Richard G. Feltbower

Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: a randomised controlled trial

BACKGROUND Infection with Helicobacter pylori is the main cause of peptic-ulcer disease. Treatment of this infection might lower the prevalence of dyspepsia in the community and improve quality of life. We investigated this possibility in a double-blind randomised controlled trial. METHODS Individuals aged 40-49 years were randomly selected from the lists of 36 primary-care centres. A researcher interviewed participants with a validated dyspepsia questionnaire and the psychological general wellbeing index (PGWB). H. pylori status was assessed by the carbon-13-labelled urea breath test. Infected participants were randomly assigned active treatment (omeprazole 20 mg, clarithromycin 250 mg, and tinidazole 500 mg, each twice daily for 7 days) or identical placebo. Participants were followed up at 6 months and 2 years. FINDINGS Of 32,929 individuals invited, 8455 attended and were eligible; 2324 were positive for H. pylori and were assigned active treatment (1161) or placebo (1163). 1773 (76%) returned at 2 years. Dyspepsia or symptoms of gastro-oesophageal reflux were reported in 247 (28%) of 880 in the treatment group and 291 (33%) of 871 in the placebo group (absolute-risk reduction 5% [95% CI 1-10]). H. pylori treatment had no significant effect on quality of life (mean difference in PGWB score between groups 0.86 [-0.33 to 2.05]). INTERPRETATION Community screening and treatment for H. pylori produced only a 5% reduction in dyspepsia. This small benefit had no impact on quality of life.

Acute Complications and Drug Misuse Are Important Causes of Death for Children and Young Adults With Type 1 Diabetes: Results from the Yorkshire Register of Diabetes in Children and Young Adults

OBJECTIVE—To examine mortality rates and causes of death among subjects diagnosed with type 1 diabetes aged ≤29 years. RESEARCH DESIGN AND METHODS— Subjects with type 1 diabetes from a population-based register in Yorkshire, U.K., diagnosed between 1978 and 2004 were linked to the U.K. National Health Service Central Register for death notifications. Deaths were coded using ICD-9 (1979–2000) and ICD-10 (2001–2005). Standardized mortality ratios (SMRs) were calculated using expected numbers of deaths from U.K. mortality rates by cause of death and age at diagnosis. RESULTS—A total of 4,246 individuals were followed up, providing 50,471 person-years of follow-up. Mean follow-up length was 12.8 years for individuals aged 0–14 years and 8.3 for those aged 15–29 years. Overall, 108 patients died, of whom 77 (71%) were male. A total of 74 (1.7/1,000 person-years) deaths occurred in inidividuals aged 0–14 years and 34 (4.6/1,000 person-years) in those aged 15–29 years. The SMR was 4.7 (95% CI 3.8–5.6) overall, similar for males and females, but higher for individuals aged 15–29 years (SMR 6.2 [95% CI 4.3–8.6]) compared with those aged 0–14 years (4.2 [3.3–5.3]). The SMR rose with increasing disease duration. A total of 47 of 108 deaths (44%) occurred from diabetes complications, 32 of which were acute and 15 chronic. Twenty-two percent (n = 24) of deaths were attributed to accidents or violence (SMR 2.1 [95% CI 1.4–3.2]), including six suicides. Sixteen percent of all deaths were related to drug misuse (including insulin but excluding tobacco and alcohol) (SMR 6.4 [95% CI 3.7–10.2]). CONCLUSIONS—Subjects with type 1 diabetes diagnosed under 30 years of age had a 4.7-fold excess mortality risk. Nearly half of the deaths were due to acute or chronic complications of diabetes. Drug misuse–related deaths may be an emerging trend in this population warranting further investigation.

Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989

Aims/hypothesisThe aims of this study were to provide a contemporary picture of mortality and causes of death in Europe following a diagnosis of type 1 diabetes made before the 15th birthday, and to examine excess mortality by country for possible links to incidence level or national prosperity.MethodsThirteen population-based EURODIAB registers in 12 countries followed-up 28,887 children diagnosed since 1989, either by record linkage to population registers or through contact with doctors providing care.ResultsThere were 141 deaths in the cohort during 219,061 person-years of follow-up compared with 69.1 deaths expected from national mortality rates, a standardised mortality ratio (SMR) of 2.0 (95% CI 1.7–2.4). The SMR varied from 0 to 4.7 between countries, but showed little relationship with the country’s incidence rate or gross domestic product (US

The proportion of upper gastrointestinal symptoms in the community associated with helicobacter pylori , lifestyle factors, and nonsteroidal anti-inflammatory drugs

per capita). The SMR did not change significantly with attained age, calendar period or time since diagnosis. The female SMR (2.7; 95% CI 2.0–3.5) was greater than the male SMR (1.8; 95% CI 1.4–2.2), although absolute numbers of excess deaths were similar in the two sexes. One-third of deaths were classified as directly attributable to diabetes (many with mention of ketoacidosis) and half were unrelated to diabetes. There was a non-significant excess of accidental/violent deaths (48 observed vs 40.7 expected; SMR 1.2; 95% CI 0.9–1.6) but little excess in suicides (11 observed, 10.2 expected; SMR 1.1; 95% CI 0.5–1.9).Conclusions/interpretationBefore the onset of late complications, significant excess mortality existed following the diagnosis of type 1 diabetes in childhood, even in recent years. Variation between countries in this excess could not be explained.

Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK.

OBJECTIVE:Upper gastrointestinal disorders are common in the community, yet the determinants of these symptoms are poorly characterized. The association between upper gastrointestinal symptoms and Helicobacter pylori (H. pylori), socioeconomic status, nonsteroidal antiinflammatory drug (NSAID) use, smoking, alcohol, and coffee intake was assessed in a cross-sectional survey.METHODS:Subjects between the ages of 40–49 yr were randomly selected from the lists of 36 primary care centers. Participants attended their local primary care center and were interviewed by a researcher using a validated dyspepsia questionnaire. H. pylori status was determined by a nonfasting 13C-urea breath test.RESULTS:A total of 32,929 subjects were invited, and 8,407 (25%) attended and were eligible. Of these, 2,329 (28%) were H. pylori positive and 3,177 (38%) had dyspepsia. Also, 44% of H. pylori-infected participants reported dyspepsia compared with 36% of uninfected subjects [odds ratio = 1.39; 95% confidence interval (CI) 1.26–1.53]. H. pylori infection remained a significant risk factor for dyspepsia in a multiple logistic regression model (odds ratio = 1.21; 95% CI 1.09–1.34), suggesting that 5% of dyspepsia in the population is attributable to H. pylori. NSAIDs, low educational attainment, renting accommodation, absence of central heating, sharing a bed with siblings, and being married were also significantly associated with dyspepsia in this model. Smoking, but not drinking alcohol or coffee, was marginally associated with dyspepsia, but this finding was not robust. These factors were not associated with any dyspepsia subtype.CONCLUSIONS:H. pylori is significantly associated with dyspepsia and may be responsible for 5% of upper gastrointestinal symptoms in the community.

The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial

Abstract. Against the background of the increasing incidence of many immune mediated childhood conditions, this study aimed to identify recent time trends and ethnic patterns of childhood nephrotic syndrome. A population-based cohort of children (0–15 years) diagnosed according to strict criteria with nephrotic syndrome (NS) was ascertained within the northern UK region of Yorkshire between 1987 and 1998. South Asian ethnicity was assigned based on the child’s full name using a dedicated computer algorithm and expert individual checks. NS was diagnosed in 194 children, 170 (88%) of whom were steroid sensitive. The incidence of steroid sensitive NS was 2.0/100,000 pyrs (95% CI 1.7–2.3), peaking in 1–4 year olds (4.1/100,000 pyrs). Over the 12-year study period incidence rates of steroid sensitive NS were fairly stable although south Asian children displayed significantly higher rates than non-south Asians (P<0.01). The size of our population-based series reflects the relative rarity of paediatric nephrotic syndrome but is nonetheless recent and includes larger numbers than previous reports. The absence of any increase in incidence over the last decade contrasts with other paediatric immune mediated conditions such as asthma and diabetes.

Type 2 and other forms of diabetes in 0–30 year olds: a hospital based study in Leeds, UK

Economic models have suggested that population Helicobacter pylori screening and treatment may be a cost‐effective method of reducing mortality from gastric cancer. These models are conservative as they do not consider that the programme may reduce health service peptic ulcer and other dyspepsia costs. We have evaluated the economic impact of population H. pylori screening and treatment over 2 years in a randomized controlled trial and have incorporated the results into an economic model exploring the impact of H. pylori eradication on peptic ulcer disease and gastric cancer.

Patient-reported outcomes of cancer survivors in England 1-5 years after diagnosis: a cross-sectional survey.

Background and Aims: Following recent reports of increased numbers of adolescents being diagnosed with the adult or type 2 form of diabetes we aimed to describe the prevalence of both type 2 and other forms of diabetes in an urban population of children and young people in northern England. Methods: A hospital based cross sectional study was performed in patients aged ≤30 years attending diabetic clinics in Leeds during the year 2000. Results: A total of 677 subjects were identified, of whom 621 (92%) and 37 (5%) had type 1 and type 2 diabetes respectively. Four patients had confirmed maturity onset diabetes of the young, while the cause was uncertain for four. Median age of all patients was 22 years, with 396 (58%) aged 20–30; 32/37 patients with type 2 diabetes were aged 20–30. The prevalence of type 2 diabetes was 0.13 per 1000 overall, compared to 2.2 per 1000 for patients with type 1 diabetes. Of all type 2 diabetes patients, 24% were south Asian compared to 5% of the background population; 87% were categorised into the two least affluent tertiles of the Townsend score. This link with deprivation was not explained by the proportion of Asian patients across tertiles (approximately 25%). Conclusions: This study shows extremely low prevalence of type 2 diabetes in 10–19 year olds, but will provide a baseline for future comparisons. Overall, type 2 diabetes is seen more commonly in south Asians, and an association with deprivation is suggested.

Rates of inclusion of teenagers and young adults in England into National Cancer Research Network clinical trials: Report from the National Cancer Research Institute (NCRI) Teenage and Young Adult Clinical Studies Development Group

Objectives To determine the feasibility of collecting population-based patient-reported outcome measures (PROMs) in assessing quality of life (QoL) to inform the development of a national PROMs programme for cancer and to begin to describe outcomes in a UK cohort of survivors. Design Cross-sectional postal survey of cancer survivors using a population-based sampling approach. Setting English National Health Service. Participants 4992 breast, colorectal, prostate and non-Hodgkins lymphoma (NHL) survivors 1–5 years from diagnosis. Primary and secondary outcome measures Implementation issues, response rates, cancer-specific morbidities utilising items including the EQ5D, tumour-specific subscales of the Functional Assessment of Cancer Therapy and Social Difficulties Inventory. Results 3300 (66%) survivors returned completed questionnaires. The majority aged 85+ years did not respond and the response rates were lower for those from more deprived area. Response rates did not differ by gender, time since diagnosis or cancer type. The presence of one or more long-term conditions was associated with significantly lower QoL scores. Individuals from most deprived areas reported lower QoL scores and poorer outcomes on other measures, as did those self-reporting recurrent disease or uncertainty about disease status. QoL scores were comparable at all time points for all cancers except NHL. QoL scores were lower than those from the general population in Health Survey for England (2008) and General Practice Patient Survey (2012). 47% of patients reported fear of recurrence, while 20% reported moderate or severe difficulties with mobility or usual activities. Bowel and urinary problems were common among colorectal and prostate patients. Poor bowel and bladder control were significantly associated with lower QoL. Conclusions This method of assessing QoL of cancer survivors is feasible and acceptable to most survivors. Routine collection of national population-based PROMs will enable the identification of, and the support for, the specific needs of survivors while allowing for comparison of outcome by service provider.

An association between type 1 diabetes and idiopathic generalized epilepsy

Poor inclusion rates into clinical trials for teenagers and young adults (TYA; aged 13–24 years) have been assumed but not systematically investigated in England. We analysed accrual rates (AR) from 1 April 2005 up to 31 March 2007 to National Cancer Research Network (NCRN) Phase III trials for the commonest tumour types occurring in TYA and children: leukaemia, lymphoma, brain and central nervous system, bone sarcomas and male germ cell tumours. AR for 2005–2007 were 43.2% for patients aged 10–14 years, 25.2% for patients aged 15–19 years, and 13.1% for patients aged 20–24 years in the tumour types analysed. Compared with accrual from 1 April 2005 to 31 March 2006, AR between 1 April 2006 and 31 March 2007 increased for those aged 10–14 and 15–19 years, but fell for those aged 20–24 years. AR varied considerably among cancer types. Despite four trials being available, patients over 16 years with central nervous system tumours were not recruited. Rates of participation in clinical trials in England from 2005 to 2007 were much lower for TYA older than 15 years compared with children and younger teenagers. The variations in open trials, trial age eligibility criteria and extent of trial activation in treatment centres in part explain this observation. Other possible influences, such as difficulties associated with the consent of TYA require further evaluation. Closer dialogue between those involved in planning and running trials for children and for adults is necessary to improve trial availability and recruitment. Further research is required to identify trends in trial availability and accrual for those tumours constituting the remaining 26% of TYA cancers.