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Biomedical subjects

H C Williams

Publications and source records attributed to H C Williams.

At least 55 records · Page 3Linked to original sources
PubMed2001

Atopic eczema and the home environment.

BACKGROUND: There is strong evidence to suggest that the prevalence of atopic eczema is increasing in developed countries. Environmental factors have been implicated in the disease. OBJECTIVES: This descriptive case-control study sheds light on the possible association between atopic eczema in school children and various home environmental factors, and generates hypotheses for further studies. METHODS: The study uses data on reported atopic eczema symptoms collected via a cross-sectional parental postal survey (n = 1350) in Nottingham, U.K. Estimates of the risk of reported eczema associated with various home environmental factors were calculated by means of odds ratios (OR), along with population attributable risk percentages. RESULTS: The study showed statistically significant associations between atopic eczema symptoms and dampness in the home [OR 1.40; 95% confidence interval (CI) 1.00-1.97], the use of a radiator to heat the child's bedroom (OR 1.50; 95% CI 1.05-2.16) and the use of synthetic pillows (OR 1.51; 95% CI 1.01-2.28). Frequent vacuuming in the home was associated with a decreased prevalence of atopic eczema (OR 0.74; 95% CI 0.58-0.94). The associations with dampness in the home, synthetic pillows and frequency of vacuuming were not altered significantly after adjustment for age, sex and socio-economic status. Population attributable risk percentages for the use of a radiator and synthetic pillows indicate that although the relative risk estimates for these factors may be small, the population impact of these factors is considerable (26% and 28%, respectively), owing to the high prevalence of exposure to these factors among this group of school children. CONCLUSIONS: Further research is needed to confirm these associations and additional research is needed to see whether they might be causative. Practical public health advice about the importance of controlling the home environment may then be targeted at families with atopic eczema.

Bedding and Linens↗
PubMed2001

Blueprint for discovery in academic medicine: plans, process and outcomes.

By the end of the decade, we had fully implemented most of the recommendations of the Molinoff Report. Our programmatic analysis is summarized in Table 11. While the space needs identified in the Molinoff Report were met by BRB I, II, and III (289,000 nsf as compared [table: see text] to 276,000 nsf as planned), it was possible to provide additional, somewhat unanticipated, research space (111,000 nsf) prior to the end of the decade. The faculty has now developed a research plan for the next decade. It is also important to emphasize that the total faculty grew by 41% [table: see text] over the decade and most of that growth occurred with faculty spending a substantial part of their time in clinical practice. Hence, the dramatic improvement in research funding of over 200% was due largely to the enhanced productivity of our faculty. By taking an organized planning approach deeply seated in the faculty, consistent with Trustee directives and with measurable outcomes, we were successful in growing the research programs within the School of Medicine of the University of Pennsylvania. We believe this particular approach, taken with a focus on multidisciplinary research, [table: see text] was the right one for the 1990s. In the final analysis, it is abundantly clear that outstanding faculty, working in an exciting supportive environment, was the most important factor for success. We are not certain what the right approach will be for the future. Clearly, with the important advances in genomics and information technology, the importance of the team, even if a virtual one world-wide, cannot be overstated. While research is only one mission of the School of Medicine, clearly, our visible success in research played an important role in the overall improvement in the School of Medicine as measured by others. For example, the ranking of the School of Medicine by U.S. News & World Report, perhaps the most widely used ranking by the lay press, went from 10th to 3rd behind only Harvard and Johns Hopkins during the period of the 90s (Table 12).

Academic Medical Centers↗
PubMed2000

Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis.

OBJECTIVES: To evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis. DESIGN: Quantitative systematic review of randomised controlled trials. SUBJECTS: 6038 patients with plaque psoriasis reported in 37 trials. MAIN OUTCOME MEASURES: Mean difference in percentage change in scores on psoriasis area and severity index, and response rate ratios for both patients' and investigators' overall assessments of marked improvement or better. Adverse effects were estimated with the rate ratio, rate difference, and number needed to treat. RESULTS: Calcipotriol was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar, and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5%. Calcipotriol caused significantly more skin irritation than potent topical corticosteroids (number needed to treat to harm for irritation 10, 95% confidence interval 6 to 34). Calcipotriol monotherapy also caused more irritation than calcipotriol combined with a potent topical corticosteroid (6, 4 to 8). However, the number needed to treat for dithranol to produce lesional or perilesional irritation was 4 (3 to 5). On average, treating 23 patients with short contact dithranol led to one more patient dropping out of treatment owing to adverse effects than if they were treated with calcipotriol. CONCLUSIONS: Calcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment. Longer term comparative trials of calcipotriol versus dithranol and topical corticosteroids are needed to see whether these short term benefits are mirrored by long term outcomes such as duration of remission and improvement in quality of life.

Administration, Topical↗
PubMed2000

Combination regimens of topical calcipotriene in chronic plaque psoriasis: systematic review of efficacy and tolerability.

OBJECTIVE: To examine the efficacy and tolerability of calcipotriene combined with phototherapy or systemic therapies compared with monotherapy for the treatment of chronic plaque psoriasis. DESIGN: Quantitative systematic review of 11 randomized controlled trials involving a total of 756 patients with plaque psoriasis. MAIN OUTCOME MEASURES: Rate ratios (RRs) for marked improvement or clearance in patient and investigator overall assessments of response; mean difference in percentage change in Psoriasis Area and Severity Index; and RRs for clearance in patient and investigator overall assessments of response. Adverse effects were estimated with the RR and the rate difference in terms of withdrawal rate, proportion of patients experiencing adverse events, and proportion of patients with cutaneous and noncutaneous adverse effects. RESULTS: Antipsoriatic effects of acitretin, cyclosporine, and psoralen-UV-A phototherapy were enhanced with the addition of topical calcipotriene using the Psoriasis Area and Severity Index as the outcome, but this is not translated into an increase in the number of patients who achieve at least marked improvement. At the end of treatment, the RRs for marked improvement or clearance in patient assessments were as follows: calcipotriene plus acitretin vs acitretin alone (12 weeks), 1.4 (95% confidence interval [CI], 1.0-1. 9); calcipotriene plus cyclosporine vs cyclosporine alone (6 weeks), 1.2 (95% CI, 0.9-1.6); and calcipotriene plus psoralen-UV-A vs psoralen-UV-A alone (12 weeks), 1.2 (95% CI, 0.9-1.6). Patients were also no more likely to obtain marked improvement or better with calcipotriene plus UV-B therapy than with UV-B therapy alone (RR, 1. 0; 95% CI, 0.8-1.1 at 8 weeks in the patient assessment). There is limited evidence that use of calcipotriene might reduce the cumulative exposure to phototherapy and systemic treatment. During the short duration of these trials, there were no significant differences in withdrawal rates or adverse effects between the combined regimens and their corresponding monotherapy control interventions. CONCLUSIONS: Overall, there is insufficient evidence to support any large effects in favor of combination treatment. In the patient assessments, the results do not show an adjuvant effect, but there is some evidence that use of calcipotriene might reduce cumulative exposure to systemic therapy to obtain clearance. There were no long-term morbidity data on the effectiveness of any of the combinations studied. Given that psoriasis is a chronic recurrent disease for most patients, longer trials are needed to determine whether the addition of topical calcipotriene to systemic therapy improves the risk-benefit ratio by reducing the long-term risk of toxic effects. Equally important is the need to examine the impact of such combinations on the duration of remission after treatment.

Administration, Cutaneous↗
PubMed2000

The British Association of Dermatologists audit of atopic eczema management in secondary care. Phase 2: audit of service process.

An audit of atopic eczema management, conducted on behalf of the British Association of Dermatologists, examined service structure (phase 1), process (phase 2) and outcome (phase 3). In phase 2, an on-site case-note audit was conducted in 19 hospital dermatology departments randomly selected from the original sample of 187 centres across the U.K. In total, 630 sets of notes were examined for completeness of: (i) information given to general practitioners (GPs) in clinic letters and (ii) facts relevant to the management of atopic eczema recorded in the patients' notes. In general, the information given to GPs in the clinic letters was good, with the recording of diagnosis, treatment and follow-up approaching the 100% working standard. Factual information such as site and severity of eczema (83% and 74%), and presence or absence of asthma (53%) were better recorded than quality of life issues such as sleep loss secondary to itching (21%) and effect on school, work or social life (6%). On average, only 51% of all audit measures were recorded across all centres, with slight variation between centres (41-61%). The centre with the best recording had a purpose-designed data sheet for doctors to complete when seeing new patients with atopic eczema. Such data sheets may help improve case-note recording. Similar data sheets for patients to complete may be more time-efficient.

Adolescent↗
PubMed2000

The Nottingham Eczema Severity Score: preliminary refinement of the Rajka and Langeland grading.

A method for assessing disease severity of atopic dermatitis (AD) in children has been developed for population-based research. Based on an index first described by Rajka and Langeland in 1989, disease severity is determined by evaluating the three elements of clinical course, disease intensity and extent of examined AD. This paper describes development of the index for use in epidemiological studies based on a community-based study of 290 pre-school children (aged 1-5 years). Construct validity of the index was evaluated with respect to clinical severity assessment according to a dermatologist, parental severity assessment, use of topical corticosteroids and impairment of quality of life. The severity distribution of AD in this community-based sample of children was: mild 82% (n = 237), moderate 12% (n = 36) and severe 6% (n = 17) according to this new index. In this sample 24% of children had suffered from AD of more than 9 months duration in the preceding 12 months, 4.5% had experienced significant sleep loss (6 or more nights of average sleep loss per week over 12 months) and 11% had experienced widespread extent of involvement (more than 10 body sites involved). Construct validity of the index was demonstrated for clinical and patient-derived severity assessment. This included a comparison between the new index and a global severity assessment by a dermatologist in which exact agreement was achieved in 88% of the cases. A small subgroup of children suffering from persistent localized forms of AD (discoid pattern, hand/ foot dermatitis, perioral dermatitis), who reported considerable morbidity, was identified using quality of life measures of severity; they would otherwise have been misclassified by the dermatologist or new index. Preliminary use of the Nottingham Eczema Severity Score would support further development as a research tool for a simple assessment of disease severity that could be used in epidemiological studies. Further validation is required with respect to use in older children, administration by researchers/health professionals and development as a wholly questionnaire-based assessment.

Administration, Topical↗
PubMed2000

Is there a geographical variation in eczema prevalence in the UK? Evidence from the 1958 British Birth Cohort Study.

Some studies have suggested that the prevalence of atopic eczema may vary between geographical regions. This descriptive study investigates the regional and subregional geography of reported and examined eczema prevalence at the age of 7, 11 and 16 years in Britain using data from the 1958 birth cohort study (n = 828). Estimates of the relative risk of reported eczema associated with residence in each region of the country were calculated and the regional distribution of reported and examined eczema prevalence was compared. The reported prevalence of eczema was mapped at the smaller county level. Comparisons were made with the county-level distribution of asthma and hay fever prevalence. The study showed a marked and statistically significant variation in eczema prevalence across the regions in Britain which was present for examined as well as reported eczema. The highest risk was associated with four regions: North Midlands; Eastern; London and the South-East; and Southern. This regional pattern was not altered significantly after adjustment for social class and family size. The geographical distribution of eczema prevalence was largely maintained when analysed at the county level. Few similarities were found between the county-level distribution of eczema prevalence and that for asthma and hay fever. Explanations for this strong regional variation now need to be sought in terms of environmental and life-style associations.

Adolescent↗
PubMed2000

The British Association of Dermatologists audit of atopic eczema management in secondary care. Phase 3: audit of service outcome.

Service outcome was examined by a preconsultation (part 1) and a 6-week postconsultation (part 2) patient questionnaire in 29 hospital dermatology departments randomly selected from an original sample of 187 centres across the U.K. The outcome measures were: quality of life as measured by the Dermatology Life Quality Index (DLQI) and Children's DLQI (CDLQI), improvement in sleep loss, improvement in worse aspect of skin disease and return to work or school. Three hundred and fifty-two questionnaires (115 adults, 237 children) were completed for part 1, and 235 (67%) replied to part 2. The mean DLQI at initial consultation was 12.5, dropping to 9.7 at 6 weeks (P = 0.001). The mean CDLQI at initial consultation was 10.5, dropping to 8.7 at 6 weeks (P < 0.001). Forty-nine per cent of adults and 44% of children had a > 25% relative improvement in score, which did not meet the 60% working standard. Forty-four per cent of adults and 47% of children had an improvement in sleep loss at 6 weeks, falling short of the 70% working standard. Sixty-one per cent of adults and 59% of children had an improvement in the worst aspect of their skin condition at 6 weeks, falling short of the 80% working standard. Of the 20 adults and eight children off work/school during part 1, 70% of adults and 87.5% of children had returned to work/school by 6 weeks. This met the 80% working standard for children but not for adults. On a national scale, only one of the eight working standards for service outcome was met, although most of the working standards were met by at least one of the 11 National Health Service administrative areas. This study presents the first national data on the outcomes of a representative sample of atopic eczema patients seen in secondary care. Small sample sizes, instruments which may be insensitive to change, as well as local factors such as case-mix, baseline severity and staff to patient ratios need to be taken into account when interpreting these results. Nevertheless, the results of this baseline audit suggest that the outcome of patients with atopic eczema following secondary care consultation may not be as good as some doctors believe. This suggests that an improvement in practice, a re-evaluation of the working standards, or both, is needed and should be examined in future audit cycles.

Adolescent↗
PubMed2000

Topical corticosteroid phobia in patients with atopic eczema.

Topical corticosteroids are widely prescribed by dermatologists caring for patients with atopic eczema. Patients' fears about using topical corticosteroids may have important implications for compliance with treatment. We carried out a questionnaire-based study of 200 dermatology outpatients with atopic eczema (age range 4 months-67.8 years) to assess the prevalence and source of topical corticosteroid phobia. We also questioned patients on their knowledge of the potencies of different topical corticosteroids. Overall, 72.5% of people worried about using topical corticosteroids on their own or their child's skin. Twenty-four per cent of people admitted to having been non-compliant with topical corticosteroid treatment because of these worries. The most frequent cause for concern was the perceived risk of skin thinning (34.5%). In addition, 9.5% of patients worried about systemic absorption leading to effects on growth and development. The most commonly used topical corticosteroid was hydrocortisone, yet 31% of patients who used this preparation classified it as either strong, very strong or did not know the potency. Only 62.5% of the 48 patients who had used both Dermovate (Glaxo) and hydrocortisone in the past were able to correctly grade Dermovate as being more potent than hydrocortisone. The most common source of patient information regarding topical corticosteroid safety was the general practitioner. Although skin thinning and systemic effects can develop very occasionally in people using topical corticosteroids, the concern expressed by people using them seems out of proportion in relation to the evidence of harm. This study highlights the need for provision of better information and education to patients and possibly general practitioners regarding the safety, potency and appropriate use of topical corticosteroids.

Administration, Topical↗
PubMed2000

The clinical genetics of hidradenitis suppurativa revisited.

A familial form of hidradenitis suppurativa (HS) with autosomal dominant inheritance was described in a study conducted 15 years ago in Nottingham but has not been systematically confirmed elsewhere. Prior to commencing molecular genetic studies, we wanted to test the validity of the previous study by assessing its reproducibility on the basis of a strict, newly devised disease definition for HS. We were also interested whether new cases of the disease had arisen meantime in the study group as should be expected for an autosomal dominant disease. We reviewed 14 surviving probands and their families. Seven of these probands had previously been noted to have a positive family history whereas the others had been classified as having a negative or possible family history. One hundred and thirty-two family members were assessed for their respective disease status. Participants were initially contacted by telephone or letter, and those who acknowledged a history of at least one previous boil were invited for a personal examination and interview. Only personally examined individuals were classified as a case. Twenty-eight relatives with HS were detected in total, and 27 of these were in the group previously labelled family history positive. Nine of these cases had not been detected in the previous study and in at least seven of these the disease had developed after the previous study had been conducted. Only twice did our criteria fail to confirm cases that had been labelled as HS in the previous study. Both times we classified the patients as 'possibly affected'. A further 16 relatives were judged to be possibly affected. In the group with positive family history we found 10 affected and nine possibly affected individuals among 37 surviving first-degree relatives of HS sufferers. Our findings support the concept of a familial form of HS with autosomal dominant inheritance. An insufficiently sensitive disease definition, a variable degree of gene penetrance and possibly a hormonal influence on gene expression may explain the reduced risk to first-degree relatives, which falls short of the expected 50% mark. Molecular genetic studies to clarify whether one or more gene(s) are involved in HS are now necessary and have been commenced.

Adult↗
PubMed2000

Epidemiology of atopic dermatitis.

Although research into atopic dermatitis (AD) has been dominated by the study of cells and chemical mechanisms over the last 40 years, the last 7 years has witnessed a respectable growth within the field of AD epidemiology. Significant advances include valid disease definitions that can be used in epidemiological studies, global prevalence studies, and studies which quantify the morbidity and economic cost of the disease. These have all helped to argue the case for more research into AD. Epidemiological studies demonstrating that AD is commoner in wealthier families, linkage with small family size, increased prevalence in migrant groups, and the increasing prevalence of the disease all argue strongly towards an important role for the environment in determining disease expression. Future research gaps include evaluation of gene-environment interactions, better studies of the natural history of AD, and better clinical trials that answer questions that are important to physicians and their patients.

Age Factors↗
PubMed2000

A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens.

Ichthyosis bullosa of Siemens (IBS; MIM: 146800) is an autosomal dominant disorder of keratinization characterized by epidermolytic hyperkeratosis without erythroderma. The clinical features are less marked than those of bullous congenital ichthyosiform erythroderma with relatively mild hyperkeratosis usually limited to the skin flexures. Mutations in the epithelial cytokeratin 2e (K2e), which is expressed in a differentiation-specific fashion in the upper spinous and granular layers of the epidermis, have been shown to cause IBS. We detected a novel mutation in a three generation kindred with IBS (1448T-->A) within exon 7 of the KRT2E gene. This is predictive of an I483N substitution in the 2B domain of K2e. This extends the range of mutations reported to date and illustrates the usefulness of molecular genetics in the diagnosis of this disorder.

DNA Mutational Analysis↗
PubMed2000

The natural history of hidradenitis suppurativa.

AIM: To investigate aspects of the natural history of hidradenitis. BACKGROUND: The natural history of hidradenitis suppurativa (HS) is not well known. There is incomplete published data on the average age of disease onset, progression of the disease, average monthly incidence and duration of boils, and factors that relieve or exacerbate disease symptoms. STUDY DESIGN: Questionnaire-based survey among HS patients identified from hospital records of three hospitals in Nottinghamshire, UK. RESULTS: One hundred and ten of 156 questionnaires (70.5%) were returned, 93 from females and 17 from males. The average patient's age was 40.1 years and the average reported age of disease onset was 21.8 years. At the time of the survey patients had suffered an average disease duration of 18.8 years. Most patients (98 of 110) still had experienced active disease within the past year. There was some evidence that in women the condition has a tendency to ease or subside after the menopause. Forty-four per cent of women felt that their condition was aggravated by menstruation. Thirty-eight per cent of patients gave a positive family history of the disorder. The average duration of painful boils was 6.9 days. In addition, 62% of patients acknowledged the presence of permanently painful boils that failed to subside. Patients developed a median of two boils per month. Factors that could aggravate the condition were primarily sweating or heat, stress or fatigue and tight clothing or friction. Factors that could improve the condition consisted largely of a variety of medical treatments and a number of life-style measures, such as swimming or baths. Twenty-four per cent of patients had failed to find anything at all to help their condition, despite an average disease duration of almost 19 years. CONCLUSIONS: The study highlights several of the factors that make HS one of the most distressing dermatological diseases, such as the average monthly incidence of painful lesions, their average duration and the chronicity of the disease. It seems striking that the mean duration of an HS boil (6.9 days) roughly equals the duration of an average course of antibiotics. The postulated response of HS to oral antibiotics may thus simply have its explanation in the natural history of the condition itself.

Adult↗
PubMed2000

Cost-effectiveness analysis of topical calcipotriol versus short-contact dithranol. In the treatment of mild to moderate plaque psoriasis.

OBJECTIVE: To examine the relative cost effectiveness of topical calcipotriol and short-contact dithranol in the treatment of mild to moderate plaque psoriasis. DESIGN AND SETTING: This was a modelling study from the perspective of the UK National Health Service as payer. METHODS: The interventions were compared using 2 decision-analytic models: one using a short term horizon (12 weeks) and the other using a longer term horizon (up to 1 year). Clinical success of treatment and relapse rates were obtained from the results of randomised controlled trials. MAIN OUTCOME MEASURES AND RESULTS: The outcome measure used was the degree of improvement in psoriasis as judged by the patient. In the short term comparison, calcipotriol was the most effective treatment (60.8% success), but it was also the most expensive (96.03 Pounds; 2000 values). The incremental cost per success was 577.50 Pounds using a 12-week course of calcipotriol compared with short-contact dithranol. Over the long term horizon, first-line treatment with calcipotriol still had the highest expected cost per successful treatment (164.91 Pounds), but the incremental cost using this strategy was 38.66 Pounds compared with short-contact dithranol. In terms of cost per successful day's treatment (i.e. the cost for a day in which the patient reported a marked improvement or cleared lesions), the cost of each additional successful day's treatment was 19.93 Pounds when using calcipotriol as first-line treatment rather than short-contact dithranol. CONCLUSION: The combination of differences in drug acquisition costs and relapse rates can lead to large differences in the comparative cost effectiveness of topical treatments for plaque psoriasis. From the perspective of the prescriber, the results of this analysis suggest that selecting short-contact dithranol as first-line treatment was the most cost-effective strategy.

Administration, Topical↗