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Hung Fu Tseng,
Lina S Sy,
Amy Liu,
Lei Qian,
S Michael Marcy,
Eric Weintraub,
Katherine Yih,
Roger Baxter,
Jason M Glanz,
James Donahue,
Allison Naleway, James Nordin,
Steven J Jacobsen
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ABSTRACT: Although no increased risk was detected for serious adverse events in the prelicensure trials for the 13-valent pneumococcal vaccine, Prevnar 13(®) (PCV13), continued monitoring of rare but serious adverse events is necessary. A surveillance system using cohort study design was set up to monitor safety of PCV13 immediately after it was included in the childhood immunization program in the United States. The exposed population included children of 1 month to 2 years old who received PCV13 from April, 2010 to January, 2012 from the eight managed care organizations participating in the Vaccine Safety Datalink Project in the United States. The historical unexposed population was children of the same age who received the 7-valent pneumococcal conjugate vaccine Prevnar 7(®) (PCV7) in 2007 (or 2005 depending on the outcome of interest) to 2009. The risk of pre-specified adverse events in the risk window following PCV13 were repeatedly compared to that in the historical comparison group. The number of doses included in the study was 599,229. No increased risk was found for febrile seizures, urticaria or angioneurotic edema, asthma, thrombocytopenia, or anaphylaxis. An increased risk for encephalopathy was not confirmed following the medical record review. The relative risk for Kawasaki disease in 0-28 days following vaccination was 1.94 (95% confidence interval: 0.79-4.86), comparing PCV13 to PCV7. Comparing to PCV7 vaccine, we identified no significant increased risk of pre-specified adverse events in the Vaccine Safety Datalink study cohort. The possible association between PCV13 and Kawasaki disease may deserve further investigation.
Vaccine 04/2013; · 3.77 Impact Factor
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ABSTRACT: Background/Aims Trivalent influenza vaccine (TIV) is the only vaccine recommended by the Advisory Committee on Immunization Practices (ACIP) for routine administration during pregnancy. The ACIP categorizes remaining vaccines as, "should be considered if indicated", "contraindicated", or with "special/conditional recommendation." The objective of this study was to describe rates of vaccination during pregnancy in seven Vaccine Safety Datalink (VSD) sites. Methods Using the VSD Pregnancy Algorithm, we identified all pregnancies ending in 2002-2006, including both live births and other birth outcomes (e.g., miscarriages, terminations). We then identified all vaccinations administered during pregnancies occurring in the study period. Results We identified 595,929 pregnancies and 68,839 vaccinations. The most commonly administered vaccine was TIV, with 58,683 doses and an incidence rate of 98.47 doses per 1,000 pregnancies. TIV was more likely to be administered during the 2nd or 3rd trimester (98.12 per 1,000 pregnancies), versus the 1st trimester (21.98 per 1,000). The total number of indicated vaccinations was 6,743 (11.32 per 1,000) and the most common vaccines in this category were tetanus-diphtheria and hepatitis B (6.65 and 4.31 per 1,000, respectively). Indicated vaccines were more likely to be given during the 1st trimester (7.42 per 1,000) than during the 2nd or 3rd trimesters combined (5.02 per 1,000). A total of 882 contraindicated vaccines were administered during the study period (1.48 per 1,000), and the majority of these were measles-mumps-rubella (MMR) (0.64 per 1,000), varicella (0.49 per 1,000) and live-attenuated influenza vaccine (LAIV) (0.19 per 1,000). The majority of contraindicated vaccines were administered during the 1st trimester (1.02 per 1,000) versus the 2nd or 3rd trimesters (0.58 per 1,000). Discussion TIV, which is recommended during pregnancy, was the most commonly administered vaccine in our study population. MMR, varicella, and LAIV were the most common contraindicated vaccines administered. With the exception of TIV, other vaccines were more likely to be administered during the 1st trimester of pregnancy, suggesting that vaccinations may occur during a period when either the woman and/or provider are unaware of the pregnancy. Given that some women were also vaccinated during later pregnancy, clearer recommendations and improved provider education may be needed.
Clinical Medicine & Research 08/2012; 10(3):187.
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ABSTRACT: Background/Aims The need for research on the safety of vaccination during pregnancy is widely recognized. Large, population-based data systems like the Vaccine Safety Datalink (VSD) may be useful for this research, but identifying pregnancies using electronic medical record (EMR) and claims data can be challenging. Methods We modified an existing pregnancy identification algorithm originally developed by Kaiser Permanente Northwest to identify pregnancy outcomes and dates using the standardized VSD data files. We validated the algorithm by calculating the percent agreement in pregnancy outcome type, end date, and gestational age between the algorithm and manual medical record review. At each site, we randomly sampled 15 episodes within four outcome type strata (live births, spontaneous abortions, elective abortions, and other pregnancy outcomes) for a total of 60 episodes per site. Seven of eight VSD sites participated. Results We identified 595,929 pregnancy episodes ending in 2002-2006 among women 12-55 years of age. Of these pregnancies, 75% ended in live births, 12% in spontaneous abortions, and 9% in elective abortions. We were able to confirm a pregnancy on or near the algorithm-specified pregnancy start and end dates for 99% of live births, 93% of spontaneous abortions, 92% of elective abortions, and 90% of other outcomes. The agreement between the algorithm-identified and the abstractor- indentified outcome date ranged from 70% (elective abortion) to 96% (live birth) depending on outcome type. When gestational age was available in the EMR, agreement ranged from 82% (other) to 98% (live birth) depending on outcome type. Discussion The VSD algorithm accurately identifies pregnancy episodes across participating sites using the standardized VSD data files. Additional manual record review may be needed to improve the precision of the pregnancy date estimates depending on specific study needs. This algorithm will allow us to conduct large, population-based studies of the safety of vaccination during pregnancy.
Clinical Medicine & Research 08/2012; 10(3):179.
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Michael Klompas,
Michael Murphy,
Dongyi Du,
Wei Hua,
Ann Von Worley,
Michael Schum,
Laura Johnson,
Cynthia Nakasato, James Nordin,
Robert Davis,
Melissa Butler,
Mayur Ramesh,
Craig Zinderman,
Richard Platt
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ABSTRACT: Background/Aims The infectious risk of human tissue allografts is unknown. Healthcare claims data from large populations may be useful for quantifying and monitoring rates of infection after tissue allograft transplantation, but require accurate algorithms to identify allograft implantations and infections. We explored the feasibility of identifying allograft implantations and infections using claims data. Methods We identified all patients with procedure codes for anterior cruciate ligament (ACL) surgery within four HMO Research Network sites during calendar years 2000-2008. Charts were randomly selected for review to determine the frequency of allograft versus autograft use. We then flagged patients with claims-based indicators of possible infection including suggestive ICD9 diagnosis codes, procedures, antibiotic prescriptions, specialty consultations, emergency department visits, and readmissions within the 90 days following surgery. We reviewed charts of patients with and without infection indicators and calculated the sensitivity and positive predictive value of individual indicators as well as combinations of multiple indicators. Results We identified 6,615 patients with codes for ACL surgeries in four HMO Research Network sites. On review of randomly selected charts, allografts were utilized in 128/536 (24%) surgeries and autografts in 392/536 (73%) surgeries. Implant type was inadequately documented in the remaining 16 charts (3%). Possible claims-based infection indicators were present in 1,827/6,615 (28%) surgeries. We reviewed 765 charts with indicators of possible infection and 475 charts without infectious indicators. There were 30 confirmed deep tissue infections, all amongst patients with possible infection indicators. Correcting for sampling weights, we estimated 1.6 versus 1.0 infections per 100 surgeries in allograft versus autograft implants (crude odds ratio 1.7, 95% CI 1.1-2.8). The sensitivity of individual indicators ranged from 0 to 70% and positive predictive value from 0 to 24%. Combining indicators increased sensitivity to >90% but positive predictive values remained poor. Discussion Procedure codes for ACL surgeries are not specific for allograft versus autograft implants. Claims-based indicators of possible infections reliably capture all patients with serious infections but also flag many false positives. We are now validating the sensitivity and positive predictive value of claims-based infection indicators using data from two additional HMO Research Network sites.
Clinical Medicine & Research 08/2012; 10(3):178.
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Nicola P Klein,
Edwin Lewis,
Roger Baxter,
Eric Weintraub,
Jason Glanz,
Allison Naleway,
Lisa A Jackson, James Nordin,
Tracy Lieu,
Edward A Belongia,
Bruce Fireman
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ABSTRACT: In the United States, children receive 2 doses of measles-mumps-rubella vaccine (MMR) and varicella vaccine (V), the first between ages 1 to 2 years and the second between ages 4 to 6 years. Among 1- to 2-year-olds, the risk of febrile seizures 7 to 10 days after MMRV is double that after separate MMR + V. Whether MMRV or MMR + V affects risk for febrile seizure risk among 4- to 6-year-olds has not been reported.
Among 4- to 6-year-old Vaccine Safety Datalink members, we identified seizures in the emergency department and hospital from 2000 to 2008 and outpatient visits for fever from 2006 to 2008 during days 7 to 10 and 0 to 42 after MMRV and MMR + V. Incorporating medical record reviews, we assessed seizure risk after MMRV and MMR + V.
From 2006 through 2008, 86 750 children received MMRV; from 2000 through 2008, 67 438 received same-day MMR + V. Seizures were rare throughout days 0 to 42 without peaking during days 7 to 10. There was 1 febrile seizure 7 to 10 days after MMRV and 0 after MMR + V. Febrile seizure risk was 1 per 86 750 MMRV doses (95% confidence interval, 1 per 3 426 441, 1 per 15 570) and 0 per 67 438 MMR + V doses (1 per 18 282).
This study provides reassurance that MMRV and MMR + V were not associated with increased risk of febrile seizures among 4- to 6-year-olds. We can rule out with 95% confidence a risk greater than 1 febrile seizure per 15 500 MMRV doses and 1 per 18 000 MMR + V doses.
PEDIATRICS 04/2012; 129(5):809-14. · 4.47 Impact Factor
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Michael Klompas,
Michael Murphy,
Aysha Akhtar,
Cynthia Nakasato, James Nordin,
Michael Schum,
Ann Von Worley,
Melissa Butler,
Robert Davis,
Laura Johnson,
Mayur Ramesh,
Craig Zinderman,
Hector Izurieta,
Richard Platt
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ABSTRACT: Background The frequency of human tissue allograft contamination leading to infection is unknown. Attributing infections to allograft contamination versus surgical factors is elusive. National claims data may facilitate study of allograft-associated infections but first require accurate algorithms to identify implantations and infections. We explored the feasibility of using claims data to identify anterior cruciate ligament (ACL) allograft implants and infections. Methods We selected candidate diagnosis, procedure, visit type, and antibiotic prescription criteria to identify ACL allograft repairs and infections. Candidate criteria were categorized by likelihood of infection and putative pathogen type. Criteria were then applied to HMO Research Network Virtual Data Warehouse files for 2000-2008 from six sites. We defined the infection risk period as 90 days following ACL repair. We reviewed charts flagged by each criterion to determine implant type and to assess for infection. Sensitivity and positive predictive values (PPV) were calculated. Results Preliminary results are available from five of six sites. Procedure codes 29888 and 81.45 (ACL repair, unspecified) flagged 11,202 episodes of care. Diagnosis codes compatible with infection flagged 139 episodes (1.2%) of which 71 were categorized as high probability (0.63%). Microbiology and infection management procedure codes flagged 1,029 episodes (9.2%) and 68 episodes (0.6%) respectively. Antibiotics were prescribed for 1,523 episodes (14%) of which 580 were deemed high likelihood prescriptions (5.2%). There were 1011 hospitalizations within 90 days of ACL implantation (9.0%), 787 emergency department visits (7.0%), and 43 infectious disease specialist visits (0.4%). Over 1500 chart reviews are planned of which 107 have been completed thus far. The PPV for allograft implantation is 33% (95% CI 25-43%). Sufficient data are currently available to confirm 14 infections. Antibiotic prescribing was the most sensitive criterion while infectious disease visit had the highest PPV (sensitivities 86% and 7%, PPVs 35% and 100% respectively). Conclusions Claims data do not discriminate between allografts and autografts in ACL repair but do identify a subset of patients with possible infections. Once chart reviews are complete we will assess whether combinations of criteria can increase accuracy.
Clinical Medicine & Research 11/2011; 9(3-4):179.
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Nicola P Klein,
Bruce Fireman,
W Katherine Yih,
Edwin Lewis,
Martin Kulldorff,
Paula Ray,
Roger Baxter,
Simon Hambidge, James Nordin,
Allison Naleway,
Edward A Belongia,
Tracy Lieu,
James Baggs,
Eric Weintraub
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ABSTRACT: In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine.
Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses.
MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6).
Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.
PEDIATRICS 07/2010; 126(1):e1-8. · 4.47 Impact Factor
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Lisa A Jackson,
Onchee Yu,
Edward A Belongia,
Simon J Hambidge,
Jennifer Nelson,
Roger Baxter,
Allison Naleway,
Charlene Gay, James Nordin,
James Baggs,
John Iskander
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ABSTRACT: Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td) vaccine and the risk of local reactions may increase with number of prior Td vaccinations.
To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004.
Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations) was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV) in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2). Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics.
Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.
BMC Infectious Diseases 10/2009; 9:165. · 3.12 Impact Factor
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ABSTRACT: Three vaccines currently recommended for adolescents (Tdap, Td, and MCV4 meningococcal conjugate vaccine) contain diphtheria toxoid. While the safety of individual diphtheria toxoid containing vaccines has been evaluated, less is known regarding the safety of administration of two or more of these vaccines, either concomitantly or sequentially. This study evaluated the risk of medically attended local reactions in adolescents and young adults with varying patterns of receipt of diphtheria toxoid containing vaccines. In general the risk of medically attended local reactions was low and did not differ with concomitant or sequential administration of diphtheria toxoid containing vaccines.
Vaccine 07/2009; 27(36):4912-6. · 3.77 Impact Factor
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ABSTRACT: This study evaluated the utility of immunization registries in identifying vaccine refusals among children. Among refusers, we studied their socioeconomic characteristics and health care utilization patterns.
Medical records were reviewed to validate refusal status in the immunization registries of two health plans. Racial, education, and income characteristics of children claiming refusal were collected based on the census tract of each child. Health care utilization was identified using both electronic medical record and insurance claims. Within the immunization registries of two HMOs in the study, some providers use refusal and medical contraindication interchangeably, and some providers tend to always use "ever refusal." Therefore, we combined medical contraindication and refusal together and treated them all as "refusal" in this study.
The immunization registry, compared to chart review, had negative predictive values of 85-92% and 90-97% for 2- and 6-year olds, and positive predictive values of only 52-74% and 59-62% to identify vaccine refusals. Refusers were more likely to reside in well-educated, higher income areas than non-refusers. Refusers had not opted out of health care system and continued, although less frequently for the age 2 and under group, to use services.
Without enhancements to immunization registries, identifying children with immunization refusal would be time consuming. Since communities where refusers live are well educated, interventions should target these communities to communicate vaccine adverse events and consequences of vaccine preventable diseases.
BMC Pediatrics 04/2009; 9:18. · 1.88 Impact Factor
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Eric K France,
Jason Glanz,
Stanley Xu,
Simon Hambidge,
Kristi Yamasaki,
Steve B Black,
Michael Marcy,
John P Mullooly,
Lisa A Jackson, James Nordin,
Edward A Belongia,
K Hohman,
Robert T Chen,
Robert Davis
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ABSTRACT: The measles-mumps-rubella vaccine has been associated with immune thrombocytopenia purpura in 2 small studies.
By using the Vaccine Safety Datalink, we identified measles-mumps-rubella-vaccinated children aged 1 to 18. A case of immune thrombocytopenia purpura was defined as a patient with a platelet count of < or = 50,000/microL with clinical bleeding and normal red and white blood cell indices. The immune thrombocytopenia purpura incidence rates during exposed (42 days after vaccination) and unexposed time periods were determined. A retrospective cohort of vaccinated children was used to determine incident rate ratios for children aged 1 to 18 years, 12 to 23 months, and 12 to 15 months.
A total of 1,036,689 children received 1,107,814 measles-mumps-rubella vaccinations; there were 259 confirmed patients with immune thrombocytopenia purpura. Because only 5 exposed cases occurred after age 2, analyses were limited to children aged 12 to 23 months. Exposed patients aged 12 to 23 months had lower median platelet counts than those who were unexposed and had similar median duration of illness (11 vs 10 days). The incident rate ratio was highest for children aged 12 to 15 months at 7.10. The incident rate ratio for boys aged 12 to 15 months was 14.59, and the incident rate ratio for girls in the same age group was 3.22. Seventy-six percent of immune thrombocytopenia purpura cases in children aged 12 to 23 months were attributable to measles-mumps-rubella vaccination. This vaccine causes 1 case of immune thrombocytopenia purpura per every 40,000 doses.
Measles-mumps-rubella vaccine that is given in the second year of life is associated with an increased risk of immune thrombocytopenia purpura.
PEDIATRICS 03/2008; 121(3):e687-92. · 4.47 Impact Factor
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Simon J Hambidge,
Jason M Glanz,
Eric K France,
David McClure,
Stanley Xu,
Kristi Yamasaki,
Lisa Jackson,
John P Mullooly,
Kenneth M Zangwill,
S Michael Marcy,
Steven B Black,
Edwin M Lewis,
Henry R Shinefield,
Edward Belongia, James Nordin,
Robert T Chen,
David K Shay,
Robert L Davis,
Frank DeStefano
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ABSTRACT: Beginning with the winter season of 2004-2005, influenza vaccination has been recommended for all children 6 to 23 months old in the United States. However, its safety in young children has not been adequately studied in large populations.
To screen for medically attended events in the clinic, emergency department, or hospital after administration of trivalent inactivated influenza vaccine in children 6 to 23 months old.
Retrospective cohort using self-control analysis, with chart review of significant medically attended events at 8 managed care organizations in the United States that comprise the Vaccine Safety Datalink. Participants were all children in the Vaccine Safety Datalink cohort 6 to 23 months old who received trivalent inactivated influenza vaccine between January 1, 1991, and May 31, 2003 (45,356 children with 69,359 vaccinations).
Any medically attended event significantly associated with trivalent inactivated influenza vaccine in risk windows 0 to 3 days, 1 to 14 days (primary analysis), 1 to 42 days, or 15 to 42 days after vaccination, compared with 2 control periods, one before vaccination and the second after the risk window. All individual ICD-9 codes as well as predefined aggregate codes were examined.
Before chart review, only 1 diagnosis, gastritis/duodenitis, was more likely to occur in the 14 days after trivalent inactivated influenza vaccine (matched odds ratio [OR], 5.50; 95% confidence interval [CI], 1.22-24.81 for control period 1, and matched OR, 4.33; 95% CI, 1.23-15.21 for control period 2). Thirteen medically attended events were less likely to occur after trivalent inactivated influenza vaccine, including acute upper respiratory tract infection, asthma, bronchiolitis, and otitis media. After chart review, gastritis/duodenitis was not significantly associated with trivalent inactivated influenza vaccine (matched OR, 4.00; 95% CI, 0.85-18.84 for control period 1; matched OR, 3.34; 95% CI, 0.92-12.11 for control period 2).
In the largest population-based study to date of the safety of trivalent inactivated influenza vaccine in young children, there were very few medically attended events, none of which were serious, significantly associated with the vaccine. This study provides additional evidence supporting the safety of universally immunizing all children 6 to 23 months old with influenza vaccine.
JAMA The Journal of the American Medical Association 11/2006; 296(16):1990-7. · 30.03 Impact Factor
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Lisa A Jackson,
Kathleen M Neuzil,
James Baggs,
Robert L Davis,
Steve Black,
Kristi M Yamasaki,
Ed Belongia,
Kenneth M Zangwill,
John Mullooly, James Nordin,
S Michael Marcy,
Frank DeStefano
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ABSTRACT: Children <9 years of age do not respond optimally to a first dose of trivalent inactivated influenza vaccine, and so 2 doses of trivalent inactivated influenza vaccine are recommended for children <9 years of age who are being vaccinated for the first time. We conducted a population-based retrospective cohort study to evaluate compliance with the 2-dose trivalent inactivated influenza vaccine recommendations.
We evaluated 125,928 children 6 months through 8 years of age who were enrolled in health maintenance organizations in the United States participating in the Vaccine Safety Datalink project and who received their first dose of trivalent inactivated influenza vaccine in the 2001-2002, 2002-2003, or 2003-2004 influenza seasons.
Compliance with the 2 dose recommendations varied by age group and influenza season. Among children 6 to 23 months of age, the proportion of first-vaccinated children who received a second vaccination was 44% in 2001-2002, 54% in 2002-2003, and 29% in 2003-2004. Among children 2 to 8 years of age, the corresponding proportions were 15%, 24%, and 12%, respectively. In all seasons, compliance with the second vaccination was highest in children first vaccinated by mid-November.
The majority of children who received their first dose of trivalent inactivated influenza vaccine did not complete the 2-dose series. The recently expanded recommendation for universal vaccination of children 6 to 59 months of age and their household contacts will substantially increase the number of children targeted for a first influenza vaccination. Noncompliance with the 2-dose trivalent inactivated influenza vaccine series may be associated with suboptimal protection against infection, which may impact the magnitude of the direct and indirect benefits achieved by the vaccination program.
PEDIATRICS 11/2006; 118(5):2032-7. · 4.47 Impact Factor
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ABSTRACT: There currently are no population-based systems in the United States to rapidly detect adverse events after newly introduced vaccines. To evaluate the feasibility of developing such systems, we used 5 years of data from 4 health maintenance organizations within the Centers for Disease Control and Prevention (CDC) Vaccine Safety Datalink.
Within every year, each week's vaccinated children were followed for 4 weeks, and rates of adverse events were compared with rates among children of similar ages before the introduction of the new vaccine. We assessed risks for intussusception after rotavirus vaccination and risks for fever, seizures, and other neurologic adverse events after the change from whole cell diphtheria-tetanus-pertussis (DTPw) to acellular DTP vaccine (DTPa). We used sequential probability ratio testing, adjusted for age, sex, calendar time, season, and HMO, and with a stopping value based on the probability of an adverse event under the null hypothesis and under a preset alternative hypothesis.
We detected an increase in intussusception after 2589 vaccine doses of rotavirus vaccine, about the same time initial reports of intussusception were made to the Vaccine Adverse Events Reporting System. Decreases in risk for fever, seizures, and other abnormal neurologic events became detectable within 12 weeks, 42 weeks, and 18 months, respectively, after the change from DTPw to DTPa.
We conclude that it is feasible to develop systems for rapid and routine population-based assessments of new vaccine safety.
Epidemiology 06/2005; 16(3):336-41. · 5.57 Impact Factor
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ABSTRACT: Widespread use of broad-spectrum antibiotics contributes to increasing rates of bacterial resistance to antibiotics. Second-generation macrolides have become popular for use among children because of their broad spectrum and favorable dosing and side-effect profiles, although experts do not generally recommend them for use as initial treatment of infections among younger children.
To assess trends in second-generation macrolide use from 1996 to 2000 among children treated as outpatients in 9 US health plans, including associated diagnoses and use as initial treatment.
We sampled claims data for 25000 children, 3 months to <18 years of age, who were enrolled between September 1, 1995, and August 31, 2000, in each of 9 US health plans. Medications dispensed were linked with ambulatory visit claims to assign diagnoses. Dispensings without another antibiotic dispensing recorded in the previous 42 days were analyzed as initial treatment of a new illness episode. We analyzed trends in prescribing overall, for initial therapy, and, within specific diagnoses, for differences among health plans.
From 1995-1996 to 1999-2000, although overall antibiotic use decreased from 1.15 to 0.91 dispensings per person-year, second-generation macrolide use increased from 0.022 to 0.063 dispensings per person-year. Use as a proportion of all antibiotic dispensings increased from 1.9% to 6.9%, and use as initial therapy increased from 1.4% to 6%. For children <6 years of age, second-generation macrolide use as initial therapy increased from 0.9% to 5.0% for otitis media and from 5.2% to 24.0% for pneumonia. There was a wide range of prescribing rates among health plans during the last year of the study, from 0.006 to 0.135 dispensings per person-year.
Despite recent trends toward decreased antibiotic use among children, the use of second-generation macrolides among children has increased dramatically, even among younger children, for whom use for initial treatment of illness is not recommended. Large differences in prescribing rates exist among health plans. Continued efforts to promote the use of narrower-spectrum agents when appropriate are needed.
PEDIATRICS 12/2004; 114(5):1206-11. · 4.47 Impact Factor
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ABSTRACT: Uncertainties among health care providers and patients about the risk of serious influenza-associated complications and the potential benefits of vaccination may contribute to unsatisfactorily low influenza vaccination rates. To quantify the risk of serious outcomes (hospitalization due to pneumonia or influenza or death due to any cause) during influenza seasons, we developed a clinical prediction rule for the probability of hospitalization due to pneumonia or influenza or death among elderly persons.
We developed the clinical prediction rule using data from linked administrative databases in a cohort of 16,280 noninstitutionalized and unvaccinated elderly persons. Validation of the rule was conducted in 5 unvaccinated and 6 vaccinated cohorts, each consisting of >11,000 elderly members of 3 managed care organizations. Logistic regression was used to produce a prognostic score on the basis of the following predictors: age; sex; presence of pulmonary, cardiac, and renal disease; dementia or stroke and cancer; number of outpatient visits; and hospitalization due to pneumonia or influenza during the previous year.
Reliability of the regression model was good (P=.65, by goodness-of-fit test), and it discriminated well between those who did and those who did not experience an outcome (area under the receiver-operating curve, 0.83; 95% confidence interval, 0.81-0.85). Validation revealed moderately lower but acceptable discriminating values (0.72-0.81). In the derivation cohort, the prognostic accuracy of the rule was high when a cutoff score for the upper 50th percentile was used: > or =10 of 1000 subjects with a score in the upper 50th percentile were predicted to have an outcome, and 89% of all outcomes were observed in this high-risk group, whereas <10 of 1000 subjects with a score in the lower 50th percentile were predicted to have an outcome, and only 11% of outcomes occurred in this group. Among unvaccinated subjects in the single-derivation cohort and the 11 validation cohorts combined, the outcome event rates were 35 events/1000 subjects in the higher-risk group and 6 events/1000 subjects in the lower-risk group. With vaccination, these event rates dropped by 15 events/1000 subjects and 2 events/1000 subjects, respectively.
This prediction rule may be a useful tool to complement other age-based strategies, to further encourage vaccination, especially among those at the highest risk of serious complications due to influenza.
The Journal of Infectious Diseases 03/2004; 189(3):450-8. · 6.41 Impact Factor
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Jonathan A Finkelstein,
Christopher Stille, James Nordin,
Robert Davis,
Marsha A Raebel,
Douglas Roblin,
Alan S Go,
David Smith,
Christine C Johnson,
Kenneth Kleinman,
K Arnold Chan,
Richard Platt
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ABSTRACT: High rates of antibiotic prescribing to children contribute to antibiotic resistance in the community. The Centers for Disease Control and Prevention, in collaboration with other national and state level organizations, have actively promoted more judicious prescribing for children.
We sought to assess changes in the rate of antibiotic prescribing from 1996-2000 in 9 US health plans, patterns of diagnosis and treatment responsible for these trends, and changes in the use of first-line antimicrobial agents.
We analyzed claims data for dispensed medications and physician visits from 9 health plans. Each provided data on 25,000 children aged 3 months to <18 years enrolled between September 1, 1995, and August 31, 2000. Antibiotic dispensings were linked with an ambulatory visit claim to assign diagnosis. Antibiotic dispensings per person-year (antibiotics/p-y) were calculated for the age groups 3 months to <3 years, 3 years to <6 years, and 6 years to <18 years. The contribution of each diagnosis to changes in the overall rate of antibiotic use was determined. Generalized linear mixed models were used to test for trend and assess differences in rates by site.
From 1996-2000, antibiotic rates for children 3 months to <3 years decreased from 2.46 to 1.89 antibiotics/p-y (24%); for children 3 years to <6 years from 1.47 to 1.09 antibiotics/p-y (25%); and for children 6 to <18 years from 0.85 to 0.69 antibiotics/p-y (16%). The reduction varied among health plans from 6% to 39% for children 3 months to <3 years. A decrease in prescriptions for otitis media accounted for 59% of the total decrease, and was primarily accounted for by a decrease in the rate of diagnosis of this condition. The proportion of first-line penicillins increased from 49% to 53%, with health plans with the lowest initial rates increasing most.
Antibiotic prescribing decreased significantly between 1996 and 2000, concurrent with decreased frequency of diagnosis of potential bacterial infections, especially otitis media. Attention by public health and professional organizations and the news media to antibiotic resistance may have contributed to changes in diagnostic thresholds, resulting in more judicious prescribing.
PEDIATRICS 09/2003; 112(3 Pt 1):620-7. · 4.47 Impact Factor
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ABSTRACT: Upper respiratory tract illnesses have been associated with an increased risk of ischemic heart disease and stroke. During two influenza seasons, we assessed the influence of vaccination against influenza on the risk of hospitalization for heart disease and stroke, hospitalization for pneumonia and influenza, and death from all causes.
Cohorts of community-dwelling members of three large managed-care organizations who were at least 65 years old were studied during the 1998-1999 and 1999-2000 influenza seasons. Administrative and clinical data were used to evaluate outcomes, with multivariable logistic regression to control for base-line demographic and health characteristics of the subjects.
There were 140,055 subjects in the 1998-1999 cohort and 146,328 in the 1999-2000 cohort, of which 55.5 percent and 59.7 percent, respectively, were immunized. At base line, vaccinated subjects were on average sicker, having higher rates of most coexisting conditions, outpatient care, and prior hospitalization for pneumonia than unvaccinated subjects. Unvaccinated subjects, however, were more likely to have been given a prior diagnosis of dementia or stroke. Vaccination against influenza was associated with a reduction in the risk of hospitalization for cardiac disease (reduction of 19 percent during both seasons [P<0.001]), cerebrovascular disease (reduction of 16 percent during the 1998-1999 season [P<0.018] and 23 percent during the 1999-2000 season [P<0.001]), and pneumonia or influenza (reduction of 32 percent during the 1998-1999 season [P<0.001] and 29 percent during the 1999-2000 season [P<0.001]) and a reduction in the risk of death from all causes (reduction of 48 percent during the 1998-1999 season [P<0.001] and 50 percent during the 1999-2000 season [P<0.001]). In analyses according to age, the presence or absence of major medical conditions at base line, and study site, the findings were consistent across all subgroups.
In the elderly, vaccination against influenza is associated with reductions in the risk of hospitalization for heart disease, cerebrovascular disease, and pneumonia or influenza as well as the risk of death from all causes during influenza seasons. These findings highlight the benefits of vaccination and support efforts to increase the rates of vaccination among the elderly.
New England Journal of Medicine 04/2003; 348(14):1322-32. · 53.30 Impact Factor
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ABSTRACT: This serial cohort study assessed the risk of hospitalization or death associated with influenza and the effectiveness of influenza vaccination among subgroups of elderly members of 3 managed-care organizations in the United States. Data on baseline characteristics and outcomes were obtained from computerized databases. A total of 122,974 (1996-1997 season) and 158,454 (1997-1998 season) persons were included in the cohorts. Among unvaccinated persons, hospitalizations for pneumonia/influenza or death occurred in 8.2 of 1000 healthy and 38.4 of 1000 high-risk persons in year 1, and in 8.2 of 1000 healthy and 29.3 of 1000 high-risk persons in year 2. After adjustments, vaccination was associated with a 48% reduction in the incidence of hospitalization or death (95% confidence interval [CI], 42-52) in year 1 and 31% (95% CI, 26-37) in year 2. Effectiveness estimates were statistically significant and generally consistent across the healthy and high-risk subgroups. The absolute risk reduction, however, was 2.4- to 4.7-fold higher among high-risk than among healthy elderly persons. All elderly individuals may substantially benefit from vaccination. However, the impact of influenza is greater in persons with high-risk medical conditions.
Clinical Infectious Diseases 09/2002; 35(4):370-7. · 9.15 Impact Factor
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W Katherine Yih,
Swati Deshpande,
Candace Fuller,
Dawn Heisey-Grove,
John Hsu,
Benjamin A Kruskal,
Martin Kulldorff,
Michael Leach, James Nordin,
Jessie Patton-Levine,
Ella Puga,
Edward Sherwood,
Irene Shui,
Richard Platt
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ABSTRACT: We evaluated a real-time ambulatory care-based syndromic surveillance system in four metropolitan areas of the United States.
Health-care organizations and health departments in California, Massachusetts, Minnesota, and Texas participated during 2007-2008. Syndromes were defined using International Classification of Diseases, Ninth Revision diagnostic codes in electronic medical records. Health-care organizations transmitted daily counts of new episodes of illness by syndrome, date, and patient zip code. A space-time permutation scan statistic was used to detect unusual clustering. Health departments followed up on e-mailed alerts. Distinct sets of related alerts ("signals") were compared with known outbreaks or clusters found using traditional surveillance.
The 62 alerts generated corresponded to 17 distinct signals of a potential outbreak. The signals had a median of eight cases (range: 3-106), seven zip code areas (range: 1-88), and seven days (range: 3-14). Two signals resulted from true clusters of varicella; six were plausible but unconfirmed indications of disease clusters, six were considered spurious, and three were not investigated. The median investigation time per signal by health departments was 50 minutes (range: 0-8 hours). Traditional surveillance picked up 124 clusters of illness in the same period, with a median of six ill per cluster (range: 2-75). None was related to syndromic signals.
The system was able to detect two true clusters of illness, but none was of public health interest. Possibly due to limited population coverage, the system did not detect any of 124 known clusters, many of which were small. The number of false alarms was reasonable.
Public Health Reports 125(1):111-20. · 1.27 Impact Factor
