The Pereyra procedure. Favorable experience with 200 operations.

This communication documents experience with 200 Pereyra operations performed for stress urinary incontinence over a 9 year period. The majority of patients were 35 to 55 years of age, were obese, and had varying degrees of uterovaginal prolapse. More than one fourth also had excessive bleeding and all were best managed by vaginal surgery. Important points in surgical technique are emphasized. Of 188 patients followed, 82 per cent had complete symptomatic relief and another 10.5 per cent were improved. There was a 7.5 per cent failure rate and morbidity was minimal. We conclude that the Pereyra procedure should be considered for stress urinary incontinence whenever vaginal surgery is indicated.     

Epitope mapping of BP230 leading to a novel enzyme-linked immunosorbent assay for autoantibodies in bullous pemphigoid

Background Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by circulating autoantibodies against BP180 and BP230. For BP180, the NC16A domain has previously been identified as the main antigenic target in BP, while data about the diagnostic value of epitopes on BP230 were inconclusive. Objectives To identify the most appropriate epitopes on BP230 to be applied in a simple, sensitive, and highly specific enzyme‐linked immunosorbent assay (ELISA) for routine detection of serum autoantibodies. Methods Ten overlapping linear fragments covering the whole length of BP230 were expressed in Escherichia coli. Based on Western blot analysis with sera from patients with BP (n = 49) and healthy controls (n = 94), the diagnostic performance of the fragments was compared by receiver operating characteristics curve analysis. The BP230‐C3 fragment comprising the C‐terminal portion (amino acids 2326–2649) was subsequently applied in a novel ELISA. The operating characteristics of this ELISA were analysed by probing sera from patients with BP (n = 118), pemphigus vulgaris (n = 50), rheumatoid arthritis and other inflammatory arthritides (n = 170), and systemic lupus erythematosus (n = 56), and from healthy blood donors (n = 483). Results Among all the fragments, BP230‐C3 provided the best efficiency in serologically diagnosing BP by Western blot. An ELISA employing BP230‐C3 revealed a diagnostic sensitivity of 56·8% and specificity of 97·6%. Its diagnostic added value amounted to 4·2% compared with the anti‐BP180‐NC16A‐4X ELISA alone. Conclusions Recombinant BP230‐C3 is a suitable target antigen for the detection of serum autoantibodies against BP230.     

Ro 13-9904, a long-acting broad-spectrum cephalosporin: in vitro and in vivo studies.

Ro 13-9904, a new parenteral cephalosporin, was found to have high in vitro activity against Enterobacteriaceae and other gram-negative bacteria, including various isolates resistant to cefuroxime, cefamandole, cefoxitin, and cefazolin. It showed promising activity against Pseudomonas aeruginosa. Although inhibitory against Staphylococcus aureus at concentrations readily achievable in plasma, it was less potent against this pathogen than cefamandole, cefazolin, or cefuroxime. Isolates of Streptococcus faecalis were uniformly resistant to all the cephalosporins tested. Ro 13-9904 was more active than cefotaxime against Proteus mirabilis, Neisseria gonorrhoeae, Neisseria meningitidis, and Haemophilus influenzae, but less active against S. aureus. Ro 13-9904 was stable to various types of beta-lactamases. Its therapeutic efficacy against experimental septicemias in mice was equal to or slightly superior to that of cefotaxime and SCE-1365 when the antibiotics were administered in repeated subcutaneous doses after bacterial challenge. Cefoperazone, and particularly cefamandole nafate, cefazolin, and mezlocillin were less effective. Although structurally related to cefotaxime and SCE-1365, Ro 13-9904 was found to differ from them in one important respect, namely, in having a long duration of action; this was observed with single-dose treatment given before bacterial challenge. Its broad spectrum of activity coupled with favorable pharmacokinetic properties make Ro 13-9904 a promising compound for clinical studies.     

The role of CD4(+)CD25(+) regulatory T cells in Leishmania infection

There is growing evidence that regulatory T cells and, in particular, the endogenous CD4(+)CD25(+) T cells (T(reg)) are playing a fundamental role in the infectious process due to the protozoan parasite Leishmania. Endogenous CD4(+)CD25(+) T cells are a population of regulatory T cells, recently described for their capacity to control excessive or misdirected immune response. During human or murine Leishmaniasis, many features characteristic of T(reg )function, such as high levels of IL-10, transforming growth factor-beta (TGF-beta) or immunosuppression, have been extensively described. Recent reports formally involved T(reg) in the control of Leishmania major infection. Such control occurs by modulation of the effector immune response; in susceptible mouse strains, CD4(+)CD25(+) T cells suppress excessive T helper (Th)2 response, while in genetically resistant mouse strains, they control protective Th1 responses, allowing for parasite survival and maintenance of memory response. The mechanisms and consequences of such control in both susceptible or resistant mouse strains are discussed.     

Information contributed by meta-analysis in exposure–response modeling: application to phase 2 dose selection of guselkumab in patients with moderate-to-severe psoriasis

Ustekinumab, a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds with high affinity to human interleukin (IL)-12 and IL-23, has been approved to treat patients with psoriasis. Guselkumab is a related human IgG1 monoclonal antibody in clinical development which specifically blocks IL-23. The objective of this study was to study the exposure–response relationship of guselkumab to guide dose selection for a Phase 2 study in patients with moderate-to-severe psoriasis. Data were available from a Phase 1 study of 47 healthy subjects and 24 patients with psoriasis who received various doses of guselkumab. Disease severity was assessed using Psoriasis Area and Severity Index (PASI) scores in all studies. Individual pharmacokinetic parameters were derived from population pharmacokinetics modeling for the purpose of exposure–response modeling to guide dosing regimen selection. A population mechanism-based exposure–response model of guselkumab was developed to evaluate the association of guselkumab dosing with PASI scores using a Type I indirect response model, with placebo effect empirically modeled. The model was subsequently updated, first by incorporating data from psoriasis patients who received placebo (n = 765) and from patients actively treated with ustekinumab 45 or 90 mg (n = 1,230) in two ustekinumab Phase 3 trials. Inclusion of this additional ustekinumab data and the consequent contributions to specific model components substantially reduced uncertainties in all model components except for one parameter. Additional sensitivity analyses showed that the dose selection decision was robust to this remaining uncertainty. The described approach underscores the importance of utilizing all available sources of information in dose selection decisions, along with the importance of effective development team interaction.     

Identification of food groups for use in a self-administered,computer-assisted diet history interview for use in Australia

The objective of this paper was to develop a set of food groups for use in a self-administered, computer-assisted diet history interview for use in Australia by combining foods into groups so as to minimise database error in the macronutrient values for the food groups. The program needs to appropriately balance the level of detail used with the burden load on respondents and errors associated with categorisation of foods into groups. Various statistical techniques were utilised to aggregate a large number of food items into compositionally and conceptually similar groups. Exploratory statistical analysis, cluster analysis, stepwise regression analysis and association rule analysis were performed. A database containing 433 food groups was created which minimised the level of database error in the resulting data collection. Although some database error was introduced by aggregating food items into groups, the magnitude of the errors was reasonable considering other error sources. These findings are useful when applied to collection of food intake information for an individual's diet history and measurement of energy and macronutrient intake.     

Dietary Assessment on a Mobile Phone Using Image Processing and Pattern Recognition Techniques: Algorithm Design and System Prototyping

Dietary assessment, while traditionally based on pen-and-paper, is rapidly moving towards automatic approaches. This study describes an Australian automatic food record method and its prototype for dietary assessment via the use of a mobile phone and techniques of image processing and pattern recognition. Common visual features including scale invariant feature transformation (SIFT), local binary patterns (LBP), and colour are used for describing food images. The popular bag-of-words (BoW) model is employed for recognizing the images taken by a mobile phone for dietary assessment. Technical details are provided together with discussions on the issues and future work.     

Delivery Complications Associated With Prenatal Care Access for Medicaid-Insured Mothers in Rural and Urban Hospitals

CONTEXT: Pregnancy complications affect many women. It is likely that some complications can be avoided through routine primary and prenatal care of reasonable quality. PURPOSE: The authors examined access to health care during pregnancy for mothers insured by Medicaid. The access indicator is potentially avoidable maternity complications (PAMCs). Potentially avoidable maternity complications are often preventable through routine prenatal care, such as infection screening and treatment. The authors examined the risks of potentially avoidable maternity complications among rural and urban hospital deliveries for groups of mothers defined by race or ethnicity. METHODS: Data are from the year 2000 Nationwide Inpatient Sample (NIS). The stratified sample represents all discharges from 20.5% of community hospitals in the United States. The Nationwide Inpatient Sample identifies hospital locations, but not patients' areas of residence. Analyses, which accounted for the sample design, included calculation of potentially avoidable maternity complication rates by race or ethnicity, chi2, t tests, and multivariate logistic regression. FINDINGS: Within groups defined by race or ethnicity, unadjusted rates for potentially avoidable maternity complications did not differ significantly by hospital location. Holding other factors constant, potentially avoidable maternity complications were less common in rural hospitals than in urban hospitals (odds ratio, 0.78; CI, 0.62 to 0.99). In rural hospitals, African Americans had notably higher risk for potentially avoidable maternity complications than did non-Hispanic whites (odds ratio, 1.72; CI, 1.26 to 2.36). In urban hospitals, risk of potentially avoidable maternity complications was not significantly higher for African Americans. Hispanics and Asians had notably lower risks of potentially avoidable maternity complications in urban hospitals than did non-Hispanic whites. CONCLUSIONS: Providers and policymakers should work to reduce the risks of potentially avoidable maternity complications for African American women in rural areas who are insured by Medicaid.     

Update: Health Insurance and Utilization of Care Among Rural Adolescents

CONTEXT: Adolescence is critical for the development of adult health habits. Disparities between rural and urban adolescents and between minority and white youth can have life-long consequences. PURPOSE: To compare health insurance coverage and ambulatory care contacts between rural minority adolescents and white and urban adolescents. METHODS: Cross-sectional design using data from the 1999-2000 National Health Interview Survey, a nationally representative sample of US households. Analysis was restricted to white, black, and Hispanic children aged 12 through 17 (8,503 observations). Outcome measures included health insurance, ambulatory visit within past year, usual source of care (USOC), and well visit within past year. Independent variables included race, residence, demographics, facilitating/enabling characteristics, and need. RESULTS: Across races, rural adolescents were as likely to have insurance (86.8% vs 87.7%) but less likely to report a preventive visit (60.1% vs 65.5%) than urban children; residence did not affect the likelihood of a visit or a USOC. Minority rural adolescents were less likely than whites to be insured, report a visit, or have a USOC. Most race-based differences were not significant in multivariate analysis holding constant living situation, caretaker education, income, and insurance. Low caretaker English fluency, limited almost exclusively to Hispanics, was an impediment to all outcomes. CONCLUSIONS: Most barriers to care among rural and minority youth are attributable to factors originating outside the health care system, such as language, living situation, caretaker education, and income. A combination of outreach activities and programs to enhance rural schools and economic opportunities will be needed to improve coverage and utilization among adolescents.