Improved Hand Function in Children with Cerebral Palsy with Repeat Doses of Group Based Hybrid Pediatric Constraint-Induced Movement Therapy

Round 1

Reviewer 1 Report

The manuscript “Improved Hand Function in Children with Cerebral Palsy with Repeat Doses of Augmented Pediatric Constraint-Induced Movement Therapy” explored children’s response (measured as the hand function via the Assisting Hand Assessment (AHA)) in response to two doses of augmented pediatric Constraint-Induced Movement Therapy provided in a group setting. The results showed improvements in AHA from pre-treatment to post-treatment for both doses with a decrease from the post-treatment AHA for dose 1 to the pre-treatment AHA for dose 2. The paper is well written and will be very interesting to the readers of this journal. However, the authors need to clarify a few issues outlined below.

Abstract

line 15: “Participants attended 10 days of camp where they received group-based training wearing a 15 constraint for a total of 50 hours, received bilateral, occupation-based activities for 10 hours (60 hours total) including 30 minutes on the Hocoma ArmeoÒSpring.” – 30 minutes each day or total across 10 days?

line 19: “55.93+-12.78” – should be 55.93±12.78; here and below.

It is unclear what Treatment 1 and Treatment 2 are. Coming back again to the Abstract after reading the entire paper, I guess that the authors call the repeated doses of the same treatment as Treatment 1 and 2 instead of Dose 1 and 2. This is very confusing and should be corrected.

line 24: “and diminished effects between doses were reversed with repeat doses” – unclear.

Methods

line 141: “Each participant attended the annual P-CIMT camp for two weeks and had six hours of therapy each day (60 hours total) during the summers of 2014-2018 [16].” – it is unclear how many doses each participant received and why the study lasted for 4 years…. What was the mean time gap between the 2 doses?

Results

line 159: “Table 1 presents demographic data for the 15 children who received at least two treatments of pCIMT.” – First, again, it is confusing when 2 doses are called 2 treatments (the latter would imply a different set of procedures). Second, what was the time period between the 2 doses in each child? Were the data on children receiving more than 2 doses included in the current analyses?

line 168: “Results from the analysis revealed that significant differences existed between pre and post camp AHA scores (F(1, 14) = 49.89, …” – do these results combine the 2 doses? If not, then there should be 2 set of results, If yes, how did the authors accounted for the non-independence of data?

line 182: “There was no significant interaction effect found for AHA scores but not between the 1st and 2nd camp attended (?(1, 14) = 3.81, ? = .071, ??????? ? 2 = .21).” – Unclear sentence. Interaction between what variables – dose (dose 1 vs 2) and time (pre- vs. post-)? Please clarify. Was this a repeated-measures mixed-design ANOVA? The authors only specified that they would use a factorial within-subjects ANOVA, which would not accommodate the repeated measures (non-independent data) within participants.

line 192: In Table 1, Mean age – is this the age at Dose 1? Both mean age at Dose 1 and Dose 2 should be presented.

line 195: Table 2 should be grouped by the Dose/Camp (pre- and post- within each dose/camp), not within the pre-/post- measurements. Current presentation of the data is extremely confusing.

Discussion

line 224: “The study findings support the recommendation of a smaller time interval between doses may need to be smaller than 1-2 years in order to limit the diminished hand function between treatments.” – This conclusion is not warranted since the current study did not manipulate the time between the doses and did not explicitly study this issue.

line 238: “With our analysis, we discovered a “wear-off” effect between doses that was reversed with repeated treatments of P-CIMT camp in children with CP.” – Meaning of the “wear-off” effect here is unclear. Moreover, although authors reported that the pre-intervention scores for dose 2 were lower than the post-intervention scores for dose 1, I did not see a formal statistical analysis showing that this difference was statistically significant. Please add one.

Author Response

Hello,

Thank you so much for your review. Please see the manuscript highlighted with changes and then the line by line item changes. Thank you so much for helping make this a better manuscript. Below are the changes and the manuscript is attached with the changes in yellow. The changes also include reviewer 2's comments. Thank you again.

Abstract

Line 17    Clarified “each day”

Line 19 changed to 55.93±12.78 and thereafter

Changed “treatment 1” to Dose 1 throughout abstract and manuscript.

Methods

Line 109- added clarification of repeat doses  All subjects attended the camp sessions consecutively, with the exception of one child who returned the following year.

Line 141- typo changed 8 to 9. All subjects completed the camps consecutively (back to back) with the exception of one subject who returned a year later.

Results

Line 159- changed treatment to doses; added mean interval of 564 days between doses

Line 168- Interaction results were moved up in the results to before main effects were reported, justifying the main effects of each factor being interpreted rather than the individual cells (since the interaction was insignificant).

Line 182- Interaction was moved to earlier in results and clarified. Analysis description changed language to state analysis as being factorial repeated measures ANOVA with a within-subjects factor, to add clarity. Both time and dose could be considered “within-subjects” since the same participants are used for both times and doses.

Line 192- Age separated by dose in Table 1

Line 195- Changed header for pre and post AHA to add clarity for table. Since the main finding of the study was a change from pre to post-intervention, we feel that the table as currently formatted allows for the comparison of the overall changes from pre to post-intervention (with there being a total pre and total post score). To re-order the table would instead yield totals for camp 1 and camp 2 instead, which, although interesting and discussed in the results of this study, did not represent statistically significant differences. Therefore, we feel that the current organization of the table best represents the overall findings of the analysis.

Discussion

Line 224- added clarification about time between doses, and added the word “may”

Line 238- statistical results for this comparison were added to the results section of the study.

Author Response File: Author Response.docx

Reviewer 2 Report

Review

Improved Hand Function in Children with Cerebral Palsy with  Repeat Doses of Augmented Pediatric Constraint-Induced  Movement Therapy

Dear Authors

I thank the group for this paper and the longitudinal approach with repeat doses of P-CIMT

I have some questions to be addressed to understand and improve the paper.

If I understand correctly you call it specifically pediatric CIMT, while bimanual use of the hands is embedded in the training period. Officially it should be named hybrid-CIMT.

This is relevant for the background of the reasoning to explain the effects on the AHA and why the AHA is chosen as primary outcome, with the focus of the assisting hand function of the affected hand.

Please explain why the primary outcome is the AHA ( assisting performance in bimanual tasks) and no measure has chosen to express hand function of the affected hand and functional independence of paretic limb. Please define hand function and functional independencce and explain why no Melbourne upper limb test or Jebsen Taylor hand function test is used.

For this paper ideally it is needed to add these outcome measures, based on your explanation of the goal of CIMT

In introduction you describe

In children with unilateral CP we do not talk about a paretic limb, but spastic upper limb.

Although CIMT is effective, there is a primary gap in the literature that suggest the need for repeat doses of CIMT of the same design among 1-year intervals in order to explore the dose-response relationship and identify the age in which a ceiling effect occurs

Please embed information about the 1 year interval and the correction for development within the use of the AHA units (instead of logits- please use the conversion table).

Is there an expected effect of age after 1 dose of CIMT and how did you correct for this expectation?

You describe

Analysis of the pilot study data aims to address the impact of repeat doses of an

augmented P-CIMT protocol delivered in a peer-supported group environment on

bimanual skills in children with UCP. The hypothesis for the study is that repeated doses

of the augmented P-CIMT camp will result in greater improvements in hand function

compared to a single dose of the intervention.

Please clarify why you name it augmented P-CIMT as repeated dose of the same program.

What is augmented in case of a repetition and what did you exactly change to make it augmented? (Roberts protocol).

I do not understand completely the description of the first doses and the second augmented doses.

Is the program that different (Boyd protocol).

Augmented can mean enlarged  or augmented reality….

It can be helpful to present a more detailed description.

In the introduction you focus on group based approach. I agree about the importance of the group based effects and I suggest you name this in the title:  group based hybrid P-CIMT

Methods

Please describe the clinical relevance value for the AHA scores in units

You describe

Data Analysis

Research records were reviewed to identify children who completed two P-CIMT

camp sessions and to extract demographic information. Next, scores on all of the outcome

measures were analyzed using a factorial within-subjects ANOVA to determine if

differences existed between pre and post camp for the 15 participants in their 1st and 2nd camps.

You name outcome measures ?  what other measures are used?

You measure pre-post, but also between first and second camp. I miss the between factor?

It is not clear for me if you see the two camps as one pre post camp??

In your figure and table it is suggested as two camps with two times pre post and two groups ( first and second period)

Results

You talk about a carry over effect, based on a higher baseline in the second camp?

Did you correct for age? Or repetition?

Based on the Sd it seems not to be an obvious carry over effect? But I can be wrong

Please present in figure 1 the SD next to the mean values and it would be nice to present individual plots for all children to see the differences per child

The presented effects size eta is 0.21. this is a very low effect size. Please incorporate this value in the discussion, and compare this with other ( deluca, Gordon, Hoare, Sakzewski, Boyd..)

Discussion

You describe

With our analysis, we discovered a “wear-off” effect between doses that was reversed with repeated treatments of P-CIMT camp in children with CP. The applicable nature of repeat doses based on the DeLuca et al. [14] study confirms repeat doses of P-CIMT can produce long-term effects in bimanual hand ability.

Please explain the wear off effect? I do not understand meaning in this context

Overall this paper is very relevant and hopefully it can be improved

Best

Author Response

Thank you so much for assisting to make this manuscript better. Below are the comments point by point. I have attached the manuscript with the revisions highlighted in yellow. These also include comments from the other reviewer. Thank you again for taking the time.

If I understand correctly you call it specifically pediatric CIMT, while bimanual use of the hands is embedded in the training period. Officially it should be named hybrid-CIMT. Line 3 changed Augmented to Hybrid

This is relevant for the background of the reasoning to explain the effects on the AHA and why the AHA is chosen as primary outcome, with the focus of the assisting hand function of the affected hand.

Please explain why the primary outcome is the AHA ( assisting performance in bimanual tasks) and no measure has chosen to express hand function of the affected hand and functional independence of paretic limb. Please define hand function and functional independencce and explain why no Melbourne upper limb test or Jebsen Taylor hand function test is used.

For this paper ideally it is needed to add these outcome measures, based on your explanation of the goal of CIMT- The AHA is chosen as the primary outcome because it is the gold standard for measuring hand function in children with unilateral CP. And a change in functional use of the upper limb is best evaluated using an activity based assessment such as the AHA versus the Melbourne or the jebson. The COPM was also used to demonstrate the children’s abilities to incorporate the changes within their daily routines.Line 123 added The AHA is administered in a play-based atmosphere and assesses how the child utilizes the non-preferred UE during usual or typical performance

In introduction you describe

In children with unilateral CP we do not talk about a paretic limb, but spastic upper limb. Line 4 changed to preferred and non-preferred and throughout the manuscript

Although CIMT is effective, there is a primary gap in the literature that suggest the need for repeat doses of CIMT of the same design among 1-year intervals in order to explore the dose-response relationship and identify the age in which a ceiling effect occurs

Please embed information about the 1 year interval and the correction for development within the use of the AHA units (instead of logits- please use the conversion table). AHA units were used and not the logits- wording changed from logits- units (2 instances).

Is there an expected effect of age after 1 dose of CIMT and how did you correct for this expectation? The AHA is not a normative assessment it is a correlational assessment. As long as the children fall with in the age of validation age does not matter.

You describe

Analysis of the pilot study data aims to address the impact of repeat doses of an augmented P-CIMT protocol delivered in a peer-supported group environment on

bimanual skills in children with UCP. The hypothesis for the study is that repeated doses of the augmented P-CIMT camp will result in greater improvements in hand function compared to a single dose of the intervention.

Please clarify why you name it augmented P-CIMT as repeated dose of the same program. It is called an augmented P-CIMT because we added the use of the Hocoma ArmeoSpring Pediatric. The campers used 30 minutes each day. The subjects completed the summer camp more than one time. The Median interval between completing the camps/doses was 511 days. Added clarification in line 164.

What is augmented in case of a repetition and what did you exactly change to make it augmented? (Roberts protocol). The camp is augmented with the addition of the use of the Hocomo ArmeopSpring Pediatric 30 minutes each day.

I do not understand completely the description of the first doses and the second augmented doses. The camp is the same each summer 2014-2019. In an effort to eliminate any contraindications, the dosage of our P-CIMT camp was consistent and followed the camp manual in order to confirm the validity of our study through replicated trials

Is the program that different (Boyd protocol). yes

Augmented can mean enlarged  or augmented reality…. Augmented was used in the first paper by Roberts et al. Augmented –meant enhanced with the use of the Hocomo ArmeoSpring Pediatric 30 minutes each day to CIMT camp

It can be helpful to present a more detailed description. I hope the above helped

In the introduction you focus on group based approach. I agree about the importance of the group based effects and I suggest you name this in the title:  group based hybrid P-CIMT-  line 3changed title to Group based hybrid

Methods

Please describe the clinical relevance value for the AHA scores in units added the following sentence- Line 123-125].  The AHA is administered in a play-based atmosphere and assesses how the child utilizes the non-preferred UE during usual or typical performance

You describe

Data Analysis

Research records were reviewed to identify children who completed two P-CIMT camp sessions and to extract demographic information. Next, scores on all of the outcome measures were analyzed using a factorial within-subjects ANOVA to determine if differences existed between pre and post camp for the 15 participants in their 1st and 2nd camps.

You name outcome measures ?  what other measures are used? The original paper reported the subjects Canadian Occupational Performance Measure and the Melbourne. There were other outcome measures collected but the focus of this manuscript was to look hand function AHA

You measure pre-post, but also between first and second camp. I miss the between factor?

It is not clear for me if you see the two camps as one pre post camp??

In your figure and table it is suggested as two camps with two times pre post and two groups ( first and second period)

Lines 155 – 159 Language was adjusted to clarify the analytical approach taken. First and second camp were considered as a within-subjects factor, and the interaction between first/second camp and pre/post intervention was considered. As such, a total of 3 influencing factors were considered (2 main effects and 1 interaction effect).

Results

You talk about a carry over effect, based on a higher baseline in the second camp?

Did you correct for age? Or repetition? There is no correction for age in AHA. The within-subjects nature of the analysis accounts for the repeated aspect of the data.

Based on the Sd it seems not to be an obvious carry over effect? But I can be wrong. Additional comment in lines 182-183 to help clarify.

Please present in figure 1 the SD next to the mean values and it would be nice to present individual plots for all children to see the differences per child  I have SPSS charts for each participant if you want to include this in an appendix?.

The presented effects size eta is 0.21. this is a very low effect size. Please incorporate this value in the discussion, and compare this with other ( deluca, Gordon, Hoare, Sakzewski, Boyd..). Gordon et al. (2008) found a small-to-moderate effect size difference from pre to post intervention AHA scores using CIMT (Hedges’ g = .34). This was not explicitly reported; the calculations were done based on the means and standard deviations reported. An additional statement was made to show the eta effect size in a standardized mean difference format (i.e., Hedges’ g) in order to make comparison to prior literature. The effect size is shown to be meaningful after comparing to literature, and supports the suggestion in the ms that a larger sample may have supported significant overall differences from camp 1 to camp 2.

Discussion

You describe

With our analysis, we discovered a “wear-off” effect between doses that was reversed with repeated treatments of P-CIMT camp in children with CP. The applicable nature of repeat doses based on the DeLuca et al. [14] study confirms repeat doses of P-CIMT can produce long-term effects in bimanual hand ability.

Please explain the wear off effect? I do not understand meaning in this context  The subjects 2nd AHA score is lower than their 1st post AHA score but it is not lower than the 2^nd pre AHA score. So the effect of the treatment remains but does not keep for the whole year.

Overall this paper is very relevant and hopefully it can be improved

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

I thank the authors for the adaptations in the paper. It is more clear.

some questions or suggestions remain:

1. title should mention Hybrid CIMT in stead of CIMT, due to the 30 min. bimanual activities.
2. one important visualisation is the AHA scores. your figure should incorporate Sd or SE.  It would be very clear if you also would present a figure in which the both dose results are presented after each other in a timeline to show the period in between and the reverse of the results.
3. I really advice you to present a figure of each child separately to show the improvement of the 2 doses and reverse in between.

Discussion:

please show more detail about the differences in effect size between the studies and your arguments and especially about the time in between, because that is the main message for the clincians

Author Response

Thank you so much for the feedback. Please see attached manuscript with edits. I did add individual figures per request of the 2 reviewer comments, however, I am worried we are over page limit. 

Reviewer #2

1. tle should mention Hybrid CIMT in stead of CIMT, due to the 30 min. bimanual activities.

The title was changed to include “hybrid”

1. one important visualisation is the AHA scores. your figure should incorporate Sd or SE.  It would be very clear if you also would present a figure in which the both dose results are presented after each other in a timeline to show the period in between and the reverse of the results.

The camp is yearly. The majority of the children completed the camp one year after the first. This was added to the paper line 18.

            Table 2 includes the SD. (line 206)

Added this figure (line 207)

1. I really advice you to present a figure of each child separately to show the improvement of the 2 doses and reverse in between.

Figures 3-17 added to show each subjects improvements (lines 203-240)

Discussion:

please show more detail about the differences in effect size between the studies and your arguments and especially about the time in between, because that is the main message for the clinician To our knowledge there is only the DeLuca article looking at multiple treatments of CIMT and their group did not use the AHA as an outcome measure. Lines259-270 discuss that both our study and hers had statistically significant differences on outcomes but they are not the same outcome measures so it is difficult to say more.

Author Response File: Author Response.docx

Round 3

Reviewer 2 Report

Dear authors

the adaptations are well written.

nu comments.

I agree with submission