Longitudinal analysis of impulse control disorders in Parkinson s disease

Transcription

1 Corvol et l., Pge S1 Longitudinl nlysis of impulse control disorders in Prkinson s disese Jen-Christophe Corvol, MD, 1 Fnny Artud, PhD, 2 Florence Cormier-Dequire, MD, 1 Olivier Rscol, MD, 3 Frnck Durif, MD, 4 Pscl Derkinderen, MD, 5 An-Rquel Mrques, MD, 4 Frédéric Bourdin, MD, 6 Jen- Philippe Brndel, MD, 7 Fernndo Pico, MD, 8 Lucette Lcomblez, MD, 1 Cecili Bonnet, MD, 1 Christine Brefel-Courbon, MD, 3 Fbienne Ory-Mgne, MD, 3 Dvid Grbli, MD, 1 Stephn Klebe, MD, 1 Grziell Mngone, MD, 1 Hn You, MD, 1 Vlérie Mesnge, MD, 9 Pei-Chen Lee, PhD, 10 Alexis Brice, MD, 1 Mrie Vidilhet, MD, 1 Alexis Elbz, MD, 2 for the DIGPD study group Supplementry mteril e-methods Tble e-1. Assocition of levodop use with ICDs. Tble e-2. Assocition of other types of ntiprkinsonin drugs with ICDs. Tble e-3. Assocition between lterntive definitions of dopmine gonist use (described in Figure e- 1) nd ICDs. Tble e-4. Assocition of dopmine gonist use with ICDs; ICDs lso include hobbyism nd hypercretivity Figure e-1. Alterntive definitions of dopmine gonist use

2 Corvol et l., Pge S2 e-methods MDS-UPDRS Prt I: Non-Motor Aspects of Experiences of Dily Living (nm-edl) Item 1.6: Fetures of dopmine dysregultion syndrome Instructions to exminer: Consider involvement in vriety of ctivities including typicl or excessive gmbling (e.g. csinos or lottery tickets), typicl or excessive sexul drive or interests (e.g., unusul interest in pornogrphy, msturbtion, sexul demnds on prtner), other repetitive ctivities (e.g. hobbies, dismntling objects, sorting or orgnizing), or tking extr non-prescribed mediction for non-physicl resons (i.e., ddictive behvior). Rte the impct of such bnorml ctivities/behviors on the ptient s personl life nd on his fmily nd socil reltions (including need to borrow money or other finncil difficulties like withdrwl ofcredit crds, mjor fmily conflicts, lost time from work, or missed mels or sleep becuse of the ctivity). Instructions to ptients [nd cregiver]: Over the pst week, hve you hd unusully strong urges tht re hrd to control? Do you feel driven to do or think bout something nd find it hrd to stop? [Give ptient exmples such s gmbling, clening, using the computer, tking extr medicine, obsessing bout food or sex, ll depending on the ptients.] 0: Norml: No problems present. 1: Slight: Problems re present but usully do not cuse ny difficulties for the ptient or fmily/cregiver. 2: Mild: Problems re present nd usully cuse few difficulties in the ptient s personl nd fmily life. 3: Moderte: Problems re present nd usully cuse lot of difficulties in the ptient s personl nd fmily life. 4: Severe: Problems re present nd preclude the ptient s bility to crry out norml ctivities or socil interctions or to mintin previous stndrds in personl nd fmily life.

3 Tble e-1. Assocition of levodop use with ICDs. Corvol et l., Pge S3 In ll ptients In LD users Chrcteristics of LD use PR (95% CI) P QIC Pliner b Pspline c QIC PR (95% CI) P QIC Pliner b Pspline c QIC LD use in the pst 12 months Yes 1.23 (0.95, 1.58) < medin verge dily LED (250mg) d 1.24 (0.95, 1.60) 0.11 medin verge dily LED 1.18 (0.89, 1.57) Per SD of verge dily LED (244mg) 1.03 (0.94, 1.13) (0.92, 1.13) Ever LD use Yes 1.24 (0.96, 1.61) < medin verge dily LED (264mg) e 1.26 (0.96, 1.65) 0.10 medin verge dily LED 1.21 (0.92, 1.59) Per SD of verge dily LED (163mg) 1.08 (0.99, 1.17) (0.97, 1.19) Cumultive durtion of LD use < medin (3.0y) 1.26 (0.97, 1.63) 0.09 medin 1.14 (0.84, 1.57) Per SD (2.1y) 0.94 (0.81, 1.09) (0.80, 1.13) Cumultive dose of LD (LED) < medin (247.2g) 1.24 (0.95, 1.61) 0.11 medin 1.30 (0.95, 1.78) Per SD (380.0g) 1.06 (0.94, 1.20) (0.97, 1.25) Averge lifetime dily LD dose + cumultive durtion of LD use Per SD of verge dily LED 1.10 (1.01, 1.20) (0.97, 1.21) Per SD of cumultive durtion 0.90 (0.76, 1.05) (0.77, 1.11) Abbrevitions: SD, stndrd devition; LD, levodop; LED, levodop equivlent dose; QIC, qusi-informtion criterion. Models re djusted for ge nd disese durtion t bseline (yers), sex, eduction, mritl sttus, cumultive dose of DA (time-dependent liner term), time since bseline (yers), time sex, nd time disese durtion. Prevlence rtios (PR), 95% confidence intervls (CI), nd P-vlues computed using Poisson generlized estimting equtions models with robust vrince. b Test of linerity: P liner 0.05 indicte significnt deprture from liner reltionship between the exposure nd ICDs, so tht splines provide better fit thn liner continuous term nd re ssocited with lower QIC. Non-significnt P liner-vlues indicte tht splines do not improve the model s fit. c Test of ssocition between splines nd ICDs nd corresponding QIC. These vlues re not reported if P liner>0.05. d Averge LED of LD over the pst 12 months. e Averge lifetime dily LED of LD.

4 Corvol et l., Pge S4 Tble e-2. Assocition of other types of ntiprkinsonin drugs with ICDs. Ever use PR (95% CI) P COMT inhibitors Yes 0.84 (0.69, 1.03) 0.10 Selegiline, rsgiline Yes 0.79 (0.62, 1.01) 0.06 Anticholinergics Yes 0.63 (0.37, 1.09) 0.10 Amntdine Yes 1.07 (0.79, 1.45) 0.64 Abbrevitions: SD, stndrd devition; DA, dopmine gonist; LED, levodop equivlent dose in milligrms; COMT, Ctechol-Omethyltrnsferse. Models re djusted for ge nd disese durtion t bseline (yers), sex, eduction, mritl sttus, ever LD use (time-dependent), verge lifetime dily DA dose (time-dependent), cumultive durtion of DA (timedependent), time since bseline (yers), time sex, nd time disese durtion. Prevlence rtios (PR), 95% confidence intervls (CI), nd P-vlues computed using Poisson generlized estimting equtions models with robust vrince.

5 Corvol et l., Pge S5 Tble e-3. Assocition between lterntive definitions of dopmine gonist use (described in Figure e-1) nd ICDs. In ll ptients In DA users Chrcteristics of DA use PR (95% CI) P QIC Pliner b Pspline c QIC PR (95% CI) P QIC Pliner b Pspline c QIC Ever DA use Yes 2.44 (1.70, 3.48) < < medin verge dily LED (181mg) d 2.36 (1.62, 3.43) <10-3 medin verge dily LED 2.58 (1.77, 3.76) < Per SD of verge dily LED (87mg) 1.29 (1.19, 1.41) < < (1.05, 1.32) Cumultive durtion < medin (3.4y) 2.29 (1.56, 3.34) <10-3 medin 2.80 (1.91, 4.09) < Per SD (2.1y) 1.42 (1.22, 1.65) < < (0.96, 1.47) Cumultive dose (LED) < medin (216.6g) 2.32 (1.59, 3.37) <10-3 medin 2.68 (1.83, 3.93) < Per SD (218.1g) 1.36 (1.22, 1.52) < < (1.07, 1.39) Averge lifetime dily DA dose + cumultive durtion of DA Per SD of verge dily LED 1.19 (1.07, 1.33) (0.98, 1.27) Per SD of cumultive durtion 1.24 (1.04, 1.48) (0.92, 1.45) Abbrevitions: SD, stndrd devition; DA, dopmine gonist; LED, levodop equivlent dose; QIC, qusi-informtion criterion. Models re djusted for ge nd disese durtion t bseline (yers), sex, eduction, mritl sttus, ever LD use (time-dependent), time since bseline (yers), time sex, nd time disese durtion. Prevlence rtios (PR), 95% confidence intervls (CI), nd P-vlues computed using Poisson generlized estimting equtions models with robust vrince. b Test of linerity: P liner 0.05 indicte significnt deprture from liner reltionship between the exposure nd ICDs; in tht cse, splines provide better fit thn liner continuous term nd re ssocited with lower QIC. Non-significnt P liner-vlues indicte tht splines do not improve the model s fit. c Test of ssocition between splines nd ICDs nd corresponding QIC. These vlues re not reported if P liner>0.05. d Averge lifetime dily LED of DA.

6 Tble e-4. Assocition of dopmine gonist use with ICDs; ICDs lso include hobbyism nd hyper-cretivity. Corvol et l., Pge S6 In ll ptients In DA users Chrcteristics of DA use PR (95% CI) P QIC Pliner b Pspline c QIC PR (95% CI) P QIC Pliner b Pspline c QIC DA use in the pst 12 months Yes 2.12 (1.52, 2.95) < < medin verge dily LED (165mg) d 1.93 (1.35, 2.75) <10-3 medin verge dily LED 2.53 (1.78, 3.59) < Per SD of verge dily LED (104mg) 1.25 (1.16, 1.35) < < (1.07, 1.27) < Ever DA use Yes 3.69 (1.82, 7.46) < < medin verge dily LED (176mg) e 3.45 (1.65, 7.20) medin verge dily LED 4.34 (2.12, 8.88) < Per SD of verge dily LED (86mg) 1.30 (1.20, 1.42) < < (1.07, 1.30) Cumultive durtion < medin (3.2y) 3.64 (1.75, 7.55) medin 4.13 (2.04, 8.35) < Per SD (2.1y) 1.56 (1.33, 1.84) < < (1.15, 1.66) < Cumultive dose (LED) < medin (193.8g) 3.57 (1.70, 7.49) medin 4.41 (2.16, 9.01) < Per SD (217.5g) 1.37 (1.23, 1.53) < <10-3 < (1.16, 1.46) < Averge lifetime dily DA dose + cumultive durtion of DA Per SD of verge dily LED 1.22 (1.11, 1.34) < (1.03, 1.26) Per SD of cumultive durtion 1.41 (1.18, 1.68) < (1.10, 1.60) Abbrevitions: SD, stndrd devition; DA, dopmine gonist; LED, levodop equivlent dose; QIC, qusi-informtion criterion. Models re djusted for ge nd disese durtion t bseline (yers), sex, eduction, mritl sttus, ever LD use (time-dependent), time since bseline (yers), time sex, nd time disese durtion. Prevlence rtios (PR), 95% confidence intervls (CI), nd P-vlues computed using Poisson generlized estimting equtions models with robust vrince. b Test of linerity: P liner 0.05 indicte significnt deprture from liner reltionship between the exposure nd ICDs, in tht cse, splines provide better fit thn liner continuous term nd re ssocited with lower QIC. Non-significnt P liner-vlues indicte tht splines do not improve the model s fit. c Test of ssocition between splines nd ICDs nd corresponding QIC. These vlues re not reported if P liner>0.05. d Averge dily LED of DA over the pst 12 months. e Averge lifetime dily LED of DA.

7 Corvol et l., Pge S7 Figure e-1. Alterntive definitions of dopmine gonist use. Both definitions re bsed on n exmple of DA use over 5 yers in the sme ptient (Box A). This ptient ws prescribed DA for 1.5 yer t dose of 50mg/dy LED; the dose ws then incresed t 75mg/dy until yer 3, when DAs were discontinued before being prescribed gin for 6 months until the end of the follow-up t 100mg/dy. Box B shows the definitions used for the min nlysis; exposure vribles were updted over time nd where fixed t their lst vlue when DA were discontinued, so tht this ptient ws considered to be exposed fter discontinution. Box C presents n lterntive definition ccording to which the ptient ws considered to be no longer exposed fter DAs were discontinued (i.e., ll exposure vribles were set to 0).