bluuebunny/crossref_metadata_2025 huggingface dataset:
Research and the configuration of nursing services
Authors: LUKER KAREN A.
Published: December 2007

This paper is concerned with the way in which nursing research has influenced changes in the organization of nursing services, particularly the shift from so‐called traditional nursing to new nursing. To this end published research and professional literature are selectively reviewed.

The case is made to support the view that change in nursing has been driven forward by the evangelical zeal of opinion leaders rather than evidence.

It is suggested that holistic care as embodied in new nursing is no longer affordable. Market pressures have precipitated a revisiting of the task basis of nursing. An effective anchor would have been a solid body of research evidence pointing up the value new nursing may have. Regrettably not enough research was done prior to the diffusion of new nursing. What was done was not always adequate, and what was adequate was not effectively deployed by nurse leaders.

Nursing is the largest workforce in the NHS and has attracted a great deal of policy interest. It is suggested that it will become increasingly important for nursing to be more strategic, and develop its own professionally driven research agenda.

The future of the nursing profession is uncertain. It is clear that evidence‐based practice is centre stage, and there is a need for nursing to re‐negotiate its professional boundaries and to develop intellectual partnerships in order to move the knowledge base of practice forward.
The therapeutic use of music in a care of the elderly setting: a literature review
Authors: KNEAFSEY ROSALEEN
Published: December 2007

This paper reviews recent literature concerning the use of music and music therapy in health care.

Focusing particularly on the elderly, the use of music in relation to patients with dementia and Parkinsonism is examined.

Brief reference is also made to the use of music in pain control.

Although in this case, literature is not specific to care of the elderly settings, the results are still relevant to gerontological nursing.

Projects which achieved positive results in controlling pain perception could be transferable to a care of the elderly scenario, where chronic pain is often part of daily life.
Survivorship and breast cancer: the psychosocial issues
Authors: RENDLE KAREN
Published: December 2007

This article addresses some of the psychosocial issues concerning survivors of breast cancer.

Issues relating to employment and social support are discussed.

Social support is also related to the significant other.

Recommendations for nursing practice and research are made, including the need for a unilateral definition of ‘survivor’ and for attitudinal changes.

As the number of survivors increase, psychosocial barriers need to be diminished by nursing practice and research.
Preparation for family care‐giving: stroke as a paradigm case
Authors: BRERETON LOUISE
Published: December 2007

This article considers the nurse's role in assisting family (informal) carers who adopt their role suddenly, following an acute health crisis. Carers of stroke survivors are used as a ‘paradigm’ case to highlight the challenges faced by family members at the time of hospital discharge.

The needs of family members who suddenly adopt a caring role are poorly understood, but greater awareness is needed as the Carers (Recognition and Services) Act (1995) provides statutory recognition of the rights of such individuals to an assessment of their needs, emphasizing the importance of carers making an informed choice based on a willingness and ability to adopt a care‐giving role.

Evidence suggests that new family carers are currently poorly prepared to take on their role, lacking the information and skills needed to provide good care. Nurses have a major role to play in preparing carers, but currently lack a systematic approach to assessment and intervention.

Further empirical work is required to establish more clearly the needs of new carers and to develop and evaluate appropriate intervention strategies to address their needs.
Admission to care: facilitating role transition amongst family carers
Authors: DELLASEGA CHERYL , NOLAN MIKE
Published: December 2007

Admission to care after a period of family care‐giving has been the focus of much recent research.

Rather than being seen as an end in itself, admission is part of a process.

This article concentrates on ‘reaching the end’ of family care‐giving and the ‘new beginning’ of entering residential care.

A cross‐national study conducted in the USA and the UK is discussed, and similarities and differences in the two cultures are highlighted.

Decisions to enter a nursing home were often taken hurriedly and with lack of information in both countries.

Issues of quality of care and emotional responses by former carers were also important in both settings.
Including patient preferences in nurses' assessment of older patients
Authors: RULAND CORNELIA M. , KRESEVIC DENISE , LORENSEN MARGARETHE
Published: December 2007

The refinement of a patient assessment tool for older patients, Lorensen's Self‐Care Capability Scale, is described where a systematic elicitation of patient preferences is included in the assessment.

This study tests a decision analytic approach as a strategy for formalizing subjective judgement, which makes it possible to include patients' own values and preferences in planning patient care.

Applying this technique to patient assessment contributes to explicitly tailoring nursing care decisions to desired outcomes as preferred by individual patients.

A shared approach to decision making between nurse and patient ensures a mutual understanding about goals, priorities and patient values through discussion and negotiation.

This pilot study supported the merit of including patient preferences systematically in the assessment of older patients.

The method provides an important decision aid for nurses in planning nursing care in accordance with patients' own values and preferences for care.
Developing clinically valid practice guidelines
Authors: Grimshaw Jeremy , Eccles Martin , Russell Ian
Published: December 2007

Valid guidelines, when appropriately disseminated and implemented, can lead to changes in clinical practice and improvements in patient outcome. Guidelines are more likely to be valid if they are developed using systematic reviews, national or regional guideline development groups (including representatives of key disciplines) and explicit links between recommenda‐ tions and scientific evidence. This paper discusses the practical implications of adopting this approach for guideline development and the role of peer review of guidelines as another element of the process to ensure validity. Considerable resources are required to develop evidence‐linked guidelines, but this investment can be recouped by relatively small changes in the process or outcome of care. Good leadership and technical support are required for the successful development of clinically valid guidelines, which is dependent upon the small‐group processes of guideline development panels and the translation of evidence into recommendations. Future guideline developers need to gain expertise in these areas. Research priorities are identified.
Clinical guidelines and the law: advice, guidance or regulation?
Authors: Hurwitz Brian
Published: December 2007

Proliferation of clinical guidelines has given rise to a number of concerns about the status of clinical advisory statements. Are guidelines advisory or mandatory? What regulatory functions do guidelines serve; do they allow clinical discretion a large enough role?

Relationships between legislation and guidelines, and the way courts go about determining the legal status of guidelines, are explained. The following questions in the context of the law of negligence are addressed. Do doctors who deviate from guidelines place themselves at increased risk of being found liable in negligence if patients suffer injury as a result? Could compliance with guidelines protect health care workers from liability in such circumstances? What legal responsibility do the developers and issuers of guidelines have if their guidance is found to be faulty?

Common law cases featuring clinical guidelines or protocols have been identified from the databaseLexis, which searches the full text of the transcripts and reports of court cases in UK, Commonwealth and United States jurisdictions. Secondary literature, identified from the bibliography of clinical guidelines maintained by the Department of Health Services Research at the University of Aberdeen (assembled fromDHSS‐DATA, Embase, GratefulMed, Medline andSIGLE) has also been consulted.

The legal status of a guideline turns on whether its development and application have statutory backing, and whether the guideline embodies clinical practices accepted as proper by a responsible body of doctors. The mandatory effects of guidelines can be gauged, to some extent, by the sanctions that apply in the event of non‐compliance. US courts have ruled that guideline developers can be held liable for faulty guidelines, and that doctors cannot pass off their liability by claiming that adherence to guidelines has corrupted clinical judgement.

Protocols and guidelines provide the courts with examples of clinical standards across a wide range of medical practice. As guidelines proliferate, so they will increasingly be used in court. However, adherence to guidelines has not automatically been equated with reasonable practice, and the courts seem unlikely to follow the standards enunciated in clinical guidelines without critically evaluating their authority, flexibility and scope of application.
Getting there from here: evidentiary quandaries of the US outcomes movement
Authors: Tanenbaum S.
Published: December 2007

The US outcomes movement assumes, and sometimes argues, the primacy for medical practice of probabilistic knowledge derived from methodologically rigorous statistical studies. ‘Evidence‐based medicine,’ then, is considered a course of clinical medicine prescribed by such research. Implementation of evidence‐based medicine has recently been uneven in the US, manifesting not only the expected ‘obstacles to implementation’ but several theoretical weaknesses of the applied science model of medical care.

Outcomes researchers claim to provide certainty ‐ certainty of what probable, as it turns out ‐ in a world of clinical uncertainty. This paper argues that outcomes research actually exacerbates the inferential uncertainty of practising physicians who would use knowledge for practice. Two quandaries are discussed: whether to privilege rigorous or relevant research, and whether to privilege universal or local knowledge. In each case, the logic of ‘evidence‐based medicine’ is insuffcient to resolve the quandary and would seem to support conflicting resolutions. Recent developments in US health policy are cited as manifestations of these quandaries. Finally, the reader is asked not to disregard the political implications of the outcomes movement.
Central dimensions of clinical practice evaluation: efficiency, appropriateness and effectiveness ‐ I
Authors: O'Neill Declan , Miles Andrew , Polychronls Andreas
Published: December 2007

Successful audit of clinical practice focuses upon the systematic investigation of key aspects of the everyday work of busy clinicians. We contend that the nature and quality of local clinical practice can be characterized by critical examinations of the effectiveness and appropriateness of practice and the efficiency with which effective, appropriate clinical care is delivered to patients. When such a baseline has been established, it becomes possible to compare and contrast characterized local practice with so‐called ‘evidence‐based’ practice and agree changes aimed at narrowing the discrepancy between the two. The nature of such changes can be described and their implementation into practice studied, with subsequent quantitative measurement and qualitative description of the resulting benefits to patients. A proper understanding of the concepts of efficiency, appropriateness and effectiveness in clinical care is clearly fundamental to the successful design and applications of methodologies aimed at securing measurable improvements in the quality of patient care. In this first of two articles we examine the concepts of efficiency and appropriateness in clinical practice, with particular emphasis on cost‐effectiveness and utilization review. The clinical effectiveness of health care intervention is treated in detail within the second paper, to be published within Volume 2 Number 2 of the Journal of Evaluation in Clinical Practice (Miles et al. 1996f).
Measuring the effects of casemix on outcomes
Authors: Orchard Carol
Published: December 2007

Participation in the measurement of population health and health care outcomes has become an explicit professional duty for doctors, but comparisons are difficult to make because outcomes are conceptually complex and largely qualitative. Observational data, particularly from routine hospital statistics, are useful complements to experimental data provided that their variable quality is taken into account and adjustments are made to minimize bias and confounding and to allow for the effects of differences in casemix, which are problematic because of the nature of severity.
Central dimensions of clinical practice evaluation: efficiency, appropriateness and effectiveness ‐ II
Authors: Miles Andrew , O'Neill Declan , Polychronis Andreas
Published: December 2007

That a treatment selected for a given condition works, or that it works better than alternative treatments, or that it was selected because it works as well as but is cheaper than alternative treatments, should be of pivotal concern to clinicians and is of central concern to patients and to health care managers. Attempts to address these concerns have resulted in what is now widely termed the ‘effectiveness movement’. The protagonists of the movement have been concerned to create a culture of evaluation and inquiry within which the formulation of evidence‐based clinical guidelines and their introduction into routine practice have played a prominent part. The need to ensure cost effectiveness of clinical intervention has been at least as emphasized as the need to ensure the clinical effectiveness of health care interventions. Although cost‐effectiveness analyses are now an indispensable feature of practice guideline formulation and treatment evaluation, few studies have examined any deterioration in patient outcome associated with successful cost containment. An adequate understanding of the concept of clinical effectiveness and the associated aims of the ‘effectiveness movement’ is central to an understanding of the future nature and extent of health service provision, not simply in the UK but also internationally. Having examined the concepts of efficiency and appropriateness previously (O'Neill, Miles & Polychronis 1996, Journal of Evaluation in Clinical Practice 2, 13–27) we move in this second of two articles to a detailed explanation of the concept of effectiveness, and to an examination of the derivation and use of clinical practice guidelines, concluding with a consideration of the role of practice guidelines in ensuring the cost effectiveness of health care intervention. The reservation is expressed that a ‘guidelines culture’, when established, will be manipulated by health care commissioners for largely political purposes, creating a systematic bias in the purchasing process that will actively disadvantage a range of patient groups.
Some methodological issues in the development of quality of life measures for the evaluation of medical interventions*
Authors: Kessler Ronald C. , Mroczek Daniel K.
Published: December 2007

This paper discusses a series of important methodological issues in developing targeted health‐related quality of life measures in studies of the effects of medical interventions. Such measures cannot be developed unless the evaluator understands the life domains that medical interventions affect. Qualitative discovery methods are needed to obtain this understanding. Once domains are targeted for measurement, careful and systematic laboratory pilot work should be used to select initial scale items. Psychometric evaluation of response patterns in subsequent field tests is needed to assess the measures. Less concern should be directed to internal consistency reliability of scales in the psychometric evaluation and more to the ability of short scales to reproduce total scale variance and to provide precise measurement within the range of the outcome where effects are expected. The paper closes with a discussion of modern methods of item response scaling that can be used to address these issues.
The involvement of pharmacists in professional and clinical audit in the UK: a review and assessment of their potential role
Authors: Panton Rhona , Fitzpatrick Raymond
Published: December 2007

This review addresses the uptake and implementation of the principles of audit by community, hospital and health authority pharmacists. The pressures to audit professional services are discussed, as are the barriers to cooperation among pharmacists and between pharmacists and prescribes in primary care. The development of standards of professional practice is then described taking into account the particular difficulty in developing standards for health care workers who are geographically separated from other members of the primary care team and are in commercial competition with each other. The review identifies audit of professional services in both community and hospital pharmacy and of clinical services in the latter. The role of pharmacists employed by health authorities to advise them and general practitioners on the optimum use of the drug budget is described and their potential role for involvement in audit is discussed. The particular advantages that pharmacists in hospital and health authorities have in developing the specific aspect of clinical audit related to medicines usage (drug utilization review) is then described. The potential for pharmacists to contribute to clinical and management audit is discussed.
Overview and critique of judgement and decision making in health care: social and procedural dimensions
Authors: Chase Jonathan , Crow Rosemary A. , Lamond Dawn
Published: December 2007

This paper presents an outline of the scope for the application of decision theory to health care. Firstly, the main approaches to and assumptions of decision theory are discussed. Secondly, health care decision making is reviewed. It is noted that decision theory can be applied to either the health care professional or to the lay person. Applications of decision theory to clinical practice, to the management of care and to resourcing are considered. Thirdly, some areas which would repay further research are identified. These include social processes in individual and group decision making, the temporal distribution of outcomes and the development of techniques capable of dealing with the complex and dynamic features of decisions. On the basis of the foregoing, some conclusions are drawn.
The progress of lay involvement in the NHS Research and Development programme
Authors: Oliver S.
Published: December 2007

The Central Research and Development Committee is seeking to involve lay perspectives in the NHS R&D Programme. This paper describes some recent examples of lay involvement in each step of the research process from setting the agenda to making use of research findings. Innovative approaches have involved lay people in identifying research need and in the subsequent commissioning process. Lay contributions have given particular emphasis to information and support, whether this is in maternity care, cancer care, HIV prevention, participation in clinical trials or systematically reviewing evidence of effectiveness. Difficulties in identifying appropriate lay people to involve in research, their different skills, their lack of resources and support and their need for time for thought and discussion with their peers have all posed problems. Suggestions for overcoming some of these obstacles are presented, including resources, training and support, and clarification of the role, nature and potential for lay involvement. Lastly this paper considers the urgent need to learn from the efforts made so far, possible approaches to evaluation and how this is being addressed by a newly convened advisory group to the Central R&D Committee.
Clinical guidelines: ways ahead
Authors: MRCGP C.W.R. Onion MD , FRCP T. Walley MD
Published: December 2007

Clinical guidelines are essential in promoting the implementation of evidence‐based practice within the NHS. But there are two broad schools of thought about their development and implementation: the first argues that guidelines should be entirely evidence‐based and tolerates a degree of complexity which may make the guideline impractical; the second argues that we need simple guidelines, and sacrifices the strength of evidence in favour of ease of application and dissemination. Both arguments have merits and flaws, which are discussed, and ways to integrate the strengths of both are considered.
Monosymptomatic hypochondriacal psychosis in a man with learning disabilities
Authors: Brooke S. , Collacott R. A. , Bhaumik S.
Published: December 2007

A case report of a male patient with moderate degree of learning disabilities and monosymptomatic hypochondriacal psychosis is described, along with its pathogenic features and response to treatment.
Autism and epilepsy (and tuberous sclerosis?) in two pre‐adolescent boys: neuropsychiatric aspects before and after epilepsy surgery
Authors: Gillberg C. , Uvebrant P. , Carlsson G. , Hedström A. , Silfvenius H.
Published: December 2007

We report on two pre‐adolescent boys with a combination of severe seizure disorders and severe‐moderate autism who underwent brain surgery for their epilepsy at the ages of 9 and 10 years, respectively. Both boys became seizure‐free and initially improved dramatically with regard to autism symptoms. One of the boys continued to improve, but the other had a relapse to his pre‐operative state in conjunction with his pubertal grovirth spurt. Several years after surgery, one of the boys remained much improved with respect to his autism. The other subject showed some improvement with respect to self‐injury and aggression, and had slightly lower scores on screens for autism symptoms than in the year preceding epilepsy surgery. The histopathological examination of the brain tissue that was removed at surgery suggested a diagnosis of tuberous sclerosis in both cases.
Selective detection of human hepatitis B virus surface and core antigens in peripheral blood mononuclear cell subsets by flow cytometry
Authors: Chemin I. , Vermot‐Desroches C. , Baginski I. , Saurin J. C. , Laurent F. , Zoulim F. , Bernaud J. , Lamelin J. P. , Hantz O. , Rigal D. , Trepo C.
Published: December 2007

SUMMARY. The presence of hepatitis B surface protein (HBs) and hepatitis B core protein (HBc) was investigated, by flow cytometry, on the surface of peripheral mononuclear cells (PBMC) from cells of the following phenotype: CD3 (T lymphocytes), CD4 (T helper/inducer), CD8 (T cytotoxic/suppressor). CD19 (B lymphocytes) and CD56 [natural killer (NK) cells] among eight patients suffering from chronic hepatitis B and five healthy HBV‐negative subjects. This study demonstrated the presence of HBsAg and HBcAg on the lymphocyte surface for most of the patients. The mean percentage of labelled cells was 17% for HBsAg and 15% for HBcAg. Among the different lymphocyte subsets only B lymphocytes and the NK cells expressed HBsAg for 57% and 26% of cells, respectively. Similarly HBcAg was also detected among CD19 and CD56 cells only. Polymerase chain reaction (PCR) was used to search for the presence of hepatitis B virus (HBV) DNA and RNA in PBMC, using primers located in the S gene. HBV DNA was detected with variable intensity in the CD3, CD4, CD19 and CD56 subsets following their separation with a cell sorter. For HBV RNA the signal obtained after PCR and Southern blotting was higher for CD56 and CD19 cells than for CD3 cells and undetectable for CD4 cells. This study demonstrates that replication and transcription of the HBV can occur in CD19‐ and CD56‐positive cells. Positive signals in CD3 cells may be due to contamination of this subpopulation by NK cells.
Serum levels of anti‐hepatitis C virus IgM core antibodies may predict the response to interferon‐α therapy in chronic hepatitis C
Authors: Tabone M. , Galatola G. , Secreto P. , Marini C. , Molinaro G. , Arico S.
Published: December 2007

SUMMARY. We measured the optical densities (OD) of serum anti‐hepatitis C virus IgM core antibodies in 40 HCV‐positive patients (24 males and 16 females) with histologically proven chronic active hepatitis but without cirrhosis. All patients were treated with i.m. injections of 3 MU thrice weekly of interferon‐α (IFN‐α) for 6 months and followed‐up monthly. Optical densities were evaluated in thawed sera before beginning treatment and 6 months after completion, and in fresh sera obtained at the end of an 8–12‐month follow‐up period. Patients were grouped into three categories according to the OD obtained: <0.3 (negative test): 0.3‐0.6 (intermediate positivity): >0.6 (high positivity). According to the response to treatment during the follow‐up period, patients were further divided into three classes: sustained responders: relapsers or partial responders: non‐responders. In each patient, the OD values were similar in the three determinations before, after therapy and at the end of the follow‐up period. All patients with an intermediate positive test for anti‐HCV IgM core antibodies were relapsers or partial responders, and all patients with high OD values were non‐responders. Conversely, 71% of the patients with a negative test were sustained responders. We conclude that this cheap and easily performed test may be useful in predicting the response to IFN therapy.
Predictive value of IgM antibodies to hepatitis C virus in patients with chronic hepatitis C undergoing interferon‐α therapy. Analysis by two different methods
Authors: Torronteras R. , Sánchez‐Quijano A. , Abad M. A. , Soto B. , Andreu J. , Medrano F. J. , Leal M. , Lissen E.
Published: December 2007

SUMMARY. To determine the predictive value of IgM anti‐hepatitis C virus (HCV) testing in patients with chronic hepatitis C infections undergoing interferon‐α (IFN‐α) therapy, IgM anti‐HCV reactivity was analysed by two different methods (non‐commercial and commercial) in 19 patients and monitored at times 0 (pre‐treatment), 3, 6, 12. and 24 months during follow‐up. Eight patients were non‐responders, five remained in sustained response 1 year after stopping treatment, and six had a relapse. No correlation between alanine transaminase (ALT) levels and IgM anti‐HCV reactivity was found by either method in baseline samples. In addition, neither the presence nor absence of IgM anti‐HCV in baseline samples, nor the loss of specific IgM reactivity during treatment, had any predictive value. Finally, no other parameters analysed (age, sex, risk group and histological diagnosis), were significantly associated with IgM anti‐HCV reactivity in our study. In summary, these results suggest that baseline detection and monitoring of IgM anti‐HCV reactivity are not useful in predicting the sustained response to IFN‐α therapy in chronic hepatitis C infection.
Hepatitis B e antigen negative chronic active hepatitis: hepatitis B virus core mutations occur predominantly in known antigenic determinants
Authors: Carman W. F. , Thursz M. , Hadziyannis S. , McIntyre G. , Colman K. , Gioustoz A. , Fattovich G. , Alberti A. , Thomas H. C.
Published: December 2007

Summary. In chronic hepatitis B virus (HBV) infection seroconversion from hepatitis B e antigen (HBeAg) to hepatitis B e antibody (HBeAb) may be followed either by remission of the disease with low‐level viraemia, or by continuing inflammation with high‐level viraemia. In both situations the virus may acquire a mutation in the precore sequence which prevents it from encoding HBeAg. We now show that the number of amino acid substitutions in the HBV core is low in viral sequences from patients with HBeAg positive chronic liver disease and HBeAg negative HBeAb positive patients in remission, but the frequency of substitutions is high in HBeAg, negative HBeAb positive patients with active liver disease. Furthermore we show that these substitutions cluster in the promiscuous CD4+ T‐helper‐cell epitope and in HBV core/e antibody binding determinants, but are not found in regions recognized by major histocompatability complex (MHC) restricted cytotoxic T lymphocytes. Sequential viral sequences from patients before and after HBeAg/HbeAb seroconversion shows that core mutations arise either at the same time or after the precore stop mutation which prevents the virus from encoding HBeAg. These results are consistent with the hypothesis that after clearance of HBeAg, mutations in regions of the virus recognized by CD4+ helper T cells and B cells allow persistence of the HBe negative virus in HBeAb positive patients with viraemia and active hepatitis.
Clinical efficacy of intramuscular human interferon‐βvs interferon‐α2b for the treatment of chronic hepatitis C
Authors: Pérez R. , Pravia R. , Artímez M. L. , Giganto F. , Rodríguez M. , Lombraña J. L. S. , Rodrigo L.
Published: December 2007

Summary. We have conducted a randomized study to compare the efficacy and tolerance of human interferon (IFN) β vs recombinant IFN‐α2b in patients with chronic active hepatitis C. Forty patients were included: 21 received IFN‐α (group A) and 19 IFN‐β (group B). IFN was administered intramuscularly at a dose of 6 MU three times a week (tiw) for 2 months (induction phase), followed by 3 MU tiw for 4 months. Clinical, epidemiological and pathological features were similar in the two groups. Normal alanine aminotransferase (ALT) values at the end of treatment was regarded as a response to therapy and the response rate was 57% (12/21) in group A and 5.2% (1/19) in group B (P < 0.01). Both types of IFN induced a significant decrease in mean ALT values by the end of the induction phase (P < 0.01). When the dose was reduced to 3 MU, a marked, but not significant increase in ALT, was seen in group B, whereas no increase was seen in group A. IFN‐β was better tolerated and haematological adverse effects (platelet and leucocyte decrease) were less pronounced with IFN‐β. Hence, human IFN‐β was less effective than IFN‐α in treating chronic hepatitis C virus (HCV). Doses of IFN‐β of 3 MU intramuscular (IM) tiw were clearly insufficient and it remains to be established whether higher doses of intramuscularly IFN‐β can be useful.
Methods of transmission of hepatitis C
Authors: Tibbs C. J.
Published: December 2007

Summary. The route of transmission of hepatitis C virus is still controversial. Parenteral exposure via blood or blood products leads to infection in the majority of cases, and the majority of intravenous drug users become infected by repetitive exposure to contaminated injection equipment. The risk of infection from a single need lipstick injury is 5–15% and may depend on the size of the innoculum. Other parenteral routes of transmission may include traditional healing practices and the use of contaminated medical equipment.

Transmission is less common within a family but the prevalence of hepatitis C viral antibodies is higher in family members and sexual partners of carriers than in the general population. There are some well‐documented instances of acute hepatitis C occurring after a defined sexual exposure. Vertical transmission is rare unless the mother has high levels of circulating HCV RNA as may occur in those also infected with HIV. The detection of hepatitis C in saliva and the higher than expected prevalence of infection in dentists may point to the possibility of transmission by salivary contamination. There remain large numbers of hepatitis C carriers in whom no route of infection can be identified.
Ethnic differences in the prevalence of anti‐hepatitis C antibodies and hepatitis B surface antigen in Israeli blood donors by age, sex, country of birth and origin
Authors: Bar‐Shany S. , Green M. S. , Slepon R. , Shinar E.
Published: December 2007

Summary. The presence of anti‐hepatitis C virus (HCV) antibodies frequently indicates both persistent infection and infectivity. Consequently, blood donors found to be anti‐HCV positive, are excluded from the donor pool. The aim of this study was to compare age, sex and ethnic differences in the prevalence of anti‐HCV antibodies with that of hepatitis B surface antigen (HBsAg) among immigrant and Israeli‐born blood donors. Anti‐HCV antibodies were assayed by a second‐generation enzyme‐immunoassay (EIA) and HBsAg by a standard EIA in a sample of 136 977 blood donors in Israel during 1992. The overall age‐adjusted prevalence of anti‐HCV antibodies was 0.66% in men and 0.55% in women, and for HBsAg, 0.85% and 0.44%, respectively. There was a significant increase in the prevalence of anti‐HCV antibody with age, and significant differences by country of birth, with the highest prevalence found among those born in the former USSR and eastern Europe. This contrasted with the findings for the prevalence of HBsAg, where the highest rates were among those born in northern Africa. Among Israeli‐born donors, differences in the prevalence of anti‐HCV antibodies by parental country of origin were minimal and much less than for HBsAg. Hence the prevalence of anti‐HCV antibodies in Israel is strongly associated with age and country of birth but not with country of origin. There is little evidence of substantial vertical or intra familial transmission of HCV infection in Israel.
The structure of hepatitis B envelope and molecular variants of hepatitis B virus
Authors: Howard C. R.
Published: December 2007

Summary. Accumulated evidence in recent years has shown that the variation of hepatitis B virus (HBV) genomes may have profound implications for our understanding of hepatitis B pathogenesis and prevention. Attention has focused on areas of the outer envelope coded by the S gene which are involved in the induction of a protective neutralising antibody response, and mutations which directly affect the production of C gene products, one of which is considered as a target for immune T cells involved in virus clearance. This review highlights recent experimental data which emphasizes the role of such mutations in the establishment and maintenance of chronic HBV infections and focuses attention on the significance of HBV variants with respect to the expanding use of HBV vaccines for mass immunization.
Identification of hepatitis C virus by immunoelectron microscopy
Authors: Li X. , Jeffers L. J. , Shao L. , Reddy K. R. , de Medina M. , Scheffel J. , Moore B. , Schiff E. R.
Published: December 2007

Summary. Sequencing of the hepatitis C virus (HCV) has provided a better understanding of the natural history, immunology, and epidemiology of this virus. However, the morphology of HCV has not been definitively characterized. In this study, through a sequence of concentration processes, virus‐like particles were isolated from human serum and liver tissue, visualized by transmission electron microscopy and identified as hepatitis C virion by immunoelectron microscopy. Spherical flavi‐like virus particles, approximately 70 nm in diameter, were observed in the fraction with 1.04–1.12 g ml‐1 sucrose density and bound to immunogold particles with monoclonal antibodies (mAb) against hepatitis C. The nucleocapsid of the particles, which were 50 nm in diameter, appeared to be icosahedral in structure and surrounded by an envelope covered with surface projections. A ‘tadpole’ form of particles was also observed. The findings indicate that the low buoyant density in sucrose and the morphological features of the hepatitis C virion are consistent with the characteristics of flaviviruses and pestiviruses.
Hepatitis B virus precore mutants in HBeAg carriers with chronic hepatitis treated with interferon
Authors: Lampertico P. , Manzin A. , Rumi M. G. , Paolucci S. , Del Ninno E. , Dementi M. , Colombo M.
Published: December 2007

Summary.Precore mutants of hepatitis B virus (HBV) were looked for in 18 hepatitis B e antigen (HBeAg) carriers who were treated with recombinant interferon‐a (rIFN) and the results were compared with those obtained in 12 untreated carriers who underwent spontaneous HBeAb seroconversion. Molecular analysis of the HBV precore region was carried out by polymerase chain reaction (PCR) amplification and direct sequencing. Precore mutants with a stop codon at codon 28 were detectable at baseline in 19/30 carriers. However, wild‐type strains predominated in the baseline sera of both treated (n= 16) and untreated (n= 10) patients. Sera from the remaining four patients contained predominantly or exclusively mutant virions. Following IFN treatment, there was a shift from the wild‐type pattern to the mutant pattern in all patients, with the precore pattern prevailing in long‐term responders (six out of nine) compared with the non‐responders (none of nine). The wild‐type pattern predominated among the non‐responders (eightvsthree), suggesting that the long‐term response to IFN was associated with take‐over of precore mutants. There were no relationships between any pre‐treatment precore molecular pattern and disease severity or outcome of treatment. Precore mutants also took over in 10 of the 12 untreated patients (83%), who underwent spontaneous HBeAb seroconversion. Thus, a shift from wild‐type to precore mutant pattern occurs in most Italian patients undergoing IFN‐induced or spontaneous HBeAb seroconversion.
A high prevalence of antibodies to hepatitis C virus among commercial plasma donors from Western India
Authors: Jha J. , Banerjee K. , Arankalle V. A.
Published: December 2007

Summary. A very high prevalence of anti‐hepatic C virus (anti‐HCV) antibodies (63/73, 86.3%) was noted among commercial plasma donors of an organization manufacturing blood products, studied in 1989. Retrospective serological analysis of these donors revealed continued high prevalence of anti‐HCV, i.e. 35/40 (87.5%) in 1988, 28/31 (90.3%) in 1987 and 86/94 (91.4%) in 1986. HCV RNA detection by polymerase chain reaction (PCR) demonstrated 15/33 (45.45%) plasma donors to be positive in 1989.

Interestingly, 3/24 (12.5%) serum samples collected from employees of the organization were also anti‐HCV positive. All three anti‐HCV positive employees were directly associated with plasmapheresis. Of the three anti‐HCV positive employees one had been anti‐HCV positive since 1985, but the other two employees were negative during 1985–1987 and then became positive in 1987 and remained positive in 1989. One of these two employees was also a plasma donor.

Commercial blood donors from a local blood bank had anti‐HCV prevalence of 13% which was significantly lower (P < 0.001) when compared with plasma donors of the organization and significantly higher than volunteer blood donors (<0.25%, P < 0.01).
Targeted delivery of antisense DNA in woodchuck hepatitis virus‐infected woodchucks
Authors: Bartholomew R. M. , Carmichael E. P. , Findeis M. A. , Wu C. H. , Wu G. Y.
Published: December 2007

Summary. An asialoglycoprotein‐based DNA delivery system containing an antisense oligo DNA against the polyadenylation region and adjacent upstream sequences of woodchuck hepatitis virus (WHV) was prepared. Experimental woodchucks were inoculated neonatally with the woodchuck virus 23 weeks before initiating the study, and all animals subsequently developed hepatitis as evidenced by the presence of measurable levels of circulating viral DNA. Animals were injected intravenously (i.v.) with asialoorosomucoid (AsOR)‐poly‐l‐lysine complexes containing 0.1 mg kg‐1 antisense DNA for five consecutive days. Levels of surface antigen did not differ substantially between treated and control animals. However, intravenous administration of complexed antisense DNA significantly decreased viraemia, as shown by a five‐to 10‐fold decrease in circulating viral DNA 25 days post treatment. The decline lasted for at least 2 weeks, after which there was a gradual increase in DNA levels. Antisense DNA alone or a complex containing a random oligo DNA of the same size and linkage failed to have any significant effect on viral DNA levels. We conclude that antisense oligo DNA can be targeted to the liver in vivo, resulting in a substantial and prolonged decrease in viral DNA levels in WHV‐infected woodchucks.
Variations of hepatitis C virus NS5B sequence (nucleotides 8261–8566) do not correlate with response to interferon‐α therapy
Authors: Nelson D. R. , Gray A. H. , Kolberg J. A. , Joh J. , Urdea M. S. , Mizokami M. , Davis G. L. , Lau J. Y. N.
Published: December 2007

Summary. Hepatitis C virus (HCV) is an RNA virus with the NS5B gene encoding an RNA‐dependent RNA polymerase. Interferon‐α (IFN‐α) is effective against HCV and its effect is believed to be related to its antiviral activity. To determine whether sequence variations of the HCV NS5B region correlate with response to IFN therapy, pretreatment serum samples from 40 patients with chronic HCV infection who were subsequently treated with IFN (≥3 MU thrice weekly for 24 weeks) and had well‐characterized biochemical responses were studied. Reverse transcription‐polymerase chain reaction (RT‐PCR) was performed to generate an approximately 365‐bp fragment from which nucleotide sequence and genotypes were determined. By comparing the nucleotide sequences and the encoded amino acid sequences of samples from each group, no response group‐specific nucleotide or encoded amino acid substitution was identified. Most of the substitutions identified were synonymous (usually by changes at the third position of the codon). These data suggest that these substitutions were selective rather than spontaneous events. Of the few non‐synonymous substitutions identified, none was correlated with subsequent response to IFN, either within or across genotypes.
Hepatitis C virus genotypes in patients with chronic liver disease and haemodialysis patients from Saudi Arabia
Authors: Al‐Faleh F. Z. , Huraib S. , Sbeih F. , Al‐Karawi M. , Al‐Rashed R. , Al‐Mofleh I. A. , Sougiyyah M. , Shaheen M. , Ramia S.
Published: December 2007

Summary. The genotypes of hepatitis C virus (HCV) were investigated in 28 Saudi patients (21 males, seven females; age range 23–68 years; mean 45.0 years) with histologically proven chronic hepatitis (13 chronic active hepatitis and 15 liver cirrhosis) and in 32 Saudi patients with chronic renal failure maintained on haemodialysis (22 males, 10 females; age range 18–60 years; mean 40.0 years) who also had liver disease due to HCV. Among the 28 patients with chronic liver disease genotype 4 was the predominant one (60.7%), followed by types 1b (21.4%), 1a (14.3%) and 2a (3.6%). The distribution of genotypes was similar in patients with chronic active hepatitis to those with liver cirrhosis. Among the 32 patients with chronic renal failure and maintained on haemodialysis, genotype 4 was also the dominant type (55.0%), followed by 1a (25.0%), 1b (21.9%) and 2a (3.1%). In all categories studied the prevalence of genotypes between males and females was the same. As our patients were selected from various regions of Saudi Arabia, we believe that genotype 4 is the predominant one throughout the whole kingdom.
Genetic control of the murine humoral response to distinct epitopes of hepatitis C virus core protein
Authors: Chen Z. , Berkower I. , Wang R. Y.‐H. , Ching W.‐M. , Alter H. J. , Shih J. W‐K.
Published: December 2007

SUMMARY. Recombinant hepatitis C virus (HCV) core protein from aal‐164, designated cpl‐10, was used to immunize mice. Antibodies to cpl‐10 were produced in all seven strains of congenic mice; none of the strains could be considered low responders relative to the others. The mouse response against individual epitopes of HCV core protein varied from one strain to another: B1O.RIII (H‐2r) recognized all three peptides aa13–30, aa77–90, aa129–145; B10.D2 (H‐2d), B10 (H‐2b) and C3M.SW (H‐2b) responded to aa13–30, aa77–90; B10, M (H‐2f), B1O.BR (H‐2k) and C3H/HeJ (H‐2k) reacted with aa13–30 only. Competitive inhibition of binding demonstrated that antibody to the peptide was inhibited by cpl‐10 protein and the corresponding peptide only. Recombinant HCV core protein is highly immunogenic and can elicit good antibody response in mice. The aa13–30 is a major epitope of HCV core protein in mice. The humoral response to the distinct epitopes was regulated by the H‐2 genes. Further analysis indicated that the I‐a locus of H‐2 genes determined the antibody response to aa13–30 and 77–90. These results suggest that the variation of antibody responses to HCV in humans may partially contribute to different outcomes of HCV infection.
Hepatitis C virus infection in the asymptomatic British blood donor
Authors: Mutimer D. J. , Harrison R. F. , O'Donnell K. B. , Shaw J. , Martin B. A. B. , Atrah H. , Ala F. A. , Skidmore S. , Hubscher S. G. , Neuberger J. M. , Elias E.
Published: December 2007

SUMMARY. Blood donor screening for hepatitis C virus (HCV) antibodies is now routine. Most blood transfusion services recommend that seropositive donors are referred for further investigation. Southern European studies suggest that many asymptomatic seropositive donors have clinically significant liver disease. Seropositive donors in areas of high prevalence may not, however, be representative of British donors. We have prospectively examined the prevalence and severity of HCV infection in a British volunteer blood donor population. During a 14 month period, only 0.35% (999/287 332) of all donors in the West Midlands were anti‐HCV (screening assay) positive. Only 5% (521999) of these were confirmed true seropositive. Nearly 80% (41/52) of seropositive donors were referred to the Queen Elizabeth Hospital Liver Unit for further investigation. Most underwent complete investigation, including liver biopsy. Forty of forty‐one donors had biochemical, histological, or virological evidence of persistent viral infection. Histological changes were generally mild and none was cirrhotic. Covertly infected patients had less severe disease than those with an overt risk factor for HCV exposure. In the British Midlands, the prevalence of blood donor seropositivity is low. In contrast with seropositive Southern European donors, the British donor is more likely to belong to an at‐risk group for parenteral exposure and is less likely to have severe histological changes. This study highlights the importance of developing locally relevant guidelines for the counselling and investigation of anti‐HCV‐positive blood donors.