건강과 대안 » 외과수술 http://www.chsc.or.kr 연구공동체 Mon, 13 Apr 2026 01:34:28 +0000 ko-KR hourly 1 http://wordpress.org/?v=3.5.2 [광우병] 산발성 CJD의 병원내 감염 : 수술 개입의 위험 근거 분석 결과 http://www.chsc.or.kr/?post_type=reference&p=2139 http://www.chsc.or.kr/?post_type=reference&p=2139#comments Sat, 10 Jul 2010 11:42:55 +0000 건강과대안 http://www.chsc.or.kr/?post_type=reference&p=2139

산발성 CJD의 병원내 감염 : 수술 개입의 위험 근거 분석 결과

스페인의 카를로스 3세 보건연구소의 국립역학센터 소속 연구원들이 일반적인 외과수술을
통한 sCJD 감염 가능성에 대한 연구결과를 [J Neurol Neurosurg Psychiatry] 에 발표했다는
소식입니다.

논문의 전문은 아래와 같습니다.

===================================

J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2009.188425



  • Research paper


Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions

This article has been Unlocked


  1. Jesús de Pedro-Cuesta1,2,
  2. Ignacio Mahillo-Fernández1,2,
  3. Alberto Rábano3,
  4. Miguel Calero2,4,
  5. Mabel Cruz5,
  6. Åke Siden5,
  7. Henning Laursen6,
  8. Gerhard Falkenhorst7,
  9. Kåre Mølbak7,
  10. EUROSURGYCJD Research Group

+ Author Affiliations




  1. 1Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain


  2. 2Consortium for Biomedical Research in Neurodegenerative Diseases (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas—CIBERNED),Madrid, Spain


  3. 3Pathology Unit, Fundación Alcorcón University Teaching Hospital, Alcorcon, Spain


  4. 4Department of Spongiform Encephalopathies, National Microbiology Center, Carlos III Institute of Health, Ctra. Majadahonda-Pozuelo, Majadahonda, Spain


  5. 5Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Stockholm, Sweden


  6. 6Neuropathology Laboratory, Copenhagen, Denmark


  7. 7Department of Epidemiology, Statens Serum Institut, Copenhagen, Denmark


  1. Correspondence to Dr Jesús de Pedro Cuesta, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Calle Monforte de Lemos 5, Madrid 28029, Spain; jpedro@isciii.es



  1. Contributors JdP-C has full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Preliminary results were presented at the EUROCJD/NEUROCJD Public Health EU Meeting, held in Paris on 5 December 2006.



  • Received 9 July 2009
  • Revised 3 March 2010
  • Accepted 12 April 2010
  • Published Online First 14 June 2010



 
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Abstract


Objectives Evidence of surgical transmission of sporadic Creutzfeldt–Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case–control study, the authors applied a risk-based classification of surgical interventions to determine the association between a history of surgery and sCJD.


Design Case–control study, allowing for detailed analysis according to time since exposure.


Setting National populations of Denmark and Sweden.


Participants From national registries of Denmark and Sweden, the authors included 167 definite and probable sCJD cases with onset during the period 1987–2003, 835 age-, sex- and residence-matched controls and 2224 unmatched. Surgical procedures were categorised by anatomical structure and presumed risk of transmission level. The authors used logistic regression to determine the odds ratio (OR) for sCJD by surgical interventions in specified time-windows before disease-onset.


Results From comparisons with matched controls, procedures involving retina and optic nerve were associated with an increased risk at a latency of ≥1 year OR (95% CI) 5.53 (1.08 to 28.0). At latencies of 10 to 19 years, interventions on peripheral nerves 4.41 (1.17 to 16.6) and skeletal muscle 1.58 (1.01 to 2.48) were directly associated. Interventions on blood vessels 4.54 (1.01 to 20.0), peritoneum 2.38 (1.14 to 4.96) and skeletal muscle 2.04 (1.06 to 3.92), interventions conducted by vaginal approach 2.26 (1.14 to 4.47) and a pooled category of lower-risk procedures 2.81 (1.62 to 4.88) had an increased risk after ≥20 years. Similar results were found when comparing with unmatched controls.


Interpretation This observation is in concordance with animal models of prion neuroinvasion and is likely to represent a causal relation of surgery with a non-negligible proportion of sCJD cases.




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Introduction


Creutzfeldt–Jakob disease (CJD) is a rare, fatal neurodegenerative disease characterised by deposition of a pathological isoform of the normal cellular prion protein (PrPC). CJD exists in various forms, namely, genetic, caused by mutations in the gene encoding PrPC, acquired (variant and iatrogenic) and sporadic. Most cases are classified as sporadic (sCJD). Twelve case–control studies1–12 and one meta-analysis13 have examined surgical transmission of sCJD. The outcomes have been partly diverging due to methodological constraints, including problems in selection of control subjects and in particular exposure assessment.9 14 Most studies have relied on surrogate informants and medical records for surgical histories, inevitably prone to recall- and selection-bias. A recent register-based case–control study,9 which by design had a less biased assessment of surgical exposures,15 corroborated that a proportion of sCJD may be transmitted by surgery following long incubation periods (20 years or more). However, a limitation shared by all the above-mentioned studies could be misclassification bias induced by the use of standard categories of surgical procedures (SP).


Case–control studies focussing on surgical transmission of sCJD have been conducted using convenient anatomical references for classification of surgical interventions1–8 10–12 or national body-system classifications of SP.9 However, such a standard classification of surgical exposures may lead to misclassification. For example, in many ophthalmic and neurosurgical procedures, surgical instruments are not likely to encounter potentially high-risk infective tissue.16 In a Swedish dataset, only 27% of ophthalmological SP were included in a risk category in which contact with retina and optic nerve was explicit or likely.17 As neither infectivity, nor cellular prion-protein expression patterns, nor the routes of experimentally transmitted infections fit broad anatomic SP classifications or groups used in prior research, we created a risk-based classification system for surgical exposures.17 Sensitivity analysis corroborated that case–control studies in this field may have been subject to misclassification bias due to the use of SP classifications that were insufficiently specific or sensitive to distinguish between low-risk and high-risk interventions for sCJD transmission.17


The aim of the present study was to apply the risk-based classification system17 to determine the association between surgery and sCJD and thereby quantify effects potentially masked in prior case–control studies.1–12



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Methods


Study design and selection of cases and controls


The study was designed9 as a case–control study including 167 probable or definite sCJD cases fulfilling established EUROCJD diagnostic criteria,18 with clinical onset during the period 1987–2003, and resident in Denmark or Sweden. Two sets of randomly selected population controls were included, that is, 835 matched (MC, 5:1 by gender, year, month of birth, and municipality of residence at death of the corresponding case) and 2224 unmatched controls (UMC, sampled from the annual, resident, national study populations aged 40 years and over). For latency analysis purposes, three time windows (TWs) were adopted as described.9 These were based on two operational dates, of death and of clinical onset for cases, and corresponding index dates, denoted index dates 1 and 2 (ID-1 and ID-2), for controls (figure 1).9 Relevant parameters for our design of TWs 1,2 and 3 were onset of surgical procedure registration at hospital discharges in the early 1970s, reported length of latency time in iatrogenic CJD due to dura mater grafts, uncertainties in symptoms onset in sCJD and the study size.



Figure 1
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Figure 1

Schematic illustration of the study design and methodological procedure for life-time-interval definition of the registered surgical history of cases and controls. Time windows included in the present study were those covering surgical history >1 year prior to clinical onset of cases or index-date-2 of controls, namely, windows 1, 2 and 3. Modified from Mahillo-Fernandez et al,9 where details of individuals’ life-time references are given.



Exposure ascertainment


The surgical history was obtained from national registers, and assigned, blind to subjects’ case or control status, to one of the three TWs, and, where required to all three pooled TWs covering registered hospital stay up to 1 year before clinical onset or ID-2.


For cases and controls, data on past hospital discharges (diagnoses, SP codes, and dates of admission and discharge) were obtained from the National Hospital Discharge Registers in Sweden and Denmark. Personal identifiers and case-status indication were removed before analysing the data with respect to exposure to SP. Reported SP codes were identified and categorised according to Swedish, Danish and Nordic (NOMESCO-NCSP) SP classifications.19–21 Codes describing procedures that were not properly surgical, for example, delivery, and non-specific codes, for example ‘investigative procedures connected with surgery’, were omitted. The 5990 remaining SP were categorised into two major groups, namely: ‘main surgical procedures’, and ‘subsidiary procedures’, a heterogeneous category that included minor surgery (punctures, needle aspiration or biopsy, superficial incision), other non-surgical, potentially invasive procedures, such as transluminal endoscopies (with or without biopsy) and, in a few instances in Denmark, blood transfusion. The selected surgical experience of cases and controls corresponded to 1445 distinct SP codes and 5990 SP associated with 3876 registered discharges during TWs 1–3, that is, dating one or more years before the operational disease onset or ID-2 used in the reported study.9


SP reclassification by risk level


A total of 1445 unrepeated SP codes were decoded, and their 5990 discharge dates were reclassified blindly to individual outcomes according to the reported method.17 The following two attributes were assigned to each SP: (a) probable use of non-disposable instruments involved; and (b) list of up to four (of the 24 reported) tissue types or anatomical structures with the highest assigned risk level most likely contacted by such instruments.22 In total, 4813 repeated or not SP codes with different discharge dates were reclassified into six putative categories of CJD-acquisition risk level16: high risk; diluted high risk; lower risk; diluted lower risk; lowest risk; no risk (when deemed to have been conducted with disposable instruments). Furthermore, 1177 SP were not reclassified, including 865 transluminal endoscopies and 198 minor surgical procedures and blood transfusions. Endoscopies were not reclassified because early registration periods did not discriminate between procedures that were and those that were not associated with invasive procedures such as biopsies.


SP reclassification by tissue/structure


Surgical exposure was defined as tissue/structure-specific by possible contact of non-disposable instruments with up to four assigned tissues/structures.17 The above-mentioned 4813 SP generated up to four of 24 binary categorical variables for 24 different types of tissue or anatomical structure.22


Individual exposure assignment by potential entry site


An individual was assigned to one out of three mutually exclusive exposure categories per window (see figure 2A for examples), namely: exposed to tissue/structure under study; exposed to other tissues/structures; and unexposed.



Figure 2
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Figure 2

(A) Example of individual categories of exposure by tissue/structure under study when focusing on retina and optic nerve, at a specific window, for three different individuals. (B) Surgical procedure risk categories after reclassification, and corresponding individual categories of exposure to surgery.





  • An individual was assigned as exposed to a specific tissue/structure under study when at least one discharge associated with a SP involving such tissue/structure was found at a date within the limits of a TW.



  • An individual was deemed as exposed to a tissue/structure other than that under study, during any given TW, when at least one discharge was associated with a tissue/structure other than that under study. Persons solely exposed to no risk and not-reclassified SP were included here.



  • Finally, unexposed individuals were defined as those who had never been discharged or undergone a discharge associated with any ‘reclassified’ or ‘not-reclassified’ SP during the TW under study.


Individual exposure assignment by putative risk level


Individual levels of exposure were collapsed to five categories, figure 2B. These were: (1) high risk; (2) lower risk; (3) lowest risk; (4) no risk or not-reclassified procedures; and (5) unexposed. The hypothetical risk level of surgical exposure assigned to a given individual during a specific TW was the highest SP risk level found to be associated with the hospital discharges registered during that TW. As done in the preceding report, an individual was classified as exposed to a specific risk category of surgery in a specific TW when at least one discharge associated with at least one code of such surgery had taken place at a date within the limits of the individually designated TW. Multiple exposures to a specific category were determined by the number of surgical discharges with one or more SP codes reclassified in that same category.


Data analysis


We determined the risk of sCJD by presumed risk level and by contacted tissue/structure. Statistical methods with regard to design of variables, choice of reference groups, latency intervals, multivariate models and procedures for calculation of 95% CIs (CI) replicate those used in the preceding analysis.9 Conditional logistic regression was used for comparisons with MCs, and logistic regression with adjustment for age, sex and country of residence at ID-1, for comparisons with UMCs. Exposures during single TWs, 1, 2 and 3, and one combined TW, 1–3, that is, predating onset/ID-2 by ≥1 year, were included in main and complementary analyses. When an association was based on a meaningful number of exposed cases, we explored the presence of a dose–response effect quantifying the linear increase in OR for the number of surgical discharges. We assessed potential confounding by associated tissue/structure types in tissue/structure-specific models, by including, as independent variables, the tissue/structure present in at least 25% of the discharges associated with the repeated or unrepeated tissue/structure-specific SP under study. Since only comparisons related to single one-at-a-time hypotheses were planned, we followed Rothman, Greenland and Last, recommendations to refrain from use of conventional procedures for widening the confidence intervals.23


The study was formally notified to the Danish Data Protection Agency (record No 2003-41-3104) and approved by the Karolinska Institute Ethics Committee (South; report No 452/02).



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Results


Figure 3 shows, separately for cases and controls, the results of the reclassification of the 5990 selected SP. Surgery on brain, retina, spinal cord and pituitary gland or dura mater accounted for approximately 2% of reclassified procedures.



Figure 3
View larger version:


Figure 3

Percentage distributions of 5990 selected surgical procedure codes associated with surgical discharges during TWs 1–3, either classified by body-system or reclassified by hypothetical transmission risk level (n=5990) or contacted tissue/structure (n=4813). Three surgical procedure categories yielding Zero values (trigeminal ganglia, olfactory mucosa and cerebrospinal fluid), are not represented. Added percentages by tissue or anatomic structure exceed 100%.



In the analyses of risk factors for sCJD, high-risk surgery among cases was almost absent in all TWs, which made statistical inference less meaningful for these SPs (table 1). However, lower-risk surgery carried out more than 20 years before disease-onset or ID-2 was associated with an increased risk of sCJD (OR for MCs (ORMC) 2.81 and an OR for UMCs (ORUMC) of 2.54). Furthermore, for lower-risk procedures there was a dose–response relation with a linear increase by discharge (ORMC 1.34 and ORUMC 1.33). In addition, point estimates of the OR increased by latency period for lower-risk surgery, and those for latencies 10 years or longer decreased moving from high risk through lower risk to lowest risk.




View this table:

Table 1

Associations for surgery by risk level for specific periods predating onset or ID-2



For surgery classified by the tissue/structure involved, results from comparisons with matched and unmatched control groups were fairly similar. Findings for surgery conducted at any time throughout the entire study period, TWs 1–3, were negative (table 2), except when instruments contacted retina and optic nerve being in such case associated with an increased risk of sCJD ORMC (95% CI) 5.53 (1.08 to 28.0) (based on three exposed cases and compared with matched controls only). However, 16 of the 23 remaining comparisons yielded statistically non-significant OR point values above the unit. No significant differences were found at 1–9 years before onset (data not shown). For surgery conducted 10–19 years before onset, TW-2 (table 3), point estimates generally exceeded 1, being statistically significantly higher in both comparisons those for surgery in contact with peripheral nerves and, when compared with MCs only, those for surgery on skeletal muscle. Several significant differences were found at TW-1, ≥20 years (table 4), for several categories, including surgery involving blood vessels, peritoneum, skeletal muscle and the group of other tissues.




View this table:

Table 2

Associations for surgery by tissue/structure contacted 1 or more years before onset or ID-2





View this table:

Table 3

Associations for surgery by tissue/structure contacted 10–19 years before onset or ID-2





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Table 4

Associations for surgery by tissue/structure contacted, 20 or more years before onset or ID-2



When complementary subgroup analyses by alternative TWs were conducted, we observed a statistically significant excess risk for lower-risk surgery performed at least 15 years before onset in both comparisons, and for putatively high-risk surgery performed 5–14 years before onset using UMCs (table 5). Positive findings similar to those yielded by the core analysis were detected for strata by country, sex, alternative study period and age at CJD onset, or for definite cases, during both TW-1 and TW-2 (data not shown).




View this table:

Table 5

Complementary analyses by risk level



We went on to explore which specific operations among cases might have contributed to the excess risk. The highest risk, observed for surgery on the retina during the combined TWs 1–3, was based on two surgical discharges after retinal detachment and one involving electrocoagulation of choroidea and retina dating back 9, 12 and 13 years before clinical onset. Surgery during TW-1 with a lower but significant risk excess included SP on: blood vessels (n=6, corresponding in all cases to veins); peritoneum (n=15, with four and 11 of them being gynaecological and gastrointestinal, respectively); skeletal muscle (n=23, with seven and five of the SP codes being gynaecological/obstetric- and bone/orthopaedic-related, respectively); and ‘other tissues’ (n=28, with the majority of these being gynaecological SP with vaginal approach, for example, uterus curettage, n=12, and interventions on cervix n=9). Surgery during TW-2 on peripheral nerves among cases (n=4) included two finger and toe phalangeal amputations, one acoustic nerve neurinoma excision and one pyloroplasty+vagotomy, and 10 of 33 SP under the ‘skeletal muscle’ heading were gynaecological procedures.



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Discussion


The key features of the present study design enabled us to address novel aspects of the potential of surgical transmission of CJD.9 The additional introduction of an aetiological classification, that is unmasking associations hidden by the body-system approach,17 24 revealed a number of statistically significant associations, associations of higher magnitude and new effects with a particular pattern at 10–19 years’ latency. Limitations, which in part are discussed elsewhere,9 comprise: the low statistical power for some latencies and exposure categories; missing information on interventions undergone prior to registration or as outpatients; and lack of control of potential confounders such as blood transfusion, overlooked dura mater implants or hospital hygiene level.


The new SP classification system was built in a tissue/structure classification reported in 200522 combining features of the first WHO Classification on Tissue infectivity25 and of experimental efficiency of prion disease transmission to animals when using different routes of inocula administration.26–29 The plausibility of the risk excess of surgery of retina and peripheral nerves seen here might be supported by studies in experimental scrapie (Sc). PrPSc injected into the eye travelling via defined neuroanatomical connections has been demonstrated to be able to reach larger brain regions.30 31 In hamsters, PrPSc spreads along the vagus nerve to the medulla, pons, midbrain, cerebellum and thalamus via neuroanatomical pathways.32 The increasing risk found for SP involving veins, peritoneal cavity and lymph nodes at longer latencies fits proposals on prion neuroinvasion and transport, suggesting that prions first replicate and accumulate in the lymphoreticular system (LRS) (see Aguzzi and Calella33 for a recent review). In addition, it would appear that risk excess and latency are inversely correlated: for surgery of retina, OR 5.53, at mean 11 years; for surgery of peripheral nerves, OR 4.41, at 10–19 years; and for lower-risk SP OR 2.4, at ≥20 years. In summary, our findings might be consistent with proposed biological mechanisms potentially underlying the rapid access to the CNS by direct contact,34 prion uptake through the skin, neuroinvasion from the spleen and spread of prions along peripheral and CNS pathways.33 35


Compared with other studies, the main contribution of the new methodology may be credibility to consistently positive results from large recent studies covering lifetime surgery and pointing to likewise underlying diluting effects.7 8 In a study with negative results, retina surgery was unfortunately not investigated separately from other ophthalmological surgery.12 Findings for lower-risk procedures at >20 years would correspond to a similar risk excess before reclassification for main surgical procedures.9 However, the association with coronary surgery seen in TW-3 when using unmatched controls as well as the body system approach does not have a corresponding finding here. Since the association of coronary surgery with sCJD has been reported for Alzheimer’s disease at a similar latency, confounding from vascular risk factors generating both dementia and coronary disease followed by coronary surgery may be proposed as a potential explanation unrelated to prion transmission consistent with absence of findings after reclassification.36


Unrecorded information potentially determining our results might be the length of the pathway to the brain, short in the case of retina and acoustic nerve. An overlooked autologous dura mater graft, implanted during the above-mentioned acoustic neurinoma intervention, was excluded by direct perusal of the surgeon’s report, issued in 1977, by an author, HL, who excluded an accidentally transmitted CJD by dura mater implant. Improved cleaning of instruments in recent times may in part explain decreased excess risk with shorter latencies.


Blood transfusion has not been identified as a risk factor for sCJD; however, Riggs et al warn about the weaknesses of case–control studies frequently reporting protective effects.37 Inability to adjust for blood transfusion is a limitation of the study, since it has been estimated that blood transfusion is present in 50% of all major surgical interventions38; blood thus comprises a potential confounder.39 Since it would appear that the excess risk seen here for some tissues, for instance for retina surgery, is difficult to attribute to simultaneous blood transfusion, some of the present results might be consistent with confounded effects of surgical instruments and blood. This view contradicts observations on variant CJD, where transmission by blood has been demonstrated,40–43 but not risk excess for surgery.44 However, differences between sCJD and vCJD or Kuru are so large that inferences should perhaps be inappropriate. Furthermore, the exposures studied might not be independent phenomena representing either a potential entry site for prions or the above-mentioned uncontrolled confounding. For example, cohorting of surgical instruments occurs, and an instrument used once for retina surgery, for example, has in all likelihood been repeatedly used for retina surgery. It is therefore possible that our findings could in part be explained by infectivity determined by tissue remnants adhered to instruments (not controlled for here) rather than by the putative entry site (ie, tissue contacted). Consequently, the 18%9 to 35%7 proportion of sCJD which has been suggested might be causally related to surgery, while in theory consistent with observations from animal models, would be difficult to ascribe to a single biological mechanism based on these data.


The results might be surprising, since identified iatrogenic events related to surgery appear to be very rare. Surveillance since 1993 by 11 countries at the EUROCJD consortium includes data on more than 6000 sCJD cases (http://www.eurocjd.ed.ac.uk/genetic.htm). The number of iatrogenic cases related to surgery are 53 assigned to dura mater, two to corneal implants and nil to neurosurgery. However, routine surveillance data will usually not recognise surgical risk exposures for iatrogenic CJD other than grafts. Reasons to explain this might be: (1) the overwhelming difference in annual cohort size, that is >100 000 surgical in-patients per million in Sweden 2004 (http://192.137.163.40/epcfs/index.asp?modul=ope), versus approximately 200 dura mater grafts per million in the 1990s in Japan45; (2) the comparatively large attrition by low survival of neurosurgical and dura mater grafted cohorts45–47; (3) surveillance encompasses the end of the iCJD epidemic48; (4) large differences in duration of incubation periods, mean 11 years for iCJD by dura mater reduce differences in cumulative risk48; (5) similar genetic susceptibility might be a strong determinant of surgical risk linked or not to grafts, and is shared by iCJD and sCJD as shown by homozygosity at codon 12948 49 but can be interpreted in different ways. CJD surveillance captures epidemiologically compelling evidences required for correct CJD diagnosis; the OR for exposure to cadaveric dura mater for CDJ in Japan50 was 32.5 95% CI (2.6 to infinity). Our three cases with history of retina surgery were first discharged with CJD diagnosis from three different hospitals, at different years, in two countries, and most probably diagnosed by different clinicians. Views for iCJD from surveillance and results of this study are perhaps not so difficult to reconcile when biology, diagnosis, epidemiology and public-health practice51 are simultaneously considered.


The potential applicability of results in prevention is complex. Cautiousness might be recommended for planning of surgical interventions for patients where CJD diagnosis has been considered, and for decontamination and quarantining of such surgical instruments, avoiding reuse during the interval CJD diagnosis has not been excluded. Established instrument-quarantining, -tracking, -cleaning and prion-disinfection policies, which generally target infrequent procedures, such as neurosurgery and ophthalmological, spine and ear surgery,38 52 are based on decontamination of remnants and applied to surgical activity defined by the type of surgeon, that is, by body-system group. Current sterilisation procedures undertaken in hospitals for delicate instrumentation are insufficient to ensure total removal of infectious prion protein, and carriers of infective prions are difficult to detect.52 53 Extension of such measures, after appropriate assessment, to instruments contacting or potentially contacting veins, female genital organs, peritoneal cavity, peripheral nerves and muscle could be a priority. In addition, new decontamination procedures54 may have a wider-than-expected field of application.


To sum up, these results suggest that surgery constitutes a risk factor for sCJD, acting with long incubation periods, and less frequently with shorter latencies when the central- or peripheral nervous system as well as skeletal muscle are implicated. In addition, results are in concordance with animal models of experimental prion transmission through various routes of inoculation that may mimic accidentally transmitted CJD, and might have implications for prevention of CJD spread in medical settings.



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Acknowledgments


EUROSURGYCJD group members. Danish team: G Falkenhorst, H Laursen, K Mølbak. Finnish team: J Kovanen. Swedish team: M Cruz, Å Siden. Spanish team: J Almazán, MJ Bleda, M Calero, I Mahillo, P Martínez-Martín, J de Pedro-Cuesta (coordinator), A Rábano. The EUROSURGYCJD group members are grateful: to M Pocchiari, Italy, for contributing to this proposal in respect of the biological plausibility of surgical transmission of prion disorders; to P Sanchez-Juan, Spain, for criticism; and to M Löfdahl (Swedish CJD Surveillance Unit), C-L Spetz, L Forsberg (Socialstyrelsen) and L Caderius (Population Statistics), Sweden, for their help with data collection.



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Footnotes




  • Funding Funding was obtained from The Research Commission EU, Concerted Action QLRG3-CT-2002-81223, NEUROPRION, and the Spanish RECSP C03-09, CIEN C03-06 and CIBERNED networks.



  • Competing interests None.



  • Ethics approval Ethics approval was provided by the Danish Data Protection Agency (record No 2003-41-3104) and Karolinska Institute Ethics Committee (South; report No 452/02).



  • Provenance and peer review Not commissioned; externally peer reviewed.



This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.



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]]> http://www.chsc.or.kr/?post_type=reference&p=2139/feed 0 [의료개혁] 보건의료 지출을 어디에 우선 배분할 것인가? http://www.chsc.or.kr/?post_type=reference&p=1154 http://www.chsc.or.kr/?post_type=reference&p=1154#comments Sat, 10 Oct 2009 19:50:12 +0000 건강과대안 http://www.chsc.or.kr/?post_type=reference&p=1154

2007년 2월 [PLoS Med]에 발표된 “보건의료 지출을 어디에 우선 배분할 것인가? 보건의료 전문가들에 대한 국제적 조사”결과입니다.

호주와 영국의 연구자 모임이 인도네시아, 태국, 인도, 이란, 남아공, 불가리아의 의료전문가 253명을 대상으로 그들이 각자 자신의 나라에서 보건의료에 사용될 재원을 분배하는 권한을 가지게 된다면 어떤 의료서비스에 재원을 우석 배분할 것인지 상위 10개 항목을 꼽도록 했습니다.

전문가 조사에서 가장 높은 점수를 받은 3가지 항목은 어린이의 예방접종(Childhood immunisation), 어린이 금연교육(Anti-smoking education for children ), 일상적인 질병을 다루는 일반의 진료(GP care for everyday illness)였으며, 가장 낮은 점수를 받은 항목은 복잡한 외과수술이었습니다.

========================================================


What Drives Health-Care Spending Priorities? An International Survey of Health-Care Professionals


Glenn Salkeld,* David Henry, Suzanne Hill, Danielle Lang, Nick Freemantle, and Jefferson D’Assunção



*To whom correspondence should be addressed: Email: glenns@health.usyd.edu.au

출처 : PLoS Med. 2007 February; 4(2): e94.

Published online 2007 February 20. doi: 10.1371/journal.pmed.0040094.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1800312

Introduction


Making the rules of health-care resource allocation transparent is a challenge for all governments. The Oregon Health Plan in the late 1980s was one such attempt to prioritise expenditure of limited Medicaid funds, based on public values [1]. For decision makers, asking the general public and health professionals to express their preferences for health-care spending priorities can be a way of ensuring that the process and resultant spending priorities are seen as legitimate and fair [2]. In a study comparing the preferences of health professionals and members of the public for setting health-care priorities, Wiseman found considerable uniformity in preferences between the two groups [2]. However, some members of the public argued that it would be better to trust health professionals to make the correct decision in the first place.

Those entrusted to set health-care priorities do so according to what is in the best interest of the public. This in turn requires those decision makers to make value judgments on what constitutes “good”. On what basis should one health program deserve a higher priority for funding than another? Several studies have found that the general public and health professionals may not agree on who and what is most deserving of scarce health resources.

Based on an opinion poll, Groves showed that the public strongly disagreed with doctors and health managers on where best to spend health resources [3]. Myllykangas and colleagues, in a study on attitudes to health-care priorities, found that doctors and nurses were less inclined to be punitive towards funding for patients with self-induced diseases than the general public [4]. Yet Dolan et al. found that when the public were given time to listen to the considered opinions of their fellow citizens and reflect on their views, fewer were willing to discriminate against people with what might be regarded as self-induced diseases [5].

In all cases it is values, the building blocks or rules which govern attitudes and behaviour, that are reflected in priorities for spending in health care [6,7]. The values of the decision makers clearly count in setting health-care expenditure priorities. So do decision makers themselves share common values about priorities for health-care spending? Are there any similarities in values between decision makers in different countries?

The purpose of this study is to compare spending priorities for health care across a selection of predominantly middle-income countries, based on the opinions of current and future decision makers. Using an opinion poll questionnaire, we surveyed 253 health professionals from six countries, asking them to rank ten health interventions in order of priority for spending from most important (rank 1) to least important (rank 10). The questionnaire was based on a short questionnaire on priorities for health-care spending developed by Groves [3].

The questionnaire asked respondents to imagine that they were responsible for health-care spending in their country. This was followed by a question on whether or not they thought that funding for health care should be unlimited. No additional information was given to respondents. The survey was designed as an introductory learning exercise for a series of intensive workshops (of three to ten days’ duration), run under the auspices of the World Health Organization or AusAID, the Australian government’s overseas aid program (South Africa workshop only), on the application of evidence-based medicine and economic evaluation to the selection and reimbursement of pharmaceuticals. The intention was to introduce course participants to the notion of priority setting. The questionnaire was administered at the beginning of each workshop. Details of the study setting and participants, questions used to prompt group discussion, and the data analysis are outlined in Text S1.

Spending Priorities

\A summary of the intervention rankings, pooled across countries, is shown in Box 1. Across all countries, childhood immunisation was the highest ranked intervention and cancer treatment for smokers was ranked as the least important priority for health-care spending (Box 1). There was little variation across countries in the median rank score for preventive health care and greatest variation for “lifesaving” interventions (Figure 1). The Kruskal-Wallis test for the null (that the median ranks were equal across countries) could not be rejected at the 5% significance level for the following interventions: childhood immunisation (p = 0.114), antismoking education for children (p = 0.327), screening for breast cancer (p = 0.355) and treatment for people with schizophrenia (p = 0.317). For all other interventions the null hypothesis was rejected at the 5% level, suggesting that the median ranks for these interventions are significantly different across countries. The Kruskal-Wallis test results did not change at the 5% significance level for the all country sample that excluded the South African pharmaceutical industry respondents


Box 1. Median Rankings of Health-Care Spending Priorities Across All Countries, in Order of Importance


  • Childhood immunisation
  • Anti-smoking education for children
  • GP care for everyday illness
  • Screening for breast cancer
  • Intensive care for neonates
  • Support for carers of the elderly
  • Treatment for people with schizophrenia
  • Hip replacement
  • Heart transplant
  • Cancer treatment for smokers









    Figure 1
    Figure 1
    Spending Priority: Intervention


Primary care (by a general practitioner [GP]) was ranked highest by participants in India (rank 2), Iran (rank 3), and public sector and industry participants in South Africa (rank 3) (see Figure 2). Conversely, heart transplant was ranked lowest in Iran (rank 8) and India (rank 9). The life-saving intervention of neonatal intensive care was ranked highest by participants in Bulgaria (rank 3) and lowest by those in India and Iran (rank 5 and 6, respectively). Most respondents thought that funding for health care should not be unlimited, ranging from 68% in Bali (Indonesia) to 90% in South Africa.








 

Figure 2
Figure 2
Spending Priority: GP Care


Key Values



Prevention.

The strongest and most consistently shared value across countries was a general preference for preventive health care over curative care. When asked to state their criteria for ranking interventions, participants regarded childhood vaccination as safe, affordable, efficacious, and cost effective. Anti-smoking education for children was seen in the same light as immunisation and breast cancer screening was regarded as a worthwhile and cost-effective intervention. This strong and consistent preference for prevention over cure is quite at odds with the actual spending priorities in most countries throughout the world. In 2004, OECD (Organisation for Economic Co-operation and Development) member countries spent on average only 2.8% of total health expenditure on organised public and private prevention programmes [8]. Reliable data on the proportion of total health expenditure spent on prevention and public health for the countries in this study are not available.


Individual responsibility.

Treatment for schizophrenia elicited the greatest variation in rankings within countries but a consistent (and statistically significant) low median ranking between countries. When discussing the reasons for this ranking, participants admitted that mental illness was stigmatised in their country and that this was reflected more generally in the low levels of funding for mental health. The visual presentation to the large group of the median ranking for treatment of schizophrenia along with the 5th and 95th percentile prompted some discussion about whether the reasons for the low ranking were acceptable or not. Often respondents who ranked the intervention as a higher spending priority would state their reasons (for example, the existence of known cost-effective pharmacological therapies), but few people expressed a desire to change their ranking. Rather there was an acceptance that variation in rankings existed within the group. Likewise there was an acceptance of the rankings for the lowest ranked intervention, cancer treatment for smokers. Here, participants seemed to invoke the principle of individual responsibility. Smokers were “blamed” for their cancer and were regarded as the least deserving of health-care spending. This belief may have been tempered by the perception that treatment for lung cancer may not produce much health gain and hence may not be cost effective.

In a study on the effect of discussion and deliberation on the public’s view of priority setting in health care, Dolan et al. found that while 57% of their lay public sample stated that smokers should have a lower priority for treatment compared to other groups on initial survey, after deliberation, only 37% gave smokers a lower priority as a final response [5]. In this study the authors found the respondents less willing to assign personal responsibility after some reflection and discussion.


Fair innings.

At the top (most important priority for spending), participants favoured giving priority in spending to children. This is consistent with other studies that have found that policy makers give priority to interventions which target the young [9]. Newborns and infants were considered to be entitled to a fair start in life within certain limits. Those limits were defined by affordability and effectiveness. Neonatal intensive care was regarded as an expensive technology with variable health outcomes but participants in many countries apparently felt it was important that equity should override efficiency concerns when dealing with the life of a newborn. Just as Nord and colleagues found that people derive a benefit from the knowledge that society is “just” [10], respondents in our survey considered “fairness” important when ranking the interventions.

In contrast, interventions such as hip replacement and caregiver support, where the primary beneficiaries were older people, were regarded as a lower priority for health-care spending. The notable exception was Iran (a country with a young population) where participants ranked caregiver support midway (rank 5). For countries other than Iran, it may be that survey respondents adopted the “fair innings” principle whereby someone who has already had a fair innings, say a fit elderly person, gets lower priority for health-care spending than a young person who, “without treatment, will certainly not reach the societal norm (through premature death and/or lifelong disability)” [11]. What’s not obvious from the results is the degree to which participants regard reducing health inequality as more important than achieving a health maximisation objective.


Rule of rescue.

Participants were willing to invoke the “rule of rescue” [12]—the moral imperative to save the life of an identified individual who would otherwise die—but only up to a point. Whilst the survey was not designed to identify any rule of rescue threshold, individual participants said that they considered the health outcomes first and then cost as part of their decision-making criteria.

The median rankings of interventions did not differ between the South African pharmaceutical industry participants and the pooled results for the public sector participants in all countries. Further studies are needed to test whether the agreement in values between the industry and public sector respondents on some of the underlying principles for public sector resource allocation are reproducible in other countries.


Opinion polls.

When asked what additional information they would have liked, participants wanted information on the benefits, harms, and costs of the intervention. Less often, participants identified the issue of scale—that is, how much more (or less) of something should be done. It is rarely the case that the decision to spend money on an intervention is dichotomous (yes/no); decisions are more likely to turn on how much should be spent. This in turn led some participants to conclude correctly that opinion polls cannot address the question of opportunity cost (the benefits forgone in sacrificing spending on one intervention for another) or the margin (how much more or less of an intervention should be funded), in the absence of data on comparative efficacy, safety, cost-effectiveness, and affordability.

Limitations of Our Approach


This survey was intended as an educational exercise to introduce workshop participants to the notion that priority setting in health care is a value-laden exercise and one that should be informed by evidence-based medicine and economics. The interventions used in the survey, replicated from the Groves study [3], are formulated in very general terms. For example, GP care for everyday illness covers a wide category of services, from preventive measures to curative services. This limits our ability to make strong conclusions about one type of intervention versus another. There is a risk of confounding in the results due to the method of selection of our sample. The study participants were self-selected; they chose to attend the course. To the extent that policy makers who attend courses are systematically different from those who do not, this may have affected the extent to which subjects are representative of a population of health decision makers.

Do the Preferences of Experts Accord with Those of General Populations?


Whilst the results of this survey do not allow for a comparison between the preferences of health professionals and the general population, other studies have shown a reasonable level of uniformity of opinion, with a few exceptions. Wiseman found that the public gave equal weighting to health professionals for public health/prevention interventions but more weight (for spending) to coronary artery bypass grafting and less to hip replacement than did the health professionals [2]. But overall, there was considerable uniformity of preferences between the two groups. Similarly, Myllykangas et al. found that the views of health professionals, local politicians, and the general public were generally similar, although the views of doctors differed substantially on some matters [4]. On the other hand, Groves found that the public tended to put life-saving interventions such as heart transplants and intensive care for babies higher up the spending priority list than doctors or National Health Service managers (who themselves ranked life-improving treatment as twice as important as lifesaving ones) [3].

Conclusion


The strongest opinions elicited from our sample of health professionals, a general preference for prevention and for spending on the young over the old, bear little semblance to how health care dollars are actually spent in many countries. Other opinions, such as a preference to rescue an identifiable life in danger and a tendency to assign blame for disease, seem to exert more influence over current health care spending. The values expressed here transcended national and sectoral boundaries. Across the world many countries are struggling with the health and financial implications of a rapid rise in non-communicable disease. If health care professionals and policy makers believe that prevention and targeting the young is an important principle for health spending priorities, then health care funders should examine the cost effectiveness evidence for intervening early in life. Whilst the “rule of rescue” will always be a significant influence in health-care spending priorities, greater attention needs to be given to those interventions that are life improving as well as life extending. 3

Supporting Information



Text S1: Research Methodology

(24 KB DOC).

Click here for additional data file.(25K, doc)

Acknowledgment



The authors would like to acknowledge the anonymous respondents who participated in the various opinion poll surveys. Approval for this study was granted by the Human Research Ethics Committee of the University of Sydney, Australia (Approval number 06-2005/1/8325).

Author contributions. GS designed the opinion poll questionnaire, was involved in the administration of the questionnaire in India, Iran, and South Africa, and was responsible for the data analysis and the writing of the paper. DH assisted in the design of the original questionnaire, was involved in the administration of the questionnaire in India, Iran, and South Africa, and contributed to the development of ideas and the writing of the paper. SH assisted in the design of the original questionnaire, was involved in the administration of the questionnaire in Bali, India, and Thailand, and contributed to the development of ideas and the writing of the paper. DL assisted in the design of the original questionnaire, was involved in the administration of the questionnaire in Thailand, and contributed to the analysis of data and the writing of the paper. NF was involved in the administration of the questionnaire in Bulgaria and contributed to the writing of the paper. JD conducted the analysis of data and contributed to the writing of the manuscript.

Footnote



Glenn Salkeld is an Associate Professor of Health Economics, Screening Test Evaluation Program, School of Public Health, University of Sydney, Sydney, Australia. David Henry is a Professor of Clinical Pharmacology, Suzanne Hill is an Associate Professor of Clinical Pharmacology, and Danielle Lang is a Senior Lecturer in Health Economics, WHO Collaborating Centre for Training in Pharmacoeconomics and Rational Pharmacotherapy, Faculty of Health, University of Newcastle, Newcastle, Australia. Nick Freemantle is a Professor of Clinical Epidemiology and Biostatistics, Department of Primary Care and General Practice, Primary Care Clinical Sciences Building, University of Birmingham, Edgbaston, Birmingham, United Kingdom. Jefferson D’Assunção is a Research Officer, Screening Test Evaluation Program, School of Public Health, University of Sydney, Sydney, Australia.


Funding: This study was performed during training programs which were funded by the World Health Organization and AusAID, the Australian Government’s overseas aid program. Neither organisation was involved in the preparation of the manuscript nor the decision to submit the paper to the journal. The opinions in this pape

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