Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Laterality and Lateralization in Autism Spectrum Disorder, Using a Standardized Neuro-Psychomotor Assessment.

A detailed assessment of laterality in children with Autism Spectrum Disorder (ASD) was realized, including handedness and other measures (muscle tone, manual performance, dominant eye), using a standardized battery for the developmental assessment of neuro-psychomotor functions. The results of the laterality tests relating to cerebral hemisphere organization (spontaneous gestural laterality and tonic laterality) were different in ASD children, and indicate that the cerebral organization could be disrupted. These assessments, added to the observations of usual laterality most often reported in the literature, provide better understanding of the developmental organization from the pathophysiological point of view in children with ASD.

Social position and nutrition: a gradient relationship in Canada and the USA.

OBJECTIVE: [corrected] To study the existence of a graded relationship between the nutrient content of the diet and some measures of social position. DESIGN AND SETTING: The graded relationship hypothesis was verified by secondary analysis performed on two different nutrition surveys: the Quebec Nutrition Survey (QNS) and the NHANES III, both based on a single 24 h recall. The data of these surveys were collected on a representative sample of two different populations, the first (n=2103) in the province of Quebec (Canada) in 1990 (QNS) and the second in the US population (n=14 877) between 1988 and 1994 (NHANES III). MAIN OUTCOMES MEASURES: The social gradient hypothesis was tested with four different social position indicators. The analyses were performed separately for men and women aged from 18 to 74 y, for all the nutrients available in the databanks. For the USA, the graded relationship for the total population, for the non-Hispanic white population and for respondents sometimes or often experiencing a lack of food was also measured. RESULTS: A graded relationship between almost all nutrients and the studied social position measurements is observed for the consumption of total calorie-adjusted nutrients, for the proportion of people eating in accordance with dietary guidelines and for the proportion of individual not meeting 75% of the respective Recommended Dietary Allowances for their country. The direction of these relationships (positive or negative) is mainly in accordance with the clinical known impacts of nutrients on chronic diseases. CONCLUSIONS: It is possible that nutrition plays a role in the graded distribution of social health inequalities in North America even in the magnitude of this contribution remains to be evaluated.

Contrast-enhanced B-mode US angiography in the assessment of experimental in vivo and in vitro atherosclerotic disease.

RATIONALE AND OBJECTIVES: This study was performed to (a) test the hypothesis that filling the arterial lumen with echoes at B-mode ultrasound (US) enables the assessment of wall and luminal abnormalities and (b) compare contrast material-enhanced B-mode US with color and power Doppler US angiography. MATERIALS AND METHODS: Atherosclerotic lesions were created in 14 rabbit aortas and imaged with color Doppler and B-mode US before and after the intravenous administration of 0.3 mL of AF0150, a US contrast agent. In addition, four replicas of diseased human carotid arteries were immersed in a tissue-mimicking phantom and imaged with B-mode and color and power Doppler US before and after the administration of 1 mL of AF0150 per liter of porcine blood. Radiopaque plastic casts of the rabbit aortas and contact radiographs of the plastic replicas served as standards. RESULTS: Although color and power Doppler US allowed immediate localization of the lumen, precise estimation of stenoses and reliable visualization of surface irregularities were not possible. After AF0150 administration, angiogram-like images of the lumen were created with B-mode US, allowing rapid assessment of the entire vessel lumen and wall. Consequently, luminal stenoses were more accurately measured than with unenhanced B-mode US (r2 = 0.94, P < .0001 vs r2 = 0.21, P = .25) or Doppler (r2 = 0.42, P < .03). In addition, plaques and ulcerations were visible only with contrast-enhanced B-mode US. CONCLUSION: Microbubbles fill the arterial lumen with echoes at B-mode US, creating an angiogram-like image. The ability to visualize the inner and outer surfaces of the vascular wall improved the evaluation of luminal and wall abnormalities.

The choice of a diet quality indicator to evaluate the nutritional health of populations.

BACKGROUND: The USA and Canada both want to reduce social health inequalities in their population. These two countries have recently begun a process of harmonization of their nutrient recommendations. OBJECTIVE: To develop a standardized indicator to measure the impact of these recommendations on the health of different social groups in North America. The authors have compared three of the methods currently used for measuring overall diet quality for a population. DESIGN AND SETTING: The three methods, adjusted to the 1990 Canadian nutrition recommendations, were used to analyse the Québec Nutrition Survey data collected by Santé Québec in 1990. RESULTS: The authors found that the indicator developed by Kennedy and collaborators works best for analysing the Québec data. Moreover, it allows comparisons with the USA. Some questions, such as whether or not to add calories from alcohol consumption to the model and whether the indicators should be adjusted to the different cultures and specific population groups remain unanswered. CONCLUSIONS: In order to determine the role of nutrition in social health inequalities, it is important to develop standard indicators that are suitable for monitoring the relationship between dietary recommendations and eating habits.

Monte Carlo calculation of the efficiency calibration curve and coincidence-summing corrections in low-level gamma-ray spectrometry using well-type HPGe detectors

Well-type high-purity germanium (HPGe) detectors are well suited to the analysis of small amounts of environmental samples, as they can combine both low background and high detection efficiency. A low-background well-type detector is installed in the Modane underground Laboratory. In the well geometry, coincidence-summing effects are high and make the construction of the full energy peak efficiency curve a difficult task with an usual calibration standard, especially in the high energy range. Using the GEANT code and taking into account a detailed description of the detector and the source, efficiency curves have been modelled for several filling heights of the vial. With a special routine taking into account the decay schemes of the radionuclides, corrections for coincidence-summing effects that occur when measuring samples containing 238U, 232Th or 134Cs have been computed. The results are found to be in good agreement with the experimental data. It is shown that triple coincidences effect on counting losses accounts for 7-15% of pair coincidences effect in the case of 604 and 796 keV lines of 134Cs.

Assessment of liver and kidney enhancement with a perfluorocarbon vapor-stabilized US contrast agent.

RATIONALE AND OBJECTIVES: The authors evaluated the time-echogenicity response of liver, kidney, and implanted VX2 tumor after injection of a microbubble contrast medium and assessed use of an avascular lesion as an internal standard. MATERIALS AND METHODS: Twenty-one New Zealand White rabbits were studied. To evaluate use of an internal standard and the dose-response relationship, nine rabbits with 7-day-old avascular liver lesions created by alcohol ablation received 0.1, 0.25, 0.5, and 1.0 mL of AF0145, a microbubble contrast agent. To evaluate tumor echogenicity, 12 rabbits implanted with VX2 tumor in the liver (six also underwent alcohol ablation) received 0.5 mL of AF0145. Videodensitometry was used to analyze echogenicity changes over 10 minutes. RESULTS: Echogenicity of the alcohol-ablated liver was not affected by contrast material administration. Liver and kidney echogenicity relative to ablation increased linearly with dose, peaking 1 minute after injection and decaying to baseline over 9 minutes. Contrast material administration defined the size and margins of VX2 lesions more clearly. In the arterial phase, the tumor rim was hyperechoic relative to surrounding liver, becoming isoechoic during the portal venous phase then hypoechoic during the late phase parenchymal phase. CONCLUSIONS: Lesions created by alcohol ablation can be used as an internal standard for quantitative analysis of adjacent tissues. AF0145 enhances perfused tissues, including vascular tumors, at gray-scale, real-time ultrasonography and enhances the liver.

Strategically integrating hospital/home care services for improved profitability.

Because hospitals and home health agencies have been predominantly separate organizations, coordination of their efforts has not been optimized. However, with the recent proliferation of hospital-based home health agencies, opportunities to integrate these health care service delivery systems have increased. Bethesda Memorial Hospital, Boynton Beach, Fla., is a 362-bed not-for-profit community hospital with a Medicare-certified home health agency organized as a department of the hospital. Until recently, the home health agency was generally perceived as a separate entity whose services were distinct from hospital services. Progress toward integration of hospital and home care services was given impetus through collaboration of the home health agency administrator and a newly appointed director of medical affairs who was given the responsibility as medical director of the home health agency. A prime responsibility of the director of medical affairs was to reduce length of stay and hospital costs through appropriate resource management.

Assessment of behavioural objectives in anaesthesia resident training.

Residency training must be based on a comprehensive curriculum. Educators use the term behavioural objectives to represent educational objectives stated as behaviours that must be accomplished by the students. Educational objectives represent an important part of the curriculum content. However, curriculum content, as defined in large academic departments, has often been described as irrelevant for practitioners outside these large centres. Behavioural objectives drawn for the year of internal medicine, the fourth year of a five-year specialty programme in anaesthesia, were evaluated for their clinical relevance for anaesthetists in clinical practice outside cities where teaching programmes are found in the province of Québec. A questionnaire based on 288 objectives, using a rating scale, was used to compare the opinions of the members of the Education Committee (6) and outside practitioners (24). There were no significant differences between the mean ratings of the two groups of raters on ten of the 14 groups of objectives. A concordance of opinion was also present when there was disagreement with the importance of certain objectives. There was disagreement with only one group (VIII) of objectives on 14. Within this group there was agreement with the clinically oriented objectives and disagreement with the laboratory oriented objectives. Objectives that were related to the acute aspects of illness were rated higher than those related to their chronic aspects. The outside practitioners made 81 suggestions or comments about the objectives.

Reliability of data on haematotoxicity of antidepressants. A retrospective assessment of haematological monitoring in clinical studies on tricyclics.

At the present time, there is some concern over the haematological adverse effects of antidepressants. The present paper examines retrospectively 314 clinical trials in depression which were published in English or French between 1958 and 1986 and which used at least one of the following tricyclics: amitriptyline, clomipramine, imipramine. Two decision tables assess the depth of detail with which haematological monitoring and safety were described by the authors of each study. The results indicate that more than 98% of the papers under scrutiny either provide no information on the subject or do so in a manner which is entirely subjective. Thus, it seems that current knowledge of haematotoxicity of antidepressants is almost entirely the result of spontaneous reports from doctors, with its well-known drawbacks.

[Automation of immunohematologic testing activities at French blood transfusion centers]. / Automatisation des activités de contrôles immunohématologiques dans les établissements de transfusion sanguine français.

In May 1982, a questionnaire was sent to all of the 170 French Blood Transfusion Services (BTS), on behalf of the French Society of Blood Transfusion. The purpose was to determine the types of automated equipment used for immunohematological controls, the way in which they are used and the result of automation and computerization in daily laboratory operations. We received 135 replies (80%). A generalized conclusion can be drawn from the collected information. 50% of the respondents are neither automated nor computerized. 30% are both automated and computerized. 10% are automated but not computerized and 8% are not automated but are computerized. In the field of automated serology there is an increased tendency to complete the ABO/Rh testing by Cc D Ee and Kell phenotyping. The use of computers allows the current test determination to be compared with previous donation data. However, no fully automated equipment, which can conduct antibody screening, exists, cost effectively, in small or average BTS. In France, there has been a significant increase in automation between 1970 and 1980 but only the most important BTS have carried out automation at the same time as computerization. The smaller BTS have usually become automated without becoming computerized. In 1978, Codabar was first used. This has been one of the principal advances of the last 10 years, allowing all the users of automation to start moving towards complete computerization. This advance was assisted by the use of prepackaged software. This questionnaire also determined that the current emphasis is now to computerize administrative and management activities before laboratory activities. This survey has been conducted during a turning point of the automation of French BTS. It shows that they are, on the whole, satisfied with their automation. As far as the safety and the efficiency of the service are concerned, it is only fair to consider that the main purposes of the automation have been achieved. But in terms of cost, and serological accuracy for antibody screening, a new generation of automated equipment should appear to satisfy the users in the nineties.