MEDICATIONS PRESCRIPTION AT HOSPITAL DISCHARGE IN PATIENTS WITH VALIDATED DIAGNOSIS OF DEMENTIA Federica Edith Pisa University Hospital Udine
BACKGROUND Polypharmacy and psychotropic medication use are very common in elderly patients with dementia [Bohlken J et al, 2015; Barry H et al, 2016; Walsh KA et al, 2016; Schmed N et al, 2016] 64.4% prevalence of potentially inappropriate prescribing [Barry H et al, 2016] Antipsychotics off-label for neuropsychiatric symptoms are discouraged by international guidelines Increased risk of severe adverse events and death [Ray WA et al, 2009; Wang PS et al 2005; Trifiro G et al, 2010 ]
Drug utilization studies based on registry [Johnell K et al, 2013] or claims data [Bohlken J et al, 2015; Barry H et al, 2016] Focus on community-dwelling patients, on the long-term care or primary care setting [Sultana J et al, 2016; Barry H et al, 2016] In hospitalized elderly, dementia associated with a 2-fold increased risk of antipsychotic initiation [Herzig SJ et al, 2016] and with high prevalence of psychotropic polypharmacy [Walsh KA et al, 2016]
Many validation studies of codes/algorithms for identifying health outcomes in health databases in Europe [Schmidt M et al, 2015; Ludvigsson J et al, 2011; Jick S et al, 2002] Dementia: o based on medical chart review [van de Vorst et al, 2015; Phung et al, 2007; Pippenger et al, 2001 USA] o based on clinical diagnosis in cohort studies [Jin et al, 2004; Solomon, 2014]
OBJECTIVES To validate discharge codes used to identify cases of dementia in an hospitalization database In patients with a confirmed diagnosis of dementia, to describe the pattern of medication: o used at hospital admission o prescribed at discharge o dispensed after discharge
This study was conducted at the University Hospital of Udine, Friuli Venezia Giulia region (FVG), Italy FVG Regional Health Services Databases with anonymized individuallevel linkable information on the use of health care resources FVG regional Ethics Committee approval FVG Region (1.2 million population)
Data sources FVG Health Databases ohospital Services METHODS ooutpatient Prescriptions (dispensing) opatient Identification (demographic and vital information) Electronic Medical Records EMR o clinical data on in- and out-patient medical care encounters
Study population any hospitalization from 1 January 2012 to 31 December 2014 at the University Hospital of Udine with primary or secondary ICD-9-CM discharge code for dementia dementia ICD-9-CM code senile 290.0, 290.2, 290.3 presenile 290.1 vascular 290.4 degenerative 290.9 alcohol persistent 291.2 drug persistent 292.82 in other diseases/ unspecified 294.1, 294.2, 294.8 frontotemporal 331.1, 331.19 Lewy body 331.82 Jakob-Creutzfeldt disease 046.1 Alzheimer s disease 331.0 general paresis 094.1 Pick s disease 331.11
Validation EMR review Gold standard: diagnosis of dementia and/or moderate-severe cognitive impairment written by treating physician or neurologist/psychiatrist Not confirmed cases: mild cognitive impairment, other diagnosis, wrong code Review and abstraction by two trained MDs Final case confirmation independently by two research epidemiologists
Data abstraction From EMR opatient demographic characteristics odischarge diagnosis written by treating physician odiagnosis written by consultant neurologist/psychiatrist oneurological / psychiatric comorbidities oother comorbidities odate of onset of dementia (when available) odischarging division omedications registered at admission (agent, formulation, dose) omedications prescribed at discharge (agent, formulation, dose)
Data abstraction From Health Databases o all prescriptions from January 1st, 2002 to December 31, 2015 o residential history (emigration from FVG) o date and cause of death up to December 31, 2015 (end of study period)
Study design Retrospective cohort study Any patient with confirmed diagnosis of dementia Follow-up for prescriptions dispensed o from date of discharge of the 1st hospitalization with confirmed diagnosis (index hospitalization) o to the earliest of the following dates: death emigration / disenrollment from regional health system 1 year after index hospitalization December 31, 2015 (end of study period)
Statistical analysis Positive Predictive Value (PPV), with 95% confidence interval (95%CI), as the ratio of hospitalizations with confirmed diagnosis to those with potential diagnosis number and distribution of selected medications prescribed at discharge in patients with confirmed dementia SAS software, version 9.3 (SAS, Cary, NC, USA)
RESULTS Table 1. Positive Predictive Value (PPV) for dementia, with 95% Confidence Interval (95%CI), ICD-9-CM primary and secondary diagnosis code. N of records Type of confirmation (written diagnosis) codes for dementia with EMR confirmed diagnosis N (%) N (%) N EMR retrieval % PPV 95%CI by discharging physician dementia 1168 0.40 0.38-0.41 cognitive impairment 1 1200 0.41 0.39-0.42 3104 (100.0) 2951 (100.0) 95.1 dementia / cognitive impairment 2368 0.80 0.79-0.82 by discharging physician / neurologist dementia / cognitive impairment 2500 0.85 0.83-0.86 code position primary 505 (16.3) 480 (16.3) 390 95.0 0.81 0.78-0.85 1 moderate-severe. any secondary 2599 (83.7) 2471 (83.7) 2110 95.1 0.85 0.84-0.87
Table 2. Positive Predictive Value (PPV) for dementia, with 95% Confidence Interval (95%CI), ICD-9-CM primary and secondary diagnosis code. By patient demographic characteristics and discharging division. age (years) sex with EMR (N= 2951) N of records confirmed diagnosis (N= 2500) PPV 95%CI N (%) N (%) <85 1341 (45.4) 1106 (44.2) 0.82 0.80-0.84 85 + 1610 (54.6) 1394 (55.8) 0.87 0.85-0.88 Women 1885 (63.9) 1612 (64.5) 0.86 0.84-0.87 Men 1066 (36.1) 888 (35.5) 0.83 0.81-0.85 discharging division neurology 271 (9.2) 209 (8.4) 0.77 0.72-0.82 surgery 216 (7.3) 186 (7.4) 0.86 0.81-0.91 medicine 2464 (83.5) 2105 (84.2) 0.85 0.84-0.87
Table 3. Positive Predictive Value (PPV), with 95% Confidence Interval (95%CI), ICD-9-CM primary and secondary diagnosis code. By type of dementia. type of dementia (ICD-9-CM code) senile (290.0; 290.2; 290.3) codes for dementia (N= 3104) N of records with EMR (N= 2591) confirmed diagnosis (N= 2500) N (%) N (%) N (%) EMR retrieval % PPV 95%CI overall 1436 (46.3) 1342 (51.8) 1161 (46.4) 93.5 0.87 0.85-0.88 primary position 169 (5.4) 158 (6.1) 126 (5.0) 93.5 0.80 0.73-0.86 secondary position 1267 (40.8) 1184 (45.7) 1035 (41.4) 93.4 0.87 0.85-0.89 vascular (290.4) overall 1205 (38.8) 1170 (45.2) 953 (38.1) 97.1 0.81 0.79-0.84 primary position 170 (5.5) 166 (6.4) 142 (5.7) 97.6 0.86 0.80-0.91 secondary position 1035 (33.3) 1004 (38.7) 811 (32.4) 97.0 0.81 0.78-0.83 presenile (290.1) overall 172 (5.5) 169 (6.5) 135 (5.4) 98.3 0.80 0.74-0.86 primary position 73 (2.3) 72 (2.8) 45 (1.8) 98.6 0.63 0.51-0.74 secondary position 99 (3.2) 97 (3.7) 90 (3.6) 98.0 0.93 0.88-0.98 Alzheimer s disease (331.0) overall 187 (6.0) 170 (6.6) 168 (6.7) 90.9 0.99 0.97-1.00 primary position 23 (0.7) 21 (0.8) 21 (0.8) 91.3 1.00 1.00-1.00 secondary position 164 (5.3) 149 (5.7) 147 (5.9) 90.9 0.99 0.97-1.00
561 patients had 1 hospitalization 1939 patients had confirmed diagnosis of dementia 254 (13.1%) patients died during in-hospital stay
Table 4. Number and distribution of patients with validated diagnosis of dementia by selected covariates. (N= 1685) N (%) age (years) <65 56 (3.3) 65-74 171 (10.1) 75-84 569 (33.8) 85+ 889 (52.8) sex female 1085 (64.4) male 600 (35.6) type of dementia (ICD-9-CM code) presenile (290.1) 105 (6.2) senile (290.0; 290.2; 290.3) 761 (45.2) vascular (290.4) 625 (37.1) Alzheimer s disease (331.0) 103 (6.1) other 1 91 (5.4) psychiatric comorbidity depression 204 (12.1) psychosis 35 (2.1) other 142 (8.4) total 381 (22.6) medications at discharge (N) 1 to 3 381 (22.6) 4 to 6 651 (38.6) 7 or more 653 (38.7) discharging division neurology 180 (10.7) surgery 165 (9.8) medicine 1340 (79.5) 1 Includes: alcohol persistent dementia (291.2), drug persistent dementia (292.82), dementia in other diseases/ unspecified (294.1, 294.2, 294.8), frontotemporal dementia (331.1, 331.19), Lewy body dementia (331.82), Jakob-Creutzfeldt disease (046.1), general paresis (094.1), degenerative dementia (290.9), Pick s disease (331.11).
Table 5. Psychotropic medication prescribed at discharge in patients with validated diagnosis of dementia. Antipsychotics (N05A) (N= 684; 40.6%) Antidepressants (N06A) (N= 337; 20.0%) Anti-dementia agents (N06D) (N= 242; 14.4%) Anxiolytics (N05B) (N= 136; 8.1%) Hypnotics and sedatives (N05C) (N= 70; 4.1%) age (years) N (%) N (%) N (%) N (%) N (%) <65 16 (2.3) 11 (3.3) 15 (6.2) 6 (4.4) 2 (2.9) 65-74 70 (10.2) 55 (16.3) 55 (22.7) 22 (16.2) 7 (10.0) 75-84 234 (34.2) 138 (40.9) 108 (44.6) 56 (41.2) 30 (42.9) 85+ 364 (53.2) 133 (39.5) 64 (26.4) 52 (38.2) 31 (44.3) sex female 427 (62.4) 235 (69.7) 140 (57.9) 97 (71.3) 47 (67.1) male 257 (37.6) 102 (30.3) 102 (42.1) 39 (28.7) 23 (32.9) type of dementia (ICD-9-CM code) presenile (290.1) 38 (5.6) 27 (8.0) 29 (12.0) 13 (9.6) 4 (5.7) senile (290.0; 290.2; 290.3) 312 (45.6) 149 (44.2) 110 (45.5) 59 (43.4) 37 (52.9) vascular (290.4) 240 (35.1) 114 (33.8) 49 (20.2) 52 (38.2) 22 (31.4) Alzheimer s disease (331.0) 48 (7.0) 26 (7.7) 41 (16.9) 7 (5.1) 4 (5.7) other 1 46 (6.7) 21 (6.2) 13 (5.4) 5 (3.7) 3 (4.3) prior psychiatric morbidity depression 87 (12.7) 102 (30.3) 58 (24.0) 17 (12.5) 13 (18.6) psychosis 22 (3.2) 11 (3.3) 3 (1.2) 6 (4.4) 1 (1.4) other 58 (8.5) 50 (14.8) 22 (9.1) 26 (19.1) 16 (22.9) total 167 (24.4) 163 (48.4) 83 (34.3) 49 (36.0) 30 (42.9) discharging division neurology 62 (9.1) 67 (19.9) 66 (27.3) 12 (8.8) 12 (17.1) surgery 85 (12.4) 41 (12.2) 39 (16.1) 17 (12.5) 11 (15.7) medicine 537 (78.5) 229 (68.0) 137 (56.6) 107 (78.7) 47 (67.1)
STRENGHTS AND LIMITATIONS Strengths EMR retrieval almost complete Linkage with outpatient prescriptions dispensing data Limitations 1 University Hospital No data on laboratory and imaging examinations No indication of prescriptions Medication at admission registered by nurses from available medical documentation or caregivers reports
CONCLUSIONS Pisa, 2016 (N= 2951) van de Vorst, 2015 (N= 340) 1 Phung, 2007 (N= 200) 1 Pippenger, 2001 (N= 240) 1 Dementia type PPV PPV PPV PPV Overall 85 93.2 96.9 76.9 Senile 87 - - 88.9 Presenile 80 - - 94.4 Vascular 81 91.3 96.3 - Alzheimer s disease 99 100.0 96.5 97.7 1 Random sample of records.
Validation of codes Setting- and study- specific factors: o local coding practices, coding purpose, attitudes and knowledge by local physicians o differences in study design (e.g. set of codes includes) o background prevalence PPV for Alzheimer s disease very high, consistently with prior research [van de Vorst, 2015; Phung, 2007; Pippenger, 2001] PPV higher in older patients, consistently with prior research [van de Vorst, 2015]
Prescriptions at discharge Anti-dementia agents o 14.4%, lower than in other studies [Bohlken J et al, 2015; Johnell K et al, 2013] o 39.8% (41/103) in Alzheimer s Disease, (a) consistently recommended by guidelines and (b) reimbursed in Italy Antidepressants o 69.7% women, consistently with previous research [Bohlken J et al, 2015]
Prescribing at discharge Antipsychotics o 40.6%, higher than in other studies [Bohlken J et al, 2015; Johnell K et al, 2013] o 30% prevalence in dementia in Italy in 2012 from GPs data [Sultana J et al, ICPE 2016]
COMMENTS The results will help us profiling true cases of dementia to develop identification algorithms Analysis of prescriptions dispensed after discharge o GPs confirm prescriptions at discharge and patients redeem prescribed medications o the use of antipsychotics is short-term as recommended
ACKNOWLEDGMENTS Prof. Giancarlo Logroscino, Neurodegenerative Disease Unit, Department of Neurosciences and Sense Organs, University of Bari, for insightful comments and suggestions. Dr. Francesca Palese and dr. Federico Romanese, collaborators
Thank you for your attention
BACK UP SLIDES
Validation strategies and case definition criteria in selected validation studies of hospital discharge codes for Dementia source for confirmation first author, year of publication gold standard coding system dementia type (codes) medical records review clinical diagnoses from cohort study van de Vorst, 2015 Phung, 2007 Pippenger, 2001 Solomon, 2014 Jin, 2004 diagnosis written by physician diagnosis written by physician diagnosis written by physician in-person cognitive tests + neuropsychological examinations screening interview + clinical evaluation ICD-9 senile (290.0, 290.3), presenile (290.1), vascular (290.4), Alzheimer D (331.0), frontotemporal (331.1), Lewy bodies (331.82), D classified elsewhere (294.1) ICD-10 Alzheimer D (F00.0, F00.1, F00.2, F00.9, G30.0, G30.1, G30.8, G30.9), vascular (F01.0, F01.1, F01.2, F01.3, F01.8, F01.9), frontotemporal (F02.0), without specification (F03.9) ICD-9 unspecified psychosis (298.9), presenile (290.1), vascular (290.4), senile (290.0, 290.2, 290.3), other organic brain syndrome (294.8), D classified elsewhere (294.1), Alzheimer D (331.0), encephalopathy (348.3), obstructive hydrocephalus (331.4), Pick s disease (331.1), other general symptoms (780.9) ICD-8 senile and presenile (290), presenile (290.10) ICD-9 dementia (290), alcohol persistent dementia (291.2), drug-induced mental disorders (292.8), dementia in other diseases (294.1), Alzheimer D (331.0), frontotemporal (331.1), other cerebrovascular disease (437.8) ICD-10 Alzheimer D (F00, G30), vascular (F01), classified elsewhere (F02), unspecified (F03), delirium superimposed (F05.1), alcohol persistent (F10.73), drug persistent (F11.73, F14.73, F16.73, F18.73, F19.73) ICD-8 Senile (290), presenile, Alzheimer D, Pick s disease, Jakob-Creutzfeldt disease with D (290.1), cerebral arteriosclerosis (293.0) ICD-9 dementia (290), due to secondary causes (294), Alzheimer D (331.0) ICD-10 Alzheimer D (F00.0, F00.1, F00.2, F00.9, G30.0, G30.1, G30.8, G30.9), Lewy bodies (G318), localized cerebral atrophy (G31.0), vascular (F01.0, F01.1, F01.2, F01.3, F01.8, F01.9), Pick s disease (F02.0), Creutzfeldt-Jakob disease (F02.1), Parkinson s disease (F02.3), classified elsewhere (F02.8), unspecified (F03.9), delirium superimposed (F05.1)
Author, year of publication Country N subjects results Solomon et al, 2014 Finland 1972-98: 1403 1998-2008: 846 1972-2008: 744 1972-98: PPV 57.1 (18.4-90.1); Se 7.3 (2.0-17.6); 1998-2008: PPV 17.7 (9.2-29.5); Se 84.6 (54.6-98.1); 1972-2008: PPV 13.7 (5.7-26.3); Se 87.5 (47.3-99.7) Jin et al, 2004 Sweden 1243 Se 43.3%; Sp 98.05%; PPV 88.53%; NPV 98.05%
Validation studies of hospital discharge codes for dementia based on medical charts review Dementia type 1 Random sample of records. Alzheimer s disease PPV sample Overall Senile Presenile Vascular Author (publication year) Country size 1 PPV PPV PPV PPV van de Vorst et al (2015) the Netherlands 340 93.2 - - 91.3 100 Phung et al (2007) Denmark 200 96.9 - - 96.3 96.5 Pippenger et al (2001) USA 240 76.9 88.9 94.4-97.7
Doblhammer G et al, 2015 Trends in dementia prevalence Claims data from a German public health insurance company Validation procedure in 3 incremental steps: 1. outpatient services: only diagnoses verified by physician inpatient services: only discharge and secondary diagnoses 2. only diagnoses with a second occurrence during the same period, e.g. diagnoses by different physicians (neurologist/psychiatrist and GP or other specialist) or concurrent diagnoses in the inpatient and outpatient services 3. insured with a dementia diagnosis followed over a moving validation period of 3 years, 2007 to 2009, only those with 2 dementia diagnoses were considered as valid cases
Chodosh J et al, 2004 Survey of physicians and review of medical records in HMO, California. Physicians (N= 365) correctly identified 81% of patients with dementia and 44% of patients with mild cognitive impairment Medical records documented cognitive impairment in 83% of patients with dementia and 26% of patients with cognitive impairment Geriatricians recognized cognitive impairment more often vs. non geriatricians Medical record documentation reflects physician recognition of dementia
Dahl A et al, 2007 N= 498 elderly cohort twin study (Gender), Sweden Follow-up 8 years Comparison of identification of dementia in cohort and medical records Review of medical records: sensitivity 57%, specificity 99%, kappa 0.65 Accuracy of medical records increased when recordings of cognitive impairment were included: sensitivity 83%, specificity 98%, kappa 0.84
Validation of codes PPV 77% discharges from neurology division: accurate diagnosis in clinical documentation, but not in coding PPV 81% primary codes: in-hospital delirium how accurate is the gold standard? o errors in reporting o dementia not diagnosed
Antipsychotics used at admission and prescribed at discharge. Patients with validated diagnosis of dementia. users at admission (N= 299) 1 prescribed at discharge (N= 684) antipsychotic agent N % 2 N % 3 atypical quetiapine 162 54.2 359 52.5 olanzapine 6 2.0 12 1.8 risperidone 6 2.0 10 1.5 clotiapine 2 0.7 7 1.0 clozapine 2 0.7 1 0.1 levosulpiride 12 4.0 23 3.4 tiapride 4 1.3 4 0.6 more than one atypical 4 1.3 12 1.8 subtotal atypical 190 63.4 404 59.1 typical promazine 85 28.4 203 29.7 haloperidol 56 18.7 174 25.4 zuclopenthixol 3 1.0 7 1.0 perphenazine 4 1.3 1 0.1 chlorpromazine 2 0.7 1 0.1 more than one typical 3 1.0 18 2.6 subtotal typical 147 49.2 368 53.8 1 Includes 38 users who died in hospital. 2 Percentages may not sum up to 100% because some subjects were prescribed more than one agent, in particular 38 subjects were prescribed both typical and atypical agents. 3 Percentages may not sum up to 100% because some subjects were prescribed more than one agent, in particular 88 subjects were prescribed both typical and atypical agents.
Antipsychotics mostly atypical, consistently with prior research [Bohlken J et al, 2015; Barry H et al, 2016; Walsh KA et al, 2016; Schmed N et al, 2016]
Linkage with outpatient prescription dispensing database - at the subject-level through individual unique identifier - data on prescription redeemed are registered continuously from 2000 - linkage almost complete (97.6%), not feasible for 46 (2.4%) patients with confirmed dementia
Not confirmed 451 records 23 repeated hospitalizations 423 patients 396 discharged alive
Number and distribution of patients with not confirmed diagnosis of dementia by selected covariates. N % age (years) <65 22 5.2 65-74 61 14.4 75-84 137 32.4 85+ 203 48.0 sex women 255 60.3 men 168 39.7 type of dementia (ICD-9-CM code) presenile dementia (2901) 33 7.8 senile dementia (2900, 2902, 2903) 167 39.5 vascular dementia (2904) 197 46.6 Alzheimer disease (3310) 2 0.5 other 1 24 5.7 psychiatric comorbidity depression 49 11.6 psychosis 6 1.4 other 56 13.2 discharging division neurology 60 14.2 surgery 25 5.9 medicine 335 79.2 1 Includes: alcohol persistent dementia (291.2), drug persistent dementia (292.82), dementia in other diseases/ unspecified (294.1, 294.2, 294.8), frontotemporal dementia (331.1, 331.19), Lewy body dementia (331.82), Jakob-Creutzfeldt disease (046.1), general paresis (094.1), degenerative dementia (290.9), Pick s disease (331.11).
Psychotropic medication prescribed at discharge in patients with not confirmed diagnosis of dementia discharged alive (N= 396). N % antipsychotics 86 21.7 antidepressants 103 26.0 anti-dementia drugs 19 4.8 anxiolytics 38 9.6 hypnotics and sedatives 23 5.8