Suppression of the Vertical Vestibulo-ocular Reflex in Older Persons at Risk of Falling

A case-control design was used to assess eye-head-trunk coordination for community-dwelling elders performing a stand-walk task. Eighteen elders with a high risk of falling were matched to 18 subjects with low risk on the basis of age, living status (living alone or with someone) and category of residence (independent living or assisted living facility). Standard electro-oculography was used in conjunction with an electromagnetic tracking device to measure eye and head-trunk motion, respectively. For the low-risk group, the mean slope of gaze-head and gaze-trunk relationships was significantly greater than zero (0.91 and 0.64, respectively), whereas high-risk elders did not demonstrate slope magnitudes significantly different from zero (0.52 and 0.16, respectively) due to large inter-subject variations. While the majority of subjects showed some counter-rotation of the eyes with head pitch, a greater percentage of subjects in the high-risk group did not suppress this response and consequently gaze and gaze velocity overcompensated for head pitch. These findings suggest that the vertical vestibulo-ocular reflex is not adequately suppressed during the stand-walk task in elders who are at a high risk of falling. Possible mechanisms contributing to these findings are discussed.     

Cost-minimization Analysis of IgPro20, a Subcutaneous Immunoglobulin,in Japanese Patients With Primary Immunodeficiency

PurposeIgPro20, Hizentra^® an L-proline−stabilized 20% human subcutaneous immunoglobulin (SCIG), has been shown in a Phase III pivotal study to be well tolerated and efficacious in adult and pediatric Japanese patients with primary immunodeficiency. Economic aspects of SCIG treatment in comparison with previous intravenous immunoglobulin (IVIG) therapy were analyzed in this Phase III study in Japan.MethodsTwenty-four Japanese patients with primary immunodeficiency on IVIG treatment were switched to IgPro20 at an equivalent dose (full analysis set). The study consisted of a screening period, an IVIG treatment period with 3 planned infusions every 3 or 4 weeks, a 12-week SCIG wash-in and wash-out period, and a 12-week SCIG efficacy period. The difference in medical cost and productivity loss resulting from changes in hospital frequency between the SCIG and IVIG treatment was evaluated. Information about treatment cost was collected as part of the Life Quality Index questionnaire. In addition, productivity loss and hospital-related absenteeism were evaluated.FindingsLife Quality Index scores for all domains were higher with SCIG than with IVIG in this patient population. In the full analysis set, the mean (SD) Life Quality Index score of the Costs domain increased from 45.1 (26.34) at Week 1 (IVIG period) to 71.9 (18.52) at Week 24 (end of the SCIG efficacy period), representing a mean change of 26.74 and a large score improvement effect size (1.01). Median productivity loss was reduced by 60% from baseline to Weeks 12 and 24. This resulted in a reduction in costs of JPY 10,875 per patient per month at Weeks 12 and 24. Subcutaneous treatment with IgPro20 also reduced hospital-related absenteeism. The number of patients, parents, or guardians who were not absent from work or housework duties and had no reduction in working time increased from 4 (17.4%) at Week 1 to 9 (39.1%) at Week 24. Similar results were obtained in the per-protocol set (n = 21).ImplicationsSwitching from IVIG to SCIG reduced markedly productivity loss and hospital-related absenteeism. The reduction in hospital visit frequency due to the use of home-based IgG therapy enabled by the change in administration route is expected to produce an important pharmacoeconomic benefit in Japan. Study Code: ZLB06_002CR, ClinicalTrials.gov identifier: NCT01199705.     

The Use of Cost‐Effectiveness Analysis for Pediatric Immunization in Developing Countries

Context: Developing countries face critical choices for introducing needed, effective, but expensive new vaccines, especially given the accelerated need to decrease the mortality of children under age five and the increased immunization resources available from international donors. Cost‐effectiveness analysis (CEA) is a tool that decision makers can use for efficiently allocating expanding resources. Its use in developing countries, however, lags behind that in industrialized countries. Methods: We explored how CEA could be made more relevant to immunization policymaking in developing countries by identifying the limitations for using CEA in developing countries and the impact of donor funding on the CEA estimation. We conducted a comprehensive literature search using formal search protocols and hand searching indexed and gray literature sources. We then systematically summarized the application of CEA in industrialized and developing countries through thematic analysis, focusing on pediatric immunization and methodological and contextual issues relevant to developing countries. Findings: Industrialized and developing countries use CEA differently. The use of the Disability‐Adjusted Life Year (DALY) outcome measure and an alternative generalized cost‐effectiveness analysis approach is restricted to developing countries. In pediatric CEAs, the paucity of evaluations and the lack of attention to overcoming the methodological limitations pertinent to children's cognitive and development distinctiveness, such as discounting and preference characterization, means that pediatric interventions may be systematically understudied and undervalued. The ability to generate high‐quality CEA evidence in child health is further threatened by an inadequate consideration of the impact of donor funding (such as GAVI immunization funding) on measurement uncertainty and the determination of opportunity cost. Conclusions: Greater attention to pediatric interventions and donor funding in the conduct of CEA could lead to better policies and thus more worthwhile and good‐value programs to benefit children's health in developing countries.     

体外诱导多黏菌素耐药肺炎克雷伯菌的适合度代价相关研究

目的 研究体外诱导多黏菌素耐药肺炎克雷伯菌的适合度代价，并分析耐药株的分子特性。方法 采用体外诱导方法将临床分离的3株多黏菌素敏感肺炎克雷伯菌诱导成多黏菌素耐药株；微量肉汤稀释法检测体外诱导耐药前后菌株对临床常用抗菌药物的最低抑菌浓度(minimal inhibititory concentration, MIC)；采用PCR方法检测多黏菌素耐药相关基因pmrA、pmrB、mgrB、phoP和phoQ，并对阳性片段进行测序比对分析；对诱导耐药菌株及其对应敏感菌株进行生长曲线分析、生物膜形成能力检测及体外竞争和抗血清试验，分析研究多黏菌素耐药肺炎克雷伯菌的适合度代价。结果 3株诱导耐药株中均检出pmrB(T157P)突变，在诱导株FK713R和FK729R携带的mgrB基因中分别检出ISkpn14和IS5like插入序列。诱导耐药株与敏感株相比，24h生长曲线未发现明显差异；生物膜形成能力检测结果发现诱导耐药株与敏感株生物膜形成能力无明显差异；3株菌获得多黏菌素耐药后均表现出一定程度的体外竞争缺陷，竞争指数(CI值)分别为0.01、0.54和5×10-4；3株诱导耐药菌中有2株(FK713R和FK729R)与其敏感菌相比出现抗血清作用增强现象。结论 肺炎克雷伯菌获得多黏菌素耐药后会出现一定的适合度改变，不同的耐药机制可能会引起不同的适合度表现。     

A centralized approach to out‐of‐province genetic testing leads to cost savings: the Alberta experience

The Genetic Resource Center (GRC) is a centralized process for requesting genetic testing that is not available within the province (Alberta, Canada). In order to assess potential cost savings associated with this process, all applications received by the GRC in 2010 were reviewed, and cost savings were recorded for statistical analysis. Seven areas of cost savings were identified: (i) negotiated pricing, (ii) laboratory selection, (iii) testing setup in‐province, (iv) duplicate testing, (v) inappropriate testing, (vi) sequential testing and (vii) testing offered within the province.The total test cost of the 615 applications submitted in 2010 without the GRC process would have been $766,783 (Canadian dollars). A total cost savings of $112,201 was achieved through the GRC, which represents 15% of the total cost of requested testing ($112,201/$766,783). This is the first study to examine areas of cost savings for genetic testing sent out‐of‐province. The greatest cost savings resulted from the areas of laboratory selection and negotiated pricing. A centralized process to manage out‐of‐province genetic test requests results in consistency in testing and significant cost savings.     

Survival after transfusion in the Netherlands

Background Cost‐effectiveness analyses of blood safety interventions require estimates of the life expectancy after blood product transfusion. These are best derived from survival after blood transfusion, per age group and blood component type. Study design and methods In the PROTON (PROfiles of TransfusiON recipients) study transfusion recipient data was collected from a hospital sample covering 28% of the total blood use between 1996 and 2006 in the Netherlands. The dataset includes date of transfusion, blood component type transfused and recipient identification details. PROTON data were individually matched to mortality data of the Netherlands. Survival after first transfusion and after any transfusion was calculated, per blood component type and age group. PROTON mortality rates were compared to mortality rates in the general population. The results were used to estimate survival beyond the study period and to estimate life expectancy after transfusion. Results Of all 2 405 012 blood product transfusions in the PROTON dataset, 92% was matched to the national Dutch Municipal Population Register, which registers all deaths. After 1 year, survival after any transfusion was 65·4%, 70·4% and 53·9% for RBC, FFP and PLT respectively. After 5 years, this was 46·6%, 58·8% and 39·3% for RBC, FFP and PLT, respectively. Ten years after transfusion, mortality rates of recipients are still elevated in comparison with the general population. Conclusion Mortality rates of transfusion recipients are higher than those of the general population, but the increase diminishes over time. The mortality rates found for the Netherlands are lower than those found in comparable studies for other countries.