The use of natural language processing to identify Tdap-related local reactions at five health care systems in the Vaccine Safety Datalink.
ABSTRACT: OBJECTIVE:Local reactions are the most common vaccine-related adverse event. There is no specific diagnosis code for local reaction due to vaccination. Previous vaccine safety studies used non-specific diagnosis codes to identify potential local reaction cases and confirmed the cases through manual chart review. In this study, a natural language processing (NLP) algorithm was developed to identify local reaction associated with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in the Vaccine Safety Datalink. METHODS:Presumptive cases of local reactions were identified among members ? 11 years of age using ICD-9-CM codes in all care settings in the 1-6 days following a Tdap vaccination between 2012 and 2014. The clinical notes were searched for signs and symptoms consistent with local reaction. Information on the timing and the location of a sign or symptom was also extracted to help determine whether or not the sign or symptom was vaccine related. Reactions triggered by causes other than Tdap vaccination were excluded. The NLP algorithm was developed at the lead study site and validated on a stratified random sample of 500 patients from five institutions. RESULTS:The NLP algorithm achieved an overall weighted sensitivity of 87.9%, specificity of 92.8%, positive predictive value of 82.7%, and negative predictive value of 95.1%. In addition, using data at one site, the NLP algorithm identified 3326 potential Tdap-related local reactions that were not identified through diagnosis codes. CONCLUSION:The NLP algorithm achieved high accuracy, and demonstrated the potential of NLP to reduce the efforts of manual chart review in vaccine safety studies.
Project description:OBJECTIVE:Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt. STUDY DESIGN:Pregnant women (gestational age 20-34?weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28?days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt. RESULTS:374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or "any" fever were uncommon (?3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p?<?0.01). CONCLUSION:Tdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust. Clinical Trial Registration@ClinicalTrials.gov. NCT02209623. https://clinicaltrials.gov/ct2/show/NCT02209623.
Project description:IMPORTANCE:The Advisory Committee on Immunization Practices (ACIP) recommends the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for pregnant women during each pregnancy, regardless of prior immunization status. However, safety data on repeated Tdap vaccination in pregnancy is lacking. OBJECTIVE:To determine whether receipt of Tdap vaccine during pregnancy administered in close intervals from prior tetanus-containing vaccinations is associated with acute adverse events in mothers and adverse birth outcomes in neonates. DESIGN, SETTING, AND PARTICIPANTS:A retrospective cohort study in 29,155 pregnant women aged 14 through 49 years from January 1, 2007, through November 15, 2013, using data from 7 Vaccine Safety Datalink sites in California, Colorado, Minnesota, Oregon, Washington, and Wisconsin. EXPOSURES:Women who received Tdap in pregnancy following a prior tetanus-containing vaccine less than 2 years before, 2 to 5 years before, and more than 5 years before. MAIN OUTCOMES AND MEASURES:Acute adverse events (fever, allergy, and local reactions) and adverse birth outcomes (small for gestational age, preterm delivery, and low birth weight) were evaluated. Women who were vaccinated with Tdap in pregnancy and had a prior tetanus-containing vaccine more than 5 years before served as controls. RESULTS:There were no statistically significant differences in rates of medically attended acute adverse events or adverse birth outcomes related to timing since prior tetanus-containing vaccination. [table: see text]. CONCLUSIONS AND RELEVANCE:Among women who received Tdap vaccination during pregnancy, there was no increased risk of acute adverse events or adverse birth outcomes for those who had been previously vaccinated less than 2 years before or 2 to 5 years before compared with those who had been vaccinated more than 5 years before. These findings suggest that relatively recent receipt of a prior tetanus-containing vaccination does not increase risk after Tdap vaccination in pregnancy.
Project description:BACKGROUND:Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. METHODS:We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination. RESULTS:A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no significant differences in the rates of injection-site reactions, systemic reactions, or serious adverse events between the vaccine groups. A robust antibody response to each pertussis antigen in the Tdap-vaccinated group was found; postvaccination-to-prevaccination geometric mean antibody concentration ratios were 8:1 (pertussis toxoid), 5.9 (filamentous hemagglutinin), 6.4 (pertactin), and 5.2 (fimbriae 2 and 3). Postvaccination geometric mean concentrations of tetanus antibody (4.20 and 4.74 IU/mL, respectively) and diphtheria antibody (10.1 and 12.6 IU/mL, respectively) were similar in the Tdap and Td groups, and the rates of seroprotection against tetanus and diphtheria were >99% in both groups. CONCLUSIONS:A second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults.
Project description:Background:Incidence of whooping cough is increasing in Korea. Since 2011, occurrence among adolescents and adults has risen putting vulnerable neonates at risk. National immunization guidelines now include Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during pregnancy and as a cocooning strategy (i.e., vaccinating adults and adolescents in contact with neonates). This study assessed post-marketing Tdap (Boostrix®, GSK, Belgium) vaccine safety in subjects ? 10 years. Methods:This open, non-comparative multi-center study was conducted over six years at 10 hospitals in Korea. Subjects received Tdap in normal clinical practice according to local prescribing information. All adverse events (AEs) were recorded, classified as expected or unexpected, and severity and relationship to Tdap were assessed. Results:The analysis included 672 Korean subjects (mean age, 44 years; range, 11-81), 451 were women and 211 were pregnant. Ninety subjects experienced 124 AEs (incidence 13.39%) of which six were serious AEs (SAEs) assessed as not related to vaccination, and 51 were non-SAEs related to vaccination (mostly administration site reactions). Overall 65/124 AEs were unexpected; the most common were 14 constipation, 5 dyspepsia, 4 common cold and 4 premature labor cases. One case of common cold was assessed as possibly related to vaccination. Pregnancy outcome was 'live infant, no apparent congenital anomaly' in 195 subjects (92.42%) or 'lost to follow-up' in 16 subjects. Conclusion:Tdap administration to Korean subjects ? 10 years, including pregnant women, for the prevention of diphtheria, tetanus and pertussis was shown to have a well-tolerated safety profile. Trial Registration:ClinicalTrials.gov Identifier: NCT01929291.
Project description:We examined the comparative performance of structured, diagnostic codes vs. natural language processing (NLP) of unstructured text for screening suicidal behavior among pregnant women in electronic medical records (EMRs).Women aged 10-64 years with at least one diagnostic code related to pregnancy or delivery (N = 275,843) from Partners HealthCare were included as our "datamart." Diagnostic codes related to suicidal behavior were applied to the datamart to screen women for suicidal behavior. Among women without any diagnostic codes related to suicidal behavior (n = 273,410), 5880 women were randomly sampled, of whom 1120 had at least one mention of terms related to suicidal behavior in clinical notes. NLP was then used to process clinical notes for the 1120 women. Chart reviews were performed for subsamples of women.Using diagnostic codes, 196 pregnant women were screened positive for suicidal behavior, among whom 149 (76%) had confirmed suicidal behavior by chart review. Using NLP among those without diagnostic codes, 486 pregnant women were screened positive for suicidal behavior, among whom 146 (30%) had confirmed suicidal behavior by chart review.The use of NLP substantially improves the sensitivity of screening suicidal behavior in EMRs. However, the prevalence of confirmed suicidal behavior was lower among women who did not have diagnostic codes for suicidal behavior but screened positive by NLP. NLP should be used together with diagnostic codes for future EMR-based phenotyping studies for suicidal behavior.
Project description:In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.
Project description:OBJECTIVES:To compare changes in vaccination rates (pneumococcal polysaccharide vaccine [PPSV]; tetanus, diphtheria, and pertussis [Tdap] vaccine; and influenza vaccine) among high-risk adults following an intervention (June 1, 2013, to January 31, 2015) that used the 4 Pillars Practice Transformation Program (4 Pillars Program). STUDY DESIGN:Post hoc analysis of data from a randomized controlled cluster trial. METHODS:Eighteen primary care practices received staff education, guidance for using the 4 Pillars Program, and support for a practice immunization champion. Paired t tests were used to compare vaccination rates separately for those with diabetes, chronic lung or chronic heart disease, or other high-risk conditions. Student's t tests were used to compare vaccination rates across high-risk conditions. Generalized estimating equation modeling was used to determine the likelihood of vaccination. RESULTS:Based on International Classification of Diseases, Ninth Revision, Clinical Modification codes, 4737 patients aged 18 to 64 years were identified as having diabetes (n = 1999), chronic heart disease (n = 658), chronic lung disease (n = 1682), or another high-risk condition (n = 764). PPSV uptake increased by 12.2 percentage points (PP), Tdap vaccination increased by 11.4 PP, and influenza vaccination increased by 4.8 PP. In regression analyses, patients with diabetes (odds ratio [OR], 2.2; 95% CI, 1.80-2.73), chronic lung disease (OR, 1.50; 95% CI, 1.21-1.87), or chronic heart disease (OR, 1.32; 95% CI, 1.02-1.71) were more likely to receive PPSV than those without the respective high-risk condition. Those with diabetes (OR, 1.14; 95% CI, 1.01-1.28) or chronic lung disease (OR, 1.14; 95% CI, 1.01-1.30) were more likely to receive an influenza vaccine than those without the respective condition. The likelihood of Tdap vaccination was not significantly associated with any of the chronic conditions tested. CONCLUSIONS:An intervention including the 4 Pillars Program was associated with significant increases in vaccination of high-risk adults. However, the overall uptake of recommended vaccines for those with high-risk conditions remained below national goals.
Project description:Repeat administration of tetanus toxoid-containing vaccines has rarely been associated with Arthus phenomenon, an immune-complex reaction. In the US, since 2013, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines (Tdap) have been recommended for administration during each pregnancy. Separately, in 2019, one Tdap was approved for repeat administration in adults in the US. We aimed to describe trends in spontaneously reported Arthus reactions following Tdap in the US and to assess the risk of this phenomenon in persons receiving Tdap repeatedly. We reviewed Arthus reports in the Vaccine Adverse Events Reporting System (VAERS), 1990-2018. Reporting rates were estimated using Tdap doses distributed data. A systematic literature review was conducted in MEDLINE for any Arthus cases reported in Tdap clinical trials and observational studies published between 2000 and 2019. We found 192 Arthus reports in VAERS after any vaccine, of which 36 occurred after Tdap and none were reported during pregnancy. The Arthus reporting rate was estimated at 0.1 per million doses distributed. We identified eight published studies of Tdap administration within five years after a previous dose of tetanus toxoid-containing vaccine; no Arthus cases were reported. We conclude that Arthus reaction following Tdap is extremely rare. Increasing frequency of repeat Tdap administration in adults in the US did not result in a detectable increase in reporting rates of this phenomenon, confirming the favorable safety profile of Tdap.
Project description:BACKGROUND:Infants younger than 6?months are at increased risk of complications and mortality from pertussis infection. In October 2012, the Advisory Committee on Immunization Practices revised its recommendation to include a Tdap dose during each pregnancy, ideally between 27 and 36?weeks gestation. OBJECTIVE:Assess trends in Tdap vaccination coverage among privately insured pregnant women from 2009 to 2016 including timing of Tdap vaccination (before, during, or after pregnancy), trimester of vaccination for women vaccinated during pregnancy, and missed vaccination opportunities for unvaccinated women. Identify factors associated with vaccination during the optimal period of 27-36?weeks gestation. STUDY DESIGN:Retrospective analysis of privately insured women 15-49?years who delivered live births during 2009-2016 conducted using 2009-2016 MarketScan data. Tdap vaccination coverage and the timing of Tdap vaccine administration were assessed for women continuously enrolled from 6?months before pregnancy to 1?month after delivery. Multivariable logistic regression was performed to identify factors independently associated with receipt of Tdap vaccine at 27-36?weeks gestation. RESULTS:Tdap vaccination coverage during pregnancy increased from 0.4% in 2009 to 6.2% in 2012 and to 53.2% in 2016. The proportion of vaccinated women receiving Tdap at 27-36?weeks gestation increased from <10% in 2009 to nearly 90% in 2016, with most vaccination occurring at 27-32?weeks gestation. Women of older age, residing in a metropolitan statistical area, residing outside the South, and having a capitated health insurance plan were more likely to receive Tdap at 27-36?weeks gestation than their counterparts. Among women not vaccinated during pregnancy, 77.7% had a pregnancy-related medical claim between 27 and 36?weeks gestation. CONCLUSION:Tdap vaccination coverage during pregnancy increased significantly from 2009 to 2016, with the greatest increase occurring after the revised Advisory Committee on Immunization Practices recommendation. Most women who did not receive Tdap vaccine had a missed vaccination opportunity during pregnancy, indicating potential for much higher vaccination coverage and consequent infant protection against pertussis.
Project description:PURPOSE:The study aims to develop and validate algorithms to identify and classify opioid overdoses using claims and other coded data, and clinical text extracted from electronic health records using natural language processing (NLP). METHODS:Primary data were derived from Kaiser Permanente Northwest (2008-2014), an integrated health care system (~n > 475 000 unique individuals per year). Data included International Classification of Diseases, Ninth Revision (ICD-9) codes for nonfatal diagnoses, International Classification of Diseases, Tenth Revision (ICD-10) codes for fatal events, clinical notes, and prescription medication records. We assessed sensitivity, specificity, positive predictive value, and negative predictive value for algorithms relative to medical chart review and conducted assessments of algorithm portability in Kaiser Permanente Washington, Tennessee State Medicaid, and Optum. RESULTS:Code-based algorithm performance was excellent for opioid-related overdoses (sensitivity = 97.2%, specificity = 84.6%) and classification of heroin-involved overdoses (sensitivity = 91.8%, specificity = 99.0%). Performance was acceptable for code-based suicide/suicide attempt classifications (sensitivity = 70.7%, specificity = 90.5%); sensitivity improved with NLP (sensitivity = 78.7%, specificity = 91.0%). Performance was acceptable for the code-based substance abuse-involved classification (sensitivity = 75.3%, specificity = 79.5%); sensitivity improved with the NLP-enhanced algorithm (sensitivity = 80.5%, specificity = 76.3%). The opioid-related overdose algorithm performed well across portability assessment sites, with sensitivity greater than 96% and specificity greater than 84%. Cross-site sensitivity for heroin-involved overdose was greater than 87%, specificity greater than or equal to 99%. CONCLUSIONS:Code-based algorithms developed to detect opioid-related overdoses and classify them according to heroin involvement perform well. Algorithms for classifying suicides/attempts and abuse-related opioid overdoses perform adequately for use for research, particularly given the complexity of classifying such overdoses. The NLP-enhanced algorithms for suicides/suicide attempts and abuse-related overdoses perform significantly better than code-based algorithms and are appropriate for use in settings that have data and capacity to use NLP.