Interventional Radiologic Treatment of Hepatocellular Carcinoma—A Cost Analysis from the Payer Perspective

PurposeTo determine whether there is a cost advantage for one of the three commonly performed interventional radiology (IR) procedures (chemoembolization, selective internal radiation therapy [SIRT], radiofrequency ablation [RFA]) in the treatment of hepatocellular carcinoma (HCC).Materials and MethodsA cost analysis from the payer perspective was performed. Primary data were collected from a university hospital, and sensitivity testing was done by comparing coding information obtained at two other tertiary care medical facilities. Medicare allowable reimbursements were used to estimate costs. Decision analytic models using decision tree analysis and Monte Carlo simulations were used to compare alternatives. Simulations were performed comparing all three procedures, followed by a two-way comparison of chemoembolization and SIRT.ResultsSimple decision tree analyses showed that RFA was less expensive compared with chemoembolization and SIRT. Monte Carlo simulations showed average reimbursements for each of the three procedures that was largely dependent on the number of repeat procedures required ($9,362 vs $30,107 vs $35,629 for RFA, chemoembolization, and SIRT; P < .001). When comparing only chemoembolization and SIRT, chemoembolization was the lower cost strategy in most scenarios, but SIRT was lower in cost in more than one-third of the simulations.ConclusionsRFA was the least costly of the three IR strategies in nearly all scenarios studied in these models. Although chemoembolization was less expensive than SIRT in most instances, Monte Carlo simulation showed a preference for SIRT in more than one-third of all scenarios. Sensitivity analyses showed that the most important variables assessed were the need for repeat procedures.     

Effect of Computer-Assisted Interviewing on Self-Reported Sexual Behavior Data in a Microbicide Clinical Trial

In a microbicide safety and effectiveness trial (HPTN 035) in Malawi, 585 women completed the same questionnaire through a face-to-face interview (FTFI) and an audio computer-assisted self-interview (ACASI). Concordance between FTFI and ACASI responses ranged from 72.0 % for frequency of sex in the past week to 95.2 % for anal intercourse (AI) in the past 3 months. Reported gel and condom use at last sex act were marginally lower with ACASI than FTFI (73.5 % vs. 77.2 %, p = 0.11 and 60.9 % vs. 65.5 %, p = 0.05, respectively). More women reported AI with ACASI than FTFI (5.0 % vs. 0.2 %, p < 0.001). Analyses of consistency of responses within ACASI revealed that 15.0 % of participants in the condom-only arm and 28.7 % in the gel arm provided at least one discrepant answer regarding total sex acts and sex acts where condom and gel were used (19.2 % reported one inconsistent answer, 8.1 % reported two inconsistent answers, and 1.4 % reported three inconsistent answers). While ACASI may provide more accurate assessments of sensitive behaviors in HIV prevention trials, it also results in a high level of internally inconsistent responses.     

Dissolution Curve Comparisons Through the F2 Parameter,a Bayesian Extension of the f2 Statistic

Dissolution (or in vitro release) studies constitute an important aspect of pharmaceutical drug development. One important use of such studies is for justifying a biowaiver for post-approval changes which requires establishing equivalence between the new and old product. We propose a statistically rigorous modeling approach for this purpose based on the estimation of what we refer to as the F₂ parameter, an extension of the commonly used f₂ statistic. A Bayesian test procedure is proposed in relation to a set of composite hypotheses that capture the similarity requirement on the absolute mean differences between test and reference dissolution profiles. Several examples are provided to illustrate the application. Results of our simulation study comparing the performance of f₂ and the proposed method show that our Bayesian approach is comparable to or in many cases superior to the f₂ statistic as a decision rule. Further useful extensions of the method, such as the use of continuous-time dissolution modeling, are considered.     

Prefrontal Cortical GABA Modulation of Spatial Reference and Working Memory

Background:

Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear.

Methods:

We assessed the effects of pharmacological reduction of GABA_A signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates susceptibility to proactive interference. Male rats were well-trained to retrieve food from the same 4 arms of an 8-arm maze, receiving 5 trials/day (1–2min intervals).

Results:

Infusions of the GABA_A receptor antagonist bicuculline (12.5–50ng) markedly increased working and reference memory errors and response latencies. Similar treatments also impaired short-term memory on an 8-baited arm task. These effects did not appear to be due to increased susceptibility to proactive interference. In contrast, PFC inactivation via infusion of GABA agonists baclofen/muscimol did not affect reference/working memory. In comparison to the pronounced effects on the 8-arm maze tasks, PFC GABA_A antagonism only causes a slight and transient decrease in accuracy on a 2-arm spatial discrimination.

Conclusions:

These findings demonstrate that prefrontal GABA hypofunction severely disrupts spatial reference and short-term memory and that disinhibition of the PFC can, in some instances, perturb memory processes not normally dependent on the frontal lobes. Moreover, these impairments closely resemble those observed in schizophrenic patients, suggesting that perturbation in PFC GABA signaling may contribute to these types of cognitive deficits associated with the disorder.     

Surfactant protein-A in bronchoalveolar lavage fluid from neonates with RDS on conventional and high-frequency oscillatory ventilation

Surfactant protein-A (SP-A) was measured in bronchoalveolar lavage (BAL) samples from ventilated neonates in order to study the concentration of SP-A with regard to: 1) high-frequency oscillatory ventilation (HFOV) vs. conventional mechanical ventilation (CMV); 2) the postnatal course and ontogeny of SP-A; and 3) the correlation with measurements of pulmonary function. Patients on HFOV had markedly lower BAL SP-A concentrations on days 1 and 2 compared to those on CMV, which may indicate influence of mode of ventilation on surfactant metabolism. The SP-A concentrations increased postnatally concurrent with resolution of acute respiratory distress syndrome. Finally, there were only weak correlations between BAL SP-A concentration and dynamic lung compliance and oxygen requirement.     

Clinical picture of cardiogenic shock as primary manifestation of sepsis originating in the knee joint

This is a case report of a male with infection in the right knee joint progressing to sepsis. However, the patient initially complained mainly of dysarthria and breathlessness. He rapidly developed respiratory insufficiency with the loss of consciousness. Echocardiography revealed severe dysfunction of the left ventricle, suggesting acute failure of the chronically failing heart. The patient was referred to a coronary care unit. Only the further course of the disease, particularly progression of the local finding on the right leg and development of fever, together with significantly elevated inflammatory parameters in laboratory findings, resulted in the diagnosis of sepsis which also included myocardial dysfunction and brain hypoperfusion manifested as dysarthria.