A total number of n = 533 items were found using scientific databases (n = 229), grey literature databases (n = 233), trial registries (n = 2) and other sources (n = 69). See Table B1 (Appendix B) for a list of the databases used and the number of results. After removal of duplicates (n = 114), a total number of n = 419 items were screened for titles and abstracts and exclusions were made where necessary (n = 321). 98 titles were analysed for eligibility and exclusions (n = 80) were made according to the protocol [96] for missing full text (n = 4) [78, 79, 81, 86], whereas three of them were abstracts of relevant trials [78, 79, 81], and one of them was an announced review of the Padovan-Method® [86]. The authors were contacted but no further full text was available. Other items did not meet inclusion criteria but contained information about basic principles of the Padovan-Method® (n = 22) as primary literature (n = 8) [16, 40–42, 118–121] or secondary literature (n = 14) [10, 35, 39, 59, 60, 65, 122–129], recommended the Padovan-Method® in a context-dependent manner (n = 29) [1, 18, 20, 43, 56, 67, 69, 71, 73–76, 80, 84, 130–144], mentioned the therapy as a possible option for certain indications without any proof of evidence (n = 10) [7, 70, 83, 145–151] or simply contained some unspecified information about the method (n = 7) [82, 152–157]. Due to manuscript language, eight potentially relevant items had to be excluded [37, 77, 158–163]. See Table B2 (Appendix B) for a reference list of excluded items. Finally, four studies (no RCT, one pseudo-RCT [49], one non-RCT/CCT [55], one CBA [44] and one retrospective self-compared cohort study [48]) and n = 14 case documentations (10 CR [46, 47, 50–53, 72, 164–166] and 4 CS [22, 36, 54, 167]) remained for inclusion. Divergent from the protocol, no further exclusion was made in the case of CS or CR with unclear documentation of the therapists qualification (therapy under supervision [52, 53, 72] or NI [50, 51, 54, 164–166]). A flowchart following the PRISMA guidelines [168] was created to illustrate the process and is shown in Fig. 1. The characteristics of the sample are shown in Table 1 and an overview of the quantitatively evaluated primary outcomes is given in Table 2.
Table 2. Table of primary outcomes quantitatively evaluated
Primary outcomes
|
early response, between one and four weeks
|
acute phase treatment response between six and 12 weeks
|
long-term and follow-up response between four and six months (or more)
|
decrease of DI90 [44]
|
changes of tongue- and lip coordination exercises [49]
swallowing examination [49]
position of tongue-tip whilst swallowing [49]
position of tongue edge whilst swallowing [49]
articulation (s-sound formation[169]) [49]
time to get up in the morning [170]
|
improvement condition of lips [36]
reduced habit of
- licking lips [36]
- biting objects [36]
improved
- sitting posture [36]
- swallowing patterns, [36]
improved axis symmetry of
- eyes, [36]
- zygomatic bone[36]
- shoulders. [36]
gained as ability
- pull the lips wide[36]
- move the tongue to the right or in a circle [36]
reduced lateral posture [36]
no preferred side of chewing [36]
rise of the AIMS Score [171] [54]
|
Notes. Details of measurements and outcomes are described in the text.
3.1 Study quality and risk of bias
The risk of bias using ROBINS-I [104, 114] is presented in Table 3. See Tables D2-D5 (Appendix C) for details and authors judgement. Although [49] described the design as a pseudo-randomised controlled trial, it was not clear, to what extent it could be interpreted as randomised or non-randomised; therefore, we classified and rated it as non-RCT.
None of the included studies had a low risk of bias; two items were at moderate [44] or serious [49] risk of bias, and two other items had a critical risk of bias [48, 55]. Bias due to confounding was present due to too short study design [44] and multi-therapy setting [48, 55]. Selection bias occurred due to retrospective design and selection into the study in relation to intervention [48]. Bias in classification of interventions was overall at low risk. Deviations from intended interventions caused moderate risk of bias due to un-balanced co-interventions [48, 55] and critical risk of bias due to potential effect of not controlled co-interventions [48]. Missing data for any participant led to a critical risk of bias [48]. Unclear conditions in measurements of outcomes were rated with moderate risk of bias due to observers knowledge of the intervention [48, 49] and serious risk of bias due to language barriers, limited condition of patients at certain measurements [55], and no available outcome data [48]. Bias in selection of reported results were detected as moderate bias due to no available study protocol [48, 49, 55], serious due to deviations between methods and results section [49], and critical due to rare outcome data in the results section [48]. Limitations were set according to the overall risk of bias, if no further limitations existed. Imprecision was judged according to GRADE [113] (see Table 4).
Table 4. Quality of evidence regarding risk of bias, limitations and imprecision
Author (Year)
|
Risk of biasa
|
Limitationsb
|
Imprecisionb
|
Bellingen 2017 [49]
|
serious risk
|
moderate
|
low
|
Lukowicz 2019 [44]
|
moderate risk
|
low
|
very low
|
Pereira et al. 2015 [48]
|
critical risk
|
high
|
high
|
Rodenacker 2007 [55]
|
critical risk
|
high
|
moderate
|
Barbosa 2019 [50]
|
-
|
high
|
high
|
Braga 2019 [51]
|
-
|
high
|
high
|
Buson 2019 [52]
|
-
|
high
|
high
|
Carmo 2019 [53]
|
-
|
high
|
high
|
Delmondes 2018 [47]
|
-
|
high
|
high
|
Froitzheim 2010 [164]
|
-
|
high
|
high
|
Großweischede 2000 [165]
|
-
|
moderate
|
high
|
Kunert 2003 [166]
|
-
|
moderate
|
high
|
Menezes 2019 [54]
|
-
|
moderate
|
moderate
|
Oertel 2015 [36]
|
-
|
moderate
|
moderate
|
Oliveira 2019 [72]
|
-
|
moderate
|
high
|
Pereira 2015 [22]
|
-
|
high
|
high
|
Pereira 2018 [167]
|
-
|
moderate
|
high
|
Wilson 2016 [46]
|
-
|
moderate
|
high
|
Notes. aAccording to ROBINS-I [104]. bAccording to GRADE [113]
The results of the CARE [106] evaluation of the CS and CR were evaluated as shown in Table 5. No retraction statements were found. One CS was found including an erratum as appendix with some corrections of the manuscript (master thesis), taken into consideration by this work [36]. None of the included CS and CR completely fulfilled the CARE [106] recommendations. Critical limitations were present in all items regarding at least one of the following domains: ‘Diagnostic assessment’ [22, 47, 50–53, 164], ‘Follow-up and outcomes’ (all items) [22, 36, 46, 47, 50–54, 72, 164–167] and ‘Discussion’ [47, 50–53, 72, 164, 166]. Limitations of CS and CR where therefore considered to be moderate [36, 46, 54, 72, 165–167] or high [22, 47, 50–53, 164]. For an overview, see also Table 4.
3.2 Ethics assessment
Approval by an ethics committee was reported only in two papers [54, 172]; the results are summarised in Table 6. No information about agreement was found in all other items [22, 36, 46–53, 55, 72, 164–167]. Patient informed consent given prior to the intervention was documented in four of the results [36, 48, 54, 165]. Lukowicz et al., 2019 [44] reported no patient informed consent had been required. Documentation was unclear in one case [166] and no information was found in the remaining items [22, 46, 47, 49–53, 55, 72, 164, 167].
3.2.1 Funding.
Only one item reported on sources of funding and stated to not have received any funding [44].
3.2.2 Declaration of interest.
Only one item had a declaration of interest declaring none [44].
3.3 Textual descriptions of included items and reported outcomes
The included studies and case reports are described textually in this section, providing general information about the setting, participants, indicating diagnoses, intervention, comparisons, variables and outcomes. If applicable, further information is presented in the Table 1.
3.3.1 Studies.
The included studies [44, 48, 49, 55] covering the period from 2007 to 2019 were found published [44, 48, 49] or as grey literature [55]. For two of the published studies [44, 49], detailed underlying thesis manuscripts were available as grey literature [45, 170], which were used to gain further information about the studies. Three of the studies were carried out in Germany [44, 55] and one in Brazil [48]. The setting was either clinical (inpatients) [44, 48] and ambulatory [49, 55], and the number of participants reanged from n = 10 [55] to n = 92 [48] and was n = 156 in total. The age of the participants reached from 2 days [48] to 15 years [49]. Amongst the prospective trials [44, 49, 55], a controlled setup was found in two cases [49, 55], one trial was retrospective, self-controlled and descriptive [48]. Indicating diagnosis were down syndrome [55], down syndrome with obstructive sleep apnoea [44], myo-functional disorders [49] and new-borns with symptoms summarised as alterations in neurological examination or presenting difficulties in sucking [48]. Nevertheless, myo-functional disorders were also present in the three other studies in included patients [44, 48, 55]. Study drop-outs (n = 35) were reported due to upper respiratory infections, recording of less than three hours of sleep (n = 24 [44]), death due to sepsis in the context of new-born (n = 7 [48]), transfer (n = 2 [48]), surgery (n = 1 [48]) or too large off intervals between therapy sessions (n = 1 [49]). All therapists were documented to be qualified for the Padovan-Method® [63]. The measured items were entirely heterogeneous without any conformity. The rating instruments used in the included papers are listed in Table C1 (Appendix C). Rodenacker, Ivdal, & van Amsterdam, 2007 [55] used the motoric test (MOT 4-6[173]), speech development test (‘Sprachentwicklungstest’ SETK 3-5 [174]) and a parental questionnaire regarding the development of the participants and their influence on the family, self-developed by Rodenacker et al., 2007 [55]. Pereira et al., 2015 [48] documented and evaluated neurological examinations [48]. Bellingen, 2017 [49] used the Iowa Oral Performance Instrument (IOPI) [175], assessment of mouth closure by therapists using a three point scale, lip strength using the MFT-‘Lippenwage’ (tool to strengthen and measure the muscles for closure of lip and mouth [176]), measurement of suction power and speed using the suction trainer developed by Beatriz A. E. Padovan and described at Abad Bender, 2017 [10], coordination of tongue and lips using certain tasks from a toolkit developed by and described at Kittel & Förster, 2010 [177], swallowing examination using a own system with different types of fluid and colour [170], observation of teeth and jaw position by therapists [170], Bruininks-Oseretsky Test of motoric proficiency (BOT-2) [178], articulation (‘Lautprüfbogen’ LPB, [169]), therapists observation and parents questionnaire developed by the author described at Bellingen, 2017 [49] with the following items: time needed for homework, concentration during homework, difficulties with orthography, difficulties with building sentences, difficulties with finding the right words, building unstructured sentences, time to get up in the morning, awakening during night, needed time to fall asleep, preference of certain food-consistency, chewing [49]. Lukowicz et al., 2019 [44] used the mixed-obstructive-apnoea/hypopnoea index (MOAHI, 44, 45, defined as the sum of obstructive and mixed apnoea and hypopnea per hour of corrected estimated sleep time[1] (CEST) 44, 45), DI3 (desaturation index ≥ 3%, events per hour of corrected estimated sleep time [44, 45]), DI90 (desaturation index < 90%, events per hour of corrected estimated sleep time [44, 45]), arterial oxygen saturation (SpO) [44].
In all studies, the core intervention were therapy sessions according to the Padovan-Method®. The duration of the sessions were 45 minutes [44, 49] (NI: [48, 55]), with application frequency varying in all studies between three times a day [44], five times per week [48], two times per week [49] and in one case accelerating from one to two times per week [55].The intervention periods were heterogeneous with one week [44], 10 weeks [55], 11 weeks [49] and due the retrospective setup two days to five months [48].
The trials resulted in heterogeneous outcomes. Statistically significant changes of tongue- and lip coordination exercises (tongue exercise 2 [177] likelihood-ratio test (LR) x2 (2, n = 12), p = 0.001 [49]; lip exercise 1[177]: LR x2 (n = 12), p = 0.005) [49], swallowing examination (swallowing fluids[170] t-Test for independent samples: t(10) = -5.331, p < 0.000 [49], position of tongue-tip whilst swallowing[170] t-Test for independent samples: t(10) = -3.429, p = 0.006 [49], position of tongue edge whilst swallowing [170] t-Test for independent samples: t(10) = -9.163, p < 0.001 [49]) [49], articulation (s-sound formation[169] t-Test for independent samples: t(10) = -2.525, p = 0.010) [49] and time to get up in the morning (parental questionnaire, Chi-square test x2 (3, n = 12, p = 0.023) [170], decrease of DI90 (2,7 (SD 4.5) to 2.1 (SD 3.7) p < 0.05) [44]. Not statistically significant, but described as noticeable, was an increase of lip strength (MFT-‘Lippenwage’[176] T1 = initial examination: 500-1017g; T2 = examination after intervention: 850-1367g) [49], and a subjective boost of development described by some of the parents [55]. No data provided, and thereby only descriptively reported, were the following: a shortening of hospital stay, avoidance of gastrostomy and palliative procedure of feeding for discharge of the treated new-borns [48]. Furthermore, no statistically significant effect of the Padovan-Method® on obstructive sleep apnoea in down syndrome patients was shown [44], and no difference between therapy methods according to Padovan-Method® and Psychomotor Performance Therapy was revealed [55]. Moreover, a change of the tongue pressure, lip strength, suction power and speed, quality of mouth closure, physiologically swallowing of food, fine and gross motor skills was not shown or not evaluable due to small sampling size [49]. None of the studies had a follow-up testing or documentation.
3.3.2 Case Reports.
The included case reports [22, 36, 46, 47, 50–54, 72, 164–167] covering the period from 2000 to 2019 were found as described above for other studies used. Nine of the cases were collected in Brazil [22, 47, 50–54, 72, 167], three in Germany [36, 165, 166], one in Great Britain [46] and one did not provide any information about the country [164]. The context of the cases were university [51–53, 72], inpatients [22, 46, 47, 54] and ambulatory setting [36, 165, 166] (no information provided [50, 164, 167]). The number of participants ranged from n = 1 to n = 11 [22] and was n = 40 in total. The items contained four case series [22, 36, 54, 167] and ten single case reports [46, 47, 50–53, 72, 164–166]. The age of the participants ranged between five days [22] to 28 years [46]. Indicating diagnosis were microcephalia (with total n = 14 in six case reports [50–54, 72]), neonatal hypoxic-ischemic encephalopathy (n = 10 [22]), myo-functional disorder (n = 8 [36]), foetal alcohol syndrome (n = 2 [167]), neurological alteration by kernicterus (n = 1 [22]), speech development disorder (n = 1 [166]), audiogenic dyslalia (n = 1 [165]), treacher collins syndrome (n = 1 [47]), tetra paresis and open bite (n = 1 [164]) and brain injury (n = 1 [46]). Study drop-outs (n = 5) were reported in one case series due to lack of time to adhere to the therapy protocol [36]. The therapists were either certified for the Padovan-Method® [22, 36, 46, 47, 167], under supervision [52, 53, 72] or had no information provided [50, 51, 54, 164–166].
The measured items were heterogeneous without any conformity. See Table C1 (Appendix C) for the rating instruments utilized. (Menezes, Menezes, Lopes, Pereira, & Tabosa, 2019 [54] used the Alberta Infant Motor Scale (AIMS [171]) and dichotomous assessment of physical assessment (grab objects, reflux, don’t follow objects, lack of cervical control, convulsion/spasm, lack of thoracical control [54]) analysed descriptively. Oertel, 2015 [36] used a logopaedic assessment tool developed for quality assessment in logopaedic therapies (‘Kölner Diagnostikbogen‘ described at [180]), the report sheet from the results and progress log for neurofunctional reorganization (‘Befund- und Verlaufsprotokoll zur Neurofunktionellen Reorganisation’ IPVP [129, 181]) and a clarification of therapeutic objectives sheet (‘Therapeutische Auftragsklärung’ following [180]). The case report of Wilson, Dhamapurkar, & Rose, 2016 [46] is mainly descriptive, but the used tools were the Wessex Head Injury Matrix (WHIM [182]) and the JFK Coma Recovery Scale-Revised (CRS-R [183]), and throughout the hospital stay replaced by the Putney Auditory Comprehension Screening Test (PACST [184]), the Functional Assessment Measure (FAM [185]) and the Functional Independence Measure (FIM [186]). No information about measured variables was given in any other item (11) [22, 47, 50–53, 72, 164–167].
Within all reports, patients received therapy sessions according to the Padovan-Method®. The duration of each session was 45-60 minutes [36, 46, 51, 52, 72, 166] or not specified [22, 47, 50, 53, 54, 164, 165, 167], with application frequencies of 1 or 2 times per week (1-2/w) [36, 46, 54, 72, 165], 5-6/w, [47, 53] and 7/w [50–52] (NI: [22, 164, 166, 167]). The intervention periods were between five days [47] and two years [165] (NI: [46]). In some case reports, other therapies were applied too and are to be accounted as confounding domains (kinesiology [51, 52], osteopathy or physiotherapy [36], multi-disciplinary setting [46], use of a lip-cheek-tongue trainer (‘Lippen-Wangen-Zungen (LWZ)-Trainer’ [187]) [36], manual therapy not further specified [50]).
The reports presented again heterogeneous results. Statistically significant changes were presented in two case reports [36, 54], though had moderately imprecise documentation according to GRADE Rating [188]. Fisher’s exact test [172] and Wilcoxon Test [189] was used to measure statistical significance between first and third (last) examination [36] and revealed the following results: no preferred side of chewing (p = 0.025), condition of lips (p = 0.024), pull the lips wide gained as ability (p = 0.046), move the tongue to the right or in a circle gained as ability (each p = 0.046), reduced habit of licking lips (p = 0.034), habit of biting objects reduced (p = 0.038), improved sitting posture (p = 0.046), reduced lateral posture (p = 0.020), improved swallowing patterns (p = 0.026), improved axis symmetry of eyes (p = 0.038), zygomatic bone (p = 0.025) and shoulders (p = 0.026). A rise of the AIMS Score ([171]) between the first and third testing was described and postulated as statistically significant without a provided confidence interval (t-Test t(8) = 2.927, p = 0.19 CI:NI, [54]) [54].
Not statistically significant but noticeable effects such as reducing dysphagia and bronchial aspirations, spasms, improvement of the abilities to roll, crawl and sit were reported [54], albeit imprecisely [188]. An improvement of the body condition (tone, posture, axial symmetry, occurrence of tension and pain) was qualitatively described as observed changes between initial and final testing [36]. A rise of the CRS-R [182] from three (T1: 4 months post injury, equal to vegetative state [183]) to eight (T2: 14 months post injury) was documented [46]. Throughout the hospital stay of the reported case, CRS-R [183] and WHIM [182] were discontinued because of ceiling both tests [46] followed by measuring PACST [184], FAM [185]) and FIM [46, 186] with no further information regarding development of numbers. A high bias of missing data (according to GRADE [190]) exists as only results of the CRS-R [183] are reported [46]. Progress in verbal expression and improvement in cognition and speech within a multimodal therapy setting was qualitatively reported [46].
No other reports provided any measurements, but reported improvements in the fields of psycho- and motoric development, speech and vegetative functions. Details are listed in Tables D20 and D21 (Appendix C). One report described a case but did not contain explicit results [166]. One of the reports mentioned a follow-up after 3 years without detailed testing showing improved motorial and speech development (high risk of bias due to confounding domains: physiotherapy and speech therapy as no Padovan-Therapy® had been available) [47].
The results of the studies and case reports were used to define the primary and secondary outcomes (see Table 2 and Appendix C Tables D20-21). Statistically significant outcomes are listed separately (see Table 2). To extract the early response from acute phase treatment, response the length of intervention was used (cut-of duration of treatment process ≤ 1 month [22, 47, 48, 55, 167] and ≤ 3 months for acute phase treatment [22, 49–53, 167], > 3 months for long-term response [36, 46, 47, 54, 72, 164, 165]). As some of the included trails or reports extended over a long period, by derogation from the protocol [96], the section ‘follow-up response between four and six months’ was extended to ‘long-term and follow-up response between four and six months and more’. Secondary outcomes in the case of drop-outs were listed in the Table C21 (Appendix C). The reported deaths in seven cases [48] were caused by sepsis of preterm babies. No adverse side effects or contra indications were found in any of the included trials or reports.
3.4 Evaluation of relationships and subgroup analysis
Despite possible methodological weaknesses in the included items, relationships and subgroup analysis were evaluated for diagnosis, outcomes, comparison and duration of the intervention.
There was some accumulation of leading diagnoses in of the studies:
- microcephalia [50–54, 72]
- down-syndrome [44, 55]
- neurological disorders (high heterogeneity) [22, 44, 46–48, 50–55, 72, 164–167]
- myo-functional disorders [36, 44, 48, 49, 55]
Due to a heterogenic setting and inclusion criteria (addressing inconsistency [191]), differences in study population, intervention protocol, and measured outcomes (addressing indirectness [192]), a comparison or subgroup analysis for indication diagnoses cannot expect a high or moderate ranking according to GRADE-Guidelines [90]. Nevertheless, a GRADE evidence profile (EP) [90] was set up for I-IV regarding the outcome ‘condition improvement or alleviation of symptoms’.
Additional analysis of the potential outcomes of the studied therapy approach was carried out with consideration of the limitations, risk of bias and methodological weaknesses. Therefore the three domains of outcomes formulated in the initial PICOT question [96] (see the introduction) were addressed:
- motoric dysfunction
- neuropsychomotoric development disorder
- oro-facial or myo-functional disorder
- any other not yet listed diagnoses
By analysing the outcomes (see Tables 2 and D21 of Appendix C), it is found that speech or articulation difficulties are addressed several times and was therefore set as separate type of outcome (D). For each of the outcome domains (A-D), several primary outcomes (see Table C21 of Appendix C) can be assigned, whereas each primary outcome can be assigned to one or more outcome domains. Mapping all primary outcomes led to a subdivision of (A) into (A.i) motoric development and coordination and (A.ii) posture and axial symmetry impairment. (C) contains (IV) as per inclusion criteria, and was the destination for all outcomes in the context of swallowing or eating, excluding speech or articulation, as this was domain (D). Table C22 (Appendix C) shows the assignment of the primary outcomes and the relevant papers. The GRADE evidence profiles (EP) [90] for each subgroup are listed in Tables 7 (I-IV) and 8 (A-D).
Regarding the comparison of intervention, little data is available, as most of the included papers do not provide a control group or placebo. To their credit, developing a placebo for hands-on therapy is challenging. Only two of the included studies had a control group [49, 55], and all other items have to therefore be considered observational studies in terms of GRADE-Evidence rating [90].
The outcome of the PICOT question ‘modify the existing symptoms and quality of life within what time’ contains the treatment duration as a variable. Within the included studies, the duration of the applied therapy varied greatly, reaching from few days to multiple years. Outcomes were qualitatively described as partly emerging already after a few therapy sessions with additional results visible after at least a few months (see Tables 2 and D20 of Appendix C). Building subgroups for further analysis was not considered due to heterogeneity, very serious indirectness [192] and inconsistency [191].
3.5 Confidence in cumulative estimate
The EP of (I), (II), (III) and (A-D) summaries of findings according to GRADE [90] are shown in Tables 9 (I), 10 (II), 11 (III) and 12-15 (A-D). (IV) is not presented separately as included in (C) (Table 14). A downrating was inevitable in all items due to inconsistency, indirectness, imprecision and risk of bias regarding an evaluation of evidence and in most of the cases, due to study design, small sample sizes, heterogeneity and methodological weaknesses. The absence of a large magnitude effect, dose response in more than one item or confounders minimizing the effect in more than one item an uprating was not to be considered. Consequently, the GRADE quality rating [113] was very low for every defined item (very uncertain about the estimate of effect). This might confuse involved therapists and trainers, but should be seen in the scientific context and high standard of evaluation this review is based on. This is not intended for discouragement but rather to encourage future research and study design with high quality standards. Table 16 contains the derived PICOT recommendations for clinicians.
3.6 Meta-bias
Publication bias is present and possibly serious. During the research process, announcements for trials [81], trial reports [78, 79] and a systematic review [86] were found as conference poster or abstracts without any hint for full-text publication. Requests for more information provided no further data. Even though 14 of the included items were published, only three of the included items were found through database research (MEDLINE via PubMed [44], Embase [166], EBSCO/Ovid TOC Premier [49]), whereas all others were found searching grey literature, cross-reference or offline research throughout a network of therapists. The language used by the authors was English only in six cases [22, 44, 46–48, 55]. The accessibility of many items was restricted, aside from the included items composed in Portuguese [50–54, 72, 167] or German [36, 49, 164, 165]; other items were only available in French [37, 77, 158–162] or Spanish [163].
Outcome reporting bias is present but difficult to estimate, no study protocol or trial register was found. In two cases of published articles [44, 49] a prior thesis manuscript was available [45, 170] to provide more information on outcome as in the final article. Deficits in presentation of results were present in a large number of included items (see Tables 3-5).
3.7 PICOT Recommendation
The PICOT question was used to build recommendations regarding the included studies, case reports and analysis of the data considering the EP and SoF of each outcome (see Tables 8-15 and Table 16 Appendix Large Tables).
[Placeholder Table 16. Clinical recommendations]
3.8 Updated PICOT-question
Derived from results of the review and the information from the umbrella organisation of the Padovan-Method® (Brazil) [12], an overview of the target group (P) can be set as stated in Table C23 (Appendix C), adding information from articles identified through research process but not included into the analysis due to research character [10, 21].
The updated PICOT review question for further research is presented in Table C24 (Appendix C).