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2.  Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects 
European Journal of Human Genetics  2013;21(11):1219-1225.
Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF syndrome: DNMT3B and ZBTB24. To characterize the clinical features of this syndrome, as well as genotype–phenotype correlations, we compared clinical and genetic data of 44 ICF patients. Of them, 23 had mutations in DNMT3B (ICF1), 13 patients had mutations in ZBTB24 (ICF2), whereas for 8 patients, the gene defect has not yet been identified (ICFX). While at first sight these patients share the same immunological, morphological and epigenetic hallmarks of the disease, systematic evaluation of all reported informative cases shows that: (1) the humoral immunodeficiency is generally more pronounced in ICF1 patients, (2) B- and T-cell compartments are both involved in ICF1 and ICF2, (3) ICF2 patients have a significantly higher incidence of intellectual disability and (4) congenital malformations can be observed in some ICF1 and ICF2 cases. It is expected that these observations on prevalence and clinical presentation will facilitate mutation-screening strategies and help in diagnostic counseling.
PMCID: PMC3798845  PMID: 23486536
ICF syndrome; DNMT3B; ZBTB24; genotype–phenotype
3.  Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency☆ 
Severe combined immunodeficiency (SCID) can be cured by using allogeneic hematopoietic stem cell transplantation, and the absence of host immunity often obviates the need for preconditioning. Depending on the underlying genetic defect and when blocks in differentiation occur during lymphocyte ontogeny, infants with SCID have absent or greatly reduced numbers of functional T cells. Natural killer (NK) cell populations are usually absent in the SCID-X1 and Janus kinase 3 forms of SCID and greatly reduced in adenosine deaminase deficiency SCID but often present in other forms of the disorder.
To determine if SCID phenotypes indicate host permissiveness to donor cell engraftment.
A retrospective data analysis considered whether host NK cells influenced donor T-cell engraftment, immune reconstitution, and long-term outcomes in children who had undergone nonconditioned allogeneic stem cell transplantation between 1990 and 2011 in the United Kingdom. Detailed analysis of T- and B-cell immune reconstitution and donor chimerism was compared between the NK+ (n = 24) and NK− (n = 53) forms of SCID.
Overall, 77 children underwent transplantation, with survival of 90% in matched sibling donor/matched family donor transplants compared with 60% when alternative donors were used. Infants with NK−SCID were more likely to survive than NK+ recipients (87% vs 62%, P < .01) and had high-level donor T-cell chimerism with superior long-term recovery of CD4 T-cell immunity. Notably, 33% of children with NK+SCID required additional transplantation procedures compared with only 8% of children with NK−SCID (P < .005).
NK−SCID disorders are highly permissive for donor T-cell engraftment without preconditioning, whereas the presence of NK cells is a strong indicator that preparative conditioning is required for engraftment of T-cell precursors capable of supporting robust T-cell reconstitution.
PMCID: PMC4048544  PMID: 24794685
Severe combined immunodeficiency; conditioning; natural killer cells; chimerism; engraftment; adenosine deaminase deficiency; ADA, Adenosine deaminase deficiency; allo-SCT, Allogeneic hematopoietic stem cell transplantation; JAK3, Janus kinase 3; MFD, Matched family donor; MSD, Matched sibling donor; NK, Natural killer; SCID, Severe combined immunodeficiency; TREC, T-cell receptor excision circle
4.  Computer-Delivered and Web-Based Interventions to Improve Depression, Anxiety, and Psychological Well-Being of University Students: A Systematic Review and Meta-Analysis 
Depression and anxiety are common mental health difficulties experienced by university students and can impair academic and social functioning. Students are limited in seeking help from professionals. As university students are highly connected to digital technologies, Web-based and computer-delivered interventions could be used to improve students’ mental health. The effectiveness of these intervention types requires investigation to identify whether these are viable prevention strategies for university students.
The intent of the study was to systematically review and analyze trials of Web-based and computer-delivered interventions to improve depression, anxiety, psychological distress, and stress in university students.
Several databases were searched using keywords relating to higher education students, mental health, and eHealth interventions. The eligibility criteria for studies included in the review were: (1) the study aimed to improve symptoms relating to depression, anxiety, psychological distress, and stress, (2) the study involved computer-delivered or Web-based interventions accessed via computer, laptop, or tablet, (3) the study was a randomized controlled trial, and (4) the study was trialed on higher education students. Trials were reviewed and outcome data analyzed through random effects meta-analyses for each outcome and each type of trial arm comparison. Cochrane Collaboration risk of bias tool was used to assess study quality.
A total of 17 trials were identified, in which seven were the same three interventions on separate samples; 14 reported sufficient information for meta-analysis. The majority (n=13) were website-delivered and nine interventions were based on cognitive behavioral therapy (CBT). A total of 1795 participants were randomized and 1480 analyzed. Risk of bias was considered moderate, as many publications did not sufficiently report their methods and seven explicitly conducted completers’ analyses. In comparison to the inactive control, sensitivity meta-analyses supported intervention in improving anxiety (pooled standardized mean difference [SMD] −0.56; 95% CI −0.77 to −0.35, P<.001), depression (pooled SMD −0.43; 95% CI −0.63 to −0.22, P<.001), and stress (pooled SMD −0.73; 95% CI −1.27 to −0.19, P=.008). In comparison to active controls, sensitivity analyses did not support either condition for anxiety (pooled SMD −0.18; 95% CI −0.98 to 0.62, P=.66) or depression (pooled SMD −0.28; 95% CI −0.75 to −0.20, P=.25). In contrast to a comparison intervention, neither condition was supported in sensitivity analyses for anxiety (pooled SMD −0.10; 95% CI −0.39 to 0.18, P=.48) or depression (pooled SMD −0.33; 95% CI −0.43 to 1.09, P=.40).
The findings suggest Web-based and computer-delivered interventions can be effective in improving students’ depression, anxiety, and stress outcomes when compared to inactive controls, but some caution is needed when compared to other trial arms and methodological issues were noticeable. Interventions need to be trialed on more heterogeneous student samples and would benefit from user evaluation. Future trials should address methodological considerations to improve reporting of trial quality and address post-intervention skewed data.
PMCID: PMC4051748  PMID: 24836465
systematic review; meta-analysis; intervention; universities; students; mental health; depression; anxiety; health promotion
5.  TTC7A mutations disrupt intestinal epithelial apicobasal polarity  
Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain–7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development.
PMCID: PMC3871247  PMID: 24292712
7.  PRKDC mutations in a SCID patient with profound neurological abnormalities  
The Journal of Clinical Investigation  2013;123(7):2969-2980.
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs; encoded by PRKDC) functions in DNA non-homologous end-joining (NHEJ), the major DNA double strand break (DSB) rejoining pathway. NHEJ also functions during lymphocyte development, joining V(D)J recombination intermediates during antigen receptor gene assembly. Here, we describe a patient with compound heterozygous mutations in PRKDC, low DNA-PKcs expression, barely detectable DNA-PK kinase activity, and impaired DSB repair. In a heterologous expression system, we found that one of the PRKDC mutations inactivated DNA-PKcs, while the other resulted in dramatically diminished but detectable residual function. The patient suffered SCID with reduced or absent T and B cells, as predicted from PRKDC-deficient animal models. Unexpectedly, the patient was also dysmorphic; showed severe growth failure, microcephaly, and seizures; and had profound, globally impaired neurological function. MRI scans revealed microcephaly-associated cortical and hippocampal dysplasia and progressive atrophy over 2 years of life. These neurological features were markedly more severe than those observed in patients with deficiencies in other NHEJ proteins. Although loss of DNA-PKcs in mice, dogs, and horses was previously shown not to impair neuronal development, our findings demonstrate a stringent requirement for DNA-PKcs during human neuronal development and suggest that high DNA-PK protein expression is required to sustain efficient pre- and postnatal neurogenesis.
PMCID: PMC3999051  PMID: 23722905
8.  Vascular invasion in hepatocellular carcinoma: is there a correlation with MRI? 
The British Journal of Radiology  2012;85(1014):736-744.
Hepatocellular carcinoma (HCC) is one of the commonest malignancies worldwide. Prognosis is predicted by size at diagnosis, vascular invasion and tumour proliferation markers. This study investigates if MRI features of histologically proven HCCs correlate with vascular invasion.
Between 2006 and 2008, 18 consecutive patients, with a total of 27 HCCs, had comprehensive MRI studies performed at our institution within a median of 36 days of histology sampling. Each lesion was evaluated independently on MRI by 3 radiologists (blinded to both the radiology and histopathology reports) using a 5-point confidence scale for 23 specific imaging features. The mean of the rating scores across readers was calculated to determine interobserver consistency. The most consistent features were then used to examine the value of features in predicting vascular invasion, using a χ2 test for trend, having eliminated those features without sufficient variability.
22 of the 23 imaging features showed sufficient variability across lesions. None of these significantly correlated with the presence of vascular invasion, although a trend was identified with the presence of washout in the portal venous phase on MRI and the median size of lesions, which was greater with vascular invasion.
This study suggests that no single MRI feature accurately predicts the presence of vascular invasion in HCCs, although a trend was seen with the presence of washout in the portal venous phase post gadolinium. Larger prospective studies are required to investigate this further.
PMCID: PMC3474106  PMID: 21385912
9.  Internet chemotherapy information: impact on patients and health professionals 
British Journal of Cancer  2012;106(4):651-657.
Reliable information can improve patients' knowledge of chemotherapy. As internet chemotherapy information (ICI) is increasingly viewed as a valuable patient education tool, we investigated the impact of ICI on patient care and analysed health professionals' (HPs') attitudes towards ICI.
The following questionnaires were distributed: (1) self-administered questionnaire randomly given to 261 patients receiving chemotherapy (80% returned); and (2) separate questionnaire given to 58 HPs at the same UK Oncology Centre (83% returned).
Just over half of the patient respondents accessed the internet regularly. They were younger, with higher incomes and qualifications. Key search topics included chemotherapy modes of action, symptom management and treatment success, and most considered ICI useful. More than half wanted to discuss ICI with HPs but most did not get the opportunity. Although the majority of HP respondents supported the need for patients to retrieve ICI, most questioned the accuracy of ICI and did not routinely recommend its use.
This study has shown that ICI is generally perceived by patients to be a valuable information resource. Given the potential impact of ICI, the following should be addressed in future studies: (1) inequalities in accessing ICI; (2) maintaining the quality of ICI (with clear guidance on recommended websites); (3) bridging the gap between the perception of ICI by patients and HPs; (4) integration of ICI with traditional consultation models.
PMCID: PMC3322953  PMID: 22262319
internet; chemotherapy; education of patients; physicians; nurses; health personnel
10.  Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia 
The commonest association of thymic stromal deficiency resulting in T-cell immunodeficiency is the DiGeorge syndrome (DGS). This results from abnormal development of the third and fourth pharyngeal arches and is most commonly associated with a microdeletion at chromosome 22q11 though other genetic and non-genetic causes have been described. The immunological competence of affected individuals is highly variable, ranging from normal to a severe combined immunodeficiency when there is complete athymia. In the most severe group, correction of the immunodeficiency can be achieved using thymus allografts which can support thymopoiesis even in the absence of donor-recipient matching at the major histocompatibility loci. This review focuses on the causes of DGS, the immunological features of the disorder, and the approaches to correction of the immunodeficiency including the use of thymus transplantation.
PMCID: PMC3814041  PMID: 24198816
DiGeorge syndrome; immunodeficiency; thymus transplantation; 22q11 deletion; T-cell development
11.  Lung cancer incidence and survival in different ethnic groups in South East England 
British Journal of Cancer  2011;105(7):1049-1053.
This study aimed to examine the incidence and survival of lung cancer patients from several different ethnic groups in a large ethnically diverse population in the United Kingdom.
Data on residents of South East England diagnosed with lung cancer between 1998 and 2003 were extracted from the Thames Cancer Registry database. Age- and socioeconomic deprivation-standardised incidence rate ratios were calculated for males and females in each ethnic group. Overall survival was examined using Cox regression, adjusted for age, socioeconomic deprivation, stage of disease and treatment. Results are presented for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese patients, apart from female survival results where only the White, South Asian and Black ethnic groups were analysed.
Compared with other ethnic groups of the same sex, Bangladeshi men, White men and White women had the highest incidence rates. Bangladeshi men had consistently higher survival estimates compared with White men (fully adjusted hazard ratio 0.46; P<0.001). Indian (0.84; P=0.048), Black Caribbean (0.87; P=0.47) and Black African (0.68; P=0.007) men also had higher survival estimates. South Asian (0.73; P=0.006) and Black (0.74; P=0.004) women had higher survival than White women.
Smoking prevention messages need to be targeted for different ethnic groups to ensure no groups are excluded. The apparent better survival of South Asian and Black patients is surprising, and more detailed follow-up studies are needed to verify these results.
PMCID: PMC3185928  PMID: 21863024
ethnicity; lung cancer; incidence; survival
12.  Allogeneic hematopoietic stem cell transplantation for Leukocyte Adhesion Deficiency 
Pediatrics  2009;123(3):836-840.
Leukocyte Adhesion Deficiency (LAD) is a rare primary immune disorder caused by defects of the CD18 β-integrin molecule on immune cells. The condition usually presents in early infancy and is characterised by deep tissue infections, leukocytosis with impaired formation of pus and delayed wound healing. Allogeneic haematopoietic stem cell transplantation (HSCT) offers the possibility of curative therapy, and with patient numbers at any individual centre being limited, we surveyed the transplant experience at 14 centres worldwide.
The course of 36 children with a confirmed diagnosis of LAD who underwent HSCT between 1993 and 2007 was retrospectively analysed. Data was collected by the registries of the European Society for Immunodeficiencies (ESID)/European Group for Blood and Marrow Transplantation (EBMT), and the Center for International Blood and Marrow Transplant Research (CIBMTR)
At median followup of 62 months (extending to 14 years) overall survival was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced intensity conditioning (RIC) in 8 patients, with no deaths in this subgroup. Survival after matched family donor and unrelated donor transplants was similar, with 11/14 matched family donor and 12/14 unrelated donor recipients alive; mortality was greatest following haplo-identical transplants, where 4/8 children did not survive. Twenty seven transplant recipients are alive, with full donor engraftment in 17 cases, mixed multi-lineage chimerism in 7 patients, and mononuclear cell restricted chimerism in a further 3 cases.
HSCT offers long term benefit in LAD and should be considered as an early therapeutic option if a suitable HLA-matched stem cell donation is available. Reduced intensity conditioning was particularly safe, and mixed donor chimersim appears sufficient to prevent significant symptoms, although careful long term monitoring will be required for these patients.
PMCID: PMC3380632  PMID: 19255011
Leukocyte adhesion deficiency; Stem cell transplantation; Reduced Intensity Conditioning
13.  Clinical Features and Outcome of Patients With IRAK-4 and MyD88 Deficiency 
Medicine  2010;89(6):403-425.
Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries. The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 25% and 25% of patients). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%).
PMCID: PMC3103888  PMID: 21057262
14.  Investigation of low 5-year relative survival for breast cancer in a London cancer network 
British Journal of Cancer  2010;103(7):1076-1080.
Breast cancer 5-year relative survival is low in the North East London Cancer Network (NELCN).
We compared breast cancer that was diagnosed during 2001–2005 with that in the rest of London.
North East London Cancer Network women more often lived in socioeconomic quintile 5 (42 vs 21%) and presented with advanced disease (11 vs 7%). Cox regression analysis showed the survival difference (hazard ratio: 1.27, 95% confidence interval (CI): 1.15–1.41) reduced to 1.00 (95% CI: 0.89–1.11) after adjustment for age, stage, socioeconomic deprivation, ethnicity and treatment. Major drivers were stage and deprivation. Excess mortality was in the first year.
Late diagnosis occurs in NELCN.
PMCID: PMC2965868  PMID: 20736945
breast cancer; stage; socioeconomic deprivation; survival; cancer network; cancer inequalities
15.  Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours 
British Journal of Cancer  2011;105(4):586-591.
Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T.
From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity.
In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype.
Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age.
PMCID: PMC3170966  PMID: 21792198
ataxia telangiectasia; ATM; ATM kinase; lymphoma; breast cancer
16.  Satya Bhushan Kapur 
BMJ : British Medical Journal  2008;336(7655):1255.
PMCID: PMC2405850
17.  Mutations in the signal transducer and activator of transcription 3 (STAT3) and diagnostic guidelines for the Hyper-IgE Syndrome 
The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in STAT3 and severe reductions of Th17 cells.
To determine whether there is a correlation between the genotype and phenotype of HIES patients and to establish diagnostic criteria to distinguish between STAT3 mutated and STAT3 wild-type patients.
We collected clinical data, determined Th17 cell numbers, and sequenced STAT3 100 patients with a strong clinical suspicion of HIES and serum IgE >1000 IU/mL. explored diagnostic criteria by using a machine-learning approach to identify which features best predict a STAT3 mutation.
In 64 patients we identified 31 different STAT3 mutations, 18 of which are novel. These included mutations at splice sites and outside the previously implicated DNA-binding and SH2 domains. A combination of five clinical features predicted STAT3 mutations with 85% accuracy. Th17 cells were profoundly reduced in patients harboring STAT3 mutations, while 10 out of 13 patients without mutations had low (<1%) Th17 cells but were distinct markedly reduced IFN-γ producing CD4+ T cells.
We propose the following diagnostic guidelines for STAT3-deficient HIES: Possible: IgE >1000 IU/mL plus a weighted score of clinical features >30 based on recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high palate. Probable: Above plus lack of Th17 cells or a family history for definitive HIES. Definitive: Above plus a dominant-negative heterozygous mutation in STAT3.
PMCID: PMC2878129  PMID: 20159255
Hyper-IgE Syndrome; HIES; Job syndrome; Th17 cells; STAT3-mutations; diagnostic guidelines
18.  Suicide in cancer patients in South East England from 1996 to 2005: a population-based study 
British Journal of Cancer  2009;101(1):198-201.
BACKGROUND: Studies from around the world have shown that suicide risk is increased in cancer patients, but no previous detailed analysis has been carried out in England.
METHODS: We calculated standardised mortality ratios (SMRs) for suicide in 206 129 men and 211 443 women diagnosed with cancer in South East England between 1996 and 2005, relative to suicide rates in the general population.
RESULTS: We found a significantly increased risk of suicide in men (SMR 1.45, 95% confidence interval (CI) 1.20–1.73) and a moderately increased risk in women (SMR 1.19, 95% CI 0.88–1.57). In both sexes, relative risk of suicide was greatest in the first year after cancer diagnosis (SMR for men 2.42, 95% CI 1.84–3.13; SMR for women 1.44, 95% CI 0.82–2.33), and was also greater in individuals diagnosed with types of cancer with high fatality (SMR for men 2.67, 95% CI 1.71–3.97; SMR for women 2.17, 95% CI 0.80–4.73).
CONCLUSION: There is a critical period immediately after the diagnosis of cancer during which the excess risk of suicide is particularly high. Carers need to be aware of the importance of attending to both the physical and emotional needs of cancer patients and cancer survivors.
PMCID: PMC2713698  PMID: 19471277
suicide; standardised mortality ratio; fatality; deprivation
19.  Breast cancer incidence, stage, treatment and survival in ethnic groups in South East England 
British Journal of Cancer  2009;100(3):545-550.
Studies from the US have shown variations in breast cancer incidence, stage distribution, treatment and survival between ethnic groups. Data on 35 631 women diagnosed with breast cancer in South East England between 1998 and 2003 with self-assigned ethnicity information available were analysed. Results are reported for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese women. Age-standardised breast cancer incidence rate ratios, patterns of stage of disease at diagnosis, treatment, overall and breast cancer-specific survival were examined. All ethnic groups studied had lower age-standardised breast cancer incidence rates than White women, with Bangladeshi women having the lowest rate ratio (0.23, 95% CI: 0.20–0.26). White women were the most likely to have a stage recorded at diagnosis (adjusted proportion 75%), and least likely to be diagnosed with metastatic disease (7%). Black African women were the least likely to have a record of cancer surgery (63%) or hormone therapy (32%), and most likely to receive chemotherapy (38%). After fully adjusting for age, socioeconomic deprivation, stage of disease and treatment received, there was no significant variation in breast cancer-specific survival. However, Black African women had significantly worse overall survival (hazard ratio 1.24, P=0.025). These findings suggest that a strategy of earlier detection should be pursued in Black and South Asian women.
PMCID: PMC2658548  PMID: 19127253
ethnicity; breast cancer; incidence; stage; treatment; survival
20.  Trends in the epidemiology of larynx and lung cancer in south-east England, 1985–2004 
British Journal of Cancer  2008;100(1):167-169.
We analysed data on 8987 larynx and 174060 lung cancer patients diagnosed between 1985 and 2004, of which 17.3% of larynx and 35.5% of lung cancers were in females. The age-standardised rates for each cancer declined in both sexes, but since the 1990s, the rates in females over 70 years of age have been diverging.
PMCID: PMC2634675  PMID: 19018256
larynx cancer; lung cancer; epidemiology; trends; incidence
21.  Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial 
Acetaminophen is often used with a non-steriodal anti-inflammatory drug for acute pain. Hitherto, these drugs have had to be given separately, typically at different time intervals. Maxigesic® tablets combine acetaminophen and ibuprofen in clinically appropriate doses to simplify administration and dosage regimen. We compared this combination with each of the constituent drugs for the relief of pain after extraction of third molar teeth.
Adults (more than 16 yr) having one or more wisdom teeth removed under general or local anaesthesia were instructed to take two tablets before operation, then two tablets every 6 h for up to 48 h of: (i) a combination of acetaminophen 500 mg and ibuprofen 150 mg per tablet (Maxigesic®); (ii) acetaminophen 500 mg per tablet alone; or (iii) ibuprofen 150 mg per tablet alone. The primary outcome measure was the area under the curve (AUC) of the 100 mm visual analogue scale pain measurements taken for up to 48 h after surgery, divided by time, at rest and on activity. Pharmacokinetic data were collected in a subset of patients.
The mean (sem) time-corrected AUC on rest and activity, respectively, were: combination group 22.3 (3.2) and 28.4 (3.4); acetaminophen group 33.0 (3.1) and 40.4 (3.3); and ibuprofen group 34.8 (3.2) and 40.2 (3.4); P<0.01 for each of the four comparisons of combination vs constituent drug. There was no pharmacokinetic interaction between acetaminophen and ibuprofen administered together.
Maxigesic® tablets provide superior pain relief after oral surgery to acetaminophen or ibuprofen alone.
PMCID: PMC2791549  PMID: 20007794
anaesthesia, dental; analgesia, postoperative; analgesics non-opioid, acetaminophen; analgesics non-opioid, ibuprofen; non-steroidal anti-inflammatory drugs
24.  Quantum Dots as Reporters in Multiplexed Immunoassays for Biomarkers of Exposure to Agrochemicals 
Analytical letters  2007;40(7):1423-1433.
The application of quantum dots (QDs) as labels in immunoassay microarrays for the multiplex detection of 3-phenoxybenzoic acid (PBA) and atrazine-mercapturate (AM) has been demonstrated. PBA and AM are biomarkers of exposure to the pyrethroid insecticides and to the herbicide atrazine, respectively. Microarrays were fabricated by microcontact printing of the coating antigens in line patterns onto glass substrates. Competitive immunoassays were successfully performed using QDs (QD560 and QD620) as reporters. The multiplexed immunoassays were characterized by fluorescence microscopy and SEM. The application of QD fluorophores facilitates multiplex assays and therefore can contribute to enhanced throughput in biomonitoring.
PMCID: PMC2600528  PMID: 19079795
Quantum dot; microarrays; immunoassay; microconatct printing; pyrethroid; atrazine
25.  Hearing the patient's voice? Factors affecting the use of patient survey data in quality improvement 
Quality & safety in health care  2005;14(6):428-432.
Objective: To develop a framework for understanding factors affecting the use of patient survey data in quality improvement.
Design: Qualitative interviews with senior health professionals and managers and a review of the literature.
Setting: A quality improvement collaborative in Minnesota, USA involving teams from eight medical groups, focusing on how to use patient survey data to improve patient centred care.
Participants: Eight team leaders (medical, clinical improvement or service quality directors) and six team members (clinical improvement coordinators and managers).
Results: Respondents reported three types of barriers before the collaborative: organisational, professional and data related. Organisational barriers included lack of supporting values for patient centred care, competing priorities, and lack of an effective quality improvement infrastructure. Professional barriers included clinicians and staff not being used to focusing on patient interaction as a quality issue, individuals not necessarily having been selected, trained or supported to provide patient centred care, and scepticism, defensiveness or resistance to change following feedback. Data related barriers included lack of expertise with survey data, lack of timely and specific results, uncertainty over the effective interventions or time frames for improvement, and consequent risk of perceived low cost effectiveness of data collection. Factors that appeared to have promoted data use included board led strategies to change culture and create quality improvement forums, leadership from senior physicians and managers, and the persistence of quality improvement staff over several years in demonstrating change in other areas.
Conclusion: Using patient survey data may require a more concerted effort than for other clinical data. Organisations may need to develop cultures that support patient centred care, quality improvement capacity, and to align professional receptiveness and leadership with technical expertise with the data.
PMCID: PMC1744097  PMID: 16326789

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