Construction and validation of a morbidity index based on the International Classification of Primary Care.

OBJECTIVES: In epidemiological studies it is often necessary to describe morbidity. The aim of the present study is to construct and validate a morbidity index based on the International Classification of Primary Care (ICPC-2). DESIGN AND SETTING: This is a cohort study based on linked data from national registries. An ICPC morbidity index was constructed based on a list of longstanding health problems in earlier published Scottish data from general practice and adapted to diagnostic ICPC-2 codes recorded in Norwegian general practice 2015 - 2017. SUBJECTS: The index was constructed among Norwegian born people only (N = 4 509 382) and validated in a different population, foreign-born people living in Norway (N = 959 496). MAIN OUTCOME MEASURES: Predictive ability for death in 2018 in these populations was compared with the Charlson index. Multiple logistic regression was used to identify morbidities with the highest odds ratios (OR) for death and predictive ability for different combinations of morbidities was estimated by the area under receiver operating characteristic curves (AUC). RESULTS: An index based on 18 morbidities was found to be optimal, predicting mortality with an AUC of 0.78, slightly better than the Charlson index (AUC 0.77). External validation in a foreign-born population yielded an AUC of 0.76 for the ICPC morbidity index and 0.77 for the Charlson index. CONCLUSIONS: The ICPC morbidity index performs equal to the Charlson index and can be recommended for use in data materials collected in primary health care.Key pointsThis is the first morbidity index based on the International Classification of Primary Care, 2nd edition (ICPC-2)It predicted mortality equal to the Charlson index and validated acceptably in a different populationThe ICPC morbidity index can be used as an adjustment variable in epidemiological research in primary care databases.

Drug-related deaths: Statistics based on death certificates miss one-third of cases.

Aims: Statistics on drug-related deaths (DRD) provide crucial information on the drug situation. The European Monitoring Centre for Drug and Drug Addiction (EMCDDA) has published a specification for extracting DRD from national mortality registers to be used in international comparisons. However, surprisingly little is known of the accuracy of DRD statistics derived from national mortality registers. This study assesses the accuracy of Swedish data derived from national mortality registers by comparing it with other sources of data. Methods: We compared five Swedish datasets. Three were derived from national mortality registers, two according to a Swedish specification and one according to the EMCDDA specification. A fourth dataset was based on toxicological analyses. We used a fifth dataset, an inventory of DRD in Stockholm, to assess the completeness and coverage of the Swedish datasets. Results: All datasets were extracted from high-quality registers, but still did not capture all DRD, and both the numbers and demographic characteristics varied considerably. However, the time trends were consistent between the selections. In international comparisons, data completeness and investigation procedures may impact even more on stated numbers. Conclusions: Basing international comparisons on numbers or rates of DRDs gives misleading results, but comparing trends is still meaningful.

Positive predictive value of ICD-10 codes to detect anaphylaxis due to vaccination: A validation study.

PURPOSE: To validate the use of selected International Classification of Disease Codes 10th revision (ICD-10) to predict (positive predictive value) anaphylaxis due to vaccination using emergency department (ED) data. METHODS: We conducted a retrospective study using ED encounter data from a large tertiary-care teaching hospital, Monash Medical Centre, Melbourne, Australia. We searched all ED encounters potentially due to anaphylaxis after vaccination, between 1 January 2010 and 31 December 2018, using ICD-10-CM codes T80.5, T80.6, T88.1, T88.6, and T78.2. Health records of potential cases were examined to determine if they met the Brighton Collaboration (BC) criteria for anaphylaxis. We calculated the PPV to evaluate the accuracy of the selected ICD-10-CM codes in predicting anaphylaxis due to vaccination. RESULTS: Of the 69 health records identified and reviewed, 29 (42.2%) met the criteria for anaphylaxis regardless of the cause, and 24.6% (17/69) of records were confirmed as anaphylaxis triggered by vaccination (low positive predictive value). However, of the 23 records identified using ICD-10-CM code T80.5, 22 were classified as anaphylaxis cases regardless of the cause, and 12 were anaphylaxis due to vaccination cases giving PPV of 95.7% and 52.2%, respectively. CONCLUSIONS: Given that there is no specific ICD-10-CM code for anaphylaxis due to vaccination, ICD-10-CM code T80.5 may be suitable to monitor anaphylaxis due to vaccination in the ED setting. The current study was conducted at a single centre and needs to be confirmed by future multicentre studies.

Registration of Amyotrophic Lateral Sclerosis: Validity in the Danish National Patient Registry.

Purpose: Health care databases are a valuable source for epidemiological research on amyotrophic lateral sclerosis (ALS) if diagnosis codes are valid. We evaluated the validity of the diagnostic codes for ALS in the Danish National Patient Registry (DNPR). Patients and Methods: We obtained data from the DNPR for all adult (>17 years) patients registered with ALS in Denmark between 1987 and 2022 (median population of 4.2 million during the study period). We randomly selected adult patients living in the North Denmark Region and Central Denmark Region (median population 1.4 million), with a primary discharge diagnosis code of ALS, diagnosed at three departments of neurology. We retrieved and reviewed medical records and estimated the positive predictive value (PPV) of the ALS diagnosis. Results: Over 36 years, we identified 5679 patients. From the validation cohort of 300 patients, we were able to retrieve 240 (80%) medical records, and 215 ALS diagnoses were confirmed. The overall positive predictive value was 89.6% (95% confidence interval (CI): 85.1-92.8). The highest PPV was achieved for diagnoses registered for patients aged ≥70 years (93.8; 95% CI: 86.2-97.3) compared to patients <60 years (83.4; 95% CI: 73.3-90.7). Conclusion: We found a high PPV of primary diagnostic codes for ALS from Danish departments of neurology, demonstrating high validity. Thus, the DNPR is a well-suited data source for large-scale epidemiological research on ALS.

Usefulness of ICD-10 diagnosis triggers to identify adverse drug events in emergency care. / Utilidad de los diagnósticos alertantes CIE-10 para identificar acontecimientos adversos por los medicamentos en los servicios de urgencias.

OBJECTIVES: To assess the usefulness of a tool based on ICD-10 diagnostic codes to identify patients who consult an emergency department for adverse drug events (ADE). METHODS: Prospective observational study, in which patients discharged from an emergency department during May to August 2022 with a diagnosis coded with one of the 27 ICD-10 diagnoses considered as triggers were included. ADE confirmation was carried out by analyzing drugs prescribed prior to admission, and through a discussion among experts and a phone interview with patients after hospital discharge. RESULTS: 1,143 patients with trigger diagnoses were evaluated, of which 310 (27.1%) corresponded to patients whose emergency visit was attributed to an ADE. A 58.4% of ADE consultations were found with three diagnostic codes: K59.0-Constipation (n = 87; 28.1%), I16.9-Hypertensive Crisis (n = 72; 23.2%) and I95.1-Orthostatic hypotension (n = 22; 7.1%). The diagnoses with the highest degree of association with consultations attributed to ADE were E16.2-Hypoglycemia, unspecified (73.7%) and E11.65-Type 2 diabetes mellitus with hyperglycemia (71.4%), while diagnoses D62-Acute posthemorrhagic anemia and I74.3-Embolism and thrombosis of arteries of the lower limbs were not attributed to any case of ADE. CONCLUSIONS: The ICD-10 codes associated with trigger diagnoses are a useful tool to identify patients who consult the emergency services with ADE and could be used to apply secondary prevention programs to avoid new consultations to the health care system.

[Translated article] Usefulness of ICD-10 diagnostic triggers to identify adverse drug events in emergency care.

OBJECTIVES: To assess the usefulness of a tool based on ICD-10 diagnostic codes to identify patients who consult an emergency department for adverse drug events (ADE). METHODS: Prospective observational study, in which patients discharged from an emergency department during May to August 2022 with a diagnosis coded with one of the 27 ICD-10 diagnoses considered as triggers were included. ADE confirmation was carried out by analyzing drugs prescribed prior to admission, and through a discussion among experts and a phone interview with patients after hospital discharge. RESULTS: 1143 patients with trigger diagnoses were evaluated, of which 310 (27.1%) corresponded to patients whose emergency visit was attributed to an ADE. A 58.4% of ADE consultations were found with three diagnostic codes: K59.0-Constipation (n = 87; 28.1%), I16.9-Hypertensive Crisis (n = 72; 23.2%) and I95.1-Orthostatic hypotension (n = 22; 7.1%). The diagnoses with the highest degree of association with consultations attributed to ADE were E16.2-Hypoglycemia, unspecified (73.7%) and E11.65-Type 2 diabetes mellitus with hyperglycemia (71.4%), while diagnoses D62-Acute posthemorrhagic anemia and I74.3-Embolism and thrombosis of arteries of the lower limbs were not attributed to any case of ADE. CONCLUSIONS: The ICD-10 codes associated with trigger diagnoses are a useful tool to identify patients who consult the emergency services with ADE and could be used to apply secondary prevention programs to avoid new consultations to the health care system.

Incidence of child maltreatment diagnosis in electronic health records of a large integrated healthcare system: 2001-2018.

The purpose of this study was to identify the number of children (<18years old) with an International Classification of Disease (ICD) diagnosis code for child maltreatment each year from 2001-2018 and examine differences by age, gender, and race/ethnicity. Data were drawn from the electronic health records of children (birth to <18years old) who were members of a large integrated healthcare system in California. We calculated the incidence rate (1 per 1000 children) for each year from 2001-2018 separately by age groups, gender, and race/ethnicity. Adolescents (11-15years old) had the overall highest incidence of all ages groups. Females had nearly twice the rate of males for the past 5years. Lastly, for race/ethnicity Black children had the highest incidence and Asian children the lowest. The findings demonstrate that maltreatment diagnosis in medical settings may be underused. Understanding the trends of these ICD codes by demographic characteristics yields information that health care providers may use to both increase the identification and documentation of child maltreatment.

A Search for Undiagnosed Charcot-Marie-Tooth Disease Among Patients Registered with Unspecified Polyneuropathy in the Danish National Patient Registry.

PURPOSE: In a recent study based on data from the Danish National Patients Registry (DNPR), we reported the prevalence of Charcot-Marie-Tooth disease (CMT) in Denmark to be 22.5 per 100.000. This prevalence is most likely a minimum estimate, as many cases of CMT may be misdiagnosed or remain undiagnosed due to the heterogeneous nature of the disorder. The aim of this study was to investigate the possible number of undiagnosed CMT cases among patients registered with unspecified polyneuropathy (UP) diagnoses in the DNPR. PATIENTS AND METHODS: From the DNPR we extracted data on all patients given an UP diagnosis in the period 1977 to 2012. We selected all patients diagnosed with a primary UP diagnosis before age 40 at a department of neurology, neurophysiology, clinical genetics or pediatrics, and excluded all patients with a specified polyneuropathy diagnosis or with diagnostic codes related to alcohol and diabetes mellitus. To assess the proportion of possible CMT patients, we performed medical record review in a random sample of patients diagnosed in the Central Denmark Region. To further investigate the possible overlap between UP and CMT in the DNPR, we performed a series of searches for ICD-8 and ICD-10 codes related to CMT. RESULTS: Between 1977 and 2012, 30.903 patients were diagnosed with UP without also being diagnosed with CMT. A total of 940 patients fulfilled the selection criteria. We found that 21.5% (95% CI 13.1%-32.2%) of the cases in the random sample fulfilled our criteria for CMT. This estimate increases the prevalence of CMT in Denmark with 3.6 per 100,000 (95% CI 2.4%-5.5%). CONCLUSION: This study illustrates how hitherto undiagnosed CMT patients may be identified in the DNPR and further reports the number of possible CMT cases. Our results support the hypothesis that the true prevalence of CMT is higher than recently reported.

Interrupted time series design to evaluate ICD-9-CM to ICD-10-CM coding changes on trends in Colorado emergency department visits related to traumatic brain injury.

BACKGROUND: The transition in 2015 to the Tenth Revision of the International Classification of Disease, Clinical Modification (ICD-10-CM) in the US led the Centers for Disease Control and Prevention (CDC) to propose a surveillance definition of traumatic brain injury (TBI) utilizing ICD-10-CM codes. The CDC's proposed surveillance definition excludes "unspecified injury of the head," previously included in the ICD-9-CM TBI surveillance definition. The study purpose was to evaluate the impact of the TBI surveillance definition change on monthly rates of TBI-related emergency department (ED) visits in Colorado from 2012 to 2017. RESULTS: The monthly rate of TBI-related ED visits was 55.6 visits per 100,000 persons in January 2012. This rate in the transition month to ICD-10-CM (October 2015) decreased by 41 visits per 100,000 persons (p-value < 0.0001), compared to September 2015, and remained low through December 2017, due to the exclusion of "unspecified injury of head" (ICD-10-CM code S09.90) in the proposed TBI definition. The average increase in the rate was 0.33 visits per month (p < 0.01) prior to October 2015, and 0.04 visits after. When S09.90 was included in the model, the monthly TBI rate in Colorado remained smooth from ICD-9-CM to ICD-10-CM and the transition was no longer significant (p = 0.97). CONCLUSION: The reduction in the monthly TBI-related ED visit rate resulted from the CDC TBI surveillance definition excluding unspecified head injury, not necessarily the coding transition itself. Public health practitioners should be aware that the definition change could lead to a drastic reduction in the magnitude and trend of TBI-related ED visits, which could affect decisions regarding the allocation of TBI resources. This study highlights a challenge in creating a standardized set of TBI ICD-10-CM codes for public health surveillance that provides comparable yet clinically relevant estimates that span the ICD transition.

Validity of Diagnostic Codes for Identification of Psoriasis Patients in Korea.

BACKGROUND: Recently, the number of nationwide medical researches on psoriasis using the National Health Insurance Service database has been on the rise. However, identification of psoriasis using diagnostic codes alone can lead to misclassification. Accuracy of the diagnostic codes and their concordance with medical records should be validated first to identify psoriasis patients correctly. OBJECTIVE: To validate the diagnostic codes of psoriasis (International Classification of Diseases, 10th Revision L40) and to find the algorithm for the identification of psoriasis. METHODS: We collected medical records of patients who received their first diagnostic codes of psoriasis during 5 years from five hospitals. Fifteen percent of psoriasis patients were randomly selected from each hospital. We performed a validation by reviewing medical records and compared 5 algorithms to identify the best algorithm. RESULTS: Total of 538 cases were reviewed and classified as psoriasis (n=368), not psoriasis (n=159), and questionable (n=11). The most accurate algorithm was including patients with ≥1 visits with psoriasis as primary diagnostic codes and prescription of vitamin D derivatives. Its positive predictive value was 96.5% (95% confidence interval [CI], 93.9%~98.1%), which was significantly higher than those of the algorithm, including patients with ≥1 visits with psoriasis as primary diagnostic codes or including ≥1 visits with diagnostic codes of psoriasis (primary or additional) (91.0% and 69.8%). Sensitivity was 90.8% (95% CI, 87.2%~93.4%) and specificity was 92.5% (95% CI, 86.9%~95.9%). CONCLUSION: Our study demonstrates a validated algorithm to identify psoriasis, which will be useful for the nationwide population-based study of psoriasis in Korea.

Positive Predictive Values of 2 Algorithms for Identifying Patients with Intravenous Drug Use-Associated Endocarditis Using Administrative Data.

BACKGROUND: Prior studies have used International Classification of Disease (ICD) diagnosis codes in administrative data to identify patients with infective endocarditis (IE) associated with intravenous drug use (IVDU). Little is known about the accuracy of ICD codes for IVDU-IE. METHODS: We used 2 previously described algorithms to identify patients with potential IVDU-IE admitted to 125 Veterans Administration hospitals from January 2010 through December 2018. Algorithm A identified patients with concurrent ICD-9/10 codes for IE and drug use during the same admission. Algorithm B identified patients with drug use coded either during the IE admission or during outpatient or other visits within 6 months of admission. We reviewed 400 randomly selected patient charts to determine the positive predictive value (PPV) of each algorithm for clinical documentation of IE, any drug use, IVDU, and IVDU-IE, respectively. RESULTS: Algorithm A identified 788 patients, and B identified 1314 patients, a 68% increase. PPVs were high for clinical documentation of diagnoses of IE (86.5% for A and 82.6% for B) and any drug use (99.0% and 96.3%). PPVs were lower for documented IVDU (74.5% and 64.1%) and combined diagnoses of IVDU-IE (65.0% and 55.2%), partly because of a lack of ICD codes specific to IVDU. Among patients identified by algorithm B but not A, 72% had clinical documentation of drug use during the IE admission, indicating a failure of algorithm A to capture cases due to incomplete recording of inpatient ICD codes for drug use. CONCLUSIONS: There is need for improved algorithms for IVDU-IE surveillance during the ongoing opioid epidemic.

Guillain-Barré syndrome in Denmark: validation of diagnostic codes and a population-based nationwide study of the incidence in a 30-year period.

Purpose: To validate the diagnostic codes for Guillain-Barré syndrome (GBS) in the Danish National Patient Registry (DNPR). Secondly, to examine 30-year trends in the incidence of GBS in Denmark. Patients and methods: We used the DNPR to identify all patients aged 16 and above diagnosed with a primary GBS diagnosis at any Danish department of neurology between 1987 and 2016. Medical files were reviewed according to the clinical criteria of the National Institute of Neurological Disorders and Stroke Committee and classified according to the Brighton criteria. The incidence rate (IR) was calculated based on data from 1987 to 2016 and stratified by season, gender, and age. Results: Over 30 years, we identified 2,319 patients aged 16 and above in the DNPR. From a validation cohort of 573 patients, we were able to retrieve 425 (74.2%) medical files; 356 GBS diagnoses were confirmed. The overall positive predictive value was 83.8% (95% confidence interval (CI): 80.0-87.0). In 99% of the confirmed patients, the Brighton criteria level 1-3 for GBS were met. The IR was fairly stable over 30 years at 1.77 per 100,000 person years (95% CI: 1.70-1.84). The incidence was higher in the winter season (IR ratio compared with summer: 1.18 (95% CI: 1.09-1.29)), and was strongly associated with male gender (IR ratio vs females: 1.44 (95% CI: 1.33-1.57)). IRs rose with age at diagnosis, particularly after the age of 50 in both men and women and a minor peak was observed for total IR in young adults. Conclusion: Primary diagnostic codes for GBS at Danish departments of neurology have high validity. The DNPR is a well-suited data source for epidemiological research on GBS. The Danish nationwide 30-year GBS IR is stable over time and similar to GBS IRs reported in other European and North American populations.

Are Registration of Disease Codes for Adult Anaphylaxis Accurate in the Emergency Department?

PURPOSE: There has been active research on anaphylaxis, but many study subjects are limited to patients registered with anaphylaxis codes. However, anaphylaxis codes tend to be underused. The aim of this study was to investigate the accuracy of anaphylaxis code registration and the clinical characteristics of accurate and inaccurate anaphylaxis registration in anaphylactic patients. METHODS: This retrospective study evaluated the medical records of adult patients who visited the university hospital emergency department between 2012 and 2016. The study subjects were divided into the groups with accurate and inaccurate anaphylaxis codes registered under anaphylaxis and other allergy-related codes and symptom-related codes, respectively. RESULTS: Among 211,486 patients, 618 (0.29%) had anaphylaxis. Of these, 161 and 457 were assigned to the accurate and inaccurate coding groups, respectively. The average age, transportation to the emergency department, past anaphylaxis history, cancer history, and the cause of anaphylaxis differed between the 2 groups. Cutaneous symptom manifested more frequently in the inaccurate coding group, while cardiovascular and neurologic symptoms were more frequently observed in the accurate group. Severe symptoms and non-alert consciousness were more common in the accurate group. Oxygen supply, intubation, and epinephrine were more commonly used as treatments for anaphylaxis in the accurate group. Anaphylactic patients with cardiovascular symptoms, severe symptoms, and epinephrine use were more likely to be accurately registered with anaphylaxis disease codes. CONCLUSIONS: In case of anaphylaxis, more patients were registered inaccurately under other allergy-related codes and symptom-related codes rather than accurately under anaphylaxis disease codes. Cardiovascular symptoms, severe symptoms, and epinephrine treatment were factors associated with accurate registration with anaphylaxis disease codes in patients with anaphylaxis.

Utilidad de los diagnósticos alertantes CIE-10 para identificar acontecimientos adversos por los medicamentos en los servicios de urgencias / Usefulness of ICD-10 diagnosis triggers to identify adverse drug events in emergency care

Objetivos: Evaluar la utilidad de una herramienta basada en los códigos diagnósticos CIE-10 para identificar a los pacientes que consultan a un servicio de urgencias por acontecimientos adversos por medicamentos (AAM). Métodos: Estudio observacional prospectivo, en el cual se incluyeron los pacientes que acudieron a un servicio de urgencias durante el periodo de mayo-agosto de 2022 con un diagnóstico codificado con alguno de los 27 diagnósticos CIE-10 establecidos como alertantes para el estudio. La confirmación de la presencia de AAM a partir de dichos diagnósticos se realizó analizando los fármacos prescritos previamente al ingreso, a través de un debate entre expertos y mediante una entrevista telefónica con los pacientes. Resultados: Se evaluaron 1.143 pacientes con diagnósticos alertantes, de los cuales 310 (27,1%) correspondieron a pacientes cuya consulta se atribuyó a un AAM. El 58,4% de los AAM se detectaron mediante 3 códigos diagnósticos: K59.0-Estreñimiento (n = 87; 28,1%), I16.9-Crisis hipertensiva (n = 72; 23,2%) e I95.1-Hipotensión ortostática (n = 22; 7,1%). Los códigos diagnósticos con mayor grado de asociación con AAM fueron: E16.2-Hipoglucemia no especificada (73,7%) y E11.65-Diabetes mellitus tipo 2 con hiperglucemia (71,4%), mientras que los diagnósticos D62-Anemia poshemorrágica aguda e I74.3-Embolia y trombosis de arterias de los miembros inferiores no identificaron ningún AAM. Conclusiones: Los códigos CIE-10 asociados a diagnósticos alertantes son una herramienta de utilidad para identificar a los pacientes que consultan los servicios de urgencias por AAM y podrían ser utilizados para abordar las intervenciones de prevención secundaria dirigidas a evitar nuevas consultas al sistema sanitario. (AU)

Objectives: To assess the usefulness of a tool based on ICD-10 diagnostic codes to identify patients who consult an emergency department for adverse drug events (ADE). Methods: Prospective observational study, in which patients discharged from an emergency department during May to August 2022 with a diagnosis coded with one of the 27 ICD-10 diagnoses considered as triggers were included. ADE confirmation was carried out by analyzing drugs prescribed prior to admission, and through a discussion among experts and a phone interview with patients after hospital discharge. Results: 1,143 patients with trigger diagnoses were evaluated, of which 310 (27.1%) corresponded to patients whose emergency visit was attributed to an ADE. A 58.4% of ADE consultations were found with three diagnostic codes: K59.0-Constipation (n = 87; 28.1%), I16.9-Hypertensive Crisis (n = 72; 23.2%) and I95.1-Orthostatic hypotension (n = 22; 7.1%). The diagnoses with the highest degree of association with consultations attributed to ADE were E16.2-Hypoglycemia, unspecified (73.7%) and E11.65-Type 2 diabetes mellitus with hyperglycemia (71.4%), while diagnoses D62-Acute posthemorrhagic anemia and I74.3-Embolism and thrombosis of arteries of the lower limbs were not attributed to any case of ADE. Conclusions: The ICD-10 codes associated with trigger diagnoses are a useful tool to identify patients who consult the emergency services with ADE and could be used to apply secondary prevention programs to avoid new consultations to the health care system. (AU)

Validation of the V66.7 Code for Palliative Care Consultation in a Single Academic Medical Center.

BACKGROUND: Use of administrative data to study the effectiveness of specialized palliative care is limited by the lack of a reliable method to identify patients receiving palliative care consultation. The International Classification of Diseases, Ninth Revision (ICD-9) code V66.7 has been used, but its validity for this purpose is unknown. OBJECTIVE: To examine the validity of the ICD-9 code V66.7 for identifying whether hospitalized patients received palliative care consultation. DESIGN: Retrospective cohort study. SETTING/SUBJECTS: All patients of age ≥18 years admitted to a single academic medical center between August 2013 and August 2015. MEASUREMENTS: Sensitivity and specificity of the V66.7 code for palliative care consultation for all patients and several a priori identified subgroups. The reference standard was the presence of a palliative care consultation note in the electronic medical record. RESULTS: Of 100,910 admissions, 1999 received a palliative care consultation (2.0%) and 1846 (1.8%) had usage of the V66.7 code. Sensitivity and specificity for the V66.7 code were 49.9% and 99.1%, respectively. Sensitivity was considerably higher for certain subgroups, such as patients with dementia (76.3%) and metastatic cancer (66.3%); addition of age restrictions further improved sensitivity while maintaining high specificity. Specificity was substantially lower for patients who died during hospitalization (sensitivity 53.9%, specificity 75.1%). CONCLUSIONS: In a single center, the ICD-9 code V66.7 had poor sensitivity and high specificity for identifying hospitalized patients who received a palliative care consultation. Appropriate use of this code for this purpose should take these characteristics into consideration.

Current Scope and Challenges in Phenome-Wide Association Studies.

PURPOSE OF REVIEW: Over many decades, researchers have been designing studies to investigate the relationship between genotypes and phenotypes to gain an understanding about the effect of genetics on disease. Recently, a high-throughput approach called phenome-wide associations studies (PheWAS) have been extensively used to identify associations between genetic variants and many diseases and traits simultaneously. In this review, we describe the value of PheWAS along with methodological issues and challenges in interpretation for current applications of PheWAS. RECENT FINDINGS: PheWAS have uncovered a paradigm to identify new associations for genetic loci across many diseases. The application of PheWAS have been effective with phenotype data from electronic health records, epidemiological studies, and clinical trials data. SUMMARY: The key strength of a PheWAS is to identify the association of one or more genetic variants with multiple phenotypes, which can showcase interconnections among the phenotypes due to shared genetic associations. While the PheWAS approach appears promising, there are a number of challenges that need to be addressed to provide additional robustness to PheWAS findings.

Validation of diagnostic codes for Charcot-Marie-Tooth disease in the Danish National Patient Registry.

PURPOSE: To validate the diagnostic codes for Charcot-Marie-Tooth disease (CMT) in the Danish National Patient Registry (DNPR) using positive predictive value (PPV) as a measure of validity. PATIENTS AND METHODS: We used the DNPR to identify all patients diagnosed with at least one primary CMT diagnosis at a specialized department in the Central Denmark Region during the period 1977-2012. From this population, we randomly selected 123 patients for the validation study. Medical files were reviewed and used as reference standard. We estimated the PPV of the CMT diagnoses and stratified the analysis according to age at diagnosis, gender, and calendar time. RESULTS: In the DNPR, 275 patients were identified. We were able to retrieve 96 medical files from the random sample of 123 patients, and 85 CMT diagnoses were confirmed. The average age at diagnosis was 42.5 years, and 34% were female. The PPV was 88.5% (95% confidence interval: 80.4-94.1). CONCLUSION: The CMT diagnoses in the DNPR have high validity. The DNPR can be used as a data source for epidemiologic research on CMT.

Validity of international classification of disease codes to identify ischemic stroke and intracranial hemorrhage among individuals with associated diagnosis of atrial fibrillation.

BACKGROUND: Because of its association with death and disability, stroke is a focus of outcomes in atrial fibrillation (AF) research. International Classification of Disease-Ninth Revision (ICD-9) edition codes are commonly used to identify stroke in research, particularly in large administrative data. We sought to assess the validity of ICD-9 codes in stroke case ascertainment and for AF across 3 institutions. METHODS AND RESULTS: Participating centers included Boston Medical Center (safety net hospital), Geisinger Health System (rural Pennsylvania), and the University of Alabama (academic center in the southeastern stroke belt). ICD-9 codes for ischemic stroke (433-434, 436) and intracranial hemorrhage (430-432) identified 1812 stroke cases with an associated code for AF (427.31) from 2006 to 2010. Cases were vetted through chart review with final adjudication by a stroke neurologist. Review considered 94.2% of ICD-9 identified stroke cases valid with decreased accuracy for concurrent AF diagnosis (82.28%) and stroke attributable to AF (72.8%). Among events with "without infarction" modifiers, 7.2% were valid strokes. ICD-9 stroke code accuracy did not differ by stroke type or site. Stroke code 434 displayed higher accuracy than 433 (94.4% versus 85.2%; P<0.01), and primary stroke codes were more accurate than nonprimary codes (97.2% versus 83.7%; P<0.0001). CONCLUSIONS: Using ICD-9 stroke and AF codes to identify patients with stroke plus AF resulted in inaccuracies. Given the expanded financial and policy implications of patient-oriented research, conclusions derived solely from administrative data without validation of outcome events should be interpreted with caution.

Phenome-Wide Association Studies: Leveraging Comprehensive Phenotypic and Genotypic Data for Discovery.

With the large volume of clinical and epidemiological data being collected, increasingly linked to extensive genotypic data, coupled with expanding high-performance computational resources, there are considerable opportunities for comprehensively exploring the networks of connections that exist between the phenome and the genome. These networks can be identified through Phenome-Wide Association Studies (PheWAS) where the association between a collection of genetic variants, or in some cases a particular clinical lab variable, and a wide and diverse range of phenotypes, diagnoses, traits, and/or outcomes are evaluated. This is a departure from the more familiar genome-wide association study (GWAS) approach, which has been used to identify single nucleotide polymorphisms (SNPs) associated with one outcome or a very limited phenotypic domain. In addition to highlighting novel connections between multiple phenotypes and elucidating more of the phenotype-genotype landscape, PheWAS can generate new hypotheses for further exploration, and can also be used to narrow the search space for research using comprehensive data collections. The complex results of PheWAS also have the potential for uncovering new mechanistic insights. We review here how the PheWAS approach has been used with data from epidemiological studies, clinical trials, and de-identified electronic health record data. We also review methodologies for the analyses underlying PheWAS, and emerging methods developed for evaluating the comprehensive results of PheWAS including genotype-phenotype networks. This review also highlights PheWAS as an important tool for identifying new biomarkers, elucidating the genetic architecture of complex traits, and uncovering pleiotropy. There are many directions and new methodologies for the future of PheWAS analyses, from the phenotypic data to the genetic data, and herein we also discuss some of these important future PheWAS developments.

Positive predictive value of primary inpatient discharge diagnoses of infection among cancer patients in the Danish National Registry of Patients.

PURPOSE: Pharmacovigilance studies of cancer treatment frequently monitor infections. Predictive values of algorithms identifying disease depend on prevalence of the disease in the population under study. We therefore estimated the positive predictive value (PPV) of primary inpatient diagnosis of infection among cancer patients in the Danish National Registry of Patients (DNRP). METHODS: The algorithm to identify infections in the DNPR was based on International Classification of Diseases, 10th revision (ICD-10) codes. A physician blinded to the type of sampled infection reviewed the medical charts and assessed the presence and type of infection. Using the physician global assessment as gold standard, we computed PPVs with and without requiring agreement on infection type. RESULTS: We retrieved 266 of 272 medical charts (98%). Presence of infection was confirmed in 261 patients, resulting in an overall PPV of 98% (95% confidence interval, 96%-99%). When requiring agreement on infection type, overall PPV was 77%. For skin infections, pneumonia, and sepsis, PPVs were 79%, 93% and 84%, respectively. For these infections, we additionally calculated PPVs using evidence-based criteria as the gold standard. PPV was similar for pneumonia, but lower for skin infections and sepsis. CONCLUSIONS: The Danish National Registry of Patients is suitable for monitoring infections requiring hospitalization among cancer patients.