Health equity monitoring for healthcare quality assurance.

Population-wide health equity monitoring remains isolated from mainstream healthcare quality assurance. As a result, healthcare organizations remain ill-informed about the health equity impacts of their decisions - despite becoming increasingly well-informed about quality of care for the average patient. We present a new and improved analytical approach to integrating health equity into mainstream healthcare quality assurance, illustrate how this approach has been applied in the English National Health Service, and discuss how it could be applied in other countries. We illustrate the approach using a key quality indicator that is widely used to assess how well healthcare is co-ordinated between primary, community and acute settings: emergency inpatient hospital admissions for ambulatory care sensitive chronic conditions ("potentially avoidable emergency admissions", for short). Whole-population data for 2015 on potentially avoidable emergency admissions in England were linked with neighborhood deprivation indices. Inequality within the populations served by 209 clinical commissioning groups (CCGs: care purchasing organizations with mean population 272,000) was compared against two benchmarks - national inequality and inequality within ten similar populations - using neighborhood-level models to simulate the gap in indirectly standardized admissions between most and least deprived neighborhoods. The modelled inequality gap for England was 927 potentially avoidable emergency admissions per 100,000 people, implying 263,894 excess hospitalizations associated with inequality. Against this national benchmark, 17% of CCGs had significantly worse-than-benchmark equity, and 23% significantly better. The corresponding figures were 11% and 12% respectively against the similar populations benchmark. Deprivation-related inequality in potentially avoidable emergency admissions varies substantially between English CCGs serving similar populations, beyond expected statistical variation. Administrative data on inequality in healthcare quality within similar populations served by different healthcare organizations can provide useful information for healthcare quality assurance.

Catheter length preference in wheelchair-using men who perform routine clean intermittent catheterization.

STUDY DESIGN: Prospective, unblinded, multicenter, randomized, controlled, cross-over study assessing user preference and ease of use characteristics of two gel intermittent catheters in 81 self-catheterizing wheelchair-using men. OBJECTIVES: To evaluate the male user's preference between a 30-cm and a 40-cm intermittent catheter (Apogee Intermittent Catheter, Hollister Incorporated, Libertyville, IL, USA) regarding the ease of insertion and removal, ability to control the catheter during insertion, bladder emptying confidence and ease of draining urine into a receptacle or connecting to a urine bag. SETTING: Multiple institutions in the United States. METHODS: Subjects were randomized to order of catheter use, using both 10 test catheters (30-cm) and 10 control catheters (40 cm). All catheters were 12 or 14 French and identical in design and composition, except length. Safety was assessed during the entire study period regarding adverse events (AE) and adverse device events (ADE). Subjects evaluated their ease of use characteristics after each catheter use and final catheter preference. RESULTS: Subjects preferred the Apogee 40-cm intermittent catheter (91.4%) over the 30-cm length (8.6%). The preference was due to subject confidence of complete bladder emptying (70%), more satisfactory length (74%) and easier to drain into a receptacle (58%) with a portable urinal being the most utilized (37%), followed by toilet (35%). The only AE/ADE reported was minor urethral bleeding in one subject and minor pain in another subject, both with the 30-cm catheter. None were reported with the 40-cm catheter. CONCLUSIONS: The Apogee 40-cm catheter was the preferred intermittent catheter due to subject confidence in bladder emptying, ease of catheter manipulation and the ease of draining urine into a receptacle.

Role of genetically engineered animals in future food production.

Genetically engineered (GE) animals are likely to have an important role in the future in meeting the food demand of a burgeoning global population. There have already been many notable achievements using this technology in livestock, poultry and aquatic species. In particular, the use of RNA interference (RNAi) to produce virus-resistant animals is a rapidly-developing area of research. However, despite the promise of this technology, very few GE animals have been commercialised. This review aims to provide information so that veterinarians and animal health scientists are better able to participate in the debate on GE animals.

Precision genetics for complex objectives in animal agriculture.

Indirect modification of animal genomes by interspecific hybridization, cross-breeding, and selection has produced an enormous spectrum of phenotypic diversity over more than 10,000 yr of animal domestication. Using these established technologies, the farming community has successfully increased the yield and efficiency of production in most agricultural species while utilizing land resources that are often unsuitable for other agricultural purposes. Moving forward, animal well-being and agricultural sustainability are moral and economic priorities of consumers and producers alike. Therefore, these considerations will be included in any strategy designed to meet the challenges produced by global climate change and an expanding world population. Improvements in the efficiency and precision of genetic technologies will enable a timely response to meet the multifaceted food requirements of a rapidly increasing world population.

Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino.

We have earlier shown that antisense morpholino oligomers are able to restore dystrophin expression by systemic delivery in body-wide skeletal muscles of dystrophic mdx mice. However, the levels of dystrophin expression vary considerably and, more importantly, no dystrophin expression has been achieved in cardiac muscle. In this study, we investigate the efficiency of morpholino-induced exon skipping in cardiomyoblasts and myocytes in vitro, and in cardiac muscle in vivo by dose escalation. We showed that morpholino induces targeted exon skipping equally effectively in both skeletal muscle myoblasts and cardiomyoblasts. Effective exon skipping was achieved in cardiomyocytes in culture. In the mdx mice, morpholino rescues dystrophin expression dose dependently in both skeletal and cardiac muscles. Therapeutic levels of dystrophin were achieved in cardiac muscle albeit at higher doses than in skeletal muscles. Up to 50 and 30% normal levels of dystrophin were induced by single systemic delivery of 3 g kg(-1) of morpholino in skeletal and cardiac muscles, respectively. High doses of morpholino treatment reduced the serum levels of creatine kinase without clear toxicity. These findings suggest that effective rescue of dystrophin in cardiac muscles can be achieved by morpholino for the treatment of Duchenne muscular dystrophy.

Microwave irradiation enhances gene and oligonucleotide delivery and induces effective exon skipping in myoblasts.

Microwave (MW) energy consists of electric and magnetic fields and is able to penetrate deep into biological materials. We investigated the effect of MW (2450 MHz) irradiation on gene delivery in cultured mouse myoblasts and observed enhanced transgene expression. This effect is, however, highly variable and critically dependent on the power levels, duration and cycle conditions of MW exposure. MW irradiation greatly enhances delivery of 2'O methyl-phosphorothioate antisense oligonucleotide (AON) targeting mouse dystrophin exon 23 and induces specific exon skipping in cultured myoblasts. Effective delivery of AON by MW irradiation is able to correct the dystrophin reading frame disrupted by a nonsense point mutation in the H2K mdx myoblasts, resulting in the restoration of dystrophin expression. MW-mediated nucleic acid delivery does not directly link to the increase in system temperature. The high variability in gene and oligonucleotide delivery is most likely the result of considerable irregularity in the distribution of the energy and magnetic field produced by MW with the current device. Therefore, achieving effective delivery of the therapeutic molecules would require new designs of MW devices capable of providing controllable and evenly distributed energy for homogenous exposure of the target cells.

The use of RNAi and transgenics to develop viral disease resistant livestock.

The possibility of genetically engineering poultry to make them resistant to avian influenza is attracting attention and has now become a real possibility with improved methods for genetic modification and the emergence of RNAi as an antiviral strategy. In order to test this possibility, we have generated transgenic mice that express RNAi molecules targeting a conserved region of the influenza A NP gene and are testing these mice for resistance to influenza infection. Transgenes were initially developed that express short hairpin RNAs (shRNAs) targeting multiple influenza A viral genes. The shRNAs were tested for inhibition of H1N1 PR8 virus in vitro. Two potent shRNAs that target the NP and PA genes were chosen for lentiviral mediated generation of transgenic mice. Transgenic founders for the NP shRNA construct and also a negative control shRNAtargeting EGFP were generated. The constitutive expression of the shRNA molecules in a range of tissue types including lung, was confirmed and so far stable transmission of the RNAi transgenes from the F0 to F3 generation has been observed. Resistance to influenza infection in these transgenic mice is now being confirmed.

Manipulation of small RNAs to modify the chicken transcriptome and enhance productivity traits.

In recent years there has been a revolution in our understanding of genes and how they come to control the physical outcomes of development. Central to this has been the understanding of the cellular processes of RNA interference (RNAi), for which the Nobel Prize for Physiology or Medicine was awarded in 2006. Coupled with this has been the recognition that microRNAs are key mediators of this process within cells. RNAi whether mediated exogenously by synthetic oligonucleotides or vector-delivered double stranded RNA or endogenously by microRNAs can have a profound and specific effect on gene expression. Elucidating and understanding these processes in the chicken will provide critical information to enable more precise control over breeding strategies for improvement of traits in production poultry, either by direct or indirect means. It will also provide alternative strategies for the control and prevention of important avian diseases.

Comparison of bovine RNA polymerase III promoters for short hairpin RNA expression.

RNA interference (RNAi) mediated by DNA-based expression of short hairpin RNA (shRNA) is a powerful method of sequence-specific gene knockdown. A number of vectors for expression of shRNA have been developed that feature promoters from RNA polymerase III (pol III)-transcribed genes of mouse or human origin. To advance the use of RNAi as a tool for functional genomic research and for future development of specific therapeutics in the bovine species, we have developed shRNA expression vectors that feature novel bovine RNA pol III promoters. We characterized two bovine U6 small nuclear RNA (snRNA) promoters (bU6-2 and bU6-3) and a bovine 7SK snRNA promoter (b7SK). We compared the efficiency of each of these promoters to express shRNA molecules. Promoter activity was measured in the context of RNAi by targeting and suppressing the reporter gene encoding enhanced green fluorescent protein. Results show that the b7SK promoter induced the greatest level of suppression in a range of cell lines. The comparison of these bovine promoters in shRNA expression is an important component for the future development of bovine-specific RNAi-based research.

Improved vectors for expression library immunization--application to Mycoplasma hyopneumoniae infection in pigs.

Expression library immunization (ELI) has previously been used in a number of disease models in mice. Here, we describe the first example of the application of ELI to a large animal model with the immunization of pigs against enzootic pneumonia, a disease caused by Mycoplasma hyopneumoniae. The development of new plasmid vectors and library screening methods facilitated the application of ELI to this disease by allowing random libraries to be screened for clones expressing recombinant proteins. In this way the vast majority of clones in random libraries that are unproductive can be eliminated, meaning that libraries are more likely to give protection and are subsequently easier to further screen and analyze. By using this approach we have used one library screen and two animal trials to progress from an original library of 20,000 clones to a group of just 96 clones.

Mother-to-child transmission of the human immunodeficiency virus in Texas.

BACKGROUND: The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. METHODS: We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. RESULTS: Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. CONCLUSIONS: Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.

Concerns of pregnant women about bing tested for HIV: a study in a predominately Mexican-American population.

More than 90% of pediatric acquired immune deficiency syndrome (AIDS) cases are due to mother-to-child (vertical) transmission. Medical intervention can reduce the risk of vertical transmission human immunodeficiency virus (HIV) from 25% to less than 8%. However, studies have suggested that approximately one-fourth of women may refuse HIV testing as part of routine prenatal care. The purpose of this study was to identify concerns that pregnant women might have that would impact their decision to undergo HIV testing in pregnancy. The study is a cross-sectional survey of 413 pregnant women in south Texas. A survey questionnaire was used to assess reasons why subjects might avoid HIV testing and to assess their risks for HIV infection. The reasons for not wanting HIV testing grouped around four themes: (1) fear of being stigmatized as sexually promiscuous or as an injecting drug user; (2) denial about the possibility of being infected; (3) fatalism; and (4) of rejection leading to loss of emotional and financial support. Overall, 15% of subjects who had not been previously tested (5% of all subjects) indicated that they would refuse HIV testing, a rate which is below rates of 20%-24% in previous studies. The lower rate of refusal for HIV testing in our study may reflect a downward trend nationally in the rate of refusal for prenatal testing. Many women have concerns about HIV testing, although these concerns may not necessarily prevent them from undergoing testing. Physicians and policy makers need to be aware of women's concerns and fears when implementing HIV testing policies.

Providing seamless community health and social services.

This article reviews a variety of Government community health policies and initiatives, from the NHS and Community Care Act 1990 to the emergence of primary care groups (PGCs). The Labour administration abolished GP fundholding and has placed considerable emphasis on its commitment to partnership with the care professions. The Government is also expecting a commitment to partnership between the community care professions in order to reflect the entwined social and health-care needs of the individual requiring care in the community. The role of the district nursing service has been brought into focus with the opportunity of representation at PCG board level. Evaluating how a district nursing service may integrate with social services is therefore, and appropriate strategy for assessing whether recent policy initiatives go far enough at grass roots level in facilitating collaboration and quality community care.

Obstacles to influenza immunization in primary care.

BACKGROUND: General practices undertake annual immunization campaigns to protect susceptible patients against influenza. Many practices, however, do not adopt effective approaches and there is great variation in the immunization rates achieved. This study aimed to assess the attitudes of primary care staff to the annual immunization programme, the obstacles they face, and possible reasons for the wide variation in immunization rates. METHOD: A semi-structured questionnaire survey of general practice groups in Salford &Trafford during winter 1997-1998 was carried out, a total of 104 practices. RESULTS: Respondents perceived influenza vaccine to be effective (93.2 per cent), well received by patients (91.7 per cent) and without significant side-effects (83.6 per cent). The annual immunization programme was seen as being necessary (91.8 per cent), cost-effective (76.7 per cent), reducing hospital admissions (82.2 per cent), but very time consuming (64.4 per cent). Practices were more likely to target patients specified in the Chief Medical Officer's guidelines; however, most (98.6 per cent) targeted the over-75s before their inclusion in the guidelines, and many (61.6 per cent) targeted the over-65s. Practices did not always use the most effective methods of contacting patients, primarily relying on posters (97.3 per cent), opportunistic contacts (95.9 per cent) and reminders on prescriptions (83.6 per cent), rather than letters (39.7 per cent) and telephone calls (11.0 per cent). Practices identified several common obstacles to immunization, relating to the cost and administrative burden of the annual immunization programme, difficulty identifying high-risk patients, and public beliefs about influenza and influenza vaccine. CONCLUSIONS: Although generally positive towards influenza immunization, practice staff differ in their ability to cope with, and the appropriateness of their response to, the pressures of the annual immunization programme. Additional support and co-operation from the Department of Health, Health Authorities and pharmaceutical companies could remove some of the obstacles to immunization of high-risk patients.

False-positive and indeterminate human immunodeficiency virus test results in pregnant women.

Guidelines from the Centers for Disease Control and Prevention, Atlanta, Ga, recommend that all pregnant women be offered human immunodeficiency virus (HIV) testing to ensure that they have the opportunity to use currently available therapeutic interventions to reduce the risk infecting their offspring with HIV. These recommendations have resulted in an increased number of low-risk women being tested and a significant rise in the percentage of false-positive results from HIV antibody screening tests and ambiguous (indeterminate) findings from confirmatory tests. Women receiving such results are generally in emotional turmoil yet must make treatment choices if they prove to be infected. This article provides guidelines to help general medical practitioners to understand the nature of HIV testing, to assess a woman's infection status when initial tests are ambiguous, and to determine when treatment is appropriate.

A large, single center investigation of the immunogenetic factors affecting liver transplantation.

BACKGROUND: Reports on the relevance of immunogenetic factors in liver transplantation are often conflicting or inconclusive. We have, therefore, investigated a range of factors that may underlie liver graft survival. METHODS: The influences of HLA, flow cytometric, and enhanced cytotoxic crossmatching and immunoglobulin (Ig)A levels on graft survival, and acute and chronic rejection were investigated for a single center involving 446 patients over 13 years. RESULTS: The effect of HLA mismatching on graft survival was significant (P<10(-2)) and was reversed in recipients with autoimmune diseases (P<0.5x10(-2)), whereas the effect of HLA mismatches on the level of acute rejection was detrimental in all recipients. There was a significant effect of a positive cytotoxic crossmatch on 3-month (P<10(-5)) and 1-year (P<10(-4)) graft survival, and an additional effect of the flow cytometric crossmatch was seen for chronic rejection (P<10(-2)) and acute rejection (P<10(-2)). Recipients with HLA-A1,B8,DRB1*0301 had higher levels of acute rejection (P<0.5x10(-2)), and recipients who received an ABO compatible-nonidentical transplant have a significantly higher risk (P<10(-2)) of developing chronic rejection. Finally, the beneficial effect of high serum IgA and, specifically, IgA anti Fab, seen in renal transplants was not evident in liver transplants, and in fact the opposite may be true, at least for acute rejection (P<0.5x10(-2)). CONCLUSIONS: By separating the recipients with autoimmune disease from other patients and by including acute and chronic rejection as outcome parameters, we have used the power of a large single-centre study to delineate the significance of some of the important immunogenetic factors involved in liver transplantation.

Immunization status of children born to human immunodeficiency virus (HIV)-infected mothers in two Texas cities.

BACKGROUND: Because HIV-infected and HIV-exposed children are at risk of acquiring infectious diseases, they should be immunized. METHODS: We abstracted charts at pediatric HIV clinics in Dallas and San Antonio, matched the children to birth certificates and assessed up-to-date immunization status. RESULTS: Of the 178 children, 108 (61%) were up to date for the diphtheria-tetanus-pertussis (DTP), polio, and measles-mumps-rubella (MMR) series. In multivariate analysis, predictors of delayed immunization included maternal high-risk sexual partners and infant antiretroviral therapy. CONCLUSION: In this population of children born to HIV-infected mothers, immunizations were up to date in 61%, a figure that exceeds or equals immunization levels for other Texas children. Texas falls short of the recommended goal of 90% immunization for children of HIV-infected mothers and healthy children.

Examining the immune response in sentinel lymph nodes of mice and men.

Recently, it was recognized that an immune response develops along one of two major pathways. One leads to a destructive immune response (type 1), while the alternative leads to a nondestructive immune response (type 2). Our studies in animal models suggest that therapeutic vaccines induce a tumor-specific type 1 immune response while ineffective vaccines induce a type 2 response. These results have led us to examine the immune response in sentinel lymph nodes draining tumor vaccines of patients entered onto clinical trials for melanoma, breast and renal cell cancer.