Effects of estrogen and progesterone on spatial memory consolidation in aged females

Interpretation of data illustrating that estrogen, with or without progestin, is detrimental to memory in post-menopausal women is complicated by the fact that little is known about the effects of progestins on memory. The present study examined if estrogen, alone or with progesterone, affects spatial memory consolidation in ovariectomized aged female mice. Mice received eight training trials in a spatial Morris water maze followed immediately by injection of water-soluble 17beta-estradiol (E(2); 0.2 mg/kg) or vehicle. Mice were re-tested 24 h later. All mice learned to find the platform on Day 1. On Day 2, the performance of control, but not E(2) mice, deteriorated, suggesting that E(2) enhanced memory for the platform location. In a second experiment, mice were injected with E(2) and 10 or 20 mg/kg water-soluble progesterone. The 10 mg/kg dose of progesterone did not affect estrogen's ability to enhance spatial memory consolidation, but 20 mg/kg blocked this effect. These data indicate that estrogen can improve spatial memory consolidation in aged females and that this effect can be attenuated by progesterone.     

Cost-Effectiveness of Contralateral Prophylactic Mastectomy for Prevention of Contralateral Breast Cancer

Background

A growing number of women with sporadic unilateral, early-stage breast cancers are undergoing ipsilateral therapeutic mastectomy with contralateral prophylactic mastectomy (CPM) to prevent the development of new cancers in the contralateral breast.

Methods

A decision-tree using TreeAge Pro 2012 software was used to model the costs and effects of CPM versus unilateral mastectomy (UM) in women younger than 50 years of age with sporadic unilateral, early stage breast cancers. Cost estimates were obtained from the Medicare Fee Schedule and the Healthcare Utilization Project. Probability estimates were obtained from the literature. Outcome effects were measured by incremental cost per quality-adjusted life year (QALY) gained. A 10-year risk period for contralateral breast cancer (CBC), a lifetime time horizon, and a societal perspective were used.

Results

Treatment with CPM results in 0.2 QALYs less than UM and $279 less in costs during a 10-year risk period and lifetime follow-up. The resulting incremental cost effectiveness ratio (ICER) is a savings of $1397 per QALY lost. The ICER is sensitive to the rate and method of postmastectomy reconstruction and the cost of radiologic surveillance after UM.

Conclusions

CPM is cost-saving for the prevention of CBC in women younger than 50 years of age with sporadic, unilateral, early-stage breast cancers, but also reduces resulting health. The savings for health lost are insufficient to be considered cost-effective at this time.     

Activism on rifapentine pricing: removing cost barriers to improve the uptake of tuberculosis research innovations

As recent advances have been made in developing tools to fight tuberculosis (TB), there is also a trend towards increasing advocacy by the civil society for TB research and access. One recent successful effort to increase access to treatment options for TB involved a collaborative effort to identify the need for and barriers to the use of rifapentine (RPT) use in the United States. Survey responses confirmed the under-utilization of RPT: 82% of survey respondents selected cost as a significant or potential barrier to use. Survey results provided data to support a year-long advocacy campaign urging the drug company Sanofi to lower the price of RPT. This campaign was based on a common evidence base built in part by the stakeholders themselves. After multiple engagements with communities and providers, Sanofi US announced on 12 December 2013 that they would drop the price of RPT to US$32 per blister pack of 32 tablets for US public health programs. While further work remains to secure access to RPT in the United States and worldwide, the lowering of the price of RPT reflects the positive impact that collaborative advocacy can accomplish, and sets an example for other drug companies to follow.     

Steps towards constructing a global comparative risk analysis for alcohol consumption: determining indicators and empirical weights for patterns of drinking, deciding about theoretical minimum, and dealing with different consequences

In order to conduct a comparative risk analysis for alcohol within the Global Burden of Disease Study (GBD 2000), several questions had to be answered. (1) What are the appropriate dimensions for alcohol consumption and how can they be categorized? The average volume of alcohol and patterns of drinking were selected as dimensions. Both dimensions could be looked upon as continuous but were categorized for practical purposes. The average volume of drinking was categorized into the following categories: abstention; drinking 1 (> 0-19.99 g pure alcohol daily for females, > 0-39.99 g for males); drinking 2 (20-39.99 g for females, 40-59.99 g for males), and drinking 3 (> or =40 g for females, > or =60 g for males). Patterns of drinking were categorized into four levels of detrimental impact based on an optimal scaling analysis of key informant ratings. (2) What is the theoretical minimum for both dimensions? A pattern of regular light drinking (at most 1 drink every day) was selected as theoretical minimum for established market economies for all people above age 45. For all other regions and age groups, the theoretical minimum was set to zero. Potential problems and uncertainties with this selection are discussed. (3) What are the health outcomes for alcohol and how do they relate to the dimensions? Overall, more than 60 disease conditions were identified as being related to alcohol consumption. Most chronic conditions seem to be related to volume only (exceptions are coronary heart disease and ischemic stroke), and most acute conditions seem to be related to volume and patterns. In addition, using methodology based on aggregate data, patterns were relevant for attributing harms for men but not women.     

Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol. A placebo controlled study.

The efficacy of pirmenol (a class I antiarrhythmic agent) as a converter of paroxysmal atrial fibrillation was investigated. Forty patients without congestive heart failure or a history of sinus node disorder were randomly allocated to receive either intravenous pirmenol (50-100 mg) or placebo in a double blind trial. In 12 of 20 patients sinus rhythm was restored 2-16 minutes after pirmenol, and in 3 of 20 patients in the control group it returned within one hour. A nodal escape rhythm was seen during sinus slowing in one patient, but in other patients there was no sinus arrest, atrioventricular conduction disturbance, or hypotension. The ventricular rate was slightly increased in patients in whom sinus rhythm was not restored by pirmenol. The results indicate that pirmenol has an antifibrillatory effect on the atria. Sinus rhythm was restored rapidly after intravenous administration. It was well tolerated in patients with atrial fibrillation of recent onset.     

Survival with total occlusion of the left main coronary artery. Significance of the collateral circulation

Four patients with total occlusion of the left main coronary artery are described. Angina pectoris was severe (NYHA class 3-4) and had lasted 20 months to seven years. Three patients had experienced a myocardial infarction. All displayed large collaterals arising from a nearly normal right coronary artery and feeding both the left anterior descending and the left circumflex arteries. The left ventricular ejection fractions ranged from 20% to 65%, and all patients had varying degrees of left ventricular asynergy. Coronary artery bypass surgery resulted in a marked improvement in three patients; one patient who underwent an aneurysmectomy died two months after the operation. The data show that total occlusion of the left main coronary artery is compatible with survival if adequate collateral supply develops from the right coronary artery. In this rare angiographic subset collateral circulation is clearly functionally significant.     

Evaluating Direct Medical Expenditures Estimation Methods of Adults Using the Medical Expenditure Panel Survey: An Example Focusing on Head and Neck Cancer

ObjectiveTo inform policymakers of the importance of evaluating various methods for estimating the direct medical expenditures for a low-incidence condition, head and neck cancer (HNC).MethodsFour methods of estimation have been identified: 1) summing all health care expenditures, 2) estimating disease-specific expenditures consistent with an attribution approach, 3) estimating disease-specific expenditures by matching, and 4) estimating disease-specific expenditures by using a regression-based approach. A literature review of studies (2005–2012) that used the Medical Expenditure Panel Survey (MEPS) was undertaken to establish the most popular expenditure estimation methods. These methods were then applied to a sample of 120 respondents with HNC, derived from pooled data (2003-2008).ResultsThe literature review shows that varying expenditure estimation methods have been used with MEPS but no study compared and contrasted all four methods. Our estimates are reflective of the national treated prevalence of HNC. The upper-bound estimate of annual direct medical expenditures of adult respondents with HNC between 2003 and 2008 was $3.18 billion (in 2008 dollars). Comparable estimates arising from methods focusing on disease-specific and incremental expenditures were all lower in magnitude. Attribution yielded annual expenditures of $1.41 billion, matching method of $1.56 billion, and regression method of $1.09 billion.ConclusionsThis research demonstrates that variation exists across and within expenditure estimation methods applied to MEPS data. Despite concerns regarding aspects of reliability and consistency, reporting a combination of the four methods offers a degree of transparency and validity to estimating the likely range of annual direct medical expenditures of a condition.