Perfect pitstops
Loeffen, Erik
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2019
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Loeffen, E. (2019). Perfect pitstops: Towards evidence-based supportive care in children with cancer.
Rijksuniversiteit Groningen.
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current variations in childhood
cancer supportive care in the
netherlands
CHAPTER 4
Published as: Loeffen EAH Mulder RL van de Wetering MD Font-Gonzalez A Abbink FC Ball LM Loeffen J Michiels EMC Segers H Kremer LCM Tissing WJE Cancer. 2016 Feb 15;122(4):642-50.4.1 ABSTRACT
BACKGROUNDCurrent treatment strategies in pediatric oncology are intensive and lead to high survival rates but also to treatment-related complications. Therefore, supportive care plays an increasingly important role. We aimed to evaluate variations in supportive care practice in children with cancer in the Netherlands, and adherence to selected existing international guidelines by conducting an in-depth review of local guidelines and protocols among all six Dutch pediatric cancer centers.
METHODS
Based on shared expert-opinion, we compiled a questionnaire regarding current supportive care practice. For each center, we extracted the required information from local supportive care guidelines and sent the list to a pediatric oncologist of that center to verify its correspondence with local daily practice. Subsequently, we evaluated if clinical practice was concordant (same in ≥5/6 centers), partly concordant (highly overlapping in ≥5/6 centers) or discordant (same in <5/6 centers). We compared local practices with strong recommendations from high-quality evidence-based guidelines.
RESULTS
The questionnaire comprised 67 questions regarding supportive care practice. We observed concordance in 11/67 practice items (16%), partial concordance in 6/67 practice items (9%) and discordance in 50/67 practice items (75%). Adherence to strong recommendations of four high-quality evidence-based guidelines varied but was generally low.
CONCLUSION
Large variations exist in pediatric oncology supportive care practice, which could negatively influence care. Adherence to existing evidence-based guidelines, and development and implementation of new clinical practice guidelines has the potential of standardizing supportive care practice, and thereby improving outcomes in children with cancer.
4.2 INTRODUCTION
With the introduction of intensive treatment strategies, survival rates of children diagnosed with cancer have increased to 75%-80%.[1] Cancer itself remains the main cause of death, followed by treatment-related death.[2] Not only may the severe adverse effects of cancer treatment lead to death, but they may also lead to morbidity, decreased quality of life and treatment delay.[3] Supportive care focuses on the prevention and management of these adverse effects. To reduce and/or prevent morbidity and mortality and to improve the quality of life of children with cancer and their families, it is of the utmost importance that children receive optimal supportive care.[4,5]
There is an increased understanding that adherence to evidence-based clinical guidelines improves patient outcomes as well as the general quality of care.[6-8] For example, a systematic review focusing on Dutch evidence-based clinical practice guidelines showed that guideline-consistent care improved the process and structure of care.[9] Within oncology, adherence to guideline recommendations for initiating antibiotic therapy in adult cancer patients with low-risk febrile neutropenia is associated with decreased mortality.[10] Bridging the gap between current evidence and current practice by clinical practice guideline implementation is a major challenge.[11,12]
Little is known about the variability in supportive care practices for childhood cancer patients. Recent studies have shown that in other fields of medical practice, such as adult oncology, neurology and pulmonology, major variations in daily practice exist which negatively influence the quality of care.[13-15]
The aim of our study was to determine the extent of agreement of current pediatric oncology supportive care practice in six Dutch hospitals. Furthermore, we aimed to compare the supportive care practices in these hospitals to strong recommendations of published, high-quality, evidence-based pediatric oncology supportive care guidelines.
4.3 METHODS
To evaluate the extent of agreement of current supportive care practices, we conducted an explorative survey among all pediatric cancer centers in the Netherlands. In each of the six centers, a pediatric oncologist with supportive care expertise provided local childhood cancer supportive care guidelines and protocols.
TOPIC SELECTION
In a previous study, we conducted a Delphi survey to prioritize childhood cancer supportive care topics for the development of clinical practice guidelines.[16] To explore variations in practice between the six centers we selected the 10 most highly prioritized topics from the final prioritization list. These were: infection, sepsis, febrile neutropenia, pain, nausea and vomiting, restrictions in daily life and activities, palliative care, procedural sedation, terminal care and oral mucositis. For these topics we created relevant subtopics (e.g. “antibiotic prophylaxis” for topic “Infection”). To do so, two researchers (first and last author) drafted a list of possible subtopics. Four topics regarding common procedures (erythrocyte transfusion, platelet transfusion, lumbar puncture, central venous access port) were added to this list.. The draft list of subtopics was sent to all authors and revised on the basis of their comments. All authors approved the final list.
For each topic we attempted to compile three key questions: “Who needs a certain
action?”, “What action should be performed?” and “When should the action be performed?”. The questions were sent to all co-authors for review and revised based on
their comments. All co-authors approved the final questions. For some topics the three key questions were not applicable. Therefore, for these topics we limited the questions to one or two questions or formulated a different question.
SURVEY
From the childhood cancer supportive care guidelines and protocols provided by the 6 pediatric oncology centers, we extracted the local recommendations on the selected topics to answer the questions developed above. The summary of local supportive care recommendations was returned to the participating oncologist at each hospital to verify that it corresponded with supportive care practice in their hospital, and to make adjustments where applicable. We repeatedly emphasized that the summary list was intended to reflect the policies and guidelines of their hospital, not their personal preference.
DEFINITIONS AND ASSESSMENT OF AGREEMENT
A topic was categorized as concordant when five or six of six centers reported the same practice. When practice was not exactly the same, but highly overlapping in five or six of six centers the topic was characterized as partly concordant. Topics were categorized as discordant when less than five centers reported the same practice. If a center did not have a policy or guideline on a topic, the definitions of concordance were not altered. Assessment of agreement between hospitals was done by one researcher (first author) and discussed individually and in detail with two other authors. Disagreements in characterization were discussed and resolved by consensus. The summary and characterizations were sent to all authors for their approval.
CONFORMITY WITH CURRENT INTERNATIONAL GUIDELINES
To identify current guidelines on the topics of interest, we asked all authors to state all contemporary high-quality evidence-based childhood cancer supportive care guidelines they were acquainted with. This yielded four guidelines, which addressed two of the prioritized topics: fever and neutropenia and chemotherapy-induced nausea and vomiting. [17-20] Within these guidelines we identified strong recommendations. As defined by the GRADE approach, strong recommendations indicate that the desirable effects of the recommended intervention clearly outweigh the undesirable effects, or clearly do not.[21] We assessed the extent of agreement between these recommendations and the identified local supportive care practices using the same methods as were used to assess agreement in inter-institutional supportive care practices.
4.4 RESULTS
Using the aforementioned procedure we developed a list of 67 questions regarding supportive care practice items. These addressed the 14 selected topics under 13 headings (Table 5.1). In total, 13 subtopics consisted of three questions, six subtopics consisted of two questions and 16 subtopics consisted of one question. Overall, we found concordance in 11 out of 67 supportive care practice items (16.4%), partial concordance in six of 67 practice items (9.0%) and discordance in 50 of 67 practice items (74.6%) (Tables 5.1-5.3).
In seven out of 11 concordant practice items (63.6%) the reported practice was concordant in all 6 participating hospitals, in four out of 11 (36.4%) this was the case for five out of six hospitals. Of all concordant areas, the majority (8/11) related to “What action should be performed?”, and focused on choice of medication (5/8), sedation (2/8) or dosage (1/8) (Table 5.2 and 5.4).Detailed information about the supportive care practices of all centers is shown in Supplementary material 4/S1.
PER TOPIC ANALYSIS
All supportive care topics had discordant areas. In infection and febrile neutropenia the extent of agreement was relatively high; 12 out of 31 practice items (38.7%) were concordant or partly concordant. Several of these (partial) concordances were medication-related, e.g. the use of ciprofloxacin as antibiotic prophylaxis. However, there were also discordant practices within these topics, e.g. the use of different empirical antibiotic treatment for febrile neutropenia. The practices within four topics were all discordant. Of these, nausea and vomiting comprised the largest number of practice items (15).”
Ta bl e 4 .1 . C onc or d an ce s a nd dis co rd an ce s a mo ng s up p or tiv e c ar e p rac tice in t he p edi at ric o nc olo g y ce nt er s i n t he N et he rla nd s. To pi c / s ub to pi c Su pp or tiv e c ar e p ra ct ic e i te m / Q ue st io n Co nc or da nt 1. Inf ec tio n A nt ib io tic pr oph yl ax is W ho “T o w ho m i s a nt ib io ti c p ro p hy la xi s p re sc ri b ed ?” D W ha t “ W ha t m ed ic at io n i s u se d a s a nt ib io ti c p ro p hy la xi s? ” C W he n “A t w hi ch m o m en t( s) i n t re at m en t s ho ul d a nt ib io ti c p ro p hy la xi s b e g iv en ?” D A sp er gi llu s p re ve nt io n W ho “ To w ho m i s A sp er g ill us p ro p hy la xi s p re sc ri b ed ?” D W ha t “W ha t m ed ic at io n i s u se d a s A sp er g ill us p ro p hy la xi s? ” C W he n “A t w hi ch m o m en t( s) i n t re at m en t s ho ul d A sp er g ill us p ro p hy la xi s b e g iv en ?” D D ia gno st ic s f or fu nga l i nf ec tio n W ho “I n w hi ch p at ie nt s w ill d ia g no st ic t es ts f o r f un g al i nf ec ti o ns b e c ar ri ed o ut ?” pC W ha t “W hi ch d ia g no st ic t es ts d o y o u p er fo rm ?” D W ha t “W ha t m ed ic at io n i s u se d a s a nt ifu ng al t he ra p y? ” C C an di di as pr oph yl ax is W ho “ To w ho m i s C an d id ia si s p ro p hy la xi s p re sc ri b ed ?” D W ha t “W ha t m ed ic at io n i s u se d a s C an d id ia si s p ro p hy la xi s? ” D PC P pr oph yl ax is W ho “ To w ho m i s P C P-p ro p hy la xi s p re sc ri b ed ?” D W ha t “W ha t m ed ic at io n i s u se d a s P C P-p ro p hy la xi s? ” C W he n “A t w hi ch m o m en t( s) i n t re at m en t s ho ul d P C P-p ro p hy la xi s b e g iv en ?” pC SD D s ur ve ill an ce c ul tu re s W ho “ In w hi ch p at ie nt s a re S D D s ur ve ill an ce c ul tu re s p er fo rm ed ?” D W ha t “F ro m w ha t s it es a re S D D s ur ve ill an ce c ul tu re s o b ta in ed ?” D W he n “H o w o ft en a re t he se S D D s ur ve ill an ce c ul tu re s o b ta in ed ?” D
Ta bl e 4 .1 . C on tin ue d To pi c / s ub to pi c Su pp or tiv e c ar e p ra ct ic e i te m / Q ue st io n Co nc or da nt ? VZ V c on ta ct W ho “W ho i s c o ns id er ed a h ig h r is k p at ie nt f o r V Z V ?” C W ha t “I n h ig h r is k p at ie nt s, w ha t i s p re sc ri b ed a ft er c o nt ac t w it h a V Z V p at ie nt ?” C W he n “W he n s ho ul d t hi s b e a d m it te d t o t he h ig h r is k p at ie nt ?” D O ra l he rpe s W ha t “W ha t i s p re sc ri b ed t o p at ie nt s w it h o ra l h er p es ?” D W he n “H o w l o ng s ho ul d t hi s b e u se d ?” D A nt ib io tic pr oph yl ax is b ef or e i m pl an ta tion o f P AC W ha t “W ha t a nt ib io ti c p ro p hy la xi s i s p re sc ri b ed b ef o re s ur g ic al i m p la nt at io n o f a P A C ?” C W he n “W he n i s t hi s a nt ib io ti c p ro p hy la xi s g iv en ?” D 2. S ep sis - 3. F eb ril e n eu tr op eni a D efi ni tio n o f f ev er -“W ha t t em p er at ur e i s c o ns id er ed f ev er i n y o ur c en te r? ” pC D efi ni tio n o f n eu tr op en ia -“W ha t n eu tr o p hi l c o un t i s c o ns id er ed n eu tr o p en ia i n y o ur c en te r? ” C D ia gn os tic s a t p re se nt at io n w ith F N W ha t “W ha t d ia g no st ic s a re p er fo rm ed a t p re se nt at io n w it h F N ?” D St an da rd a nti bi oti cs W ha t “R eg ar d in g F N , w ha t i s t he s ta nd ar d a nt ib io ti c t o s ta rt t re at m en t w it h? ” D Fe ve r > 72 h ou rs W ha t “I f f ev er p er si st s a ft er 7 2 h o ur s o f a nt ib io ti c t he ra p y, w ha t d o y o u d o? ” D C = c on co rd an t, D = d is co rd an t, p C = p ar tly c on co rd an t, P C P = P ne um oc ys tis c ar in ii p ne um on ia , S D D = s el ec tiv e d ig es tiv e d ec on ta m in at io n, V ZV = V ar ic el la Z os te r v ir us , P A C = P or t- a-ca th , F N = f eb ril e n eu tr op en ia , C T = c om p ut ed t om og ra p hy , M RI = m ag ne tic r es on an t i m ag in g, L P = l um b ar p un ct ur e, C V L = c en tr al v en ou s l in e
04
Ta bl e 4 .1 . C on tin ue d To pi c / s ub to pi c Su pp or tiv e c ar e p ra ct ic e i te m / Q ue st io n Co nc or da nt Sto p a nt ib io tic t he ra py i f b lo od c ul tu re s r et ur n n eg at iv e W ho “W he n i s a b lo o d c ul tu re r eg ar d ed n eg at iv e? ” C W he n “I f t he b lo o d c ul ur e i s r eg ar d ed n eg at iv e, w he n i s t he a nt ib io ti c t he ra p y s to p p ed ?” D 4. P ai n M ed ic ati on W ha t “W ha t m ed ic at io n s ch em e i s u se d f o r n o ci ce p ti ve p ai n? ” pC 5. N au se a / v om iti ng N on em et ogen ic W ho “W hi ch ( ch em ot he ra p eu ti c) d ru g s a re c at eg o ri ze d a s n o n e m et o g en ic ?” D W ha t “W ha t a nt ie m et ic m ed ic at io n ( sc he m e) i s p re sc ri b ed t o t he se p at ie nt s? ” D W he n “W he n s ho ul d t hi s m ed ic at io n b e a d m in is te re d ?” D Lo w em et ogen ic W ho “W hi ch ( ch em ot he ra p eu ti c) d ru g s a re c at eg o ri ze d a s l o w e m et o g en ic ?” D W ha t “W ha t a nt ie m et ic m ed ic at io n ( sc he m e) i s p re sc ri b ed t o t he se p at ie nt s? ” D W he n “W he n s ho ul d t hi s m ed ic at io n b e a d m in is te re d ?” D M oder at e em et ogen ic W ho “W hi ch ( ch em ot he ra p eu ti c) d ru g s a re c at eg o ri ze d a s m o d er at e e m et o g en ic ?” D W ha t “W ha t a nt ie m et ic m ed ic at io n ( sc he m e) i s p re sc ri b ed t o t he se p at ie nt s? ” D W he n “W he n s ho ul d t hi s m ed ic at io n b e a d m in is te re d ?” D H ig h em et ogen ic W ho “W hi ch ( ch em ot he ra p eu ti c) d ru g s a re c at eg o ri ze d a s h ig h e m et o g en ic ?” D W ha t “W ha t a nt ie m et ic m ed ic at io n ( sc he m e) i s p re sc ri b ed t o t he se p at ie nt s? ” D W he n “W he n s ho ul d t hi s m ed ic at io n b e a d m in is te re d ?” D Ver y h ig h em et ogen ic W ho “W hi ch ( ch em ot he ra p eu ti c) d ru g s a re c at eg o ri ze d a s v er y h ig h e m et o g en ic ?” D W ha t “W ha t a nt ie m et ic m ed ic at io n ( sc he m e) i s p re sc ri b ed t o t he se p at ie nt s? ” D
Ta bl e 4 .1 . C on tin ue d To pi c / s ub to pi c Su pp or tiv e c ar e p ra ct ic e i te m / Q ue st io n Co nc or da nt ? W he n “W he n s ho ul d t hi s m ed ic at io n b e a d m in is te re d ?” D 6. R es tr ic tio ns i n d ai ly l ife a nd a ct iv iti es Lo w b ac te ria l d ie t W ho “T o w ho m i s a l o w b ac te ri al d ie t p re sc ri b ed ?” D W ha t “W ha t i s n ot a llo w ed i n t hi s d ie t? ” pC 7. P al lia tive c ar e Sp ec ifi c p ro to co l -“I s t he re a s p ec ifi c p ed ia tr ic o nc o lo g ic al p ro to co l f o r p al lia ti ve c ar e? ” D 8. P ro ced ur al s ed at io n Lum ba r p un ct ur e W ha t “W ha t t yp e o f s ed at io n i s g iv en w he n a c hi ld u nd er g o es a l um b ar p un ct ur e? ” D Bo ne m ar ro w p un ct ur e W ha t “W ha t t yp e o f s ed at io n i s g iv en w he n a c hi ld u nd er g o es a b o ne m ar ro w p un ct ur e?” C Cy tol og ic al bo ne p un ct ur e W ha t “W ha t t yp e o f s ed at io n i s g iv en w he n a c hi ld u nd er g o es a c yt o lo g ic al b o ne p un ct ur e?” C Im agi ng s tu di es ; C T/ M RI W ha t “W ha t t yp e o f s ed at io n i s g iv en w he n a c hi ld u nd er g o es a C T- o r M R I-sc an ?” D C = c on co rd an t, D = d is co rd an t, p C = p ar tly c on co rd an t, P C P = P ne um oc ys tis c ar in ii p ne um on ia , S D D = s el ec tiv e d ig es tiv e d ec on ta m in at io n, V ZV = V ar ic el la Z os te r v ir us , P A C = P or t- a-ca th , F N = f eb ril e n eu tr op en ia , C T = c om p ut ed t om og ra p hy , M RI = m ag ne tic r es on an t i m ag in g, L P = l um b ar p un ct ur e, C V L = c en tr al v en ou s l in e
04
Ta bl e 4 .1 . C on tin ue d To pi c / s ub to pi c Su pp or tiv e c ar e p ra ct ic e i te m / Q ue st io n Co nc or da nt 9. T er m in al c ar e Sp ec ifi c p ro to co l -“I s t he re a s p ec ifi c p ed ia tr ic o nc o lo g ic al p ro to co l f o r p al lia ti ve c ar e? ” D 10 . M uc os iti s ( or al ) Br us hi ng te et h W ho “W hi ch p at ie nt s r ec ei ve s p ec ifi c i ns tr uc ti o ns f o r b ru sh in g t ee th ?” D W ha t “W ha t s ho ul d b e u se d f o r b ru sh in g t ee th ?” D W he n “H o w o ft en s ho ul d p at ie nt s b ru sh t he ir t ee th ?” D A d d it io na l t o pic s A1 . E ry th ro cy te t ra ns fu si on W ho “A t w hi ch h em o g lo b in v al ue ( in m m o l/ L) a nd i n w hi ch s it ua ti o n i s a n e ry th ro cy te tr an sf us ion p re sc ri b ed ?” D W ha t “W ha t i s t he d o sa g e o f a n e ry th ro cy te t ra ns fu si o n? ” C W he n “W ha t i s t he t im e s p an o f a d m in is te ri ng a n e ry th ro cy te t ra ns fu si o n? ” pC A 2. P la te le t t ra ns fu si on W ho “A t w hi ch p la te le t c o un t ( in 1 0 9/L ) a nd i n w hi ch s it ua ti o n i s a p la te le t t ra ns fu si o n p re sc ri b ed ?” D W ha t “W ha t i s t he d o sa g e o f a p la te le t t ra ns fu si o n? ” D A 3. L um ba r p un ct ur e P la te le t t ra ns fu si on b ef or e L P
Ta bl e 4 .1 . C on tin ue d To pi c / s ub to pi c Su pp or tiv e c ar e p ra ct ic e i te m / Q ue st io n Co nc or da nt ? W ho “B ef o re p er fo rm in g a n L P, a t w hi ch p la te le t c o un t ( in 1 0 9/L ) i s a p ro p hy la ct ic p la te le t tr an sf us ion p re sc ri b ed ?” D L ie d ow n a ft er L P W he n “F o r h o w l o ng d o p at ie nt s h av e t o l ie d o w n a ft er a n L P w it h i nt ra th ec al t he ra p y? ” D A 4. P or t-a -Ca th F lu sh in g t he P AC W he n “W he n n ot i n u se , h o w o ft en s ho ul d a P A C b e fl us he d ( o nl y P A C , n ot f o r C V L) ?” D S te ril ity w he n a cc es sin g t he P AC W ha t “W ha t s te ri lit y m ea su re s a re r eq ui re d w he n a cc es si ng t he P A C ?” D C = c on co rd an t, D = d is co rd an t, p C = p ar tly c on co rd an t, P C P = P ne um oc ys tis c ar in ii p ne um on ia , S D D = s el ec tiv e d ig es tiv e d ec on ta m in at io n, V ZV = V ar ic el la Z os te r v ir us , P A C = P or t- a-ca th , F N = f eb ril e n eu tr op en ia , C T = c om p ut ed t om og ra p hy , M RI = m ag ne tic r es on an t i m ag in g, L P = l um b ar p un ct ur e, C V L = c en tr al v en ou s l in e
04
Ta bl e 4 .2 . C on co rd an t s up p or tiv e c are p ra cti ce it em s To pi c Q ue sti on Pr ac tic e A nt ib io tic p ro p hy la xi s W ha t m ed ic at io n i s u se d a s a nt ib io tic p ro p hy la xi s? C ip ro flo xac in A sp erg ill us p re ve nti on W ha t m ed ic at io n i s u se d a s A sp er g ill us p ro p hy la xi s? It rac on az ole Fu nga l i nf ec tio n W ha t m ed ic at io n i s u se d a s a nt ifu ng al t he ra p y? A mp ho ter ic in B * PC P-p ro p hy la xis W ha t m ed ic at io n i s u se d a s P C P-p ro p hy la xi s? C o -t ri mo xa zole VZV -c on ta ct W ho i s c on si d er ed a h ig h r is k p at ie nt f or V ZV ? Im m un oc omp ro m is ed p ati en t wit h a n ega tiv e an tib o d y tit re * VZV -c on ta ct In h ig h r is k p at ie nt s, w ha t i s p re sc rib ed a ft er c on ta ct w ith a V ZV p at ie nt ? Va ric el la z os te r i m m un e g lo b ul in D efi ni tio n o f n eu tr op en ia W ha t i s t he d efi ni tio n o f n eu tr op en ia ? N eu tr op hi l g ra nu lo cy te s < 0, 5× 10 9/l D is co nti nu e an tib io tic s W he n i s a b lo o d c ul tu re r eg ar d ed n eg at iv e? N o g ro w th a ft er 7 2 h ou rs B on e m ar ro w p un ct ur e W ha t t yp e o f s ed at io n i s g iv en w he n a c hi ld u nd er g oe s a b on e m ar ro w p un ct ur e? G ene ra l a ne st he si a C yt olo g ic al b one p unc tu re W ha t t yp e o f s ed at io n i s g iv en w he n a c hi ld u nd er g oe s a cy tolo g ic al b one p unc tu re ? G ene ra l a ne st he si a Er yt hr oc yt e t ra ns fu sio n W ha t i s t he d os ag e o f a n e ry th ro cy te t ra ns fu si on ? 10 -1 5 m L/ kg * = fi ve o ut o f s ix h os p it al s r ep or te d t he s am e p ra ct ic e V ZV = V ar ic el la z os te r v ir us , P C P = P ne um oc ys tis c ar in ii p ne um on ia
Table 4.3. Partly concordant supportive care practice items Topic
Question Explanation of partly concordant practice items Fungal infection
In which patients will diagnostic tests for fungal infections be carried out?
In five out of six hospitals, diagnostic tests are carried out after persisting fever despite antibiotic treatment, however the timeframe and secondary conditions vary. PCP-prophylaxis
How often should the PCP-prophylaxis be administered?
In five out of six hospitals, PCP-prophylaxis is
administered three days a week, once daily. However in one center this is prescribed for alternating days, as in all others these are consecutive days.
Definition of fever
What is the definition of fever?
All hospitals use 38.5°C as cut-off limit for fever, but types and moments of measurement vary slightly. Pain medication
What medication scheme is used for nociceptive pain?
In five out of six hospitals, the medication scheme is 1) acetaminophen, 2) tramadol and 3) morphine, however recommendations regarding NSAIDs vary slightly. Dietary restrictions
“What do the dietary restrictions comprise?”
Dietary restrictions vary somewhat, but all aim at a low bacterial diet.
Erythrocyte transfusion
What is the time span of administering an erythrocyte transfusion?
In five out of six hospitals there is a minimum time span of 3 hours, with maximum time span ranging from 4 to 6 hours.
PCP = Pneumocystis carinii pneumonia, NSAID = nonsteroidal anti-inflammatory drugs
Ta bl e 4 .4 . M ed ic ati on -re la te d s up p or tiv e c are p ra cti ce it em s* . Subt op ic Q ue sti on Hos pita l 1 Hos pita l 2 Hos pita l 3 Hos pita l 4 Hos pita l 5 Hos pita l 6 Conc orda nce 1 A nt ib io tic p ro p hy la xi s St an d ar d a nt ib io ti c p ro p hy la xi s Ci Ci Ci Ci Ci Ci C 2 A sp er g ill us p ro p hy la xi s St an d ar d A sp er g ill us p ro p hy la xi s It It It It It It C 3 Fu nga l i nf ec tio n St an d ar d a nt ifu ng al t he ra p y Vo Am Am Am Am Am C 4 C an d id ia sis p ro p hy la xis St an d ar d Can d id ia sis p ro p hy la xis ns N a Fl It Fl Fl D 5 PC P-p ro p hy la xis St an d ar d P C P-p ro p hy la xis Co Co Co Co Co Co C 6 VZV -c on ta ct St an d ar d m ed ic at io n i n H R p at ie nt s a ft er V Z V c o nt ac t Va Va Va Va Va Vv C 7 O ra l h er p es St an d ar d m ed ic at io n o ra l h er p es Va Ac * ns Va ns Va * D 8 Impl an ta tio n o f P A C A nt ib io ti c p ro p hy la xi s b ef o re i m p la nt at io n o f P A C Ce No Ce No No No D 9 St an d ar d an tib io tic s St an d ar d a nt ib io ti c t re at m en t i n F N Cv * C g* Cf * Cf * Cf * M e* D 10 No n e m et og en ic Fi rs t s te p a nt ie m et ic m ed ic at io n No ns No No No On D 11 Lo w e m et oge ni c Fi rs t s te p a nt ie m et ic m ed ic at io n On No On ns On Od D 12 M o de ra te e m et og en ic Fi rs t s te p a nt ie m et ic m ed ic at io n ns On ns On ns Od D 13 H ig h e m eto g en ic Fi rs t s te p a nt ie m et ic m ed ic at io n On Od Od On On Oa D 14 Ve ry h ig h e m et og en ic Fi rs t s te p a nt ie m et ic m ed ic at io n Od ns Op ns Od ns D 15 Lu mb ar p un ct ure Ty p e o f s ed at io n f o r a l um b ar p un ct ur e Mi Ga Mi Mi K e Mi D 16 B on e m ar ro w p un ct ur e Ty p e o f s ed at io n f o r a b o ne m ar ro w p un ct ur e Ga Ga Ga Ga Ga Ga C 17 C yt olo g ic al b one p unc tu re Ty p e o f s ed at io n f o r a c yt o lo g ic al b o ne p un ct ur e Ga Ga Ga Ga Ga Ga C 18 C T- o r M RI s ca n Ty p e o f s ed at io n f o r a C T- o r M R I-sc an Al C h* C h* No C h* Se D
C = c on co rd an t, p C = p ar tly c on co rd an t, D = d is co rd an t, n s = n ot s p ec ifi ed , * a d d iti on al c on d iti on b ou nd i nf or m at io n, s ee S up p le m en ta l m at er ia l 4 /S 1 PC P = p ne um oc ys tis c ar in ii p ne um on ia , H R = h ig h r is k, V ZV = V ar ic el la Z os te r v ir us , P A C = P or t- a-ca th , F N = f eb ril e n eu tr op en ia , C T = c om p ut ed to m og ra p hy , M RI = m ag ne tic r es on an ce i m ag in g 1. C i = c ip ro flo xa ci n 2. I t = i tr ac on az ol e 3. V o = v or ic on az ol e, A m = a m p ho te ric in B 4. N a = N ys ta tin / a m p ho te ric in B , F l = fl uc on az ol e, I t = i tr ac on az ol e 5. C o = C o -t ri m ox az ol e 6. V z = V ar ic el la z os te r i m m un e g lo b ul in , V v = V ar ic el la z os te r i m m un e g lo b ul in a nd v al ac yc lo vi r p er o s 7. V a = v al ac yc lo vi r, A c = a cy cl ov ir 8. C e = c ef az ol in , N o = n on e 9. C v = c ef ta zi d im e & v an co my ci n, C g = c ef ur ox im e & g en ta m ic in , C f = c ef ta zi d im e, M e = m er op en em 10 -1 4. N o = n on e, O n = o nd an se tr on , D e = d ex am et ha so ne , O d = o nd an se tr on + d ex am et ha so ne , O a = o nd an se tr on + a p re p it an t, O p = o nd an se tr on + d ex am et ha so ne + a p re p it an t 15 -1 8. M i = m id az ol am , G a = g en er al a ne st he si a, K e = k et am in e, A l = a lim em az in e, C h = c hl or al hy d ra te , N o = n on e, S e = s ed at io n o nl y u nd er 5 y ea rs of a g e ( ty p e n ot s p ec ifi ed )
04
Ta bl e 4 .5 . A ll q ue st io ns r eg ar d in g e as ily i d en tifi ab le i te m s ( e. g . n um b er s / d eg re es ) Subt op ic Q ue sti on Hos pita l 1 Hos pita l 2 Hos pita l 3 Hos pita l 4 Hos pita l 5 Hos pita l 6 Conc orda nce 1 M uc os iti s ( or al ) In st ru ct ed t im es d ai ly b ru sh in g t ee th 2 ad 2-4 ns 2-4 > 2 D 2 Er yt hr oc yt e t ra ns fu sio n H b l im it f o r a p ro p hy la ct ic E T ( in m m o l/ L) * 4. 3 5 4 4 5 4-5 D 3 Er yt hr oc yt e t ra ns fu sio n D o sa g e o f a n E T ( in m L/ kg ) 10 -1 5 10 -1 5 10 -1 5 10 -1 5 10 -1 5 10 -1 5 C 4 Er yt hr oc yt e t ra ns fu sio n Ti m e s p an o f a d m in is tr at io n o f a n E T ( in h o ur s) 3-4 3 ns 3 3-4 3-6 p C 5 Pl at el et t ra ns fu si on b ef or e L P Pl at el et l im it f o r a p ro p hy la ct ic P T b ef o re a n L P <5 0 fs <5 0 <2 0 <5 0 fs D 6 Li e d ow n a ft er L P H o ur s l yi ng d o w n a ft er a n L P w it h I T t he ra p y tr 2 4 1 2 4 D 7 Fl us hi ng t he P A C Fl us hi ng t he P A C e ve ry X w ee ks w he n n ot i n u se 13 6 ne 13 ne 6-8 D 8 St er ili ty w he n a cc es si ng P A C R eq ui re d s te ri lit y m ea su re s w he n a cc es si ng P A C ns ns sg sf sg sf D C = c on co rd an ce , p C = p ar tly c on co rd an t, D = d is co rd an t, n s = n ot s p ec ifi ed * i n c hi ld re n w ith n o c om p la in ts d ue t o a l ow H b a nd n o c o -m or b id it y t ha t i s a k no w n i nd ic at io n t o c ha ng e t he l ow er H b l im it f or a n E T H b = h em og lo b in , E T = e ry th ro cy te t ra ns fu si on , L P = l um b ar p un ct ur e ( re g ul ar , n on -fi rs t), P T = p la te le t t ra ns fu si on , I T = i nt ra th ec al , P A C = P or t- a-ca 1. a d = a g e d ep en d en t, n s = n ot s p ec ifi ed 5. f s = d iff er en t v al ue s f or fi rs t a nd s ub se q ue nt L Ps , r es p ec tiv el y < 10 0 a nd < 20 f or h os p it al 2 a nd < 50 a nd < 20 f or h os p it al 6 6. t r = 6 h ou rs i n r ev er se T re nd el en b ur g p os iti on , s ub se q ue nt ly 6 h ou rs fl at 7. n e = n ev er 8. s g = s te ril e g lo ve s, s f = s te ril e fi el d + s te ril e g lo ve s
CONFORMITY WITH CURRENT INTERNATIONAL GUIDELINES
We compared our findings on the management of febrile neutropenia in children with cancer with the strong recommendations from the recent guideline by Lehrnbecher et al.[17] In this guideline, it is recommended that empirical treatment of high-risk febrile neutropenia should consist of monotherapy with antipseudomonal β-lactam or carbopenem.[17] In our study, two out of six hospitals recommended initial dual therapy. Four out of six hospitals reported monotherapy with the recommended antibiotics. However, these hospitals suggested the addition of a second antibiotic agent in conditions that were neither described nor recommended in the guideline by Lehrnbecher et al. On the other hand, one concordant practice identified in our study, the prescription of Amphotericin B as antifungal therapy, was in line with the Lehrnbecher et al. guideline’s strong recommendation regarding antifungal therapy.
In relation to nausea and vomiting, we found that all hospitals have their own classification system regarding the potential emetogenicity of chemotherapy. All classifications differed from the recent classification guideline by Dupuis et al.[20] For instance, in our study in the category non-emetogenic there was one chemotherapeutic agent (procarbazine) that was classified in the guideline as highly emetogenic and four
chemotherapeutic agents (cyclophosphamide <500mg/m2, etoposide, methotrexate
<1g/m2, vinorelbine) that were classified in the guideline as moderately emetogenic.
Regarding prophylaxis of acute nausea and vomiting due to antineoplastic medication, we identified varying agreement with the guideline by Dupuis et al. Practice was alike in four out of six centers for minimally emetogenic chemotherapy, in three out of six centers for chemotherapy of low emetogenicity, in one out of six centers for moderately emetogenic chemotherapy and in zero out of six centers for highly emetogenic chemotherapy (see Supplemental material 4/S1 for details).[19]
4.5 DISCUSSION
Our study showed that major variations exist in daily practice in supportive care in childhood cancer across pediatric centers in the Netherlands. In this nationwide study, 75% of supportive care practice items showed discordant practice among the participating centers. Variations in care can lead to suboptimal treatment or conflicting recommendations, which might result in increased mortality and morbidity in children with cancer.[7] Familiarity with and adherence to existing high-quality evidence-based guidelines, and the development and implementation of new clinical practice guidelines can contribute to an increased use of evidence-based medicine and a decrease in
practice variation, which might ultimately contribute to improved outcomes in children with cancer.
This study was conducted in the Netherlands where approximately 550 children a year are newly diagnosed with cancer and with approximately 40 pediatric oncologists.[22] As variations in care already exist on such a geographically small scale, we also expect them to exist on the same or even on a greater scale in larger countries. Factors that have been shown to play a role in variations in provided care include: availability of medication and supplies, number of patients, patients’ and physicians’ preferences and availability of evidence.[10,23] In the Netherlands, availability of medication and supplies does not differ substantially between pediatric oncology hospitals, and number of patients are relatively equally distributed among the hospitals. Patients’ and physicians’ preferences will naturally continue to play a role in decision making. The last factor in explaining variation, availability of evidence, can be improved substantially with the use of clinical practice guidelines. Therefore we expect them to play an important role in decreasing practice variations in the Netherlands.[7,8]
For some topics in childhood cancer there are existing guidelines that are evidence-based and developed with a thorough and well-defined methodology. These guidelines comprise two of our Delphi top-10 topics, i.e. febrile neutropenia and nausea and vomiting.[17-20] Surprisingly, even though good evidence-based guidelines exist, all 15 nausea and vomiting items showed discordant practice among the participating centers. However, it should be noted that this study was carried out in the summer of 2014, before the publication in 2015 of two important studies that promote the use of aprepitant in children receiving highly emetogenic chemotherapy.[24,25] If the present study were performed now that these studies have been published, practice in the various centers might have shown a higher extent of agreement with the guideline recommendation to prescribe aprepitant to children receiving highly emetogenic chemotherapy.[19] Thus, our results showed that supportive care practices among the different centers are most often discordant across centers, but also, in the case of febrile neutropenia and nausea and vomiting, not in line with the strong recommendations of current high-quality evidence-based guidelines. This might be due to non-familiarity with these guidelines, which hinders their uptake in daily practice. Among other things our findings underline the importance of a well-developed implementation strategy.
Regarding the areas with a high extent of agreement, most practice items that were answered in a concordant manner by the various centers focused on “What action should be performed?”. Three out of 11 concordant practice items focused on prophylactic medication for infections, which were all in line with the nationwide Dutch Childhood
Oncology Group (DCOG) pediatric primary cancer treatment protocols. These protocols cover primary cancer treatment only, including prophylactic medication for infections and do not include dedicated supportive care sections / protocols. Therefore, we suspect that some of the concordances can be explained by the use of these nationally endorsed protocols. This further strengthens our idea that guidelines decrease practice variability.
Our explorative survey-study sheds new light on current variations in daily supportive care practice for childhood cancer patients. Naturally, this study has its limitations. First, we let one pediatric oncologist per center verify our list with the extracted local practices. By asking one individual to provide information, we did not measure intra-institutional variability. Nevertheless we tried to compensate for this by clearly asking the participating oncologists to report institutional practice, not personal preference. In addition, we suspect that measuring intra-institutional variability would even have increased the documented rate of discordance. Second, we did not validate if the reported daily practice was indeed the actual daily practice, for instance by reviewing patient records. Thus, differences herein might exist. However, we asked explicitly that respondents report institutional actual daily practice and not personal preference or guideline statements that are not implemented in daily practice. Third, there will not be an evidence base to support the answer to every survey question. These practice items will therefore be primarily based on (shared) expert opinion and local consensus. Last, in the Netherlands there are no nationally endorsed supportive care guidelines for childhood cancer. In countries where these exist, practice variability might be substantially lower, although published data to support this is lacking.
To our knowledge this is the first study to assess variations in supportive care practice in childhood cancer patients in general. Previously, there has been some attention to practice variations in this field but limited to certain subtopics. For instance, one study found a wide variation in recommendations for non-pharmacological anti-infective measures in childhood cancer.[26] Our study underlines that these practice variations are not limited to specific topics, but likely exist in the entire childhood cancer supportive care practice.
In an effort to bridge the gap between current evidence and current practice in supportive care, we initiated a project entitled “Towards evidence-based guidelines for supportive care in childhood oncology”. We aim to develop and implement clinical practice guidelines regarding supportive care for childhood cancer patients by using existing international guidelines and new summaries of evidence. Naturally, we feel that international collaboration in the development and implementation of these guidelines would allow us to take full advantage of international expertise and effort. To this end we invite all experts who are willing to participate in this project.
4.6 CONCLUSION
We found that practice in three out of every four supportive care practice items in our questionnaire was discordant in our nationwide study. In addition, practice was generally not in line with strong recommendations from current international high-quality evidence-based supportive care guidelines. Familiarity with and adherence to existing high-quality evidence-based guidelines, and the development and implementation of new clinical practice guidelines in daily practice have the potential to greatly facilitate evidence-based practice, and therefore to contribute to better outcomes in children with cancer. ACKNOWLEDGEMENTS
The project “Towards evidence-based guidelines for supportive care in childhood oncology” is supported by the Alpe d’HuZes foundation / Dutch Cancer Society (RUG 2013-6345).
We would like to thank all participating oncologists. SUPPLEMENTAL MATERIALS
The following supplemental materials are available online:
4.7 REFERENCES
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[2] Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol 2012;30:1663–9. [3] Creutzig U, Zimmermann M, Reinhardt D, Dworzak M, Stary J, Lehrnbecher T. Early
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[4] Sung L, Aplenc R, Alonzo T. Effectiveness of supportive care measures to reduce infections in pediatric AML: a report from the Children’s Oncology Group. Blood 2013;121:3573–7. [5] Jastaniah W, Burhan Abrar M, Khattab TM. Improved Outcome in Pediatric AML
Due To Augmented Supportive Care. Pediatr Blood Cancer 2012;59:919–21. [6] Ansari S, Rashidian A. Guidelines for guidelines: are they up to the task? A
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[8] Grimshaw JM, Thomas RE, MacLennan G, Fraser C, Ramsay CR, Vale L, et al. Effectiveness and efficiency of guideline dissemination and implementation strategies. Health Technol Assess 2004;8:iii – iv, 1–72.
[9] Lugtenberg M, Burgers JS, Westert GP. Effects of evidence-based clinical practice guidelines on quality of care: a systematic review. Qual Saf Health Care 2009;18:385–92. [10] Wright JD, Neugut AI, Ananth C V, Lewin SN, Wilde ET, Lu Y-S, et al. Deviations from
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[11] Califf RM, Peterson ED, Gibbons RJ, Garson A, Brindis RG, Beller G a, et al. Integrating quality into the cycle of therapeutic development. J Am Coll Cardiol 2002;40:1895–901. [12] Grimshaw JM, Eccles MP, Walker AE, Thomas RE. Changing physicians’ behavior:
what works and thoughts on getting more things to work. J Contin Educ Health Prof 2002;22:237–43.
[13] Griggs RC, Herr BE, Reha A, Elfring G, Atkinson L, Cwik V, et al. Corticosteroids in Duchenne muscular dystrophy: major variations in practice. Muscle Nerve 2013;48:27–31.
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[15] Raijmakers NJH, van Zuylen L, Furst CJ, Beccaro M, Maiorana L, Pilastri P, et al. Variation in medication use in cancer patients at the end of life: a cross-sectional analysis. Support Care Cancer 2013;21:1003–11.
[16] Loeffen EAH, Mulder RL, Kremer LCM, Michiels EMC, Abbink FCH, Ball LM, et al. Development of clinical practice guidelines for supportive care in childhood cancer-prioritization of topics using a Delphi approach. Support Care Cancer 2015;23:1987-95. [17] Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, et al. Guideline
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