Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses.

INTRODUCTION: Patients with atherosclerotic cardiovascular disease (ASCVD), especially those with recent (< 1 year) acute coronary syndrome (ACS), are at high risk for recurrent cardiovascular events. This risk can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) levels. A comprehensive meta-analysis on the LDL-C-lowering efficacy of ezetimibe is lacking. This study attempts to address this gap. METHODS: A systematic literature review of randomized controlled trials evaluating the LDL-C-lowering efficacy of ezetimibe in the ASCVD population was conducted. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for publications from database inception to August 2018 and for conference abstracts from 2015 to August 2018. Meta-analyses were conducted to evaluate the LDL-C-lowering efficacy of ezetimibe in the ASCVD population and the recent ACS subgroup. RESULTS: In total, 12 studies were eligible for the meta-analyses. Treatment with combination ezetimibe plus statin therapy showed greater absolute LDL-C reduction than statin monotherapy (mean difference - 21.86 mg/dL; 95% confidence interval [CI] - 26.56 to - 17.17; p < 0.0001) after 6 months of treatment (or at a timepoint closest to 6 months). Similarly, in patients with recent ACS, combination ezetimibe plus statin therapy was favorable compared with statin monotherapy (mean treatment difference - 19.19 mg/dL; 95% CI - 25.22 to - 13.16; p < 0.0001). CONCLUSIONS: Ezetimibe, when added to statin therapy, provided a modest additional reduction in LDL-C compared with statin monotherapy. However, this may not be sufficient for some patients with ASCVD who have especially high LDL-C levels despite optimal statin therapy.

Efficacy and Safety of Basal Analog Regimens in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: This study compared basal analog (BA: glargine U100/mL and detemir) and premix (PM: human, lispro and aspart biphasic) insulin regimens in terms of their efficacy and safety in type 2 diabetes mellitus patients. METHODS: Searches of MEDLINE, Embase, and CENTRAL identified primary randomized controlled trials (RCTs) ≥ 12 weeks in duration that compared BA or PM insulin regimens in adults with T2DM, with ≥ 30 patients per arm. A systematic literature review and a pairwise meta-analysis were performed using a random effects model adjusted for between-study variability. Analyses were conducted based on frequency of bolus insulin and PM injections, PM ratio and type, BA type, race, follow-up period, and baseline glycosylated hemoglobin (HbA1c). RESULTS: Twenty-two primary RCTs with 9691 patients were included. The BA and PM regimens yielded similar changes in HbA1c and postprandial glucose levels, with a statistically significant reduction in fasting glucose [mean difference (MD) - 0.61 mmol/L (95% confidence interval (CI) - 0.90, - 0.32), I2 = 89.6%]. The BA regimens showed significantly reduced rates of total hypoglycemia [odds ratio (OR) 0.77 (95% CI 0.64, 0.92), I2 = 65.3%] and changes in body weight [MD - 0.48 kg (95% CI - 0.86, - 0.11), I2 = 75.7%] compared to PM regimens. Stratification by PM type and dosing ratio demonstrated statistically significant reductions in HbA1c favoring BA compared to human [MD - 0.39% (95% CI - 0.60, - 0.18), I2 = 61.8%] or 50/50-ratio [MD - 0.22% (95% CI - 0.40, - 0.04), I2 = 0.0%] PM regimens. Other subgroup analyses found no difference in HbA1c change between the BA and PM regimens. CONCLUSION: When compared to PM regimens, BA regimens yielded similar efficacies and better safety profiles in patients with type 2 diabetes mellitus. FUNDING: Sanofi (Shanghai, China).

Costs of managing anemia with erythropoiesis-stimulating agents during hemodialysis: a time and motion study.

Use of erythropoiesis-stimulating agents (ESAs) presents a significant time and cost burden in the management of anemia of chronic kidney disease (CKD). We conducted a prospective, observational, activity-based costing study to estimate the health care personnel time and resulting direct medical costs associated with administering epoetin 3 times weekly to patients with end-stage renal disease on dialysis. The study was conducted at 5 US hemodialysis centers. The personnel time and costs were derived from time and motion observations. Predicted time and cost savings were modeled for switching patients to once-monthly ESA therapy. Patients also completed a survey questionnaire to assess their level of CKD knowledge and information needs. Total per-patient-per-year (PPPY) time expended on anemia management with epoetin averaged 608 minutes (range 512-915 minutes), with an average PPPY cost of $548 (range $342-$651). Use of a once-monthly ESA, compared with epoetin, could decrease average PPPY time expenditure by 79% (127 minutes [range 96-173 minutes]) and reduce PPPY costs by 81% ($104 [range $79-$136]). The patient questionnaire reported insufficient education on CKD. Use of a once-monthly ESA to correct anemia in dialysis patients may provide substantial time, resource, and cost savings compared with current treatment practices.

Effect of erythropoiesis-stimulating agents on healthcare utilization, costs, and outcomes in chronic kidney disease.

BACKGROUND: Anemia commonly complicates chronic kidney disease (CKD). Treating anemia of CKD with erythropoiesis-stimulating agents (ESAs) may attenuate cardiovascular and renal sequelae, reducing morbidity, mortality, and healthcare costs. OBJECTIVE: To compare clinical outcomes, healthcare utilization, and costs in ESA-treated and untreated patients with anemia of CKD who are not on dialysis. METHODS: This retrospective claims analysis considered more than 13 million US health plan members for outpatient, inpatient, emergency department, and prescription experience. Eligible patients were aged 15 years or older with 2 or more ICD-9 diagnoses of CKD or 1 or more CKD diagnosis and 1 or more claims for ESA within 12 months. The first CKD diagnosis within the study period (January 1, 2000-December 31, 2003) defined the index date. Anemia was ascertained by ICD-9 codes or ESA claims on or after the CKD index date. Patients were censored for dialysis, transplant, inpatient death, disenrollment, or study end. Utilization and costs per patient per month were compared between ESA and non-ESA patients. Generalized linear modeling identified predictors of total and anemia-related costs. RESULTS: Of 26,244 patients with CKD, 8188 (31.2%) had anemia; of those, only 14.6% (n = 1197) received ESAs. ESA recipients had lower total monthly healthcare costs than did untreated anemic patients ($3876 vs $4758; p = 0.0061). Lower monthly inpatient and emergency department costs in treated versus untreated anemic patients ($2507 vs $3849 and $46.56 vs $81, respectively; both p < 0.0001) outweighed higher outpatient and laboratory costs from ESA use ($602 vs $397 and $23.50 vs $14.34, respectively; both p < 0.0001). Multivariate analysis revealed that ESA users had lower adjusted monthly total costs ($2962 vs $3373) compared with non-ESA patients. CONCLUSIONS: ESA use was associated with mean total cost savings of $411 per patient per month, reflecting reduced inpatient and emergency department visits and costs, and with lower inpatient mortality and longer time to dialysis. The low (14.6%) ESA treatment rate for anemia highlights the continuing deficit in CKD care.

Randomized pilot study to disseminate caries-control services in dentist offices.

BACKGROUND: To determine whether education and financial incentives increased dentists' delivery of fluoride varnish and sealants to at risk children covered by capitation dental insurance in Washington state (U.S.). METHODS: In 1999, 53 dental offices in Washington Dental Service's capitation dental plan were invited to participate in the study, and consenting offices were randomized to intervention (n = 9) and control (n = 10) groups. Offices recruited 689 capitation children aged 6-14 and at risk for caries, who were followed for 2 years. Intervention offices received provider education and fee-for-service reimbursement for delivering fluoride varnish and sealants. Insurance records were used to calculate office service rates for fluoride, sealants, and restorations. Parents completed mail surveys after follow-up to measure their children's dental utilization, dental satisfaction, dental fear and oral health status. Regression models estimated differences in service rates between intervention and control offices, and compared survey measures between groups. RESULTS: Nineteen offices (34%) consented to participate in the study. Fluoride and sealant rates were greater in the intervention offices than the control offices, but the differences were not statistically significant. Restoration rates were lower in the intervention offices than the control offices. Parents in the intervention group reported their children had less dental fear than control group parents. CONCLUSION: Due to low dentist participation the study lacked power to detect an intervention effect on dentists' delivery of caries-control services. The intervention may have reduced children's dental fear.

Cessation of periodontal care during pregnancy: effect on infant birthweight.

The goal of this study was to assess whether interruption of care for chronic periodontitis during pregnancy increased the risk of low-birthweight infants. A population-based case-control study was designed with 793 cases (infants < 2,500 g) and a random sample of 3,172 controls (infants >or= 2,500 g). Generalized estimating equation models were used to relate periodontal treatment history to low birthweight risk and to common risk factors. The results indicate that periodontal care utilization was associated with a 2.35-fold increased odds of self-reported smoking during pregnancy (95% confidence interval: 1.48-3.71), a 2.19-fold increased odds for diabetes (95% confidence interval: 1.21-3.98), a 3.90-fold increased odds for black race (95% confidence interval: 2.31-6.61), and higher maternal age. After adjustment for these factors, interruption of periodontal care during pregnancy did not lead to an increased risk for a low-birthweight infant when compared to women with no history of periodontal care (odds ratio, 0.96; 95% confidence interval, 0.60-1.52). In conclusion, women receiving periodontal care had genetic and environmental characteristics, such as smoking, diabetes and race, that were associated with an increased risk for low-birthweight infants. Periodontal care patterns, in and of themselves, were unrelated to low-birthweight risk.

The ABCDs of treating the most prevalent childhood disease.

Dental caries is a potentially preventable infectious disease that, untreated, can cause significant morbidity requiring costly treatment. The Access to Baby and Child Dentistry (ABCD) program increases access to prevention and early treatment for Medicaid-eligible children aged younger than 6 years in Washington State. The program is a partnership of Washington Dental Service Foundation, the University of Washington School of Pediatric Dentistry, the state Medical Assistance Administration, and local stakeholders. Through training in pediatric dental techniques and enhanced reimbursement, ABCD equips and encourages dentists to serve young Medicaid patients. Family counseling increases oral care compliance and reduces no-show rates. Program evaluation demonstrates changing attitudes and behavior among participating families and dentists, with more young, low-income Washington children receiving oral health care.

Practice patterns among male and female general dentists in a Washington State population.

BACKGROUND: Women make up about 14 percent of general dentists in the United States, and the proportion is projected to exceed 29 percent by 2020. METHODS: The authors obtained dental benefits claims data from the Washington Dental Service (WDS), Seattle, and used them to examine the practice patterns of 265 women and 1,947 men engaged in general dentistry for at least 26 days in 2001. Practice variables of interest included age, days worked, procedures performed and total income from WDS reimbursements and patient copayments. The number, age and sex of patients treated also were obtained. Using productivity data, the authors also estimated the potential impact of an increase in the percentage of female dentists in the state. RESULTS: The authors found no differences between male and female dentists in the number of procedures per patient, income per patient or income per day of work. Frequency distributions of various services were highly similar for both groups. Multiple regression models showed no influence of dentist's sex on total income. However, the mean and median numbers of days worked were about 10 percent lower for female dentists than for male dentists. This difference was consistent with the finding that female dentists treated approximately 10 percent fewer patients, performed about 10 percent fewer procedures and had a combined income of about 10 percent less than that of male dentists. CONCLUSION: Practice patterns of male and female dentists generally were equivalent in this WDS population. CLINICAL IMPLICATIONS: Female and male dentists provided a similar range of services and earned an equal income per patient treated and per day worked. However, women worked fewer days per year than did men, irrespective of age. If the dental work force and practice patterns remain unchanged otherwise, the total number of patients treated per dentist will decrease slightly as women make up an increasing proportion of dentists.

Ambulatory activity in men with diabetes: relationship between self-reported and real-world performance-based measures.

The measurement of physical activity, especially walking activity, is important for many outcome studies. In many investigations, the Physical Activity scale of the short-form-36 (SF-36) health assessment questionnaire is used in lieu of an actual physical measurement of walking. This study determined the relationship between the SF-36 questionnaire and the Step Activity Monitor (SAM), a real-world performance-based tool that counts the actual number of steps taken during daily activities. We studied the physical activity of 57 men with diabetes using step count monitoring and the SF-36 questionnaire. The subjects averaged 3,293 steps/day, but had a very wide range (111-11,654) and a large standard deviation (SD = 2,037). The correlations between total daily steps and the SF-36 Physical Component Summary score, and the Physical Function, Bodily Pain, and Vitality scales of the SF-36 were only fair (Pearson's r = 0.376, 0.488, 0.332, 0.380, respectively). The corresponding coefficients of determination range from only 7.7% to 23.8%. Physical activity is a complex concept not completely represented by either the SF-36 or the step counts. The correlation between actual walking activity and the SF-36 is not as strong as many researchers believe. Caution should be exercised with the use of the SF-36 to specifically measure walking activity.

Orthodontic care in an insured population in Washington: demographic factors.

Few studies have used insurance claims data to investigate demographic factors related to orthodontic care. This study sought to describe age and sex distributions in a large, insured population in Washington. Additionally, the demand for orthodontic care was evaluated with respect to county population, and the impact of the availability of orthodontists was investigated. All orthodontic claims in 2001 were retrieved from the Washington Dental Service database, along with associated provider and patient information. A total of 102,984 claims were included in this study. A large percentage of subjects (86%) were less than 20 years old, with most patients in their early teens. Overall, about 64% of all orthodontic patients were female. The demand for orthodontic treatment was the highest in the counties with the largest populations. Although there was considerable variation in the data, the number of orthodontic claims submitted by general dentists tended to decline as the availability of orthodontists increased.

Antepartum dental radiography and infant low birth weight.

CONTEXT: Both high- and low-dose radiation exposures in women have been associated with low-birth-weight offspring. It is unclear if radiation affects the hypothalamus-pituitary-thyroid axis and thereby indirectly birth weight, or if the radiation directly affects the reproductive organs. OBJECTIVE: To investigate whether antepartum dental radiography is associated with low-birth-weight offspring. DESIGN: A population-based case-control study. PARTICIPANTS AND SETTING: Enrollees of a dental insurance plan with live singleton births in Washington State between January 1993 and December 2000. Cases were 1117 women with low-birth-weight infants (<2500 g), of whom 336 were term low-birth-weight infants (1501-2499 g and gestation > or =37 weeks). Four control pregnancies resulting in normal-birth-weight infants (> or =2500 g) were randomly selected for each case (n = 4468). MAIN OUTCOME MEASURES: Odds of low birth weight and term low birth weight by dental radiographic dose during gestation. RESULTS: An exposure higher than 0.4 milligray (mGy) during gestation occurred in 21 (1.9%) mothers of low-birth-weight infants and, when compared with women who had no known dental radiography, was associated with an adjusted odds ratio (OR) for a low-birth-weight infant of 2.27 (95% confidence interval [CI], 1.11-4.66, P =.03). Exposure higher than 0.4 mGy occurred in 10 (3%) term low-birth-weight pregnancies and was associated with an adjusted OR for a term low-birth-weight infant of 3.61 (95% CI, 1.46-8.92, P =.005). CONCLUSION: Dental radiography during pregnancy is associated with low birth weight, specifically with term low birth weight.

Distribution of orthodontic services and fees in an insured population in Washington.

Previous attempts to quantify the amount and type of orthodontic therapy provided by nonorthodontists in the United States have relied on survey data. Although there are advantages to surveys, such as control over survey recipients and inclusion of specific questions, they also have limitations, such as low response rates, response bias, and recall bias. This study used insurance claims data from a large dental benefits provider in Washington to assess the distribution of orthodontic services and fees among various dental providers. All orthodontic claims allowed by Washington Dental Service in 2001 were retrieved, along with treatment codes, fees, and demographic information for both patients and providers. A total of 102,984 orthodontic claims were included in the study. General dentists submitted 7.0% of these claims, orthodontists submitted 90.9%, and pedodontists submitted 1.9%. Orthodontists submitted higher average fees for space maintainers, first payments, and records. The percentage of orthodontic treatment preformed by general dentists and pedodontists in this claims-based study was substantially less than what has been previously reported in survey-based studies. Additionally, a smaller percentage of general dentists and pedodontists in this study performed comprehensive treatment, compared with previous studies. This study illustrates the value of insurance claims data to assess the provision of orthodontic care.

Patterns of endodontic care for a Washington state population.

Endodontic care, provided by 3,402 dental offices, was assessed from claims data maintained by the Washington Dental Service for 1999. Approximately 5.7 million dental procedures were provided to 880,317 patients by 2,796 general practitioners, 105 endodontists, and 494 other specialists. Of all dental services, 63,321 (1%) were endodontic procedures involving 52,911 (6%) patients. General dentists, endodontists, and other specialists performed 64.7%, 33.7%, and 1.6% of endodontic procedures, the majority of which were root canal therapy. The most frequent tooth types treated by root canal therapy were mandibular first molars (17.0%), maxillary first molars (15.2%), mandibular second molars (11.8%), maxillary second bicuspids (10.3%), maxillary second molars (9.1%), maxillary central and lateral incisors (8.8%), and mandibular second bicuspids (8.0%). Direct and indirect pulp caps by generalists and conventional retreatment and surgical therapy by endodontists made up the majority of the remaining endodontic services. Men had a greater procedure rate than women for most endodontic procedures.

Analyses of Streptococcus mutans in saliva with species-specific monoclonal antibodies.

Three species-specific monoclonal antibodies (MAbs) against Streptococcus mutans were used to detect and quantify S. mutans levels in saliva. This study shows that MAb-based salivary S. mutans tests exhibit significantly higher specificity and sensitivity than the commonly used selective culture method. Examination of nearly 2,000 human saliva samples shows that S. mutans counts in human saliva vary from less than 10,000 to a high 36 million cells/mL. Over 15% of the saliva samples examined have salivary S. mutans counts over 500,000 cells/mL. When saliva samples were collected at different time points during a day, the number of salivary S. mutans in the same human subject varied, especially before and after sugar uptake. Additionally, data obtained from stimulated versus unstimulated saliva in the same human subjects differed greatly and appear to be completely uncorrelated. This study provides useful information and tools for analyzing the role of S. mutans in human dental caries.

Patterns of oral care in a Washington State dental service population.

BACKGROUND: The authors compare patterns of oral health care reported by the Washington Dental Service, or WDS, Seattle, in 1993 and 1999 to assess changes in patient populations, practice characteristics, procedures and treatment costs in the state. METHODS: Data were obtained from dental benefits claims from a population of about 1.25 million people. Variables of interest included patient age and other demographic information, character of dental practice, dental procedures and treatment costs that combined WDS payment and patient copayment. RESULTS: The results showed high agreement (97 percent) between the database and randomly surveyed patient records. For both 1993 and 1999, general dental offices were responsible for more than 80 percent of patient care. Single crowns (21 percent), restorative services (15 percent) and dental prophylaxis (13 percent) made up about half of the costs of dental care. Broad categories of service were similar in 1993 and 1999, and anticipated major declines in restorative procedures related to caries were not apparent. The mix of services varied considerably by patient age and between generalists and specialists in both years. CONCLUSIONS: Patterns of oral health care among this insured patient population largely remained unchanged from 1993 to 1999, with some shifts in specific procedures and specialty care. During this period, dentists saw more patients and performed fewer treatments per patient, while total treatment costs per patient increased. CLINICAL IMPLICATIONS: Patterns of oral health care in the United States are projected to undergo major changes linked to improved oral health, declining trends in caries and periodontal diseases, scientific advances in treatment approaches and a patient population that is living longer. Changes in care patterns during this six-year period may reflect patient and provider preferences, as well as the influence of reimbursement policies. Dental benefits databases can serve as a critical resource for monitoring such changes.