Abstract

In an era of limited healthcare budgets, mathematical models can be useful tools to identify cost-effective programs and to support policymakers in informed decision making. This paper reports results of our work carried out over several years with the Asian Liver Center at Stanford University, a nonprofit outreach and advocacy organization that is an international leader in the fight against hepatitis B and liver cancer. Hepatitis B is a vaccine-preventable viral disease that, if untreated, can lead to death from cirrhosis and liver cancer. Infection with hepatitis B is a major public health problem, particularly in Asian populations. We used new combinations of decision analysis and Markov models to analyze the cost-effectiveness of several interventions to combat hepatitis B in the United States and China. The results of our OR-based analyses have helped change United States public health policy on hepatitis B screening for millions of people and have helped encourage policymakers in China to enact legislation to provide free catch-up vaccination for hundreds of millions of children. These policies are an important step in eliminating health disparities, reducing discrimination, and ensuring that millions of people who need it can now receive hepatitis B vaccination or lifesaving treatment.

Abstract

BACKGROUND:

To determine which of 3 interventions was most effective in improving blood pressure (BP) control, we performed a 4-arm randomized trial with 18-month follow-up at the primary care clinics at a Veterans Affairs Medical Center.

METHODS:

Eligible patients were randomized to either usual care or 1 of 3 telephone-based intervention groups: (1) nurse-administered behavioral management, (2) nurse- and physician-administered medication management, or (3) a combination of both. Of the 1551 eligible patients, 593 individuals were randomized; 48% were African American. The intervention telephone calls were triggered based on home BP values transmitted via telemonitoring devices. Behavioral management involved promotion of health behaviors. Medication management involved adjustment of medications by a study physician and nurse based on hypertension treatment guidelines.

RESULTS:

The primary outcome was change in BP control measured at 6-month intervals over 18 months. Both the behavioral management and medication management alone showed significant improvements at 12 months-12.8% (95% confidence interval [CI], 1.6%-24.1%) and 12.5% (95% CI, 1.3%-23.6%), respectively-but not at 18 months. In subgroup analyses, among those with poor baseline BP control, systolic BP decreased in the combined intervention group by 14.8 mm Hg (95% CI, -21.8 to -7.8 mm Hg) at 12 months and 8.0 mm Hg (95% CI, -15.5 to -0.5 mm Hg) at 18 months, relative to usual care.

CONCLUSIONS:

Overall intervention effects were moderate, but among individuals with poor BP control at baseline, the effects were larger. This study indicates the importance of identifying individuals most likely to benefit from potentially resource intensive programs.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00237692.

Abstract

BACKGROUND- The majority of current implantable cardioverter-defibrillator (ICD) recipients are significantly older than those in the ICD trials. Data on periprocedural complications among the elderly are insufficient. We evaluated the influence of age on perioperative complications among primary prevention ICD recipients in the United States. METHODS AND RESULTS- Using the National Cardiovascular Data's ICD Registry, we identified 150 264 primary prevention patients who received ICDs from January 2006 to December 2008. The primary end point was any adverse event or in-hospital mortality. Secondary end points included major adverse events, minor adverse events, and length of stay. Of 150 264 patients, 61% (n=91 863) were 65 years and older. A higher proportion of patients ≥65 years had diabetes, congestive heart failure, atrial fibrillation, renal disease, and coronary artery disease. Approximately 3.4% of the entire cohort had any complication, including death, after ICD implant. Any adverse event or death occurred in 2.8% of patients under 65 years old; 3.1% of 65- to 69-year-olds; 3.5% of 70- to 74-year-olds; 3.9% of 75- to 79-year-olds, 4.5% of 80- to 84-year-olds; and 4.5% of patients 85 years and older. After adjustment for clinical covariates, multivariate analysis found an increased odds of any adverse event or death among 75- to 79-year-olds (1.14 [95% confidence interval, 1.03 to 1.25], 80-to 84-year-olds (1.22 [95% confidence interval, 1.10 to 1.36], and patients 85 years and older (1.15 [95% confidence interval, 1.01 to 1.32], compared with patients under 65 years old. CONCLUSIONS- Older patients had a modestly increased-but acceptably safe-risk of periprocedural complications and in-hospital mortality, driven mostly by increased comorbidity.

Abstract

OBJECTIVES:

To estimate the potentially inappropriate use of implantable cardioverter-defibrillator ICDs in older U.S. adults.

DESIGN:

Retrospective study.

SETTING:

The National Cardiovascular Data ICD Registry.

PARTICIPANTS:

Forty-four thousand eight hundred five individuals in the National Cardiovascular Data's ICD Registry(™) who had received ICDs for primary prevention from January 2006 to December 2008. Individuals with a prior myocardial infarction and ejection fraction less than 30% were included.

MEASUREMENTS:

Mortality risk was categorized using the Multicenter Automatic Defibrillator Implantation (MADIT) II risk-stratification system. Low-risk and very-high-risk individuals were considered potentially inappropriate recipients.

RESULTS:

Of 44,805 individuals, 67% (n=29,893) were aged 65 and older, of whom 51% were aged 75 and older. A significant proportion of ICD recipients had a low risk of death (16%, n=6,969) or very high risk of nonarrhythmic death (8%, n=3,693). Potentially inappropriate ICD use was 10% in those aged 75 and older, much less than in younger groups (40%,

CONCLUSION:

Potentially inappropriate ICD use appears significantly less-and at modest rates-in older Americans than in younger age groups. Overall, almost one-quarter of individuals may have received ICDs inappropriately based on their risk of death. Physicians appear to be conservatively referring older adults and wisely deferring those with high comorbid burden.

Abstract

The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity.

BACKGROUND:

We sought to determine the safety and preliminary efficacy of transcatheter intramyocardial administration of myoblasts in patients with heart failure (HF).

METHODS:

MARVEL is a randomized placebo-controlled trial of image-guided, catheter-based intramyocardial injection of placebo or myoblasts (400 or 800 million) in patients with class II to IV HF and ejection fraction <35%. Primary end points were frequency of serious adverse events (safety) and changes in 6-minute walk test and Minnesota Living With HF score (efficacy). Of 330 patients intended for enrollment, 23 were randomized (MARVEL-1) before stopping the study for financial reasons.

RESULTS:

At 6 months, similar numbers of events occurred in each group: 8 (placebo), 7 (low dose), and 8 (high dose), without deaths. Ventricular tachycardia responsive to amiodarone was more frequent in myoblast-treated patients: 1 (placebo), 3 (low dose), and 4 (high dose). A trend toward improvement in functional capacity was noted in myoblast-treated groups (Δ6-minute walk test of -3.6 vs +95.6 vs +85.5 m [placebo vs low dose vs high dose; P = .50]) without significant changes in Minnesota Living With HF scores.

CONCLUSIONS:

In HF patients with chronic postinfarction cardiomyopathy, transcatheter administration of myoblasts in doses of 400 to 800 million cells is feasible and may lead to important clinical benefits. Ventricular tachycardia may be provoked by myoblast injection but appears to be a transient and treatable problem. A large-scale outcome trial of myoblast administration in HF patients with postinfarction cardiomyopathy is feasible and warranted.

Author information: IOM (Institute of Medicine) and NRC (National Research Council). (Committee: Goldstein BD, DeSimone JM, Ascher MS, Buehler JW, Cook KS, Crouch NA, Doyle FJ, Foldy S, Gursky EA, Hoffman S, Johnson CB, Keim P, Kellerman AL, Kleinman KP, Layton M, Lee EK, Mayor SD, Moshier TF, Murphy FA, Murray RW, Owens DK, Pollock SM, Resnick IG, Schaudies RP, Schultz JS)

Following the attacks of September 11, 2001 and the anthrax letters, the ability to detect biological threats as quickly as possible became a top priority. In 2003 the Department of Homeland Security (DHS) introduced the BioWatch program--a federal monitoring system intended to speed detection of specific biological agents that could be released in aerosolized form during a biological attack. 

The present volume evaluates the costs and merits of both the current BioWatch program and the plans for a new generation of BioWatch devices. BioWatch and Public Health Surveillance also examines infectious disease surveillance through hospitals and public health agencies in the United States, and considers whether BioWatch and traditional infectious disease surveillance are redundant or complementary.

BACKGROUND: Induction of labor is on the rise in the U.S., increasing from 9.5 percent in 1990 to 22.1 percent in 2004. Although, it is not entirely clear what proportion of these inductions are elective (i.e. without a medical indication), the overall rate of induction of labor is rising faster than the rate of pregnancy complications that would lead to a medically indicated induction. However, the maternal and neonatal effects of induction of labor are unclear. Many studies compare women with induction of labor to those in spontaneous labor. This is problematic, because at any point in the management of the woman with a term gestation, the clinician has the choice between induction of labor and expectant management, not spontaneous labor. Expectant management of the pregnancy involves nonintervention at any particular point in time and allowing the pregnancy to progress to a future gestational age. Thus, women undergoing expectant management may go into spontaneous labor or may require indicated induction of labor at a future gestational age.

OBJECTIVES: The Stanford-UCSF Evidence-Based Practice Center examined the evidence regarding four Key Questions: What evidence describes the maternal risks of elective induction versus expectant management? What evidence describes the fetal/neonatal risks of elective induction versus expectant management? What is the evidence that certain physical conditions/patient characteristics are predictive of a successful induction of labor? How is a failed induction defined?

METHODS: We performed a systematic review to answer the Key Questions. We searched MEDLINE(1966-2007) and bibliographies of prior systematic reviews and the included studies for English language studies of maternal and fetal outcomes after elective induction of labor. We evaluated the quality of included studies. When possible, we synthesized study data using random effects models. We also evaluated the potential clinical outcomes and cost-effectiveness of elective induction of labor versus expectant management of pregnancy labor at 41, 40, and 39 weeks' gestation using decision-analytic models.

RESULTS: Our searches identified 3,722 potentially relevant articles, of which 76 articles met inclusion criteria. Nine RCTs compared expectant management with elective induction of labor. We found that overall, expectant management of pregnancy was associated with an approximately 22 percent higher odds of cesarean delivery than elective induction of labor (OR 1.22, 95 percent CI 1.07-1.39; absolute risk difference 1.9, 95 percent CI: 0.2-3.7 percent). The majority of these studies were in women at or beyond 41 weeks of gestation (OR 1.21, 95 percent CI 1.01-1.46). In studies of women at or beyond 41 weeks of gestation, the evidence was rated as moderate because of the size and number of studies and consistency of the findings. Among women less than 41 weeks of gestation, there were three trials which reported no difference in risk of cesarean delivery among women who were induced as compared to expectant management (OR 1.73; 95 percent CI: 0.67-4.5, P=0.26), but all of these trials were small, non-U.S., older, and of poor quality. When we stratified the analysis by country, we found that the odds of cesarean delivery were higher in women who were expectantly managed compared to elective induction of labor in studies conducted outside the U.S. (OR 1.22; 95 percent CI 1.05-1.40) but were not statistically different in studies conducted in the U.S. (OR 1.28; 95 percent CI 0.65-2.49). Women who were expectantly managed were also more likely to have meconium-stained amniotic fluid than those who were electively induced (OR 2.04; 95 percent CI: 1.34-3.09). Observational studies reported a consistently lower risk of cesarean delivery among women who underwent spontaneous labor (6 percent) compared with women who had an elective induction of labor (8 percent) with a statistically significant decrease when combined (OR 0.63; 95 percent CI: 0.49-0.79), but again utilized the wrong control group and did not appropriately adjust for gestational age. We found moderate to high quality evidence that increased parity, a more favorable cervical status as assessed by a higher Bishop score, and decreased gestational age were associated with successful labor induction (58 percent of the included studies defined success as achieving a vaginal delivery anytime after the onset of the induction of labor; in these instances, induction was considered a failure when it led to a cesarean delivery). In the decision analytic model, we utilized a baseline assumption of no difference in cesarean delivery between the two arms as there was no statistically significant difference in the U.S. studies or in women prior to 41 0/7 weeks of gestation. In each of the models, women who were electively induced had better overall outcomes among both mothers and neonates as estimated by total quality-adjusted life years (QALYs) as well as by reduction in specific perinatal outcomes such as shoulder dystocia, meconium aspiration syndrome, and preeclampsia. Additionally, induction of labor was cost-effective at $10,789 per QALY with elective induction of labor at 41 weeks of gestation, $9,932 per QALY at 40 weeks of gestation, and $20,222 per QALY at 39 weeks of gestation utilizing a cost-effectiveness threshold of $50,000 per QALY. At 41 weeks of gestation, these results were generally robust to variations in the assumed ranges in univariate and multi-way sensitivity analyses. However, the findings of cost-effectiveness at 40 and 39 weeks of gestation were not robust to the ranges of the assumptions. In addition, the strength of evidence for some model inputs was low, therefore our analyses are exploratory rather than definitive.

CONCLUSIONS: Randomized controlled trials suggest that elective induction of labor at 41 weeks of gestation and beyond may be associated with a decrease in both the risk of cesarean delivery and of meconium-stained amniotic fluid. The evidence regarding elective induction of labor prior to 41 weeks of gestation is insufficient to draw any conclusion. There is a paucity of information from prospective RCTs examining other maternal or neonatal outcomes in the setting of elective induction of labor. Observational studies found higher rates of cesarean delivery with elective induction of labor, but compared women undergoing induction of labor to women in spontaneous labor and were subject to potential confounding bias, particularly from gestational age. Such studies do not inform the question of how elective induction of labor affects maternal or neonatal outcomes. Elective induction of labor at 41 weeks of gestation and potentially earlier also appears to be a cost-effective intervention, but because of the need for further data to populate these models our analyses are not definitive. Despite the evidence from the prospective, RCTs reported above, there are concerns about the translation of such findings into actual practice, thus, there is a great need for studying the translation of such research into settings where the majority of obstetric care is provided.

Objective To determine whether the Mexico City Policy, a United States government policy that prohibits funding to nongovernmental organizations performing or promoting abortion, was associated with the induced abortion rate in sub-Saharan Africa.

Methods Women in 20 African countries who had induced abortions between 1994 and 2008 were identified in Demographic and Health Surveys. A country’s exposure to the Mexico City Policy was considered high (or low) if its per capita assistance from the United States for family planning and reproductive health was above (or below) the median among study countries before the policy’s reinstatement in 2001. Using logistic regression and a difference-in-difference design, the authors estimated the differential change in the odds of having an induced abortion among women in high exposure countries relative to low exposure countries when the policy was reinstated.

Findings The study included 261 116 women aged 15 to 44 years. A comparison of 1994–2000 with 2001–2008 revealed an adjusted odds ratio for induced abortion of 2.55 for high-exposure countries versus low-exposure countries under the policy (95% confidence interval, CI: 1.76–3.71). There was a relative decline in the use of modern contraceptives in the high-exposure countries over the same time period.

Conclusion The induced abortion rate in sub-Saharan Africa rose in high-exposure countries relative to low-exposure countries when the Mexico City Policy was re- introduced. Reduced financial support for family planning may have led women to substitute abortion for contraception.Regardless of one’s views about abortion, the findings may have important implications for public policies governing abortion.