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Biomedical subjects

C Griffiths

Publications and source records attributed to C Griffiths.

At least 19 recordsLinked to original sources
PubMed2006

Changes to the daily pattern of methadone-related deaths in England and Wales, 1993-2003.

Previous studies suggest that fatal poisoning deaths involving methadone occur more frequently on the weekends. We assessed changes in the daily pattern of mortality because of methadone poisoning following a review of drug misuse services in 1996 and publication of revised clinical guidelines in 1999. We also compared this to the daily pattern of deaths involving heroin/morphine. The Office for National Statistics provided data on all deaths in England and Wales between 1993 and 2003 for which methadone and heroin/morphine were mentioned on the coroner's certificate of death registration after inquest, with or without alcohol or other drugs. There were 3098 deaths involving methadone. The death rate increased up to 1997 and then declined. Initially, there was a marked excess of deaths occurring on Saturdays. The rate of decline was greatest for deaths occurring on Saturdays. As a result, the Saturday peak disappeared (P = 0.006). There were 6328 deaths involving heroin/morphine. No change in the daily pattern of heroin/morphine deaths was observed during the study period. Although the marked change in the epidemiology of methadone deaths coincided with recommendations for service redevelopment and clinical management of methadone treatment, the contribution of improved prescribing practice or treatment services is unclear.

Death Certificates↗
PubMed2006

Is screening for tuberculosis acceptable to immigrants? A qualitative study.

BACKGROUND: Screening of immigrants has been a widespread response to the global resurgence of tuberculosis but has been criticized as discriminatory and stigmatising. Acceptability is an essential but neglected ethical prerequisite of screening programmes, particularly those targeting vulnerable groups such as refugees. No data exist concerning acceptability of tuberculosis screening. We therefore examined the responses of immigrants to screening for tuberculosis in a range of settings. METHODS: We carried out a qualitative interview study of a maximum diversity sample of 53 immigrants offered screening for tuberculosis in east London. We recruited people screened in three settings: a social service centre for asylum seekers, a hospital clinic for new entrants and primary care. We confirmed validity of our findings at a focus group of asylum seekers. RESULTS: The opportunity to be screened for tuberculosis was valued highly by recipients. Moreover, many saw being screened as a socially responsible activity. Of the minority raising concerns, few mentioned the possibility of discrimination. Acceptability was high irrespective of setting, with respondents expressing preference for their chosen place of screening. CONCLUSION: Screening for tuberculosis was highly acceptable to recipients in these settings. Screening should be offered in a range of settings.

Adolescent↗
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2006

Mortality from all cancers and lung, colorectal, breast and prostate cancer by country of birth in England and Wales, 2001-2003.

Mortality from all cancers combined and major cancers among men and women aged 20 years and over was compared by country of birth with that of the whole of England and Wales as the reference group. Population data from the 2001 Census and mortality data for 2001-2003 were used to estimate standardised mortality ratios. Data on approximately 399 000 cancer deaths were available, with at least 400 cancer deaths in each of the smaller populations. Statistically significant differences from the reference group included: higher mortality from all cancers combined, lung and colorectal cancer among people born in Scotland and Ireland, lower mortality for all cancers combined, lung, breast and prostate cancer among people born in Bangladesh (except for lung cancer in men), India, Pakistan or China/Hong Kong, lower lung cancer mortality among people born in West Africa or the West Indies, higher breast cancer mortality among women born in West Africa and higher prostate cancer mortality among men born in West Africa or the West Indies. These data may be relevant to causal hypotheses and in relation to health care and cancer prevention.

Adult↗
PubMed2006

Variation in invasive and noninvasive measurements of isovolumetric bladder pressure and categorization of obstruction according to bladder volume.

PURPOSE: We developed a noninvasive test that provides an estimate of isovolumetric bladder pressure by measuring the pressure required to interrupt voiding using controlled inflation of a penile cuff. We noted variation in serial measurements obtained during a single void and, therefore, we determined whether this represents variation in detrusor contraction strength, as predicted in previous studies, or measurement error. MATERIALS AND METHODS: A total of 36 symptomatic men underwent simultaneous invasive and noninvasive pressure flow studies. Corresponding values of isovolumetric bladder pressure and cuff interruption pressure were recorded at each flow interruption and grouped according to bladder volume to calculate measurement error and bias at various points during a void. Individual variation in the 2 measurements across a range of normalized bladder volumes was then examined using ANOVA. RESULTS: Cuff interruption pressure showed a consistent level of accuracy as an estimate of isovolumetric bladder pressure across a range of volumes. There were similar, statistically significant differences in isovolumetric bladder pressure and cuff interruption pressure recorded at specific volume increments with the highest values seen in the mid range and the lowest seen at lower bladder volumes (each p <0.01). When plotting, the maximum recorded value of cuff interruption pressure in each individual on our proposed noninvasive pressure flow nomogram provided the best diagnostic accuracy for obstruction. CONCLUSIONS: This study shows that cuff interruption pressure varies in the expected manner with bladder volume and provides a consistent estimate of isovolumetric bladder pressure throughout a void. These data provide important guidance for interpreting noninvasive pressure flow studies and classifying obstruction on the proposed nomogram.

Adult↗
PubMed2006

A formative evaluation of the potential role of nurse practitioners in a central London HIV outpatient clinic.

In-house audit demonstrated that 49% (173/352) of patients attending routine HIV outpatient care are asymptomatic and have needs that could potentially be met by other health care professionals. We therefore evaluated the potential development and acceptability of nurse practitioner roles in contributing to HIV outpatient care. Data were collected through 26 consultation observations, 25 patient interviews, 2 patient focus groups, 22 provider interviews and 8 provider focus groups. Service users were key members of the evaluation team. With increasing HIV incidence and the change in focus of doctor-patient consultations from acute to chronic disease management, there are concerns about the sustainability of easily available routine HIV outpatient appointments using the same model of care that has prevailed over the past 20 years. Nurse practitioner models of care were considered acceptable for asymptomatic patients, including those who do not have complex issues related to highly active antiretroviral therapy (HAART). Key considerations for the role include training, supervision, referral pathways, and a clear understanding of the limitations of nursing practice. There is an emphasis on the need to consider 'new ways of working' throughout the service, rather than merely substituting or transferring clinical roles between professionals. Funding pending, nurse practitioner roles are planned for implementation in late 2004. Evaluation will determine impact on service utilization, health and economic outcomes.

Ambulatory Care↗
PubMed2005

Fatal poisoning in childhood, England & Wales 1968-2000.

We analysed deaths certified as due to poisoning in England & Wales, 1968-2000, in children aged <10 years by age, sex, circumstances of death, intent, and agents involved. The number of deaths fell from 165 (20.6 per million children) in 1968 to 30 (4.6 per million) in 2000, a decrease of approximately 80%. The age-specific death rates were similar in boys and girls. The rate was initially much higher, and fell more, in those aged <5 years. Most deaths (n=1923) occurred in fires, and had been attributed to inhaling combustion products. A small number (n=104) occurred in fires resulting from motor vehicle and other transport accidents. From 1979 (use of ICD-9) the coding of some of these deaths changed from poisoning with carbon monoxide to poisoning with 'other gases, fumes or vapours'. These 'fire deaths' do not appear as poisonings in mortality statistics based on a single underlying cause of death, and cannot be tabulated as poisoning in many countries. Fire deaths and deaths coded to accidental, deliberate, or undetermined poisoning (n=702) decreased substantially with time, and by 2000 numbered 14 and 10, respectively. Accidental deaths declined from 151 in 1968 to 23 in 2000, but homicides and open verdicts varied from 5 to 20 per year, with no clear trend. Deaths attributed to carbon monoxide and to 'other gases, fumes or vapours' (mostly fire-related) totalled 2431 (84% of all poisoning deaths). Overall, 10% of these deaths were either certified as homicides or open verdicts. However, homicide or open verdict was recorded in half of the 47 fatal opiate poisonings. Opioids have now superseded antidepressants as the commonest agents encountered in fatal poisoning with drugs in children.

Accidents↗
PubMed2005

Leukocyte extravasation as a target for anti-inflammatory therapy - Which molecule to choose?

In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this - surprisingly complex - process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the - as yet unresolved and still rather controversially discussed - critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.

Anti-Inflammatory Agents↗
PubMed2005

Fatal poisoning with antipsychotic drugs, England and Wales 1993-2002.

Prescription of atypical antipsychotics has increased in recent years. There have also been changes in the guidance on using older drugs, particularly the restriction in the use of thioridazine. We analysed deaths due to poisoning involving antipsychotics in England and Wales, 1993-2002, by age, sex, intent, and agents involved. We also studied antipsychotic prescribing in the community and poisoning deaths in England. Deaths attributed to adverse reactions in the course of normal treatment were not studied because these deaths are not classified as 'poisonings'. The number of deaths involving antipsychotics increased from around 55 per year 1993-1998 to 74 in 2000, and then fell to 53 in 2002. Around 25% of deaths had a verdict of accidental death and in about 60% of deaths a verdict of suicide or an open verdict was recorded. There were no deaths involving thioridazine in 2002, following its removal from use in 2001. However, the number of deaths associated with atypicals, most notably olanzapine and clozapine, has increased. Age-specific death rates were highest in those aged 30-39 and 40-49 years, and were very low in those aged under 20 and 70 or over. Death rates in males were greater than in females. For many drugs the proportion mentions either alone or with ethanol, was 25-45%, but for clozapine and olanzapine such mentions totalled 65-69%. Deaths per million prescriptions (clozapine excluded) were highest for quetiapine (31.3 per million), chlorpromazine (29.4 per million) and thioridazine (15.5 per million).

Accidents↗
PubMed2004

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Animals↗
PubMed2004

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗
PubMed2004

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome Mapping↗
PubMed2004

Biological therapies in the systemic management of psoriasis: International Consensus Conference.

Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

Age Factors↗
PubMed2003

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗
PubMed2003

Can a self-management programme delivered by a community pharmacist improve asthma control? A randomised trial.

BACKGROUND: No randomised studies have addressed whether self-management for asthma can be successfully delivered by community pharmacists. Most randomised trials of asthma self-management have recruited participants from secondary care; there is uncertainty regarding its effectiveness in primary care. A randomised controlled study was undertaken to determine whether a community pharmacist could improve asthma control using self-management advice for individuals recruited during attendance at a community pharmacy. METHODS: Twenty four adults attending a community pharmacy in Tower Hamlets, east London for routine asthma medication were randomised into two groups: the intervention group received self-management advice from the pharmacist with weekly telephone follow up for 3 months and the control group received no input from the pharmacist. Participants self-completed the North of England asthma symptom scale at baseline and 3 months later. RESULTS: The groups were well matched at baseline for demographic characteristics and mean (SD) symptom scores (26.3 (4.8) and 27.8 (3.7) in the intervention and control groups, respectively). Symptom scores improved in the intervention group and marginally worsened in the control group to 20.3 (4.2) and 28.1 (3.5), respectively (p<0.001; difference adjusted for baseline scores=7.0 (95% CI 4.4 to 9.5). CONCLUSIONS: A self-management programme delivered by a community pharmacist can improve asthma control in individuals recruited at a community pharmacy. Further studies should attempt to confirm these findings using larger samples and a wider range of outcome measures.

Administration, Inhalation↗