Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

BACKGROUND AND PURPOSE: Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. MATERIALS AND METHODS: Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. RESULTS: Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized ß = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized ß = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity (F2,12 = 0.284, P = .757, R2 = 0.045). CONCLUSIONS: In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis.

Cost-effectiveness of alternative strategies for integrating MRI into breast cancer screening for women at high risk.

BACKGROUND: Magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer. We evaluated the cost-effectiveness of alternative screening strategies involving MRI. METHODS: Using a microsimulation model, we generated life histories under different risk profiles, and assessed the impact of screening on quality-adjusted life-years, and lifetime costs, both discounted at 3%. We compared 12 screening strategies combining annual or biennial MRI with mammography and clinical breast examination (CBE) in intervals of 0.5, 1, or 2 years vs without, and reported incremental cost-effectiveness ratios (ICERs). RESULTS: Based on an ICER threshold of $100,000/QALY, the most cost-effective strategy for women at 25% lifetime risk was to stagger MRI and mammography plus CBE every year from age 30 to 74, yielding ICER $58,400 (compared to biennial MRI alone). At 50% lifetime risk and with 70% reduction in MRI cost, the recommended strategy was to stagger MRI and mammography plus CBE every 6 months (ICER=$84,400). At 75% lifetime risk, the recommended strategy is biennial MRI combined with mammography plus CBE every 6 months (ICER=$62,800). CONCLUSIONS: The high costs of MRI and its lower specificity are limiting factors for annual screening schedule of MRI, except for women at sufficiently high risk.

A systematic review of care delivery models and economic analyses in lymphedema: health policy impact (2004-2011).

A project of the American Lymphedema Framework Project (ALFP), this review seeks to examine the policy and economic impact of caring for patients with lymphedema, a common side effect of cancer treatment. This review is the first of its kind undertaken to investigate, coordinate, and streamline lymphedema policy initiatives in the United States with potential applicability worldwide. As part of a large scale literature review aiming to systematically evaluate the level of evidence of contemporary peer-reviewed lymphedema literature (2004 to 2011), publications on care delivery models, health policy, and economic impact were retrieved, summarized, and evaluated by a team of investigators and clinical experts. The review substantiates lymphedema education models and clinical models implemented at the community, health care provider, and individual level that improve delivery of care. The review exposes the lack of economic analysis related to lymphedema. Despite a dearth of evidence, efforts towards policy initiatives at the federal and state level are underway. These initiatives and the evidence to support them are examined and recommendations for translating these findings into clinical practice are made. Medical and community-based disease management interventions, taking on a public approach, are effective delivery models for lymphedema care and demonstrate great potential to improve cancer survivorship care. Efforts to create policy at the federal, state, and local level should target implementation of these models. More research is needed to identify costs associated with the treatment of lymphedema and to model the cost outlays and potential cost savings associated with comprehensive management of chronic lymphedema.

Effects of dietary supplementation of Chinese medicinal herbs on polymorphonuclear neutrophil immune activity and small intestinal morphology in weanling pigs.

The purpose of this study was to evaluate the effects of dietary Chinese medicinal herbs (CMH) supplementation composed of Panax ginseng, Dioscoreaceae opposite, Atractylodes macrocephala, Glycyrrhiza uralensis, Ziziphus jujube and Platycodon grandiflorum, on the performance, intestinal tract morphology and immune activity in weanling pigs. Two hundred and forty weaned pigs were assigned randomly to four dietary groups including the negative control (basal diet), 0.1% CMH, 0.3% CMH and 0.114% antibiotic (Chlortetracycline calcium Complex, Sulfathiazole and Procaine Penicillin G) supplementation groups for a 28-day feeding trial. Results indicated that both CMH supplementation groups had a better gain and feed/gain than control group (CT) during the first 2 weeks of the experimental period. The 0.3% CMH had a significant decrease in the diarrhoea score in first 10 days of experimental period when compared with other groups. The CMH supplementation groups had a higher villous height, increased lactobacilli counts in digesta of ileum and decreased coliform counts in colon compared with CT. The immune activities of polymorphonuclear leucocytes (PMNs), including the respiratory burst and Salmonella-killing ability, were significantly enhanced in CMH supplementation groups at day 7 of experiment period. The CMH and antibiotic supplementations increased the nutrient digestibility such as dietary dry matter, crude protein and gross energy in weanling pigs. In conclusion, the dietary CMH supplementation improved intestinal morphology and immune activities of PMNs, thus giving rise to nutrient digestibility and reduce diarrhoea frequency in weanling pigs.

Risk factors and incidence of thromboembolic events (TEEs) in older men and women with breast cancer.

BACKGROUND: The purpose of this study is to evaluate the risk factors and the prevalence of thromboembolic events (TEEs) in breast cancer patients. PATIENTS AND METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare database. Breast cancer patients diagnosed from 1992 to 2005 ≥66 years old were identified. International Classification of Diseases, Ninth Revision, and Healthcare Common Procedure Coding System codes were used to identify TEEs within 1 year of the breast cancer diagnosis. Analyses were conducted using descriptive statistics and logistic regression. RESULTS: A total of 89 841 patients were included, of them 2658 (2.96%) developed a TEE. In the multivariable analysis, males had higher risk of a TEE than women [odd ratio (OR) = 1.57; confidence interval (CI) 1.10-2.25] and blacks had higher risk than whites (OR = 1.20; CI 1.04-1.40). Compared with stage I patients, patients with stage II, III and IV had 22%, 39% and 98% increase, respectively, in risk. Placement of central catheters (OR = 2.71; CI 2.43-3.02), chemotherapy treatment (OR = 1.66; CI 1.48-1.86) or treatment with erythropoiesis-stimulating agents (ESAs) (OR = 1.33; CI 1.33-1.52) increase the risk. Other significant predictors included comorbidities, age, receptor status, marital status and year of diagnosis. Similar estimates were seen for pulmonary embolism, deep vein thromboembolism and other TEEs. CONCLUSIONS: In total, 2.96% of patients in this cohort developed a TEE within 1 year from breast cancer diagnosis. Stage, gender, race, use of chemotherapy and ESAs, comorbidities, receptor status and catheter placement were associated with the development of TEEs.

Schwannoma mimicking liver tumor.

Thoracic neurogenic tumors typically originate from the posterior mediastinum and the intercostal nerves. No report of a chest wall schwannoma extending toward the subphrenic areas and making a significant indentation into liver parenchyma exists to date. We present a liver tumor-mimicking schwannoma of the intercostal nerves. A 58-year-old woman presented with a painful lesion in the right subphrenic area and abdominal pain in the right upper quadrant for two months. Abdominal ultrasonography and magnetic resonance imaging revealed a tumor, 9.1 x 7.1 x 8.9 cm in size, with an inner cystic change in segment V and VI of the liver. The tumor was completely resected together with part of the 9th rib. Pathology confirmed a schwannoma and showed a tumor composed of spindle cells with oval to wavy nuclei. The patient was still asymptomatic at follow-up after 36 months, with no sign of recurrence.

An 8×8 Row-Column Summing Readout Electronics for Preclinical Positron Emission Tomography Scanners.

This work presents a row/column summing readout electronics for an 8×8 silicon photomultiplier array. The summation circuit greatly reduces the number of electronic channels, which is desirable for pursuing higher resolution positron emission tomography scanners. By using a degenerated common source topology in the summation circuit, more fan-in is possible and therefore a greater reduction in the number of electronic channels can be achieved. The timing signal is retrieved from a common anode, which allows the use of a single fast-sampling analog to digital converter (ADC) for the timing channel and slower, lower power ADCs for the 64 spatial channels. Preliminary results of one row summation of the 8×8 readout electronics exhibited FWHM energy resolution of 17.8% and 18.3% with and without multiplexing, respectively. The measured timing resolution is 2.9ns FWHM.

Mercury transport and resistance.

Resistance to mercuric ions in bacteria is conferred by mercuric reductase, which reduces Hg(II) to Hg(0) in the cytoplasmic compartment. Specific mercuric ion transport systems exist to take up Hg(II) salts and deliver them to the active site of the reductase. This short review discusses the role of transport proteins in resistance and the mechanism of transfer of Hg(II) between the mercury-resistance proteins.

The economics of selective serotonin reuptake inhibitors in depression: a critical review.

The prevalence of depression and the high costs associated with its treatment have increased interest in pharmacoeconomic evaluations of drug treatment, particularly in the 1990s as the use of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) expanded substantially. This review presents results from specific studies representing the key study designs used to address the pharmacoeconomics of SSRI use: retrospective administrative database analyses, clinical decision analysis models, and randomised clinical trials. Methodological considerations in interpreting results are highlighted. In retrospective administrative database analyses, most comparisons have been made between SSRIs and tricyclic antidepressants (TCAs). A few studies have addressed differences between SSRIs. The studies focused on healthcare cost (to payer) and cost-related outcomes (e.g. treatment duration, drug switching). Although SSRIs are generally associated with higher drug acquisition costs than are TCAs, total healthcare costs are at least offset, if not decreased, by reductions in costs associated with use of SSRIs. Although studies from the early 1990s show some advantage for fluoxetine, the results are limited by use of data from shortly after the introduction of paroxetine and sertraline; studies from the mid- 1990s on that compare drugs within the SSRI class show general equivalence in terms of cost. Important methodological advances are occurring in retrospective studies, with selection bias and other design limitations being addressed statistically. Clinical decision analysis models permit flexibility in terms of ability to specify different alternative treatment scenarios and varying durations. Sensitivity analysis aids interpretability, although model inputs are limited by data availability. Results from short term (1 year duration or less) studies comparing SSRIs and TCAs suggest that SSRIs are more cost effective or that there is no difference. Longer term studies (lifetime Markov models) focus more on the impact of maintenance antidepressant therapy and show more mixed results, generally favouring SSRIs over TCAs. The results indicate that the effect of SSRIs is mainly through prevention of relapse. Important assumptions of these models include fewer serious adverse effects and lower treatment discontinuation rates with SSRIs. Naturalistic clinical trials provide greater generalisability than traditional randomised clinical trials. One naturalistic trial found that nearly half of TCA-treated patients switched to another antidepressant within 6 months; only 20% of SSRI-treated patients switched. Cost differences between groups were minimal. These studies indicate few differences in medical costs, depression outcomes and health-related quality of life between TCAs and fluoxetine, although fewer fluoxetine-treated patients switched treatment.

Using full probability models to compute probabilities of actual interest to decision makers.

The objective of this paper is to illustrate the advantages of the Bayesian approach in quantifying, presenting, and reporting scientific evidence and in assisting decision making. Three basic components in the Bayesian framework are the prior distribution, likelihood function, and posterior distribution. The prior distribution describes analysts' belief a priori, the likelihood function captures how data modify the prior knowledge; and the posterior distribution synthesizes both prior and likelihood information. The Bayesian approach treats the parameters of interest as random variables, uses the entire posterior distribution to quantify the evidence, and reports evidence in a "probabilistic" manner. Two clinical examples are used to demonstrate the value of the Bayesian approach to decision makers. Using either an uninformative or a skeptical prior distribution, these examples show that the Bayesian methods allow calculations of probabilities that are usually of more interest to decision makers, e.g., the probability that treatment A is similar to treatment B, the probability that treatment A is at least 5% better than treatment B, and the probability that treatment A is not within the "similarity region" of treatment B, etc. In addition, the Bayesian approach can deal with multiple endpoints more easily than the classic approach. For example, if decision makers wish to examine mortality and cost jointly, the Bayesian method can report the probability that a treatment achieves at least 2% mortality reduction and less than $20,000 increase in costs. In conclusion, probabilities computed from the Bayesian approach provide more relevant information to decision makers and are easier to interpret.

Regulation of acetylcholine release by extracellular matrix proteins at developing motoneurons in Xenopus cell cultures.

Integrins mediate cell-extracellular matrix connections and are particularly important during neuronal development. We here investigated the regulatory role of extracellular matrix (ECM) proteins on the synaptic transmission at developing motoneurons. Synaptic currents were recorded from innervated myocytes of 1-day-old Xenopus cultures by whole-cell recordings. Soluble fibronectin and laminin had no significant effect on the frequency of spontaneous synaptic currents (SSCs) by themselves and markedly increased SSC frequency in the presence of low concentration of protein kinase C (PKC) activators. Pretreatment with Gly-Arg-Gly-Asp-Ser peptide inhibited the SSC increasing action of 12-o-tetradecanoyl-phorbol-13-acetate (TPA, 0.5 microM) plus fibronectin, but not that of TPA plus laminin. Genistein but not cytochalasin D inhibited the SSC increasing action of TPA plus fibronectin or laminin. High concentration of TPA (5 microM) markedly increased the SSC frequency by itself and occluded the SSC increasing action of fibronectin. Very low concentration of TPA (0.05 microM) markedly enhanced the SSC frequency when the cells were plated onto fibronectin- or laminin-coated substratum for 1 day. The SSC frequency increased markedly right after a train stimulation, which was defined as post-train potentiation (PTrP), when the cultures were plated onto fibronectin substratum and chronically treated with brain-derived neurotrophic factor (BDNF). The PTrP phenomenon is not observed upon chronic treatment with neurotrophin-3, glial cell line-derived neurotrophic factor, or ciliary neurotrophic factor. Our results suggest that the activation of PKC and tyrosine kinase but not actin reorganization plays a role in the SSC potentiating action of fibronectin. BDNF exerts synergistic effects in increasing synaptic transmission in neurons grown on fibronectin substratum. ECMs in concert with neurotrophic factor may play a role in regulating synaptic function at developing motoneurons.

Cost-benefit analysis of sumatriptan tablets versus usual therapy for treatment of migraine.

We performed a systematic assessment of the costs and benefits of sumatriptan and usual therapy for migraine from society's perspective. A decision tree was constructed with probability estimates based on data from an open-label clinical trial assessing the economic and human impacts of sumatriptan and usual therapy on nursing personnel. Direct medical care costs including costs for drug, physician, and emergency room visits were considered. Benefits were estimated using the human capital approach based on the national average of weekly earnings and productivity loss estimated from a migraine clinical trial. The net benefits of sumatriptan and usual therapy for the treatment of a single migraine attack were estimated to be $50 and $20, respectively. The annual incremental net benefit of sumatriptan over usual therapy was estimated to be $114-540/patient. The price difference was offset by benefits of sumatriptan in reducing use of health care resources and productivity loss.

Cytotoxic constituents of Polyalthia longifolia var. pendula.

A new halimane diterpene, 3beta,5beta, 16alpha-trihydroxyhalima-13(14)-en-15,16-olide (1), and a new oxoprotoberberine alkaloid, (-)-8-oxopolyalthiaine (2), along with 20 known compounds, were isolated from a methanolic extract of Polyalthia longifolia var. pendula. The structures of compounds 1 and 2 were established by spectroscopic analysis. Several of these compounds were evaluated for cytotoxicity toward a small panel of human cell lines.

Trends in full-time pharmacists' labor market characteristics.

OBJECTIVE: To provide a historical overview of the pharmacy profession for the past 30 years, using trends in full-time pharmacists' labor market characteristics. METHODS: A retrospective longitudinal sample of pharmacists from 1968 to 1996 was constructed from the March Current Population Survey data. A three-period centered moving average method was used to describe the labor market trends over time. Pharmacists' labor market was characterized by age, sex, race, education, geographic distribution, salary, working hours, and wage. RESULTS: The dominant age group among full-time pharmacists was 36-45 in the late 1960s and early 1970s, 26-35 between the mid-1970's and early 1990's, and 36-45 in the mid-1990's. Historically, a significant proportion of full-time pharmacists were white men, holding bachelor's degrees. The number of pharmacists has been highest in the South and lowest in the West. In general, pharmacists' annual salary and wage rates have grown steadily, whereas average hours worked per week have decreased from 50 hours to less than 45. CONCLUSION: Findings suggest a growing trend of three demographic groups: aged 36-45, women, and nonwhite. In addition, an increasing proportion of pharmacists holding "higher than bachelor" degrees was observed. The distribution of pharmacists was highest in the South and lowest in the West. The Midwest has the highest pharmacist/population ratio, the South the lowest. On average, full-time pharmacists in the 1990s work 40-45 hours per week, have an annual salary higher than $55,000 (in 1996 dollars), and an hourly wage rate above $25.

Effect of insurance on prescription drug use by ESRD beneficiaries.

In this article the author reviews the prescription drug coverage policy in the Medicare End Stage Renal Disease (ESRD) program and examines the relationship between secondary insurance status and the number of medications prescribed for dialysis patients who had Medicare as their primary payer. Negative binomial models were used to examine this relationship. Findings in this study indicate that the number of secondary payers has a significant impact on the number of prescription drugs received by Medicare ESRD patients. Further research is needed to determine whether Medicare beneficiaries without secondary insurance are obtaining fewer prescriptions than needed or if those with greater coverage are obtaining more than needed.

Reconciling decision models with the real world. An application to anaemia of renal failure.

OBJECTIVE: The choice of evidence used in decision modelling of healthcare interventions divides analysts into 2 groups: (i) those who favour randomised clinical trial (RCT) data; and (ii) those who prefer 'real world' data. This preference may have serious consequences if the end result is to inform healthcare policy. This paper uses Medicare coverage of epoetin-alpha [erythropoietin (EPO)] as a case study to illustrate a technique which can be used to overcome some of the bias inherent in RCT data while avoiding some of the common pitfalls associated with the use of observational data. DESIGN AND SETTING: Cost analysis of 2 treatments for anaemia of renal failure primarily in an outpatient setting is modelled in a decision tree. This method can be used to analyse healthcare interventions or policies in any setting. PATIENTS AND PARTICIPANTS: Patients with nontransplanted end-stage renal disease (ESRD) who received either EPO or blood transfusion for treatment of anaemia at any time during the 1-year study period (July 1989 to June 1990) were included in the sample. METHODS: Outcome effects in the natural setting are decomposed into 2 parts: a treatment effect and a population effect. This is then extended to the special case of policy analysis. Logistic and multiple regression are used to estimate branch probabilities and payoffs, respectively, for 2 treatment options. MAIN OUTCOME MEASURES AND RESULTS: Under standard methods of decision analysis, an increase of $US7032 per patient following EPO coverage is observed. With the decomposition technique, the policy effect is estimated to be less, $US6172, the difference coming from the population effect. CONCLUSIONS: Failure to remove population effects from observed outcome effects may lead to biased decision-making. Although not directly observable, the population effect can be imputed from secondary data. The decomposition and imputting technique allows for a more meaningful interpretation of the results for the purpose of policy analysis.

Growth and geographic distribution of selected health professions, 1971-1996.

This article examines the growth and geographic distribution of selected health professions in a 26-year period. The health professionals investigated were physicians, dentists, pharmacists, registered nurses, other health practitioners, dieticians and therapists, medical technologists and technicians, and health service workers. Allied health professions are represented by the last three of these groups. Samples of health professionals were extracted from the Current Population Survey from 1971 to 1996. The ratio technique and GIN1 index are used to describe the growth trend and geographic distribution of each health professional group over time. This historical overview reveals the following general trends in the 1990s: 1) growth of every selected health professional group has slowed down; 2) workforce disparities between the most and least abundantly supplied geographic areas have decreased; 3) selected health professions have become less evenly distributed among the population; and 4) the trends in pharmacy and dentistry call for immediate attention in workforce planning. The findings suggest that with the exception of dentistry, health personnel shortages are no longer an issue in such planning. Future health workforce policies should continue focusing on improving the distribution of workers among the general population.