Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial

ObjectiveTo assess the effectiveness of nurse led follow up in the management of patients with lung cancer.DesignRandomised controlled trial.SettingSpecialist cancer hospital and three cancer units in southeastern England.Participants203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months.InterventionNurse led follow up of outpatients compared with conventional medical follow up.ResultsPatient acceptability of nurse led follow up was high: 75% (203/271) of eligible patients consented to participate. Patients who received the intervention had less severe dyspnoea at 3 months (P=0.03) and had better scores for emotional functioning (P=0.03) and less peripheral neuropathy (P=0.05) at 12 months. Intervention group patients scored significantly better in most satisfaction subscales at 3, 6, and 12 months (P<0.01 for all subscales at 3 months). No significant differences in general practitioners'' overall satisfaction were seen between the two groups. No differences were seen in survival or rates of objective progression, although nurses recorded progression of symptoms sooner than doctors (P=0.01). Intervention patients were more likely to die at home rather than in a hospital or hospice (P=0.04), attended fewer consultations with a hospital doctor during the first 3 months (P=0.004), had fewer radiographs during the first 6 months (P=0.04), and had more radiotherapy within the first 3 months (P=0.01). No other differences were seen between the two groups in terms of the use of resources.ConclusionNurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes.

What is already known on this topic

Most patients with cancer are routinely seen in outpatient clinics for many years despite lack of evidence of effectivenessDoctors and nurses often fail to detect patients'' emotional distress, and patients have little time to raise concerns

What this study adds

Follow up of patients with lung cancer by clinical nurse specialists is safe, acceptable, and cost effectiveBoth patients and general practitioners were highly satisfied with the nurse led model of follow up     

Cost effectiveness analysis of intensive versus conventional follow up after curative resection for colorectal cancer

Objective To determine the cost effectiveness of intensive follow up compared with conventional follow up in patients with colorectal cancer.Design Incremental cost effectiveness analysis recognising differences in follow up strategies, based on effectiveness data from a meta-analysis of five randomised trials.Setting United Kingdom.Main outcome measures Taking a health service perspective, estimated incremental costs effectiveness ratios for each life year gained for five trials and four trials designed for early detection of extramural recurrences (targeted surveillance).Results Based on five year follow up, the numbers of life years gained by intensive follow up were 0.73 for the five trial model and 0.82 for the four trial model. For the five trials, the adjusted net (extra) cost for each patient was £2479 (€3550; $4288) and for each life year gained was £3402, substantially lower than the current threshold of NHS cost acceptability (£30 000). The corresponding values for the four trial model were £2529 and £3077, suggesting that targeted surveillance is more cost effective. The main predictor of incremental cost effectiveness ratios was surveillance costs rather than treatment costs. Judged against the NHS threshold of cost acceptability, the predicted incremental cost threshold was ninefold and the effectiveness threshold was 3%.Conclusions Based on the available data and current costs, intensive follow up after curative resection for colorectal cancer is economically justified and should be normal practice. There is a continuing need to evaluate the efficacy of specific surveillance tools: this study forms the basis for economic evaluations in such trials.     

Insecticide impregnated curtains to control domestic transmission of cutaneous leishmaniasis in Venezuela: cluster randomised trial

ObjectiveTo measure the impact on transmission of leishmaniasis of curtains impregnated with insecticide.DesignCluster randomised controlled trial: household interview survey, observational study of people''s behaviour, entomological study with light trap captures of sandflies inside houses.Setting14 urban sectors in Trujillo, Venezuela.Participants2913 inhabitants of 569 houses.InterventionSectors were paired according to their 12 month cumulative incidence of cutaneous leishmaniasis, one sector in each pair was randomly allocated to receive polyester curtains impregnated with lambdacyhalothrin (intervention group) while the other sector received curtains without insecticide or no curtains (control groups). After 12 months a follow up household survey was conducted.ResultsTransmission of cutaneous leishmaniasis occurred mainly in the domestic setting, with the incidence over 12 months of 4%. The mean number of sandflies per trap per night was 16. After follow up the 12 month incidence of cutaneous leishmaniasis was 0% in the intervention group and 8% in the six pairs in the control group that received unimpregnated curtains (mean difference 8, 95% confidence interval 4.22 to 11.78; P=0.001). There were significantly fewer sandflies in the intervention group (2 v 15, mean difference 13 sandflies per trap; 9 to 17; P<0.001).ConclusionCurtains impregnated with insecticide provide a high degree of protection against indoor transmission of cutaneous leishmaniasis.

What is already known on this topic

The transmission of cutaneous leishmaniasis is increasingly in urban and domestic settingsHouse spraying, space spraying, and insecticide treated material reduce the number of vectors

What this paper adds

Pyrethroid impregnated curtains can considerably reduce the incidence rate of cutaneous leishmaniasis in areas where indoor transmission is predominant     

Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study

ObjectiveTo investigate the importance of sensitisation and exposure to allergens and viral infection in precipitating acute asthma in adults resulting in admission to hospital.DesignCase-control study.SettingLarge district general hospital.Participants60 patients aged 17-50 admitted to hospital over a year with acute asthma, matched with two controls: patients with stable asthma recruited from the outpatient department and patients admitted to hospital with non-respiratory conditions (inpatient controls).ResultsViruses were detected in 31 of 177 patients. The difference in the frequency of viruses detected between the groups was significant (admitted with asthma 26%, stable asthma 18%, inpatient controls 9%; P=0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised and exposed to either mite, cat, or dog allergen than patients with stable asthma (37%) and inpatient controls (15%; P<0.001). Being sensitised and exposed to allergens was an independent associate of the group admitted to hospital (odds ratio 2.3, 95% confidence interval 1.0 to 5.4; P=0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably increased the risk of being admitted with asthma (8.4, 2.1 to 32.8; P=0.002).ConclusionsAllergens and viruses may act together to exacerbate asthma.

What is already known on this topic

Studies on segmental allergen challenge of the lung and experimental rhinovirus infection show synergistic effects between allergens and respiratory virus infectionNo studies have investigated an interaction between sensitisation, exposure to allergens, and virus infections in real life exacerbations of asthma

What this study adds

Allergens and viruses may act together to exacerbate asthma, indicating that domestic exposure to allergens acts synergistically with viruses in sensitised patients, increasing the risk of hospital admissionStrategies to reduce the impact of asthma exacerbations in adults should include interventions directed at both viruses and reducing exposure to allergens     

Longevity of screenwriters who win an academy award: longitudinal study

ObjectiveTo determine whether the link between high success and longevity extends to academy award winning screenwriters.DesignRetrospective cohort analysis.ParticipantsAll screenwriters ever nominated for an academy award.ResultsA total of 850 writers were nominated; the median duration of follow up from birth was 68 years; and 428 writers died. On average, winners were more successful than nominees, as indicated by a 14% longer career (27.7 v 24.2, P=0.004), 34% more total films (23.2 v 17.3, P<0.001), 58% more four star films (4.8 v 3.1, P<0.001), and 62% more nominations (2.1 v 1.3, P<0.001). However, life expectancy was 3.6 years shorter for winners than for nominees (74.1 v 77.7 years, P=0.004), equivalent to a 37% relative increase in death rates (95% confidence interval 10 to 70). After adjustment for year of birth, sex, and other factors, a 35% relative increase in death rates was found (7% to 70%). Additional wins were associated with a 22% relative increase in death rates (3% to 44%). Additional nominations and additional other films in a career otherwise caused no significant increase in death rates.ConclusionThe link between occupational achievement and longevity is reversed in screenwriters who win academy awards. Doubt is cast on simple biological theories for the survival gradients found for other members of society.

What is already known on this topic

High achievement has been associated with decreased all cause mortality for people in many different occupationsSuch an association is compatible with behavioural and biological theories for the role of social determinants

What this study adds

Screenwriters nominated for an academy award show a paradoxical survival pattern, where greater success is associated with a large decrease in life expectancyThe paradox is not easily explained by talent, prestige, financial earnings, material conditions, reverse causality, measurement error, or simple demographicsIt might reflect the unusual lifestyles of writers, where success is not linked to exemplary conduct or control; this underscores the importance of behaviour     

Measuring later health status of high risk infants: randomised comparison of two simple methods of data collection

ObjectiveTo test two methods of providing low cost information on the later health status of survivors of neonatal intensive care.DesignCluster randomised comparison.SettingNine hospitals distributed across two UK health regions. Each hospital was randomised to use one of two methods of follow up.ParticipantsAll infants born ⩽32 weeks'' gestation during 1997 in the study hospitals.MethodFamilies were recruited at the time of discharge. In one method of follow up families were asked to complete a questionnaire about their child''s health at the age of 2 years (corrected for gestation). In the other method the children''s progress was followed by clerks in the local community child health department by using sources of routine information.Results236 infants were recruited to each method of follow up. Questionnaires were returned by 214 parents (91%; 95% confidence interval 84% to 97%) and 223 clerks (95%; 86% to 100%). Completed questionnaires were returned by 201 parents (85%; 76% to 94%) and 158 clerks (67%; 43% to 91%). Most parents found the forms easy to complete, but some had trouble understanding the concept of “corrected age” and hence when to return the form. Community clerks often had to rely on information that was out of date and difficult to interpret.ConclusionNeither questionnaires from parents nor routinely collected health data are adequate methods of providing complete follow up data on children who were born preterm and required neonatal intensive care, though both methods show potential.

What is already known on this topic

Outcome of neonatal intensive care should include later health status not just early mortalityAlthough these data are commonly sought, for various reasons no existing routine system currently delivers the information for ⩾95% of the population (95% representing the minimum acceptable standard)Running one-off studies to gain later follow up data is difficult and costly

What this study adds

Potentially these data could come from parents but to reach 95% ascertainment perhaps 5-10% of parents would require help and support to provide informationExisting data flows may be able to provide the required information if the timing of routine reviews and methods of data recording were harmonised across the United KingdomThe costs attached to introducing such a system seem to be low     

KRAS Mutations in Primary Colorectal Cancer Tumors and Related Metastases: A Potential Role in Prediction of Lung Metastasis

Background

KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status.

Methodology/Principal Findings

KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006).

Conclusions/Significance

Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung.     

Stressful life experiences and risk of relapse of breast cancer: observational cohort study

ObjectiveTo confirm, using an observational cohort design, the relation between severely stressful life experiences and relapse of breast cancer found in a previous case-control study.DesignProspective follow up for five years of a cohort of women newly diagnosed as having breast cancer, collecting data on stressful life experiences, depression, and biological prognostic factors.SettingNHS breast clinic, London; 1991-9.ParticipantsA consecutive series of women aged under 60 newly diagnosed as having a primary operable breast tumour. 202/222 (91%) eligible women participated in the first life experiences interview. 170 (77%) provided complete interview data either up to 5 years after diagnosis or to recurrence.ResultsWe controlled for biological prognostic factors (lymph node infiltration and tumour histology), and found no increased risk of recurrence in women who had had one or more severely stressful life experiences in the year before diagnosis compared with women who did not (hazard ratio 1.01, 95% confidence interval 0.58 to 1.74, P=0.99). Women who had had one or more severely stressful life experiences in the 5 years after diagnosis had a lower risk of recurrence (0.52, 0.29 to 0.95, P=0.03) than those who did not.ConclusionThese data do not confirm an earlier finding from a case-control study that severely stressful life experiences increase the risk of recurrence of breast cancer. Differences in case control and prospective methods may explain the contradictory results. We took the prospective study as the more robust, and the results suggest that women with breast cancer need not fear that stressful experiences will precipitate the return of their disease.

What is already known on this topic

Women with apparently similar tumours at the time of presentation with breast cancer differ considerably in their disease-free survival and overall survivalSuch differences in outcome may well be explained by host and environmental factors, which could include psychological and social variablesData on the relation between severely stressful life experiences and cancer progression have been contradictory

What this study adds

Women who have a severely stressful life experience in the year before being diagnosed with breast cancer, or in the five years afterwards, do not seem to be at increased risk of developing a recurrence of the diseaseWomen with breast cancer need not fear that stressful experiences will precipitate the return of their disease.     

Influence of hospital and clinician workload on survival from colorectal cancer: cohort study

ObjectiveTo determine whether clinician or hospital caseload affects mortality from colorectal cancer.DesignCohort study of cases ascertained between 1990 and 1994 by a region-wide colorectal cancer register.ResultsOf the 3217 new patients registered over the period, 1512 (48%) died before 31 December 1996. Strong predictors of survival both in a logistic regression (fixed follow up) and in a Cox''s proportional hazards model (variable follow up) were Duke''s stage, the degree of tumour differentiation, whether the liver was deemed clear of cancer by the surgeon at operation, and the type of intervention (elective or emergency and curative or palliative intent). In a multilevel model, surgeon’s caseload had no significant effect on mortality at 2 years. Hospital workload, however, had a significant impact on survival. The odds ratio for death within 2 years for cases managed in a hospital with a caseload of between 33 and 46 cases per year, 47 and 54 cases per year, and ⩾55 cases per year (compared to one with ≤23 cases per year) were respectively 1.48 (95% confidence interval 1.03 to 2.13), 1.52 (1.08 to 2.13), and 1.18 (0.83 to 1.68).ConclusionsThere was no detectable caseload effect for surgeons managing colorectal cancer, but survival of patients treated in hospitals with caseloads above 33 cases per year was slightly worse than for those treated in hospitals with fewer caseloads. Imprecise measurement of clinician specific “events rates” and the lack of routinely collected case mix data present major challenges for clinical audit and governance in the years ahead.

Key messages

• Various benefits have been described for multidisciplinary cancer care, but the precise relation between a surgeon''s or hospital''s caseload and the outcome for the patient is not known
• Any investigation of a caseload effect at the hospital or practitioner level has to simultaneously account for each factor and adjust adequately for case mix
• Surgeon had no significant effect on caseload, but patients treated in hospitals with low caseloads (<33 cases per year) had a slightly better survival at 2 years than those treated in hospitals with a higher caseload
• Defining surgical expertise in terms of volume of activity may be a misdirected and imprecise yardstick for the quality of cancer care; other aspects of the organisation of services may be far more important

     

The Impact of National Institutes of Health Funding on U.S. Cardiovascular Disease Research

Background

Intense interest surrounds the recent expansion of US National Institutes of Health (NIH) budgets as part of economic stimulus legislation. However, the relationship between NIH funding and cardiovascular disease research is poorly understood, making the likely impact of this policy change unclear.

Methods

The National Library of Medicine''s PubMed database was searched for articles published from 1996 to 2006, originating from U.S. institutions, and containing the phrases “cardiolog,” “cardiovascular,” or “cardiac,” in the first author''s department. Research methodology, journal of publication, journal impact factor, and receipt of NIH funding were recorded. Differences in means and trends were tested with t-tests and linear regression, respectively, with P≤0.05 for significance.

Results

Of 117,643 world cardiovascular articles, 36,684 (31.2%) originated from the U.S., of which 10,293 (28.1%) received NIH funding. The NIH funded 40.1% of U.S. basic science articles, 20.3% of overall clinical trials, 18.1% of randomized-controlled, and 12.2% of multicenter clinical trials. NIH-funded and total articles grew significantly (65 articles/year, P<0.001 and 218 articles/year, P<0.001, respectively). The proportion of articles receiving NIH funding was stable, but grew significantly for basic science and clinical trials (0.87%/year, P<0.001 and 0.67%/year, P = 0.029, respectively). NIH-funded articles had greater journal impact factors than non NIH-funded articles (5.76 vs. 3.71, P<0.001).

Conclusions

NIH influence on U.S. cardiovascular research expanded in the past decade, during the period of NIH budget doubling. A substantial fraction of research is now directly funded and thus likely sensitive to budget fluctuations, particularly in basic science research. NIH funding predicts greater journal impact.     

Analysis of the Relationships between Clinicopathologic Factors and Survival in Gallbladder Cancer following Surgical Resection with Curative Intent

Background

This study elucidated the relationships between various clinicopathologic factors and the outcome of patients with gallbladder cancer (GBC) treated by surgical resection with curative intent.

Methods

Between January 2003 and January 2011, 76 patients with GBC underwent surgical resection with curative intent at our department. We then conducted a retrospective analysis of clinicopathologic data. Fourteen clinicopathological variables were selected for univariate and multivariate analysis to evaluate their influence on the outcome.

Results

The actuarial 1-, 3-, and 5-year survival rates in the 76 resected cases were 56.6%, 32.7%, and 23.8%, respectively. The univariate analysis revealed that curative resection (P<0.001), lymph node metastasis (P<0.001), AJCC stage (P = 0.030), tumor location (P = 0.008), histologic differentiation (P = 0.028), intraoperative blood loss (P = 0.011), and preoperative jaundice (P = 0.012) were significant risk factors for survival. Multivariate analysis revealed that noncurative resection and tumor location on gallbladder neck were significant risk factors for poor outcome. Among jaundiced patients, we discovered that gallbladder carcinoma with tumor thrombus in common bile duct (CBD) was very rare but with relatively special clinical manifestation and characteristic radiography manifestation. The prognosis of gallbladder carcinoma with tumor thrombus in CBD after surgical procedure was apparently better than gallbladder carcinoma with invasion of hilar tissues.

Conclusions

Curative surgical resection remains the only effective approach to the treatment of GBC. This series confirm that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (when R0 resection is achievable). Gallbladder carcinoma with tumor thrombus in CBD has special clinical characteristics, which need to be awared by radiologists and clinicians.     

Identification of Kininogen-1 as a Serum Biomarker for the Early Detection of Advanced Colorectal Adenoma and Colorectal Cancer

Background

Serum markers represent potential tools for the detection of colorectal cancer (CRC). The aim of this study was to obtain proteomic expression profiles and identify serum markers for the early detection of CRC.

Methods

Proteomic profiles of serum samples collected from 35 healthy volunteers, 35 patients with advanced colorectal adenoma (ACA), and 40 patients with CRC were compared using Clinprot technology. Using enzyme-linked immunosorbent assays (ELISAs), 366 sera samples were additionally analyzed, and immunohistochemistry studies of 400 tissues were used to verify the expression of kininogen-1 and its value in the early detection of CRC.

Results

Predicting models were established among the three groups, and kininogen-1 was identified as a potential marker for CRC using Clinprot technology. ELISAs also detected significantly higher serum kininogen-1 levels in ACA and CRC patients compared to controls (P<0.05). Furthermore, the area under the receiver operating characteristic curve (AUC) for serum kininogen-1 in the diagnosis of ACA was 0.635 (P = 0.003), and for serum carcinoembryonic antigen (CEA) was 0.453 (P = 0.358). The sensitivity, specificity, and accuracy of serum kininogen-1 for diagnosing Duke’s stage A and B CRC was 70.13%, 65.88%, and 67.90%, respectively, whereas serum CEA was 38.96%, 85.88%, and 63.58%, respectively. Moreover, immunohistochemistry showed that expression of kininogen-1 was significantly higher in CRC and ACA tissues than in normal mucosa (48.39% vs. 15.58% vs. 0%, P<0.05).

Conclusions

These results suggest that Clinprot technology provides a useful tool for the diagnosis of CRC, and kininogen-1 is a potential serum biomarker for the early detection of advanced colorectal adenoma and CRC.     

Efficacy of handrubbing with alcohol based solution versus standard handwashing with antiseptic soap: randomised clinical trial

ObjectiveTo compare the efficacy of handrubbing with an alcohol based solution versus conventional handwashing with antiseptic soap in reducing hand contamination during routine patient care.DesignRandomised controlled trial during daily nursing sessions of 2 to 3 hours.SettingThree intensive care units in a French university hospital.Participants23 healthcare workers.InterventionsHandrubbing with alcohol based solution (n=12) or handwashing with antiseptic soap (n=11) when hand hygiene was indicated before and after patient care. Imprints taken of fingertips and palm of dominant hand before and after hand hygiene procedure. Bacterial counts quantified blindly.ResultsWith handrubbing the median percentage reduction in bacterial contamination was significantly higher than with handwashing (83% v 58%, P=0.012), with a median difference in the percentage reduction of 26% (95% confidence interval 8% to 44%). The median duration of hand hygiene was 30 seconds in each group.ConclusionsDuring routine patient care handrubbing with an alcohol based solution is significantly more efficient in reducing hand contamination than handwashing with antiseptic soap.

What is already known on this topic

To improve compliance with hand hygiene during patient care, handrubbing with an alcohol based solution has been proposed as a substitute for handwashing because of its rapid action and accessibilityExperimental studies show that handrubbing is at least as effective as medicated soap in reducing artificial contamination of handsMany healthcare workers still have reservations regarding its efficacy and are reluctant to use this technique

What this study adds

When used in routine practice, handrubbing with an alcohol based solution after contact with patients achieved a greater reduction in bacterial contamination of hands than conventional handwashing with medicated soap     

Prognostic Significance of Complications after Laparoscopic Colectomy for Colon Cancer

Aims

This study sought to evaluate the prognostic significance of postoperative complications for colon cancer patients undergoing laparoscopic surgery.

Methods

From May 2006 to May 2009, a total 224 patients who underwent laparoscopic curative resection (R0) for colon cancer were included in our retrospective study. Postoperative complications were evaluated according to a standardized grading system. The main outcome measurements of our study were overall survival (OS) and relapse-free survival (RFS), which were then compared between the no complication and complication groups. Univariate and multivariate analysis were used to assess the correlation between complications and prognosis.

Results

Fifty-nine postoperative complications occurred in 43 patients. The overall morbidity rate was 26.3%. The 5-year OS in the complication group was 41.4% compared with 78.5% in the no complication group (P<0.001). The cumulative incidence of relapse was also more aggressive in patients with complications (5-year RFS: complication group 40.9% vs. no complication group 82.1%, P<0.001). Multivariate analysis identified complications as a significant factor increasing the risk for both OS (RR 2.737; 95% CI 1.512–4.952; P = 0.001) and RFS (RR 4.247; 95% CI 2.291–7.876; P<0.001).

Conclusion

Postoperative complications could pose a significant adverse impact not only on OS but also on RFS in patients with colon cancer even when laparoscopic R0 resection is available.     

Predictors of poor outcome and benefits from antibiotics in children with acute otitis media: pragmatic randomised trial

ObjectivesTo identify which children with acute otitis media are at risk of poor outcome and to assess benefit from antibiotics in these children.DesignSecondary analysis of randomised controlled trial cohort.SettingPrimary care.Participants315 children aged 6 months to 10 years.InterventionImmediate or delayed (taken after 72 hours if necessary) antibiotics.ResultsDistress by day three was more likely in children with high temperature (adjusted odds ratio 4.5, 95% confidence interval 2.3 to 9.0), vomiting (2.6,1.3 to 5.0), and cough (2.0, 1.1 to 3.8) on day one. Night disturbance by day three was more likely with high temperature 2.4 (1.2 to 4.8), vomiting (2.1,1.1 to 4.0), cough (2.3,1.3 to 4.2), and ear discharge (2.1, 1.2 to 3.9). Among the children with high temperature or vomiting, distress by day three was less likely with immediate antibiotics (32% for immediate v 53% for delayed, χ²=4.0; P=0.045, number needed to treat 5) as was night disturbance (26% v 59%, χ²=9.3; P=0.002; number needed to treat 3). In children without higher temperature or vomiting, immediate antibiotics made little difference to distress by day three (15% v 19%, χ²=0.74; P=0.39) or night disturbance (20% v 27%, χ²=1.6; P=0.20). Addition of cough did not significantly improve prediction of benefit.ConclusionIn children with otitis media but without fever and vomiting antibiotic treatment has little benefit and a poor outcome is unlikely.

What is already known on this topic

Most children with otitis media will not benefit symptomatically from immediate use of antibioticsIt is unclear which children are more likely to benefit from antibiotics and which features predict poor outcome

What this study adds

Children with high temperature or vomiting were more likely to be distressed or have night disturbance three days after seeing the doctorChildren with high temperature or vomiting were more likely to benefit from antibiotics, although it is still reasonable to wait 24-48 hours as many children will settle anywayChildren without high temperature or vomiting were unlikely to have poor outcome and unlikely to benefit from immediate antibiotics     

Effect of iron supplementation on incidence of infectious illness in children: systematic review

ObjectiveTo evaluate the effect of iron supplementation on the incidence of infections in children.DesignSystematic review of randomised controlled trials.InterventionsOral or parenteral iron supplementation or fortified formula milk or cereals.OutcomesIncidence of all recorded infectious illnesses, and individual illnesses, including respiratory tract infection, diarrhoea, malaria, other infections, and prevalence of positive smear results for malaria.ResultsThe pooled estimate (random effects model) of the incidence rate ratio (iron v placebo) was 1.02 (95% confidence interval 0.96 to 1.08, P=0.54; P<0.0001 for heterogeneity). The incidence rate difference (iron minus placebo) for all recorded illnesses was 0.06 episodes/child year (−0.06 to 0.18, P=0.34; P<0.0001 for heterogeneity). However, there was an increase in the risk of developing diarrhoea (incidence rate ratio 1.11, 1.01 to 1.23, P=0.04), but this would not have an overall important on public health (incidence rate difference 0.05 episodes/child year, –0.03 to 0.13; P=0.21). The occurrence of other illnesses and positive results on malaria smears (adjusted for positive smears at baseline) were not significantly affected by iron administration. On meta-regression, the statistical heterogeneity could not be explained by the variables studied.ConclusionIron supplementation has no apparent harmful effect on the overall incidence of infectious illnesses in children, though it slightly increases the risk of developing diarrhoea.

What is already known on this topic

Iron supplementation is recommended to prevent iron deficiency, which is a major health problem, especially in the developing countriesConflicting data exist regarding the possibility of an increase in the incidence of infections with iron supplementation, resulting in concern about the safety of this intervention

What this study adds

Iron supplementation has no apparent harmful effect on the overall incidence of infectious illnesses in childrenIron administration increases the risk of developing diarrhoeaFortification of foods may be the safest and most beneficial mode of supplementation in relation to infectious illnesses     

Open randomised trial of intermittent very low energy diet together with nicotine gum for stopping smoking in women who gained weight in previous attempts to quit

ObjectiveTo determine whether attempts to prevent weight gain will increase success rates for stopping smoking.Design16 week, open, randomised study with 1 year follow up.SettingObesity unit.Subjects287 female smokers who had quit smoking before but started again because of weight concerns.InterventionCombination of a standard smoking cessation programme with nicotine gum and a behavioural weight control programme including a very low energy diet. A control group was treated with the identical programme but without the diet.ResultsAfter 16 weeks, 68/137 (50%) women had stopped smoking in the diet group versus 53/150 (35%) in the control group (P=0.01). Among these women, weight fell by mean 2.1 (95% confidence interval 2.9 to 1.3) kg in the diet group but increased by 1.6 (0.9 to 2.3) kg in the control group (P<0.001). After 1 year the success rates in the diet and control groups were 38/137 (28%) and 24/150 (16%) respectively (P<0.05), but there was no statistical difference in weight gain.ConclusionsCombining the smoking cessation programme with an intervention to control weight helped women to stop smoking and control weight.     

Randomised controlled trial of structured personal care of type 2 diabetes mellitus

ObjectiveTo assess the effect of a multifaceted intervention directed at general practitioners on six year mortality, morbidity, and risk factors of patients with newly diagnosed type 2 diabetes.DesignPragmatic, open, controlled trial with randomisation of practices to structured personal care or routine care; analysis after 6 years.Setting311 Danish practices with 474 general practitioners (243 in intervention group and 231 in comparison group).Participants874 (90.1%) of 970 patients aged ⩾40 years who had diabetes diagnosed in 1989-91 and survived until six year follow up.InterventionRegular follow up and individualised goal setting supported by prompting of doctors, clinical guidelines, feedback, and continuing medical education.ResultsPredefined non-fatal outcomes and mortality were the same in both groups. The following risk factor levels were lower for intervention patients than for comparison patients (median values): fasting plasma glucose concentration (7.9 v 8.7 mmol/l, P=0.0007), glycated haemoglobin (8.5% v 9.0%, P<0.0001; reference range 5.4-7.4%), systolic blood pressure (145 v 150 mm Hg, P=0.0004), and cholesterol concentration (6.0 v 6.1 mmol/l, P=0.029, adjusted for baseline concentration). Both groups had lost weight since diagnosis (2.6 v 2.0 kg). Metformin was the only drug used more frequently in the intervention group (24% (110/459) v 15% (61/415)).Intervention doctors arranged more follow up consultations, referred fewer patients to diabetes clinics, and set more optimistic goals.ConclusionsIn primary care, individualised goals with educational and surveillance support may for at least six years bring risk factors of patients with type 2 diabetes to a level that has been shown to reduce diabetic complications but without weight gain.

What is already known on this topic

Evidence is increasing that control of hyperglycaemia, hypertension, and dyslipidaemia may postpone the development of diabetic complications in patients with type 2 diabetesMaintaining good control over a long period can be difficult

What this study adds

Structured individualised personal care with educational and surveillance support for general practitioners reduced levels of risk factors in type 2 diabetic patients after six yearsRisk factors were reduced to a level that has been shown to have a beneficial effect on diabetic complicationsParticipants also showed modest weight loss     

Attaching and Effacing Escherichia coli Downregulate DNA Mismatch Repair Protein In Vitro and Are Associated with Colorectal Adenocarcinomas in Humans

Background

Mucosa-associated Escherichia coli are frequently found in the colonic mucosa of patients with colorectal adenocarcinoma, but rarely in healthy controls. Chronic mucosal E. coli infection has therefore been linked to colonic tumourigenesis. E. coli strains carrying eae (encoding the bacterial adhesion protein intimin) attach intimately to the intestinal mucosa and are classed as attaching and effacing E. coli (AEEC). Enteropathogenic Escherichia coli (EPEC) are the most common form of AEEC identified in man. EPEC utilise a type III secretion system to translocate effector proteins into host cells and infection induces wide-ranging effects on the host cell proteome. We hypothesised that EPEC infection could influence molecular pathways involved in colorectal tumourigenesis.

Methodology/Principal Findings

When co-cultured with human colorectal cell lines, EPEC dramatically downregulated the expression of key DNA mismatch repair proteins MSH2 and MLH1 in an attachment specific manner. Cytochrome c staining and TUNEL analysis confirmed that this effect was not a consequence of apoptosis/necrosis. Ex vivo human colonic mucosa was co-cultured with EPEC and probed by immunofluorescence to locate adherent bacteria. EPEC entered 10% of colonic crypts and adhered to crypt epithelial cells, often in the proliferative compartment. Adenocarcinoma and normal colonic mucosa from colorectal cancer patients (n = 20) was probed by immunofluorescence and PCR for AEEC. Mucosa-associated E. coli were found on 10/20 (50%) adenocarcinomas and 3/20 (15%) normal mucosa samples (P<0.05). AEEC were detected on 5/20 (25%) adenocarcinomas, but not normal mucosa samples (P<0.05).

Significance/Conclusions

The ability of EPEC to downregulate DNA mismatch repair proteins represents a novel gene-environment interaction that could increase the susceptibility of colonic epithelial cells to mutations and therefore promote colonic tumourigenesis. The potential role of AEEC in colorectal tumourigenesis warrants further investigation.