Management of COPD in primary care in north-east Scotland

INTRODUCTION: We wished to obtain a snapshot of current service provision and how this could best be developed approximately one year on from the introduction of the National Institute for Clinical Excellence (NICE) guidelines for the management of chronic obstructive pulmonary disease (COPD) and the inclusion of COPD care in the New GMS Contract Quality and Outcomes Framework (QOF). METHODOLOGY: A questionnaire-based survey sent to every general practice (n = 84) in Grampian. RESULTS: Responses were received from 75 of 84 practices (89%). Questionnaires were returned by both general practitioners (GPs) and practice nurses in 45 practices (54%). All responding practices reported that they had COPD registers. 60/75 (80%) of practices reported having a dedicated COPD clinic; 70/75 (93%) had a spirometer. Areas identified for service development were: quality assuring training in COPD care and spirometry; expanding pulmonary rehabilitation provision (86%), delivering this service locally (54%) and in primary care (75%); standardising referral, assessment and communication about provision of home oxygen; training in pulse oximetry (71%). CONCLUSION: This data has important implications for the validity of the quality indicators (QOF) under the new GMS contract. Our respondents identified areas where the new GMS contract QOF could be improved, as well as providing useful suggestions for service development. Respondents recognised that not all clinical services can be effectively delivered by general practice with data supporting the development of intermediate care services for people with COPD.     

The social shaping of childhood vaccination practice in rural and urban Gambia

Improving childhood vaccination coverage is a key health policyobjective in Africa, and as availability increases, it willdepend on addressing issues of demand and timely schedule completion.This paper explores vaccination demand in urban and rural areasof The Gambia as shaped by prevailing local vaccination cultures(comprising maternal knowledge and understandings, socio-culturalcontexts and interactions with health providers). A survey of1600 mothers constructed on the basis of prior ethnography findsa high level of social demand for vaccination, based on laytheories of the general value of immunization in complementingtraditional child protection practices. For most rural mothers,strong social networks encourage routine clinic attendance andvaccination ‘default’ arises only through day-to-dayproblems and contingencies. However, more pervasive patternsof schedule non-completion are found amongst poorer urban mothers,including recent immigrants, who experience social exclusionat infant welfare clinics. These findings point to the needfor health education dialogue grounded in mothers’ ownunderstandings and for particular policy attention to improvingthe clinic experiences of vulnerable social groups in rapidlyexpanding urban areas.     

Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy

PURPOSE: To further characterize the mutations within the CHST6 gene responsible for causing macular corneal dystrophy in a cohort of affected patients from the United States. DESIGN: Experimental study. METHODS: Genomic DNA was extracted from buccal epithelium of 16 affected patients (14 families), 17 unaffected relatives, and 127 controls, followed by polymerase chain reaction amplification and direct sequencing of the CHST6 coding region. Subtyping of affected patients into type I and II macular corneal dystrophy was performed by measuring antigenic keratan sulfate (AgKS) serum levels. Haplotype analysis was performed in families that demonstrated common mutations. RESULTS: CHST6 coding region analysis in 10 patients identified as having type I macular corneal dystrophy revealed 10 sequence changes: eight missense mutations, four of which are novel (Met104Val, Tyr110Cys, Gln122Pro, and Leu276Pro) and four of which have been reported previously (Ser51Leu, Pro72Ser, Cys102Gly, and Leu200Arg); one novel homozygous nonsense mutation in two patients from a single family (c. 1683C>T, Gln331X); and one frameshift mutation in a heterozygous state in a single patient (c.1744_1751dupGTGCGCTG). Mutation analysis in the four patients identified as having type II macular corneal dystrophy (serum samples were not obtained from two affected patients) revealed three patients heterozygous for either the c.923G>C, c.969C>A, or c.1519T>C sequence changes. The fourth patient was compound heterozygous for c.969C>A and c.1291T>G. None of these changes was observed in 127 control individuals. Haplotype analysis using microsatellite markers flanking the CHST6 gene did not reveal a common founder for the Leu200Arg (1291T>G) missense mutation, present in five families, identifying this position as a mutation hot-spot. CONCLUSIONS: A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I macular corneal dystrophy in a cohort of patients from the United States.     

Time to disease progression to evaluate a novel protein kinase C inhibitor, UCN-01, in renal cell carcinoma

BACKGROUND: Renal cell carcinoma (RCC) is characterized by von Hippel-Lindau gene inactivation and vascular endothelial growth factor (VEGF) overproduction. The mechanism of VEGF overproduction may involve protein kinase C (PKC) delta and zeta isoforms. UCN-01 (7-hydroxystaurosporine) is a selective inhibitor of PKC. Given the historically low objective response rate in RCC, time to disease progression (TTP) as an alternative endpoint was employed to evaluate the antitumor activity of UCN-01 in RCC. METHODS: Patients with progressive, metastatic RCC received UCN-01 intravenously on Day 1 of each 21-day cycle. The initial dose was 90 mg/m(2) and all subsequent doses were 45 mg/m(2) unless modified for toxicity. TTP was the primary endpoint, defined as the period from the first day of treatment until disease progression. Detection of circulating EpCAM-positive renal carcinoma cells was undertaken for predictive or prognostic potential. RESULTS: Twenty-one patients were enrolled in this Phase II study. Accrual was halted after failure to reach a predetermined efficacy requirement with 7 patients remaining disease progression free after 4 months (6 cycles). The median TTP for all patients was 2.67 months (range, 0.4-7.6 months). There were no objective responses. Therapy was generally well tolerated. Thirteen patients had < 0.6 EpCAM-positive cells/mL (considered negative) at all time points measured. Two patients had detectable EpCAM-positive cells at a single time point with other measurements being negative. CONCLUSIONS: TTP is a novel endpoint for the evaluation of agents in RCC. UCN-01 did not demonstrate significant antitumor activity. No evidence for significant circulating EpCAM-positive cells was found in this study cohort.     

Second-line chemotherapy for hormone-refractory prostate cancer: has the time come?

Prostate-specific antigen testing has not only led to an earlier diagnosis of prostate cancer, but also to an earlier identification of hormone-refractory prostate cancer (HRPC). Many patients identified early with HRPC may receive first-line taxane-based chemotherapy. Patients who progress after first-line chemotherapy are still quite healthy and desire further therapy. No proven treatment options exist for the second-line treatment of HRPC. Finding new agents that are active in the second-line setting and identifying relevant outcome variables and predictive pretreatment variables are crucial in improving survival and quality of life for this patient population.     

Novel therapeutic targets for appetite regulation

Obesity is currently the major cause of premature death in the UK, killing almost 1000 individuals per week, and worldwide, its prevalence is accelerating. Many peptides are synthesized and released from the gastrointestinal tract and, while their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that they also physiologically influence eating behavior. Therefore, manipulation of gastrointestinal hormones provides the prospect of an effective and well-tolerated treatment for obesity. Whereas drugs targeting appetite-signaling neuropeptides in the brain may also affect other aspects of the central nervous system, agents based on gut hormones themselves have the advantage of targeting specific appetite circuits within the brain without producing any unacceptable side effects.     

Lattice dystrophy-like localized amyloidosis of the cornea secondary to trichiasis

PURPOSE: To report a case of stellate and branching linear corneal stromal amyloid deposits secondary to trichiasis and the use of molecular genetic analysis to exclude lattice corneal dystrophy. METHODS: Case report and review of the literature. A 30-year-old man with a history of chronic ocular irritation was found to have distichiasis, epiblepharon, and unilateral corneal amyloidosis indistinguishable from lattice corneal dystrophy. Screening of the TGFBI gene was performed to rule out a previously reported mutation associated with lattice corneal dystrophy. RESULT: A corneal biopsy performed before presentation to the authors confirmed the presence of corneal amyloidosis. Screening of exons 4, 11, 12, and 14 in the TGFBI gene identified 2 previously reported polymorphisms, Leu472Leu and Phe540Phe, but no other coding region changes. CONCLUSION: Corneal stromal amyloidosis clinically resembling lattice corneal dystrophy may be associated with trichiasis. The exclusion of a TGFBI-associated corneal dystrophy in this case, leaving trichiasis as the most likely cause of the corneal amyloid deposition, demonstrates the utility of molecular genetic analysis in confirming or refuting a presumptive clinical diagnosis.     

A hermeneutic science: health economics and Habermas

PURPOSE: Mainstream health economics labours under a misleading understanding of the nature of the topic area and suffers from a concomitant poverty of thinking about theory and method. The purpose here is to explore this critical position and argue that health economics should aspire to being more than a technical discipline. It can, and should, engage with transformative discourse. DESIGN/METHODOLOGY/APPROACH: It is argued that the hermeneutic sciences, emphasising interpretation not instrumentality or domination, offer a route into the change to which one seeks to contribute. The article specifically focuses on the way Habermas provides insights in his approach to knowledge, reason and political economy. How he emphasises complexity and interaction within cultural milieu is explored and primacy is given to preserving the life-world against the encroachments of a narrow rationalization. FINDINGS: The argument for a critical re-imagining of health economics is presented in three stages. First, the antecedents, current assumptions and critical voices from contemporary economics and health economics are reviewed. Second, the way in which health is best understood via engaging with the complexity of both the subject itself and the society and culture within which it is embedded is explored. Third, the contribution that hermeneutics, and Habermas' critical theory, could make to a new health economics is examined. ORIGINALITY/VALUE: The paper offers a radical alternative to health economics. It explores the shortcomings of current thinking and argues an optimistic position. Progress via reason is possible if one reframes both in the direction of communication and in the appreciation of reflexivity and communality. This is a position that resonates with many who challenge prevailing paradigms, in economics and elsewhere.