Primaire Idiopathische Klompvoet

Initiatief: NOV Aantal modules: 22

Ponseti met gipsredressies vs kunststof gips

Uitgangsvraag

4. Heeft binnen de Ponsetibehandeling het gebruik van kunststof gips de voorkeur boven het gebruik van Plaster of Paris?

Aanbeveling

Zie aanbevelingen bij hoofdmodule 'Behandeling van klompvoet'.

Overwegingen

Het Plaster of Paris gips voldoet qua resultaat van de behandeling prima, maar is relatief zwaar. In enkele behandelcentra wordt lichter, kunststof (Fiberglass) materiaal (Soft cast®) gebruikt. De lange termijn resultaten blijven het belangrijkst en zijn nog niet bekend bij gebruik van andere materialen dan het Plaster of Paris-gips. De beoordeelde studie is de enige studie die valide bevonden werd over deze deelvraag een uitspraak te doen. Uit de studie blijkt dat kunststofgips een lagere effectiviteit heeft in het primair corrigeren van idiopathische klompvoeten. Ondanks een gemiddeld hoger aantal benodigde redressies (statistisch niet significant), wordt een minder goede voetcorrectie bereikt (statistisch significant en klinisch relevant hogere Diméglioscores). Verschillen in oudertevredenheid met betrekking tot comfort, duurzaamheid en gewicht van de redressies zijn marginaal en statistisch niet significant. De werkgroep ziet derhalve geen reden om af te wijken van het standaard protocol en adviseert de Ponsetibehandeling uit te voeren met Plaster of Paris-gips.

Onderbouwing

LAAG

 

GRADE

De standaard klompvoetbehandeling volgens Ponseti met Plaster of Paris gipsredressies heeft een hogere effectiviteit dan dezelfde methode waarbij kunststofgips wordt gebruikt in het primair corrigeren van idiopathische klompvoeten.

 

Bronnen (Pittner et al., 2008)

Eén studie werd geïncludeerd (Pittner et al., 2008), een RCT waarin de klassieke Ponsetibehandeling van sequentiële gipsredressies wordt vergeleken met een variatie op Ponseti waarin kunststofredressies worden gebruikt. De Cochrane review (Gray) includeert dezelfde RCT en analyseert Diméglio scores voor voetcorrectie.

 

De RCT van Pittner, uitgevoerd in een Noord-Amerikaans ziekenhuis, randomiseert klompvoetpatiënten naar een standaard Ponsetibehandeling (n=18 patiënten) of Ponsetibehandeling met kunststof gipsredressies in plaats van de standaard Plaster of Paris (POP) gipsredressies (n=13). Een Achillespees tenotomie maakte deel uit van beide interventies (respectievelijk 87% en 88% van de patiënten). Diméglioscores voor voetcorrectie werden bepaald na de laatste gipsredressie voorafgaand aan een eventuele Achillespees tenotomie en waren statistisch significant en klinisch relevant in het voordeel van de standaard Ponsetigroep (gemiddelde Diméglioscore= 4,2 in de Ponseti gipsgroep versus 6,4 in de Ponseti kunststofgroep; p=0,04). Er bleken meer redressies nodig in de kunststofgroep, maar dit verschil was niet statistisch significant (aantal redressies = 5,2 in de Ponseti gipsgroep versus 6,1 in de Ponseti kunststofgroep; p=0,2). Lange termijn effecten werden niet onderzocht.

 

Bewijskracht

Bij beoordelen van de studies volgens GRADE is de bewijskracht laag voor effecten van klompvoetbehandeling (Ponsetibehandeling met Plaster of Paris gipsredressies versus de Ponsetibehandeling met redressies met behulp van kunststofgips) op voetcorrectie na behandeling (belangrijke uitkomstmaat). De bewijskracht is met twee punten verlaagd vanwege imprecisie (één enkele studie van geringe omvang) en ernstige tekortkomingen in studiekwaliteit (gebrekkige randomisatie en ontbreken blindering). Door een gebrek aan relevante gegevens in de geïncludeerde studies is er geen conclusie mogelijk ten aanzien van de overige uitkomstmaten.

In de databases Medline, Embase en Cochrane is met relevante zoektermen gezocht vanaf 1990 naar RCT’s, systematische reviews en zowel vergelijkend als niet-vergelijkend observationeel onderzoek (cohortstudies en case series) waarin gipsredressie en chirurgische methodes ter behandeling van klompvoet worden toegepast. De zoekstrategie is weergegeven in de tabel in bijlage 'Lijst met afkortingen'. De literatuurzoekactie leverde 381 treffers op. Studies die voldeden aan de volgende selectiecriteria zijn opgenomen in de samenvatting van de literatuur:

 

  • behandeling van overwegend jonge kinderen (jonger dan zes maanden) met congenitale idiopathische klompvoet, origineel vergelijkend onderzoek (deelvraag 1 tot 5) of origineel niet-vergelijkend onderzoek met een minimale omvang van twintig patiënten en een minimale follow-up van één jaar (alleen bij deelvraag 1);
  • behandeling volgens de klassieke Ponsetibehandeling of door middel van een posteromediale release (deelvraag 1), vergelijking van behandeling volgens Ponseti met behandeling volgens Kite (deelvraag 2), vergelijking van de klassieke Ponsetibehandeling met variaties op de klassieke Ponsetibehandeling (deelvragen 3 en 4), vergelijking van nabehandelingen volgend op Ponseti of posteromediale release (deelvraag 5);
  • met zowel korte als lange termijn en zowel functionele als niet-functionele uitkomstmaten.

 

Aan de literatuurselectie is één sleutelpublicatie toegevoegd; een Cochrane review verschenen na de zoekactie (Gray et al., 2012). De werkgroep benoemde de volgende uitkomstmaten als kritisch: voetfunctie op jonge leeftijd, stands- en degeneratieafwijkingen op volwassen leeftijd, voetfunctie en kwaliteit van leven op volwassen leeftijd. Als belangrijke uitkomstmaten werden benoemd: voetcorrectie na behandeling, het optreden van recidieven, het optreden van complicaties, patiënt- en oudertevredenheid en kosteneffectiviteit. Voor deelvraag 6 is geen aparte systematische search verricht, bij beantwoording is gebruik gemaakt van de zoekresultaten van deelvraag 1 tot 5. Voor deelvraag 7 is geen systematische zoekactie uitgevoerd.

  1. Adegbehingbe, O.O., Oginni, L.M., Ogundele, O.J., Ariyibi, A.L., Abiola, P.O., & Ojo, O.D. (2010). Ponseti clubfoot management: changing surgical trends in Nigeria. Iowa Orthop J., 30, 7-14.
  2. Andriesse, H., Hägglund, G., & Isberg, P.E. (2009). Reliability and validity of motion analysis in children treated for congenital clubfoot according to the Clubfoot Assessment Protocol (CAP) using inexperienced assessors. BMC Res Notes, 2, 103.
  3. Andriesse, H., Hägglund, G., & Jarnlo, G.B. (2005). The Clubfoot assessment protocol (CAP): description and reliablility of a structured multi-level instrument for follow-up. BMC Musculoskelet Disord, 6, 40.
  4. Andriesse, H., Roos, E.M., Hägglund, G., & Jarnlo, G.B. (2006). Validity and responsiveness of the Clubfoot Assessment Protocol (CAP). A methodological study. BMC Musculoskelet Disord, 7, 28.
  5. Atar, D., Lehman, W.B., Grant, A.D., & Strongwater, A.M. (1992). Revision surgery in clubfeet. Clin Orthop Relat Res., 283, 223-230.
  6. Blakeslee, T.J., & DeValentine, S.J. (1995). Management of the resistant idiopathic clubfoot: the Kaiser experience from 1980-1990. J Foot Ankle Surg., 34, 167-176.
  7. Bor, N., Coplan, J.A., & Herzenberg, J.E. (2009). Ponseti treatment for idiopathic clubfoot: minimum 5-year follow-up. Clin Orthop Relat Res., 467, 1263-1270.
  8. Changulani, M., Garg, N.K., Rajagopal, T.S,, Bass, A., Nayagam, S.N., … Bruce, C. E. (2006). Treatment of idiopathic club foot using the Ponseti method. Initial experience. J Bone Joint Surg Br., 88, 1385-1387.
  9. Church, C., Coplan, J.A., Poljak, D., Thabet, A.M., Kowtharapu, D., Lennon, N., … Miller, F. (2012). A comprehensive outcome comparison of surgical and Ponseti clubfoot treatments with reference to pediatric norms. J Child Orthop, 6, 51–59.
  10. Clarke, N.M., Uglow, M.G., & Valentine, K.M. (2011). Comparison of Ponseti versus surgical treatment in congenital talipes equinovarus. J Foot Ankle Surg., 50, 529-534.
  11. Cohen-Sobel, E., Caselli, M., Giorgini, R., Giorgini, T., & Stummer, S. (1993). Long-term follow-up of clubfoot surgery: analysis of 44 patients. J Foot Ankle Surg., 32, 411-423.
  12. Cooper, D.M., & Dietz, F.R. (1995). Treatment of idiopathic clubfoot. A thirty-year follow-up note. J Bone Joint Surg Am., 77, 1477-1489.
  13. Dobbs, M.B., Nunley, R., Schoenecker, P.L. (2006). Long-term follow-up of patients with clubfeet treated with extensive soft-tissue release. J Bone Joint Surg Am., 88, 986-996.
  14. Edmondson, M.C., Oliver, M.C., Slack, R., & Tuson, K.W. (2007). Long-term follow-up of the surgically corrected clubfoot. J Pediatr Orthop B., 16, 204-208.
  15. Esser, R.D. (1994). The medial sagittal approach in the treatment of the congenital clubfoot. A follow-up report of a 15-year experience. Clin Orthop Relat Res., 302, 156-163.
  16. Ferreira, L.F.A., Nogueira, M.P., Pereira, J.C.R, & Duarte, P.S. (2011). Comparison of hospital costs and duration of treatment with two different clubfoot protocols. Iowa Orthop J., 31, 49-51.
  17. Gelder, J.H. van, Ruiten, A.G. van, Visser, J.D., & Maathuis, P.G. (2010). Long-term results of the posteromedial release in the treatment of idiopathic clubfoot. J Pediatr Orthop., 30, 700-704.
  18. Graaf, J.C. de, Werff, D.B.M. van der, & Kalkman, C.J. (2013). Beschadigt anesthesie de hersenontwikkeling bij kinderen? Ned Tijdschr Geneeskd., 157, A5198.
  19. Graf, A., Hassani, S., Krzak, J., Long, J., Caudill, A., Flanagan, A., ... Smith, P. (2010). Long-term outcome evaluation in young adults following clubfoot surgical release. J Pediatr Orthop., 30, 379-385.
  20. Gray, K., Pacey, V., Gibbons, P., Little, D., Frost, C., & Burns, J. (2012). Interventions for congenital talipes equinovarus (clubfoot). Cochrane Database Syst Rev., 18, CD008602.
  21. Halanski, M.A., Davison, J.E., Huang, J.C., Walker, C.G., Walsh, S.J., & Crawford, H.A. (2010). Ponseti method compared with surgical treatment of clubfoot: a prospective comparison. J Bone Joint Surg Am., 92, 270-278.
  22. Halanski, M.A., Huang, J.C., Walsh, S.J., & Crawford, H.A. (2009). Resource utilization in clubfoot management. Clin Orthop Relat Res, 467, 1171-1179.
  23. Harnett, P., Freeman, R., Harrison, W.J., Brown, L.C., & Beckles, V. (2011). An accelerated Ponseti versus the standard Ponseti method: a prospective randomised controlled trial. J Bone Joint Surg Br., 93, 404-408.
  24. Janicki, J.A., Wright, J.G., Weir, S., & Narayanan, U.G. (2011). A comparison of ankle foot orthoses with foot abduction orthoses to prevent recurrence following correction of idiopathic clubfoot by the Ponseti method. J Bone Joint Surg Br., 93, 700-704.
  25. Kite, J.H. (1935). The treatment of congenital clubfoot. Surg Gynaec. Obstet., 61, 190.
  26. Magone, J.B., Torch, M.A, Clark, R.N., & Kean, J.R. (1989). Comparative review of surgical treatment of the idiopathic clubfoot by three different procedures at Columbus Children's Hospital. J. Pediatr. Orthop., 9, 49-58.
  27. Morcuende, J.A., Abbasi, D., Dolan, L.A., & Ponseti, I.V. (2005). Results of an accelerated Ponseti protocol for clubfoot. J Pediatr Orthop., 25, 623-626.
  28. Morcuende, J.A., Dolan, L.A., Dietz, F.R., & Ponseti, I.V. (2004). Radical reduction in the rate of extensive corrective surgery for clubfoot using the Ponseti method. Pediatrics., 113, 376-380.
  29. Papavasiliou, V.A., & Papavasiliou, A.V. (2004). A novel surgical option for the operative treatment of clubfoot. Acta Orthop Belg., 70, 155-161.
  30. Pittner, D.E., Klingele, K.E., & Beebe, A.C. (2008). Treatment of clubfoot with the Ponseti method: a comparison of casting materials. J Pediatr Orthop., 28, 250-253.
  31. Ponseti, I.V., Zhivkov, M., Davis, N., Sinclair, M., Dobbs, M.B., & Morcuende, J.A. (2006). Treatment of the complex idiopathic clubfoot. Clin Orthop Relat Res., 451, 171-176.
  32. Ponseti, I.V. (1996). Congenital Clubfoot. Fundamentals of treatment. Oxford University Press.
  33. Rijal, R., Shrestha, B.P., Singh, G.K., Singh, M., Nepal, P., Khanal, G.P., & Rai, P. (2010). Comparison of Ponseti and Kite's method of treatment for idiopathic clubfoot. Indian J Orthop., 44, 202-207.
  34. Sanghvi, A.V., & Mittal, V.K. (2009). Conservative management of idiopathic clubfoot: Kite versus Ponseti method. J Orthop Surg (Hong Kong)., 17, 67-71.
  35. Schlegel, U.J., Batal, A., Pritsch, M., Sobottke, R., Roellinghoff, M., Eysel, P., & Michael, J.W. (2010). Functional midterm outcome in 131 consecutive cases of surgical clubfoot treatment. Arch Orthop Trauma Surg., 130, 1077-1081.
  36. Segev, E., Keret, D., Lokiec, F., Yavor, A., Wientroub, S., Ezra, E., & Hayek, S. (2005). Early experience with the Ponseti method for the treatment of congenital idiopathic clubfoot. Isr Med Assoc J., 7, 307-310.
  37. Sud, A., Tiwari, A., Sharma, D., & Kapoor, S. (2008). Ponseti's vs. Kite's method in the treatment of clubfoot--a prospective randomised study. Int Orthop., 32, 409-413.
  38. Templeton, P.A., Flowers, M.J., Latz, K.H., Stephens, D., Cole, W.G., & Wright, J.G. (2006). Factors predicting the outcome of primary clubfoot surgery. Can J Surg., 49, 123-127.
  39. Uglow, M.G., & Clarke, N.M. (2000). The functional outcome of staged surgery for the correction of talipes equinovarus. J Pediatr Orthop., 20, 517-523.
  40. Zionts, L.E., & Dietz, F.R. (2010). Bracing following correction of idiopathic clubfoot using the Ponseti method. J Am Acad Orthop Surg., 18, 486-493.
  41. Zwick, E.B., Kraus, T., Maizen, C., Steinwender, G., & Linhart, W.E. (2009). Comparison of Ponseti versus surgical treatment for idiopathic clubfoot: a short-term preliminary report. Clin Orthop Relat Res., 467, 2668-2676.

Evidence table for intervention studies

Research question: how should congenital idiopathic clubfoot be treated?

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Level of evidence

Comments

Ponseti versus PMR (comparative studies) 2 RCTs / 3 cohort studies

Church et al, 2012

 

 

 

 

 

 

 

 

 

Retrospective cohort; 2 cohorts compared

 

Group-1 (PMR)

N=26 patients

N= 43 clubfeet

73% male

Age 9.2 ± 1.3 y

 

Group-2 (Pons)

N=22 patients

N= 35 clubfeet

41% male

Age 6.3 ± 1.4 y

 

Time period =

1999 – 2003 (initial treatment)

 

Setting/country:

hospitals; USA

 

Source of funding, declaration of proprietary or financial interest: no conflicts of interest or sources of funding

Inclusion criteria:

diagnosis of isolated clubfoot treated from birth and minimum follow-up (post treatment) of 5 years; time period 1999–2003

 

recruited at 2 sites: Ponseti site versus surgical site; all children who fitted the criteria were contacted

 

Two groups were age-matched but not matched according to severity (pre-operative data were not available for operative site)

 

Exclusion criteria:

None mentioned

 

Groups comparable at baseline? No; possible difference in severity; age range similar but mean age differs; treated at 2 different sites

 

Diagnosis: based on

absence of other identified diagnoses; only idiopathic clubfeet included

I: Ponseti

N=22 patients

N= 35 clubfeet

 

 

 

 

 

 

 

 

 

Ponseti

Ponseti with average 5 casts for 5 weeks; foot abduction brace (FAB); 18/22 (82%) had percutaneous Achilles tenotomies

 

Relapse requiring surgery: 3/35 (9%; 2 with TATT, 1 TAL) ; total relapse, requiring additional casting or surgery 5/35 feet (14%)

C:Surgical (PMR)

N=26 patients

N= 43 clubfeet

 

In addition, normative data were collected from a convenience sample of subjects with no reported foot deformity, motor disorder, or pain, and no observable gait deviations

 

Surgical (PMR)

Initially casted (3–4 casts), and then traditional PMR (Turco); casted with pins for 4 weeks and followed up with splinting

 

Relapse requiring surgery: 14/43 feet (33%) required repeat surgical intervention 11/14 feet (79%; 26% of all clubfeet) required major surgery

 

Minor = joint-sparing; tendon lengthenings and transfers

 

Major = joint-opening procedures or boney realignment procedures

 

Endpoint of follow-up: minimum 5 years

 

Group-1 (PMR)

Age at operation

10 months (range, 2-33 m);

Age at end follow-up 9.2 ± 1.3 y

 

Group-2 (Pons)

Treated from birth; Age at end follow-up 6.3 ± 1.4 y

 

For how many participants were no complete outcome data available?

Not mentioned (only patients with ≥5 years follow-up were included ..)

 

Reasons for incomplete outcome data described?

Not relevant

 

Significant differences between groups?

Not relevant

 

Treatment quality; gait, pedobarograph, physical examination,

questionnaires, radiographs; relapse (requiring surgery)

 

Gait: kinematic analysis; multi-segment foot model

 

Pedobarograph: heel pressure and medial and lateral column pressures

 

Physical examination:

passive ROM, flexibility, static rotational alignment, manual muscle-testing strength

 

Questionnaires:

pediatric Outcomes Data Collection Instrument (PODCI; normal=100; higher=better); Activities Scale for Kids (ASK; normal=100; higher=better); clubfoot disease-specific instrument (DSI; 10-40; higher=better QOL); Diméglio scale (0-20; lower=better)

 

Radiographs: standing anteroposterior and lateral radiographs (: angles)

 

Gait

 Pedobarograph

Physical examination

Radiographs

Ponseti group had significantly better plantarflexion and dorsiflexion range, greater push-off power, less residual in-toeing; PMR group had significantly increased varus and decreased medial foot pressure, greater stiffness in dorsiflexion, plantarflexion, ankle inversion, and midfoot abduction and adduction; greater equinus and cavus and increased foot internal rotation profile (for details see full text)

 

Questionnaires

median (IQR)

 

PODCI – global funct.

I: 99 (5)

C: 97 (8)

P=0.008

 

ASK

I: 98 (6)

C: 93 (8)

P= NS

 

DSI

I: 12 (3)

C: 16 (6)

P<0.001

 

Diméglio scale

I: 4 (3)

C: 15 (7)

P<0.001

 

Relapse

Requiring surgery

I: 3/35 feet (9%)

C: 14/43 (33%)

 

11/14 relapsed feet in C (PMR) required major surgery (26% of total); in I (Ponseti), only minor surgery (2 TATT and 1 TAL)

Low number of patients; intermediate (no long-term) follow-up; retrospective comparison of 2 cohorts recruited and treated at different sites (potential confounding); groups differ (age at end of follow-up); functional evaluation

 

No reasons to upgrade the level of evidence

 

 

See GRADE-profile per intervention (comparison) and outcome measure (taking all relevant studies together)

 

 

Outcome measure = Treatment quality

 

Level of evidence = LOW

 

Authors conclude that Ponseti-treated group required fewer repeat surgical interventions, walked with a better quality of gait, showed better static alignment and foot mobility, and had better global functioning; residual deformity persists, but is much less severe in the Ponseti group

 

Note: almost no baseline characteristics of the treatment groups are mentioned (considerable risk for confounding), and no data on brace compliance

 

Intermediate length of follow-up, i.e. not into skeletal maturity

Halanski et al, 2010

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Prospective cohort

 

N=55 patients

N= 86 clubfeet

 

Time period =

Nov 2001 – Jan 2005

 

Setting/country:

National children’s hospital; New Zealand

 

56% bilateral; 69% male; 60% Polynesian; 47% with pos family history; average Pirani score of 5.2; average follow-up of 3.7 y (range 2.2-5.7 y)

 

 

Source of funding, declaration of proprietary or financial interest: no external funding

Inclusion criteria:

newborns referred for clubfoot treatment; idiopathic clubfoot; only patients with ≥2 years follow-up were included in analysis

 

Families chose randomization (9 families) or selected their choice of treatment (majority) based on information supplied by clubfoot nurse coordinator, handouts and websites; data analyzed together (prospective cohort); clinical data collected prospectively; the two treatments managed by two separate surgeons (one favoring Ponseti, the other favoring surgical treatment)

 

Exclusion criteria:

None mentioned

 

Groups comparable at baseline? Yes; with respect to sex, ethnicity, family history, bilaterality, mean age at 1st cast, and Pirani score

 

Diagnosis: not specified; only idiopathic clubfeet included

I: Ponseti

N= 26 patients

N= 40 clubfeet

 

Weekly intervals with above-the-knee casting (Ponseti); followed by percutaneous Achilles tenotomy and final cast for three weeks; abduction orthosis (open-toed, high-top shoes; M.J. Markell Shoe) attached at shoulder width Denis Browne bar

 

Parents instructed to ensure full-time brace wear for 3 months, followed by night and naptime wear until at least age of 2 years

 

Compliance defined as full-time brace wear for 3 months followed

by at least 9 months of night and naptime use

 

Initial percutaneous Achilles tenotomy was not considered a primary surgical procedure but part of Ponseti method

 

Characteristics (mean)

age at 1st cast = 21 d

number of casts = 6

95% of clubfeet had Achilles tenotomy

age at tenotomy = 2.4 m

 

C:Surgical (PMR)

N= 29 patients

N= 46 clubfeet

 

Feet treated with below-the knee plaster casts with upward directed

pressure to progressively correct the equinus deformity; changed weekly or biweekly until six months of age

 

When indicated (subjective; by surgeon; 93% of the cases), surgery was scheduled; majority underwent posterior or posteromedial release and subsequent cast changes (Cincinnati incision); typically one subsequent cast or splint change; after final cast or splint removal, patients followed clinically without additional bracing; patients in whom deformity was corrected after below-the-knee casting alone were managed with a similar orthosis as those in the Ponseti group

 

 

Characteristics (mean)

age at 1st cast = 18 d

number of casts = 13

age prim. surgery = 6.7 m

prim. surgery = 43 (93%)

of which, major = 42 (91%) with posterior release (11) or posteromedial release (31)

Endpoint of follow-up: minimum 2 years; average of 3.7 years

 

For how many participants were no complete outcome data available?

Not mentioned (only patients with ≥2 years follow-up were included ..)

 

Reasons for incomplete outcome data described?

Not relevant

 

Significant differences between groups?

Not relevant

 

 

Treatment quality; proportion (%), p-values

 

Treatment failure, defined as surgical recurrence (minor / major); complications; risk factors (multivariate model)

 

Surgical recurrence: recurrence of foot deformity requiring operative interventions (note that initial surgery in control group is not considered a surgical recurrance)

 

Severity of surgical recurrence:

Minor= extra-articular soft-tissue procedure such as open Achilles tendon lengthening;

Major= intra-articular surgical procedure, including corrective osteotomies

 

Revision surgery= feet undergoing an initial surgical procedure that subsequently were found to have a recurrence requiring surgery

 

Surgical recurrence

Feet (%) / patients (%)

 

Total recurrence

I: 15(38%) / 12(46%)

C: 14(30%) / 8(28%)

P: 0.5 (NS) / 0.17 (NS)

NS: non-specific

 

Minor recurrence

I: 11(28%) / 9(35%)

C: 2(4.3%) / 2(6.9%)

P: 0.003 / 0.03

 

Major recurrence

I: 4(10%) / 3(12%)

C: 12(26%) / 7(24%)

P: 0.003 / 0.03

 

Revision surgery

I: 1(2.5%) / 1(3.8%)

C: 14(30%)* / 8(28%)

P: <0.001 / 0.03

 

* one foot operated twice and counted twice

 

Model for recurrence

logistic regression

 

Family history:

OR= 3.81 [1.11; 13.04]

 

Other variables: treatment type, race, Pirani, statistically non-significant (only p-values given; P>0.15)

 

Separate model for Ponseti to test influence of brace compliance (non-significant; P=0.67)

 

Post-operative complications

I: 2 patients

C: 2 patients

P: NS

Post-operative URTI, cellulitis, wound slough and / or infection

Patients with < 2 years follow-up were excluded (selection bias); there were no set criteria for defining an operative recurrence (potential bias); the minor/major surgical recurrence classification system is biased to the Ponseti method because the surgeon attempted to avoid intra-articular surgery unless absolutely necessary (and this was not the case for the surgeon of the surgical group; potential selection bias); low number of patients; no long-term follow-up; no functional evaluation

 

No reasons to upgrade the level of evidence

 

 

See GRADE-profile per intervention (comparison) and outcome measure (taking all relevant studies together)

 

 

Outcome measure = Treatment quality

 

Level of evidence = LOW

 

Authors conclude that both treatments had a relatively high recurrence rate, but that Ponseti group was managed with less operative intervention and required less revision surgery

 

A recent parallel study shows that Ponseti is more cost-effective than the surgical method (Halanski et al, 2009)

 

The authors observed ‘poor compliance with orthotic wear’, even ‘despite lowering recommended total brace wear from the age of 3-4 years (recommended by Ponseti) to 1 year’; this lack of compliance must be taken into account in clinical decision-making

 

Note that difference in functional outcome between the two interventions is not known, and long-term functional data are needed

 

Note that this study was performed in New Zealand, and 1/5 of the population claims a Polynesian ethnic background; the estimated incidence of 6.8 clubfeet per 1000 in Polynesian populations, is considerably higher than the incidence of 1 per 1000 estimated for European populations; local orthopaedic

community believes that clubfeet in the Polynesian population may be more resistant to treatment

 

Note that in this study, below-the-knee casts were applied in the surgical group, which may have reduced the need for full PMR, and may also have affected the need for subsequent surgery

 

Note the 30% to 40% relapse rate, higher than reported in the literature; may relate to the New Zealand population

Adegbehingbe et al., 2010

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

RCT

Double-blind

 

N=105 patients

N=153 clubfeet

ITT

 

Time period =

Oct 2007 – Nov 2009

 

Setting/country:

University Teaching Hospital; Nigeria

 

46% bilateral; sex not mentioned; severity (Diméglio-Bensahel score; max 20):

0-5 (34%)

6-10 (33%)

11-15 (23%)

16-20 (10%); age newborns and children upto 360 months; non-diopathic (23%)

 

 

Source of funding, declaration of proprietary or financial interest: not mentioned

Inclusion criteria:

All cases of consenting clubfoot, at any age, idiopathic, syndromic/asyndromic, unilateral or bilateral clubfoot, with or without previous treatment and/or post surgical recurrence; patients with minimum follow-up of three months post last casting were included

 

randomization using computer-generated random numbers; assessors and patients/parents blinded to allocations; assigned to study group by chief nursing officer blinded to managing team and study protocol; consultant orthopaedic surgeon as blinded clinical outcome evaluator; orthopedic managing teams were blinded to clubfoot patient’s selection

 

Exclusion criteria:

patients not primarily treated at participating institution; patients

discharged against medical advice; patients with acquired clubfoot

 

Groups comparable at baseline? No; despite randomization, large difference in age (I versus C, 58% versus 28% with age < 6 months)

 

Diagnosis: not specified; both idiopathic, and syndromic/asyndromic clubfeet included

I: Ponseti

N= 55 patients

 

according to Ponseti; manipulation performed and retention casts changed weekly; correction of neglected idiopathic clubfeet by Ponseti with

minimal modification; foot abducted to 30-40 degrees; Equinus corrected via percutaneous tenotomy of the tendo Achilles

 

Locally fabricated abduction foot braces made available; patient’s compliance braces was generally good (no details provided)

 

Initial percutaneous Achilles tenotomy (performed in only 5.5% of patients) was considered a primary surgical procedure (: prim. outcome measure)!

 

 

 

C: Non-Ponseti (“PMR”)

N= 50 patients

 

routine clubfoot manipulation and soft tissue (tendon and ligament) stretching; mothers taught to do manipulation; Robert Jones strapping, Denis Browne splints and Kite’s methods were non-operative treatments utilized.

 

 

 

 

 

 

 

 

Clubfeet that failed ended up receiving (extensive) soft tissue/bony surgery (66% had surgery; 34 % had extensive surgery); considered a primary surgical procedure (: prim. outcome measure)!

 

 

Endpoint of follow-up: minimum 3 months after last casting (inclusion criterium)

 

Fup varies from <12 m to upto 120 months

 

For how many participants were no complete outcome data available?

None?: (but note difference in length of follow-up between groups ..)

 

Reasons for incomplete outcome data described?

Not relevant

 

Significant differences between groups?

Yes; much longer follow-up in non-Ponseti group: 84% > 12months, versus 36% in Ponseti group

 

 

Treatment quality; proportion (%), p-values

 

Treatment failure, defined as requiring extensive soft tissue (ST) surgery; number of casts required; costs of care; complications; recurrence; succesful treatment (Diméglio score ≤6)

 

Note that initial surgery (Achilles tenotomy, PMR) is part of primary outcome measure

 

Minor surgery = achilles tenotomy;

Major surgery = extensive soft tissue surgery, anterior tibialis tendon transfer, posterior capsulotomy, triple arthrodesis

 

Clubfoot treatment judged satisfactory if Diméglio-Bensahel score < 6 at the last follow-up clinic (satisfactory ‘early outcome’)

 

Costs: judged low when patient received max 6 casts with or without minor surgery

 

Extensive ST surgery

Patients (%)

I: 0/55 (0%)

C: 17/50 (34%)

P<0.000

 

No Surgery required

Patients (%)

I: 52/55 (94.5%)

C: 17/50 (34%)

P<0.000

 

Number of casts

Patients with >6 casts

I: 13 / 55 (23.6%)

C: 35 / 50 (70.0%)

P< 0.000

 

Satisfactory treatment

Diméglioscore≤6

I: 55 / 55 (100%)

C: 29 / 50 (58%)

P< 0.000

 

 Recurrence

I: 2 / 55 (3.6%)

C: 24 / 50 (48%)

P< 0.000

 

Treatment complicat

Ugly scar, recurr(?), blister, infection

I: 2 / 55 (3.6%)

C: 21 / 50 (42.0%)

P< 0.003

Patients with < 3 months follow-up were excluded (selection bias); Large differences between treatment groups at baseline (age) and at end of follow-up (length of follow-up); mixed cases (idipathic, non-idiopathic, neglected clubfeet); treatment in control group not well-defined (mix of non-Ponseti treatments); setting (Nigeria) has low relevance for situation in NL; low number of patients; no long-term follow-up; no functional evaluation

 

reasons to downgrade the level of evidence

 

 

See GRADE-profile per intervention (comparison) and outcome measure (taking all relevant studies together)

 

Outcome measure = Treatment quality

 

Level of evidence = LOW

 

Authors conclude that Ponseti method has reduced clubfoot surgery frequency and reduced cast utilization, resulting in reduced total care costs

 

Note that the difference in functional outcome between the two interventions is not known, and long-term functional data are needed

 

Note that this study was performed in Nigeria

 

The authors observed ‘maintaining correction with the foot abduction bar is paramount to succesful treatment’, and ‘relapsing cases in Ponseti group were related to delay in procurement and use of abduction foot braces’(no details mentioned)

 

Authors note ‘Competent

surgical management of clubfeet should yield about 90%

satisfactory results at skeletal maturity’

 

‘Good results imply a flexible, plantigrade foot with the ability to bear weight on the forefoot through strong gastrocneumius muscle contraction, minimal cavus and a slightly externally rotated foot-progression axis’

 

‘When the re-operation rate is more than 5 to10%, the surgical method employed requires re-evaluation’

Clarke et al, 2011

 

(re-uses data from Uglow and Clarke, 2000)

 

 

 

 

 

 

 

 

 

 

 

 

 

Retrospective

Cohort

 

Historical control (prospective)

 

Period-I: June 2002 – Dec 2004

N=70 patients

N=107 clubfeet

 

Period-II: 1988 – 1995

N=86 patients

N=120 clubfeet

Data on period-II from Uglow and Clarke, 2000

 

General hospital; UK

 

Inclusion criteria: children with clubfeet and ≥2 years of follow-up after beginning treatment, or relapse

 

Exclusion criteria: genetic deformity, or neurologic involvement

 

Groups comparable at baseline? Yes; similar Diméglio scores (but note considerable loss to follow-up; no details on these patients)

 

Diagnosis: not specified; idiopathic clubfeet

I: Ponseti

N= 50 patients

N=75 clubfeet

 

 

 

 

 

Standard Ponseti treatment, including percutaneous tenotomy (in 85% patients); ‘most patients treated within the first few weeks after birth’

 

 

Tenotomy is considered part of treatment

 

Same center / same surgeons

 

Diméglio score:

At baseline; number feet (% total feet)

1 (1.3%)   grade-1

11 (14.7%) grade-2

46 (61.3%) grade-3

17 (22.7%) grade-4

No statistically significant differences between intervention and control groups

 

 

C: surgical (PMR)

N= 68 patients

N= 91 clubfeet

 

Physiotherapy, passive stretching and serial plaster casts; followed by

 

2-stage PMR; at mean age 8.9 months; plantar medial release + posterolateral release 2 weeks later; followed by above the knee plaster casts; splints at night, usually upto age 2 years

2-stage PMR is considered part of treatment

 

Same center / same surgeons

 

Diméglio score:

 

 

0 (0%)     grade-1

11 (12.1%) grade-2

54 (59.3%) grade-3

26 (28.6%) grade-4

 

 

 

Endpoint of follow-up: minimum 2 years or relapse (inclusion criterium)

 

Fup varies from ‘2.5-year presentation period’ (Ponseti) to ‘7-year presentation period’ (PMR)

 

For how many participants were no complete outcome data available?

I: 11 out of 61 patients had follow-up <2 years (18%); C: 18 out of 91 feet had fup <2 years (20%); no details provided on these patients

 

Reasons for incomplete outcome data described?

No

 

Significant differences between groups?

.....

Treatment quality; rate (%), p-values

 

Treatment failure defined as relapse; relapse = requiring recasting or additional operative procedures (after initial Ponseti/tenotomy, or 2-stage PMR)

 

Relapse rate as function of baseline Diméglio grade (severity)

 

Overall:

I: 24/75 (32%)

C: 28/91 (31%)

P=NS

 

Grade-2

I: 2/11 (18.2%)

C: 0/11 (0%)

P=NS

 

Grade-3

I: 16/46 (36.2%)

C: 11/54 (20.4%)

P=NS (P= 0.106)

 

Grade-4

I: 6/17  (35.3%)

C:17/26 ( 65.4%)

P= NS (P= 0.053)

‘near significance’

 

All p-values non-significant

Multiple testing (not adjusted for in statistical methods); much longer follow-up period in control group (PMR); use of historical control group; small sample size

 

No reasons to upgrade the level of evidence

 

 

See GRADE-profile per intervention (comparison) and outcome measure (taking all relevant studies together)

 

 

Outcome measure = Treatment quality

 

Level of evidence = LOW

 

Authors conclude that the Ponseti method is as valid as the 2-stage operative method (based on a comparison of relapse rates)

 

Note: (1) no functionale outcomes of the treatment methods were collected; (2) no data are provided on compliance to bracing; (3) follow-up is (much) longer in the surgical group which may bias data on relapse rate

 

Authors suggest that surgery should still be chosen in certain circumstances, but restricted to grade 2 or 3 feet (and not be used in grade 4 feet)

 

Findings for grade-4 clubfeet (very severe) was near statistical significance, in favor of Ponseti treatment

 

Relation Diméglio score (severity) and relapse: not significant in Ponseti group, but highly significant in PMR group (P= 0.001)

Farsetti et al, 2009

 

Follow-up study on Ippolito et al, 2003

 

Not analyzed: also see Ippolito et al, 2003, studies compare PMR with a modified Ponseti method which involves mild PMR instead of tenotomy

 

EXCLUDED

 

 

 

 

 

EXCLUDED

 

 

Zwick et al, 2009

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

RCT

Unblinded

 

ITT

N= 19 patients

N= 28 clubfeet

 

Single center; university hospital; Austria

Inclusion criteria: otherwise healthy infants younger than 2 weeks born with

clubfoot/clubfeet and without any other congenital anomalies

 

Exclusion criteria: none mentioned

 

Groups comparable at baseline? Yes; similar Pirani scores (severity)

 

Diagnosis: not specified; idiopathic clubfeet

I: Ponseti

N= 9 patients (ITT)

N=12 clubfeet (ITT)

 

Standard Ponseti treatment, including percutaneous tenotomy (in all patients); 6 to 8 plaster casts; Orthotic management for 24 months (Tibax bar with GloboPed shoes and a splint); molded insoles when walking

 

 

Per protocol analysis (PP):

N= 7 patients

N=10 clubfeet

Parental reasons for opting out the 2 patients were discomfort of the infant in the orthoses

 

 

C: surgical (PMR)

N= 10 patients (ITT)

N= 16 clubfeet (ITT)

 

PMR

Plaster casts for 5.5 to 11.4

months followed by PMR; posteromedial release plaster casts after surgery for 6 months; rigid knee-ankle-foot orthoses for nighttime splinting to the age of 36 months; molded insoles when walking

 

No protocol violations

Endpoint of follow-up: mean 3.5 years (range 3.3-3.8 years)

 

For how many participants were no complete outcome data available?

None (no loss to follow-up)

 

Reasons for incomplete outcome data described?

Not relevant

 

Significant differences between groups?

Not relevant

Treatment quality; foot function (score), health status (score), radiographic outcome (angle): median scores, p-values

 

Foot function measured using Functional Rating System (FRS) of Laaveg and Ponseti: Satisfaction (max 20 points), Function (20), Pain (30), Position of heel when standing (10), Passive motion (dorsiflexion [5], Varus-valgus motion of heel [3], Anterior inversion-eversion of foot [2]), Gait (10), Total score (100); treatment succes defined as FRS ≥ 75 (out of 100 points)

 

Health status at 3.5 years of age according to PODCI score (Pediatric Outcomes Data Collection Instrument) for transfer and basic mobility, sports and physical functioning, pain and comfort, happiness, and the global function scale

 

Radiographic outcome measures: from radiographs, using handhold goniometer; Lateral tibiocalcaneal angle, Anteroposterior talocalcaneal angle, Lateral talocalcaneal angle

 

Foot function (FRS)

Passive dorsiflexion

I: 4

C: 2

P= 0.006

 

Varus-valgus motion

I: 2

C: 1

P= NS

 

inversion-eversion

I: 1.5

C: 1

P= 0.026

 

Total score

I: 94.5 (95 in PP)

C: 84 (84 in PP)

P= 0.002

P= 0.0001 in per protocol (PP) analysis

 

Health status (PODCI)

I: 94.4

C: 94.8

P= NS

 

Radiographic outcome

No significant differences

 

Similar outcomes in per protocol (PP) analysis

Randomization procedure not well-described (‘using a randomization table’); no blinding; very small number of patients; trial stopped early for ethical reasons (because of apparent efficacy in intervention group); multiple testing (significance level < 0.0004 with Bonferroni adjustment); independent outcome accessor (but not blinded?); relatively short follow-up

 

 

reasons to downgrade the level of evidence

 

 

See GRADE-profile per intervention (comparison) and outcome measure (taking all relevant studies together)

 

Outcome measure = Treatment quality

 

Level of evidence = LOW

 

None of the patients experienced foot pain, and all feet had a plantigrade position when standing; the FRS category for gait was comparable in both groups; health status and radiographic variables (foot angles) were also similar between groups

 

The Ponseti group scored significantly higher in FRS total score (in parental satisfaction, and in categories for passive motion: passive maximal dorsiflexion, and total anterior inversion-eversion mobility)

 

Overall, foot function can be classified as good for the control group (PMR), and excellent for the Ponseti group

 

Very small study; stopped early for ethical reasons before reaching sufficient power (at 23 clubfeet per treatment)

Non-comparative studies (including studies with healthy controls): Ponseti  5 cohort studies

Bor et al, 2009

 

 

 

 

 

 

 

 

 

 

 

Retrospective cohort

 

N= 74 patients

N= 117 clubfeet

 

Time period = 1997 – 2002 (initial treatment)

 

2 Pediatric orthopedic units; Israel and USA

Inclusion: 88 patients with idiopathic clubfoot between 1997 and 2002

 

Exclusion: 14 because loss to follow-up

 

74 patients (117 clubfeet); 48 boys; 43 bilateral, 31 unilateral

 

Graded (Pirani 6-point severity score)

 

Diagnosis: not specified; idiopathic clubfeet

 

Pirani score

6-point initial severity;

Mean (SD)

5.1 (1.3)

 

 

 

 

 

 

 

I: Ponseti

N= 74 patients

N= 117 clubfeet

 

Ponseti treatment

strict Ponseti protocol; including percutaneous Achilles tenotomy (if required; in 86% patients)

 

 

C: no controls

Endpoint of follow-up: mean 6.3 y (range 5– 9 y)

 

Mean age at presentation 67 days

 

14 patients (16%) lost to follow-up (were excluded)

 

Treatment success; brace use; ROM; parent’s satisfaction

 

Treatment succes defined as requiring no or only minor additional surgery (apart from tenotomy); minor (TATT), moderate (posterior release), major (PMR)

 

Good brace use defined as full-time use for >3 months followed by >9 months nighttime use (based on questioning parents )

 

Parent’s satisfaction using 10-item clubfoot Disease Specific Instrument (DSI)

 

Brace compliance

31/70 (44.3%) poor

39/70 (55.7%) good

 

ROM

Final dorsiflexion

97/109 feet ‘adequate’

 

Treatment success

99/111 (89.2%) ‘good’

Did not require surgery or only minor surgery

 

Parent’s satisfaction 10-item DSI

 Mean score (1=best, 4=worst)

 

Satisfaction index

1.2 (range 1-4)

 

Brace compliance and need for additional surgery

 

Poor compl: 45.2%

Good compl: 20.5%

P=0.03

No comparison of treatments (not rated with GRADE); association analyses were not corrected for confounders; use of parent-reported data for brace use; intermediate follow-up (not into adulthood); no functional outcome measures

 

Outcome measure = Treatment quality

 

Level of evidence = VERY LOW

 

 

 

 

 

 

Authors conclude that 89% achieved a good outcome (requiring no additional surgery or only minor additional surgery), and that parent’s satisfaction is high

 

In addition, good brace use (compliance) was associated with a reduced need for additional surgery

 

Changulani et al, 2006

 

 

 

 

 

 

 

 

 

 

 

 

Retrospective cohort

 

N= 66 patients

N= 100 clubfeet

 

Time period = Nov 2002 – Nov 2004

 

Children’s hospital; UK

Inclusion criteria: 66 consecutive children with clubfeet; Referred from maternity units, general practitioners, and other orthopaedic centres

 

Often (32%) after other methods of treatment

had resulted in little or incomplete correction

 

Exclusion: children with other congenital deformities, syndromes or neurological causes of club feet

 

 

I: Ponseti

N= 66 patients

N= 100 clubfeet

 

Ponseti treatment

Ponseti; as soon as possible after birth; aboveknee plaster cast at weekly intervals for 4-12 weeks; Achillis tenotomy if necessary (85%); foot-abduction orthosis (Denis Browne splint), full-time 3 months followed by night- time up to 4 years

C: no controls

Endpoint of follow-up: mean 18 months (range 6-30 months)

 

Mean age at presentation 12 weeks (range 1-60 weeks)

 

No loss to follow-up

Treatment success (Pirani score); non-response; relapse; compliance

 

Poor compliance defined as failure to use splint continuously for at least 10 hours a day (parents answer)

 

Non-response

4/100 (4%) required PMR (‘resistant clubfeet’)

 

96(96%) clubfeet were responsive

 

Relapse

31/96 (32%)

16/96 repeat casting

15/96 (16%) PMR

 

Compliance

21/31 (68%) of relapsed clubfeet had poor compliance (no statistics mentioned)

 

Pirani (mean[ range])

Before/after follow-up

 

Hind-foot contracture

2.5[2-3] / 0.5[0-1]

Mid- foot contracture

2.5[2-3] / 0

Total Pirani score

5.0[4-6] / 0.5[0-1]

No comparison of treatments (not rated with GRADE); use of parent-reported data for brace use; short follow-up; small study; no functional outcome measures

 

Outcome measure = Treatment quality

 

Level of evidence = VERY LOW

 

Authors conclude that in more than 80% of feet, the deformity was corrected avoiding PMR

 

Percutaneous tenotomy required in 85%; damage to neurovascular structures in 1 child

 

Most cases of relapse seem related to poor compliance: parents

reported difficulty in keeping foot in splint; some found it difficult to apply the splint single-handed and others reported that their child was unable to kick the legs freely and was unable to roll over in bed; these problems caused frustration in the family and often sleepless nights leading to poor compliance

Ponseti et al, 2006

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Retrospective cohort

 

N= 50 patients

N= 75 clubfeet

 

Time period = Oct 1992 – Feb 2004

 

Orthopaedic dept; multicentre (USA, UK, Bulgaria, Germany)

 

Inclusion criteria: congenital idiopathic

clubfoot treated Oct 1992 – Feb 2004; with complex clubfeet

 

complex clubfeet:

in severe equinus and supination, short and stubby, with adducted metatarsals in plantar flexion and deep creases across sole of foot and above heel

 

Exclusion: patients

with arthrogryposis, syndromic, or neuromuscular clubfeet

 

762 patients; 50 patients with 75 complex clubfeet; 31 (62%) male; 31 (62%) had initial (plaster cast) treatment elsewhere with 11 (22%) percutaneous Achillis tenotomy

I: Modified Ponseti

N= 50 patients

N= 75 clubfeet (complex)

 

Modified Ponseti

Requires precise identification of subtalar joint and head of talus; plaster splint applied over calf, heel, and sole; knee immobilized in at least 110° flexion by plaster splint; patients required average of 5 casts (range, 1–10 casts) for full correction; all patients had tendo Achillis tenotomy*

 

*in previously treated patients, a 2nd tenotomy was not performed if foot could be dorsiflexed few degrees above neutral (5°)

C: no controls

Endpoint of follow-up: mean 20 months

 

Mean age at presentation 3 months weeks (range 1-9 months)

 

Mean age at end of follow-up 23 months (6-46 months)

 

No loss to follow-up

Treatment success: correction of deformity components, degree of ankle dorsiflexion, need for extensive soft tissue releases, relapse; complications

 

Correction deformity

All feet were well corrected with mean ankle dorsiflexion of 15° (range, 10°–25°)

 

Relapse

7/50 (14%)

2/50 (4%) 2nd relapse

 

all relapses related to problems with shoe fit

with standard foot abduction brace

 

No relapses occurred after using a new, premolded foot-ankle abduction brace

 

Relapses treated succesfully with 2nd series manipulations

and casting, and 3 patients with 2nd tenotomy

 

Complications

11 (22%) : erythema,

slight swelling forefoot and toes, mild rocker-bottom deformity, midfoot hyperabduction, downward cast slippage

 

No infections or profuse bleeding observed after the tenotomy

No comparison of treatments (not rated with GRADE); concerns ‘complex clubfeet’ (without using severity classification system); no radiographic follow-up; short follow-up; small study; no functional outcome measures

 

Outcome measure = Treatment quality

 

Level of evidence = VERY LOW

 

Authors conclude that a modified Ponseti

treatment protocol for complex clubfeet successfully corrected

the deformity without the need for extensive corrective surgery

 

Note: short follow-up and no functional outcome measures.

 

Authors note that ‘natural history of relapses in clubfoot is that most (80%) will happen during the first 2 years of life’

 

Bracing: all relapses related to problems with shoe fit

with standard foot abduction brace

 

Morcuende et al, 2004

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Retrospective cohort

 

N= 157 patients

N= 256 clubfeet

 

Time period = Jan 1991 – Dec 2001

 

Orthopaedic dept, university hospital; USA

 

Inclusion criteria: consecutive patients; congenital idiopathic clubfoot;under supervision of senior author (Ponseti)

 

157 patients; 256 clubfeet; 107 (68%) male; 128 (81%) < 6 months; 113 (73%) had initial (plaster cast) treatment elsewhere with 14 (9%) percutaneous Achillis tenotomy

 

95% patients came to the clinic with all of the components of the deformity uncorrected

 

I: Ponseti

N= 157 patients

N= 256 clubfeet

 

Ponseti

guidelines treatment developed by senior author (Ponseti); including simple percutaneous tendoachilles tenotomy under local anesthesia (86% if cases); all casts in all patients under supervision of senior author; foot-abduction brace (bar with shoes); full-time for 2-3 months and at night and during naptime for 3 to 4 years

 

Relapses after initial correction are treated with additional manipulation and serial casting in marked foot abduction; tendoachilles tenotomy is indicated when dorsiflexion of the ankle

is <15°

 

No severity classification is used because the deformity is not necessarily related to the resistance to correction

 

Number of casts required to obtain full correction used as proxy for severity of the deformity

C: no controls

Endpoint of follow-up: mean ~20 months

 

Mean age at last follow-up 26 months (range: 6 months to 8 years)

 

128/157 (81%) presented at age < 6 months

 

No loss to follow-up

 

 

Treatment success: correction deformity, ankle dorsiflexion, relapse; complications

 

Noncompliance defined when brace was not used for at least 10 hours a day (parent self-report)

 

Relapse defined as appearance of any of the components of the deformity, including cavus, adductus, varus, and/or equinus

 

Correction deformity

In all but 3 (98%);

ankle dorsiflexion posttenotomy was 20° (range: 0–35°)

 

The 3 patients were previously treated in

other institutions and presented with very severe deformities

 

Relapse

17/157 (11%)

4/157 (2.5%) required extensive corrective surgery (1 PMR, 3 posterior releases with tendoachilles tenotomy)

 

Relapse not significantly related to age at presentation, previous unsuccessful treatment at other institution, or number of casts required for correction (used as a

measure of severity; all P> 0.05).

 

Relapses were associated with noncompliance with foot-abduction brace (P= 0.001);

noncompliance

associated with a 17 times greater odds of relapse (15 of 17) compared with compliance (6 of 140; P= 0.0001)

 

Complications

12/157 (8%) patients had cast complication: erythema, slight swelling of toes, or downward slippage of cast; no infections, skin necrosis, or neutenotomy

No comparison of treatments (not rated with GRADE); short follow-up; relatively large study; no functional outcome measures

 

Outcome measure = Treatment quality

 

Level of evidence = VERY LOW

 

Authors conclude that Ponseti method is a safe and effective

treatment that

radically decreases need for extensive corrective surgery; technique can be used in children up to 2 years of age even after previous unsuccessful nonsurgical

treatment

 

Authors believe that the discrepancy in the results of treatment with earlier studies is attributable to deficient understanding of the nature of the deformity and the normal functional anatomy of the foot: ‘lack of understanding has led to poor corrective manipulation and casting techniques, in particular application of counterpressure on the calcaneocuboid joint during manipulation’

 

Authors also stress the importance of parent education to increase brace compliance (which is a key determinant of the relapse rate)

 

Cooper and Dietz, 1995

 

 

 

 

 

 

 

 

 

 

 

Retrospective cohort

 

N= 45 patients

N= 71 clubfeet

 

Time period = 1950 – 1967

(initial treatment)

 

N = 97 healthy control patients

 

Orthopaedic dept, university hospital; USA

 

Inclusion criteria: consecutive patients; congenital idiopathic clubfoot;treated under supervision of Ponseti

 

126 patients; < 4 months old when first seen; 61 could be contacted, 4 refused to collaborate, 12 were not evaluated for time of financial restrictions;

 

Remaining 45 patients, 71 clubfeet

 

 34 (76%) male; 26 (28%) bilateral clubfeet

 

65/71 (92%) percut. Achillis tenotomy:

5 no tenotomy,

27 tenotomy,

28 tenotomy + additional surgery

 

 

I: Ponseti

N= 45 patients

N= 71 clubfeet

 

Ponseti

Patients managed under direction of Ponseti; including tendoachilles tenotomy (92%); foot-abduction brace (bar with shoes); full-time for 2-3 months and at night and during naptime for 2 to 6 years

 

C: healthy controls

N= 97 control patients

 

 

Randomly selected from waiting room of opthalmology outpatient clinic; within age-range of clubfoot patients (patients with congenital deformity of the foot were excluded); Note: groups are not comparable In a number of (demographic) characteristics

Endpoint of follow-up: mean ~34 years

 

Mean age at last follow-up 34 years (range, 25-42 y)

 

Presented at age < 4 months

 

For how many participants were no complete outcome data available? 81 (62%), mainly due to loss to follow-up

 

 

Treatment success: questionnaire (pain, function, satisfaction, etc); physical examination (incl gait analysis); radiography (angles); electrogoniometric analysis; pedobaric analysis

 

In addition, simple association analyses performed (excellent/good outcome versus poor outcome); Note: no proper correction for confounders

 

Foot function questionnaire (pain, limitation of foot function) = ‘modified Laaveg and Ponseti’

 

I: 28 (62%) ‘excellent’

C: 61 (63%) ‘excellent’

 

I: 7 (16%) ‘good’

C: 21 (22%) ‘good’

 

I: 10 (22%) ‘poor’

C: 15 (15%) ‘poor’

 

No significant differences

 

Note: ‘mild residual deformity was common, but only minimum signs of early degenerative osteoarthrosis were found’

 

 

 

 

 

No comparison of treatments (not rated with GRADE); great loss to follow-up; confounding (association analyses); relatively small study; very long follow-up; functional outcome measures

 

Outcome measure = Treatment quality

 

Level of evidence = VERY LOW

 

Authors conclude that with the use of pain and functional limitation as the outcome measure, 78% of the clubfoot patients had an excellent or good outcome, compared to 85% of individuals who did not have congenital deformity of the foot

 

Based on simple (!) association analyses, the authors suggest that a sedentary occupation, and avoidance of overweight may improve overall long-term results

 

The functional outcome could not be predicted from the radiographic results

 

Notes: no data on compliance with bracing; no proper correction for confounders in association analyses

 

Excellent = does not limit activities of daily living, never painful

 

Good = occasionally limits activities, only painful after strenuous activities

 

Poor = limits activities, or is painful during daily activities&a

Autorisatiedatum en geldigheid

Laatst beoordeeld  : 07-02-2014

Laatst geautoriseerd  : 07-02-2014

Uiterlijk in 2018 bepaalt het bestuur van de Nederlandse Orthopedische Vereniging of deze richtlijn nog actueel is. Zo nodig wordt een nieuwe werkgroep geïnstalleerd om de richtlijn te herzien. De geldigheid van de richtlijn komt eerder te vervallen indien nieuwe ontwikkelingen aanleiding zijn een herzieningstraject te starten.

De Nederlandse Orthopedische Vereniging is als houder van deze richtlijn de eerstverantwoordelijke voor de actualiteit van deze richtlijn. De andere aan deze richtlijn deelnemende wetenschappelijk verenigingen of gebruikers van de richtlijn delen de verantwoordelijkheid en informeren de eerstverantwoordelijke over relevante ontwikkelingen binnen hun vakgebied.

Initiatief en autorisatie

Initiatief:
  • Nederlandse Orthopaedische Vereniging

Algemene gegevens

In samenwerking met

Nederlandse Vereniging Klompvoetjes

 

Met ondersteuning van

Kennisinstituut van Medisch Specialisten

 

Financiering

De richtlijnontwikkeling werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS)

Doel en doelgroep

Doel van de richtlijn

Het doel van de richtlijn is om te komen tot optimalisatie van de zorg rondom pasgeborenen met klompvoeten. Hierbij is het wenselijk om in Nederland te streven naar homogeniteit van deze zorg en een zoveel mogelijk eenduidig behandelingsadvies naar de ouders. Op basis van de richtlijn kan de patiëntenvoorlichting geüniformeerd worden, hetgeen houvast biedt voor de ouders en de patiëntenvereniging. Ook kan met de richtlijn in de hand wellicht overtuigender getracht worden de ouders tot therapietrouw te bewegen; uniformiteit in de wijze van behandeling zal ook door de richtlijn worden ondersteund.

 

Afbakening van de richtlijn

De richtlijn heeft betrekking op kinderen waarbij de diagnose congenitale idiopathische pes equinovarus adductus is gesteld voor de leeftijd van zes maanden, en die nog niet eerder zijn behandeld. De richtlijn is bedoeld om een handvat te bieden aan de behandelend orthopedisch chirurgen en aan de ouders van patiënten met klompvoeten. De richtlijn wil een uitspraak doen over de diagnostiek, behandeling, follow-up en organisatie van zorg, waarbij zoveel mogelijk basis gezocht zal worden in de beschikbare literatuur voor zover deze aan gedefinieerde kwaliteitscriteria voldoet en waar nodig aangevuld met expert opinies.

 

De richtlijn beoogt een antwoord te geven op de volgende uitgangsvragen:

  • Wat is de optimale diagnostische methode om een klompvoet vast te stellen en te classificeren?
  • Wat is de optimale behandeling van de klompvoet?
  • Wat is het belang van patiëntgerelateerde prognostische factoren voor het behandelsucces bij behandeling volgens Ponseti?
  • Wat is de plaats voor systematische screening naar dysplastische heupontwikkeling bij kinderen met een idiopathische klompvoet?
  • Welke aspecten zijn randvoorwaardelijk voor het verlenen van zorg aan patiënten met klompvoet?

 

Beoogde gebruikers van de richtlijn

Deze richtlijn is geschreven voor alle leden van de beroepsgroepen die betrokken zijn bij de zorg voor patiënten met klompvoeten. Hierbij wordt in eerste instantie geadresseerd aan (kinder-) orthopedisch chirurgen, maar ook aan kinderartsen, gynaecologen/verloskundigen en huisartsen. Tevens kan de richtlijn gebruikt worden door de patiëntenvereniging om uniforme voorlichting mogelijk te maken

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijn is in 2011 een werkgroep ingesteld, bestaande uit kinderorthopaedisch chirurgen die betrokken zijn bij de zorg voor patiënten met klompvoet (zie hiervoor de samenstelling van de werkgroep). De werkgroepleden zijn door hun beroepsvereniging gemandateerd voor deelname. Daarnaast maakten twee vertegenwoordigers van de patiëntenvereniging (Nederlandse Vereniging Klompvoetjes; NVK) deel uit van de werkgroep. De werkgroep werkte gedurende twee jaar aan de totstandkoming van de richtlijn. De werkgroep is verantwoordelijk voor de integrale tekst van deze richtlijn.

 

Samenstelling van de werkgroep

  • Drs. A.T. Besselaar, orthopedisch chirurg, Nederlandse Orthopaedische Vereniging, voorzitter
  • Drs. M.M.E.H. Witbreuk, orthopedisch chirurg, Nederlandse Orthopaedische Vereniging
  • Dr. A.V.C.M. Zeegers, orthopedisch chirurg, Nederlandse Orthopaedische Vereniging
  • Dr. R.J.B. Sakkers, orthopedisch chirurg, Nederlandse Orthopaedische Vereniging
  • Drs. H.A. Schuppers, orthopedisch chirurg, Nederlandse Orthopaedische Vereniging
  • Dr. J. Visser, orthopedisch chirurg, Nederlandse Orthopaedische Vereniging
  • R.A. Boekestijn, voorzitter en penningmeester Nederlandse Vereniging Klompvoetjes
  • Drs. S.D. Margés, bestuurslid Nederlandse Vereniging Klompvoetjes

 

Met ondersteuning van:

  • Dr. K.N.J. Burger, medisch bioloog en epidemioloog, adviseur van het Kennisinstituut van Medisch Specialisten
  • Drs. M. Wessels, literatuurspecialist van het Kennisinstituut van Medisch Specialisten

 

Met dank aan:

  • S.K. Josso, secretaresse van het Kennisinstituut van Medisch Specialisten

Belangenverklaringen

De werkgroepleden hebben schriftelijk verklaard of ze in de laatste vijf jaar een (financieel ondersteunde) betrekking onderhielden met commerciële bedrijven, organisaties of instellingen die in verband staan met het onderwerp van de richtlijn. Tevens is navraag gedaan naar persoonlijke financiële belangen, belangen door persoonlijke relaties, belangen door middel van reputatiemanagement, belangen vanwege extern gefinancierd onderzoek en belangen door kennisvalorisatie. De belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van Medisch Specialisten, een overzicht vindt u hieronder.

 

Werkgroeplid

Functie

Nevenfuncties

Persoonlijke financiele belangen

Persoonlijke relaties

Reputatie-management

Extern gefinan-cierd onderzoek

Kennis-valorisatie

Overige belangen

Gete-kend

Besselaar

Orthopedisch chirurg, Catharina Ziekenhuis Eindhoven

Voorzitter AO trauma cursus Nederland (onkostenvergoeding)

Bestuurslid Werkgroep kinderothodepie (onbetaald)

Lid AO Internationaal Lid werkgroep voet en enkel Nederland (DOFAA)

 

 

 

 

 

Op verzoek van de Ponseti International Association heeft men mij vermeld op hun website als gecertificeerde behandelaar van klompvoeten volgens de Ponseti methode. Dit betreft geen lidmaatschap, er is geen enkele financiele of andere verplichting aan gekoppeld.

Ja

Schuppers

Orthopedisch chirurg, Orthopedisch Centrum Oost Nederland, Hengelo

Geen

Geen

Geen

Geen

Geen

Geen

Geen

Ja

Visser

Hoogleraar kinderorthopedie UMC Groningen

ontwikkelen en promoten van dr. Visser schoenen waarvoor een jaarlijkse toelage

Geen

Geen

Geen

Geen

Geen

Geen

Ja

Margés

bestuurslid Nederlandse Vereniging klompvoetjes

 

Geen

Zoon met klompvoet 5 jaar, dus niet meer in primaire behandeling

Bestuur Nederlandse Vereniging Klompvoetjes

Geen

Geen

Geen

Ja

Boekestijn

bestuurslid Nederlandse Vereniging klompvoetjes

Voorzitter Nederlandse Vereniging klompvoetjes (onbetaald)

Geen

Geen

Geen

Geen

Geen

Geen

Ja

Witbreuk

Orthopedisch chirurg, VUmc, Amsterdam

nvt

nvt

nvt

nvt

nvt

nvt

Geen

Ja

Zeegers

Orthopaedisch chirurg, Medisch Spectrum Twente

 

Geen

Geen

Geen

nvt

nvt

nvt

Ja

Sakkers

(kinder) orthopaedisch chirurg, UMC Utrecht

 

Geen

Geen

Geen

nvt

nvt

nvt

Ja

 

Inbreng patiëntenperspectief

Er werd aandacht besteed aan het patiëntenperspectief door een afvaardiging van de patiëntenvereniging in de werkgroep en een door de patiëntenvereniging uitgevoerde enquête onder haar leden. Een verslag van de enquête is besproken in de werkgroep en de belangrijkste knelpunten zijn verwerkt in de richtlijn. Het verslag is terug te vinden in bijlage 'Klompvoetdebat'. Ook is er in de oriënterende fase gezocht naar literatuur vanuit patiëntenperspectief, hierbij is gebruik gemaakt van een gestandardiseerd zoekfilter (zie hieronder).

 

Zoekfilter patiëntenperspectief

46. exp Consumer Participation/

47. ((patient or consumer*) adj3 (participat* or decisi* or decid*)).ti,ab.

48. "Patient Acceptance of Health Care"/

49. exp Attitude to Health/

50. *exp consumer satisfaction/ or patient preference/

51. "patient-focused".ti,ab.

52. "patient-centred".ti,ab.

53. (patient adj3 (attitude? or preference)).ti,ab.

54. "patient satisfaction".ti.

55. cooperative behavior/

56. exp self efficacy/ or self-efficacy.ti,ab.

57. exp Adaptation, Psychological/

58. coping.ti,ab.

59. ("self perception" or "self concept").ti,ab.

60. exp health education/ or patient education as topic/

61. exp attitude to health/ or health knowledge, attitudes, practice/

62. ("informed choice" or "shared decision making").ti,ab.

63. empowerment.tw.

64. ("focus group*" adj3 (patient* or parent* or famil* or spouse*)).ti,ab.

65. *"Quality of Life"/ or "Quality of Life"/px [Psychology]

66. (QoL or "Quality of life").ti.

67. Personal Autonomy/ or self concept/

68. consumer advocacy/ or freedom/

69. Needs Assessment/

70. Patient Advocacy/

71. Self-Help Groups/

72. Life Change Events/

73. Attitude to Death/

74. Patient-Centered Care/

75. exp Professional-Patient Relations/

76. Self Care/ \

77. self-management.ti.

78. ((patient* or consumer* or parent* or famil* or spouse*) adj (attitude* or involvement or desir* or perspective* or activation or view* or preference*)).ti,ab.

79. "expert patient*".ti,ab.

80. or/45-79

81. exp Decision Making/

82. exp Communication/

83. Stress, Psychological/

84. Emotions/

85. vignette*.ti,ab.

86. or/81-85

87. exp Patients/px [Psychology]

88. (patient* or consumer*).ti.

89. 87 or 88

90. 86 and 88

91. "focus group*".ti,ab.

92. focus groups/ or narration/

93. qualitative.ti.

94. 91 or 92 or 93

95. 80 or 90 or 94

Methode ontwikkeling

Evidence based

Implementatie

In de verschillende fasen van de richtlijnontwikkeling is rekening gehouden met de implementatie van de richtlijn en de praktische uitvoerbaarheid van de aanbevelingen. Daarbij is uitdrukkelijk gelet op factoren die de invoering van de richtlijn in de praktijk kunnen bevorderen of belemmeren.

 

De richtlijn wordt digitaal verspreid onder alle relevante beroepsgroepen. Ook is de richtlijn te downloaden vanaf de website van de Richtlijnendatabase.

Werkwijze

AGREE

Deze richtlijn is opgesteld conform de eisen volgens het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit (www.kwaliteitskoepel.nl). Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) dat een internationaal breed geaccepteerd instrument is en op ‘richtlijnen voor richtlijn’ voor de beoordeling van de kwaliteit van richtlijnen (www.cvz.nl).

 

Knelpuntenanalyse

Tijdens de voorbereidende fase inventariseerden de voorzitter van de werkgroep en de adviseur de knelpunten. Tevens zijn er knelpunten aangedragen door kinderorthopeden, de werkgroep Kinderorthopedie van de Nederlandse Orthopeadische Vereniging (NOV), gipsverbandmeesters, orthopedisch instrumentmakers, kinderfysiotherapeuten, orthopedisch schoentechnici, de Nederlandse Patiënten en Consumenten Federatie (NPCF) en patiëntvertegenwoordigers van de NVK via een invitational conference georganiseerd door de NVK. Een verslag is terug te vinden in bijlage 'Klompvoetdebat'.

 

Uitgangsvragen en uitkomstmaten

Op basis van de uitkomsten van de knelpuntenanalyse zijn door de voorzitter en de adviseur concept-uitgangsvragen opgesteld. Deze zijn met de werkgroep besproken waarna de werkgroep de definitieve uitgangsvragen heeft vastgesteld. Vervolgens inventariseerde de werkgroep per uitgangsvraag welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. De werkgroep waardeerde deze uitkomstmaten als cruciaal, belangrijk of onbelangrijk. Tevens definieerde de werkgroep, voor zover mogelijk, wat zij voor een bepaalde uitkomstmaat een klinisch relevant verschil vond, dat wil zeggen wanneer de verbetering in uitkomst een verbetering voor de patiënt is. 

 

Kwaliteitsbeoordeling individuele studies

Individuele studies werden systematisch beoordeeld, op basis van op voorhand opgestelde methodologische kwaliteitscriteria, om zo het risico op vertekende studieresultaten (bias) te kunnen inschatten. Deze beoordelingen kunt u vinden in de methodologische checklijsten. De relevante onderzoeksgegevens van alle geselecteerde artikelen werden overzichtelijk weergegeven in evidencetabellen.

 

Beoordelen van de kracht van het wetenschappelijke bewijs

A)   voor interventievragen:

de kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (http://www.gradeworkinggroup.org/) (Atkins et al., 2004);

B)   voor vragen over de waarde van diagnostische tests, schade of bijwerkingen, etiologie en prognose:

bij dit type vraagstelling kan GRADE (nog) niet gebruikt worden. De bewijskracht van de conclusie is bepaald volgens de EBRO-methode (Van Everdingen et al., 2004).

 

Bij interventievragen verwijst de conclusie niet naar één of meer artikelen, maar wordt getrokken op basis van alle studies samen (body of evidence). Hierbij maakten de werkgroepleden de balans op van elke interventie. Bij het opmaken van de balans werden de gunstige en ongunstige effecten voor de patiënt afgewogen.

 

Formuleren van aanbevelingen

De aanbevelingen geven een antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk. De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen.

 

Randvoorwaarden (Organisatie van zorg)

In de knelpuntenanalyse en bij de ontwikkeling van de richtlijn is expliciet rekening gehouden met de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg, zoals coördinatie, communicatie, (financiële) middelen, menskracht en infrastructuur. Randvoorwaarden die relevant zijn voor het beantwoorden van een specifieke uitgangsvraag maken onderdeel uit van de overwegingen bij de bewuste uitgangsvraag. Meer algemene, overkoepelende of bijkomende aspecten van de organisatie van zorg worden behandeld in module 'Randvoorwaarden'.

 

Indicatorontwikkeling

Gelijktijdig met het ontwikkelen van de conceptrichtlijn werden er interne kwaliteitsindicatoren ontwikkeld om het toepassen van de richtlijn in de praktijk te volgen en te versterken. Meer informatie over de methode van indicatorontwikkeling is op te vragen bij het secretariaat van OPK.

 

Commentaar- en autorisatiefase

De conceptrichtlijn werd aan de betrokken (wetenschappelijke) verenigingen voorgelegd voor commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijn aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijn werd aan de betrokken (wetenschappelijke) verenigingen voorgelegd voor autorisatie en door hen geautoriseerd.

 

 

  • Atkins, D., Best, D., Briss, P.A., Eccles, M., Falck-Ytter, Y., Flottorp, S., ..., GRADE Working Group. (2004). Grading quality of evidence and strength of recommendations. BMJ Jun; 19, 328(7454):1490.
  • Everdingen, J.J.E. van, Burgers, J.S., Assendelft, W.J.J., Swinkels, J.A., Barneveld, T.A. van, Klundert, J.L.M. van de (2004). Evidence-based richtlijnontwikkeling. Bohn Stafleu Van Loghum.

Zoekverantwoording

Zoekacties zijn opvraagbaar. Neem hiervoor contact op met de Richtlijnendatabase.

Volgende:
Patiëntgerelateerde prognostische factoren