David L. McClure

Parental Refusal of Pertussis Vaccination Is Associated With an Increased Risk of Pertussis Infection in Children

OBJECTIVE. The objective of this study was to determine if children who contracted pertussis infection were more likely to have parents who refused pertussis vaccinations than a similar group of children who did not develop pertussis infection. METHODS. We conducted a case-control study of children enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each pertussis case was matched to 4 randomly selected controls. Pertussis case status and vaccination status were ascertained by medical chart review. RESULTS. We identified 156 laboratory-confirmed pertussis cases and 595 matched controls. There were 18 (12%) pertussis vaccine refusers among the cases and 3 (0.5%) pertussis vaccine refusers among the controls. Children of parents who refused pertussis immunizations were at an increased risk for pertussis compared with children of parents who accepted vaccinations. In a secondary case-control analysis of children continuously enrolled in Kaiser Permanente of Colorado from 2 to 20 months of age, vaccine refusal was associated with a similarly increased risk of pertussis. In the entire Kaiser Permanente of Colorado pediatric population, 11% of all pertussis cases were attributed to parental vaccine refusal. CONCLUSIONS. Children of parents who refuse pertussis immunizations are at high risk for pertussis infection relative to vaccinated children. Herd immunity does not seem to completely protect unvaccinated children from pertussis. These findings stress the need to further understand why parents refuse immunizations and to develop strategies for conveying the risks and benefits of immunizations to parents more effectively.

Impact of Repeated Vaccination on Vaccine Effectiveness Against Influenza A(H3N2) and B During 8 Seasons

The effect of prior influenza vaccination history on vaccine effectiveness was assessed in a community cohort over 8 seasons. Current- and previous-season vaccination generated similar levels of protection; vaccine-induced protection was greatest for individuals with no recent vaccination history.

Adherence to cardioprotective medications and mortality among patients with diabetes and ischemic heart disease

BackgroundPatients with diabetes and ischemic heart disease (IHD) are at high risk for adverse cardiac outcomes. Clinical practice guidelines recommend multiple cardioprotective medications to reduce recurrent events. We evaluated the association between cardioprotective medication adherence and mortality among patients with diabetes and IHD.MethodsIn a retrospective cohort study of 3,998 patients with diabetes and IHD, we evaluated use of ACE inhibitors or angiotensin receptor blockers, β-blockers, and statin medications. Receipt of cardioprotective medications was based on filled prescriptions. Medication adherence was calculated as the proportion of days covered (PDC) for filled prescriptions. The primary outcome of interest was all-cause mortality.ResultsThe majority of patients (92.8%) received at least 1 cardioprotective medication. Patients receiving any medications had lower unadjusted mortality rates compared to patients not receiving any medications (7.9% vs. 11.5%; p = 0.03). In multivariable analysis, receipt of any cardioprotective medication remained associated with lower all-cause mortality (OR 0.65; 95% CI 0.43–0.99). Among patients receiving cardioprotective medications, the majority (80.3%) were adherent (PDC ≥ 0.80). Adherent patients had lower unadjusted mortality rates (6.7% vs. 12.1%; p < 0.01). In multivariable analysis, medication adherence remained associated with lower all-cause mortality (OR 0.52; 95% CI 0.39–0.69) compared to non-adherence. In contrast, there was no mortality difference between patients receiving cardioprotective medications who were non-adherent compared to patients not receiving any medications (OR 1.01; 95% CI 0.64–1.61).ConclusionIn conclusion, medication adherence is associated with improved outcomes among patients with diabetes and IHD. Quality improvement interventions are needed to increase medication adherence in order for patients to maximize the benefit of cardioprotective medications.

Parental refusal of varicella vaccination and the associated risk of varicella infection in children.

OBJECTIVE To quantify both the individual-level and attributable risk of varicella infection requiring medical care in children whose parents refuse varicella immunizations. DESIGN Matched case-control study with conditional logistic regression analysis. SETTING Kaiser Permanente of Colorado (KPCO) health plan between 1998 and 2008. PARTICIPANTS Each pediatric physician-diagnosed case of varicella (n = 133) was matched to 4 randomly selected controls (n = 493). Cases were matched by age, sex, and length of enrollment in KPCO. Main Exposures Varicella vaccine refusal. OUTCOME MEASURES Varicella infection. RESULTS There were 7 varicella vaccine refusers (5%) among the cases and 3 (0.6%) among the controls. Children of parents who refused varicella immunizations were at a greatly increased risk of varicella infection requiring medical care (odds ratio, 8.6; 95% confidence interval, 2.2-33.3) compared with children of parents who accepted vaccinations (P = .004). In the entire KPCO pediatric population, 5% of varicella cases were attributed to parental vaccine refusal. CONCLUSIONS Children of parents who refuse varicella immunizations are at high risk of varicella infection relative to vaccinated children. These results will be helpful to health care providers and parents when making decisions about immunizing children.

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season

BACKGROUND Recent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2). METHODS Patients with acute respiratory illness were actively recruited during the 2007-2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders. RESULTS There were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p=0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable. CONCLUSIONS Identification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.

The Risk of Immune Thrombocytopenic Purpura After Vaccination in Children and Adolescents

BACKGROUND: The risk of immune thrombocytopenic purpura (ITP) after childhood vaccines other than measles-mumps-rubella vaccine (MMR) is unknown. METHODS: Using data from 5 managed care organizations for 2000 to 2009, we identified a cohort of 1.8 million children ages 6 weeks to 17 years. Potential ITP cases were identified by using diagnostic codes and platelet counts. All cases were verified by chart review. Incidence rate ratios were calculated comparing the risk of ITP in risk (1 to 42 days after vaccination) and control periods. RESULTS: There were 197 chart-confirmed ITP cases out of 1.8 million children in the cohort. There was no elevated risk of ITP after any vaccine in early childhood other than MMR in the 12- to 19-month age group. There was a significantly elevated risk of ITP after hepatitis A vaccine at 7 to 17 years of age, and for varicella vaccine and tetanus-diphtheria-acellular pertussis vaccine at 11 to 17 years of age. For hepatitis A, varicella, and tetanus-diphtheria-acellular pertussis vaccines, elevated risks were based on one to two vaccine-exposed cases. Most cases were acute and mild with no long-term sequelae. CONCLUSIONS: ITP is unlikely after early childhood vaccines other than MMR. Because of the small number of exposed cases and potential confounding, the possible association of ITP with hepatitis A, varicella, and tetanus-diphtheria-acellular pertussis vaccines in older children requires further investigation.

Parental Decline of Pneumococcal Vaccination and Risk of Pneumococcal Related Disease in Children

BACKGROUND An increasing number of parents are choosing to decline immunizations for their children. This study examined the association between the parental decision to decline pneumococcal conjugate (PCV7) vaccinations and the risk of hospitalization due to pneumococcal disease or lobar pneumonia in children. METHODS We conducted a case-control study nested within a cohort of children enrolled in the Kaiser Permanente Colorado (KPCO) health plan between 2004 and 2009. Each child hospitalized with pneumococcal disease or lobar pneumonia (n=106) was matched to 4 randomly selected controls (n=401). Cases were matched to controls by age, sex, high-risk status, calendar time, and length of enrollment in KPCO. Disease status and parental vaccination decisions were validated with medical record review. Cases and controls were classified as vaccine decliners or vaccine acceptors. RESULTS Among 106 cases, there were 6 (6%) PCV7 vaccine decliners; among 401 controls, there were 4 (1%) vaccine decliners. Children of parents who declined PCV7 immunization were 6.5 times (OR=6.5; 95% CI=1.7, 24.5) more likely to be hospitalized for invasive pneumococcal disease or lobar pneumonia than vaccinated children. CONCLUSIONS Parental decline of pneumococcal vaccination apparently increases the risk for hospitalization due to pneumococcal disease or lobar pneumonia in children. Providers can use this information when helping parents weigh the benefits and risks of immunizing their children.

Comparison of epidemiologic methods for active surveillance of vaccine safety

OBJECTIVE We performed a simulation study to compare four study designs [(matched-cohort, vaccinated-only (risk-interval) cohort, case-control, and self-controlled case-series (SCCS)] in the context of vaccine safety active surveillance. METHODS For each combination of various incidence levels (3, 30, 300 per 10(5) person-years) and relative risks (RR 1.5-18), 100 case sets were infused into the cohort, matching 10(5) vaccinated to 10(5) unvaccinated on age and gender. The matched-cohort was converted into weekly accumulated data intervals with the other three study design samples drawn from each. Analyses were with appropriate regression models. The signal detection time was the first week where the log likelihood ratio (LLR) exceeded the upper boundary from the MaxSPRT sequential analysis method. Empirical type I (false positive) and type II (power) error rates and risk estimate bias were also calculated. RESULTS The matched-cohort design exhibited the shortest detection time, lowest false positive rate and highest empirical power followed by the risk-interval cohort, SCCS, and case-control. In most monitoring weeks, the risk estimate bias was smallest for the cohort, followed by the risk-interval, SCCS and case-control designs. CONCLUSIONS The cohort study design performed the best in the sequential analysis of active surveillance for vaccine safety. The risk-interval cohort and SCCS designs offer reasonable and efficient alternatives, especially if selection bias is a concern. Future research should address seasonality or age effects.

Laboratory Evaluation of Potassium and Creatinine Among Ambulatory Patients Prescribed Spironolactone: Are We Monitoring for Hyperkalemia?

Background: Serum potassium and creatinine evaluation is recommended in patients prescribed spironolactone, yet the proportion of ambulatory patients chronically dispensed spironolactone receiving evaluation is not well understood. Objective: To estimate the rate of potassium and creatinine evaluation and identify factors associated with conducting these tests among ambulatory patients dispensed spironolactone. Methods: A retrospective cohort study was designed to evaluate patients at 10 health maintenance organizations with ongoing spironolactone dispensing for one year (N = 2257). Potassium and creatinine evaluation were determined from administrative data. Associations between patient characteristics and laboratory testing were assessed, using logistic regression modeling. Results: Serum creatinine and potassium were evaluated in 72.3% of patients during a 13 month period. The likelihood of potassium and creatinine monitoring was greater among patients who were older (OR 1.28; 95% CI 1.17 to 1.41 per decade of life); male (OR 1.25; 95% CI 1.01 to 1.54); had diabetes (OR 1.63; 95% CI 1.31 to 2.03); received concomitant therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (OR 2.23; 95% CI 1.74 to 2.87), potassium supplements (OR 1.96; 95% CI 1.51 to 2.54), or digoxin (OR 2.10 95% CI 1.48 to 2.98); or had more outpatient visits (OR 1.31; 95% CI 1.19 to 1.44). Among patients with heart failure (n = 790), factors associated with the incidence of laboratory testing were diabetes (OR 1.64, 95% CI 1.14 to 2.34), outpatient visits (OR 1.20; 95% CI 1.02 to 1.41), and digoxin therapy (OR 2.26; 95% CI 1.38 to 3.69). Conclusions: Three-fourths of ambulatory patients dispensed spironolactone receive recommended laboratory evaluation, with monitoring more likely to be completed in patients prescribed concomitant therapy with drugs that increase hyperkalemia risk, older patients, and those with diabetes.

Influenza Vaccination Is Not Associated With Detection of Noninfluenza Respiratory Viruses in Seasonal Studies of Influenza Vaccine Effectiveness

Influenza vaccination was not associated with detection of noninfluenza respiratory viruses in young children or older adults with acute respiratory illness. Use of influenza-negative controls did not generate a biased estimate of vaccine effectiveness due to an effect of vaccination on other respiratory virus infections.