Estimating the cost of inappropriate antibiotic prophylaxis prior to dental procedures.

Inappropriate dental antibiotic prescriptions to prevent infective endocarditis in the United States results in ∼$31 million in excess costs to the healthcare system and patients. This includes out-of-pocket costs ($20.5 million), drug costs ($2.69 million) and adverse event costs (eg, Clostridioides difficile and hypersensitivity) of $5.82 million (amoxicillin), $1.99 million (clindamycin), and $380,849 (cephalexin).

Cost-Effectiveness Analysis of Four Common Diagnostic Methods for Clostridioides difficile Infection.

BACKGROUND: No studies have evaluated the cost-effectiveness of single and two-step different diagnostic test strategies for Clostridioides difficile infection (CDI), including direct and indirect costs. OBJECTIVE: To evaluate the cost-effectiveness of commonly available diagnostic tests for CDI including nucleic acid amplification testing (NAAT) alone, glutamate dehydrogenase followed by enzyme immunoassay for toxin (GDH/EIA), GDH then NAAT (GDH/NAAT), and NAAT then EIA (NAAT/EIA). DESIGN: Decision tree model from the US societal perspective with inputs derived from the literature. Willingness-to-pay threshold was set at $150,000 per quality-adjusted life year (QALY) gained. To assess the impact of uncertainty in model inputs on the findings, we performed one-way and probabilistic sensitivity analyses. PARTICIPANTS: We conducted the analysis to represent a population aged 65 years old with diarrhea who received a CDI diagnostic test. MAIN MEASURES: Incremental cost-effectiveness ratios (ICER) and incremental net monetary benefits (INMB). KEY RESULTS: NAAT alone was the most cost-effective approach overall; GDH/NAAT was the most cost-effective two-step option. NAAT alone led to the highest QALYs gained, at an incremental cost of $54,547 (vs. GDH/NAAT), $55,410 (vs. GDH/EIA), and $50,231 (vs. NAAT/EIA) per QALY gained. NAAT/EIA was not cost-effective compared to any other strategy. GDH/NAAT resulted in a higher QALY compared to GDH/EIA, at an incremental cost of $96,841 per QALY gained. Variability in the likelihood of comorbidities, CDI probability, and age at disease onset did not substantially change the results. One-way sensitivity analyses showed that results were most sensitive to likelihood of recurrence, followed by CDI mortality rate and probability of severe CDI. Probabilistic sensitivity analyses explored known uncertainties in the base case and confirmed the robustness of the results. CONCLUSIONS: NAAT alone and GDH/NAAT (among the two-step options) were the most cost-effective diagnostic test approaches for CDI.

Early onset sepsis calculator-based management of newborns exposed to maternal intrapartum fever: a cost benefit analysis.

OBJECTIVE: To determine potential net monetary benefit of an early onset sepsis calculator-based approach for management of neonates exposed to maternal intrapartum fever, compared to existing guidelines. STUDY DESIGN: We performed a cost-benefit analysis comparing two management approaches for newborns >34 weeks gestational age exposed to maternal intrapartum fever. Probabilities of sepsis and meningitis, consequences of infection and antibiotic use, direct medical costs, and indirect costs for long-term disability and mortality were considered. RESULTS: A calculator-based approach resulted in a net monetary benefit of $3998 per infant with a 60% likelihood of net benefit in probabilistic sensitivity analysis. Our model predicted a 67% decrease in antibiotic use in the calculator arm. The absolute difference for all adverse clinical outcomes between approaches was ≤0.6%. CONCLUSIONS: Compared to existing guidelines, a calculator-based approach for newborns exposed to maternal intrapartum fever yields a robust net monetary benefit, largely by preventing unnecessary antibiotic treatment.

Behavioral Economics Interventions to Improve Outpatient Antibiotic Prescribing for Acute Respiratory Infections: a Cost-Effectiveness Analysis.

BACKGROUND: Behavioral economics interventions have been shown to effectively reduce the rates of inappropriate antibiotic prescriptions for acute respiratory infections (ARIs). OBJECTIVE: To determine the cost-effectiveness of three behavioral economic interventions designed to reduce inappropriate antibiotic prescriptions for ARIs. DESIGN: Thirty-year Markov model from the US societal perspective with inputs derived from the literature and CDC surveillance data. SUBJECTS: Forty-five-year-old adults with signs and symptoms of ARI presenting to a healthcare provider. INTERVENTIONS: (1) Provider education on guidelines for the appropriate treatment of ARIs; (2) Suggested Alternatives, which utilizes computerized clinical decision support to suggest non-antibiotic treatment choices in lieu of antibiotics; (3) Accountable Justification, which mandates free-text justification into the patient's electronic health record when antibiotics are prescribed; and (4) Peer Comparison, which sends a periodic email to prescribers about his/her rate of inappropriate antibiotic prescribing relative to clinician colleagues. MAIN MEASURES: Discounted costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. KEY RESULTS: Each intervention has lower costs but higher QALYs compared to provider education. Total costs for each intervention were $178.21, $173.22, $172.82, and $172.52, and total QALYs were 14.68, 14.73, 14.74, and 14.74 for the control, Suggested Alternatives, Accountable Justification, and Peer Comparison groups, respectively. Results were most sensitive to the quality-of-life of the uninfected state, and the likelihood and costs for antibiotic-associated adverse events. CONCLUSIONS: Behavioral economics interventions can be cost-effective strategies for reducing inappropriate antibiotic prescriptions by reducing healthcare resource utilization.

Cost-benefit analysis of hospital based postpartum vaccination with combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap).

OBJECTIVE: To assess the economic benefits associated with hospital-based postpartum Tdap (combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination. METHODS: A decision tree model was constructed to calculate the potential cost-benefit of this strategy from both a health care system and a societal perspective. Probabilities and costs were derived from published literature, data reported to Centers for Disease Control and Prevention, and recommendations from expert panels. The maternal vaccination protection period for infants was defined as 7 months, and 10 years of waning immunity following Tdap for birth mothers was estimated in the model. All cost estimates were inflated to year 2012 US dollars and discounted at a 3% annual discount rate. RESULTS: In the base case from a societal perspective, the expected costs per vaccinated and unvaccinated mother were estimated at $129.27 and $187.97, respectively, suggesting an expected net benefit of $58.70 per vaccinated mother. The overall societal benefits in the cohort of 3.6 million U.S. birth mothers ranged from $52.8-126.8 million, depending on the vaccination coverage level. If including direct medical costs only, the strategy would not generate net savings from a health care system perspective. Annual incidence of pertussis in birth mothers and Tdap efficacy exhibited substantial impact on the model as shown in one-way and two-way sensitivity analyses. CONCLUSIONS: Although postpartum Tdap vaccination is not cost-beneficial from a health care system perspective in the base case, this strategy is likely to generate net benefits from a societal perspective.

Cost-benefit analysis of in-hospital influenza vaccination of postpartum women.

OBJECTIVE: To estimate the potential economic benefits associated with hospital-based postpartum influenza vaccination. METHODS: We constructed a decision analysis model to estimate the potential cost benefit of this strategy from both a societal perspective and a third-party perspective. We included a hypothetical cohort of 1.47 million U.S. postpartum women, assuming an influenza season beginning September 1 and ending April 30. Probabilities and costs were derived from published literature, Centers for Disease Control and Prevention data, and expert recommendations. We used one-way and two-way sensitivity analyses. All cost estimates were inflated to year 2010 U.S. dollars and discounted at a 3% annual discount rate. RESULTS: From the societal perceptive, the expected costs per vaccinated and unvaccinated mother were $328.45 and $341.02 respectively, resulting in an expected net benefit of $12.57 per vaccinated mother. The overall savings in the cohort were predicted to range from $3.69 to $14.75 million, depending on the vaccination coverage rate. This strategy would be cost-beneficial, holding all other variables to the base case, if the annual maternal influenza attack rate is more than 2.8%, influenza vaccine efficacy is more than 47%, or if vaccine acquisition and administration cost per dose are less than $32.78. The strategy would not generate net savings from the third-party perspective. Sensitivity analyses were robust, but disease incidence and vaccine efficacy were important drivers. CONCLUSION: Our model suggests that postpartum influenza vaccination is a cost-beneficial approach for prevention of maternal and infantile influenza from a societal perspective. LEVEL OF EVIDENCE: III.

Compliance with multiple-dose vaccine schedules among older children, adolescents, and adults: results from a vaccine safety datalink study.

OBJECTIVES: We studied compliance with multiple-dose vaccine schedules, assessed factors associated with noncompliance, and examined timeliness of series completion among older children, adolescents, and adults. METHODS: We conducted a large, multisite, retrospective cohort study of older children, adolescents, and adults in the Vaccine Safety Datalink population from 1996 through 2004. We quantified the rates of completion of all required doses for varicella, hepatitis A, and hepatitis B vaccines according to their recommended schedules. RESULTS: Among those who received a first dose of varicella (n = 16 075), hepatitis A (n = 594 917), and hepatitis B (n = 590 445) vaccine, relatively few completed the series (55%-65% for hepatitis B vaccine and 40%-50% for hepatitis A and varicella vaccines in most age groups). Compliance was lowest among adolescents (35.9%) and Medicaid recipients (29.7%) who received varicella vaccine and among younger adult age groups who received hepatitis A vaccine (25%-35% across those age groups). Even among series completers, there was a relatively long interval of undervaccination between the first and last doses. CONCLUSIONS: Compliance with multiple-dose vaccine series among older children, adolescents, and adults is suboptimal. Further evaluations of strategies to improve compliance in these populations are needed.

Evaluation of vaccine coverage for low birth weight infants during the first year of life in a large managed care population.

OBJECTIVE: There are few recent population-based assessments of vaccine coverage in premature infants available. This study assesses and compares age- and dose-specific immunization coverage in children of different birth weight categories during the first year of life. METHODS: We performed a retrospective cohort analysis of computerized vaccination data from a large managed care organization in southern California. The participants were children born between January 1, 1997, and December 31, 2002, and continuously enrolled from birth to at least 12 months of age in the Southern California Kaiser Permanente health plan. We measured age-specific up-to-date and age-appropriate immunization rates according to birth weight (extremely low birth weight: <1000 g; very low birth weight: 1000-1499 g; low birth weight: 1500-2499 g; normal birth weight: >/=2500 g) for 4 vaccines (hepatitis B, diphtheria and tetanus toxoids with pertussis, Haemophilus influenzae type b, and poliovirus) through the first year of life. RESULTS: We identified 127 833 infants born during the study period and continuously enrolled through the first year of life; 120 048 were normal birth weight infants; 6491 were low birth weight infants; 788 were very low birth weight infants; and 506 were extremely low birth weight infants. Vaccine-specific age-appropriate immunization rates were 3% to 15% lower for low birth weight infants and 17% to 33% lower for extremely low birth weight infants compared with the rates for normal birth weight infants in the first 6 months of life. Extremely low birth weight infants had the lowest age-specific up-to-date immunization levels (5%-31% lower) compared with normal birth weight infants at each age assessed. By 12 months, extremely low birth weight infants still had significantly lower up-to-date levels (87%) compared with very low birth weight, low birth weight, and normal birth weight infants (91%-92%). CONCLUSIONS: Despite recommendations that lower birth weight infants be vaccinated as the same chronological age as normal birth weight infants, extremely low birth weight and very low birth weight infants are immunized at significantly lower rates relative to low birth weight and normal birth weight infants at 2, 4, and 6 months of age. However, by 12 months of age this finding persists only in extremely low birth weight infants.

Incidence of neonatal herpes simplex virus infections in two managed care organizations: implications for surveillance.

OBJECTIVES: To estimate the incidence of neonatal herpes simplex virus (HSV) infections and to assess the utility of surveillance methods for neonatal herpes in 2 managed care populations. METHODS: We identified potential cases using 15 discharge International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes for neonatal HSV and other diseases clinically consistent with this diagnosis. We also searched laboratory databases for positive HSV tests and investigated deaths during the neonatal period. We performed medical chart review using a standardized form. Two pediatric infectious disease specialists reviewed the forms of infants who had a positive HSV test or received a herpes-related diagnosis and made a determination as confirmed, probable, or not a case. RESULTS: Among 270,703 infants born from 1997 to 2002, we identified 737 potential cases and completed medical chart abstraction for 699 (95%). Final review identified 35 confirmed or probable cases of neonatal HSV, and the incidence was 12.9 per 100,000 live births. Only 24 (69%) of the 35 cases were confirmed by laboratory testing. Among the 24 confirmed cases, 22 (92%) received an ICD-9 code of 054.xx or 771.2. Among the 60 infants that received an ICD-9 code of 054.xx or 771.2, only 31 (52%) were confirmed or probable cases of neonatal HSV after final review. CONCLUSIONS: About 30% of neonatal HSV cases were not laboratory confirmed. The use of ICD-9 codes of 054.xx and 771.2 was a sensitive but not specific method to identify cases of neonatal herpes.

Compliance with national immunization guidelines for children younger than 2 years, 1996-1999.

OBJECTIVES: To evaluate compliance with national immunization guidelines among a large cohort of children cared for at health maintenance organizations (HMOs) and to examine effects on immunization status. METHODS: A cohort study of 176134 children born between January 1, 1994, and December 31, 1997, and monitored from birth to the second birthday was performed. Subjects belonged to the Vaccine Safety Datalink Project, a study of children enrolled in 1 of 4 HMOs. Children were continuously enrolled in a HMO for the first 2 years of life. Prevailing recommendations regarding optimal ages of immunization and intervals between doses were applied to define appropriate immunization timing and immunization status. Noncompliance was defined as having a missing or late immunization or an immunization error. Immunization errors included invalid immunizations (too early to be acceptable), extra immunizations (superfluous immunizations or make-up immunizations for invalid immunizations), and missed opportunities resulting in late or missing immunizations. RESULTS: Although 75.4% of children in these HMOs were up to date for all immunizations at 2 years, only 35.6% of children were fully compliant with recommended immunization practices. Less than 8% of children received all immunizations in accordance with strict interpretation of recommended guidelines. Fifty-one percent of children had at least 1 immunization error by age 2 years; 29.7% had a missed opportunity with subsequent late or missing immunization, 20.4% had an invalid immunization, and 11.6% had an extra immunization. Common reasons for noncompliance included missed opportunities for the fourth Haemophilus influenzae type b vaccine (14.6%), invalid fourth diphtheria-tetanus-pertussis/acellular pertussis immunizations (11.0%), and superfluous polio immunizations (9.8%). CONCLUSIONS: Approximately 35.6% of children were compliant with prevailing childhood immunization recommendations from 1996 to 1999. Efforts to improve compliance with guidelines are recommended, to optimize childhood infectious disease prevention.

Safety of the trivalent inactivated influenza vaccine among children: a population-based study.

BACKGROUND: To our knowledge, there are no published population-based studies on the safety of the inactivated trivalent influenza vaccine among children. OBJECTIVE: To screen a large population of children for evidence of increased medical visits in the 2 weeks after influenza vaccination compared with 2 control periods. Secondary analyses included shorter risk periods and restricted age categories. DESIGN: Self-control screening analysis. Children vaccinated from January 1, 1993, through December 31, 1999, were randomly divided into 2 equal groups. In group 1, risks of outpatient, emergency department, and inpatient visits during the 14 days after vaccination were compared with the risks of visits in 2 control periods. Significant plausible medically attended events identified in group 1 were then analyzed in group 2, using the same 2 control periods. Medically attended events significant in both groups were considered potentially associated with vaccination and were assessed by medical record review. SETTING: Five managed care organizations in the United States. PARTICIPANTS: Children younger than 18 years who received an influenza vaccination in one of the managed care settings (N = 251 600). MAIN OUTCOME MEASURE: Among vaccinated children seen for a medically attended event, the odds of the visit occurring in the 2 weeks after vaccination vs during 1 of the 2 control periods. RESULTS: Study participants incurred 1165, 230, and 489 different diagnoses during the 14 days after vaccination according to the outpatient, emergency department, and inpatient data, respectively. Four diagnoses were positively associated with the vaccine in both groups 1 and 2: impetigo, dermatitis, uncomplicated diabetes mellitus, and ureteral disorder not otherwise specified. After medical record review, impetigo (9 cases) in children 6 to 23 months old remained significantly associated with vaccination. CONCLUSION: This large screening safety study did not reveal any evidence of important medically attended events associated with pediatric influenza vaccination.

Polio extraimmunization in children younger than 2 years after changes in immunization recommendations.

OBJECTIVE: To investigate trends over time in polio extraimmunization among children in 4 large health maintenance organizations and to study the association with recent changes in polio immunization policy. METHODS: Using 176 169 children who were born after 1994 and enrolled for their first 2 years of life, we assessed rates and trends of polio extraimmunization in the Vaccine Safety Datalink project. We used logistic regression to test the association of extraimmunization with different polio immunization schedules and with sociodemographic characteristics and used Poisson regression to test changes in rates over time. RESULTS: Overall, 10.5% were extraimmunized for poliovirus; children on the all inactivated polio virus or sequential schedule were one half as likely as those on the all oral polio virus schedule to be extraimmunized by 2 years of age. There was a significant decrease in extraimmunization over time, with <5% of children born at the end of 1997 being extraimmunized, compared with >15% at the beginning of 1994. CONCLUSIONS: Poliovirus extraimmunization rates have fallen dramatically in association with the change-over to the all inactivated polio virus schedule.

Lack of association between rotavirus infection and intussusception: implications for use of attenuated rotavirus vaccines.

BACKGROUND: Withdrawal of the tetravalent rhesus-human rotavirus vaccine Rotashield because of its association with intussusception raised concerns about a potential link between natural rotavirus disease and intussusception. Our objective was to determine whether such an association exists. METHODS: In the Southern California Kaiser Permanente Health Care Plan, a large health maintenance organization, from October, 1992, to July, 1999, we retrospectively identified by computerized data and medical charts all children <3 years old with intussusception, and from 1997 to 1999 we independently identified by prospective clinical and laboratory evaluation children <3 years old with rotavirus diarrhea. We compared the epidemiologic characteristics of intussusception and rotavirus infection in our study population and evaluated for the presence of both diseases in individual patients. RESULTS: Using computerized data we identified 124 cases of intussusception, 101 (81%) of which were confirmed by medical chart and radiologic reviews. The incidences for infants <1 year old and for children <3 years old were 41 (95% confidence interval, 32 to 55) and 17 (95% confidence interval, 13 to 20) per 100,000 child years, respectively. Between November 1997 and July 1999, we identified 470 cases of rotavirus diarrhea and none had intussusception. Although rotavirus diarrhea had a distinct peak incidence between December and February, intussusception had no apparent seasonality. The age distributions overlapped, but intussusception occurred at an earlier age than rotavirus disease. CONCLUSIONS: We found no epidemiologic evidence for an association between intussusception and natural rotavirus infection, but our study was limited by an insufficient number of cases to definitively exclude a causal link. The dramatic winter peak of rotavirus disease had no discernable parallel in the incidence of intussusception. Our data suggest that the association between tetravalent rhesus-human rotavirus vaccine and intussusception may possibly result from the nonhuman rotavirus components of that vaccine.