Sensitivity and specificity of serologic assays for detection of human infection with 2009 pandemic H1N1 virus in U.S. populations

Swine origin 2009 H1N1 influenza virus has spread globally to cause the first influenza pandemic of the 21st century. Serological studies can improve our understanding of the extent of human infection and risk factors associated with the transmission of this pandemic virus. The "gold standard" for serodiagnosis of human influenza virus infection is the detection of seroconversion between acute- and convalescent-stage samples. However, the timing of seroepidemiological investigations often precludes the collection of truly acute-phase sera, requiring development of serological criteria for evaluating convalescent-phase sera that optimize detection of true positives and true negatives. To guide seroepidemiological investigations into the spread of the novel 2009 pandemic H1N1 virus, we characterized serum antibody responses to 2009 H1N1 virus in 87 individuals with confirmed viral infection and 227 nonexposed U.S. individuals using microneutralization (MN) and hemagglutination inhibition (HI) assays. Sensitivity and specificity were determined for each assay alone and in combination for detection of 2009 H1N1 virus-specific antibodies in convalescent-phase sera. Although the HI assay was more specific for detecting antibody to 2009 H1N1, the MN assay was more sensitive, particularly for detecting low-titer seroconversions. A combination of titers (MN ≥ 40 and HI ≥ 20) provided the highest sensitivity (90%) and specificity (96%) for individuals aged <60 years and 92% specificity for adults aged ≥ 60 years for detection of serologically confirmed 2009 H1N1 infections in U.S. populations during the first pandemic waves. These studies provide an approach to optimize timely serological investigations for future pandemics or outbreaks of novel influenza viruses among humans.     

Transdermal Delivery of Insulin Using Microneedles in Vivo

PURPOSE: The purpose of this study was to design and fabricate arrays of solid microneedles and insert them into the skin of diabetic hairless rats for transdermal delivery of insulin to lower blood glucose level. METHODS: Arrays containing 105 microneedles were laser-cut from stainless steel metal sheets and inserted into the skin of anesthetized hairless rats with streptozotocin-induced diabetes. During and after microneedle treatment, an insulin solution (100 or 500 U/ml) was placed in contact with the skin for 4 h. Microneedles were removed 10 s, 10 min, or 4 h after initiating transdermal insulin delivery. Blood glucose levels were measured electrochemically every 30 min. Plasma insulin concentration was determined by radioimmunoassay at the end of most experiments. RESULTS: Arrays of microneedles were fabricated and demonstrated to insert fully into hairless rat skin in vivo. Microneedles increased skin permeability to insulin, which rapidly and steadily reduced blood glucose levels to an extent similar to 0.05-0.5 U insulin injected subcutaneously. Plasma insulin concentrations were directly measured to be 0.5-7.4 ng/ml. Higher donor solution insulin concentration, shorter insertion time, and fewer repeated insertions resulted in larger drops in blood glucose level and larger plasma insulin concentrations. CONCLUSIONS: Solid metal microneedles are capable of increasing transdermal insulin delivery and lowering blood glucose levels by as much as 80% in diabetic hairless rats in vivo.     

Hospital pharmacy staff development programs in Ohio

Although staff development programs have been used to implement clinical services in Ohio hospital pharmacies, the majority of clinical services have been implemented without the use of staff development programs. The results of this study show that less than half of Ohio hospital pharmacy departments provide staff development programs. In those hospitals where the programs were provided, the average number of clinical services implemented through staff development was not significantly different from the average number implemented without these programs. Nor was there a significant difference in the average number of clinical services implemented through staff development between small hospitals (199 beds or less), medium hospitals (200 to 399 beds), and larger hospitals (400 or more beds); between government (city, county, or state) and private, nonprofit hospitals; and between hospitals whose staff development program coordinators were directors and hospitals whose coordinators were not directors. For the majority of departments that provided staff development programs, certification or testing of pharmacists was not required before providing clinical services. Results from the survey indicated that certification may not be necessary for all clinical services. Commitment to staff development programs in terms of management support and participation, awarding of continuing-education credit, and use in pharmacist performance evaluations was demonstrated by no more than 34 percent of all departments that responded. Financial commitment to these programs was low. Overall, since less than half of the departments reported providing staff development programs, the level of commitment to staff development appeared to be low.     

Construction of a series of congenic mice with recombinant chromosome 1 regions surrounding the genetic loci for resistance to intracellular parasites (Ity, Lsh, and Bcg), DNA repair responses (Rep-1), and the cytoskeletal protein villin (Vil).

The interval of mouse chromosome 1 extending from Idh-1 to Pep-3 harbors the natural resistance gene Ity/Lsh/Bcg; it controls the outcome of infection with Salmonella typhimurium, Leishmania donovani, and several Mycobacterium species. This region also contains a DNA repair gene, Rep-1, which determines the rapidity with which double-strand breaks in chromatin are repaired. BALB/cAnPt and DBA/2N mice differ in their phenotypic expression of these genes. To generate appropriate strains of mice for the study of these genes, a series of 10 C.D2 congenic strains recombinant across a 28-centimorgan interval of mouse chromosome 1 extending from Idh-1 to Pep-3 were derived from crosses of the C.D2-Idh-1 Pep-3 congenic strain back to BALB/cAn. Analyses of these recombinant strains will allow the correlation of biological-immunological phenotypes with defined genetic regions.     

Lumbar sympathectomy in critical limb ischaemia: surgical, chemical or not at all?

The value of surgical and chemical lumbar sympathectomy was studied in patients with critical lower-limb ischaemia without the option of vascular reconstruction. Clinical success rates, defined as improvement of ischaemia stage, and limb salvage rates were recorded for 76 limbs of 70 consecutive patients. Chemical lumbar sympathectomy patients were older and had more concomitant diseases than surgical lumbar sympathectomy patients. The short-term (6-week) success rate in 36 cases treated with surgical lumbar sympathectomy (44%) was better than in 40 cases treated with chemical lumbar sympathectomy (18%) (P = 0.01). The long-term (1-year) success rate was 47% for surgical lumbar sympathectomy and 45% for chemical lumbar sympathectomy (P = NS). The 1-year limb salvage rates were 61% for surgical lumbar sympathectomy and 58% for chemical lumbar sympathectomy (P = NS). Complications were minor in both groups. Lumbar sympathectomy still has a limited role in the treatment of critical limb ischaemia in patients without the option of vascular reconstruction. Both surgical and chemical lumbar sympathectomy can be performed with very little morbidity and may provide a benefit over the natural course of the arterial insufficiency.     

6-minute walk work for assessment of functional capacity in patients with COPD

The 6-min walk (6MW) test is commonly used to assess exercise capacity in patients with COPD and to track functional change resulting from disease progression or therapeutic intervention. Not surprisingly, distance covered has been the preferred outcome for this test. However, distance walked does not account for differences in body weight that are known to influence exercise capacity. OBJECTIVE: The aim of this study was to evaluate the 6-min distance x body weight product (6MWORK) as an improved outcome measure with a solid physiologic foundation. PATIENTS AND METHODS: One hundred twenty-four men and women with moderate-to-severe COPD volunteered and completed the testing sequence, which included pulmonary function, a peak effort ramp cardiopulmonary exercise study with gas exchange, and the 6MW. Means and SD were generated for the variables of interest. Differences were analyzed using analysis of variance techniques. Correlation coefficients and receiver operating characteristic (ROC) curves were calculated for the 6-min walk distance (6MWD) and 6MWORK with indexes of pulmonary function, work performance, and Borg scores for dyspnea and effort. RESULTS: Men and women presented with a significant smoking history that also differed by gender (48 vs 66 pack-years, respectively; p < 0.01). The mean (+/- SD) FEV(1) values were 45 +/- 12.6% and 48 +/- 12.1%, respectively (not significant), while the diffusing capacity of the lung for carbon monoxide (DLCO) was 14.7 +/- 6.1 vs 10.3 +/- 3.9 mL/min/mm Hg, respectively (p < 0.001), for men and women. The 6MWD averaged 416.8 +/- 79.0 m for men and 367.8 +/- 78.6 m for women, and these differences were significant (p < 0.002). When 6MWD was compared as the percent predicted of normal values, each gender presented with a similar reduction of 78.6 +/- 14.5% vs 79.9 +/- 17.5% (p > 0.05), respectively. 6MWORK averaged 35,370 +/- 9,482 kg/m and 25,643 +/- 9,080 kg/m (p < 0.0001) for men and women, respectively. 6MWORK yielded higher correlation coefficients than did 6MWD when correlated with DLCO, lung diffusion for alveolar ventilation, FEV(1), FEV(1)/FVC ratio, watts, peak oxygen uptake, peak minute ventilation, and peak tidal volume. The ROC curve demonstrated that 6MWORK had a significantly larger calculated area under the curve (p < 0.05) [plot of 100-sensitivity to specificity for each variable of interest for all subjects] than 6MWD when differentiating an objectively selected definition of low work capacity vs high work capacity (bike ergometry work, < 55 vs > 55 W, respectively). CONCLUSIONS: We conclude that work calculated as the product of distance x body weight is an improved outcome measure for the 6MW. 6MWORK can be used whenever the 6MW is required to estimate a patient's functional capacity. This measure is also a common measure, which can be converted to indexes of caloric expenditure for direct cross-modality comparisons.     

Bone Health in Immigrant Hispanic Women Living in Texas

Osteoporosis is a serious national public health problem, and is expected to increase significantly over the next few decades, especially in women. A limitation of bone health research exists since few studies have involved Hispanic women, and even fewer, Hispanic immigrant women. For this study we examined the effects of anthropometric, behavioral, and health history variables on bone mineral density (BMD) in 84 immigrant Hispanic women, age 40 and above. BMD was assessed at the spine, femur, and forearm using dual energy x-ray absorptiometry (DXA). Demographic information, health histories, and behavioral risk factors were obtained from a questionnaire. In the younger group (mean age = 44.1 years) 61% had spinal osteopenia, and in the postmenopausal group (mean age = 53.0 years) 59% had osteopenia and 13% had osteoporosis. Femur sites were free of osteoporosis. Mean body mass index (BMI) was 31.8 ± 6.1 and mean waist girth was 95.6 ± 12.5 cm, indicating overall and abdominal obesity. Partial correlations indicated a significant positive relationship between body fat variables and total femur BMD values. ANOVAs revealed no differences in BMD values at any bone site across tertile levels for calcium intake or for physical activity. However, supplemental and dietary calcium intakes were very low and few participants engaged in regular physical activity outside of work and activities of daily living (ADL). In light of the expected increase in osteoporosis in this population and the prevalence of spinal osteopenia in the younger participants, education about the health risks of osteoporosis should be made available to this group.