What Drives Prescribing of Asthma Medication to Children? A Multilevel Population-Based Study. Ann Fam Med 2009;7: DOI: /afm.910.
|
|
- Vivien Parker
- 5 years ago
- Views:
Transcription
1 Wht Drives Prescribing of Asthm Mediction to Children? A Multilevel Popultion-Bsed Study Mir G. P. Zuidgeest, PhrmD, PhD 1,3 Liset vn Dijk, PhD 2 Peter Spreeuwenberg, MA 2 Henriëtte A. Smit, MD, PhD 3 Bert Brunekreef, PhD 4,5 Hubertus G. M. Arets, MD, PhD 6 Mdelon Brcke, PhD 1 Hubert G. M. Leufkens, PhrmD, PhD 1 1 Division of Phrmcoepidemiology & Phrmcotherpy, Utrecht Institute for Phrmceuticl Sciences (UIPS), Fculty of Science, Utrecht University, Utrecht, The Netherlnds 2 NIVEL (Netherlnds Institute for Helth Services Reserch), Utrecht, The Netherlnds 3 Centre of Prevention nd Helth Services Reserch, Ntionl Institute for Public Helth nd the Environment (RIVM), Bilthoven, The Netherlnds 4 Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlnds 5 Julius Center for Helth Sciences nd Primry Cre, University Medicl Center, Utrecht, The Netherlnds 6 Deprtment of Peditric Pulmonology, Wilhelmin Children s Hospitl, University Medicl Centre, Utrecht, The Netherlnds Confl ict of interest: The deprtment employing uthors M.G.P.Z, M.B. nd H.G.M.L. hs received n eductionl grnt from GSK for the conduct of phrmcoepidemiologicl reserch. All other uthors declre tht they hve no confl ict of interest. CORRESPONDING AUTHOR Bert Leufkens, PhD Division of Phrmcoepidemiology & Phrmcotherpy Utrecht University PO Box 80082, 3508 TB Utrecht, The Netherlnds h.g.m.leufkens@uu.nl ABSTRACT PURPOSE Dignosing sthm in children with sthmtic symptoms remins chllenge, prticulrly in preschool children. This chllenge cretes n opportunity for vribility in prescribing. The im of our study ws to investigte how nd to wht degree ptient, fmily, nd physicin chrcteristics influence prescribing of sthm mediction in children. METHODS We undertook multilevel popultion-bsed study using the second Dutch ntionl survey of generl prctice (DNSGP-2), Prticipnts were 46,371 children ged 1 to 17 yers belonging to 25,537 fmilies registered with 109 generl prctitioners. Using multilevel multivrite logistic regression nlysis with 3 levels, our min outcome mesure ws the prescribing of sthm mediction, defined s t lest 1 prescription for β 2 -drenergic gonists, inhled corticosteroids, cromones, or montelukst during the 1-yer study period. RESULTS We identified chrcteristics significntly ssocited with prescribing sthm mediction on ll 3 levels (child, fmily, nd physicin). The vrince in prescribing mong physicins ws significntly higher with children who were younger thn 6 yers thn with children ged 6 yers nd older (95% CI, 3.5%- 25.2% vs 2.4%-13.4%). Severl dignoses other thn sthm nd sthmtic complints were strongly ssocited with prescribing sthm mediction, including bronchitis/bronchiolitis (OR = 9.04; 95% CI, ) nd cough (OR = 6.51; 95% CI, ). CONCLUSIONS Our study shows much higher vrince in prescribing ptterns mong generl prctitioners for children younger thn 6 yers compred with older children, which could be direct result of the dignostic complexities found in young children with sthmtic symptoms. Thus dignostic gps my led to more physicin-driven prescribing irrespective of the clinicl context. Ann Fm Med 2009;7: DOI: /fm.910. INTRODUCTION Asthm in children hs been recognized s mjor clinicl nd public helth problem. 1,2 Reported dt on the prevlence of sthm symptoms in children vry signifi cntly, from 1% to more thn 30% in different popultions. 3 Despite ll scientifi c nd clinicl progress, dignosing sthm in children nd treting children with sthmtic symptoms remin chllenge. 4-6 First, children often receive mediction to reduce symptoms during wheezing episodes to prevent further excerbtions nd to serve more or less s dignostic tool. At young ge, however, vlid dignostic possibilities for sthm re still limited. Although most children will eventully turn out to be trnsient wheezers, there is lck of objective dignostic tools to distinguish these trnsient wheezers from the true sthmtics. 6 Second, the fmily of the child my ply role, for exmple, with its specifi c help-seek- 32
2 ing behvior 7 nd genetic infl uence on disese susceptibility. 8 Lst but not lest, it is the treting physicin who mkes the decision whether to prescribe sthm mediction. To id in this decision, guidelines re vilble with informtion on how sthmtic symptoms in children should be treted nd which kind of sthm mediction should be used There is generl consensus tht dignosis of sthm cnnot be mde with resonble certinty erlier thn the ge of 5 to 6 yers; therefore, different tretment recommendtions re mde for children who re younger thn 5 to 6 yers thn for children ged 6 yers nd older Prescribing sthm mediction to children is the result of complex interply mong the child, the cregivers or prents of the child, nd the treting physicin. Given the bsence of cler dignostic guidnce in children, prticulrly in preschool children, vribility in prescribing is to be expected. As result, drug utiliztion studies describing ctul use of sthm medicines in children show mple diversity in the pplied therpies Other studies hve reported mismtch between sthm mediction use nd dignosis of sthm A key question driven by these observtions is whether this diversity seen in peditric sthm therpy is minly determined by the ptient itself, the fmily, or the treting physicin. The ttitude of the physicin or preferences of the cregivers or prents could ply much lrger role in the decisionmking process t young ge, when the dignosis is uncertin, thn t n older ge, when the dignosis of sthm cn be more fi rmly estblished. The im of this study ws to investigte how nd to wht degree prescribing sthm mediction to children is infl uenced by ptient, fmily, nd physicin chrcteristics. We investigted to wht extent vrince in prescribing is ssocited with differences mong children, how much vrince cn be ttributed to the fmily or physicin or both, nd whether these vrinces differ for younger nd older children. METHODS Setting nd Study Popultion In the Netherlnds children with sthmtic symptoms nd morbidity re primrily seen by the physicins in generl prctice. This study ws therefore undertken within the frmework of the Second Dutch Ntionl Survey of Generl Prctice (DNSGP-2). This ntionwide survey ws crried out in 2001 by the NIVEL (Netherlnds Institute for Helth Services Reserch) in coopertion with the Ntionl Institute for Public Helth nd the Environment (RIVM). Prctices lredy prticipting in the Dutch Ntionl Informtion Network of Generl Prctice were invited to prticipte in this study becuse of their experience in the use of electronic medicl records. All prctices within the DNSGP-2 mde use of electronic medicl records. The prticipting generl prctitioners (GPs) were representtive of ll Dutch GPs. 18 A pilot study lso showed no differences in prctice style between GPs prticipting in registrtion network nd those who were not. 19 The DNSGP-2 survey hs been described in detil elsewhere. 18,20 In short, 195 GPs in 104 prctices serving pproximtely 400,000 ptients registered ll physicin-ptient contcts during 12 consecutive months. The DNSGP-2 provides dt on ll dignoses mde nd prescriptions written by the GP. Every single helth problem reported within consulttion ws coded by the GP using the Interntionl Clssifi ction for Primry Cre (ICPC). 21 Additionl informtion on ptient nd GP chrcteristics ws collected through questionnires. In the Netherlnds ll noninstitutionlized inhbitnts re registered in single generl prctice, with few chnges over time. The DNSGP-2 survey ws crried out ccording to Dutch legisltion on privcy. The privcy regultion of the study ws pproved by the Dutch Dt Protection Authority. For the present study we nlyzed dt from 72 GP prctices. The other prctices were excluded for vrious resons: 20 prctices were excluded becuse the informtion on which ptient belongs to which individul GP ws not vilble, 10 becuse of incomplete dt collection on morbidity items, nd 2 more becuse of lck of informtion on GP chrcteristics. The remining 109 GPs within the 72 prctices did not differ signifi cntly from the totl group of GPs prticipting in the DNSGP-2 except for higher percentge of solo prctices (becuse of our selection criterion of including only ptients tht could be linked to specifi c GP). A totl of 1,804 children (3.7%) who could not be linked to single fmily were lso excluded. The fi nl study popultion consisted of 46,371 children ged 1 to 17 yers within 25,537 fmilies, belonging to 109 GPs within 72 prctices. Children, fmilies, nd GPs seem to be representtive for the Dutch sitution on bsic chrcteristics. 18,20 Mesurements Outcome Vrible: Prescribing of Asthm Mediction Drug prescriptions were registered by the GP ccording to the Antomic Therpeutic Chemicl Clssifi ction system. 22 The following medictions were considered sthm mediction: inhled nd orl short-cting β 2 -gonists, inhled long-cting β 2 -gonists, inhled corticosteroids, inhled cromones, nd montelukst. We determined whether child from the study popultion received t lest 1 prescription for 1 of these med- 33
3 icine groups in the yer under study (ie, 2001), clling them children prescribed sthm mediction. Child Chrcteristics At the level of the individul child, the following vribles were tken into ccount: ge (ctegorized into children younger thn 6 yers nd children ged 6 yers nd older to conform with the guidelines), sex, the number of prescriptions child received for ntibiotics in the yer under study, the number of prescriptions child received for orl glucocorticosteroids in the yer under study, the number of contcts child hd with the GP in the yer under study, nd whether child hd t lest 1 referrl for respirtory complints/diseses or to lung specilist in the yer under study. Every helth problem reported during consulttion ws coded by the GP using the ICPC. 21 We included the following ICPC dignoses of respirtory complints nd diseses s dichotomous vribles: R02 (shortness of breth/dyspne), R03 (wheezing), R05 (cough), R74 (cute upper respirtory trct infection), R78 (cute bronchitis/bronchiolitis), R81 (pneumoni), R96 (sthm), nd R97 (llergic rhinitis). If child hd t lest 1 consulttion coded with 1 of these ICPC codes, then the dichotomous vrible for tht specifi c code for tht child would be positive. Fmily Chrcteristics At the fmily level the following vribles were tken into ccount: ethnicity (whether 1 or both prents hd non-western culturl bckground bsed on the country of birth), the highest socil economic sttus of the prent(s) using the Interntionl Socio-Economic Index of Occuptionl Sttus, nd prentl sthm (t lest 1 prent with registered ICPC code R96 during the study period). GP Chrcteristics At the GP level the following vribles were tken into ccount: ge; sex; prctice type (solo vs group prctice); degree of urbniztion of prctice loction (s clssifi ed by Sttistics Netherlnds on 5-point scle); GP informtion system used to register contcts, prescriptions, etc; whether the GP is dispensing doctor ( doctor, uthorized or required by the Helth Authority to provide phrmceuticl services to his or her ptients); whether the GP is working full-time or prt-time by the number of full-time equivlents (FTEs); worklod of the GP (totl number of ptients divided by the number of FTEs per 1,000 ptients); prescribing volume of the GP (verge number of prescriptions issued per ptient during 1 yer); proportion of 0- to 17-yer-old ptients per GP; nd the proportion of children with sthm dignosis per GP. We divided the GPs into 2 groups: those who within their ptient popultion of children prescribed sthm mediction to 7.4% of children or less (the verge t the GP level is 7.4%), nd those who prescribed sthm mediction to more thn 7.4% of children. Sttisticl Anlyses We performed multilevel logistic regression nlysis with 3 levels, nmely, children within fmilies clustered within GPs, which enbled us to study not only the infl uence of the child, fmily, nd GP chrcteristics on sthm mediction use in children simultneously, but lso the vrince in prescribing t the 2 higher levels. The vrince t the level of the child ws not determined, s the outcome mesure is dichotomous: child either receives sthm mediction or not. The ssocition between prescribing sthm mediction nd the vribles described bove ws fi rst tested by univrite nlysis for ech vrible. Only vribles signifi cntly ssocited (P <.05) with prescribing sthm mediction were included in the multivrite nlysis. All vribles tht no longer showed signifi cnt ssocition in the multivrite nlysis were excluded. A sensitivity nlysis including ll child chrcteristics irrespective of signifi cnce showed tht including the nonsignifi cnt vribles did not lter the estimtes for the signifi cnt vribles. The child chrcteristics of sex nd ll dignoses of respirtory complints nd diseses were tested for n ge interction. The multivrite nlysis ws computed in severl steps to differentite between the infl uence of child, fmily, nd GP chrcteristics on the vrious estimtes. Step 1, the empty model, gives the unexplined vrince t the upper 2 levels (fmily nd GP) without correcting for ny differences tht might exist in the popultion of children belonging to these fmilies nd these GPs. In step 2 we seprted the vrince in prescribing t the GP level nd t the fmily level for children younger thn 6 yers nd older children. At ech level this nlysis rendered unique vrince ccording to ge-group nd covrince. If the covrince turned out to be much higher thn the 2 unique vrinces t certin level, seprting the vrince for the 2 ge-groups t this level ws not meningful. In step 3 we dded the child chrcteristics (including the ge-interction terms) to the model. This step serves 2 purposes: (1) to mke the popultions seen by the GP nd belonging to fmily s similr s possible, nd (2) to determine which child chrcteristics re ssocited with prescribing sthm mediction. The vrince in this model is the vrince unexplined by the child chrcteristics introduced in the model. In step 4 we dded the fmily chrcteristics to the model. In step 5 we dded the GP chrcteristics to the model. 34
4 The vribles included in the models described here were rescled by subtrcting the men, so tht the intercepts represent prescribing sthm mediction to the verge child. The percentge of children receiving sthm mediction cn be clculted by tking the inverse logit of the intercept. The ssocition between chrcteristics on ll 3 levels nd prescribing sthm mediction is expressed using odds rtios) nd 95% confi dence intervls. The 95% confi dence intervl of prescribing sthm mediction t the GP level cn be clculted for ech ge-group using the sum of the unique vrince of tht ge-group nd the covrince. All models were estimted using multilevel logistic regression, with PQL (penlized qusi-likelihood), 1st order, nd constrined level-1 vrince (MLwinN 2.02; Centre for Multilevel Modeling, University of Briston, Bristol, Englnd). RESULTS Chrcteristics of the Study Popultion Tble 1 displys the chrcteristics of the study popultion t the child level nd the results for the univrite nlyses. During the yer under study 7.3% of ll children (n = 3,374) received sthm mediction. All child chrcteristics were signifi cntly ssocited with prescribing sthm mediction when tested univritely. An overview of the pplied therpies strtifi ed by ge-groups is displyed in Tble 2. We see tht prescribing sthm mediction declines with the rising ge of the child. Short-cting β 2 -gonists nd inhled corticosteroids were the medicine groups most prescribed t ll ges. The children within our study popultion belonged to 3,081 fmilies (Tble 3); therefore, in 12.1% of the fmilies, 1 or more children were prescribed sthm mediction. The chrcteristics of the GPs re displyed in Tble 4. The Multivrite Model Tble 5 shows the stepwise-built, multivrite, multilevel, logistic regression model. We found tht in the empty model the vrince t the fmily level (0.567) ws much higher thn the vrince t the GP level (0.119). Compring 2 Age-Groups When seprting the vrince in prescribing t the GP level for children younger thn 6 yers nd for older children (model 1) we found tht the vrince is signifi cntly higher (χ 2 = 7.3) in younger children thn in older children. This ge infl uence ws not found t the fmily level; t this level the covrince ws much higher thn the 2 unique vrinces (model Tble 1. Child Chrcteristics nd Results From the Univrite Anlyses Child Chrcteristics Children Without n Asthm Prescription (n = 42,997) Children Prescribed Asthm Mediction (n = 3,374) OR (95% CI) Men ge (SD; rnge), y 9.1 (4.8; 1-17) 7.7 (4.9; 1-17) 0.94 ( ) Age <6 y, No. (%) 11,948 (25.8) 1,386 (41.1) 1.82 ( ) Sex, mle, No. (%) 21,798 (50.7) 1,922 (57.0) 1.29 ( ) Antibiotic prescriptions, No. (SD; rnge) b 0.2 (0.6; 0-13) 0.6 (1.0; 0-12) 1.85 ( ) Orl corticosteroid prescriptions, No. (SD; rnge) b (0.11 ;0-12) (0.26;0-5) 4.69 ( ) Contcts with GP, No. (SD; rnge) c 2.1 (2.6; 0-35) 5.2 (4.0; 0-34) 1.30 ( ) Children with 0 contcts in registrtion yer, No. (%) 13,786 (32.1) 129 (3.8) Referrls, No. (%) d 93 (0.3) 94 (3.6) 13.0 ( ) Registered diseses nd complints, e No. (%) Asthm 227 (0.5) 1,739 (51.5) 260 ( ) Shortness of breth/dyspne 92 (0.2) 144 (4.3) 21.1 ( ) Wheezing 16 (0.0) 63 (1.9) 55.2 ( ) Cough 2082 (4.8) 873 (25.9) 6.90 ( ) Acute bronchitis/ bronchiolitis 769 (1.8) 622 (18.4) 13.5 ( ) Acute URTI 3,267 (7.6) 674 (20.0) 3.06 ( ) Pneumoni 241 (0.6) 133 (3.9) 7.24 ( ) Allergic rhinitis 1,029 (2.4) 252 (7.5) 3.24 ( ) CI = confidence intervl; GP = generl prctitioner; ICPC = Interntionl Clssifiction for Primry Cre; OR = odds rtio; URTI = upper respirtory trct infection. Significnt vlues P <.05. b Averge number of prescriptions issued per ptient during 1 yer. c Averge number of contcts with GP during 1 yer. d Referrls for respirtory complints/diseses or to lung specilist. e Dichotomous vribles of the ICPC codes R02 (shortness of breth/dyspne), R03 (wheezing), R05 (cough), R74 (cute upper respirtory trct infection), R78 (cute bronchitis/bronchiolitis), R81 (pneumoni), R96 (sthm), nd R97 (llergic rhinitis). 35
5 Tble 2. Prescription of Asthm Mediction by Age-Group nd Type of Mediction Age-Groups, Yers Mediction Type 1-2 n = 5, n = 8, n = 8, n = 8, n = 8, n = 8,156 Totl n = 46,371 All sthm mediction, % Mediction groups, % SABA ICS LABA Cromones Montelukst Therpy groups, % SABA ICS SABA + ICS Other medicines ICS = inhled corticosteroids; LABA = long-cting β2-gonists; SABA = short-cting β2-gonists. We clculted percentge of children using some sort of sthm mediction, not percentge of totl popultion; therpy groups therefore dd up to 100%. Therpy groups re defined s follows: SABA = monotherpy with short-cting β 2-gonists; ICS = monotherpy with inhled corticosteroids; SABA + ICS = combintion therpy of these 2 mediction groups (10.3% of children in this group lso received 1 or more other sthm medicines, of which 82% were LABA); other medicines = ll other therpies. Tble 3. Fmily Chrcteristics nd Results From the Univrite Anlyses Fmily Chrcteristics No Child With Asthm Mediction Within Fmily (n = 22,456) 1 Child Within Fmily With Asthm Prescription (n = 3,081) OR (95% CI) 1 or both prents non-western culturl 1,834 (10.6) 275 (11.1) 1.01 ( ) bckground, No. (%) Men SES highest (SD; rnge) b 50.4 (15.5;16-87) 49.5 (15.4;16-87) 1.00 ( ) Prentl sthm, No. (%) c 821 (3.7) 256 (8.3) 2.33 d ( ) CI = confidence intervl; ICPC = Interntionl Clssifiction for Primry Cre; OR = odds rtio; SES = socioeconomic sttus. Ethnicity bsed on the country of birth. b The highest SES of prent(s) using the Interntionl Socio-Economic Index of Occuptionl Sttus. c At lest 1 prent with registered ICPC code for sthm during the study period. d Significnt vlues P <.05. not shown). In children younger thn 6 yers, GPs prescribed sthm mediction to 9.9% of children (95% CI, 3.5%-25.2%); in the older ge-group they prescribed sthm mediction to 5.8% of children (95% CI, 2.4%-13.4%). The correltion between the 2 ge-groups t the GP level ws 0.83, indicting tht GPs who tended to prescribe sthm mediction to young children more often lso tended to do so for older children. Assocition Between Child Chrcteristics nd Prescribing The next step ws to dd the child chrcteristics to the model (model 2). In this model the correltion between the vrinces for the 2 ge-groups t the GP level incresed to 0.89, but the unique vrinces were still signifi cntly different (χ 2 = 9.5). Model 2 lso shows tht the different complints nd disese dignoses were strongly relted to prescribing sthm mediction. Children with dignosed cute bronchitis/bronchiolitis were much more likely to receive sthm mediction thn ws the verge child (OR = 9.04; 95% CI, ), s were children experiencing shortness of breth (OR = 20.7; 95% CI, ), wheezing (OR = 51.5; 95% CI, ), or cough (OR = 6.51; 95% CI, ). The number of ntibiotic prescriptions, the number of orl corticosteroid prescriptions, nd referrls were no longer signifi cntly ssocited with prescribing sthm mediction in the multivrite nlyses. Although children younger thn 6 yers were more frequently prescribed sthm mediction, no significnt ge interctions were found for sex of the child or ny of the dignoses. From the intercept in model 2, we see tht when correcting for child chrcteristics, young children no longer hd higher chnce of receiving sthm mediction thn older children. 36
6 Tble 4. GP Chrcteristics nd Results From the Univrite Anlyses GP Chrcteristics GPs Prescribing Asthm Mediction Averge nd Below Averge (n = 58) GPs Prescribing Asthm Mediction Above Averge (n = 51) OR (95% CI) Men ge (SD; rnge), y 47.6 (5.7; 36-59) 46.2 (6.2; 33-56) 1.00 ( ) Sex, mle, No. (%) 50 (86.2) 37 (72.6) 0.83 ( ) Prctice type, solo, No. (%) 27 (46.6) 20 (39.2) 0.88 ( ) Urbn prctice loction, men (SD; rnge) b 2.8 (1.4;1-5) 3.1 (1.0;1-5) 1.03 ( ) Men FTE (SD; rnge) c 0.91 (0.15; ) 0.88 (0.17; ) 0.79 ( ) Dispensing doctor, No. (%) d 5 (8.6) 3 (5.9) 0.97 ( ) Worklod, men (SD; rnge) e 2.8 (0.7; ) 2.6 (0.6; ) 0.89 ( ) Prescribing volume, men (SD; rnge) f 1.5 (0.5; ) 1.8 (0.5; ) 1.55 g ( ) 25% of ptients 0-17 y, No. (%) h 15 (25.9) 6 (11.8) 0.77 g ( ) Children with n sthm dignosis, % (SD; rnge) 3.5 (1.4; ) 5.4 (2.1; ) 1.10 g ( ) CI = confidence intervl GP = generl prctitioner; FTE = full-time equivlent; OR = odds rtio. To disply the GP chrcteristics, we divided the GPs into 2 groups: those who prescribed sthm medicton to the verge percentge of children or less, nd those who prescribed bove verge (which, on the GP level, is 7.4%) within their childhood ptient popultion. b As clssified by Sttistics Netherlnds on 5-point scle, in which 1 = high level of urbnizton nd 5 = low urbniztion. c Full-time or prt-time working in number of FTEs. d Authorized or required by the Helth Authority to provide phrmceuticl services to his/her ptients. e Totl number of ptients divided by the number of FTEs per 1,000 ptients. f Averge number of prescriptions issued per ptient during 1 yer. g Significnt vlues P <.05. h GPs with 25% or more of their totl ptient popultion of children ged 0-17 yers. Tking Into Account the Fmily nd GP Chrcteristics Model 3 is the fi nl model nd includes both the fmily nd the GP chrcteristics. On the fmily level prentl sthm ws the only vrible signifi cntly correlted with prescribing sthm mediction in the univrite nlyses (Tble 3), nd this ssocition ws sustined in the multivrite model, where we djusted for sthm dignosis of the child (OR = 1.74; 95% CI, ). Adding fmily nd GP chrcteristics did not hve signifi cnt impct on the ssocitions of the child s chrcteristics. This fi nl model shows tht in older children bout one-hlf of the unexplined vrince t the 2 upper levels occurs t the GP level, nd the other one-hlf occurs t the fmily level (intrclss correltion = 0.51). In younger children, however, the intrclss correltion ws 0.64; thus, more of the unexplined vrince lies on the GP level in this ge-group. Further nlysis of the GP chrcteristics showed tht GPs who prescribe more mediction in generl (the verge number of prescriptions per ptient per GP) prescribe more sthm mediction s well (OR = 1.99; 95% CI, ). GPs who serve reltively lrge childhood ptient popultion (GPs for whom more thn 25% of their totl ptient popultion consisted of children) were less likely to prescribe sthm mediction to the verge child (OR = 0.59; 95% CI, ) s were GPs who hd higher percentge of children dignosed with sthm within their ptient popultion (OR = 0.88; 95% CI, ). DISCUSSION Our results show tht substntil number of children received sthm mediction during the 1-yer study period (7.3%). Through studying the infl uence of the child, fmily, nd GP chrcteristics simultneously in multilevel fshion, we were identifi ed chrcteristics t ll 3 levels tht were signifi cntly ssocited with prescribing sthm mediction. Compring 2 Age-Groups Bsed on the ssumption tht dignosis of sthm cn be mde with more certinty from the ge of 6 yers nd onwrd, we expected to fi nd more differences mong GPs when prescribing sthm medictions to children younger thn 6 yers thn when prescribing to older children. Indeed, we found tht the vrince in prescribing mong GPs ws much higher with young children thn with children ged 6 yers nd older. Only smll prt of the difference in prescribing between these 2 ge ctegories could be ttributed to differences in the chrcteristics of the child. Our fi ndings re in line with the current gp in the dignosis of sthm prticulrly in preschool children, 6,23,24 despite the ongoing serch for better dignostics. Such gp provides mple opportunity for interphysicin vri- 37
7 nce in prescribing sthm medictions bsed on personl preferences nd prescribing ttitudes in generl. Relted to this spect ws the fi nding tht the overll mediction prescribing volume of the GP ws positively ssocited with prescribing sthm medictions irrespective of complints nd illnesses of the child. Fmily Influence We lso found tht fmily infl uence on prescribing sthm mediction to children ws substntil. These fi ndings re in line with reports of genetic infl uence on disese susceptibility, 8 helth-seeking behvior, 7,25 nd the ttitude of the cregivers or prents regrding mediction use. 26 In our study, we found tht prentl sthm ws positively ssocited with prescribing sthm medictions. Since guidelines concerning sthm tretment stte tht prentl sthm sttus should be tken into ccount when evluting sthmtic symptoms in children, 9-11 this fi nding is not unexpected. Moreover, we found tht every dditionl contct with the GP renders 10% incresed chnce of receiving sthm mediction, indicting tht helthseeking behvior of the fmily hs relevnt impct on the tretment of the child. Tble 5. Multilevel Logistic Regression Anlyses With 3 Levels: Child, Fmily, nd Generl Prctitioner (GP) Explntory Vribles Empty Model Intercept (SE) Model 1 Intercept (SE) Model 2,b Intercept (SE) Model 3,b Intercept (SE) Age 1-17 y (0.039) Age 1-5 y (0.054) (0.100) (0.091) Age 6-17 y (0.039) (0.071) (0.060) OR (95% CI) OR (95% CI) Sex, mle 1.25 ( ) 1.25 ( ) Shortness of breth/dyspne 20.7 ( ) 20.2 ( ) Wheezing 51.5 ( ) 49.7 ( ) Cough 6.51 ( ) 6.46 ( ) Acute bronchitis/bronchiolitis 9.04 ( ) 8.91 ( ) Acute upper respirtory trct infection 1.47 ( ) 1.47 ( ) Pneumoni 2.10 ( ) 2.11 ( ) Allergic rhinitis 2.12 ( ) 2.10 ( ) No. of contcts with GP 1.10 ( ) 1.10 ( ) Presence of prentl sthm 1.74 ( ) Prescribing volume of GP 1.99 ( ) Ptients 0-17 y 25% per GP 0.59 ( ) Percentge of children with sthm dignosis per GP 0.88 ( ) Vrince (SE) c Vrince (SE) Vrince (SE) Vrince (SE) Between-fmily vrince (0.071) (0.071) (0.112) (0.111) Between-GP vrince Age 1-17 y (0.022) Age 1-5 y (0.042) (0.134) (0.106) Age 6-17 y (0.022) (0.071) (0.047) Covrince (0.025) (0.083) (0.058) Correltions Correltions Correltions Correltions Correltion of GP vrince between ge-groups d Intrclss correltion e Age 1-17 y 0.17 Age 1-5 y Age 6-17 y CI = confidence intervl; GP = generl prctitioner; OR = odds rtio; SE = stndrd error. Model 1 (ge-groups), model 2 (ge-groups, child chrcteristics), model 3 (ge-groups, child chrcteristics, fmily chrcteristics, GP chrcteristics). b In these models we corrected for the presence of n sthm dignosis in the child (model 2: OR = 262; 95% CI, ; model 3: OR = 264; 95% CI, ). c The vrince t the lowest level (children) is not determined becuse the outcome is dichotomous. d Correltion between the vrinces of the 2 defined ge-groups on the GP level. e ICC between the 2 upper levels (fmilies nd GPs). ICC is the reltive contribution of GP to sum of fmily nd GP vrince. 38
8 Respirtory Morbidities Other Thn Asthm As expected, we found tht dignosis of sthm nd typicl sthmtic complints, such s wheezing, were strongly ssocited with prescribing sthm mediction. Our dt, however, showed tht sthm mediction ws used to tret not only sthm nd sthmtic complints but lso other respirtory morbidities, such s cute bronchitis nd cute upper respirtory trct infections. These fi ndings re similr to fi ndings from other studies showing discrepncy between sthm mediction use nd sthm dignosis, 15,16 nd they could indicte off-lbel use nd overtretment. Studies evluting the effectiveness of sthm mediction for indictions other thn sthm re inconclusive The ssocition between the child being mle nd receiving prescription for sthm mediction is in line with previous fi ndings. 14,31 Becuse none of the disese nd complints dignoses showed signifi cnt interction with ge, we cn conclude tht GPs do not regrd certin complints or illnesses s more or less importnt t young ge thn t n older ge when it comes to prescribing sthm mediction. Limittions of the Study The current study hs some limittions. First, the time reltionship between the event of prescribing nd the mesurement of the independent vribles ws not evluted. Also, we did not determine whether nd for how long use of sthm mediction ws continued. Second, the complints nd disese dignoses re not bsolute chrcteristics of the child; they re registered by the GP nd re the result of n interply between the child with certin complints nd the interprettion of the GP. Further, possible differences in disese severity re not expressed in these dichotomized vribles. Third, vribles vilble to chrcterize GPs nd fmilies were limited. Model 3 shows how much of the vrince is still unexplined fter introducing the vribles included in this model. Especilly t the two higher levels, but lso t the ptient level, one could think of chrcteristics not vilble in our study tht might be ssocited with prescribing sthm mediction to children, including culturl nd environmentl fctors (eg, prticulte mtter ir pollution, indoor climte). Strengths of the Study The strengths of this study re the gret number of children in our study popultion, the representtiveness of the smple, nd the dt bout dignosing nd prescribing derived directly from the GP s clinicl records. Furthermore, the wide rry of vribles tht might be ssocited with prescribing sthm mediction, which we hd vilble for multilevel nlysis, surpssed by fr tht of most vilble studies to dte. As result, we were ble to identify importnt fctors ssocited with prescribing sthm mediction to children nd their independent contribution to the vrince in prescribing. The reltively lrge vrinces found t the GP nd fmily level indicte substntil infl uence of both GP nd fmily on prescribing sthm mediction. As consequence, substntil smple size of GPs nd fmilies will be required to cross-vlidte these fi ndings elsewhere. In conclusion, our study showed tht ll 3 evluted prties (ptient, fmily, nd GP) hve signifi cnt infl uence on whether children re given prescription for sthm mediction. At the level of the child we found tht prescribing sthm mediction ws strongly relted not only to sthm nd sthmtic symptoms but lso to mny other respirtory diseses. Furthermore, helth-seeking behvior, prentl sthm, nd the ttitude nd experience of the GP seemed to be ssocited with prescribing sthm medictions to children. We found much higher vrince mong GPs when prescribing to children younger thn 6 yers compred with older children, which we consider to be result of the dignostic complexities especilly present in preschool children with sthmtic symptoms. Dignostics uncertinties my result in more physicin- nd fmilydriven prescribing irrespective of the clinicl context, feture not lwys in the interest of the child. To red or post commentries in response to this rticle, see it online t Key words: Asthm/child; sthm/child, preschool; fmily prctice; professionl prctice; multilevel; phrmcoepidemiology; prescribing Submitted Februry 27, 2008; submitted, revised, June 11, 2008; ccepted June 24, Funding support: This study ws prtly funded by the Ntionl Institute for Public Helth nd the Environment (RIVM) nd the Division of Phrmcoepidemiology & Phrmcotherpy, Utrecht University, Utrecht, Amsterdm. References 1. Msoli M, Fbin D, Holt S, Besley R. The globl burden of sthm: executive summry of the GINA Dissemintion Committee report. Allergy. 2004;59(5): O Connell EJ. The burden of topy nd sthm in children. Allergy. 2004;59(Suppl 78): Pocket Guide for Asthm Mngement nd Prevention in Children, Revised Globl Inititive for Asthm (GINA) Townshend J, Hils S, McKen M. Dignosis of sthm in children. BMJ. 2007;335(7612): Townshend J, Hils S, McKen M. Mngement of sthm in children. BMJ. 2007;335(7613): Bchrier LB, Boner A, Crlsen KH, et l. Dignosis nd tretment of sthm in childhood: PRACTALL consensus report. Allergy. 2008;63(1):
9 7. Crdol M, Groenewegen PP, de Bkker DH, Spreeuwenberg P, vn Dijk L, vn den Bosch W. Shred help seeking behviour within fmilies: retrospective cohort study. BMJ. 2005;330(7496): vn Beijsterveldt CE, Boomsm DI. Genetics of prentlly reported sthm, eczem nd rhinitis in 5-yr-old twins. Eur Respir J. 2007;29(3): Globl Strtegy for Asthm Mngement nd Prevention. Globl Inititive for Asthm (GINA) British Thorcic Society. British Guideline on the Mngement of Asthm. A Ntionl Clinicl Guideline. Revised ed. Scottish Intercollegite Guidelines Network; Ntionl Hert, Lung, nd Blood Institute. Expert Pnel Report 3: Guidelines for the Dignosis nd Mngement of Asthm, Ntionl Asthm Eduction nd Prevention Progrm Clvenn A, Rossi E, Berti A, Pedrzzi G, De Ros M, Bonti M. Inpproprite use of nti-sthmtic drugs in the Itlin peditric popultion. Eur J Clin Phrmcol. 2003;59(7): Goodmn DC, Lozno P, Stukel TA, Chng C, Hecht J. Hs sthm mediction use in children become more frequent, more pproprite, or both? Peditrics. 1999;104(2 Pt 1): Beimfohr C, Mzik W, von Mutius E, et l. The use of nti-sthmtic drugs in children: results of community-bsed survey in Germny. Phrmcoepidemiol Drug Sf. 2001;10(4): Stempel DA, Sphn JD, Stnford RH, Rosenzweig JR, McLughlin TP. The economic impct of children dispensed sthm medictions without n sthm dignosis. J Peditr. 2006;148(6): Yetts K, Dvis KJ, Sotir M, Herget C, Shy C. Who gets dignosed with sthm? Frequent wheeze mong dolescents with nd without dignosis of sthm. Peditrics. 2003;111(5 Pt 1): Zuidgeest MG, vn Dijk L, Smit HA, et l. Prescription of respirtory mediction without n sthm dignosis in children: popultion bsed study. BMC Helth Serv Res. 2008;8: Westert GP, Schellevis FG, de Bkker DH, Groenewegen PP, Bensing JM, vn der Zee J. Monitoring helth inequlities through generl prctice: the Second Dutch Ntionl Survey of Generl Prctice. Eur J Public Helth. 2005;15(1): Westert GP, Hoonhout LHF, De Bkker DH, Vn den Hoogen HJM, Schellevis FG. Huisrtsen met en zonder elektronisch medisch dossier: weinig verschil in medisch hndelen. Huisrts Wet. 2002;45: Westert GP, Jbij L, Schellevis FG. Morbidity, Performnce nd Qulity in Primry Cre. Dutch Generl Prctice on Stge. Oxford: Rdcliffe Publishing; Lmberts H, Wood M, Hofmns-Okkes I. The Interntionl Clssifiction of Primry Cre in the Europen Community. Oxford: Oxford University Press; Norwegin Institute of Public Helth. WHO Collborting Centre for Drug Sttistics Methodology. Antomicl Therpeutic Chemicl (ATC) Clssifiction Index Beydon N, Dvis SD, Lombrdi E, et l. An officil Americn Thorcic Society/Europen Respirtory Society sttement: pulmonry function testing in preschool children. Am J Respir Crit Cre Med. 2007;175(12): Bush A. Dignosis of sthm in children under five. Prim Cre Respir J. 2007;16(1): de Jong BM, vn der Ent CK, vn Putte Ktier N, et l. Determinnts of helth cre utiliztion for respirtory symptoms in the first yer of life. Med Cre. 2007;45(8): Bokhour BG, Cohn ES, Cortes DE, et l. Ptterns of concordnce nd non-concordnce with clinicin recommendtions nd prents explntory models in children with sthm. Ptient Educ Couns. 2008;70(3): Epub 2007 Dec Smucny J, Becker L, Glzier R. Bet2-gonists for cute bronchitis. Cochrne Dtbse Syst Rev. 2006;(4):CD Blom D, Ermers M, Bont L, vn Alderen WM, vn Woensel JB. Inhled corticosteroids during cute bronchiolitis in the prevention of post-bronchiolitic wheezing. Cochrne Dtbse Syst Rev. 2007;(1): CD Bisgrd H, Hermnsen MN, Lolnd L, Hlkjer LB, Buchvld F. Intermittent inhled corticosteroids in infnts with episodic wheezing. N Engl J Med. 2006;354(19): Chvsse R, Seddon P, Br A, McKen M. Short cting bet gonists for recurrent wheeze in children under 2 yers of ge. Cochrne Dtbse Syst Rev. 2002;(3):CD Wright AL, Stern DA, Kuffmnn F, Mrtinez FD. Fctors influencing gender differences in the dignosis nd tretment of sthm in childhood: the Tucson Children s Respirtory Study. Peditr Pulmonol. 2006;41(4):
XII. HIV/AIDS. Knowledge about HIV Transmission and Misconceptions about HIV
XII. HIV/AIDS Knowledge bout HIV Trnsmission nd Misconceptions bout HIV One of the most importnt prerequisites for reducing the rte of HIV infection is ccurte knowledge of how HIV is trnsmitted nd strtegies
More informationPNEUMOVAX 23 is recommended by the CDC for all your appropriate adult patients at increased risk for pneumococcal disease 1,2 :
PNEUMOVAX 23 is recommended y the CDC for ll your pproprite dult ptients t incresed risk for pneumococcl disese 1,2 : Adults ged
More informationInhaled Corticosteroid Is Associated With an Increased Risk of TB in Patients With COPD
CHEST Originl Reserch Inhled Corticosteroid Is Associted With n Incresed Risk of TB in Ptients With COPD Jung-Hyun Kim, MD ; Ji-Soo Prk, MD ; Kyung-Ho Kim, MD ; Hye-Cheol Jeong, MD ; Eun-Kyung Kim, MD
More informationkey words: chronic obstructive pulmonary disease, beta agonists, Medicare, health care costs, health care utilization
reserch report Helth Cre Use nd Costs Among Medicre Ptients With Chronic Obstructive Pulmonry Disese Treted With Short-Acting Bet Agonists or Long-Acting Bet Agonists Flvi Ejzykowicz, PhD; 1 Vmsi K Bollu,
More informationSupplementary Online Content
Supplementry Online Content Zulmn DM, Pl Chee C, Ezeji-Okoye SC, et l. Effect of n intensive outptient progrm to ugment primry cre for high-need Veterns Affirs ptients: rndomized clinicl tril. JAMA Intern
More informationCommunity. Profile Yellowstone County. Public Health and Safety Division
Community Helth Profile 2015 Yellowstone County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl
More informationCommunity. Profile Powell County. Public Health and Safety Division
Community Helth Profile 2015 Powell County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl Risk
More informationCommunity. Profile Lewis & Clark County. Public Health and Safety Division
Community Helth Profile 2015 Lewis & Clrk County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl
More informationCommunity. Profile Missoula County. Public Health and Safety Division
Community Helth Profile 2015 Missoul County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl Risk
More informationCommunity. Profile Big Horn County. Public Health and Safety Division
Community Helth Profile 2015 Big Horn County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl
More informationImpact of Pharmacist Intervention on Diabetes Patients in an Ambulatory Setting
Impct of Phrmcist Intervention on Dibetes Ptients in n Ambultory Setting Julie Stding, PhrmD, CDE, Jmie Herrmnn, PhrmD, Ryn Wlters, MS, Chris Destche, PhrmD, nd Aln Chock, PhrmD Dibetes is the seventh-leding
More informationCommunity. Profile Anaconda- Deer Lodge County. Public Health and Safety Division
Community Helth Profile 2015 Ancond- Deer Lodge County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12
More informationTrends in antihypertensive and lipidlowering therapy in subjects with type II diabetes: clinical effectiveness or clinical discretion?
ORIGINAL ARTICLE Trends in ntihypertensive nd lipidlowering therpy in subjects with type II dibetes: clinicl effectiveness or clinicl discretion? MC Gulliford, J Chrlton nd R Ltinovic Deprtment of Public
More informationOpioid Use and Survival at the End of Life: A Survey of a Hospice Population
532 Journl of Pin nd Symptom Mngement Vol. 32 No. 6 December 2006 NHPCO Originl Article Opioid Use nd Survivl t the End of Life: A Survey of Hospice Popultion Russell K. Portenoy, MD, Un Sibircev, BA,
More informationEpidemiological survey and analysis of asthma in children aged 0-14 years old in urban and rural areas of Chengdu region
Originl Article Epidemiologicl survey nd nlysis of sthm in children ged 0-14 yers old in urbn nd rurl res of Chengdu region Min Li 1, Qiong Zhng 2, Wei-Jun Shi 2, Ln Li 1, Yn Li 2, Ying Png 1, Bin Yo 1,
More informationInvasive Pneumococcal Disease Quarterly Report. July September 2017
Invsive Pneumococcl Disese Qurterly Report July September 2017 Prepred s prt of Ministry of Helth contrct for scientific services by Rebekh Roos Helen Heffernn October 2017 Acknowledgements This report
More informationUtilization of dental services in Southern China. Lo, ECM; Lin, HC; Wang, ZJ; Wong, MCM; Schwarz, E
Title Utiliztion of dentl services in Southern Chin Author(s) Lo, ECM; Lin, HC; Wng, ZJ; Wong, MCM; Schwrz, E Cittion Journl Of Dentl Reserch, 2001, v. 80 n. 5, p. 1471-1474 Issued Dte 2001 URL http://hdl.hndle.net/10722/53200
More informationInhaled Corticosteroids and the Risk of Pneumonia in People With Asthma
CHEST Originl Reserch Inhled Corticosteroids nd the Risk of Pneumoni in People With Asthm A Cse-Control Study Trici McKeever, PhD ; Timothy W. Hrrison, MD ; Richrd Hubbrd, MD ; nd Dominick Shw, MD ASTHMA
More informationOut-of-hours primary care: a population-based study of the diagnostic scope of telephone contacts
Fmily Prctice, 2016, Vol. 33, No. 5, 504 509 doi:10.1093/fmpr/cmw048 Advnce Access publiction 21 June 2016 Helth Service Reserch Out-of-hours primry cre: popultion-bsed study of the dignostic scope of
More informationFat intake in patients newly diagnosed with type 2 diabetes: a 4-year follow-up study in general practice
Originl ppers Ft intke in ptients newly dignosed with type 2 dibetes: 4-yer follow-up study in generl prctice Floris A vn de Lr, Eloy H vn de Lisdonk, Peter L B J Lucssen, J M H Tigchelr, Sski Meyboom,
More informationEstimated Prevalence and Economic Burden of Severe, Uncontrolled Asthma in the United States
Estimted Prevlence nd Economic Burden of Severe, Uncontrolled Asthm in the United Sttes Cheryl S. Hnkin 1 ; Amy Bronstone 1 ; Zhohui Wng 1 ; Mry Butti-Smll 2 ; Philip O. Buck 2 1 BioMedEcon, Moss Bech,
More informationThe Quality and Outcomes Framework (QOF) is a pay-for-performance
Effect of UK Py-for-Performnce Progrm on Ethnic Disprities in Dibetes Outcomes: Interrupted Time Series Anlysis Riydh Alshmsn, MSc John Tyu Lee, MSc Azeem Mjeed, MD Goplkrishnn Netuveli, PhD Christopher
More informationRecall Bias in Childhood Atopic Diseases Among Adults in The Odense Adolescence Cohort Study
Syddnsk Universitet Recll Bis in Childhood Atopic Diseses Among Adults in The Odense Adolescence Cohort Study Mørtz, Chrlotte G; Andersen, Klus Ejner; Bindslev-Jensen, Crsten Published in: Act Dermto-Venereologic
More informationCheckMate 153: Randomized Results of Continuous vs 1-Year Fixed-Duration Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer
CheckMte 53: Rndomized Results of Continuous vs -Yer Fixed-Durtion Nivolumb in Ptients With Advnced Non-Smll Cell Lung Cncer Abstrct 297O Spigel DR, McCleod M, Hussein MA, Wterhouse DM, Einhorn L, Horn
More informationCommunity. Profile Carter County. Public Health and Safety Division
Community Helth Profile 2015 Crter County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl Risk
More informationFactors influencing help seeking in mentally distressed young adults: a cross-sectional survey
L Biddle, D Gunnell, D Shrp nd J L Donovn Fctors influencing help seeking in mentlly distressed young dults: cross-sectionl survey Lucy Biddle, Dvid Gunnell, Debbie Shrp nd Jenny L Donovn SUMMARY Bckground:
More informationAssessment of Depression in Multiple Sclerosis. Validity of Including Somatic Items on the Beck Depression Inventory II
Assessment of Depression in Multiple Sclerosis Vlidity of Including Somtic Items on the Beck Depression Inventory II Peggy Crwford, PhD; Noh J. Webster, MA Signs nd symptoms of multiple sclerosis (MS)
More informationResearch Article Patterns of Cancer Genetic Testing: A Randomized Survey of Oregon Clinicians
Hindwi Publishing Corportion Journl of Cncer Epidemiology Volume 2012, Article ID 294730, 11 pges doi:10.1155/2012/294730 Reserch Article Ptterns of Cncer Genetic Testing: A Rndomized Survey of Oregon
More informationChronic obstructive pulmonary disease (COPD) is the third
METHODS Clims-Bsed Risk Model for First Severe COPD Excerbtion Richrd H. Stnford, PhrmD, MS; Arpit Ng, PhD, MBA, MS; Dougls W. Mpel, MD; Todd A. Lee, PhD; Richrd Rosiello, MD; Michel Schtz, MD; Frncis
More informationMetabolic Syndrome and Health-related Quality of Life in Obese Individuals Seeking Weight Reduction
Metbolic Syndrome nd Helth-relted Qulity of Life in Obese Individuls Seeking Weight Reduction Adm Gilden Tsi 1, Thoms A. Wdden 1, Dvid B. Srwer 1, Robert I. Berkowitz 1, Leslie G. Womble 1, Louise A. Hesson
More informationHealth-Related Quality of Life and Symptoms of Depression in Extremely Obese Persons Seeking Bariatric Surgery
Oesity Surgery, 15, 3-39 Helth-Relted Qulity of Life nd Symptoms of Depression in Extremely Oese Persons Seeking Britric Surgery Anthony N. Frictore, PhD; Thoms A. Wdden, PhD; Dvid B. Srwer, PhD; Myles
More informationClinical Study Report Synopsis Drug Substance Naloxegol Study Code D3820C00018 Edition Number 1 Date 01 February 2013 EudraCT Number
EudrCT Number 2012-001531-31 A Phse I, Rndomised, Open-lbel, 3-wy Cross-over Study in Helthy Volunteers to Demonstrte the Bioequivlence of the Nloxegol 25 mg Commercil nd Phse III Formultions nd to Assess
More informationUS Food and Drug Administration-Mandated Trials of Long-Acting b -Agonists Safety in Asthma. Samy Suissa, PhD ; and Amnon Ariel, MD, FCCP
CHEST Commentry US Food nd Drug Administrtion-Mndted Trils of Long-Acting b -Agonists Sfety in Asthm Will We Know the Answer? Smy Suiss, PhD ; nd Amnon Ariel, MD, FCCP For 2 decdes, long-cting b -gonists
More informationUniversity of Groningen
University of Groningen Qulity of life in children with undignosed nd dignosed sthm vn Gent, R.; vn Essen, L.E.; Rovers, M.M.; Kimpen, J.L.; vn der Ent, C.K.; de Meer, G. Published in: Europen Journl of
More informationWill All Americans Become Overweight or Obese? Estimating the Progression and Cost of the US Obesity Epidemic
nture publishing group rticles Will All s Become Overweight or Obese? Estimting the Progression nd Cost of the US Obesity Epidemic Youf Wng 1, My A. Beydoun 1, Ln Ling 2, Benjmin Cbllero 1 nd Shiriki K.
More informationClinical statistics analysis on the characteristics of pneumoconiosis of Chinese miner population
Originl Article Clinicl sttistics nlysis on the chrcteristics of pneumoconiosis of Chinese miner popultion Mei-Fng Wng 1 *, Run-Ze Li 2 *, Ying Li 2, Xue-Qin Cheng 1, Jun Yng 1, Wen Chen 3, Xing-Xing Fn
More informationAddendum to the Evidence Review Group Report on Aripiprazole for the treatment of schizophrenia in adolescents (aged years)
Addendum to the Evidence Review Group Report on Aripiprzole for the tretment of schizophreni in dolescents (ged 15-17 yers) Produced by Authors Correspondence to Southmpton Helth Technology Assessments
More informationSummary. Effect evaluation of the Rehabilitation of Drug-Addicted Offenders Act (SOV)
Summry Effect evlution of the Rehbilittion of Drug-Addicted Offenders Act (SOV) The Rehbilittion of Drug-Addicted Offenders Act (SOV) ws lunched on April first 2001. This lw permitted the compulsory plcement
More informationENERGY CONTENT OF BARLEY
ENERGY CONTENT OF BARLEY VARIATION IN THE DIETARY ENERGY CONTENT OF BARLEY Shwn Firbirn, John Ptience, Hnk Clssen nd Ruurd Zijlstr SUMMARY Formultion of commercil pig diets requires n incresing degree
More informationOriginal Article. T Akter 1, N Islam 2, MA Hoque 3, S Khanam 4, HA khan 5, BK Saha 6. Abstract:
Fridpur Med. Coll. J. 214;9(2):61-67 Originl Article Nebuliztion by Isotonic Mgnesium Sulphte Solution with Provide Erly nd Better Response s Compred to Conventionl Approch ( Plus Norml Sline) in Acute
More informationImpact of GP reminders on follow-up of abnormal cervical cytology:
Reserch Bettin Kjær Kristinsen, Berit Andersen, Flemming Bro, Hns Svnholm nd Peter Vedsted Impct of GP reminders on follow-up of bnorml cervicl cytology: before fter study in Dnish generl prctice Abstrct
More informationDiabetes affects 29 million Americans, imposing a substantial
CLINICAL Comprtive Effectiveness nd Costs of Insulin Pump Therpy for Dibetes Ronld T. Ackermnn, MD, MPH; Amish Wlli, MD, MS; Rymond Kng, MA; Andrew Cooper, MPH; Theodore A. Prospect, FSA, MAAA; Lewis G.
More informationMetformin and breast cancer stage at diagnosis: a population-based study
ORIGINAL ARTICLE METFORMIN AND BREAST CANCER STAGE AT DIAGNOSIS, Leg et l. Metformin nd brest cncer stge t dignosis: popultion-bsed study I.C. Leg md msc,* K. Fung msc,* P.C. Austin phd, nd L.L. Lipscombe
More informationEffectiveness of Belt Positioning Booster Seats: An Updated Assessment
ARTICLES Effectiveness of Belt Positioning Booster Sets: An Updted Assessment AUTHORS: Kristy B. Arbogst, PhD, Jessic S. Jermkin, DSc, Michel J. Klln, MS, b nd Dennis R. Durbin, MD, MSCE,b Center for Injury
More informationGeographical influence on digit ratio (2D:4D): a case study of Andoni and Ikwerre ethnic groups in Niger delta, Nigeria.
Journl of Applied Biosciences 27: 1736-1741 ISSN 1997 5902 Geogrphicl influence on digit rtio (2D:4D): cse study of Andoni nd Ikwerre ethnic groups in Niger delt, Nigeri. Gwunirem, Isrel U 1 nd Ihemelndu,
More informationAbstract. Background. Aim. Patients and Methods. Patients. Study Design
Impct of the Use of Drugs nd Substitution Tretments on the Antivirl Tretment of Chronic Heptitis C: Anlysis of Complince, Virologicl Response nd Qulity of Life (CHEOBS). Melin, 1 J.-. Lng, D. Ouzn, 3 M.
More informationDid introduction of pneumococcal vaccines in the Netherlands decrease the need for respiratory antibiotics in children? Analysis of 2002 to 2013 data
Reserch rticles Did introduction of pneumococcl vccines in the Netherlnds decrese the need for respirtory ntibiotics in children? Anlysis of 2002 to 2013 dt G Gefenite (g.gefenite@lumnus.rug.nl) 1,2, M
More informationURINARY incontinence is an important and common
Urinry incontinence in older people in the community: neglected problem? Helen Stoddrt, Jenny Donovn, Elise Whitley, Deborh Shrp nd In Hrvey SUMMARY Bckground: The prevlence nd impct of urinry incontinence
More informationWork-related musculoskeletal disorders (WMSDs) among nursing personnel
Work-Relted Musculoskeletl Injuries nd Disorders Among Occuptionl nd Physicl Therpists Amy R. Drrgh, Wendy Huddleston, Phyllis King KEY WORDS ccidents, occuptionl moving nd lifting ptients musculoskeletl
More informationEpilepsy & Behavior 20 (2011) Contents lists available at ScienceDirect. Epilepsy & Behavior. journal homepage:
Epilepsy & Behvior 20 (2011) 52 56 Contents lists vilble t ScienceDirect Epilepsy & Behvior journl homepge: www.elsevier.com/locte/yebeh Detecting helth disprities mong Cucsins nd Africn-Americns with
More informationMany authors have recognized the lack of continuity in cancer
Fmily Physicin Involvement in Cncer Cre Follow-up: The Experience of Cohort of Ptients With Lung Cncer Michèle Aubin, MD, PhD, CCFP, FCFP 1,2,3,4 Lucie Vézin, MA 4 René Verreult, MD, PhD, FCFP, CCFP 1,5
More informationMay 28, Congressional Requesters
United Sttes Government Accountbility Office Wshington, DC 20548 My 28, 2010 Congressionl Requesters Subject: Federl Funds: Fiscl Yers 2002-2009 Obligtions, Disbursements, nd Expenditures for Selected
More informationBMI and Mortality: Results From a National Longitudinal Study of Canadian Adults
nture publishing group BMI nd Mortlity: Results From Ntionl Longitudinl Study of Cndin Adults Hether M. Orpn 1, Jen-Mrie Berthelot 2,3, Mrk S. Kpln 4, Dvid H. Feeny 5,6, Bentson McFrlnd 7 nd Nncy A. Ross
More informationBody mass index, waist-to-hip ratio, and metabolic syndrome as predictors of middle-aged men's health
Originl Article - Sexul Dysfunction/Infertility pissn 2005-6737 eissn 2005-6745 Body mss index, wist-to-hip rtio, nd metbolic syndrome s predictors of middle-ged men's helth Jung Hyun Prk *, In-Chng Cho
More informationCourse of Skin Symptoms and Quality of Life in Children Referred for Patch Testing A Long-term Follow-up Study
Act Derm Venereol 2015; 95: 206 210 CLINICAL REPORT Course of Skin Symptoms nd Qulity of Life in Children Referred for Ptch Testing A Long-term Follow-up Study Anne B. SIMONSEN 1, Mette SOMMERLUND 1, Mette
More informationAppendix J Environmental Justice Populations
Appendix J Environmentl Justice s [This pge intentionlly left blnk] Tble of Contents REFERENCES...J-2 Pge LIST OF TABLES Pge Tble J-1: Demogrphic Overview of Bruinsburg Site Project Are... J-3 Tble J-2:
More informationThe diagnosis of autism and Asperger syndrome: findings from a survey of 770 families
The dignosis of utism nd Asperger syndrome: findings from survey of 770 fmilies Ptrici Howlin*, Deprtment of Psychology, St George s Hospitl Medicl School, London; Ann Asghrin, Deprtment of Psychology,
More informationImpact of Positive Nodal Metastases in Patients with Thymic Carcinoma and Thymic Neuroendocrine Tumors
Originl Article Impct of Positive Nodl Metstses in Ptients with Thymic Crcinom nd Thymic Neuroendocrine Tumors Benny Weksler, MD, Anthony Holden, MD, nd Jennifer L. Sullivn, MD Introduction: Thymic crcinoms
More informationComputer-Aided Learning in Insulin Pump Training
Journl of Dibetes Science nd Technology Volume 4, Issue 4, July 2010 Dibetes Technology Society TECHNOLOGY REPORTS Computer-Aided Lerning in Insulin Pump Trining Sergey V., M.Sc., 1 nd Chrles J. George,
More informationHuman Immunodeficiency Virus / Acquired Immunodeficiency Syndrome Knowledge and Risk Factors in Ethiopian Military Personnel
MILITARY MEDICINE, 169, 3:221, 2004 Humn Immunodeficiency Virus / Acquired Immunodeficiency Syndrome Knowledge nd Risk Fctors in Ethiopin Militry Personnel Gurntor: Ludmil N. Bkhirev, MD MPH Contributors:
More informationDietary Characteristics of Hong Kong Young Children: Implications for Nutrition Education
HK J Peditr (new series) 2006;11:255-262 Dietry Chrcteristics of Hong Kong Young Children: Implictions for Nutrition Eduction LL HUI, EAS NELSON Abstrct Key words Objectives: To exmine the dietry pttern
More informationManagement and Outcomes of Binge-Eating Disorder in Adults: Current State of the Evidence
Clinicin Summry Mentl Helth Eting Disorders Mngement nd Outcomes of Binge-Eting Disorder in Adults: Current Stte of the Evidence Focus of This Summry This is summry of systemtic review evluting the evidence
More informationReducing the Risk. Logic Model
Reducing the Risk Logic Model ETR (Eduction, Trining nd Reserch) is nonprofit orgniztion committed to providing science-bsed innovtive solutions in helth nd eduction designed to chieve trnsformtive chnge
More informationA cross-sectional and follow-up study of leukopenia in tuberculosis patients: prevalence, risk factors and impact of anti-tuberculosis
Originl Article A cross-sectionl nd follow-up study of leukopeni in tuberculosis ptients: prevlence, risk fctors nd impct of nti-tuberculosis tretment Fei-Shen Lin 1 *, Mei-Ying Wu 2 *, Wen-Jun Tu 3, Hong-Qiu
More information3.3 Verotoxigenic E. coli
3.3 Verotoxigenic E. coli Summry Number of VTEC cses, 215: 73 Crude incidence rte, 215: 15.9/1, Number of VTEC-ssocited HUS, 215: 22 Number of VTEC cses, 214: 77 Introduction For mny yers, Irelnd hs the
More informationUniversity of Texas Health Science Center, San Antonio, San Antonio, Texas, USA
Lung Cncer Chemotherpy Given Ner the End of Life by Community Oncologists for Advnced Non-Smll Cell Lung Cncer Jose R. Murillo, Jr., Jim Koeller b,c Methodist Hospitl, Houston, Texs, USA; b University
More informationLongitudinal Association of Maternal Attempt to Lose Weight During the Postpartum Period and Child Obesity at Age 3 Years
nture publishing group Longitudinl Assocition of Mternl Attempt to Lose Weight During the Postprtum Period nd Child Obesity t Age 3 Yers Kendrin R. Sonneville 1,2, Sheryl L. Rifs-Shimn 3, Emily Oken 3,
More informationMultiple sclerosis (MS) affects approximately. Triaging Patients with Multiple Sclerosis in the Emergency Department. Room for Improvement
Systemtic Review of Tools for Anxiety in MS MS CARE DELIVERY: CHALLENGES AND INVATIONS Triging Ptients with Multiple Sclerosis in the Emergency Deprtment Room for Improvement Heshm Abboud, MD, PhD; Krin
More informationStaffing Model for Dental Wellness and Readiness
MILITARY MEDICINE, 169, 8:604, 2004 Stffing Model for Dentl Wellness nd Rediness Gurntor: LTC Jeffrey Chffin, DC USA Contributors: COL Lrry G. Rothfuss, DC USA* ; LCDR Scott A. Johnson, NC USN* ; MAJ Stephen
More informationTeacher motivational strategies and student self-determination in physical education
Loughborough University Institutionl Repository Techer motivtionl strtegies nd student self-determintion in physicl eduction This item ws submitted to Loughborough University's Institutionl Repository
More informationSupplementary Online Content
Supplementry Online Content Rieckmnn N, Kronish IM, Shpiro PA, Whng W, Dvidson KW. Serotonin reuptke inhibitor use, depression, nd long-term outcomes fter n cute coronry : prospective cohort study. JAMA
More informationCough: impact, beliefs, and expectations from a national survey
Dl Negro et l. Multidisciplinry Respirtory Medicine (2016) 11:34 DOI 10.1186/s40248-016-0072-1 ORIGINAL RESEARCH ARTICLE Open Access Cough: impct, eliefs, nd expecttions from ntionl survey Roerto W. Dl
More informationOverweight can be used as a tool to guide case-finding for cardiovascular risk assessment
Fmily Prctice, 2015, Vol. 32, No. 6, 646 651 doi:10.1093/fmpr/cmv080 Advnce Access publiction 17 October 2015 Helth Service Reserch Overweight cn be used s tool to guide cse-finding for crdiovsculr risk
More informationSingle-Molecule Studies of Unlabelled Full-Length p53 Protein Binding to DNA
Single-Molecule Studies of Unlbelled Full-Length p53 Protein Binding to DNA Philipp Nuttll, 1 Kidn Lee, 2 Pietro Ciccrell, 3 Mrco Crminti, 3 Giorgio Ferrri, 3 Ki- Bum Kim, 2 Tim Albrecht 1* 1 Imperil College
More informationDiabetes is a chronic and highly prevalent condition that
Mediction Adherence nd Improved Outcomes Among Ptients With Type 2 Dibetes Srh E. Curtis, MPH; Kristin S. Boye, PhD; Mureen J. Lge, PhD; nd Luis-Emilio Grci-Perez, MD, PhD Dibetes is chronic nd highly
More informationPrevalence, Correlates and Characteristics of Chronic Pruritus: A Population-based Cross-sectional Study
Act Derm Venereol 2011; 91: 674 679 INVESTIGATIVE REPORT Prevlence, Correltes nd Chrcteristics of Chronic Pruritus: A Popultion-bsed Cross-sectionl Study Uwe Mtterne 1, Christin J. Apfelbcher 1, Adrin
More informationOutcome and severity of adult onset asthma Report from the obstructive lung disease in northern Sweden studies (OLIN)
Respirtory Medicine (2007) 101, 2370 2377 Outcome nd severity of dult onset sthm Report from the obstructive lung disese in northern Sweden studies (OLIN) Ev Rönmrk,b,, Anne Lindberg, Louise Wtson c, Bo
More informationHypertension, hyperinsulinaemia and obesity in middle-aged Finns with impaired glucose tolerance
Journl of Humn Hypertension (1998) 12, 265 269 1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 ORIGINAL ARTICLE Hypertension, hyperinsulinemi nd obesity in middle-ged Finns with impired glucose
More informationRelationship Between Hospital Performance on a Patient Satisfaction Survey and Surgical Quality
Reserch Originl Investigtion Reltionship Between Hospitl Performnce on Ptient Stisfction Survey nd Surgicl Qulity Greg D. Scks, MD, MPH; Elise H. Lwson, MD, MSHS; Aron J. Dwes, MD; Mrci M. Russell, MD;
More informationRisks for All-Cause Mortality: Stratified by Age, Estimated Glomerular Filtration Rate and Albuminuria
Clinicl Prctice: Mini-Review Received: My 20, 2016 Accepted fter revision: December 14, 2016 Published online: Jnury 27, 2017 Risks for All-Cuse Mortlity: Strtified by Age, Estimted Glomerulr Filtrtion
More informationFertility in Norwegian testicular cancer patients
DOI: 0.054/ bjoc.999.0989, vilble online t http://www.idelibrry.com on Fertility in Norwegin testiculr cncer ptients SD Fosså nd Ø Krvdl 2 The Norwegin Rdium Hospitl, Montebello, N-030 Oslo, Norwy; 2 The
More informationInadequate health literacy is a
Testing the BRIEF Helth Litercy Screening Tool Jolie Hun, PhD, Virgini Nolnd-Dodd, PhD, MPH, Jill Vrnes, EdD, John Grhm-Pole, MD, Brbr Rienzo, PhD, nd Ptrici Donldson, RN Due to the oppressive strins lid
More informationT.S. Kurki a, *,U.Häkkinen b, J. Lauharanta c,j.rämö d, M. Leijala c
Europen Journl of Crdio-thorcic Surgery 20 (2001) 1183 1187 www.elsevier.com/locte/ejcts Evlution of the reltionship between preopertive risk scores, postopertive nd totl length of stys nd hospitl costs
More informationRisk factors for testicular germ cell tumours by histological tumour type
Article no. bjoc.1999.0611 Risk fctors for testiculr germ cell tumours by histologicl tumour type CAC Couplnd 1, CED Chilvers 1, G Dvey 2, MC Pike 3, RTD Oliver 4 nd D Formn 2 on behlf of the United Kingdom
More informationWater fl uoridation and dental caries in 5- and 12-year-old children from Canterbury and Wellington
18 10 NEW ZEALAND DENTAL JOURNAL MARCH 004 Wter fl uoridtion nd dentl cries in 5- nd 1-yer-old children from Cnterbury nd Wellington MARTIN LEE AND PETER J DENNISON New Zelnd Dentl Journl 100, No. 1: 10-15;
More informationInput from external experts and manufacturer on the 2 nd draft project plan Stool DNA testing for early detection of colorectal cancer
Input externl experts nd mnufcturer on the 2 nd drft project pln Stool DNA testing for erly detection of colorectl cncer (Project ID:OTJA10) All s nd uthor s replies on the 2nd drft project pln Stool DNA
More informationPhysicians prescribing a new medication often fail to discuss basic. Intervention to Enhance Communication About Newly Prescribed Medications
to Enhnce Communiction About Newly Prescribed Medictions Derjung M. Trn, MD, PhD 1 Debor A. Pterniti, PhD 2 Deborh K. Orosz, BA 3 Chi-Hong Tseng, PhD 4 Neil S. Wenger, MD, MPH 4 1 Deprtment of Fmily Medicine,
More informationBright Futures Medical Screening Reference Table 2 to 5 Day (First Week) Visit
Bright Futures Medicl Reference Tle 2 to 5 Dy (First Week) Visit Universl Action Metolic nd Verify documenttion of neworn metolic screening results, pproprite rescreening, nd needed follow-up. Document
More informationTime trends in repeated spirometry in children
Eur Resplr J 199, 6, 55:H559 Time trends in repeted spirometry in children G. Hoek*t, B. Brunekreef* Time trends in repeted spirometry in children. G. Hoek, B. Brunekreef. BSTRCT: In study on cute helth
More informationProstate cancer is among the most common malignancies
Implictions of Evolving Delivery System Reforms for Prostte Cncer Cre Brent K. Hollenbeck, MD, MS; Mggie J. Bierlein, MS; Smuel R. Kufmn, MS; Lindsey Herrel, MD; Ted A. Skolrus, MD, MPH; Dvid C. Miller,
More informationReport of the Conference on Low Blood
1046 Report of the Conference on Low Blood Cholesterol: Mortlity Associtions Dvid Jcobs, PhD; Henry Blckburn, MD; Millicent Higgins, MD; Dwyne Reed, MD, PhD; Hiroysu Iso, MD; Grdner McMilln, MD, PhD; Jmes
More informationA Four-System Comparison of Patients With Chronic Illness: The Military Health System, Veterans Health Administration, Medicaid, and Commercial Plans
MILITARY MEDICINE, 174, 9:936, 2009 A Four-System Comprison of Ptients With Chronic Illness: The Militry Helth System, Veterns Helth Administrtion, Medicid, nd Commercil Plns Teres B. Gibson, PhD * ; Todd
More informationReports of cases of AIDS, HIV infection, and HIV/AIDS 1
Reports of cses of AIDS, HIV infection, nd HIV/AIDS 1 The HIV/AIDS Surveillnce Report is published nnully by the Division of HIV/AIDS Prevention Surveillnce nd Epidemiology, Ntionl Center for HIV, STD,
More informationEffect on Glycemic, Blood Pressure, and Lipid Control according to Education Types
Originl Article http://dx.doi.org/10.4093/dmj.2011.35.6.580 pissn 2233-6079 eissn 2233-6087 D I A B E T E S & M E T A B O L I S M J O U R N A L Effect on Glycemic, Blood Pressure, nd Lipid Control ccording
More informationMortality of patients with multiple sclerosis: a cohort study in UK primary care
Mortlity of ptients with multiple sclerosis: cohort study in UK primry cre The Hrvrd community hs mde this rticle openly vilble. Plese shre how this ccess benefits you. Your story mtters Cittion Jick,
More informationEthnic Disparities in Stroke Recognition in Individuals with Prior Stroke
Reserch Articles Ethnic Disprities in Stroke Recognition in Individuls with Prior Stroke Chrles Ellis, PhD Leonrd E. Egede, MD, MS,c SYNOPSIS Ojective. Studies of stroke wreness suggest tht knowledge of
More informationDifferent type 2 diabetes risk assessments predict dissimilar numbers at high risk :
Reserch Benjmin J Gry, Richrd M Brcken, Dniel Turner, Kerry Morgn, Michel Thoms, Slly P Willims, Meurig Willims, Sm Rice nd Jeffrey W Stephens on behlf of the Prosiect Sir Gâr Group Different type 2 dibetes
More informationEXPOSURE TO EXCESSIVE SOUNDS AND HEARING STATUS IN ACADEMIC CLASSICAL MUSIC STUDENTS
Interntionl Journl of Occuptionl Medicine nd Environmentl Helth 2017;30(1):55 75 https://doi.org/10.13075/ijomeh.1896.00709 EXPOSURE TO EXCESSIVE SOUNDS AND HEARING STATUS IN ACADEMIC CLASSICAL MUSIC STUDENTS
More information