A Multi-Modal Sensor Array for Human-Robot Interaction and Confined Spaces Exploration Using Continuum Robots.

Safe human-robot interaction requires robots endowed with perception. This paper presents the design of a multi-modal sensory array for continuum robots, targeting operation in semi-structured confined spaces with human users. Active safety measures are enabled via sensory arrays capable of simultaneous sensing of proximity, contact, and force. Proximity sensing is achieved using time-of-flight sensors, while contact force is sensed using Hall effect sensors and embedded magnets. The paper presents the design and fabrication of these sensors, the communication protocol and multiplexing scheme used to allow an interactive rate of communication with a high-level controller, and an evaluation of these sensors for actively mapping the shape of the environment and compliance control using gestures and contact with the robot. Characterization of the proximity sensors is presented with considerations of sensitivity to lighting, color, and texture conditions. Also, characterization of the force sensing is presented. The results show that the multi-modal sensory array can enable pre and post-collision active safety measures and can also enable user interaction with the robot. We believe this new technology allows for increased safety for human-robot interaction in confined and semi-structures spaces due to its demonstrated capabilities of detecting impending collision and mapping the environment along the length of the robot. Future miniaturization of the electronics will also allow possible integration in smaller continuum and soft robots.

Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Challenges in the value assessment, pricing and funding of targeted combination therapies in oncology.

BACKGROUND: The use of targeted combination therapy (TCT) is becoming the standard of care in oncology as cancers are attacked through multiple inhibition mechanisms. TCTs pose a budget challenge to health systems and an economic return challenge for companies developing them. METHODS: We conducted a systematic literature review to identify challenges specific to TCTs and reviewed publicly available reports by health technology assessment and pricing and reimbursement bodies. We synthesized our findings into a problem map. RESULTS AND DISCUSSION: Challenges and policy solutions linked to TCTs remain almost fully unexplored; we identified few resources that explicitly addressed TCTs. Contributors to the budget challenge are found at different layers; they and include static willingness-to-pay (WTP) for TCTs and inefficiencies in managing prices of backbone therapies. Economic return challenges are related to payer-imposed restrictions, peculiarities of TCT development, and conflicting incentives of pharmaceutical companies that own constituent therapies. Consequences are delayed or restricted patient access to TCTs, disincentives for research and development, and fewer life years gained. CONCLUSIONS: Multiple issues will lead to the unsustainability of funding systems and possible conflict between stakeholders around access to TCTs. To manage these, new value assessment and attribution methodologies, modified trial designs and differentiated WTP thresholds can be considered in ways that are customized to the characteristics of different health systems.

Management of post-myocardial infarction ventricular septal defects: A critical assessment.

BACKGROUND: Post-myocardial infarction (MI) ventricular septal defects (PIVSD) are an uncommon but life-threatening complication of acute MI. Although surgical closure has been the standard of care, mortality, and recurrence of VSD remain high even after emergent surgery. Transcatheter VSD closure (TCC) devices have become an alternative or adjunct to surgical closure. METHODS: Online database search was performed for studies that included adults with PIVSD who underwent medical treatment (MT) alone, surgical closure (SC) (early or late), and TCC (early, late, or for post-surgical residual VSD). RESULTS: Twenty-six studies were included with a total of 737 patients who underwent either MT (N = 100), SC (early (n = 167), late (n = 100)), and TCC (early (n = 176), late (n = 115), or post-surgical residual VSD (n = 79)). The 30-day mortality among MT group was 92 ± 6.3%, among SC was 61 ± 22.5% (early 56 ± 23%, late 41 ± 30%), and for all TCC patients was 33 ± 24% (early 54 ± 32.7%, late 16 ± 26%), and TCC for post-surgical residual VSD 11 ± 34.9%. The mortality among overall SC, overall TCC and early TCC groups was significantly lower as compared with the MT (P < 0.001 for all comparisons). The overall mortality among all TCC, and late TCC groups was significantly lower when compared with the late SC (P < 0.0001, P < 0.0001, respectively). CONCLUSION: Closure of PIVSD decreases mortality as compared with MT alone and should be attempted as early as possible after diagnosis. Selection of TCC versus SC should be based on factors including complexity of the defect, availability of closure devices, expertise of the operator, and clinical condition of patient.

The materials irradiation experiment for testing plasma facing materials at fusion relevant conditions.

The Materials Irradiation Experiment (MITE-E) was constructed at the University of Wisconsin-Madison Inertial Electrostatic Confinement Laboratory to test materials for potential use as plasma-facing materials (PFMs) in fusion reactors. PFMs in fusion reactors will be bombarded with x-rays, neutrons, and ions of hydrogen and helium. More needs to be understood about the interactions between the plasma and the materials to validate their use for fusion reactors. The MITE-E simulates some of the fusion reactor conditions by holding samples at temperatures up to 1000 °C while irradiating them with helium or deuterium ions with energies from 10 to 150 keV. The ion gun can irradiate the samples with ion currents of 20 µA-500 µA; the typical current used is 72 µA, which is an average flux of 9 × 10(14) ions/(cm(2) s). The ion gun uses electrostatic lenses to extract and shape the ion beam. A variable power (1-20 W), steady-state, Nd:YAG laser provides additional heating to maintain a constant sample temperature during irradiations. The ion beam current reaching the sample is directly measured and monitored in real-time during irradiations. The ion beam profile has been investigated using a copper sample sputtering experiment. The MITE-E has successfully been used to irradiate polycrystalline and single crystal tungsten samples with helium ions and will continue to be a source of important data for plasma interactions with materials.

Simultaneous remediation of nutrients from liquid anaerobic digestate and municipal wastewater by the microalga Scenedesmus sp. AMDD grown in continuous chemostats.

AIMS: The primary aim of this study was to investigate the capacity of a microalga, Scenedesmus sp. AMDD, to remediate nutrients from municipal wastewater, either as the sole nutrient source or after blending with wastewater obtained from the anaerobic digestion of swine manure. A complimentary aim was to study and define the effects of these wastewaters on microalgal growth, biomass productivity and composition which have important implications for a commercial biofuels production system. METHODS AND RESULTS: A microalga, Scenedesmus sp. AMDD, was grown in continuous chemostats in municipal wastewater or wastewater supplemented with 1·6× or 2·4× higher levels of nitrogen (N) obtained through supplementation with anaerobic digestates. Biomass productivity increased with increasing nutrient supplementation, but was limited by light at high cell densities. Cellular quotas of carbon (C), nitrogen and phosphorus (P) all increased in direct proportion to their concentrations in the combined wastewaters. At higher cell densities, total carbohydrate decreased while protein increased. Fatty acid content remained relatively constant. Under high nutrient levels, the fatty acid profiles contained a higher concentration of polyunsaturated fatty acids at the expense of monounsaturated fatty acids. Chlorophyll a was 2·5 times greater in the treatment of greatest nutrient supplementation compared to the treatment with the least. Ammonium (NH4(+)) and phosphate (PO4(3-)) were completely removed by algal growth in all treatments and with maximal removal rates of 41·2 mg N l(-1) d(-1) and 6·7 mg P l(-1) d(-1) observed in wastewater amended with 2·4× higher N level. SIGNIFICANCE AND IMPACT OF THE STUDY: The study is the first to report stable, long-term continuous algal growth and productivity obtained by combining wastewaters of different sources. The study is supported by detailed analyses of the composition of the cultivated biomass and links composition to the nutrient and light availabilities in the cultures. Simultaneous remediation of these wastes by algal growth is discussed as a strategy for the valorization of the biomass.

Direct healthcare costs of selected diseases primarily or partially transmitted by water.

Despite US sanitation advancements, millions of waterborne disease cases occur annually, although the precise burden of disease is not well quantified. Estimating the direct healthcare cost of specific infections would be useful in prioritizing waterborne disease prevention activities. Hospitalization and outpatient visit costs per case and total US hospitalization costs for ten waterborne diseases were calculated using large healthcare claims and hospital discharge databases. The five primarily waterborne diseases in this analysis (giardiasis, cryptosporidiosis, Legionnaires' disease, otitis externa, and non-tuberculous mycobacterial infection) were responsible for over 40 000 hospitalizations at a cost of $970 million per year, including at least $430 million in hospitalization costs for Medicaid and Medicare patients. An additional 50 000 hospitalizations for campylobacteriosis, salmonellosis, shigellosis, haemolytic uraemic syndrome, and toxoplasmosis cost $860 million annually ($390 million in payments for Medicaid and Medicare patients), a portion of which can be assumed to be due to waterborne transmission.

The effects of exenatide bid on metabolic control, medication use and hospitalization in patients with type 2 diabetes mellitus in clinical practice: a systematic review.

The objective of this systematic review was to assess the published literature on the effectiveness of exenatide twice daily (exenatide) in clinical practice, specifically its effects on haemoglobin A1c (A1C), fasting glucose (FG), weight, systolic blood pressure (SBP), medication use, hospitalization and cardiovascular disease (CVD) outcomes. A systematic literature search using the MEDLINE database of English language literature published between January 2005 and May 2011 was performed. The review included retrospective or prospective observational studies that included 100 or more patients per treatment group. A total of 15 studies meeting the inclusion criteria were identified. The studies revealed significant reductions of -0.4 to -0.9% in A1C, -10 mg/dl in FG, -2 to -11 kg in body weight and -2 to -11 mmHg in SBP. Statistically significant reductions in the use or dosage of either oral glucose-lowering medications or insulin after initiating exenatide treatment were found in every observational study that assessed medication changes, including reductions in dosage of up to 75% in sulphonylureas dosages, 22% in metformin, 66% in thiazolidinediones (TZD) or TZD combination therapy and 75% in prandial insulin. Exenatide-treated patients experienced significantly lower rates of all-cause and CVD-related hospitalization and CVD events than patients treated with other therapies overall. In this review of observational studies, exenatide initiation was associated with significant reductions in clinically relevant outcomes. Improvements in A1C, FG, weight and SBP in the observational studies in this review were consistent with improvements observed in controlled clinical trials.

Can modeling of health outcomes facilitate regulatory decision making? The benefit-risk tradeoff for rosiglitazone in 1999 vs. 2007.

Rosiglitazone was initially approved for type 2 diabetes monotherapy. We tested health-outcomes modeling as an aid to regulatory decision making by quantifying the incremental net benefit (INB) value of rosiglitazone (relative to a comparator), both at the time of first approval (1999) and at the FDA advisory committee review (2007). Using 1999 data, rosiglitazone was projected to provide an additional 0.639 years of life (0.373 quality-adjusted life years (QALYs)) relative to placebo but a loss of 0.312 years (0.173 QALYs) relative to glyburide, with uncertainty in reduction of hemoglobin A(1c) (HbA(1c)) level having the greatest impact on the benefit-risk profile. By 2007, rosiglitazone was projected to provide an additional 0.222 years (0.091 QALYs) vs. glyburide and 0.026 years vs. metformin (0.009 QALYs). Modeling suggested that the use of rosiglitazone as monotherapy was not initially warranted, given the uncertainty with regard to benefit. Despite similar net benefit (NB) as metformin shown in postmarketing data, residual cardiovascular (CV) concerns did not support the use of rosiglitazone as first-line therapy. We adapted a mathematical diabetes model to estimate NB and uncertainty of diabetes monotherapy.

Deuterium anions in inertial electrostatic confinement devices.

A magnetic deflection-energy analyzer and Faraday trap diagnostic have been used to make measurements of divergent deuterium anion flow in the inertial electrostatic confinement experiment at the University of Wisconsin-Madison (UW-IEC) [J. F. Santarius, G. L. Kulcinski, R. P. Ashley, D. R. Boris, B. B. Cipiti, S. K. Murali, G. R. Piefer, R. F. Radel, I. E. Radel, and A. L. Wehmeyer, Fusion Sci. Technol. 47, 1238 (2005)], a device to confine high-energy light ions in a spherically symmetric electrostatic potential well. Deuterium anion current densities as high as 8.5 microA/cm2 have been measured at the wall of the UW-IEC device, 40 cm from the surface of the device cathode with a detector assembly of admittance area 0.7 cm2. Energy spectra obtained using a magnetic deflection-energy analyzer diagnostic indicate the presence of D2(-), and D- ions produced through thermal electron attachment near the device cathode, as well as D- ions produced via charge-transfer processes between the anode and cathode of the device.

Scheduling of measles vaccination in low-income countries: projections of a dynamic model.

Large-scale vaccination campaigns (SIAs) and improved routine immunization (RI) have greatly reduced measles incidence in low-income countries. However, the interval between SIAs required to maintain these gains over the long term is not clear. We developed a dynamic model of measles transmission to assess measles vaccination strategies in Cambodia, Ghana, India, Morocco, Nigeria, and Uganda. We projected measles cases from 2008 to 2050 under (a) holding SIAs every 2, 4, 6, or 8 years, (b) improvements in first dose routine measles vaccine (MCV1) coverage of 0%, 1%, 3% annually, and (c) introducing MCV2 once MCV1 coverage reaches 70%, 80%, 90%. If MCV1 continues improving, then India and Nigeria could hold SIAs every 4 years without significant probability of large outbreaks, and the other countries every 6-8 years. If RI remains stagnant, India and Nigeria should hold SIAs every 2 years, and the other countries every 4-6 years.

Will pharmacogenomics disrupt the U.S. health care system? No.

There is a widely held view that the scientific breakthroughs represented by pharmacogenomics and other new biomarkers portend a new 'personalized medicine' that will disrupt and revolutionize the U.S. health care system. This paper explores this hypothesis, arguing that while this exciting new science will enhance our understanding of human biology and our ability to develop new measures against disease over the long term, there is little reason to expect it to undermine or fundamentally alter the current U.S. health care system. This system is under attack from other, broader societal forces and will necessarily change; however, the argument made here is that the current system can easily cope with the changes that pharmacogenomics will bring and that it is unlikely to be disruptive to the current system because (1) it will probably unfold gradually and incrementally over a time span of decades and (2) our drug development and health care system--from development to delivery--has demonstrated sufficient flexibility to adapt to these kinds of incremental changes. Nonetheless, the sustainability of the projected growth in health spending is in question. Profound reforms are likely, but improved knowledge of our human biology will more likely be a constructive factor as we adapt to these changes.

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial.

Oral capecitabine (Xeloda) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings pound3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial.

UNLABELLED: Interleukin-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, expression of VCAM-1 on endothelium, mucin production, 15-lipoxygenase activity, and Th2 lymphocyte stimulation leading to the secondary synthesis of IL-4, IL-5, and IL-13. Soluble recombinant human IL-4 receptor (IL-4R; Nuvance; altrakincept) inactivates naturally occurring IL-4 without mediating cellular activation. Nebulized IL-4R has a serum half-life of approximately 1 wk. In this double-blind, placebo-controlled trial, 25 patients with moderate asthma requiring inhaled corticosteroids were randomly assigned to receive a single nebulized dose of IL-4R 1,500 microg, IL-4R 500 microg, or placebo after stopping inhaled corticosteroids. No drug-related toxicity was observed. Treatment with IL-4R produced significant improvement in FEV(1) on Day 4 (1,500 microg versus placebo; p < 0.05) and in FEF(25-75) on Days 2 and 4 (1,500 microg versus placebo; p < 0.05). Asthma symptom scores stabilized among patients treated with IL-4R 1, 500 microg, despite abrupt withdrawal of corticosteroids, but not in the IL-4R 500 microg group or the placebo group (p < 0.05). Patients in the IL-4R 1,500 microg group also required significantly less beta(2)-agonist rescue use (p < 0.05). Anti-inflammatory effects were further demonstrated by significantly reduced exhaled nitric oxide (p < 0.05). CONCLUSIONS: A single dose of IL-4R appears safe and effective in moderate asthma. The 1,500 microg dose appears as safe but significantly more effective than the 500 microg dose.

Etanercept: therapeutic use in patients with rheumatoid arthritis.

Tumour necrosis factor (TNF) plays a central part in the pathophysiology of rheumatoid arthritis (RA). TNF initiates signal transduction by interacting with surface bound TNF receptors. Soluble tumour necrosis factor receptors (sTNFRs) act as natural inhibitors of TNF activity. Etanercept, recombinant p75 sTNFR:Fc fusion protein, has received approval from the US Food and Drug Administration for patients with RA and juvenile RA (JRA) who have failed treatment with at least one other drug. Etanercept has demonstrated excellent safety and efficacy in large scale, randomised, double blind, placebo controlled trials of patients with RA and JRA who are refractory to other disease modifying anti-rheumatic drugs. The therapeutic effects mediated by etanercept are rapid and sustained. Combining etanercept with methotrexate was found to be safe and more effective than treatment with methotrexate alone in the treatment of RA. These clinical findings demonstrate that etanercept can result in symptomatic improvement in patients with RA and JRA. Etanercept is an important new addition to the treatment of these diseases.

Randomized, double-blind, placebo-controlled trial to evaluate the hematopoietic growth factor PIXY321 after moderate-dose fluorouracil, doxorubicin, and cyclophosphamide in stage II and III breast cancer.

PURPOSE: To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 750 mg/m(2) (FAC) chemotherapy in patients with stage II and III breast cancer. PATIENTS AND METHODS: In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 microg/m(2) subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/microL. RESULTS: PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P <.05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug. CONCLUSION: PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.

Comparison of seven antibiotic treatments with no treatment for bacteriological efficacy against bovine mastitis pathogens.

Milk culture results were retrospectively reviewed from 9007 cases of subclinical mastitis affecting cows housed in dairy herds located in New York and northern Pennsylvania. Cases included in this analysis had at least one mastitis pathogen isolated from the initial milk sample, were recultured within 1 mo, had permanent cow identification, and had records of whether mastitis was treated with an antibiotic or no treatment at all. Overall bacteriological cure rate for 21 mastitis pathogens was 68% (6097 of 9007). Antibiotic treated cases had a higher cure rate (75%) than did untreated cases (65%). Antibiotic treatments that significantly differed from the untreated cure rate of 65% were amoxicillin (82%), erythromycin (76%), cloxacillin (73%), and pirlimycin (44%). Cure rates for antibiotic treatments with cephapirin, hetacillin, or penicillin did not differ from the untreated cure rate. Agents for which some antibiotics were associated with increased cure rates compared with no treatment were Streptococcus agalactiae, streptococci other than Strep. agalactiae, and coagulase-negative staphylococci. The antibiotic most commonly associated with higher cure rates was amoxicillin. Most of the 21 mastitis agents showed no difference in bacteriologic cure rates between any of the 7 antibiotic treatments and no treatment.

Computer-assisted anthropometry for outcome assessment of cleft lip.

Anthropometry and clinical examination best evaluate the morphology of repaired cleft lip and nose. An original, accurate, and practical image analysis of the lip and nose, which takes advantage of the mathematic, geometric, and organizational capabilities of public domain NIH-Image software (http://rsb.info.nih.gov/nih-image/), has been developed and tested over the past 6 years. A modified structured physical examination form that complements this analysis is under study. Accuracy of NIH-Image-based anthropometry was compared with direct measurements of 22 linear distances on the lip and nose. Twenty-five sets of direct measurements were taken, prospectively, on 15 children with repaired cleft lip over a 6-year period. The results were submitted to regression analysis. Then, relevant lip and nasal tip aesthetics were evaluated by the measuring capabilities of NIH-Image to create a quantitative assessment tool. For each episode, 15 possible faults were weighted, according to aesthetics and deformity, to provide an adverse score. The sum of the 5 lip scores, 10 nose scores, and combination gave respective grades. The analysis was modified to stratify congenital deformity to relate severity of disease to outcome. This analysis was applied to digitized images of 19 consecutive children, immediately prior to repair of complete unilateral cleft lip and nose, at the time of palate repair, and annually from the age of 3 to 6 years. There were 19 NIH-Image-based measurements of the congenital deformity and 35 measurements of surgical results; four children had three sets of records, eight had two sets, and seven had one set Descriptive statistics were applied. Following 556 paired direct and computer-assisted measurements, exceptional linear correlation was shown with a Pearson R coefficient of 0.96. The best correlation was lines within the plane of the camera lens, with the average difference ranging between 0.025 and 0.997 mm. Visual inspection of frontal and submental photographs of excellent, good, and poor results substantiates the ability of this analysis to quantify and grade a spectrum of relevant cleft lip and nasal anatomy. For these 19 patients, there was a broad range of performance scores, approximating a normal distribution. The mean of the NIH-Image-based analysis scores, 16.91, was a (very) good grade. A single standard deviation of 6.88 extended up into excellent and down to fair. The congenital analysis indicated a range of deformity. Comparing deformity with outcome, simple regression analysis had a coefficient of determination (R2) of 0.223, indicative of a weak positive relationship. An accurate and practical morphologic computer-assisted outcome assessment of repaired cleft lip and nasal deformity has been developed. There is a weak direct correlation between severity of deformity and outcome. Testing in multiple clinics is warranted.

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial.

BACKGROUND: In a phase II study, etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. OBJECTIVE: To confirm the benefit of etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. SETTING: 13 North American centers. PATIENTS: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. INTERVENTION: Twice-weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6 months. MEASUREMENTS: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. RESULTS: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. CONCLUSIONS: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.