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Glyceryltrinitraat versus topicale nifedipine

Beoordeeld: 07-05-2024

Uitgangsvraag

Wat is de beste behandeling voor acute anale fissuren?

Aanbeveling

Start met basistherapie in de vorm van leefstijl- en dieetadviezen*, aangevuld met laxantia ten behoeve van het verzachten van de ontlasting.

 

Overweeg het gebruik van diltiazem 2% (crème of gel, zes weken, twee tot drie keer daags).

 

Voer geen chirurgische ingreep uit bij acute fissuren.

 

Zie eveneens stroomdiagram in bijlage onder ‘chronische fissuren’.

 

* Voldoende bewegen, voldoende water drinken.

Overwegingen

Voor- en nadelen van de interventie en kwaliteit van het bewijs

Sinds 2015 wordt aanbevolen om acute fissuren te behandelen met conservatieve therapie (in de vorm van zalf, dieetadviezen en/of laxantia). Diltiazem 2% (twee tot drie keer daags, zes weken lang) is dan aan te bevelen in het kader van therapietrouw. Eventueel kan ook gekozen worden voor ISDN-zalf 1% (vijf tot zes keer daags intra-anaal, zes weken lang). Er is geen indicatie voor chirurgische ingreep bij acute fissuren.

 

Op basis van de conclusies uit de literatuursamenvatting van zowel de cruciale (geen genezing van de fissuur en incontinentie) als belangrijke uitkomstmaat (pijn) kan niet met zekerheid worden gezegd welke interventie in de meeste heling van de fissuur, minste incontinentie en minste pijn resulteert. Dit heeft er vooral mee te maken dat de studies een verhoogd risico op bias hebben en de trials die dit onderzocht hebben maar een klein aantal patiënten includeren, tezamen met een korte (maximaal zes weken) follow up.

Het is zoals altijd nodig om dit grondig uit te zoeken in een grote trial maar deze is ook in deze nieuwe literatuursearch niet te vinden.

Belangrijk is dat waarschijnlijk 90% van de acute fissuren spontaan geneest, zonder enige interventie en zonder dat beoordeling van een specialist plaats heeft gevonden (Farooq 2012). Alle gepubliceerde onderzoeken naar acute fissuren zijn in ziekenhuissetting verricht waarvoor al een selectie heeft plaats gevonden.

 

De werkgroep is van mening dat, ondanks een substantieel risico op falen van de therapie en progressie naar chronische kenmerken, topicale therapie kan worden toegepast in de behandeling van acute fissuren (Farooq, 2012; Ahktar, 2016; Akinci, 2020).

 

Waarden en voorkeuren van patiënten (en evt. hun verzorgers)

Diltiazem (calciumantagonist) crème verdient de voorkeur aangezien deze maar twee tot driemaal daags hoeft te worden aangebracht en minder vaak hoofdpijn als bijwerking geeft (Nelson, 2012). Er wordt geadviseerd alleen chirurgische behandeling toe te passen bij patiënten met een refractaire fissuur na lokale therapie voor minimaal zes weken. Een vezelrijk dieet lijkt de recidiefkans op een (acute) fissuur te verkleinen. Zie voor het patiëntenperspectief de module Patiëntenperspectief bij proctologie.

 

Kosten (middelenbeslag)

Voor het kostenaspect verwijzen we graag naar de overwegingen van de chronische fissuren. 

 

Aanvaardbaarheid, haalbaarheid en implementatie  

Voor de aanvaardbaarheid, haalbaarheid en implementatie verwijzen we graag naar de overwegingensectie van de chronische fissuren. 

Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies

Bij de behandeling van een acute fissura ani is het noodzakelijk een soepele/zachte ontlasting te hebben en de patiënten dieetadviezen mee te geven. Van belang is de pijnklachten te verminderen en heling van de fissuur te bevorderen zodat ook het bloedverlies stopt. Het gebruik van zalven heeft de voorkeur boven een LIS om zo kans op soiling of incontinentie te voorkomen op langere termijn. Het gebruik van botox heeft geen plaats in de behandeling van acute fissuren.

Onderbouwing

Een acute anale fissuur is waarschijnlijk gerelateerd aan plaatselijk trauma, zoals harde ontlasting of langdurige diarree. Naast bloedverlies is een anale fissuur vaak pijnlijk voor en tijdens de ontlasting en houdt de pijn nog één tot twee uur aan na de ontlasting. De fissuur (zweer) komt meestal voor in de posterieure middellijn van het anale kanaal (80-90%). In 10% van de gevallen bevindt de fissuur (zweer) zich anterieur en in minder dan 1% zijn de fissuren lateraal of multipel. Persistentie is te wijten aan spasme van de interne anale sluitspier. De behandeling van acute anale fissuren is over het algemeen conservatief en bestaat uit middelen die de ontlasting zacht maken, topische zalven, bekkenfysiotherapie of botulinetoxine-injecties. Als een acute fissuur na zes tot acht weken niet genezen is, wordt deze chronisch. Als conservatieve behandeling faalt, is een chirurgische ingreep nodig.

Non-healing of the fissure (critical)

Very low GRADE

The evidence is very uncertain about the effect of glyceryl trinitrate on non-healing of the fissure compared to topical nifedipine in patients with acute anal fissure.

 

Sources: Akinci (2020).

 

Incontinence (critical)

No GRADE

None of the studies reported the outcome incontinence for conservative treatments compared to other conservative treatments.

 

Sources: -

 

Pain (important)

Very low GRADE

The evidence is very uncertain about the effect of glyceryl trinitrate on pain compared to topical nifedipine in patients with acute anal fissure. 

 

Sources: Akinci (2020).

Description of studies

 

Akinci (2020) described a prospective randomized controlled trial that aimed to compare the effect of 0.2% glyceryl trinitrate with 0.5% topical nifedipine in patients with acute anal fissures. Patients diagnosed with acute anal fissures were included and randomly divided in two equally distributed groups. Patients with chronic anal fissure, inflammatory bowel disease, hemorrhoid, tuberculosis, anal cancer, history of anal surgery, pregnant and lactating patients, patients under the age of eighteen years, and patients who did not want to enroll in the study were excluded. The first group was treated with 0.2% glyceryl trinitrate. The second group was treated with 0.5% topical nifedipine. The maximum length of follow-up was 21 days. The reported outcome measure in the study was recovery.

 

The randomized controlled trial of Akhtar (2016) compared the frequency of healing in patients with acute anal fissure undergoing lateral internal sphincterotomy versus medical management with glyceryl trinitrate 0.2% cream. Patients with acute anal fissures either male or female having age from 20 to 60 years were included and randomly divided in two equally distributed groups. Patients with recurrent anal fissure (assessed on history and physical examination), external or internal hemorrhoids (assessed on history, physical examination and proctoscopy), patients with chronic anal fissure (assessed on history and physical examination), patients with sentinel pile (assessed on history and physical examination), patients treated by Hakeems (acids, corrosive) assessed on history and physical examination and parturition trauma (assessed on history and physical examination) were excluded. The first group underwent lateral internal sphincterotomy. The second group were treated with 0.2% glyceryl trinitrate cream. The maximum length of follow-up was six weeks. The reported outcome measure in the study was recovery.

 

The quasi-experimental study of Farooq (2012) compared the efficacy of surgical sphincterotomy with chemical sphincterotomy in patients with acute anal fissures. Patients with acute anal fissures between twenty and 50 years of age were included in the study and divided in two equal groups. Patients with other anal pathology (i.e., inflammatory bowel diseases, hemorrhoids, anal fistula, or anal abscess), cardiac patients, pregnant or planning to be pregnant patients were excluded. The first group was treated with chemical sphincterotomy on the basis of outdoor patients’ department and advised to apply 0.2% glyceryl trinitrate ointment locally three to four times daily along with sitz bath and stool softeners for the period of six weeks. The second group was treated with lateral internal sphincterotomy (surgical sphincterotomy) under spinal or general anesthesia according to patients or anesthetist preference. Three doses of antibiotic [Ceftriaxone (Rocephen) 500 milligram BD diluted in five milliliter of distal water IV, and Metronidazole (Flagyl Rohne-tounene) 500 milligram TDS into IV in 100 milliliter solution form] were given during their hospital stay and two doses of injectable analgesia [Inj. Diclofenac sodium (Voren Yungshin) 75 milligram BD I/M in three milliliter solution] were given. They were advised to take a hot sitz bath along with stool softener [syrup Lactulose (Duphalac Highnoon) ten milligram is fifteen milliliter] twice daily. They were examined on the second postoperative day during their hospital stay and followed up at the end of first week, third week, sixth week and after three months. The reported outcomes in the study were recovery and incontinence. 

 

The prospective, randomized, controlled trials of Hassan (2022) investigated the effect of 0.2% glyceryl trinitrate ointment in comparison to 2% diltiazem hydrochloride gel in patients with acute, anal fissures. In total, 112 patients were included and randomly assigned to one of the treatments. The length of follow-up was eight weeks. No patients were lost to follow-up. Hassan (2022) reported non-healing of the fissure.

 

Results

 

Non-healing of the fissure (critical)

One study compared GTN with topical nifedipine in patients with acute anal fissures (Akinci, 2020). The incidence of non-healing of the fissure in the GTN group was 18/50 (36.0%), compared to 7/50 (14%) in the topical nifedipine group. RR 2.57 (95% CI 1.18 to 5.61), favoring the topical nifedipine group. This is considered as a clinically (for the patient) important difference.

 

Incontinence (critical)

None of the included studies reported the outcome measure incontinence in patients who were treated with GTN versus topical nifedipine.

 

Pain (important)

One study compared GTN with topical nifedipine in patients with acute anal fissures (Akinci, 2020). Akinci (2020) reported the Visual Analogue Scale for the mean postoperative pain score at 21 days follow-up. The mean (SD) postoperative pain score in the study of Akinci (2020) in the GTN group was 2.92 (1.75), compared to 1.54 (1.43) in the topical nifedipine group. MD 1.38 (95% CI 0.75 to 2.01), favoring the topical nifedipine group. This is not considered as a clinically (for the patient) important difference.

 

Level of evidence

 

Non-healing of the fissure (critical)

  • Glyceryl trinitrate (GTN) versus topical nifedipine - The level of evidence regarding the outcome measure non-healing of the fissure comes from a randomized controlled trial and therefore starts high. The level of evidence was downgraded by three levels because of unclear allocation sequence, lack of blinding (both risk of bias) and the small number of included patients (imprecision). The level of evidence is very low.

Incontinence (critical)

  • Glyceryl trinitrate (GTN) versus topical nifedipine – None of the included studies reported information regarding incontinence for the comparison of glyceryl trinitrate (GTN) versus topical nifedipine. Therefore, the level of evidence could not be graded.

Pain

  • Glyceryl trinitrate (GTN) versus topical nifedipine - The level of evidence regarding the outcome measure pain comes from randomized controlled trials and therefore starts high. The level of evidence was downgraded by three levels because of lack of blinding (risk of bias), wide confidence intervals crossing both boundaries of clinical relevance, and the small number of included patients (both imprecision). The level of evidence is very low.

A systematic review of the literature was performed to answer the following questions:

  • What is the best treatment for acute anal fissures?
    • What are the (un)beneficial effects of conservative medical treatment in comparison with other conservative medical treatment in patients with acute anal fissures?
    • What are the (un)beneficial effects of conservative medical treatment in comparison with surgical treatment in patients with acute anal fissures?

Relevant outcome measures

The guideline development group considered non-healing of the fissure and incontinence as critical outcome measures for decision making; and pain as an important outcome measure for decision making.

 

For all outcome measures, the workgroup considered a 25% difference in relative risk (RR) for dichotomous outcomes, and 10% difference for continuous outcomes as a clinically relevant difference.

 

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until 24 February 2021. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 142 hits. Studies were selected based on the following criteria: systematic reviews and randomized controlled trials. Four studies regarding acute anal fissures were initially selected based on title and abstract screening. After reading the full text, one study was excluded (see the table with reasons for exclusion under the tab Methods). Finally, three studies regarding acute anal fissures were included.

Secondly, an update of the literature was performed. The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from the 24th of February 2021 until the 17th of April 2023. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 76 extra hits. Three studies regarding acute anal fissures were initially selected based on title and abstract screening. After reading the full text, two studies were excluded (see the table with reasons for exclusion under the tab Methods). One extra study was included added to the literature analysis of acute anal fissures.

 

Results

Four studies were included in the analysis of the literature for acute anal fissures. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.

  1. Boland PA, Kelly ME, Donlon NE, Bolger JC, Larkin JO, Mehigan BJ, McCormick PH. Management options for chronic anal fissure: a systematic review of randomised controlled trials. Int J Colorectal Dis. 2020 Oct;35(10):1807-1815. doi: 10.1007/s00384-020-03699-4. Epub 2020 Jul 25. PMID: 32712929.
  2. Sahebally, S. M., Meshkat, B., Walsh, S. R., & Beddy, D. (2018). Botulinum toxin injection vs topical nitrates for chronic anal fissure: an updated systematic review and meta‐analysis of randomized controlled trials. Colorectal Disease, 20(1), 6-15.
  3. Sahebally SM, Walsh SR, Mahmood W, Aherne TM, Joyce MR. Anal advancement flap versus lateral internal sphincterotomy for chronic anal fissure- a systematic review and meta-analysis. Int J Surg. 2018 Jan;49:16-21. doi: 10.1016/j.ijsu.2017.12.002. Epub 2017 Dec 9. PMID: 29233787.
  4. Nelson RL, Manuel D, Gumienny C, Spencer B, Patel K, Schmitt K, Castillo D, Bravo A, Yeboah-Sampong A. A systematic review and meta-analysis of the treatment of anal fissure. Tech Coloproctol. 2017 Aug;21(8):605-625. doi: 10.1007/s10151-017-1664-2. Epub 2017 Aug 9. PMID: 28795245.
  5. ANSARI, N. A., BHORE, A., & MUSA, O. (2020). A Comparative Study of Topical Diltiazem (2%) with Topical Glyceryl Trinitrate (0.2%) as a Conservative Treatment for Anal Fissure. Journal of Clinical & Diagnostic Research, 14(7).
  6. Ahmed, F., Mengal, M. A., Ahmed, M., Akbar, S., Elahi, B., & Khan, A. (2018). Comparison of Complications of Open versus Closed Lateral Internal Sphincterotomy in Chronic Anal Fissures. PAKISTAN JOURNAL OF MEDICAL & HEALTH SCIENCES, 12(3), 1072-1074.
  7. Ruiz-Tovar J, Llavero C. Percutaneous Posterior Tibial Nerve Stimulation vs Perianal Application of Glyceryl Trinitrate Ointment in the Treatment of Chronic Anal Fissure: A Randomized Clinical Trial. Dis Colon Rectum. 2017 Jan;60(1):81-86. doi: 10.1097/DCR.0000000000000736. PMID: 27926561.
  8. Akinci, O., Abdulrahman, S. M. F., Güngör, Ö., Yüceyar, N. S., Perek, A., & Ertürk, M. S. (2020). Randomised Comparison of the Effect of 0.2% Glyceryl Trinitrate and 0.5% Topical Nifedipine in Acute Anal Fissure Treatment/Akut Anal Fissur Tedavisinde% 0, 2 Gliseril Trinitrat ile% 0, 5 Topikal Nifedipinin Etkilerinin Randomize Karsilastirilmasi. Turkish Journal of Colorectal Disease, 30(4), 246-253.
  9. Farooq, U., Farooq, S., Zahir, S., & Chaudhry, A. M. (2012). Comparison of surgical and chemical sphincterotomy in the management of acute anal fissures. Pak J Med Health Sci, 6, 24-31.

Evidence table

 

Systematic reviews

Study reference Study characteristics Patient characteristics Intervention & control Outcome measures and effect size Comments
Nelson (2017)  

Inclusion criteria SR surgical part:
Trials in which participants were randomized to a surgical procedure and either no treatment or an alternative surgical procedure. Participants eligible for this portion of the review were patients with chronic anal fissure. Chronic anal fissure is typically described as an anal fissure which lasts more than 4–6 weeks, or which has characteristic features such as a sentinel pile, bare internal sphincter, heaped up edges or hypertrophied anal papillae.

Exclusion criteria SR surgical part:
Studies that compared any surgical procedure to any non-surgical procedure were not included in this section.

Inclusion criteria SR conservative part:
Studies in which participants were randomized to non- surgical treatment for anal fissure are the focus of this part of the review. Comparison groups in each of these studies may include a surgical procedure, medical therapy, or a control group consisting of no treatment, supportive care or placebo. Supportive care may consist of dietary fiber, laxatives or warm baths, lubricants, and even topical anesthetics, applied sometimes equally to both groups and sometimes only to the control group.

Exclusion criteria SR conservative part:
Not reported.

31 studies included in the surgical part of the review and 117 studies included in the non-surgical part of the review.

Important patient characteristics at baseline:
Not reported for individual studies.

Literature search up to March 7, 2017.

Surgical intervention studies:
A. Arroyo (2004)
B. Boulus (1984)
C. Dudhamal, 2014
D. Ellis (2004)
E. Elsebae (2007)
F. Filingeri (2005)
G. Fischer (1976)
H. Gupta (2003)
I. Gupta (2008)
J. Gupta (2014)
K. Hancke (2003)
L. Jensen (1984)
M. Kang (2008)
N. Kortbeek (1992)
O. Magdy (2012)
P. Marby (1979)
Q. Mentes (2005)
R. Mentes (2008)
S. Mousavi (2009)
T. Olsen (1987)
U. Pujahari (2010)
V. Ram (2007)
W. Renzi (2008)
X. Saad (1992)
Y. Tauro (2011)
Z. Wang (2005)
AA. Wang (2011)
BB. Weaver (1987)
CC. Wiley (2004)
DD. Yucel (2009)

Conservative intervention studies:
EE. Abd Elhady (2009)
FF. Agrawal (2013)
GG. Ahmad (2007)
HH. Ahmad (2012)
II. Ala (2012) 50
JJ. Altomare (2000)
KK. Antripoli (1999)
LL. Arroyo (2005)
MM. Arslan (2013)
NN. Asim (2014)
OO. Aslam (2014)
PP. Bacher (1997)
QQ. Bailey (2002)
RR. Bansal (2016)
SS. Berkel (2014) 60
TT. Bielecki (2003)
UU. Boschetto (2004)
VV. Brillantino (2014)
WW. Brisinda (1999)
XX. Brisinda (2002)
YY. Brisinda (2004)
ZZ. Brisinda (2007)
AAA. Boulos (2013)
BBB. Buyukyavuz (2010
CCC. Carapeti (1999) 70
DDD. Carroccio (2013)
EEE. Cevik (2012)
FFF. Chaudhuri (2001)
GGG. Chen (1992)
HHH. Colak (2003)
III. Colak (2003)
JJJ. DeNari (2006)
KKK. Dinç (2014)
LLL. Di Visconte (2006)
MMM. Di Visconte (2009) 80
NNN. El-Labban (2010)
OOO. Elwakeel (2007)
PPP. Emami (2008)
QQQ. Eshghi (2007)
RRR. Evans (2001)
SSS. Ezri (2003)
TTT. Farooq (2012)
UUU. Festen (2009)
VVV. Fruehauf (2006)
WWW. Gagliardi (2010) 90
XXX. Gaj (2006)
YYY. Gandomkar (2015)
ZZZ. Giridhar (2014)
AAAA. Golfam (2019)
BBBB. Grekova (2015)
CCCC. Gupta (2006)
DDDD. Hanumanthappa (2012)
EEEE. Ho (2005)
FFFF. Iswariah (2005)
GGGG. Jawaid (2009) 100
HHHH. Jensen (1986)
IIII. Jensen (1987)
JJJJ. Jonas (2001)
KKKK. Jones (2006)
LLLL. Host (1999)
MMMM. Katsinelos (2006)
NNNN. Kennedy (1999)
OOOO. Kenny (2001)
PPPP. Khaledifar (2015)
QQQQ. Kocher (2010) 110
RRRR. Libertiny (2002)
SSSS. Lund (1997)
TTTT. Maan (2004)
UUUU. Maria (1998)
VVVV. Maria (2000)
WWWW. MacDonald (1983)
XXXX. Mentes (2003)
YYYY. Mishra (2005)
ZZZZ. Moghimi (2006)
AAAAA. Motie (2016) 120
BBBBB. Mustafa (2006)
CCCCC. Muthukumarassamy (2005)
DDDDD. Nasr (2010)
EEEEE. Oettle (1997) 124
FFFFF. Othman (2010) 126
GGGGG. Parellada (2004)
HHHHH. Peng (2013)
IIIII. Perrotti (2002)
JJJJJ. Peshala (2014) 130
KKKKK. Pitt (2001)
LLLLL. Prudente (2011)
MMMMM. Richard (2000)
NNNNN. Rosa (2012) 134
OOOOO. Sahakitrungruang (2011) 136
PPPPP. Samin (2012) 138
QQQQQ. Sanei (2009)
RRRRR. Scholefield (2003) 140
SSSSS. Shrivastava (2007)
TTTTT. Siddique (2008)
UUUUU. Simpson (2003)
VVVVV. Siproudhis (2003)
WWWWW. Sonmez (2002)
XXXXX. Suknaic (2008)
YYYYY. Suvarna (2012)
ZZZZZ. Tander (1999)
AAAAAA. Tankova (2002)
BBBBBB. Tankova (2009) 150
CCCCCC. Tauro (2011)
DDDDDD. Torrabadella (2006)
EEEEEE. Uluutku (2001)
FFFFFF. Vaithianathan (2015)
GGGGGG. Valizadeh (2012)
HHHHHH. Weinstein (2004)
IIIIII. Werre (2001)
JJJJJJ. Yakoot (2009)
KKKKKK. Yetisir (2012)
LLLLLL. Youssef (2015) 160
MMMMMM. Zuberi (2000)
NNNNNN. Gough (1983)

Study design:
SR and meta-analysis of RCTs.

Setting and Country:
Not reported.

Source of funding and conflicts of interest:
The authors declare that they have no conflict of interest.

Describe interventions:

Surgical comparisons

Manual anal stretch vs LIS:

Anal stretch versus LIS sensitivity analysis:

Open LIS vs Closed LIS:

LIS to the apex of the fissure vs Lis to dentate line; subgroup anal:

Fissurectomy vs LIS:

LIS versus V-Y flap cover:

Lis posterior versus LIS lateral:

Levatorplasty versus LIS:
D

LIS closed wound versus LIS open wound:
M

Pneumatic balloon dilation to 3 cm versus LIS:
W

Speculum dilation 4.8 cm vs LIS:
DD

Dilation + fissurectomy vs LIS:
K

LIS + polyp removal vs LIS alone:
H

Unilateral LIS vs Bilateral LIS:
U

Sphincterolysis vs Closed LIS:
I

V-Y flap vs Fissurectomy:
AA

Ayurvedic suture of the fissure vs Dilation + anal stretch:
C

Conservative comparisons

GTN vs control:
JJ; QQ; CCC; FFF; PPP; NNNN; OOOO; SSSS; TTTT; HHHHH; LLLLL; RRRRR; SSSSS; WWWWW; ZZZZZ; AAAAAA; BBBBBB; HHHHHH; IIIIII

GTN vs Lidocaine:
GG; PP; EEE; WWWWW; ZZZZZ

GTN high dose vs GTN low dose:
QQ; CCC; RRRRR; UUUUU

GTN vs pt. self-dilation:
UU; LLL; MMM; XXX

GTN vs botox:
EE; SS; WW; ZZ; JJJ; UUU; VVV; EEEEEE

GTN vs CCB:
EE; II; RR; TT; AAA; EEE; SSS; GGGG; PPPP; QQQQ; AAAAA; BBBBB; QQQQQ; SSSSS; EEEEEE

Botox vs control:
HHH; UUUU; VVVVV

CCB topical vs control:
FF; KK; EEE; AAAA; DDDD; IIIII; SSSSS

LIS vs any medical therapy:
EE; HH LL; OO; KKK; NNN; RRR; TTT; YYY; ZZZ; EEEE; FFFF; MMMM; RRRR; XXXX; YYYY; AAAAA; DDDDD; EEEEE; GGGGG; MMMMM; NNNNN; PPPPP; TTTTT; XXXXX; YYYYY; CCCCCC; FFFFFF; GGGGGG; KKKKKK; LLLLLL

Lis vs any medical therapy follow-up >6 months:
EE; LL; MM; YYY; FFFF; RRRR; AAAAA; GGGGG; XXXXX; CCCCCC; GGGGGG; KKKKKK; LLLLLL

Solcodem vs control:
GGG

Minoxadil vs lidocaine:
CCCCC

Sildenafil vs control:
ZZZZ

Arginine vs LIS:
QQQ

Clove oil vs lidocaine:
OOO

Lanolin vs control:
BBB

Lanolin vs collagen spray:
BBB

Healer cream vs GTN:
JJJJJJ

Healer cream vs control
JJJJJJ

Metronidazole vs control:
BBBB

Ayurvedic concoction vs Ayurvedic + CCB:
JJJJJ

Indoramin vs control:
KKKKK

GTN vs ISMN:
AAAAAA

GTN topical vs GTN intra-anal:
DDDDDD

Botox anterior vs botox posterior:
VVVV

Botox posterior vs botox bilateral:
FFFFF

GTN 40 days vs GTN 80 days:
WWW

Diet vs control:
DDD

Lidocaine vs hydrocortisone:
HHHH

PTNS vs LIS:
LLLLLL

Psyllium husk gum vs control:
VV

Sitz baths vs control:
CCCC

Botox low dose vs botox high dose:
XX; LLLL

Botox vs botox + GTN:
NN; KKKK

GTN ointment vs GTN dermal patch:
III; MMMMMM

Lidocaine vs lidocaine. + dilator:
WWWW; NNNNNN

Botox vs Boxox disport:
YY

Lidocaine vs control children:
WWWWW; XXXXX

CCB vs botox:
PPPPP; EEEEE

PTNS vs GTN
…

CCB topical vs CCB oral:
FF; JJJJ

Bran vs Lactulose:
IIII

Describe interventions:

Surgical comparisons

Manual anal stretch vs LIS:

Anal stretch versus LIS sensitivity analysis:

Open LIS vs Closed LIS:

LIS to the apex of the fissure vs Lis to dentate line; subgroup anal:

Fissurectomy vs LIS:

LIS versus V-Y flap cover:

Lis posterior versus LIS lateral:

Levatorplasty versus LIS:
D

LIS closed wound versus LIS open wound:
M

Pneumatic balloon dilation to 3 cm versus LIS:
W

Speculum dilation 4.8 cm vs LIS:
DD

Dilation + fissurectomy vs LIS:
K

LIS + polyp removal vs LIS alone:
H

Unilateral LIS vs Bilateral LIS:
U

Sphincterolysis vs Closed LIS:
I

V-Y flap vs Fissurectomy:
AA

Ayurvedic suture of the fissure vs Dilation + anal stretch:
C

Conservative comparisons

GTN vs control:
JJ; QQ; CCC; FFF; PPP; NNNN; OOOO; SSSS; TTTT; HHHHH; LLLLL; RRRRR; SSSSS; WWWWW; ZZZZZ; AAAAAA; BBBBBB; HHHHHH; IIIIII

GTN vs Lidocaine:
GG; PP; EEE; WWWWW; ZZZZZ

GTN high dose vs GTN low dose:
QQ; CCC; RRRRR; UUUUU

GTN vs pt. self-dilation:
UU; LLL; MMM; XXX

GTN vs botox:
EE; SS; WW; ZZ; JJJ; UUU; VVV; EEEEEE

GTN vs CCB:
EE; II; RR; TT; AAA; EEE; SSS; GGGG; PPPP; QQQQ; AAAAA; BBBBB; QQQQQ; SSSSS; EEEEEE

Botox vs control:
HHH; UUUU; VVVVV

CCB topical vs control:
FF; KK; EEE; AAAA; DDDD; IIIII; SSSSS

LIS vs any medical therapy:
EE; HH LL; OO; KKK; NNN; RRR; TTT; YYY; ZZZ; EEEE; FFFF; MMMM; RRRR; XXXX; YYYY; AAAAA; DDDDD; EEEEE; GGGGG; MMMMM; NNNNN; PPPPP; TTTTT; XXXXX; YYYYY; CCCCCC; FFFFFF; GGGGGG; KKKKKK; LLLLLL

Lis vs any medical therapy follow-up >6 months:
EE; LL; MM; YYY; FFFF; RRRR; AAAAA; GGGGG; XXXXX; CCCCCC; GGGGGG; KKKKKK; LLLLLL

Solcodem vs control:
GGG

Minoxadil vs lidocaine:
CCCCC

Sildenafil vs control:
ZZZZ

Arginine vs LIS:
QQQ

Clove oil vs lidocaine:
OOO

Lanolin vs control:
BBB

Lanolin vs collagen spray:
BBB

Healer cream vs GTN:
JJJJJJ

Healer cream vs control
JJJJJJ

Metronidazole vs control:
BBBB

Ayurvedic concoction vs Ayurvedic + CCB:
JJJJJ

Indoramin vs control:
KKKKK

GTN vs ISMN:
AAAAAA

GTN topical vs GTN intra-anal:
DDDDDD

Botox anterior vs botox posterior:
VVVV

Botox posterior vs botox bilateral:
FFFFF

GTN 40 days vs GTN 80 days:
WWW

Diet vs control:
DDD

Lidocaine vs hydrocortisone:
HHHH

PTNS vs LIS:
LLLLLL

Psyllium husk gum vs control:
VV

Sitz baths vs control:
CCCC

Botox low dose vs botox high dose:
XX; LLLL

Botox vs botox + GTN:
NN; KKKK

GTN ointment vs GTN dermal patch:
III; MMMMMM

Lidocaine vs lidocaine. + dilator:
WWWW; NNNNNN

Botox vs Boxox disport:
YY

Lidocaine vs control children:
WWWWW; XXXXX

CCB vs botox:
PPPPP; EEEEE

PTNS vs GTN
…

CCB topical vs CCB oral:
FF; JJJJ

Bran vs Lactulose:
IIII

Surgical interventions

 

Non-healing of the fissure/recurrence

 

Open LIS vs Closed LIS:

A; B; F; J; N; CC

OR 1.00 (95% CI 0.4 to 2.48)

 

LIS to the apex of the fissure vs Lis to dentate line; subgroup anal:

Q; R

OR 7.1 (95% CI 1.2 to 50)

 

Fissurectomy vs LIS:

S; Z

OR 8.07 (95% CI 1.42 to 45.8)

 

LIS versus V-Y flap cover:

S; Z

OR 0.17 (95% CI 0.07 to 0.41)

 

Lis posterior versus LIS lateral:

X; Y

OR 0.3 (95% CI 0.01 to 7.87

 

Levatorplasty versus LIS:

D

OR 0.2 (95% CI 0.01 to 7.11

 

LIS closed wound versus LIS open wound:

M

OR 0.65 (95% CI 0.10 to 4.10)

 

Pneumatic balloon dilation to 3 cm versus LIS:

W

OR 1.47 (95% CI 0.29 to 7.37)

 

LIS + polyp removal vs LIS alone:

H

OR 1

 

Unilateral LIS vs Bilateral LIS:

U

OR 6.91 (95% CI 1.97 to 24.2)

 

Sphincterolysis vs Closed LIS:

I

OR 0.58 (95% CI 0.13 to 2.63)

 

V-Y flap vs Fissurectomy:

AA

OR 0.17 (95% CI 0.04 to 0.81

 

LIS vs V-Y anoplasty:

O

RR 0.44 (95% CI 0.20 to 0.97

 

Incontinence

 

Open LIS vs Closed LIS:

A (Arroyo, 2004)

Open LIS 2 months: 3/40 (7.5%)

Open LIS 6 months: 2/40 (5%)

Open LIS 1-2 years: 2/40 (5%)

Closed LIS 2 months: 2/40 (5%)

Closed LIS 6 months: 1/40 (2.5%)

Closed LIS 1-2 years: 1/40 (5%)

 

B (Boulos, 1984)

Open LIS incontinence of faeces: 0/14 (0%)

Open LIS incontinence of flatus: 2/14 (14.3%)

Closed LIS incontinence of faeces: 0/14 (0%)

Closed LIS incontinence of flatus: 3/14 (21.4%)

 

F (Filingeri, 2005)

Open LIS: 0/20 (0%)

Close LIS: 0/20 (0%)

 

J (Gupta, 2014)

Open LIS: 0/68 (0%)

Closed LIS: 0/68 (0%)

 

N (Kortbeek, 1992)

Incontinence not reported.

 

CC (Wiley, 2004)

Open LIS 1 year: 2/41 (4.9%)

Closed LIS 1 year: 1/38 (2.6%)

 

LIS to the apex of the fissure vs Lis to dentate line; subgroup anal:

Q (Mentes, 2005)

LIS apex mean (SD) postop anal incontinence score: 0.42 (0.76)

LIS dentate line mean (SD) postop anal incontinence score: 0.58 (1.13)

 

R (Mentes, 2008)

LIS apex mean (SD) postop anal incontinence score:

7 days: 0.71 (0.73)

28 days: 0.74 (0.68)

2 months: 0.39 (0.76)

6 months 0.35 (0.75)

 

Fissurectomy vs LIS:

S (Mousavi, 2009)

Fissurectomy incontinence to flatus or fecal soiling: 2/30 (6.7%)

LIS incontinence to flatus or fecal soiling: 0/32 (0%)

 

Z (Wang, 2005)

Studie alleen beschikbaar in chinees.

 

LIS versus V-Y flap cover:

Geen studies

 

Lis posterior versus LIS lateral:

X (Saad, 1992)

Full tekst niet beschikbaar.

 

Y (Tauro, 2011)

LIS posterior flatus incontinence and anal seepage: 4/30

LIS posterior fecal incontinence: 0/30

LIS lateral flatus incontinence and anal seepage: 1/30

LIS lateral fecal incontinence: 0/30)

 

Levatorplasty versus LIS:

D (Ellis, 2004)

Incontinence not reported.

 

LIS closed wound versus LIS open wound:

M (Kang, 2008)

LIS closed wound first week: 1/45

LIS closed wound fourth week: 1/45

LIS closed wound ninth week: 0/45

LIS open wound first week: 4/45

LIS open wound fourth week: 1/45

LIS open wound ninth week: 0/45

 

Pneumatic balloon dilation to 3 cm versus LIS:

W (Renzi, 2008)

Pneumatic balloon dilation 24 months: 0/24 (0%)

LIS 24 months: 4/25 (16%)

 

Speculum dilation 4.8 cm vs LIS:

DD (Yucel, 2009)

Speculum dilation anal incontinence: 0/20 (0%)

LIS anal incontinence: 0/20 (0%)

 

Dilation + fissurectomy vs LIS:

K (Hancke, 2009)

Dilation fecal incontinence: 3/27 (11%)

LIS fecal incontinence: 6/30 (20%)

 

LIS + polyp removal vs LIS alone:

H (Gupta, 2003)

Incontinence not reported.

 

Unilateral LIS vs Bilateral LIS:

U Pujahari, 2010)

ULIS incontinence for flatus: 4/104 (3.8%)

ULIS incontinence to liquid stools: 0/104 (0%)

BLIS incontinence for flatus: 2/107 (1.9%)

BLIS incontinence for liquid stools: 0/107 (0%)

 

Sphincterolysis vs Closed LIS:

I (Gupta, 2008)

Sphincterolysis detoration in continence 4 weeks: 2/42 (4.8%)

Sphincterolysis detoration in continence 54 weeks: 0/42 (0%)

Closed LIS detoration in continence 4 weeks: 3/43 (7.0%)

Closed LIS detoration in continence 54 weeks: 1/43 (2.3%)

 

V-Y flap vs Fissurectomy:

AA (wang, 2011)

Artikel in chinees

 

Ayurvedic suture of the fissure vs Dilation + anal stretch:

C (Dudhamal, 2014)

Incontinence not reported.

 

LIS vs V-Y anoplasty:

O

RR 15.00 (95% CI 0.88 to 255.78

 

Outcome measures (non-surgical interventions)

 

Non-healing of the fissure/recurrence

 

GTN vs control:

JJ; QQ; CCC; FFF; PPP; NNNN; OOOO; SSSS; TTTT; HHHHH; LLLLL; RRRRR; SSSSS; WWWWW; ZZZZZ; AAAAAA; BBBBBB; HHHHHH; IIIIII

OR 0.69 (95% CI 0.63 to 0.77)

 

GTN vs Lidocaine:

GG; PP; EEE; WWWWW; ZZZZZ

OR 0.19 (95% CI 0.11 to 0.33)

 

GTN high dose vs GTN low dose:

QQ; CCC; RRRRR; UUUUU

OR 0.91 (95% CI 0.57 to 1.45)

 

GTN vs pt. self-dilation:

UU (Boschetto, 2014)

GTN non healing: 11/18 61.1%)

Pt. self-dilation: 1/185.5%)

 

LLL (Di Visconte, 2006)

GTN non healing: 5/16

Pt. Self-dilation non-healing: 4/16

 

XXX (Gaj, 2006)

 

OR 4.18 (95% CI 2.10 to 8.33)

 

GTN vs botox:

EE; SS; WW; ZZ; JJJ; UUU; VVV; EEEEEE

OR 1.78 (95% CI 0.83 to 1.96)

 

GTN vs CCB:
EE; II; RR; TT; AAA; EEE; SSS; GGGG; PPPP; QQQQ; AAAAA; BBBBB; QQQQQ; SSSSS; EEEEEE
OR 1.45 (95% CI 1.10 to 1.91)

 

Botox vs control:
HHH; UUUU; VVVVV

OR 0.29 (95% CI 0.02 to 3.61

 

CCB topical vs control:

FF; KK; EEE; AAAA; DDDD; IIIII; SSSSS

OR 0.27 (95% CI 0.18 to 0.39)

 

LIS vs any medical therapy:

EE; HH LL; OO; KKK; NNN; RRR; TTT; YYY; ZZZ; EEEE; FFFF; MMMM; RRRR; XXXX; YYYY; AAAAA; DDDDD; EEEEE; GGGGG; MMMMM; NNNNN; PPPPP; TTTTT; XXXXX; YYYYY; CCCCCC; FFFFFF; GGGGGG; KKKKKK; LLLLLL

OR 0.22 (95% CI 0.16 to 0.28)

 

Lis vs any medical therapy follow-up >6 months:

EE; LL; MM; YYY; FFFF; RRRR; AAAAA; GGGGG; XXXXX; CCCCCC; GGGGGG; KKKKKK; LLLLLL

OR 0.12 (95% CI 0.07 to 0.21)

 

Solcodem vs control:

GGG

OR 0.26 (95% CI 0.1 to 0.67)

 

Minoxadil vs lidocaine:

CCCCC

OR 1.0 (95% CI 0.35 to 1.32)

 

Sildenafil vs control:

ZZZZ

OR 0 (95% CI 0.0 to 0.05)

 

Arginine vs LIS:

QQQ

OR 3.6 (95% CI 1.2 to 10.64)

 

Clove oil vs lidocaine:

OOO

OR 0.09 (95% CI 0.02 to 0.37)

 

Lanolin vs control:

BBB

OR 0.22 (95% CI 0.05 to 0.95)

 

Lanolin vs collagen spray:

BBB

OR 0.08 (95% CI 0 to 1.31)

 

Healer cream vs GTN:

JJJJJJ

OR 0.05 (95% CI 0.01 to 0.27)

 

Healer cream vs control

JJJJJJ

OR 0.17 (95% CI 0.03 to 0.92)

 

Metronidazole vs control:

BBBB

OR 0.15 (95% CI 0.02 to 1.12)

 

Ayurvedic concoction vs Ayurvedic + CCB:

Indoramin vs control:

JJJJJ

OR 0.78 (95% CI 0.39 to 1.54)

 

GTN vs ISMN:

KKKKK

OR 1.25 (95% CI 0.54 to 4.64)

 

GTN topical vs GTN intra-anal:

DDDDDD

OR 3.33 (95% CI 0.46 to 24.5)

 

Botox anterior vs botox posterior:

VVVV

OR 0.20 (95% CI 0.05 to 0.96)

 

 

Botox posterior vs botox bilateral:

FFFFF

OR 1.00 (95% CI 0.39 to 2.56)

 

GTN 40 days vs GTN 80 days:

WWW

OR 1.13 (95% CI 0.63 to 2.0)

 

PTNS vs LIS:

LLLLLL

OR 20.6 (95% CI 2.91 to 495)

 

Botox low dose vs botox high dose:

XX; LLLL

OR 1.93 (95% CI 0.75 to 4.93)

 

Botox vs botox + GTN:

NN; KKKK

OR 1.38 (95% CI 0.75 to 4.93)

 

GTN ointment vs GTN dermal patch:

III; MMMMMM

OR 1.07 (95% CI 0.50 to 2.27)

 

Botox vs Boxox disport:

YY

OR 2.80 (95% CI 1.17 to 6.72)

 

CCB vs botox:

PPPPP; EEEEE

OR 1.39 (95% CI 0.82 to 2.35)

 

PTNS vs GTN

OR 3.14 (95% CI 1.12 to 8.82)

 

CCB topical vs CCB oral:

FF; JJJJ

OR 0.76 (95% CI 0.33 to 1.76)

 

 

 

Incontinence

 

GTN vs control:

PPP (Emami, 2008):

GTN incontinence: 0/21 (0%)

Placebo incontinence: 0/21 (0%)

 

AAAAAA (Tankova, 2002):

GTN: 0/10 (0%)

Placebo: 0/9 (0%)

 

BBBBBB (Tankova, 2009)

GTN: 0/21 (0%)

Placebo: 0/10 (0%)

 

GTN vs Lidocaine:

None of the studies reported incontinence.

 

GTN high dose vs GTN low dose:

None of the studies reported incontinence.

 

GTN vs pt. self-dilation:

UU (Boschetto, 2004)

GTN: 0/18 (0%)

Pt. self-dilation: 0/18 (0%)

 

LLL (Di Visconte, 2006)

GTN fecal incontinence: 0/16

Pt. self-dilation: 0/16

 

MMM (Di Visconte, 2009)

GTN fecal soiling: 0/30 (0%)

GTN fecal incontinence: 0/30 (0%)

Pt. self-dilation fecal soiling: 0/30 (0%)

Pt. self-dilation fecal incontinence: 0/30 (0%)

 

GTN vs botox:

SS (Berkel, 2014)

GTN incontinence: 4/33 (12.1%)

Botox: 5/27 (18.5%) 

 

WW (Brisinda, 1999)

GTN: 0/25 (0%)

Botox: 0/25 (0%)

 

ZZ (Brisinda, 2007)

GTN feal incontinence: 0/50 (0%)

Botox fecal incontinence: 3/50 (6%) > disappeared spontaneously after 3 weeks.

 

JJJ (DeNardi, 2006)

GTN: 0/15 (0%)

Botox: 0/15 (0%)

 

VVV (Fruehauf, 2006)
GTN: 0/25 (0%)

Botox: 0/25 (0%)

 

GTN vs CCB:

GGGG (Jawaid, 2009)

GTN flatus incontinence: 1/40 (2.5%)

CCB flatus incontinence: 0/40 (0%)

 

BBBBB (Mustafa, 2006)

GTN: 0/10 (0%)

CCB: 0/10 (0%)

 

Botox vs control:

None of the studies reported incontinence.

 

CCB topical vs control:

None of the studies reported incontinence.

 

Surgical vs non-surgical

LIS vs any medical therapy:

LL (Arroyo, 2005)

LIS 2 month incontinence: 3/40 (7.5%)

LIS 6 month incontinence: 2/40 (5%)

LIS 1-2-3 years incontinence: 2/40 (5%)

Botox 2 month incontinence: 2/40 (5%)

Botox 6 month incontinence: 0/40 (0%)

Botox 1-2-3- years incontinence: 0/40 (0%)

 

OO (Aslam, 2014)

LIS: 2/30 (6.7%)

GTN: 0/30 (0%)

 

KKK (Dinç, 2014)
LIS: 3/30 (10%)

Botox: 0/30 (0%)

 

NNN (El-Labban, 2010)

LIS: incontinence to flatus: 3/40 (7.5%)

LIS: mild soiling: 2/40 (5%) 

GTN: 0/40 (0%)

 

RRR (Evans. 2001)

LIS: minor incontinence for flatus: 2/31 (6.5%)

GTN: 0/34 (0%)

 

TTT (Farooq, 2012)

LIS: mild incontinence flatus: 5/50 (10%)

Chemical sphincterotomy: 0/50 (0%) 

 

YYY (Gandomkar, 2015)

Partial LIS: incontinence: 8/50 (16%)

Botox: 2/49 (4.1%)

 

FFFF (Iswariah, 2005)

LIS: mean incontinence score 26 weeks (range) 0 (0)

Botox: mean incontinence score 26 weeks (range): 0.18 (0-2)

 

MMMM (Katsinelos, 2005)

LIS: 4/32 (12.5%)

CCB: 0/32 (0%)

 

YYYY (Mishra, 2005)

GTN: 0/20 (0%)

LIS: flatus incontinence: 3/20 (15%)

 

DDDDD (Nasr, 2010)

LIS: 6/40 (15%)

Botox: 0/40 (0%)

 

GGGGG (Parellada, 2004)

LIS: fecal incontinence: 0/12 (0%)

GTN: fecal incontinence: 0/12 (0%)

 

NNNNN (De Rosa, 2013)

LIS: flatus incontinence: 2/68 (3%)

LIS: fecal incontinence: 0/68 (0%)

CCB: flatus incontinence: 0/74 (0%)

CCB: fecal incontinence: 0/74 (0%)

 

PPPPP (Samim, 2012)

CCB: incontinence 4 weeks: 8/74 (10.8%)

CCB: incontinence 8 weeks: 6/74 (8.1%)

CCB: incontinence 12 weeks: 6/74 (8.1%)

Botox: incontinence 4 weeks 7/60 (11.7%)

Botox incontinence 8 weeks: 3/60 (5%)

Botox: incontinence 12 weeks: 3/60 (5%)

 

TTTTT (Siddique, 1970)
LIS: incontinence to flatus: 2/33 (6.1%)

GTN: incontinence to flatus: 0/31 (0%)

 

YYYYY (Suvarna, 2012)

LIS: flatus incontinence: 9/97 (9.3%)

LIS: fecal incontinence: 5/97 (5.2%)

CCB: flatus incontinence: 0/91 (0%)

CCB: fecal incontinence: 0/91 (0%)

 

CCCCCC (Tauro, 2011)

LIS: flatus incontinence: 1/30

LIS: anal seepage: 2/30

LIS: fecal incontinence: 0/30 (0%)

GTN: faltus, fecal incontinence and anal seepage: 0/30 (0%)

 

FFFFFF (Vaithianathan, 2015)

LIS: fecal or flatus incontinence: both 0/45 (0%)

CCB: fecal of flatus incontinence: both 0/45 (0%)

 

GGGGGG (Valizadeh, 2012)

LIS: incontinence 2 months: 12/25 (48%)

LIS: incontinence 3 months: 5/25 (20%)

LIS: incontinence 6 months: 4/25 (16%)

LIS: incontinence 12 months: 1/25 (4%)

Botox: incontinence 2 months: 3/25 (12%)

Botox: incontinence 3 months: 0/25 (0%)

Botox incontinence 6 months: 0/25 (0%)

Botox: incontinence 12 months: 0/25 (0%)

 

LLLLLL (Youssef, 2015)

LIS: anal incontinence 1 month: 3/37 (8.1%)

LIS: anal incontinence 1 year: 1/37 (2.7%)

TENS: anal incontinence 1 month: 0/36 (0%)

TENS: anal incontinence 1 year: 0/36 (0%)

 

Solcodem vs control:

Incontinence not reported.

 

Minoxadil vs lidocaine:

Incontinence not reported.

 

Sildenafil vs control:

Incontinence not reported.

 

Arginine vs LIS:

Incontinence not reported.

 

Clove oil vs lidocaine:

Incontinence not reported.

 

Lanolin vs control:

Incontinence not reported.

 

Lanolin vs collagen spray:

Incontinence not reported.

 

Healer cream vs GTN:

Incontinence not reported.

 

Healer cream vs control

Incontinence not reported.

 

Metronidazole vs control:

Incontinence not reported.

 

Ayurvedic concoction vs Ayurvedic + CCB:

Incontinence not reported.

 

Indoramin vs control:

Incontinence not reported.

 

GTN vs placebo:

GTN: fecal incontinence: 0/10 (0%)

Placebo: 0/9 (0%)

 

GTN topical vs GTN intra-anal:

Incontinence not reported.

 

Botox anterior vs botox posterior:

Incontinence not reported.

 

Botox posterior vs botox bilateral:

Incontinence not reported.

 

GTN 40 days vs GTN 80 days:

Incontinence not reported.

 

Lidocaine vs hydrocortisone:

Incontinence not reported.

 

PTNS vs LIS:

Incontinence not reported.

 

Botox low dose vs botox high dose:

Incontinence not reported.

Facultative:

 

LIS is the most effective treatment for anal fissure, curing all but 6% of patients. Late recurrences are very rare after LIS versus with medical therapy [179]. Minor incontinence is

more likely with LIS than medical therapy (Fig. 4). The difference between LIS and medical therapy is significant, but the absolute risk alteration is small, increasing from 3 cases per 1000 patients with medical therapy to 14 cases per 1000 with LIS (95% CI 6–31). Open and closed (a euphe- mism meaning less open) LIS are equally effective. Manual anal dilation is inferior to LIS, but recent small studies suggest that more controlled dilation, either pneumatic, by speculum or by patients at home are just as effective as LIS and are not associated with any risk of incontinence. GTN, Botox and CCBs have been extensively investigated as treatments for acute and chronic anal fissure. They appear to be effective, but most studies have been marred by inade- quate follow-up, thus missing late recurrences, which are common. Of the three, CCBs may be the most effective. More research is needed for all three with adequate follow- up. There is virtually no research on sequencing these drugs, i.e., if one fails, what is best to try next? Many other medi- cations have been tried because of the less-than-perfect track record of the three above, but none have proven better, and in any case, the studies are too small and too few. Clove oil and sildenafil may be worth further investigation. Many unpub- lished studies can be found in this field, especially in ICTRP, but no results are available.
Sahebally (2018a)

SR and meta-analysis of RCTs.

Literature search up to March 2017.

Study design:
Systematic review

Setting and Country:
Not reported.

Source of funding and conflicts of interest:
This research received no specific funding and there are no conflicts of interest to declare.

A. Brisinda, 1999
B. De Nardi, 2006
C. Brisinda, 2007
D. Festen, 2009
E. Berkel, 2014
Abd Elhady, 2009

Inclusion criteria SR
− RCTs in English language;
− Direct comparison of local botulinum toxin injection versus topical nitrates;

Exclusion criteria SR
− Studies that examined acute fissures only;
− Studies that examined chronic fissures in children;
− Studies that examined anal stenosis/stricture;
− Studies that evaluated botulinum toxin (or topical nitrates) only, without direct comparison to the other therapeutic strategy.

Six studies included in the review.

Important patient characteristics at baseline:

Sample size, N:
A. N=50
B. N=30
C. N=100
D. N=108
E. N=60
F. N=80

Age, mean (SD or median (range):
A. 42.15 (14.75) years
B. 41.8 (24-71) years
C. 44.1 (16.5) years
D. 40 (5.5) years
E. 42 (25-82) years
34.4 (20.6)

Describe intervention & intervention:

A. 0.2% GTN ointment 6 weeks (N=25) vs 10 U botulinum toxin to each side of the anterior midline (20 U in total)
B. 0.2% GTN ointment TDS 8 weeks vs 10 U botulinum toxin to each side of the anterior midline (20 U in total)
C. 0.2% GTN ointment TDS 8 weeks vs 30 U botulinum toxin or 90 U disport in total to anterior midline (2 injections of equal volume)
D. 10 U BT A to each side of anterior midline (20 U in total) + placebo ointment six times daily vs 1% ISDN + placebo injection
E. 30 U Dysport ® * to each side of anterior midline (60 U in total) vs 1% ISDN paste five times daily x 8 weeks
20 U of BT A to each side of IAS (40 U in total) vs 0.2% GTN ointment BD x 4-6 weeks

Non-healing of the fissure at 8 weeks, n/N (%)

Sphincterotomy, n/N (%):
17/349 (4.9%)

Botulinum toxin, n/N (%):
44/132 (33.3%)

Nitrates, n/N (%):
75/206 (36.4%)

Minoxidil, n/N (%):
22/44 (50%)

Diltiazem (CCB), n/N (%):
23/44 (52.3%)

Overall incontinence, n/N (%):

Sphincterotomy, n/N (%):
35/349 (10.0%)

Botulinum toxin, n/N (%):
19/132 (14.4%)

Nitrates, n/N (%):
4/206 (1.9%)

Minoxidil, n/N (%):
0/44 (0%)

Diltiazem (CCB), n/N (%):
0/44 (0%)

Permanent incontinence, n/N (%)

Sphincterotomy, n/N (%):
8/349 (2.3%)

Botulinum toxin, n/N (%):
0/132 (0%)

Nitrates, n/N (%):
0/206 (0%)

Minoxidil, n/N (%):
0/44 (0%)

Diltiazem (CCB), n/N (%):
0/44 (0%)

Non-healing of the fissure, n/N (%)

A. BT: 1/25 vs GTN: 10/25
B. BT: 7/15 vs GTN: 5/15
C. BT 4/50 vs GTN: 15/50
D. BT: 23/37 vs GTN: 15/36
E. BT: 9/27 vs GTN: 22/33

Pooled effect RR (95% CI) random effects:
OR 0.47 (95% 0.13 to 1.68)

Incontinence, n/N (%)
A. BT: 0/25 vs GTN: 0/25
B. BT: 0/15 vs GTN: 0/15
C. BT: 3/50 vs GTN: 0/50
D. BT: 8/37 vs GTN: 3/36
E. BT: 5/27 vs GTN: 4/23

Pooled effect RR (95% CI) random effects:
OR 2.53 (95% 0.98 to 6.57)

Author’s conclusion:

From a patient’s perspective, CAF is often an extremely debilitating and distressing condition, and it also represents a significant proportion of the coloproctology clinic workload. Though a benign problem, it can be considerably frustrating for patients, particularly given its recurrent nature. This review highlights the limited number of high-quality RCTs examining treatment modalities for CAF, specifically sphincter sparing procedures. It also highlights a lack of quality of life assessment. This study observed that lateral internal sphincterotomy has excellent healing rates at 8 weeks although topical nitrates and BT administration have reasonable results. Although the risk of permanent incontinence with LIS is low, its consideration should be tailored to the individual patient. This data demonstrates that the key in managing this benign, non-life-threatening condition with a range of acceptable treatments and variable complication profiles is open, high quality, documented patient counselling and consent. This tailored approach to the management of CAF is reflected in the proposed treatment algorithm
           
           
           
           
           
           
           

 

Randomized controlled trials

Study reference

Study characteristics

Patient characteristics 2

Intervention (I)

Comparison / control (C) 3

Follow-up

Outcome measures and effect size 4

Comments

Hassan (2022)

Type of study:

RCT.

 

Setting and country:

Al-Kindy Teaching Hospital

 

Funding and conflicts of interest:

None declared.

Inclusion criteria:

  • Patients with inflammatory bowel disease, perianal fistula, anal cancer, tuberculosis, pregnant, lactating, or wishing to become pregnant, patients with significant cardiovascular conditions, haemorrhoidectomy in the previous year and migraine excepted. Pain of anal with ulcer for 6 weeks and less, and vague sentry acute anal fissure, while pain with a non-healing ulcer > 8 weeks was taken as chronic anal fissure “nonetheless of attendance or nonappearance of the sentry tag”. Patients with earlier management for the fissure were included if the end of treatment was 3 months before inclusion (washout period is more than 3 months). Patients aged between ≥ 18 years and ≤ 65 years are included in the study

 

Exclusion criteria:

  • No information.

 

N total at baseline: N=100

GTN: N=52

LIS: N=60

 

Important prognostic factors2:

age ± range:

32.3 years (18-65)

 

Sex:

60 males, 52 females.

 

 

Groups comparable at baseline?

 Yes

Describe intervention (treatment/procedure/test:

GTN

Describe control (treatment/procedure/test:

Diltiazem

Length of follow-up:

8 weeks.

 

Loss-to-follow-up:

None.

Non-healing of the fissure, n/N (%)

I: 17/52 (32.7%)

C: 10/60 (16.7%)

 

 

Author’s conclusion

Both (0.2%) GTN ointment and (2%) DTZ gel are quietly effective in treating acute fissure in anus. However, topical DTZ gel is superior to topical GTN ointment, better tolerated with few side effects and recurrence rate.

Herreros (2021)

Type of study:

RCT.

 

Setting and country:

a tertiary care center, Spain.

 

Funding and conflicts of interest:

None declared.

Inclusion criteria:

  • The presence of a fissure at the posterior anal verge with visible internal sphincteric fibers or fibrotic edges that could be accompanied by a cutaneous tag;
  • Age >18 years;
  • Adequate mental status to fill out a symptom diary.

 

Exclusion criteria:

  • Anterior/lateral fissure, acute fissure;
  • Complications (stenosis, abscess, fis- tula, hemorrhoids);
  • Comorbidity (AIDS, sexually transmitted disease, IBD, tuberculosis, leukemia);
  • Pregnancy;
  • Anal surgery;
  • Coumarin therapy;
  • Prescription of CCBs or nitrites;
  • Hypersensitivity to diltiazem or BT;
  • Absence of anal pain.

 

N total at baseline:

Intervention: N = 25

Control: N = 30

 

Important prognostic factors2:

age ± SD:

I: 51.17 (13.6)

C: 48.86 (11.7)

 

Sex:

I: 62.9 % M

C: 54.3% M

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test:

Diltiazem after botox injection.

 

Describe control (treatment/procedure/test:

Placebo after botox injection.

Length of follow-up:

12 weeks.

 

Loss-to-follow-up:

None.

Non-healing

I: 12/25 (48%)

C: 19/30 (63.3%)

 

Author’s conclusion:

Our results suggest that combined therapy with BT injection and topical diltiazem is not superior to BT injection alone in the treatment of CAF. Both options offer suboptimal healing rates. Clearly, late recurrences are high (more than 80% at 10 years) and may appear at any time after healing. Further randomized controlled trials, including more patients with long-term follow-up, are needed to confirm our results and to identify subgroups of patients with CAF who could potentially benefit from nonsurgical treatments.

 

Khan (2021)

Type of study:

RCT.

 

Setting and country:

General surgery department, Peshawar.

 

Funding and conflicts of interest:

None declared.

Inclusion criteria:

  • All patients age 18 to 60 were included in the study after clinical diagnosis of chronic anal fissure and informed consent.

 

Exclusion criteria:

  • Patients who had any other anorectal disease were excluded from the study. Patients with secondary fissures from clinical history and examination, with a history of comorbidity (Tuberculosis, hypertension. diabetes, malignancies and ischemic heart disease), pregnancy, patient on treatment with nitrates, and patients with a history of anal trauma or surgery were excluded.

 

N total at baseline:

Intervention: N = 30

Control: N = 30

 

Important prognostic factors2:

age ± SD:

I: 30 (2.77)

C:29 (2.53)

 

Sex:

I: 43% M

C: 40% M

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test:

LIS

 

Describe control (treatment/procedure/test:

Topical Nitroglycerin.

Length of follow-up:

Six weeks.

 

Loss-to-follow-up:

None.

Fissure healing

I: 27/30 (90%)

C: 20/30 (66.7%)

Author’s conclusion:

Lateral internal sphincterotomy is comparatively of increased effectiveness than topical Glyceryl trinitrate in treating chronic anal fissure.

 

Malik (2021)

Type of study:

RCT.

 

Setting and country:

Hospital, Rawalpindi Pakistan.

 

Funding and conflicts of interest:

No information.

Inclusion criteria:

  • Patients ages were ranging between 18 to 70 years with chronic anal fissures.

 

Exclusion criteria:

  • Patients on nitrates for medical conditions like IHD, pregnant women. inflammatory Bowel Disease and Crohn’s disease, and patients with immunocompromised state were excluded.

 

N total at baseline:

Intervention: N = 50

Control: N = 50

 

Important prognostic factors2:

age ± SD:

I: 31.48 (8.88)

C: 30.26 (8.76)

 

Sex:

I: 34/50 (68%) M

C: 30/50 (60(%) M

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test)

LIS

Describe control (treatment/procedure/test:

Topical GTN

Length of follow-up:

2 weeks.

 

Loss-to-follow-up:

None.

Painfree

I: 48/50 (96%)

C: 35/50 (70%)

 

Author’s conclusion:

It is concluded that 2% nifedipine paste is as effective as 0.5% GTN ointment in terms of efficacy in management of chronic anal fissure. However, the study was conducted on a limited number of patients and many aspects of nifedipine, e.g., side effects were not compared with GTN, it is suggested that further research could help in adapting the nifedipine as a first line treatment in chronic anal fissure.

 

Mustafa (2022)

Type of study:

RCT.

 

Setting and country:

Colorectal surgery unit, department of surgery, Bagabandhu Sheikh Mujib Medical University.

 

Funding and conflicts of interest:

No information.

Inclusion criteria:

  • Chronic anal fissures;
  • Fissure in anterior and posterior midline;
  • Adult patients of both sexes.

 

Exclusion criteria:

  • Acute anal fissure;
  • Secondary cause of chronic anal fissure;
  • Patients having severe co-morbidities, including diabetes mellitus, poor nutritional status;
  • Patients taking oral or sublingual nitroglycerin, steroid;
  • Anal fissure with complications like abscess, fistula.

 

N total at baseline:

Intervention: N = 47

Control: N = 47

 

Important prognostic factors2:

age ± SD:

I: 34.6 (10.4)

C: 33.2  (8.6)

 

Sex:

I: 25/47 (53.2%) M

C: 19/47 (40.4%) M

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test:

GTN

 

 

Describe control (treatment/procedure/test:

LIS

Length of follow-up:

6 months.

 

Loss-to-follow-up:

I: N = 4

C: N = 3

Non-healing of the fissure:

I: 11/43

C: 2/44

 

Incontinence

I: 0/43

C: 4/44

Author’s conclusion:

See original publication.

Tahir (2022)

Type of study:

RCT.

 

Setting and country:

Hospital, Lahore Pakistan.

 

Funding and conflicts of interest:

None declared.

Inclusion criteria:

  • patients were enrolled after their complete clinical diagnosis of chronic anal fissure. The clinical symptoms were correlated with their physical presentation of the condition.

 

Exclusion criteria:

  • Those patients who were suffering from perianal disease such as hemorrhoids, abscess, fistula and having 2-3 weeks’ acute anal fissure or undergone previous surgical procedure for anal fissure were excluded from the research

 

N total at baseline:

Intervention: N = 50

Control: N = 50

 

Important prognostic factors2:

age ± SD:

I: 39.5 (4.7)  

C: 38.9 (5.1)

 

Sex:

I: 23/50 46(%) M

C: 27/50 (44%) M

 

Groups comparable at baseline?

Yes.

 

Describe intervention (treatment/procedure/test:

LIS

 

Describe control (treatment/procedure/test:

Anal advancement flap.

Length of follow-up:

3 months.

 

Loss-to-follow-up:

None.

Fissure healing

I: 44/50 (88%)

C: 48/50 (96%)

Author’s conclusion:

Anal advancement flap surgical method is considerably a better treatment method for the treatment of anal fissures. Low post- operative infections rate was also observed anal fissure flap group as compared to lateral sphinecterotomy group.

 

Nour, 2020

Type of study:

Randomized comparative clinical trial

 

Setting and country:

General surgery department, Zagazig Faculty of Medicine, Egypt.

 

Funding and conflicts of interest:

Not reported.

Inclusion criteria:

  • Patients suffering chronic anal fissure aged above 16 years old.

 

Exclusion criteria:

  • Those with specific previous anal surgery;
  • Complicated anal fissure;
  • Patients unfit for surgery;
  • Patients with specific diseases as Crohn’s disease, ulcerative colitis and anorectal malignancy;
  • Malignancy;
  • Anal fistula or abscess;
  • Those with systematic disease requiring treatment with calcium channel blockers and/or nitrates;
  • Hypersensivity to botulinum toxins.

 

N total at baseline:

Botox: N=48

LIS: N=48

 

Important prognostic factors2:

age ± SD:

Botox: 33.46 (10.18)

LIS: 32.29 (9.88)

P=0.29

 

Sex:

I: 32/48 (66.7%) M

C: 26/48 (54.2%) M

P=0.21

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test:

 

Botulinum toxin (BOTOX) injection; was performed under general anesthesia in the lithotomy position, where 80 IU of (BOTOX) was injected in four positions each 20 IU namely in 5, 7, 11, and 1 O’clock positions in the internal sphincter not deeper than the midpoint of the anal canal.

Describe control (treatment/procedure/test:

 

Lateral internal sphincterotomy; was performed under general anesthesia where the lower part of the internal sphincter was cut by electerocautery after opening the skin of the intersphincteric groove, on the left lateral site and not extending beyond the proximal end of the fissure, the chronic fissure complex was also removed. The wound was left open at the end of the procedure after sufficient hemostasis.

Length of follow-up:

1 week and 1, 2, 3, 6, 9, and 12 months.

 

Loss-to-follow-up:

None.

 

Incomplete outcome data:

None.

Non-healing per month, 1st month, n/N (%):

Botox: 31/48 (64.6%)

LIS: 30/48 (62.5%)

P=0.42

 

Non-healing per month, 2nd month, n/N (%):

Botox: 11/48 (22.9%)

LIS: 4/48 (8.3%)

P=0.024

 

Incontinence to flatus 1st months, n/N (%):

Botox: 8/48 (16.6%)

LIS: 5/48 (10.4%)

P=0.37

 

Incontinence to flatus after 6 months, n/N (%):

Botox: 0/48 (0%)

LIS: 2/48 (4.2%)

P=0.15

 

 

 

Author’s conclusion:

 

(BOTOX) injection is safer than (LIS) in treatment of CAF but with less efficacy, its dose need to be adjusted, (LIS) is more efficient but anal sphincter tone need to be assessed before the operation.

Venkatesh (2019)

Type of study:

Comparative randomized controlled trial.

 

Setting and country:

Rajarajeswari Medical College and Hospital Bengaluru

 

Funding and conflicts of interest:

None declared.

Inclusion criteria:

  • Patients with chronic anal fissure.

 

Exclusion criteria:

  • Patients with AF secondary to other diseases like inflammatory bowel disease, malignancy, sexually transmitted diseases, previous treatment with local ointment or surgery;
  • Patients who needed anal surgery for any concurrent disease like hemorrhoids, pregnant women;
  • Patients with significant cardiovascular conditions.

 

N total at baseline:

Diltiazem (CCB): N=50

GTN: N=50

 

Important prognostic factors2:

age ± SD:

Diltiazem: 38

GTN: 36

 

Sex:

Diltiazem: 24/50 (48%) M

GTN: 27/50 (54%) M

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test:

 

Patients were advised to apply a pea size (approx. 250 mg) quantity of 2% DTZ cream by fingertip to the anal verge twice daily for 8 weeks.

 

Describe control (treatment/procedure/test:

 

Patients were advised to apply a pea size (approx. 250 mg) quantity of 0.2% GTN ointment by fingertip to the anal verge twice daily for 8 weeks.

Length of follow-up:

8 weeks

 

Loss-to-follow-up:

None.

 

Incomplete outcome data:

None.

Non-healing of the fissure, n/N (%)

 

2nd week:

Diltiazem: 49/50 (98.0%)

GTN: 48/50 (96.0%)

 

4th week:

Diltiazem: 18/50 (36%)

GTN: 20/50 (40%)

 

6th week:

Diltiazem: 10/50 (20%)

GTN: 12/50 (24%)

Author’s conclusion:

 

To conclude, CAF healing was found in 80% of the cases who received topical DTZ. The duration of the treatment was quite long with topical agents hence causing less patient compliance. Topical 2% DTZ appeared to be well tolerated and effective preferred first-line method of chemical sphincterotomy with less side effects.

Ahmed (2018)

Type of study:

Prospective, randomized clinical study.

 

Setting and country:

Department of general surgery, Bolan Medical Complex Hospital, Quetta Pakistan.

 

Funding and conflicts of interest:

Not reported in the study.

Inclusion criteria:

Patients with CAF having age 20 years to 70 years.

 

Exclusion criteria:

Patients with anal fissure with associated other anorectal disorders e.g. anorectal abscess or fistula, with history of previous dilatation of anus and previous perineal surgery were excluded.

 

N total at baseline: N=100

Closed LIS: N=50

Open LIS: N=50

 

Important prognostic factors2:

age ± SD:

CLIS: 39.12 (12.34)

OLIS: 41.40 (11.6)

P=0.35

 

Sex:

CLIS: 32/50 (64%) M

OLIS: 35/50 (70%) M

P=0.52

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

 

IN CLIS patients, a cut entry point was made with a Von Graffe's sharp edge, either into the inter-sphincteric groove or into the submucosa. The front line of the cutting edge was pivoted toward the interior sphincter and a halfway sphincterotomy was finished. The skin wound entry point was left open.

Describe  control (treatment/procedure/test):

 

For OLIS, we use endoscope for anal canal visualization. A longitudinal entry point was made in the anoderm, and the distal portion of the internal anal sphincter was partitioned under direct vision took after by closing of the mucosa.

Length of follow-up:

5 days post-op

 

Loss-to-follow-up:

None.

 

Incomplete outcome data:

None.

(fecal) Incontinence, n/N (%):

 

CLIS: 3/50 (6.0%)

OLIS: 9/50 (18.0%)

P=0.06

 

Pain, mean (SD), 12 hours postop

CLIS: 5.76 (0.91)

OLIS: 6.45 (0.79)

P<0.0001

 

Pain, mean (SD), 24 hours postop

CLIS: 2.00 (0.29)

OLIS: 2.39 (0.61)

P=0.01

Author’s conclusion:

 

Closed lateral internal sphincterotomy (CLIS) is superior to open lateral internal sphincterotomy (OLIS) for the surgical management of chronic anal fissure (CIF).

Ruiz-Tovar (2017)

Type of study:

Prospective randomized study.

 

Setting and country:

Garcilaso Clinic, Madrid, Spain.

 

Funding and conflicts of interest:

Not reported in the study.

Inclusion criteria:

`patients with a diagnosis of chronic anal fissure treated at the Garcilaso Clinic between January 2014 and July 2015.

 

Exclusion criteria:

Patients with associated anal pathologies, intestinal inflammation disorders, immunosuppression, or fissures secondary to underlying diseases (eg, aiDs, tuberculosis, or sexually transmitted diseases). Also excluded were patients with a history of headaches, heart disease, or intolerance to nitrates; pregnant or lactating women; patients with closed angle glaucoma; and patients <18 years of age.

 

N total at baseline: N=80

GTN: N=40

PPTNS: N=40

 

Important prognostic factors2:

age ± SD:

GTN: 46.8 (8.1)

PPTNS: 50.0 (9.0)

P=0.34

 

Sex:

GTN: 16/40 (40%) M

PPTNS: 18/40 (45%) M

P=0.82

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

 

375.0 mg of ointment (containing 1.5mg of glyceryl trinitrate), applied with a gloved finger to the distal anal canal, every 12 hours for 8 weeks.

Describe  control (treatment/procedure/test):

 

Subjects underwent one 30-minute session 2 days per week for 8 consecutive weeks. The patients attended the outpatient clinic to undergo the treatments. All of the patients went on their own, without medical transport. Patients were placed in the su- pine position without anesthesia. PPtns was delivered using a needle electrode that was inserted 3 to 4 cm cepha- lad and 2cm posterior to the medial malleolus at a 60o angle toward the ankle joint to a depth of ≈0.5 to 1.0 cm. successful placement was confirmed by the presence of an electric sensation 5 cm above and below the insertion site or a digital plantar flexion. PPtns was delivered at the highest amplification (0–20 ma) at a frequency of 20 hz, causing neither a motor response nor pain.

Length of follow-up:

 

 

Loss-to-follow-up:

Intervention:

N=6 (%)

Reasons (describe)

 

Control:

N=0 (0%)

Non-healing of the fissure, n/N (%):

 

2 weeks

GTN: 14/40 (35%)

PPTNS: 10/40 (25%)

 

8 weeks

GTN: 13/40 (32.5%)

PPTNS: 5/40 (12.5%)

 

Pain, median (IQR)

GTN: 4 (0-9)

PTNS: 3 (0-8)

Author’s conclusion:

 

GTN treatment is associated with incapacitating headache that leads to treatment discontinuation in 15% of patients. By contrast, PPTNS achieved an 87.5% healing rate (vs 65.0% for GTN) with no adverse effects. PPTNS can thus be considered a safe and effective alternative to GTN for treatment of chronic anal fissure, which is in some ways superior to GTN.

Akinci, 2020

Type of study:

Prospective, randomized controlled trial.

 

Setting and country:

Hakkari State Hospital General Surgery Clinic, Hakkari, Turkey.

 

Funding and conflicts of interest:

None declared.

Inclusion criteria:

  • Patients with acute anal fissures;
  • Aged 18 years or older;
  • Acute anal fissures for the first time.

 

Exclusion criteria:

  • Patients with chronic anal fissures;
  • Patients with inflammatory bowel disease, hemorrhoid, tuberculosis, anal cancer;
  • Patients with a history of anal surgery;
  • Pregnant and lactating patients;
  • Aged under 18;
  • Patients who did not want to enroll in the study.

 

N total at baseline: N=100

GTN: N=50

Topical nifedipine (ND): N=50

 

Important prognostic factors2:

age ± SD:

GTN: 29.36 (8.97)

ND: 30.78 (8.55)

P=0.288

 

Sex:

GTN: 25/50 (50%) M

ND: 27/50 (54%%) M

P=0.689

 

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

 

0.2% glyceryl trinitrate (GTN)

Describe  control (treatment/procedure/test):

 

0.5% topical nifedipine (ND)

Length of follow-up:

21 days

 

Loss-to-follow-up:

None.

 

Incomplete outcome data:

None.

Non-healing of the fissure, n/N (%):

 

GTN: 18/50 (36%)

ND: 7/50 (14%)

P=0.011

 

Recurrence, n/N (%):

 

GTN: 19/50 (38%)

ND: 9/50 (18%)

P=0.026

Author’s conclusion

 

Data obtained from our study shows that both glyceryl trinitrate and topical nifedipine have favorable effects on anal fissure treatment. However, topical 0.5% nifedipine is superior to 0.2% glyceryl trinitrate in the treatment of anal fissure in terms of symptomatic relief, decrease in pain score, healing, drug side effects, and recurrence. But, it is a fact that there is a need for prospective clinical studies with a larger number of patients, long-term follow-up, and that are supported with manometric measurements.

Akhtar, 2016

Type of study:

Randomized controlled trial

 

Setting and country:

Department of Surgery Nishter Hospital Multan, Pakistan

 

Funding and conflicts of interest:

Not reported.

Inclusion criteria:

  • Patients with acute anal fissures;
  • Aged between 20 and 60 years.

 

Exclusion criteria:

  • Patients with recurrent anal fissure;
  • Patients with external or internal hemorrhoids;
  • Patients with chronic anal fissures;
  • Patients treated by Hakeems assessed on history and physical examination and parturition trauma.

 

N total at baseline: N=94

LIS: 47

GTN: N=47

 

Important prognostic factors2:

age ± SD:

LIS:

GTN:

 

Sex:

LIS: 30/47 (63.8%) M

GTN: 17/47 (36.2%) M

 

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

 

Lateral internal sphincterotomy (LIS)

Describe  control (treatment/procedure/test):

 

Glyceryl trinitrate (GTN) 0.2% cream

Length of follow-up:

Six weeks

 

Loss-to-follow-up:

None.

 

Incomplete outcome data:

None.

Non-healing of the fissure, n/N (%)

 

LIS: 6/47 (12.77%)

GTN: 18/47 (38.3%)

Author’s conclusion

 

Results of this study revealed that frequency of healing in patients with acute anal fissure is better in patients managed with Lateral internal sphincterotomy as compare to patients managed the GTN cream. In male patients there is no statistical difference between healing rate of both groups but female patients found with higher healing rate in Lateral internal sphincterotomy group as compare to GTN cream group.

Farooq, 2012

Type of study:

Quasi-experimental study.

 

Setting and country:

Department of surgery (unit-I), Sir Ganga Ram Hospital, Lahore.

 

Funding and conflicts of interest:

Not reported.

Inclusion criteria:

  • Patients with acute anal fissure;
  • Patients aged between 20 and 50 years of age;

 

Exclusion criteria:

  • Patients with other anal pathologies;
  • Cardiac patients;
  • Pregnant or planning to be pregnant patients;

 

N total at baseline: N=100

GTN: N=50

LIS: N=50

 

Important prognostic factors2:

age ± SD:

GTN: 36.56 (8.42)

LIS: 35.14 (9.48)

P>0.05

 

Sex:

GTN: 22/50 (44%) M

LIS: 17/50 (34%)% M

P>0.05

 

Groups comparable at baseline?

 Yes

Describe intervention (treatment/procedure/test):

 

0.2% GTN ointment locally 3 to 4 times daily along with sitz bath and stool softeners

Describe  control (treatment/procedure/test):

 

Lateral internal sphincterotomy (LIS)

Length of follow-up:

2nd postoperative day, the end of the first week, third week, sixth week, and after 3 months.

 

Loss-to-follow-up:

None.

 

Incomplete outcome data:

None.

Non-healing of the fissure, n/N (%)

 

GTN: 18/50 (36%)

LIS: 0/50 (0%)

P<0.05

 

(flatus) Incontinence, n/N (%):

GTN: 0/50 (0%)

LIS: 5/50 (10%)

Author’s conclusion

 

Surgical sphincterotomy is better than chemical sphincterotomy in the management of acute anal fissure in terms of early symptomatic relief and high healing rates. However, chemical sphincterotomy heals 54% of patients in out patient setting, associated with less work loss that is no hospital admission is required and is not detrimental to continence so it has a definite role in the management of acute anal fissure.

 

Risk of bias table

 

Systematic review(s)

Study

 

 

 

 

First author, year

Appropriate and clearly focused question?1

 

 

 

Yes/no/unclear

Comprehensive and systematic literature search?2

 

 

 

Yes/no/unclear

Description of included and excluded studies?3

 

 

 

Yes/no/unclear

Description of relevant characteristics of included studies?4

 

 

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?5

 

 

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?6

 

 

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?7

 

Yes/no/unclear

Potential risk of publication bias taken into account?8

 

 

Yes/no/unclear

Potential conflicts of interest reported?9

 

 

 

Yes/no/unclear

Nelson, 2017

Yes

Yes

Yes

Yes

Not applicable

Yes

Yes

Yes

Yes

 

 

Randomized controlled trial(s)

Study reference

 

(first author, publication year)

Was the allocation sequence adequately generated? a

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?b

 

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?c

 

Were patients blinded?

 

Were healthcare providers blinded?

 

Were data collectors blinded?

 

Were outcome assessors blinded?

 

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?d

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?e

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?f

 

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measureg

 

 

 

LOW

Some concerns

HIGH

Hassan (2022)

Probably yes.

No information

No information

Definitely no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: Allocation of concealment process not reported; blinding unclear.

Mustafa (2022)

Definitely yes.

 

Reason: Randomization with lottery.

No information.

No information.

Probably no

 

Reason: LTFU almost equal in both groups.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: Allocation of concealment process not reported; blinding unclear.

Tahir (2022)

Definitely yes.

 

Reason: The patients were randomly selected by computer generated numbers into two groups.

No information.

No information.

Definitely no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: Allocation of concealment process not reported; blinding unclear.

Herreros (2021)

Definitely yes

 

Reason: A randomized, controlled, double-blind, 2-arm, parallel- group trial was conducted

Probably yes.

 

Reason: All patients received a local injection of BT. They were randomly assigned to local gel by a free computer-gener- ated table of random numbers with a 1:1 allocation rate

Definitely yes.

 

Reason: All patients and researchers involved in the different phases of the study were blinded to treatments.

Definitely no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Low

Malik (2021)

Definitely yes.

 

Reason: The patients were randomly selected by computer generated numbers into two groups.

No information.

No information.

Definitely no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: Allocation of concealment process not reported; blinding unclear.

Khan (2021)

Definitely yes.

 

Reason: The patients were randomly selected by computer generated numbers into two groups.

No information.

No information.

Definitely no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: Allocation of concealment process not reported; blinding unclear.

Nour, 2020

Definitely yes

 

Reason: The participants were randomly allocated into two groups.

Definitely yes

 

Reason: Randomization was achieved using computer generated cards. , study sample size was calculated by the statistical unit of IRB in our institute.

No information

Definitely no

 

Reason: no lost to follow-up in the study.

Definitely yes

 

Reason: all predefined outcome measures were reported.

Probably yes

Low

Venkatesh, 2019

No information

No information

No information

Definitely no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: randomization and allocation of concealment process not reported; blinding unclear.

Akinci, 2020

No information

No information

No information

Definitely no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns/high

 

Reason: no information regarding allocation sequence, allocation concealment, blinding and other problems that could put it at a risk of bias.

Ahmed (2018)

No information

No information

No information

Probably no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns: randomization process not reported; allocation concealment not reported; blinding not reported.

Ruiz-Tovar, 2017

Definitely yes

 

Reason: patients were randomly assigned to one of the treatment groups.

Definitely yes

 

Reason A simple computerized randomization scheme at a 1:1 ratio was used.

Probably yes

 

Reason: Data were collected by an independent data manager and

analyzed by an independent statistician. An independent

data monitoring committee supervised the compliance

with the study protocol and the correct collection of the

data.

Probably yes:

 

Reason: more lost to follow-up in GTN group compared to PPTNS group (N=6 vs N=0).

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns:

Differences in lost to follow-up.

Akhtar, 2016

Definitely yes

 

Reason: All included patients were offered to pick up a slip from total mixed up slips (half-slips were contain letter “A” and other half-slips contain letter “B”) and he/she was placed in that group (Group-A or Group-B according to slip).

Definitely yes

 

Reason: All included patients were offered to pick up a slip from total mixed up slips (half-slips were contain letter “A” and other half-slips contain letter “B”) and he/she was placed in that group (Group-A or Group-B according to slip).

No information

Probably no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: blinding not reported of outcome assessors not reported.

Farooq, 2012

Probably yes

 

Reason: Patients were randomly divided into two treatment groups A and B.

No information

No information

Probably no

 

Reason: no lost to follow-up in the study.

Probably yes

 

Reason: all predefined outcome measures were reported.

No information

Some concerns

 

Reason: no information regarding allocation concealment, blinding and other possible bias.

 

Table of excluded studies

Author and year

Reason for exclusion

Gupta (2023)

Does not match PICO.

Van Reijn-Baggen (2022)

Does not match PICO.

Shahid (2022)

Does not match PICO.

Sungurtekin (2022)

Does not match PICO.

Mert (2022)

Does not match PICO.

Nordholm-Carstensen, 2020

Does not match PICO

Mosleh, 2020

Does not match PICO

Emile, 2020

Does not match PICO

Nelson, 2020

Does not match PICO

Sekmen, 2020

Does not match PICO

Emile, 2020

Does not match PICO

Yilmaz, 2020

Intervention not relevant for Dutch practice.

Acharya, 2019

Does not match PICO

Tavakoli-Dastjerdi, 2019

Does not match PICO

Alvandipour, 2018

Does not match PICO

Chiaretti, 2018

Does not match PICO

Pilkington, 2018

Does not match PICO

Ebinger, 2017

No additional studies/information compared to Nelson (2017), Boland (2020), and Sahebally (2018a)

Ala, 2016

Does not match PICO

Lin, 2016

Does not match PICO

Bockiewicz, 2016

Does not match PICO

Khaledifar, 2015

Does not match PICO

Vaithianathan, 2015

Does not match PICO

 

Autorisatiedatum en geldigheid

Laatst beoordeeld  : 07-05-2024

Laatst geautoriseerd  : 07-05-2024

Geplande herbeoordeling  : 07-05-2026

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging voor Heelkunde
Geautoriseerd door:
  • Nederlandse Vereniging van Maag-Darm-Leverartsen
  • Nederlandse Vereniging voor Dermatologie en Venereologie
  • Nederlandse Vereniging voor Heelkunde
  • Patiëntenfederatie Nederland
  • Stichting Bekkenbodem4All

Algemene gegevens

De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS). De financierder heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodule is in 2020 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor hemorroïden, anusscheurtjes en perianale fistels.

Belangenverklaringen

Werkgroeplid

Functie

Nevenfuncties

Gemelde belangen

Ondernomen actie

Mw. dr. M.S. (Mich) Dunker

Colorectaal chirurg

Geen.

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

 

Geen restricties.

Dhr. dr. D.D.E. (David) Zimmerman

Colorectaal chirurg

* Lid Executive Committee European Society Coloproctology (onbetaald)

* Lid Education Committee European Society Coloproctology (onbetaald)

* Voorzitter werkgroep richtlijn 'Perianal Fistula', European Society Coloproctology (onbetaald)

* Secretaris Examencommissie UEMS, Divisie Coloproctologie (onbetaald)

* Vice voorzitter Dutch Society of Colorectal Surgery (onbetaald).

 

Persoonlijke financiële belangen

Adviseur, Takeda, eenmalig, onkostenvergoeding ontvangen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

Geen restricties.

Mw. dr. S.O. (Stefanie) Breukink

Chirurg

Chair guideline commitee ESCP, onbetaald.

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

PI RCT Napoleon study: Cost-effectiveness and effectiveness of rubber band ligation versus sutured mucopexy versus haemorrhoidectomy in patients with recurrent haemorrhoidal disease: a multicentre, randomized controlled trial. ZonMw subsidie.

 

Intellectuele belangen en reputatie

PI van richtlijn ESCP haemorrhoidal disease

 

ESCP = European Society of Coloproctology

 

escp.eu.com/images/guidelines/documents/escp-guidelines-haemorrhoidal-disease.

 

Overige belangen

Geen.

 

Geen restricties.

Mw. dr. O. (Oddeke) van Ruler

 

Chirurg

Geen.

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

PI ALERT-CD trial. Onderzoek naar praktijkvariatie en kwaliteit van leven bij patiënten met Crohnse perianale fistels. Funding TAKEDA. Crohnse fistels zijn geen onderdeel van deze richtlijn.

 

Intellectuele belangen en reputatie

PI onderzoek naar autologe celtherapie bij cryptoglandulaire en Crohnse perianale fistels. Nog in experimentele fase derhalve geen onderdeel van deze richtlijn.

 

Overige belangen

Geen.

 

Geen restricties.

Mw. dr. J.M.T. (Jikke) Omloo

Chirurg, Gelre ziekenhuizen

Geen.

Persoonlijke financiële belangen

Niet van toepassing.

 

Persoonlijke relaties

Niet van toepassing.

 

Extern gefinancierd onderzoek

Niet van toepassing.

 

Intellectuele belangen en reputatie

Niet van toepassing.

 

Overige belangen

Niet van toepassing.

 

Geen restricties.

Mw. dr. R.J.F. (Richelle) Felt - Bersma

Maag- Darm – Leverarts

MDL-arts aan de VU regulier, daarbij 1 dag ge/outsourced naar de Proctoskliniek te Bilthoven.

Voorts 12/13x per jaar op de vrijdagmiddag Proctologie in MCV de Veluwe.

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

 

Geen restricties.

Mw. dr. N.H.N. (Nynke) Meijer – de Vrieze

Dermatoloog

Geen.

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

 

Geen restricties.

Inbreng patiëntenperspectief

Er werd aandacht besteed aan het patiëntenperspectief door het uitnodigen van de Patiëntenfederatie Nederland voor de schriftelijke knelpuntenanalyse. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptmodules zijn tevens voor commentaar voorgelegd aan de Patiëntenfederatie Nederland en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.

Methode ontwikkeling

Evidence based

Implementatie

Wkkgz & Kwalitatieve raming van mogelijke substantiële financiële gevolgen

Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz

Bij de richtlijn is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling zijn richtlijnmodules op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).

 

Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn, zie onderstaande tabel.

 

Module

Uitkomst raming

Toelichting

Aanvullende diagnostiek bloedverlies per anum

Geen financiële gevolgen

Uit de toetsing volgt dat de aanbeveling(en) niet breed toepasbaar zijn (<5000 patiënten) en zal daarom naar verwachting geen substantiële financiële gevolgen hebben voor de collectieve uitgaven.

 

Perianale fistels

Geen financiële gevolgen

Uit de toetsing volgt dat de aanbeveling(en) niet breed toepasbaar zijn (<5000 patiënten) en zal daarom naar verwachting geen substantiële financiële gevolgen hebben voor de collectieve uitgaven.

 

Acute anale fissuren

Geen financiële gevolgen

Uit de toetsing volgt dat de aanbeveling(en) niet breed toepasbaar zijn (<5000 patiënten) en zal daarom naar verwachting geen substantiële financiële gevolgen hebben voor de collectieve uitgaven.

 

Chronische anale fissuren

Geen financiële gevolgen

Uit de toetsing volgt dat de aanbeveling(en) niet breed toepasbaar zijn (<5000 patiënten) en zal daarom naar verwachting geen substantiële financiële gevolgen hebben voor de collectieve uitgaven.

 

Werkwijze

AGREE

Deze richtlijnmodule is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).

 

Knelpuntenanalyse en uitgangsvragen

Tijdens de voorbereidende fase inventariseerde de werkgroep de knelpunten in de zorg voor patiënten die hemorroïden, anusscheurtjes of perianale fistels ervaren. Tevens zijn er knelpunten aangedragen door middel van een schriftelijke knelpuntenanalyse. Een verslag hiervan is opgenomen onder aanverwante producten.

 

Op basis van de uitkomsten van de knelpuntenanalyse zijn door de werkgroep concept-uitgangsvragen opgesteld en definitief vastgesteld.

 

Uitkomstmaten

Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.

 

Methode literatuursamenvatting

Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’ onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. Review Manager 5.4 werd gebruikt voor de statistische analyses. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.

 

Beoordelen van de kracht van het wetenschappelijke bewijs

De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie http://www.gradeworkinggroup.org/). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).

GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).

 

GRADE

Definitie

Hoog
  • er is hoge zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • het is zeer onwaarschijnlijk dat de literatuurconclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Redelijk
  • er is redelijke zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • het is mogelijk dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Laag
  • er is lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • er is een reële kans dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Zeer laag
  • er is zeer lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • de literatuurconclusie is zeer onzeker.

 

Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).

 

Overwegingen (van bewijs naar aanbeveling)

Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.

 

Formuleren van aanbevelingen

De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. 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 a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.

In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.

 

Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers

 

 

Sterke aanbeveling

Zwakke (conditionele) aanbeveling

Voor patiënten

De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet.

Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet. 

Voor behandelaars

De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen.

Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren.

Voor beleidsmakers

De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid.

Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen. 

 

Organisatie van zorg

In de knelpuntenanalyse en bij de ontwikkeling van de richtlijnmodule is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de module Organisatie van zorg.

 

Commentaar- en autorisatiefase

De conceptrichtlijnmodule werd aan de betrokken (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijnmodule werd aan de deelnemende (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.

Zoekverantwoording

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

Volgende:
Chronische anale fissuren