Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding. METHODS: We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96. FINDINGS: Between Sept 14, 2012, and Nov 22, 2017, 30 166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9-6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41-2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62-4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14-0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55-3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients). INTERPRETATION: H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term. FUNDING: National Institute for Health and Care Research Health Technology Assessment.

Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: evidence from a National Audit of Cancer Diagnosis in Primary Care.

Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the 'patient interval'). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consultations with general practitioners among 10,297 English patients subsequently diagnosed with one of 18 cancers (bladder, brain, breast, colorectal, endometrial, leukaemia, lung, lymphoma, melanoma, multiple myeloma, oesophageal, oro-pharyngeal, ovarian, pancreatic, prostate, renal, stomach, and unknown primary) using data from of the National Audit of Cancer Diagnosis in Primary Care (2009-2010). Proportions of patients with 'prompt'/'non-prompt' presentation (0-14 or 15+ days from symptom onset, respectively) were described and respective odds ratios were calculated by multivariable logistic regression. The overall median recorded patient interval was 10 days (IQR 0-38). Of all patients, 56% presented promptly. Prompt presentation was more frequent among older or housebound patients (p < 0.001). Prompt presentation was most frequent for bladder and renal cancer (74% and 70%, respectively); and least frequent for oro-pharyngeal and oesophageal cancer (34% and 39%, respectively, p <.001). Using lung cancer as reference, the adjusted odds ratios of non-prompt presentation were 2.26 (95% confidence interval 1.57-3.25) and 0.42 (0.34-0.52) for oro-pharyngeal and bladder cancer, respectively. Sensitivity analyses produced similar findings. Routinely recorded patient interval data reveal considerable variation in the promptness of presentation. These findings can help to prioritise public awareness initiatives and research focusing on symptoms of cancers associated with greater risk of non-prompt presentation, such as oro-pharyngeal and oesophageal cancer.

Gender inequalities in the promptness of diagnosis of bladder and renal cancer after symptomatic presentation: evidence from secondary analysis of an English primary care audit survey.

OBJECTIVES: To explore whether women experience greater delays in the diagnosis of bladder and renal cancer when first presenting to a general practitioner with symptoms caused by those cancers and potential reasons for such gender inequalities. DESIGN: Prospective national audit survey of cancer diagnosis. SETTING: English primary care (2009-2010). PARTICIPANTS: 920 patients with bladder and 398 patients with renal cancer (252 (27%) and 165 (42%), respectively, were women). PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of patients with three or more pre-referral consultations; number of days from first presentation to referral; proportion of patients who presented with haematuria and proportion of patients investigated in primary care. RESULTS: Women required three or more prereferral consultations more often than men (27% (95% CI 21% to 33%) vs 11% (9% to 14%) for bladder (p<0.001); and 30% (22% to 39%) vs 18% (13% to 25%) for renal cancer (p=0.025)) and had a greater number of days from presentation to referral. In multivariable analysis (adjusting for age, haematuria status and use of primary care-led investigations), being a woman was independently associated with higher odds of three or more pre-referral consultations (OR=3.29 (2.06 to 5.25, p<0.001) for bladder cancer; and OR=1.90 (1.06 to 3.42, p=0.031) for renal cancer). Although presentation with haematuria was associated with more timely diagnosis of bladder cancer, gender inequalities did not vary by haematuria status for either cancer (p=0.18 for bladder and p=0.27 for renal). Each year in the UK, approximately 700 women with either bladder or renal cancer experience a delayed diagnosis because of their gender, of whom more than a quarter (197, or 28%) present with haematuria. CONCLUSIONS: There are notable gender inequalities in the timeliness of diagnosis of urological cancers. There is a need to both reinforce existing guidelines on haematuria investigation and develop new diagnostic decision aids and tests for patients who present without haematuria.

Intentional and inadvertent non-adherence in adult coeliac disease. A cross-sectional survey.

Adherence to a gluten-free diet is the mainstay of treatment for coeliac disease. Non-adherence is common as the diet is restrictive and can be difficult to follow. This study aimed to determine the rates of intentional and inadvertent non-adherence in adult coeliac disease and to examine the factors associated with both. A self-completion questionnaire was mailed to adult coeliac patients identified from the computer records of 31 family practices within the North East of England. We received 287 responses after one reminder. Intentional gluten consumption was reported by 115 (40%) of respondents. 155 (54%) had made at least one known mistaken lapse over the same period and 82 (29%) reported neither intentional nor mistaken gluten consumption. Using logistic regression analysis, low self-efficacy, perceptions of tolerance to gluten and intention were found to be independently predictive of intentional gluten consumption. A statistical model predicted 71.8% of cases reporting intentional lapses. Intentional non-adherence to the GFD was found to be common but not as frequent as inadvertent lapses. Distinguishing the factors influencing both intentional and inadvertent non-adherence is useful in understanding dietary self-management in coeliac disease.

Interventions to increase clinical incident reporting in health care.

BACKGROUND: Reporting of adverse clinical events is thought to be an effective method of improving the safety of healthcare. Underreporting of these adverse events is often said to occur with consequence of missing of opportunities to learn from these incidents. A clinical incident can be defined as any occurrence which is not consistent with the routine care of the patient or the routine operation of the institution. OBJECTIVES: To assess the effects of interventions designed to increase clinical incident reporting in healthcare settings. SEARCH METHODS: We searched the the following databases: Cochrane Effective Practice and Organisation of Care Group Specialised Register, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Social Science Citation Index and Science Citation Index (Web of Knowledge), Healthstar (OVID), INSPEC, DHSS-DATA, SIGLE, ISI Conference Proceedings, Web of Science Conference Proceedings Citation Index (Science), Database of Abstracts of Reviews of Effectiveness (DARE). SELECTION CRITERIA: Randomised controlled trials (RCT), controlled before-after studies (CBA) and interrupted time series (ITS) of interventions designed to increase clinical incident reporting in healthcare. DATA COLLECTION AND ANALYSIS: At least two review authors assessed the eligibility of potentially relevant studies, extracted the data and assessed the quality of included studies. MAIN RESULTS: Four studies (one CBA and three ITS studies) met our inclusion criteria and were included in the review. The CBA study showed a significant improvement in incident reporting rates after the introduction of the new reporting system. Just one of the ITS studies showed a statistically significant improved effectiveness of the new reporting system from nine months. The other two studies reported no statistically significant improvements. AUTHORS' CONCLUSIONS: Because of the limitations of the studies it is not possible to draw conclusions for clinical practice. Anyone introducing a system into practice should give careful consideration to conducting an evaluation using a robust design.

Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England.

BACKGROUND: Information from patient surveys can help to identify patient groups and cancers with the greatest potential for improvement in the experience and timeliness of cancer diagnosis. We aimed to examine variation in the number of pre-referral consultations with a general practitioner between patients with different cancers and sociodemographic characteristics. METHODS: We analysed data from 41,299 patients with 24 different cancers who took part in the 2010 National Cancer Patient Experience Survey in England. We examined variation in the number of general practitioner consultations with cancer symptoms before hospital referral to diagnose cancer. Logistic regression was used to identify independent predictors of three or more pre-referral consultations, adjusting for cancer type, age, sex, deprivation quintile, and ethnic group. FINDINGS: We identified wide variation between cancer types in the proportion of patients who had visited their general practitioner three or more times before hospital referral (7·4% [625 of 8408] for breast cancer and 10·1% [113 of 1124] for melanoma; 41·3% [193 of 467] for pancreatic cancer and 50·6% [939 of 1854] for multiple myeloma). In multivariable analysis, with patients with rectal cancer as the reference group, those with subsequent diagnosis of multiple myeloma (odds ratio [OR] 3·42, 95% CI 3·01-3·90), pancreatic cancer (2·35, 1·91-2·88), stomach cancer (1·96, 1·65-2·34), and lung cancer (1·68, 1·48-1·90) were more likely to have had three or more pre-referral consultations; conversely patients with subsequent diagnosis of breast cancer (0·19; 0·17-0·22), melanoma (0·34, 0·27-0·43), testicular cancer (0·47, 0·33-0·67), and endometrial cancer (0·59, 0·49-0·71) were more likely to have been referred to hospital after only one or two consultations. The probability of three or more pre-referral consultations was greater in young patients (OR for patients aged 16-24 years vs 65-74 years 2·12, 95% CI 1·63-2·75; p<0·0001), those from ethnic minorities (OR for Asian vs white 1·73, 1·45-2·08; p<0·0001; OR for black vs white 1·83, 1·51-2·23; p<0·0001), and women (OR for women vs men 1·28, 1·21-1·36; p<0·0001). We identified strong evidence of interactions between cancer type and age group and sex (p<0·0001 for both), and between age and ethnicity (p=0·0013). The model including these interactions showed a particularly strong sex effect for bladder cancer (OR for women vs men 2·31, 95% CI 1·98-2·69) and no apparent ethnic group differences in young patients aged 16-24 years, whilst the only cancers without an apparent age gradient were testicular cancer and mesothelioma. INTERPRETATION: Our findings could help to prioritise and stratify early diagnosis initiatives and research, focusing on patients with cancers and sociodemographic characteristics with the largest potential for improvement. FUNDING: None.

Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control. OBJECTIVES: The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. SEARCH STRATEGY: Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review. SELECTION CRITERIA: Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of  bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included. MAIN RESULTS: A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of  global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review. AUTHORS' CONCLUSIONS: There is no evidence that bulking agents are effective for treating IBS.  There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures.

Psychological treatments for the management of irritable bowel syndrome.

BACKGROUND: No consensus exists on the optimal treatment for irritable bowel syndrome (IBS). Psychological treatments are increasingly advocated but their effectiveness is unclear. OBJECTIVES: To evaluate the efficacy of psychological interventions for the treatment of irritable bowel syndrome. SEARCH STRATEGY: A computer assisted search of MEDLINE, EMBASE, PsychInfo, CINAHL, Web of Science, The Cochrane Library and Google Scholar was performed for the years 1966-2008. Local databases were searched in Europe. SELECTION CRITERIA: Randomised trials comparing single psychological interventions with either usual care or mock interventions in patients over 16 years of age. No language criterion was applied. DATA COLLECTION AND ANALYSIS: The search identified 25 studies that fulfilled the inclusion criteria. The relative risk (RR), risk difference (RD), number needed to treat (NNT) and standardized mean difference (SMD) along with 95% confidence intervals were calculated using a random effects model for each outcome. MAIN RESULTS: Psychological interventions as a group The SMD for symptom score improvement at 2 and 3 months was 0.97 (95% CI 0.29 to 1.65) and 0.62 (95% CI 0.45 to 0.79) respectively compared to usual care. Against placebo, the SMDs were 0.71 (95% CI 0.08 to 1.33) and -0.17 (95% CI -0.45 to 0.11) respectively. For improvement of abdominal pain, the SMDs at 2 and 3 months were 0.54 (95%CI 0.10 to 0.98) and 0.26 (95% CI 0.07 to 0.45) compared to usual care. The SMD from placebo at 3 months was 0.31 (95% CI -0.16 to 0.79). For improvement in quality of life, the SMD from usual care at 2 and 3 months was 0.47 (95%CI 0.11 to 0.84) and 0.31 (95%CI -0.16 to 0.77) respectively. Cognitive behavioural therapy The SMD for symptom score improvement at 2 and 3 months was 0.75 (95% CI -0.20 to 1.70) and 0.58 (95% CI 0.36 to 0.79) respectively compared to usual care. Against placebo, the SMDs were 0.68 (95% CI -0.01 to 1.36) and -0.17 (95% CI -0.45 to 0.11) respectively. For improvement of abdominal pain, the SMDs at 2 and 3 months were 0.45 (95% CI 0.00 to 0.91) and 0.22 (95% CI -0.04 to -0.49) compared to usual care. Against placebo the SMD at 3 months was 0.33 (95% CI -0.16 to 0.82). For improvement in quality of life, the SMDs at 2 and 3 months compared to usual care were 0.44 (95% CI 0.04 to 0.85) and 0.92 (95% CI 0.07 to 1.77) respectively.Interpersonal psychotherapy The RR for adequate relief of symptoms was 2.02 (95% CI 1.13 to 3.62), RD 0.30 (95% CI 0.13 to 0.46), NNT 4 for comparison with care as usual. The SMD for improvement of symptom score was 0.35 (95% CI -0.75 to 0.05) compared with usual care. Relaxation/Stress management The SMD in symptom score improvement at 2 months was 0.50 (95%CI 0.02 to 0.98) compared with usual care. The SMD in improvement of abdominal pain at 3 months was 0.02 (95%CI -0.56 to 0.61) compared with usual care. Long term results Very few long term follow-up results were available. There was no convincing evidence that treatment effects were sustained following completion of treatment for any treatment modality. AUTHORS' CONCLUSIONS: Psychological interventions may be slightly superior to usual care or waiting list control conditions at the end of treatment although the clinical significance of this is debatable. Except for a single study, these therapies are not superior to placebo and the sustainability of their effect is questionable. The meta-analysis was significantly limited by issues of validity, heterogeneity, small sample size and outcome definition. Future research should adhere to current recommendations for IBS treatment trials and should focus on the long-term effects of treatment.

Medication beliefs among patients with inflammatory bowel disease who report low quality of life: a qualitative study.

BACKGROUND: Non-adherence to drug therapy is common in Inflammatory Bowel Disease (IBD). Patients' beliefs about treatment have an important influence on adherence. An in-depth understanding of this area is, therefore, important for patient-centred care. The aim of the study was to assess patients' perspectives and beliefs about their medication and to determine how this relates to medicine taking and other related health behaviour as part of a larger qualitative study on health care related behaviour in patients with IBD. METHODS: Individual semi-structured interviews and focus groups. An iterative approach following principles of grounded theory was applied to data collection and analysis. RESULTS: Main emerging themes were: balance of perceived necessity versus concerns, perceived impact of symptoms and willingness to self-manage medication. There was a clear distinction made between steroids and other preparations. Concerns included the fear of both short and long-term side-effects (mainly steroids), uncertainties about drug interactions and development of long-term immunity. Adapting to and accepting medication use was linked to acceptance of IBD. CONCLUSION: A concordant approach including flexible and pro-active support as well as accurate information is important in assisting patients with IBD to self-manage their medication effectively. Health professionals should be aware that attitudes to medicine taking and other related behaviours may be medicine specific and change over time.

Irritable bowel syndrome.

INTRODUCTION: The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but ranges from about 5% to over 15%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS have an increased likelihood of having a cholecystectomy or hysterectomy compared with people without IBS. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2006 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT(3) receptor antagonists other than alosetron, 5HT(4) receptor agonists (tegaserod), alosetron, antidepressants, antispasmodics, cognitive behaviour therapy, hypnotherapy, insoluble fibre supplementation, loperamide.

The fight for 'health-related normality': a qualitative study of the experiences of individuals living with established inflammatory bowel disease (ibd).

This article reports on the experiences of individuals living with IBD and identifies a range of coping strategies used by them. Qualitative data from 15 individual interviews and three focus groups were analysed using a grounded theory approach. The main focus is on the emergent core concept of 'health-related normality'. A theoretical framework is proposed to explain how individuals with IBD assess their health-related normality, their fight to maintain it and their need to retain the appearance of normality to others. It is concluded that individuals maintain their health-related normality along certain time and context sensitive continuums rather than fitting into a distinct typology.