Depletion-of-susceptibles bias in influenza vaccine waning studies: how to ensure robust results.

Vaccine effectiveness studies are subject to biases due to depletion-of-persons at risk of infection, or at especially high risk of infection, at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination to assess waning in vaccine protection as a function of vaccination time (namely whether earlier vaccination would result in lower subsequent protection compared to later vaccination). Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomised trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable to depletion-of-susceptibles bias in its inference of waning as a function of vaccination time under the null hypothesis that none exists, and will - if waning does actually occur - underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomised.

A comparison of health care experiences for medicaid and commercially enrolled children in a large, nonprofit health maintenance organization.

BACKGROUND: Proponents of Medicaid managed care have argued that this type of care offers the potential to provide mainstream health care for poor children and the elimination of the 2-tier system of care that has long existed for poor and nonpoor children. However, few studies have attempted to assess whether differences in access, utilization, and satisfaction exist between Medicaid and commercially sponsored children who are enrolled in the same managed care plan. OBJECTIVE: To systematically answer the following research question: Within the same large, nonprofit, group-model health maintenance organization (HMO), how do children enrolled in Medicaid compare with children enrolled commercially across the domains of access, utilization, and satisfaction with care? METHODS: We compared access, satisfaction, and utilization of services between Medicaid and commercially sponsored children enrolled in Kaiser Permanente of Northern California during 1998 through use of a telephone survey and administrative data. Kaiser Permanente is a nonprofit, integrated, group HMO that serves 2.8 million members in more than 15 counties in northern California. The sample for this survey included 510 Medicaid-enrolled children and 512 commercially enrolled children. An overall response rate of 82% was achieved. Bivariate and multivariate analyses were used to compare Medicaid and commercially enrolled children. RESULTS: We found few differences between commercial and Medicaid enrollees across the domains of access, utilization, and satisfaction. Where access differences were present (problems in finding a personal care provider, problems getting care overall, and experiencing 1 or more barriers to care), the differences favored Medicaid-enrolled children. That is, Medicaid enrollees were reported to experience significantly fewer access problems and barriers than commercial enrollees, even after adjustment for confounding factors. Only one difference was found between Medicaid and commercial enrollees across the 6 utilization variables examined (volume of emergency department visits), and no differences were found among the 4 satisfaction and 2 global assessments of care received. Taken together, our results suggest that Medicaid-enrolled children experience as good as or better care than their commercially enrolled counterparts. However, there are other possible explanations for our findings. It may be that families of Medicaid-enrolled children hold their care providers to a lower standard than families of commercially enrolled children, given historic inequities in care between poor and nonpoor families. In addition, some degree of selection bias may be present in our sample, although that is true for both the Medicaid and commercial populations. CONCLUSIONS: Our findings suggest that large commercial HMOs are capable of eliminating the access barriers and stigma traditionally associated with the Medicaid program. However, this conclusion must be tempered with the knowledge that other explanations for our findings may also be at play.

Comparing the medical expenses of children with Medicaid and commercial insurance in an HMO.

BACKGROUND: In recent years, growing numbers of children with Medicaid have been enrolled in managed care plans nationwide. Yet, large, commercial managed care plans are increasingly discontinuing their participation in Medicaid because of low Medicaid payment rates. OBJECTIVE: To compare the healthcare utilization and costs of children with Medicaid and children with commercial insurance within the same health maintenance organization (HMO). STUDY DESIGN: Retrospective study using electronically captured cost and utilization data. PATIENTS AND METHODS: We compared the healthcare utilization and costs of children with Medicaid (n = 42,636) and children with commercial insurance (n = 159,651) who were members of the same large, nonprofit HMO at any time between January 1, 1995, and December 31, 1997. Medicaid children were grouped as income eligible, medically needy, and blind or disabled. RESULTS: The unadjusted costs of income-eligible, Medicaid-insured children were not significantly different from those of commercially insured children. The medically needy were $25 per month more expensive than commercially insured children (P = 0.02), and the blind or disabled were $213 per month more expensive (P < .01). After adjusting for age and sex, income-eligible children were $5 per month more expensive than children with commercial insurance (P = .07), the medically needy were $20 per month more expensive (P = .02), and the blind or disabled were $216 per month more expensive (P < .01). CONCLUSIONS: The costs of income-eligible, Medicaid-insured children in this HMO were similar to those of commercially insured children, but the costs for the medically needy and the blind and disabled were substantially higher.

The hidden costs of infant vaccination.

Combination vaccines to minimize injections required for infant vaccination, and new vaccines with improved safety profiles, will pose increasingly complex choices for vaccine purchasers in the future. How much of a premium to pay for such vaccines might be determined by taking into account (1) the psychological burden of multiple injections during a single clinic visit, and the costs of any additional visits to minimize these, and (2) the medical, work-loss, and incidental costs of common vaccine-associated symptoms. This cross-sectional survey included randomly-selected parents of 1-8-month-old infants who received vaccines in a Northern California health maintenance organization (HMO) in 1997. Interviewers called parents 14 days after the infant's vaccination to administer a 10-minute closed-ended interview in English or Spanish. Parents were asked about infant symptoms after vaccination, their preferences regarding multiple injections and their (theoretical) willingness to pay to reduce the number of injections their infant would receive, or to avoid the adverse symptoms experienced. Among 1769 eligible infants, interviews were completed with parents of 1657 (93%). The psychological cost of multiple injections was estimated by the willingness of parents to pay a median of $25 to reduce injections from 4 to 3, $25 from 3 to 2, and $50 from 2 to 1. Vaccine-associated symptoms caused mean costs of $42 in medical utilization and $192 in work-loss among the families who experienced those events (Ns=62 and 35, respectively). When averaged among all 1657 study infants, vaccine-associated symptoms after the index vaccination visit resulted in $2.91 in medical utilization, $4.05 in work-loss, and $0.74 in direct nonmedical costs, yielding total financial costs of $7.70. Parents of infants who had vaccine-associated symptoms said they would have paid a median of $50 to avoid these symptoms. Fever and fussiness were associated in logistic regression analysis with a two-fold increase in the odds of medical utilization, and fever with more than a three-fold increase in work loss. We conclude that multiple injections during a single clinic visit entail psychological costs. The psychological costs of vaccine-associated symptoms, as measured by willingness-to-pay methods, are higher than those resulting from multiple injections. The financial costs of medical utilization and work-loss resulting from common vaccine-associated symptoms are non-negligible and should be incorporated in economic analyses.

Newborn circumcision decreases incidence and costs of urinary tract infections during the first year of life.

OBJECTIVE: To assess the effect of newborn circumcision on the incidence and medical costs of urinary tract infection (UTI) during the first year of life for patients in a large health maintenance organization. SETTING: Kaiser Permanente Medical Care Program of Northern California (KPNC). PATIENTS: The population consisted of members of KPNC. The study group consisted of a cohort of 28 812 infants delivered during 1996 at KPNC hospitals; of the 14 893 male infants in the group, 9668 (64.9%) were circumcised. A second cohort of 20 587 infants born in 1997 and monitored for 12 months was analyzed to determine incidence rates. DESIGN: Retrospective study of all infants consecutively delivered at 12 facilities. OUTCOME MEASURES: Diagnosis of UTI was determined from the KPNC computerized database using the International Classification of Diseases, Ninth Revision code for inpatients and KPNC Outpatient Summary Clinical Record codes for outpatients. A sample of 52 patient charts was reviewed to confirm the International Classification of Diseases, Ninth Revision and KPNC Outpatient Summary Clinical Record codes and provide additional data. RESULTS: Infants <1 year old who were born in 1996 had 446 UTIs (292 in females; 154 in males); 132 (86%) of the UTIs in males occurred in uncircumcised boys. The mean total cost of managing UTI was 2 times as high in males ($1111) as in females ($542). This higher total cost reflected the higher rate of hospital admission in uncircumcised males with UTIs (27.3%) compared with females (7.5%); mean age at hospitalization for UTI was 2.5 months old for uncircumcised boys and 6.5 months old for girls. In 1996, total cost of managing UTI in uncircumcised males ($155 628) was 10 times higher than for circumcised males ($15 466) despite the fact that uncircumcised males made up only 35.1% of the male patient base in 1996, reflecting the more frequent occurrence of UTI in uncircumcised males (132 episodes) than in circumcised males (22 episodes), and the larger number of hospital admissions in uncircumcised males (38) than in circumcised males (4). The incidence of UTI in the first year of life was 1:47 (2.15%) in uncircumcised males, 1:455 (.22%) in circumcised males, and 1:49 (2. 05%) in females. The odds ratio of UTI in uncircumcised:circumcised males was 9.1:1. CONCLUSIONS: Newborn circumcision results in a 9. 1-fold decrease in incidence of UTI during the first year of life as well as markedly lower UTI-related medical costs and rate of hospital admissions. Newborn circumcision during the first year of life is, thus, a valuable preventive health measure, particularly in the first 3 months of life, when uncircumcised males are most likely to be hospitalized with severe UTI.

Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children.

CONTEXT: Pneumococcal conjugate vaccine for infants has recently been found effective against meningitis, bacteremia, pneumonia, and otitis media. OBJECTIVE: To evaluate the projected health and economic impact of pneumococcal conjugate vaccination of healthy US infants and young children. DESIGN: Cost-effectiveness analysis based on data from the Northern California Kaiser Permanente randomized trial and other published and unpublished sources. SETTING AND PATIENTS: A hypothetical US birth cohort of 3.8 million infants. INTERVENTIONS: Hypothetical comparisons of routine vaccination of healthy infants, requiring 4 doses of pneumococcal conjugate vaccine (at 2, 4, 6, and 12-15 months), and catch-up vaccination of children aged 2 to 4.9 years requiring 1 dose, with children receiving no intervention. MAIN OUTCOME MEASURES: Cost per life-year saved and cost per episode of meningitis, bacteremia, pneumonia, and otitis media prevented. RESULTS: Vaccination of healthy infants would prevent more than 12000 cases of meningitis and bacteremia, 53000 cases of pneumonia, 1 million episodes of otitis media, and 116 deaths due to pneumococcal infection. Before accounting for vaccine costs, the vaccination program would save $342 million in medical and $415 million in work-loss and other costs from averted pneumococcal disease. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose. At the manufacturer's list price of $58 per dose, infant vaccination would cost society $80000 per life-year saved or $160 per otitis media episode prevented (other estimated costs would be $3200 per pneumonia case prevented, $15000 for bacteremia, and $280000 for meningitis). The cost-effectiveness of an additional program to administer 1 dose of vaccine to children aged 2 to 4.9 years would vary depending on the children's ages, relative risks of pneumococcal disease, and vaccine cost. CONCLUSIONS: Pneumococcal conjugate vaccination of healthy US infants has the potential to be cost-effective. To achieve cost savings, its cost would need to be lower than the manufacturer's list price. In addition to tangible costs, the vaccine should be appraised based on the less tangible value of preventing mortality and morbidity from pneumococcal disease.

The cost of health conditions in a health maintenance organization.

In this retrospective cohort analysis of all adults who were members of Kaiser Permanente, Northern California, between July 1995 and June 1996 (N = 2,076,303), the authors estimated the prevalence, average annual costs per person, and percentage of total direct medical expenditures attributable to each of 25 chronic and acute conditions. Ordinary least squares regression was used to adjust for age, gender, and comorbidities. The costs attributable to the 25 conditions accounted for 78 percent of the health maintenance organization's total direct medical expense for this age-group. Injury accounted for a higher proportion (11.5 percent) of expenditures than any other single condition. Three cardiovascular conditions--ischemic heart disease, hypertension, and congestive heart failure--together accounted for 17 percent of direct medical expense and separately accounted for 6.8 percent, 5.7 percent, and 4.0 percent, respectively. Renal failure ($22,636), colorectal cancer ($10,506), pneumonia ($9,499), and lung cancer ($8,612) were the most expensive conditions per person per year.

Cost of care for patients in cancer clinical trials.

BACKGROUND: Information on the costs of medical care for patients enrolled in clinical trials is needed by policymakers evaluating ways to facilitate clinical research in a managed care environment. We examined the direct costs of medical care for patients enrolled in cancer clinical trials at a large health maintenance organization (HMO). METHODS: Costs for 135 patients who entered 22 cancer clinical trials (including 12 breast cancer trials) at Kaiser Permanente in Northern California, from 1994 through 1996 were compared with costs for 135 matched control subjects who were not enrolled in such trials. Cancer registry data and medical charts were used in matching the control subjects to the trial enrollees with respect to cancer site, stage, date of diagnosis, age, sex, and trial eligibility. The direct costs of medical care were compared between trial enrollees and the control subjects for a 1-year period, with data on costs and utilization of services obtained from Kaiser Permanente databases and medical charts. RESULTS: Mean 1-year costs for the enrollees in trials were 10% higher than those for the control subjects ($17 003 per enrollee compared with $15 516 per control subject; two-sided P =.011). The primary component of this difference was a $1376 difference in chemotherapy costs ($4815 per trial enrollee versus $3439 per control subject; two-sided P<.001). Costs for the 11 enrollees in trials that had a bone marrow transplant (BMT) arm were approximately double the costs for their matched control subjects (borderline significance: two-sided P=.054). The $15 041 mean cost for the enrollees in trials without BMT was similar to the $15 186 mean cost for their matched control subjects. CONCLUSIONS: Participation in cancer clinical trials at a large HMO did not result in substantial increases in the direct costs of medical care.

Assessing costs and cost effectiveness of pneumococcal disease and vaccination within Kaiser Permanente.

OBJECTIVE: To review studies of the costs of pneumococcal disease and the cost effectiveness of pneumococcal conjugate vaccination conducted in association with the Kaiser Permanente Pneumococcal conjugate Efficacy Trial. RESULTS: for each birth cohort of 3.8 million infants, routine pneumococcal conjugate vaccination program for healthy infants would prevent more than 12000 (78% of potential) meningitis and bacteremia cases, 53000 (69% of potential) pneumonia cases, and 1 million (8% of potential) otitis media episodes. Before accounting for vaccine costs, the vaccination program would reduce the costs of pneumococcal disease by $342 million in medical and $415 million in work-loss and other costs. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose.

Second-trimester serum chorionic gonadotropin concentrations and complications and outcome of pregnancy.

BACKGROUND: Maternal serum chorionic gonadotropin is measured to screen for fetal chromosomal abnormalities. Whether the results can also be used to predict the risk of complications or an adverse outcome of pregnancy is not known. METHODS: We reviewed the medical records of 28,743 girls and women in whom chorionic gonadotropin was measured during the second trimester of pregnancy (between July 1, 1995, and January 31, 1997), seeking information about the complications and outcome of their pregnancies. We excluded girls and women who had preexisting risk factors for complications or an adverse outcome of pregnancy. RESULTS: Higher serum chorionic gonadotropin concentrations were associated with higher rates of stillbirth (odds ratio for every increase in chorionic gonadotropin of 1 multiple of the median, 1.4; 95 percent confidence interval, 1.1 to 1.9). There was no relation between higher serum chorionic gonadotropin concentrations and the risk of gestational diabetes, premature rupture of membranes or intrauterine growth retardation or small size for gestational age (odds ratio, 1.1; 95 percent confidence interval, 0.9 to 1.2). Higher serum chorionic gonadotropin concentrations were associated with a risk of placental abnormalities (odds ratio, 1.5; 95 percent confidence interval, 1.3 to 1.7), pregnancy-induced hypertension (odds ratio, 1.4; 95 percent confidence interval, 1.3 to 1.5), and preterm delivery without pregnancy-induced hypertension (odds ratio, 1.1; 95 percent confidence interval, 1.0 to 1.2). Inclusion in certain racial or ethnic categories (black, Filipino or Pacific Islander, unknown race or ethnic group, and "other," which included those of Middle Eastern descent and Native Americans) was a better predictor of the risk of an adverse outcome than serum chorionic gonadotropin values. CONCLUSIONS: Measurements of serum chorionic gonadotropin are of little clinical value for predicting the risk of complications and the outcome of pregnancy.

Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants.

OBJECTIVES: To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%. RESULTS: Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was /=28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12,000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33,000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39,000 to $420,000 per hospitalization averted or $110,000 to $1,200,000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization. CONCLUSION: In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.

The cost of medical care for patients with cystic fibrosis in a health maintenance organization.

BACKGROUND: Cystic fibrosis (CF) is the most common life-shortening genetic disorder among white individuals worldwide. Previous estimates of the costs of medical care have been based on expert opinion rather than observed costs. Accurate cost estimates are needed to enable evaluation of the cost-effectiveness of new interventions and prenatal genetic screening recommendations. OBJECTIVE: To evaluate the cost of medical care for patients (N = 136) served by a health maintenance organization with a CF center. METHODS: Retrospective analysis of data from computerized cost databases and the Cystic Fibrosis Foundation annual survey. Severity of disease was classified based on the percent predicted forced expiratory volume at 1 second. RESULTS: The annual cost of medical care in 1996 averaged $13 300 and ranged from $6200 among patients with mild disease to $43 300 among patients with severe disease. Of total costs, 47% were from hospitalization, 18% were from DNase (Pulmozyme), 12% were from clinic visits, and 10% were from outpatient antibiotics. When the observed costs were used to estimate the costs of medical care for the entire population of CF patients in the United States, these costs were estimated to be $314 million per year in 1996 dollars. CONCLUSIONS: We conclude that the cost of medical care for CF varies greatly with severity but is substantial even among patients with mild disease. These findings underscore the need for strategies to ensure good health insurance coverage and high quality care for all individuals with this condition.

Preventing neonatal group B streptococcal disease: cost-effectiveness in a health maintenance organization and the impact of delayed hospital discharge for newborns who received intrapartum antibiotics.

OBJECTIVES: To estimate the cost and health benefits of implementing a risk factor-based prevention strategy for early-onset neonatal group B streptococcal (GBS) disease, using baseline assumptions and costs from a health maintenance organization. With the risk factor-based strategy, intrapartum antibiotics (IPAs) would be provided to women with fever, prolonged rupture of membranes, or preterm labor. A second objective was to determine the impact of an increased length of stay for well term infants with mothers who received IPAs. METHODS: We used decision analysis to compare the costs and benefits of the prevention strategy with usual obstetric practice for a cohort of 100 000 women and their newborn infants. We derived baseline values from a previous study based on chart review and automated cost data from a health maintenance organization in Northern California. In sensitivity analyses, we varied baseline assumptions, including additional costs for observing well term infants who received IPAs. RESULTS: If adherence to guidelines were 100%, 17% of mothers would receive IPAs at a cost of $490,000; $1.6 million would be saved by preventing 66 GBS cases (64% reduction). The net savings would be $1.1 million and 61 life-years. The net cost is sensitive to the cost of caring for well infants who received IPAs. If each term infant of a mother who received IPAs had 1 more day of observation than other term infants, there would be a net cost of $8.1 million; the cost per GBS case prevented would be $120,000 and the cost per life-year saved would be $130,000. CONCLUSIONS: Implementation in a health maintenance organization of a risk factor-based strategy to prevent neonatal GBS disease can prevent substantial disease and be cost saving. However, if the length of hospital stay were extended among well term infants whose mothers received IPAs, the strategy would be relatively costly compared with other medical interventions.

Affinity modulation of small-molecule ligands by borrowing endogenous protein surfaces.

A general strategy is described for improving the binding properties of small-molecule ligands to protein targets. A bifunctional molecule is created by chemically linking a ligand of interest to another small molecule that binds tightly to a second protein. When the ligand of interest is presented to the target protein by the second protein, additional protein-protein interactions outside of the ligand-binding sites serve either to increase or decrease the affinity of the binding event. We have applied this approach to an intractable target, the SH2 domain, and demonstrate a 3-fold enhancement over the natural peptide. This approach provides a way to modulate the potency and specificity of biologically active compounds.

Parent reports on willingness to accept childhood immunizations during urgent care visits.

OBJECTIVES: To 1) describe whether parents would be willing to accept childhood immunizations at urgent care visits; and 2) identify predictors of parents' willingness to accept childhood immunizations at urgent care visits. DESIGN AND PARTICIPANTS: Cross-sectional telephone survey of parents of children aged 18 to 24 months who were underimmunized according to a computerized immunization tracking system and who had recently made an urgent care visit in a regional group-model health maintenance organization in Northern California. Chart review was conducted to confirm immunization status and to identify contraindications to vaccination. RESULTS: Of the 424 eligible participants, 351 (83%) completed interviews. Children with contraindications to vaccination and children who were actually up-to-date at the time of the urgent care visit were excluded, leaving 263 families in the final analysis. Among these parents, 75% said they would have been willing to have their child immunized at the urgent care visit in question if the physician had suggested it. An additional 11% said they would have accepted vaccination if the physician told them that the shot would be safe and strongly encouraged them to accept it. Overall, 86% reported they theoretically would have accepted an immunization during the urgent care visit. In the multivariate analysis, the strongest predictors of stated willingness to accept shots at the urgent care visit were the parent: 1) not being aware that their child was underimmunized (odds ratio [OR] 3.5, 95% confidence interval [CI], 1.6-7.7); 2) perceiving that the child was not very sick at the visit (OR 1.8, 95% CI, 1.1-3.0); 3) being less concerned about the risk of shots (OR 1.8, 95% CI, 1.2-2.5); and 4) being of nonwhite race (OR 3.6, 95% CI, 1.6-7.7). Income and education were not significantly associated with reported willingness to accept immunization. CONCLUSIONS: We conclude that most parents of underimmunized toddlers report being willing to accept immunizations during urgent care visits if the clinician recommends it. More effective ways of alerting providers in urgent care settings when immunizations are due, such as indications on a chart or registration form, hold promise for improving immunization coverage rates.

Neonatal group B streptococcal infection in a managed care population. Perinatal Group B Streptococcal Infection Study Group.

OBJECTIVE: In a health maintenance organization population, we determined the incidence of early-onset (at less than or equal to 7 days) neonatal group B streptococcal (GBS) disease, the sensitivity and prevalence of labor risk factors, the adherence to a protocol for intrapartum antibiotics, and the costs for care of and outcomes of affected infants. METHODS: Mothers and infants at four health maintenance organization hospitals in northern California in 1989 to 1995 were studied retrospectively using computerized databases and chart review. In 1994, two of the four hospitals had adopted protocols similar to the ACOG recommendations for intrapartum antibiotics for women with labor risk factors (preterm, temperature 100.4F or higher, or rupture of membranes (ROM) 18 hours or more). RESULTS: Among the 79,940 live births, the incidence of early-onset neonatal GBS infection was higher among preterm than among term infants (3.1 compared with 0.9 per 1000). Before protocol adoption, 68% of 65 infants with GBS had mothers with labor risk factors. Approximately 18% of all mothers had labor risk factors: 7.7% had preterm delivery, and 10.6% had term delivery with fever and/or ROM 18 hours or more. At the two hospitals that adopted GBS protocols, GBS incidence was reduced from 1.3 per 1000 in the preprotocol period to 0.8 per 1000 in the postprotocol period (P=.08). Six cases of neonatal GBS occurred after protocol adoption. Of these, four were not preventable under the protocol and two might have been preventable if protocol had been followed. Three of the 19 preterm infants with group B streptococcal disease died. CONCLUSION: Risk factor-based protocols hold some promise to reduce GBS disease, but clinical strategies to promote protocol adherence are needed.

Projected cost-effectiveness of primary angioplasty for acute myocardial infarction.

OBJECTIVES: This study sought to evaluate the cost-effectiveness of primary angioplasty for acute myocardial infarction under varying assumptions about effectiveness, existing facilities and staffing and volume of services. BACKGROUND: Primary angioplasty for acute myocardial infarction has reduced mortality in some studies, but its actual effectiveness may vary, and most U.S. hospitals do not have cardiac catheterization laboratories. Projections of cost-effectiveness in various settings are needed for decisions about adoption. METHODS: We created a decision analytic model to compare three policies: primary angioplasty, intravenous thrombolysis and no intervention. Probabilities of health outcomes were taken from randomized trials (base case efficacy assumptions) and community-based studies (effectiveness assumptions). The base case analysis assumed that a hospital with an existing laboratory with night/weekend staffing coverage admitted 200 patients with a myocardial infarction annually. In alternative scenarios, a new laboratory was built, and its capacity for elective procedures was either 1) needed or 2) redundant with existing laboratories. RESULTS: Under base case efficacy assumptions, primary angioplasty resulted in cost savings compared with thrombolysis and had a cost of $12,000/quality-adjusted life-year (QALY) saved compared with no intervention. In sensitivity analyses, when there was an existing cardiac catheterization laboratory at a hospital with > or = 200 patients with a myocardial infarction annually, primary angioplasty had a cost of < $30,000/QALY saved under a wide range of assumptions. However, the cost/QALY saved increased sharply under effectiveness assumptions when the hospital had < 150 patients with a myocardial infarction annually or when a redundant laboratory was built. CONCLUSIONS: At hospitals with an existing cardiac catheterization laboratory, primary angioplasty for acute myocardial infarction would be cost-effective relative to other medical interventions under a wide range of assumptions. The procedure's relative cost-ineffectiveness at low volumes or redundant laboratories supports regionalization of cardiac services in urban areas. However, approaches to overcoming competitive barriers and close monitoring of outcomes and costs will be needed.

Excess costs of medical care for patients with diabetes in a managed care population.

OBJECTIVE: To estimate the excess costs of medical care for patients with diabetes in a managed care population and to determine the proportion of costs spent on treating the complications of diabetes. RESEARCH DESIGN AND METHODS: A comparison of 1-year (1994) costs of medical care in the 85,209 members of the diabetes registry of Kaiser Permanente, Northern California, and in 85,209 age- and sex-matched nondiabetic control subjects. Costs were obtained from automated program databases. Costs specifically related to treating acute and long-term complications of diabetes were identified, and the excess costs attributable to each complication in individuals with diabetes were calculated. RESULTS: Excess expenditures in individuals with diabetes totaled $282.7 million, or $3,494 per person. Per person expenditures for members with diabetes were 2.4 times those for matched control subjects. The largest proportion of total excess costs was for hospitalizations within the health maintenance organization (38.5%). Nearly 38% of the total excess was spent treating the long-term complications of diabetes, predominantly coronary heart disease and end-stage renal disease. CONCLUSIONS: Diabetes is a costly condition by virtue of its high prevalence and high per person costs. A large proportion of these costs are related to treating complications of diabetes. Available evidence indicates that several measures can reduce complication rates. Thus, effective disease management programs that aim to prevent complications could potentially lead to cost savings in managed care settings.

Initial cost of primary angioplasty for acute myocardial infarction.

OBJECTIVES: We sought to evaluate the initial economic cost of primary angioplasty for acute myocardial infarction under varying assumptions about whether a cardiac catheterization laboratory exists, whether services are provided during night and weekend hours and how cardiovascular surgical backup is arranged. BACKGROUND: Primary angioplasty for acute myocardial infarction has resulted in clinical outcomes superior or equal to those obtained with thrombolysis in recent studies, but its future implementation depends greatly on its cost and cost-effectiveness. There is a gap in knowledge about the true economic costs of this procedure, and understanding costs under a variety of hypothetic scenarios is important in planning whether and how the procedure should be offered to broad groups of patients. METHODS: A generalizable spreadsheet model was constructed to calculate the cost of primary angioplasty at a single hospital with assumptions based on data from a large nonprofit health maintenance organization (Kaiser Permanente). The following baseline assumptions were made: 1) A total of 200 patients with myocardial infarction presented to the hospital each year; 2) primary angioplasty was offered for 10 years; 3) the hospital had a cardiac catheterization laboratory; 4) costs of night call for technical personnel and cardiovascular surgical backup were already covered. Other scenarios were modeled to represent different assumptions about existing resources. RESULTS: Under the baseline assumptions, primary angioplasty cost $1,597/procedure. If night call for technical personnel were a new expense, the average cost would be > or = $3,206. If a new cardiac catheterization laboratory needed to be built, costs would range from $3,866 to $14,339/procedure, depending on how cardiovascular surgical backup was provided. Results were sensitive to assumptions about the annual volume of myocardial infarctions, the number of years the procedure was offered and the costs of labor, construction and equipment. CONCLUSIONS: The initial cost of providing primary angioplasty for acute myocardial infarction varies greatly, depending on the setting in which it is provided. To provide information for clinical policy decisions, a cost-effectiveness model is needed that combines these initial costs with data on survival, quality of life and rates and costs of subsequent cardiac procedures.