease and can be automated as a replacement for RT-PCR. AI has been used in forecasting the upcoming waves of the COVID-19 outbreak. By employing different ML, DL, and AI-based models, sentiment analysis of the public opinions regarding the pandemic has been performed. Also, these models have been used to identify hoax or fake information regarding the COVID-19 pandemic. Which eventually helped to raise public awareness against the pandemic. The ML, DL, and AI-based classification and screening techniques have been used to fine-tune and explore new methods that can more adequately classify and improve the accuracy of detecting the COVID-19 disease. Thus these techniques can be helpful for COVID-19 management. The widespread use of various techniques of AI for different purposes is driving the way to manage and combat of COVID-19 more efficiently.
Therefore, we have taken the initiative to analyze and explore studies that utilized various techniques in the field of AI to combat COVID-19-related challenges. The following are some of the contributions of our review study:• Various techniques currently utilized in the field of AI have been explored, and the optimal and most utilized techniques with respect to various data types have been filtered.
• This study outlines future research directions and challenges to the researchers who wants to pursue study in the related field.
• The proposed six state-of-the-art questionnaires that tend to uncover issues, future perspectives, and analysis of the current studies to manage COVID-19 have been addressed.
The organization of the remaining sections is as follows: the review methodology used to conduct the study is discussed in section 2. Section 3 of this study presents the analysis and findings. Section 4 of this study presents finding and analysis of the proposed research questions. Section 5 discusses the challenges and the potential scopes for future research to combat COVID-19. Finally, the study is concluded in section 6.
2 Review methodology
As shown by Brereton et al. [11], a review of studies is a technique of discovering, analyzing, and interpreting every accessible material on a particular study topic or topic of attention.
In this study, a comprehensive literature search has been carried out in response to a collection of research queries. Besides, a safe, robust, and quantifiable procedure has been utilized to provide the answer to those concerns.
2.1 Search strategy
Multiple online academic search engines such as Scopus, Web of Science, ERIC, PubMed, Science Direct, IEEE Xplore, DOAJ, and Google Scholar were utilized to obtain related studies. Table 1 summarizes the keywords that have been applied to extract the relevant works. Relevant studies were mostly chosen by manually using these keywords in various combinations. Some samples of the combinations are (‘COVID-19′ or 'coronavirus' or ‘CoV2′ and ‘machine learning’), (‘coronavirus' or ‘CoV2′ or ‘COVID-19′ and ‘deep learning’), (‘COVID-19′ or 'coronavirus' or ‘CoV2′, ‘machine learning’, and ‘prediction’), etc.Table 1 Applied keyword
Table 1machine learning artificial intelligence deep learning coronavirus prediction classification detection
diagnosis identification pandemic sentiment analysis CoV2 covid-19 ML
combination DL AI
2.2 inclusion and exclusion criteria
In this study, only the relevant works published in the English language have been considered. The inclusion and exclusion criteria for considering the related works are as followings:
Inclusion criteria:(a) Papers that propose at least one ML, DL, or combinations of ML/DL/AI models.
(b) Studies that discuss at least one of the COVID-19 issues.
(c) Studies performing experimental works on different datasets related to COVID-19.
Exclusion criteria:(a) Research works published before 2020.
(b) AI, ML, and DL-based techniques mentioned in research articles which are not associated with the COVID-19 epidemic.
(c) COVID-19 issues mentioned in a research work that does not employ ML, DL, or combinations of ML/DL/AI approaches.
(d) Theoretical research with no practical applicability, survey papers, and review papers.
2.3 Selection of the study
In this step, the primary relevant works were selected based on the search strategy discussed earlier. By applying the aforementioned search strategy, 600 studies were identified and selected initially. The duplicate records or studies were then removed in the next phase. After removing the duplicate studies, a total of 512 works remained. 382 studies were excluded during the screening process. Abstract analysis, dataset analysis, and inclusion and exclusion criteria were used to filter the studies. A total of 130 research works became eligible for full-text analysis through the screening process. Later, these 130 research works were reviewed, and 26 of them were eliminated. In the last stage, a total of 104 studies remained to be checked for their methodological qualities. Among those studies, a total of 16 studies were then excluded based on the methodological quality. After completing all these procedures, only 88 studies remained for the systematic review. Among the selected studies, 29 studies are from the Elsevier journals, 16 studies are from the Springer journals, 11 studies are from the MDPI journals, and 6 studies are from the Nature journals. On the other hand, equal numbers of studies have been collected from the Hindawi and the Wiley journals. From each of these two publishers, 3 studies have been considered. The least number of studies have been collected from the IOP science journals. Only 2 studies have been considered from the journals of this publisher. The remaining 8 studies are conference papers.
2.4 Extraction of the data
After selecting the studies, data extraction is very much important to analyze and interpret the studies properly. A general structure is required for the extracted data from studies to obtain meaningful findings. As a response, tables with some preset attributes were developed, and various data from the studies were added to the tables. The first attribute of the tables, “References and Year,” contains the authors’ name and the publication year. The second attribute defines the purposes of the studies. The third and the fourth attributes describe the data types used in the studies and the sample size of the studies, respectively. The fifth attribute specifies the major techniques applied in the studies. Finally, the last attribute mentions the best performing model with its performance.
2.5 Research questions (RQs)
This comprehensive and in-depth review mainly focuses on summing up, evaluating, and synthesizing different research works where several ML, DL, and combinations of ML, DL, and AI-based techniques have been considered. The primary goal of this study is to acquire the answers to the subsequent six research questions and to have a profound as well as a comprehensive understanding of the responses to these questions.RQ 1 What ML, DL, and combinations of ML, DL, and AI-based mechanisms are widely used in the studies related to COVID-19?
RQ 2 Until now, are there any standard datasets that are publicly available and may be used to analyze different ML, DL, and combinations of ML, DL, and AI-based techniques?
RQ 3 Are there any End-to-End Solutions (E2ES) available for COVID-19 diagnosis?
RQ 4 Which countries performed the most research relating COVID-19 by involving ML, DL, and combinations of ML, DL, and AI-based techniques?
RQ 5 What are the most widely utilized criteria for assessing various works already in existence related to COVID-19 using ML, DL, or combinations of ML, DL, and AI-based techniques? Are those criteria enough that have been employed in most of these studies?
RQ 6 What are the biggest challenges for the researchers who are currently planning to do research on COVID-19 using ML, DL, or combinations of ML, DL, and AI-based techniques?
3 Analysis and findings
Multiple studies have analyzed the application of ML, DL, and AI methods in COVID-19-related studies. Dogan et al. [12] have analyzed and reviewed the studies related to the uses of AI and ML mechanisms in the context of various COVID-19-related tasks. In that review study, various studies related to COVID-19 transmission prediction, diagnosis, and detection, and drug/vaccine development have been analyzed, and six predefined questions have been explored. However, the entire context of the COVID-19 pandemic and the application of DL techniques have not been explored in the study.
In another study, Islam et al. [13] reviewed various studies that have employed various AI and ML mechanisms in the process of fighting against the COVID-19 pandemic. Based on the objectives, the studies have been categorized into four groups such as disease detection, epidemic forecasting, sustainable development, and disease diagnosis. The application of various models has been reviewed and summarized. Furthermore, six research opportunities have been identified and summarized in the study. However, other objectives (sentiment analysis, vaccine development, etc.) and the application of DL techniques have not been explored.
A comprehensive review of the role of AI, drones, blockchain, and 5G to manage the COVID-19 pandemic has been done by Chamola et al. [14] The study explored the use of current technologies to combat the epidemic as well as its effect on the global economy. The role of Unmanned Aerial Vehicles (UAVs), blockchain, AI, and 5G, among others, in mitigating the effects of the COVID-19 outbreak has been explored and discussed in the studies.
Alballa et al. [15] reviewed recent reports on ML algorithms used in relation to the COVID-19 pandemic. In the study, the applications of ML for diagnosis and predicting patient mortality risk and severity were analyzed. The review includes studies published between January 2020 and January 2021. By assessing the studies, a small number of real-time E2E systems and a selection bias due to imbalanced data were identified. Despite analyzing the ML models for diagnosis and prediction, other COVID-19-related objectives such as detection, epidemic forecasting, etc. have not been considered.
Alafif et al. [16] review the studies conducted on the uses of ML and DL towards COVID-19 diagnosis and treatment. The review study provides a summary of the AI-based ML and DL procedures, the available datasets, performance, and currently available tools. By performing a comprehensive analysis of the current ML and DL approaches used to diagnose COVID-19, obstacles to conducting the studies have been highlighted. In addition, the study made some directions for future work. Although the study analyzed the uses of ML and DL approaches only for the diagnosis and treatment of COVID-19, other perspectives on the probable combination of ML, DL, and the COVID-19 pandemic were not covered.
Although various studies have been conducted to review the studies related to the use of ML, DL, and AI-based techniques for COVID-19 management. Very few studies have explored the uses of the possible combination of ML, DL, and AI mechanisms. Moreover, this study explored diverse perspectives on the COVID-19 pandemic, utilizing a variety of data types and combinations of data types. In addition, most recent studies conducted on ML, DL, and the combination of ML, DL, and AI-based mechanisms have been included, as well as some earlier relevant studies.
3.1 Distribution and context of the study
Among all the considered works, 92% of studies have been collected from different journals, and 8% of studies have been collected from different conferences. From Fig. 4 , it can be found that 96% of studies using ML models have been published in different journals, while the rest 4% of studies have been published in different conferences. The percentages of studies employing DL techniques published in journals and conferences are 80% and 20%, respectively. In terms of applying the combination of ML, DL, and AI-based techniques, 97% of the considered studies are journal papers. The remaining 3% of studies are conference papers.Fig. 4 Percentage of studies from different Journal & Conferences.
Fig. 4
Among the studies collected from the journals, 36% of the studies are from Elsevier, 20% are from Springer, 14% are from MDPI, 7% are from Nature, 4% are from Hindawi, 4% are from Wiley, 3% are from IOP Science, and 12% are from other journals according to Fig. 5 .Fig. 5 Percentage of the Journal paper collected from different publishers.
Fig. 5
The yearly distribution of the studies that were chosen for analysis is shown in Fig. 6 . In terms of the publication year, a total of 41 studies were published in 2022. On the other hand, 39 studies were included from 2021. Only 8 studies were included from 2020. In 2022, the studies using the combination of ML, DL, and AI-based models have the highest frequency. The majority of the included studies applying ML techniques were published in 2021. Only a limited numbers of studies employing ML and DL techniques were performed in 2020. Furthermore, no studies applying the combination of ML, DL, and AI-based techniques were included from 2020.Fig. 6 Year-wise distribution of the final selected studies.
Fig. 6
Fig. 7 shows the types of data that were used in various studies. The majority of the studies utilized datasets in image formats. Studies employing datasets in image formats used mainly MRI, CT, CXR, ECG, and X-ray images. The studies that used non-image datasets had mainly worked with different clinical, time-series, textual, and audio data. 54% of the total studies employed datasets of image format, the rest 46% studies used non-image datasets. 54% of the total studies employed datasets of image format. The rest 46% of the studies used non-image datasets.Fig. 7 Different types of data used in various studies.
Fig. 7
Among the image data types, CXR has the most significant percentage, with a percentage of 57%, followed by CT images with a percentage of 28%. X-rays and other images make up the remaining 15% of the data types.
Among the non-image data types, clinical data is the most frequently utilized data format, representing 41% of all the non-image data, followed by laboratory data, which represents 12% of all the non-image data. 11% data of the non-image data are in time series format. On the other hand, 9% data of the non-image data are in text format. Furthermore, the percentages of audio-sound data, blood test data, and RT-PCR data are 8%, 5%, and 3%, respectively. 11% of the non-image data are of other different data formats.
3.2 Applications of machine learning to combat COVID-19
ML is the area of AI that mainly focuses on building systems that are capable of learning without explicit programming to do so. At the beginning of the COVID-19 pandemic, ML algorithms were primarily utilized. Initially, these algorithms were utilized exclusively for geographical and area-wise COVID-19 spread analysis. These algorithms are now being used for various purposes in combating COVID-19. Currently, ML approaches not only can predict COVID-19 by using clinical and laboratory data but also can be used to derive much more complicated aspects of COVID-19. ML approaches show significant performance in the diagnostic process of COVID-19 by utilizing diverse data such as blood images, X-rays, ECG, CT scans, etc. Due to the usage of ML methods for extracting features from images, signals, and audio data, COVID-19's classification is improving day by day. As ML models achieve more desirable outcomes, they are increasingly being combined with other approaches. The use of several ML methods to address different COVID-19-related problems has been reviewed and presented in this section. Table II Table 2 shows the summary of various studies employing ML models to combat COVID-19.Table 2 A summary of different Machine learning-related studies for COVID-19.
Table 2References and Year Purposes Data Type Sample Size Model Best Model with Performance
Abdulkareem et al. [17],(2021) Classification Laboratory 600 RF, BERNOULLI NB, SVM SVM (Accuracy 95%)
Callejon-Leblic et al. [18],(2021) Prediction RT-PCR 777 LR, RF, SVM SVM (Mean Sensitivity of 80.74%)
Faisal et al. [19], (2021) Prediction Time Series, Categorical 92,400 LR, KNN, RBFK-SVM,
PK-SVM, ADB, NB, DT, RF, GB, QDA, ANN DT(Accuracy 90%)
Cabitza et al. [20],(2020) Detection Blood Test, Clinical 3 datasets (1624 patients) LR, NB, KNN, SVM CBC dataset (RF Accuracy 93%)COVID-19 dataset (KNNAccuracy 90%)CBC dataset (KNN Accuracy 90%)
Guan et al. [21],(2020) Prediction Clinical 1270 LASSO R, XGB XGB(Sensitivity 85%)
Alves et al. [22],(2021) Classification RT-PCR,Laboratory 5644 LR, RF, XGB, SVM, MLP, ENSEMBLE RF(Accuracy 88%)
Kukar et al. [23],(2021) Diagnosis Blood test, Clinical 5333 RF,SVM,NN, XGB XGB(Sensitivity 81.9%)
Muhammad et al. [24],(2020) Prediction Clinical 263,007 DT, LR, NB, SVM, ANN DT (Accuracy 94.99%)
Zargari Khuzani et al. [25],(2021) Classification X-ray 420 PCA,NN NN(Accuracy 94%)
Statsenko et al. [26],(2021) Prediction Clinical 560 GB, ADB, ET,RF, NN,LR NN(with top value AUC 0.86, With all value AUC 0.90)
Tran et al. [27],(2021) Detection Clinical 226 MILO MILO(Accuracy of 98.3%)
Rezaeijo et al. [28],(2021) Classification X-ray 178 ADB, BAG, GNB, DT, GBDT, KNN, RF, L-SVM, LR,RFE,MNB RFE + KNN(AUC 0.997)
Jimenez-Solem et al. [29],(2021) Prediction Clinical 5594 RF RF(ROC-AUC of ICU admission 0.802, ventilator treatment 0.815,and death 0.902)
Hassan et al. [30],(2021) Prediction Time Series COVID-19 Data.Jan 22- Feb 13 NN, SVM, BN, PR NN(R-Square score Confirmed Cases 0.989086182,Recoveries Cases 0.989356735,Deaths Cases 0.932880987)
Saadatmand et al. [31],(2022) Prediction PCR, Clinical 398 LR, RF, XGB, C 5.0, NN LR, and NNs achieved the highest Accuracy (86.42%)
Rehman et al. [32],(2021) Prediction X-ray,Clinical 646 DT, KNN, NB, ET, RF, SVM RF(Recall = 0.96)
Guerrero-Romero et al. [33],(2022) Identification Clinical Laboratory 1064 LR LR(Sensitivity 83%)
Debjit et al. [34],(2022) Prediction Clinical, Laboratory 1,023,426 HHOXGB, HHOLGB, HHOCAT, HHORF, HHOSVC HHOXGB(Accuracy 92.23%)
Almustafa [35],(2021) Prediction Laboratory 200,000 NB, SGD, J48, RF, KNN J48(Accuracy 94.41%)
Erdoğan and Narin [36],(2022) Classification Signal 1187 records ENSEMBLE, BT, SVM-LINEAR, LR, LDA, MKNN Ensemble-BT(Recall 90.54%)
Sciavicco et al. [37],(2022) Classification Audio 9986 TRF, TDT TRF(Accuracy 99.4%)
Pourhomayoun and Shakibi [38],(2020) Prediction Clinical 2,670,000 SVM, NN, RF, DT, LR,KNN NN(Accuracy 89.98%)
Li et al. [39],(2020) Diagnosis Clinical 413 XGB XGB(Sensitivity 92.5%)
Bayat et al. [40],(2021) Diagnosis Clinical, Laboratory 75,991 XGB XGB(Accuracy 86.4%)
Hussain et al. [41],(2022) Prediction Clinical 1085 SVM, DT, RF, LR RF(Accuracy 0.9924)
Fig. 8 shows the frequency of different ML models that have been used in the considered studies. The most frequently used ML model is RF in the considered works. The SVM model has achieved the second-highest spot, followed by the LR model with the third-highest spot. Models like NB, DT, XGB, KNN, and NN have also been used frequently on the other hand.Fig. 8 Applied ML models.
Fig. 8
Fig. 9 shows the percentage of studies by different countries employing ML models to combat COVID-19. The majority of the studies come from the United States. 20% of the studies were conducted in the United States. Each of the countries such as Bangladesh, Iran, and Italy contributed 8% of the studies. However, the remaining 14 countries provided significantly fewer studies using ML models to fight COVID-19-related issues (see Fig. 10).Fig. 9 Country-wise percentage of studies using ML Techniques.
Fig. 9
Fig. 10 Applied DL models.
Fig. 10
From Table 2, it is observed that, various types of data have been used to perform the various studies. According to our in-depth analysis and observations, in the majority of studies for classification purposes, the RF and XGB classification models performed most optimally with the clinical data type. Moreover, regardless of data type or study objective, XGB, RF, and NN models consistently outperform other machine learning algorithms.
3.3 Applications of deep learning to combat COVID-19
DL is a branch of ML that utilizes representation learning to tackle complicated problems. DL-based models, such as CNN, proposed Custom CNN, DCNN, and other methods have lately been used for COVID-19 classification, diagnostics, and detection, by researchers to combat the COVID-19 outbreak. This study has reviewed the application of various DL approaches for combating the COVID-19 epidemic as well as performed comparisons between them. Table III Table 3 shows the summary of the studies employing DL techniques relating to COVID-19 issues.Table 3 A summary of different deep learning-related studies for COVID-19.
Table 3References and Year Purposes Data Type Sample Size Model Best Model with Performance
Ferroukhi [42],(2022) Diagnosis CT 4708 VGG16, RESNET 50, MOBILENET, GOOGLENET, XCEPTION, DENSENET121 RESNET 50 (Accuracy 90%)
Sitaula and Hossain [43], (2020) Classification CXR Three datasets of(1125,1638,2138 image per dataset) VGG16,VGG19,PROPOSED(ATTENTION-BASED VGG-16) ATTENTION-BASED VGG-16(Accuracy (79.58%, 85.43%, 87.49%))
Gour and Jain [44], (2021) Classification CXR Three datasets includes (3040,627,2905) CXR VGG19,RESNET-152, XCEPTION,DENSENET-169,MOBILENET, NASNET LARGE,INCEPTION-V3, EFFICIENTNET(B0–B5),PROPOSED(UA-CONVNET) UA-ConvNet(Sensitivity multiclass = 98.02%, binary = 99.16%)
Khan et al. [45],(2022) Diagnosis Clinical, Demographic,CXR 270 DEEP CNN, FFNN, EFFICIENTNETB7,FUSION MODEL Fusion model (Recall of 0.986)
Irmak [46],(2022) Classification ECG Trace 1937 CNN, RESNET-101,VGG-19, DENSENET,RESNET-50 V,GG-16,INCEPTIONV3 CNN-proposed model (Accuracy of 98.57%, 93.20%, 96.74%)
Shiri et al. [47],(2021) Detection CT 2558 COLI-NET COLI-Net(mean Dice coefficients 0.98 and 0.91 l for lung and lesions segmentation)
Malik et al. [48],(2021) Classification CT 660 RESNET-50, BDCNET, VGG-16, INCEPTION V3,,VGG-19, BDCNet(Recall of 98.31%)
Kumar et al. [49],(2021) Detection CXR 13,975 VGG-16, VGG-19,RESNET18,
ALEX NET,RESNET-50,SARS-NET
CNN,SARS-NET SARS-Net(Sensitivity 92.90%)
Mousavi et al. [50],(2022) Detection CXR 12,931 PROCEED (CNN-LSTM),
XCEPTION, RESNET50,INCEPTION,VGG 19 CNN-LSTM (Accuracy 90% all scenarios)
Kavya et al. [51],(2022) Detection CXR 15,153 VGG16, RESNET50 ResNet50 (Accuracy 91.39%)
Sundaram et al. [52],(2021) Classification CXR 4050 RSQZ-SEGNET RSqz-SegNet(Accuracy 99.69% binary 99.48% three class)
Luz et al. [53],(2021) Detection CXR 13,800 EFFICIENTNET B0-X,EFFICIENTNET B1-X
,EFFICIENTNET B2-X,EFFICIENTNET B3-X
,EFFICIENTNET B4-X,EFFICIENTNET B5-X
,MOBILE NET,MOBILE NET V2,RESNET50, VGG-16,VGG-19 Approach Flat EfficientNet B3-X(
Sensitivity of 96.8%)
Djuniadi et al. [54],(2022) Detection Images 4095 MOBILENETS V2 MobileNets V2(Accuracy 99%)
Chaudhary et al. [55],(2020) Detection CXR 14,000 EFFICIENTNET-B1 VGG-19, RESNET-50 COVIDNET EFFICIENTNet-B1 (Accuracy 95%)
Kogilavani et al. [56],(2022) Detection CT 3873 VGG16, DESENET121, MOBILENET
,NASNET, XCEPTION, EFFICIENTNET VGG16(Accuracy 97.68%)
Muralidharan et al. [57],(2022) Detection CXR D1 contains 1225 images, D2 contains 9000 images. MULTISCALE DCNN Multiscale DCNN(dataset A(multiclass and binary accuracy of 96% and100%)dataset B(multiclass and binary accuracy of 97.17% and 96.06%))
Haghanifar et al. [58],(2022) Detection CXR 9600 CHEXNET, COVID-CXNET. COVID-CXNet(Accuracy 87.88%)
Nassif et al. [59],(2022) Detection CXR,Audio 1159 sound samples 13,808 CXR Image LSTM, VGG16, VGG19, DENSNET201,RESNET50, INCEPTIONV3
INCEPTIONRESNETV2, XCEPTION LSTM (Accuracy of 98%)VGG16(Accuracy 89.64%)InceptionResNetV2(Accuracy 82.22%)
Nayak et al. [60],(2020) Detection CXR 406 ALEXNET,VGG16,GOOGLE NET,MOBILE NET-V2,SQUEEZENET,RESNET-34, RESNET-50,INCEPTION-V3 ResNet-34 (Accuracy 98.33%).
Verma et al. [61],(2022) Detection CT 63,849 RESNET50 V2, EFFICIENTNET B0 EfficientNet B0 (Sensitivity 99.69%)
Sim et al. [62],(2022) Detection CXR 5717 DENSENET121 DenseNet121(Sensitivity 95%)
Srivastava and Ruchilekha [63],(2022) Detection CXR, CT 4271 DEEPCOVX, DEEPCOVCT DeepCovX (Sensitivity 100%) DeepCovCT(Sensitivity 97.06%)
Muljo [64],(2022) Detection CXR 133,280 DENSENET121 DenseNet121(AUC average of 82.16, best AUC 99.99%)
Panwar et al. [65],(2021) Classification CXR 4563 CNN, ALEXNET CNN (Accuracy 98%)
Nasser et al. [66],(2021) Detection CXR 6000 RESNET50 ResNet50(Sensitivity 97.3%)
Among different DL models, the custom models have the highest frequency of 14, followed by the RESNET50 with the count of 12. Various versions of EFFICIENTNET, which are referred to as EFFICIENTNET(X) algorithms, have achieved the third highest spot with a number of 11. Among the next-most used DL models, VGG-16 and VGG-19 have been applied in 10 and 9 studies, respectively. Other models that consist of various DL models such as (NASNET, COVIDNet, INCEPTIONREST, LSTM, SQUEEZENE, etc.) have achieved the next position with a frequency of 8, followed by MOBILENET(X) with count of 7. Xception, InceptionV3, and DENSENET(X) have achieved the next spots. Each of these models have been used in 5 research works. Besides, various versions of RESNET, referred to as RESNET(X) have been used in studies with a count of 4.
From Table 3, it is observed that despite extensive uses of transfer-learning-based models, in the majority of the studies customized models have outperformed the transfer-learning-based model. From our analysis and observation, for COVID-19 detection-based works with CXR data type, proposed customized CNN models have outperformed the utilized transfer-learning-based CNN models. However, irrespective of the study's purpose and utilized data type in the uses of transfer-learning-based models, RESNET and DENSENET architecture-based models consisting of various versions have performed best in the majority of the studies. However, regardless of the type of image data used in deep learning-based research work, the usage of customized models may improve performance.
The country-wise percentage of the studies employing DL models is shown in Fig. 11 . In terms of using DL models to combat COVID-19, the majority of the research works were performed in India with a percentage of 44%. 8% of the research works were conducted in each of the following countries: Indonesia and Saudi Arabia. On the other hand, countries such as Algeria, Australia, Turkey, Switzerland, and all other countries have ranked in third place in terms of the number of research works employing DL methods.Fig. 11 Country-wise percentage of studies using DL models.
Fig. 11
3.4 Application of combination of ML/DL/AI to combat COVID-19
The combinations of ML, DL, and AI-based techniques are crucial in better understanding and dealing with the COVID-19 situation. The combinations of these methods are rapidly being used since these approaches can open up new avenues for various forms of diagnosis, sentiment analysis, public surveillance, and illness prevention. Several COVID-19 diagnostic approaches based on images aided by DL and AI-based techniques have been developed, and their association with RT-PCR has been evaluated. Image and non-image types of data are integrated by the combination of ML, DL, and AI-based methods to investigate several new alternatives to combat COVID-19.
The study demonstrates the combination of ML, DL, and AI methodologies and applications for COVID-19 warfare. Table 4 shows the summary of the combination of ML, DL, and AI-based techniques to combat COVID-19.Table 4 A summary of different combination of ml/dl/ai related studies for COVID-19.
Table 4References and Year Purposes Data Type Sample Size Model Best Model with Performance
Tariq et al. [67],(2021) Prediction EMR, Clinical 3194 FM, LR, LASSO R, XGB, RF, CNN FM (F1-score 84%)
Wang et al. [68],(2021) Classification CT 1418 V-NET, 3D U-NET++, DPN-92,RESNET-50, RESNET, FCN–8S, U-NET, INCEPTION NET-WORKS, ATTENTION RESNET-50 ResNet-50 with 3D U-Net++(Sensitivity 97.4%)
Chung et al. [69],(2021) Prediction Clinical 5601 ADB, RF, XGB, DNN DNN(Sensitivity 90.2%)
Afshar et al. [70],(2022) Diagnosis CT, Clinical 160 MLP, DNN Two‐stage time‐distributed capsule network(Sensitivity of 94.3%)
Sheela and Arun [71], (2022) Identification MRI 200 HYBRID PSO-SVM, SVM, PSO, DBN, SAE Hybrid PSO-SVM (Sensitivity 0.956)
Babaei Rikan [72],(2021) Diagnosis Laboratory, Blood Tests D1 279,D2 1624, D3 600 SVM, NB, ET, RF,LR, KNN, DT, XGB, DNN, CNN, LSTM, RNN DNN(D1 (accuracy 92.11%) D2 (Accuracy 93.16%) D3 (Accuracy 93.16%)
Yildirim et al. [73],(2022) Classification CXR 15,470 ALEXNET, RESNET50, GOOGLENET, DENSENET201,,DARKNET53, MOBILENETV2, EFCIENTNETB0,INCEPTIONV3, NCA, DT, DA, NB, SVM, KNN, SE Darknet53 + NCA + SVM(Accuracy 99.05 and 97.1%)
De Falco et al. [74],(2021) Classification CXR 13,808 BN, NB, RBF, SVM, AB, OR, DEREX RBF(Average Accuracy 79.60%) DEREx(Best Accuracy 80.67%)
Lella and Pja [75],(2021) Diagnosis Sound,Clinical 18,000 DAE, GFCC, IMFCC,DCNN, VGG NET, SVM DCNN (Accuracy 95.45%)
Hipolito Canario et al. [76],(2022) Identification CXR 722 M-QXR M-qXR(Identify pulmonary opacities Sensitivity 94) detecting pulmonary opacities were Sensitivity 94%) Identify pulmonary consolidation Sensitivity 91%) PPV 89.7% and NPV 80.4%
Kini et al. [77],(2022) Screening CT 12,146 JLM, AGGDF, WSDL, DECNN, DLCRD, PARL, GCNN, GOOGLENET,, IPCNN, RESNET152V2, DENSENET201, IRNV2, ENSEMBLED DL(PROPOSED) Proposed(Recall 98.58%)
Messaoud et al. [78],(2022) Detection Clinical, X-ray, CT 270 patient,2251 and 746 image LR, KNN, SVM, VGG19 VGG19(Accuracy 90%)
Liang et al. [79],(2022) Diagnosis CT 1,552,988 RESNET-18, RESNEXT50, GRU, DCNN, SVM, LK, PK, RBF KERNEL, DEEPLABV3, DENSENET121, GPR, FL FRAMEWORK Boosting (AUC 0.98), DL + FL(Dice's coefficient of 0.77)
Tan et al. [80],(2022) Classification CXR and CT Covid-19 1394, Pneumonia 11,712,Negative 20,431 COVID-NET, MULTI-MODAL Multi-modal(AUC 0.93)
Chen et al. [81],(2022) Diagnosis Sounds 1486 KNN, CNN, MFCCS CNN (Accuracy 97%)
Alkhaldi et al. [82],(2022) Sentiment Analysis Text 2750 TF-IDF,CRNN, RNN, RF,XGB,SVM, ET, DT, SFO, SFODLD-SAC SFODLD-SAC(Accuracy 99.65%)
Mahbub et al. [83],(2022) Screening CXR C1: COVID-191,200,C2: Pneumonia 3,875,C3:Tuberculoss 3,500,C4: Healthy 6182 RESNET50,RESNET152V2, PROPOSED DNN(COVTBPNNET),INCEPTIONNETV3,MOBILENETV2 CovTbPnNet Accuracy (healthy CXR Screening(99.87% on COVID-19, 99.55% on Pneumonia versus, for TB versus 99.76%) non–healthy CXR Screening(98.89% on COVID-19 versus Pneumonia, 98.99% on COVID-19 versus TB, and Pneumonia versus TB 100%))
Koç and Türkoğlu [84],(2021) Forecasting Time Series 77-day DEEP LSTM NETWORK, ADAM, LSTM, ARIMA, SVM, DT, LR The Deep LSTM network (beds, respiratory equipment, and cases number yielded MAPE values of (2.89%, 3.29%, and 4.80%) and R2 values (99.90%, 99.85%, and 99.72%), respectively)
Elharrouss et al. [85],(2021) Segmentation CT 100 U-NET,ATTENTION-UNET,GATED-UNET,DENSE-UNET,U-NET++, SEMI–INF–NET,MULTI-CLASS U-NET,DEEPLABV3+, FC8S, PROPOSED METHOD (MULTI-TASK DL METHOD) Proposed Method (78..6% Dice Score, 71.1% Sensitivity, 99.3% Specificity, 85.6% Precision, 0.062 Mean Average Error metric)
Loey et al. [86],(2022) Detection CXR 10,848 PROPOSED MODEL (BAYESIAN-BASED OPTIMIZED DEEP LEARNING MODEL) Proposed Model(Accuracy 96%)
Shastri et al. [87],(2021) Forecasting Time Series 421-days LSTM, BD-LSTM, CONVLSTM, COBID-NET ENSEMBLE CoBiD-Net ensemble model(Accuracy 98.10–99.13%)
Zhang et al. [88],(2022) Classification Time Series, Text 11,303,850 FINE-TUNING BERT, LRG, TF-IDF, KNN, SVM, DPCNN, EXPERT SYSTEM Fine-tuning BERT(Recall 99%)
Tavakolian et al. [89],(2022) Screening Clinical 5,435,996 LR, RF, XGB, SGAN SGAN (Accuracy 99.2%, 99.6% for COVID-19 and H1N1)
Choudrie et al. [90],(2021) Classification Text 143 SVM, DT, RF,SGD,LSTM, CNN DT (Accuracy 86.7%,Sensitivity 88.89%)
Saha et al. [91],(2021) Diagnosis
CXR 4600 EMCNET, CNN, RF,SVM, DT, ADB, ENSEMBLING EMCNet(Accuracy 98.91%,Precision 100%)
Zulfiker et al. [92],(2022) Sentiment Analysis Text 1075 LSTM, 1D-CNN, BI LSTM, TCN, DT, GB, SVM, LDA Bi LSTM with word2vec embedding(Sensitivity 88.52%)
Shiri et al. [93],(2021) Classification CT Images 14,339 CNN, LR, LASSO, LDA,RF, ADB, NB,MLP,ANOVA,KW, RFE,RELIEFv ANOVA feature selector, and RF classifier(Sensitivity 81%)
Aslan et al. [94],(2022) Classification CXR 2905 ALEXNET, INCEPTIONV3, RESNET18, SVM, RESNET50, ANN, DT, NB, DENSENET201, INCEPTIONRESNETV2, MOBILENETV2, GOOGLENET,KNN DenseNet201 and SVM (Sensitivity 96.42%)
Goel et al. [95],(2021) CXR 2700 2700 DT,KNN, SVM, NB,RF, CNN, SE,RESNET50,INCEPTIONV3,EDLN,
PROPOSED(MULTI-COVID-NET) Multi-COVID-Net(Sensitivity 99.63%)
Kanwal et al. [96],(2021) Detection CXR 18,394 DNN, CNN, 2DCNN, BDLSTM,SVM LINEAR,SVM RBF
,SVM POLYNOMIAL, LR COVID-OPT-AINET COVID-opt-aiNet(Accuracy SVM 98%–99%,
70.85%–71% CNN-96%–97% DNN)
Bhattacharyya et al. [97],(2021) Detection CXR 247 C-GAN, VGG-19,SCNN,DENSENET-169, VGG-16,DENSENET-201,SOFTMAX,SVM,RF, XGB,SIFT, BRISK VGG-19 with BRISK(Accuracy 96.6%)
Davazdahemami et al. [98],(2022) Prediction Clinical, Time Series 27,215 RF, GA, DNN, SHAP GA with DNN (AUC 0.883)
Karim et al. [99],(2022) Detection CXR 27,605 CNN, NB, SVM, SOFTMAX, KNN, DT NB + Ant Lion Optimization + CNN (98.31% Accuracy, 100% Precision)
Khan et al. [100],(2021) Prediction Epidemiological 2,676,311 DT, LR, RF, XGB,KNN, DNN DNN(Sensitivity 97%)
Dhruv et al. [101],(2022) Diagnosis CT 17,104 INRFNET AND INNET,DENSENET-121.RESIDUAL
ATTENTION, ENSEMBLE WITH FC,ENSEMBLE WITH FC + SVM InRFNet Sensitivity (94.48%)
Janbi and Elnazer [102], (2021) Diagnosis CXR 6308 SVM-LINEAR,SVM-POLYNOMIAL, SVM-RBF, VGG-16, INCEPTIONV3, XCEPTION, RESNET50, CCGAN, RESNET50(Recall 99.49%)
Islam and Nahiduzzaman [103], (2022) Detection X-ray 2482 GNB, SVM, DT, LR, RF, CNN, ENSEMBLE Ensemble (Recall 99.73%)
Alabrah et al. [104],(2022) Sentiment Analysis Text 464 records LSTM, SVM, FINE-KNN, ENSEMBLE, BOOST, TOTAL BOOST Fine-KNN and Ensemble boost (Accuracy 94.01%)
Fig. 12 shows that among the ML techniques, SVM has been the most frequently used model in the studies that utilized the combination of ML, DL, and AI-based It has been used in twenty-three studies. Other ML models like ARIMA, LRG, GB, Total Boost, etc., models have been used in 15 studies. Among the other ML models, RF, DT, KNN, LR, NB, and XGB models have been used in 13, 12, 10, 9, 8 and 7 studies, respectively. The ADB model has been used less frequently among the ML techniques.Fig. 12 Applied combination of ml/dl/ai models.
Fig. 12
Various AI techniques have been used most frequently in the studies. 44 works employed different AI-techniques to combat COVID-19. Different DL models such as ATTENTION RESNET-50, DBN, IPCNN, DECNN, DEEPLABV3, SGAN, etc., models have appeared in 19 different studies in total. CNN has been used in 14 studies. Various versions of RESNET, referred to as RESNET (X) has been used in 12 studies. Furthermore, LSTM is the next most frequently used model, followed by various versions of DENSENET and INCEPTION, which have been referred to as DENSENET(X) and INCEPTION(X).
From Fig. 12, it is observed that there is a trend to use custom models among the studies, which outperformed other DL models in terms of usage in different studies. However, various transfer learning DL models have been used frequently.
From Table 4, it is observed that there are diverse patterns or combinations of mechanisms that have been used to perform the studies. In studies using ML in combination with other techniques, the SVM (ML model) has been utilized and tends to perform better compared to other ML models. Therefore, to construct mechanisms combining the ML model with other techniques, researchers might consider using the SVM model. Furthermore, to perform the study on the amalgam of the various data types, it is important to combine techniques from various domains and examine the performance.
Fig. 13 Depicts the country-wise percentages of the studies employing the combination of ML, DL, and AI models. In India, 18% of the studies were conducted. Saudi Arabia carried out 13% of the studies. China, Bangladesh, and Turkey each conducted 11% of the studies. 8% of the studies conducted in the United States, whereas 5% were performed in Iran. The remaining 3% of the studies were conducted in other regions of the world.Fig. 13 Country-Wise Percentage of Studies Using Combination of ML/DL/AI models.
Fig. 13
3.5 Evaluation procedure for different study
Evaluation is studying a system, an initiative to determine how effectively a system fulfills its objectives. Evaluations assist in determining what works effectively and where improvements can be made in a program.
According to Fig. 14 , accuracy is the most used evaluation metric, followed by sensitivity/recall and AUC. Other metrics have been employed in a limited number of studies. Accuracy has been applied most frequently in the combination of ML, DL, and AI-based studies, while in ML and DL studies, accuracy metrics have been used equally. The sensitivity/recall metric has been mostly used in the studies employing the combination of ML, DL, and AI-based techniques followed by DL and ML-models-based studies. AUC metric has been used in all these three types of studies.Fig. 14 Performance evaluation metrics used in various studies.
Fig. 14
Specificity and R-Square have been only used in ML models-based and combinations of ML, DL, and AI models-based studies. ML-based studies haven't used the Dice scores. F1 score, precision, MAPE, and RMSE have been only employed in the combination of ML, DL, and AI models-based studies.
From Fig. 14 it is obvious that all three approaches use accuracy as the primary evaluation metric. Despite sensitivity/Recall being the second most utilized metric ML and DL-based studies have used this metric less frequently compared to accuracy. As misclassification of the COVID-19 disease can threaten the patient and their family's lives in addition to complicating COVID-19's spread control. Therefore, it is necessary to emphasized the sensitivity/recall metric more for evaluating the model's performance.
4 Finding and analysis of proposed research questions
In this section, the predefined research questions have been discussed. For each of the research questions, we have discussed the significance of the question as well as the findings based on the question that has been explored via the analysis of the studies. In addition, we have provided directions and some precautions for the researchers who aspire to conduct COVID-19 pandemic-related studies.
In the domain of AI, there are different types of algorithms, each with its own set of advantages and disadvantages. Many factors influence the model's performance in a positive or negative manner, resulting in less optimum performance and complicating the task of finding ways to combat COVID-19. As a result, it is necessary to identify widely used specific ML, DL, and AI mechanisms so that model selection for a certain purpose becomes simple and effective.
Various models have been applied in the application of the ML model in COVID-19-related tasks. The majority of the studies employed multiple ML models and compared the results. Therefore, the finding of some top-utilized models can be very beneficial. RF, SVM, LR, NB, XGB, and KNN are some of the most frequently used models. In addition to the use of specific ML models, various diversified but not widely used models have also been applied.
Analyzing the studies, it can be observed that XGB has performed as the best model among utilized ML mechanisms, followed by RF and NN. Therefore, while using the ML model for prediction, classification, detection, and diagnosis, XGB, RF, and NN models can be considered, which may aid in achieving the best possible result.
Many studies have developed custom models and compared them to other existing mechanisms in the use of DL relevant to the COVID-19 study. In the use of specific DL models, RESTNET50, EFFICIENTNET, VGG-16, VGG-19, and MOBIELNET have been the most widely applied models. Analyzing the studies, it can be shown that custom models performed the best among the used DL mechanisms, followed by ResNet-(X) referring to various versions of ResNet particularly ResNet-50.
In the application of the combination of ML, DL, and AI techniques related to the COVID-19 study, many studies applied the combination of diverse mechanisms and analyzed the performance, limitations, and potential of those mechanisms. Among the mechanisms, various AI techniques, SVM (ML model), custom models, diverse but not widely used DL models, CNN (DL model), and RF (ML model) are some of the widely applied mechanisms in the studies. Analyzing the studies and the best model, it can be found that the majority of the studies employed Al methods with ML or DL models and emphasize increasing the performance.
By analyzing the studies, we have observed that there is a significant association between model's performance and the pattern of data used in the studies. This was discovered by analyzing and observing the results of studies with a similar type of data that applied a variety of techniques. As a result, it is essential for the researcher to choose standard dataset and select the suitable model according to the data type. To perform a study with the usage of ML models in COVID-19-related work, the researcher might consider using XGB, RF, and NN models since they have outperformed other models and are widely used too. For performing a DL-based study, researchers should concentrate on constructing customized CNN models since they outperform transfer-learning-based DL algorithms most of the time. However, in the uses of the combination of ML, DL, and AI-based techniques, various studies have been used a diverse amalgam of techniques. Therefore, while conducting a study based on a combination of several techniques, it is essential to select and analyze possible combinations of techniques by reviewing previously conducted related work.
A dataset is one of the main defining parts of any study. Therefore, the dataset used in the studies needs to be trustworthy and standard. As the COVID-19 virus can mutate quickly, collecting virus-specific data is very challenging. To stop the spread and identify any mutated COVID-19 data should be collected in a short span of time. For this reason, sometimes there could be some lagging in the data collection procedure, which can create unbalanced and nonstandard data. Therefore, creating a standard dataset is important. Comparing the study results with the standard dataset is also important.
As COVID-19 is a global pandemic, many governments and NGOs have released open-access COVID-19 datasets, which mostly involve vaccination-related and spread-related datasets. But to identify the COVID-19 virus in the human body, an image type dataset is needed. Due to various constraints, there was a shortage of publicly available image datasets at the beginning of the period. Now there are some individual studies that have given open access to their dataset. But most of the individual datasets have some limitations, such as being unbalanced, lacking representative data samples, biased, and so on. Due to the data sample size quantity, some blanched datasets can't be categorized as standard datasets. Therefore, there is still storage of the global standard dataset, which can be used to reevaluate studies applying model performance. Furthermore, there is a lack of standard datasets related to sound and audio types of data for the COVID-19 disease. Also, there are very limited open-access sound-related standard datasets.
As there are shortages and limitations of data regarding COVID-19, the researchers have to check the quality and limitations of the dataset before conducting the research work. In addition, the collection procedure for research datasets should be standard, and the privacy of volunteers should be protected.
RT-PCR is the traditional method used to detect COVID-19 disease in the human body. Patients must physically visit a hospital to give samples for testing the suspected COVID-19 present in their bodies while using the traditional testing method. However, between the waves of the COVID-19 pandemic, visiting the hospital is a risky step. Because visiting the hospital in the middle of the COVID-19 wave can affect healthy people, who can further act as hosts and further spread the disease. Therefore, it is important to find some End-to-End solution based on AI, which can remotely and effectively diagnose COVID-19 in a suspected person.
But most of the studies have not emphasized building an End to End solution for diagnosis. Despite that, many studies have been conducted in order to develop an application for an End-to-End diagnosis solution [56,76]. Most studies consider image data types such as X-ray, CT, MRI, etc. To build COVID-19 diagnosis E2ES. As a result, using those applications, the patient's standard form of X-ray, CT, and MRI data sample needs, which must be primarily obtained from the clinic or hospital. Therefore, the E2ES hardly solves the problem of remote E2ES systems. Some studies have considered using sound and audio data to build E2ES for the COVID-19 diagnosis system, which can diagnose COVID-19 remotely. However, low sound-quality recording devices and environmental noise can downgrade the quality of captured audio and sound data, which may affect the performance of the application. Furthermore, these studies and applications have some certain circumscribed. Therefore, there is still a lack of standard and reliable E2ES for the diagnosis of COVID-19.
As there is a lack of E2E systems regarding various COVID-19-related work. The researchers should more focus on the issue and develop more E2E systems. Furthermore, the researcher should concentrate on removing the issues that users encounter when using the E2E system and improve quality (noise reduction, low-quality images handling). The system should be available and compatible with the maximum possible number of devices and platforms. In addition, researchers must promote campaign of the E2E system so that the wider populace can utilize the resource.
As COVID-19 spread as a global pandemic, the virus's devastation was felt throughout the country and regions. Therefore, the majority of the country's governmental and non-governmental organizations and NGOs have taken COVID-19-fighting measures, such as allocating funds, encouraging researchers, providing data, applauding researchers, and so on. These steps and opportunities have aided in the local and global combat of the COVID-19 pandemic by encouraging researchers to work on the issue of the COVID-19 pandemic. As a result, determining which country contributes the most to combating COVID-19 by conducting more research is a useful step toward appreciating their contribution. Furthermore, identifying countries with less significant contributions to research work is important so that those countries can be encouraged and financially aided so that as human civilizations, we can advance equally. Identifying the countries contributing to the COVID-19 pandemic, on the other hand, is a broad perfective work that requires dedicated research work, which may include research type, the technology used, and the discovery of performed studies.
Analyzing the studies considered in this research work reveals that India has conducted the most studies using ML, DL, and combinations of ML, DL, and AI-based techniques, followed by Saudi Arabia and the USA. Other developed countries as well as developing countries have contributed more or less to conducting research work regarding combating the COVID-19 pandemic.
For combating the COVID-19 pandemic, many studies have been conducted for various purposes and using various mechanisms. Various domains of AI have been used with diverse modifications and combinations. Furthermore, various types of data and a mixture of data types have been used to perform studies. Therefore, there is a need to evaluate the studies with a standard form of evolution metrics. Additionally, there is a need to identify the criteria that have been used in those studies to evaluate the trustworthiness of the studies. Most of the studies have used some of the evolution metrics such as accuracy, sensitivity/recall, precision, F1 score, AUC-ROC curve, etc. From analyzing the studies' utilized metrics, the accuracy metric has been used in most of the studies, followed by sensitivity and recall. Other evaluation metrics have been used less frequently in the review studies. However, the researchers should focus on the True Positive Rate instead of accuracy.
As COVID-19 is a pandemic and can transmit from person to person very rapidly, the top priority is to stop the spread. Therefore, it is crucial not to misidentify an infected person rather than misidentify a healthy person. Therefore, the researchers should prioritize the True Positive Rate or recall value rather than accuracy, as recall value focuses on capturing all true positives, even if it increases false positive rate.
Due to the COVID-19 pandemic, there have been instanced number of research works conducted to manage and combat the pandemic by the use of ML, DL, and combinations of ML, DL, and AI-based techniques. Those research works have been analyzed and identified various factors and purposes associated with COVID-19 using ML, DL, and combinations of ML, DL, and AI-based techniques. However, from those studies, some common challenges and limitations can be outlined. Identifying those challenges can be beneficial for the researchers who are planning to do research by applying the ML, DL, and AI methods as they can study those challenges to overcome in their study or can make their study particularly based on finding the solution to those challenges.
Selection of an effective model from the variety of models available from various domains of ML, DL, and AI is a challenging and time-consuming task. Some traditional ML, DL, and AI methods have already been extensively researched. However, there is still scope for improvements, but it will be challenging. Additionally, finding an effective combination of ML, DL, and AI is a challenging task that requires a significant amount of time and expertise. The scarcity of standards and enough sample data is one of the fundamental challenges when it comes to working with COVID-19. These are the two most fundamental challenges for researchers who intend to conduct research using ML, DL, or combinations of ML, DL, and AI-based techniques.
5 Challenges and future research opportunities
Many ML, DL, and other AI approaches depend on massive training data, such as clinical data, medical images, and other types of medical data. Large-scale training data is scarce and unavailable. It should be noted that determining the best models for COVID-19 diagnosis was challenging because of the scarcity of data. Further research is required to solve this issue. Moreover, a benchmark dataset is required for diagnosing COVID-19.
Since the COVID-19 virus's arrival, various variants have appeared due to mutations. Gathering data for different variants in a short period is complex, and there is always a shortage of COVID-19-related updated datasets. A combined and effective data gathering strategy is required to address this issue. Furthermore, a change in the variant might alter the performance of a model, which has been trained by a different variant previously. Hence, more research works are needed to investigate the performance of the previous studies on the new variants of COVID-19.
COVID-19 samples have a low count of CT, MRI, and X-ray images compared to pneumonia infection and healthy human case samples. Data argumentation tries to generate new image sample from the existing samples by flipping rotating, zooming, adding random nose in the existing images. Further studies are needed to measure the performance of this strategy and its limitations.
Using imbalanced datasets is an obvious shortcoming of recent studies. Data balancing is required for handling imbalanced datasets. The performances of the different models before and after balancing the datasets need to be compared.
Similarly, there are many potential combinations of various sorts of data type, namely demographics, MRI, X-ray and CT images, sound/audio data, and clinical, laboratory, and blood test data. However, combining multiple types of datasets (organized and unstructured) for various purposes of COVID-19 is needed for additional investigation.
Furthermore, some factors in COVID-19 research impede AI-based ML and DL applications. Some of these factors are as follows.● Slow Legislation process
● Security equipment and resource
● Lack of large-scale data.
● Vast rumors and noisy data.
● The researchers have limited expertise at the intersection of computer science and medical science.
● Data security and privacy issues in collecting data.
For tackling COVID-19, one of the necessary steps is to coordinate the participation of specialists who belong to other sectors and to include data from several studies. Most researchers' backgrounds are in computer science. However, a strong specialty in bioinformatics and various other relevant domains is needed for applying ML and DL to include additional knowledge of medical science in the COVID-19-related studies.
In the middle of a pandemic wave, using the traditional diagnosis method to identify COVID-19 is a dangerous process. Because visiting a hospital for a COVID-19 test can spread the virus to others who haven't already been exposed to the virus. Therefore, a remote COVID-19 End-to End diagnosis solution must be established in order to resolve the problem. In the future, it will be necessary to examine the problem by overcoming constraints and developing reliable and accurate End-to-End diagnosis solutions.
Remote video diagnostics and consultations are available nowadays in different clinics and hospitals. In the future, by combining AI and NLP-based technologies, remote video diagnostic programs can be developed to replace the COVID-19 patients' primary visits to the hospital.
In ML, DL, and AI-based systems, various simulations may be utilized to examine how different social approaches affect the spread of disease. Furthermore, this technique may be applied to verify the trustworthiness and explore scientific methods for the control and prevention of disease among citizens.
AI-powered ML, DL, and other systems can create social networks and knowledge graphs to keep an eye on and follow the traits of individuals living next to COVID-19-affected patients, precisely anticipating and monitoring the disease's spread.
Intelligent robots can be utilized in initiatives such as, product distribution programs and medical treatment where human resources can be replaced. Taking those initiatives may halt the propagation of the COVID-19 epidemic.
6 Conclusion
This study focuses on ML, DL, and combinations of ML, DL, and AI-based studies that may help fight the COVID-19 pandemic. The primary objective of this study is to outline prior research works and how these works have been used to fight COVID-19. For that purpose, multiple academic search engines have been searched by using various keywords to find relevant studies. Those studies are filtered by using the defined criteria. Based on the abstract analysis, dataset analysis, inclusion and exclusion criteria, and methodological quality, a final selection of 88 studies has been made. Among these studies, 25 studies employed ML techniques, 25 studies employed DL techniques, and the rest 38 studies utilized the combination of ML, DL, and AI-based methods. This study has analyzed the prior research works by summarizing the applied methods in those works, comparing the performance of different models used and identifying the purpose of those works.
92% of these studies are from different journals, and the rest 8% of these studies are conference papers. Most of the studies analyzed in this work are from 2022. USA conducted the maximum number of research works employing ML methods. On the other hand, the maximum number of works utilizing DL methods and the combination of ML, DL, and AI-based methods have been performed in India. RF model has been used most frequently in studies employing ML models, whereas different custom models have the highest frequency in DL-based studies. A variety of AI-based techniques have the highest frequency in the studies utilizing the combination of ML, Dl, and AI-based methods. In the evaluation process, most studies have emphasized accuracy to evaluate the performance of the proposed models.
The significant information discovered, investigated, and reported in this study are contemporary and up-to-date regarding COVID-19. For the appropriate content, we utilized precise keywords. These search terms yielded valuable results to achieve the aim of this study, though there is a chance we may have missed significant resources that are not shown by these terms. Some data might have been missed in the extraction of data from the selected studies.
Various ML, DL, and combinations of ML, DL, and AI-based methods have emerged in recent years. In future, more combinations of different methods and complicated approaches can be analyzed for fighting against COVID-19. Future research works can consider combining a variety of data formats to precisely identify COVID-19.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
General Nomenclature
MERS Middle East Respiratory Syndrome ML Machine Learning
AI Artificial Intelligence SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2
CXR Chest X-ray DL Deep Learning
MRI Magnetic Resonance Imaging WHO The World Health Organization
SARS Severe Acute Respiratory Syndrome NLP Natural Language Processing
CT Computerized Tomography MAPE Mean Absolute Percentage Error
RT-PCR Reverse Transcription-Polymerase Chain Reaction DOAJ Directory of Open Access Journals
ECG Electrocardiogram RMSE Root Mean Square Error
Data availability
No data was used for the research described in the article.
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