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     

Prospective,randomised, double blind trial of prophylaxis with single dose of co-amoxiclav before percutaneous endoscopic gastrostomy

ObjectiveTo determine the efficacy of antibacterial prophylaxis in preventing infectious complications after percutaneous endoscopic gastrostomy.DesignProspective, randomised, placebo controlled, double blind, multicentre study.SettingDepartments of internal medicine at six German hospitals.SubjectsOf 106 randomised adult patients with dysphagia, 97 received study medication, and 84 completed the study. The median age of the patients was 65 years. Most had dysphagia due to malignant disease (65%), and many (76%) had serious comorbidity.InterventionsA single intravenous 2.2 g dose of co-amoxiclav or identical appearing saline was given 30 min before percutaneous endoscopic gastrostomy performed by the thread pull method.ResultsThe incidence of peristomal and other infections within one week after percutaneous endoscopic gastrostomy was significantly reduced in the antibiotic group (8/41 (20%) v 28/43 (65%), P<0.001). Similar results were obtained in an intention to treat analysis. Several peristomal wound infections were of minor clinical significance. After wound infections that required no or only local treatment were excluded from the analysis, antibiotic prophylaxis remained highly effective in reducing clinically important wound infections (1/41 (2%) v 11/43 (26%), P<0.01) and non-wound infections (2 (5%) v 9 (21%), P<0.05).ConclusionsAntibiotic prophylaxis with a single dose of co-amoxiclav significantly reduces the risk of infectious complications after percutaneous endoscopic gastrostomy and should be recommended.

Key messages

• Percutaneous endoscopic gastrostomy for enteral feeding can be associated with substantial rates of infectious complications, notably peristomal wound infection
• Small, single centre studies on prevention of wound infection by antibiotic prophylaxis have given conflicting results
• This prospective, randomised, placebo controlled, double blind, multicentre study showed that a single dose of 2.2 g co-amoxiclav significantly reduced the rate of infection
• The favourable effect of antibiotic prophylaxis included a reduction in the rate of clinically important peristomal wound infection
• Intention to treat analysis indicated a significant reduction in the need for therapeutic antibiotics

     

How to evaluate and improve the quality and credibility of an outcomes database: validation and feedback study on the UK Cardiac Surgery Experience

ObjectivesTo assess the quality and completeness of a database of clinical outcomes after cardiac surgery and to determine whether a process of validation, monitoring, and feedback could improve the quality of the database.DesignStratified sampling of retrospective data followed by prospective re-sampling of database after intervention of monitoring, validation, and feedback.SettingTen tertiary care cardiac surgery centres in the United Kingdom.InterventionValidation of data derived from a stratified sample of case notes (recording of deaths cross checked with mortuary records), monitoring of completeness and accuracy of data entry, feedback to local data managers and lead surgeons.ResultsThe database was incomplete, with a mean (SE) of 24.96% (0.09%) of essential data elements missing, whereas only 1.18% (0.06%) were missing in the patient records (P<0.0001). Intervention was associated with (a) significantly less missing data (9.33% (0.08%) P<0.0001); (b) marginal improvement in reliability of data and mean (SE) overall centre reliability score (0.53 (0.15) v 0.44 (0.17)); and (c) improved accuracy of assigned Parsonnet risk scores (κ 0.84 v 0.70). Mortality scores (actual minus risk adjusted mortality) for all participating centres fell within two standard deviations of the mean score.ConclusionA short period of independent validation, monitoring, and feedback improved the quality of an outcomes database and improved the process of risk adjustment, but with substantial room for further improvement. Wider application of this approach should increase the credibility of similar databases before their public release.

What is already know in this topic

Release of healthcare outcomes into the public domain has altered referral patterns and has led to improvement in some centres and elimination of othersThe tacit assumption is that such outcomes data are accurate and can be relied on by the public and by healthcare providers to guide improvements

What this study adds

Sampling of a published national cardiac surgery database in England revealed it to be both incomplete and unreliable in its ability to yield accurate, risk adjusted outcomes dataAn independent short process of monitoring, validation, and feedback improved the quality of the databaseSuch databases probably require an ongoing process of monitoring in order to allow data of adequate quality to be generated for the purpose of improving healthcare outcomes     

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     

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.     

Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up

ObjectiveTo evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year.DesignPlacebo controlled, double blind trial.SettingReykjavik health centre.Subjects237 smokers aged 22-66 years living in or around Reykjavik.InterventionsNicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment.ResultsThe log rank test for 6 years (χ²=8.5, P=0.004) shows a significant association between abstinence from smoking and type of treatment. Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (P=0.011 (χ²), 95% confidence interval 1.17% to 3.32%), 37% v 25% after 3 months (P=0.045, 1.01% to 3.08%), 31% v 16% after 6 months (P=0.005, 1.27% to 4.50%), 27% v 11% after 12 months (P=0.001, 1.50% to 6.14%), and 16% v 9% after 6 years (P=0.077, 0.93% to 4.72%).ConclusionsShort and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch.

Key messages

• Combined methods of nicotine replacement therapy have a potential advantage over one method because of high levels of substitution
• Nicotine patches release nicotine slowly, but nicotine nasal spray delivers nicotine more rapidly, enabling the smoker to respond quickly to any smoking urges
• Treatment with a patch and nicotine nasal spray was significantly more effective than patch and placebo from day 15 after stopping smoking
• Using a patch for 5 months with a nicotine nasal spray for 1 year provides a more effective means of stopping smoking than using a patch only
• It is not cost effective to use a nicotine nasal spray for longer than 7 months after stopping a patch

     

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     

Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial

ObjectiveTo evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day. DesignRandomised controlled trial.SettingCopenhagen, Denmark.Subjects42 alcoholic patients without liver disease admitted for elective colorectal surgery.InterventionsWithdrawal from alcohol consumption for 1 month before operation (disulfiram controlled) compared with continuous drinking.ResultsThe intervention group developed significantly fewer postoperative complications than the continuous drinkers (31% v 74%, P=0.02). Delayed type hypersensitivity responses were better in the intervention group before (37 mm² v 12 mm², P=0.04), but not after surgery (3 mm² v 3 mm²). Development of postoperative myocardial ischaemia (23% v 85%) and arrhythmias (33% v 86%) on the second postoperative day as well as nightly hypoxaemic episodes (4 v 18 on the second postoperative night) occurred significantly less often in the intervention group. Surgical stress responses were lower in the intervention group (P⩽0.05).ConclusionsOne month of preoperative abstinence reduces postoperative morbidity in alcohol abusers. The mechanism is probably reduced preclinical organ dysfunction and reduction of the exaggerated response to surgical stress.

Key messages

• Recent data have shown alcohol misusers to have a threefold increase in postoperative morbidity
• In misusers recovery from organ dysfunction induced by alcohol is seen after abstinence
• Abstinence from alcohol for 1 month before surgery reduces postoperative morbidity after colorectal surgery
• Mechanisms may involve reduced responses to surgical stress and improved cardiac and immune dysfunction
• Withdrawal from alcohol before an operation is recommended in alcohol abusers

     

The Potential Involvement of E-cadherin and β-catenins in Meningioma

Objective

To investigate the potential involvements of E-cadherin and β-catenin in meningioma.

Methods

Immunohistochemistry staining was performed on samples from patients with meningioma. The results were graded according to the positive ratio and intensity of tissue immunoreactivity. The expression of E-cadherin and β-catenin in meningioma was analyzed by its relationship with WHO2007 grading, invasion, peritumoral edema and postoperative recurrence.

Results

The positive rates of E-cadherin in meningioma WHO I, II, III were 92.69%, 33.33% and 0, respectively, (P<0.05); while the positive rates of β-catenin in meningioma WHO I, II, III were 82.93%, 33.33% and 20.00%, respectively, (P<0.05). The positive rate of E-cadherin in meningioma without invasion (94.12%) was higher than that with invasion (46.67%) (P<0.05). The difference in the positive rate of β-catenin between meningioma without invasion (88.24%) and meningioma with invasion (33.33%, P<0.05) was also statically significant. The positive rates of E-cadherin in meningioma with peritumoral edema 0, 1, 2, 3 were 93.75%, 85.71%, 60.00% and 0 respectively, (P<0.05); the positive rates of β-catenin in meningioma with peritumoral edema 0, 1, 2, 3 were 87.50%, 85.71%, 30.00% and 0 respectively, (P<0.01). The positive rates of E- cadherin in meningioma with postoperative recurrence were 33.33%, and the positive rate with postoperative non-recurrence was 90.00% (P<0.01). The positive rates of β-catenin in meningioma with postoperative recurrence and non-recurrence were 11.11%, 85.00%, respectively (P<0.01).

Conclusion

The expression levels of E- cadherin and β-catenin correlated closely to the WHO 2007 grading criteria for meningioma. In atypical or malignant meningioma, the expression levels of E-cadherin and β-catenin were significantly lower. The expression levels of E- cadherin and β-catenin were also closely correlated with the invasion status of meningioma, the size of the peritumoral edema and the recurrent probabilities of the meningioma, all in an inverse correlationship. Taken together, the present study provided novel molecular targets in clinical treatments to meningioma.     

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     

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     

Population-Based Surveillance for Invasive Pneumococcal Disease in Homeless Adults in Toronto

Background

Identification of high-risk populations for serious infection due to S. pneumoniae will permit appropriately targeted prevention programs.

Methods

We conducted prospective, population-based surveillance for invasive pneumococcal disease and laboratory confirmed pneumococcal pneumonia in homeless adults in Toronto, a Canadian city with a total population of 2.5 M, from January 1, 2002 to December 31, 2006.

Results

We identified 69 cases of invasive pneumococcal disease and 27 cases of laboratory confirmed pneumococcal pneumonia in an estimated population of 5050 homeless adults. The incidence of invasive pneumococcal disease in homeless adults was 273 infections per 100,000 persons per year, compared to 9 per 100,000 persons per year in the general adult population. Homeless persons with invasive pneumococcal disease were younger than other adults (median age 46 years vs 67 years, P<.001), and more likely than other adults to be smokers (95% vs. 31%, P<.001), to abuse alcohol (62% vs 15%, P<.001), and to use intravenous drugs (42% vs 4%, P<.001). Relative to age matched controls, they were more likely to have underlying lung disease (12/69, 17% vs 17/272, 6%, P = .006), but not more likely to be HIV infected (17/69, 25% vs 58/282, 21%, P = .73). The proportion of patients with recurrent disease was five fold higher for homeless than other adults (7/58, 12% vs. 24/943, 2.5%, P<.001). In homeless adults, 28 (32%) of pneumococcal isolates were of serotypes included in the 7-valent conjugate vaccine, 42 (48%) of serotypes included in the 13-valent conjugate vaccine, and 72 (83%) of serotypes included in the 23-valent polysaccharide vaccine. Although no outbreaks of disease were identified in shelters, there was evidence of clustering of serotypes suggestive of transmission of pathogenic strains within the homeless population.

Conclusions

Homeless persons are at high risk of serious pneumococcal infection. Vaccination, physical structure changes or other program to reduce transmission in shelters, harm reduction programs to reduce rates of smoking, alcohol abuse and infection with bloodborne pathogens, and improved treatment programs for HIV infection may all be effective in reducing the risk.     

Images of the good doctor in Western medicine: The doctor-patient relationship

ObjectiveTo determine whether the management of head injuries differs between patients aged ⩾65 years and those <65.DesignProspective observational national study over four years.Setting25 Scottish hospitals that admit trauma patients.Participants527 trauma patients with extradural or acute subdural haematomas.ResultsPatients aged ⩾65 years had lower survival rates than patients <65 years. Rates were 15/18 (83%) v 165/167 (99%) for extradural haematoma (P=0.007) and 61/93 (66%) v 229/249 (92%) for acute subdural haematoma (P<0.001). Older patients were less likely to be transferred to specialist neurosurgical care (10 (56%) v 142 (85%) for extradural haematoma (P=0.005) and 56 (60%) v 192 (77%) for subdural haematoma (P=0.004)). There was no significant difference between age groups in the incidence of neurosurgical interventions in patients who were transferred. Logistic regression analysis showed that age had a significant independent effect on transfer and on survival. Older patients had higher rates of coexisting medical conditions than younger patients, but when severity of injury, initial physiological status at presentation, or previous health were controlled for in a log linear analysis, transfer rates were still lower in older patients than in younger patients (P<0.001).ConclusionsCompared with those aged under 65 years, people aged 65 and over have a worse prognosis after head injury complicated by intracranial haematoma. The decision to transfer such patients to neurosurgical care seems to be biased against older patients.

What is already known on this topic

Older patients with acute intracranial haematomas have significantly higher mortality and poorer functional outcome than younger patients with similar injuriesIntracranial haematomas are larger and more common in older patients with head injury than in younger patientsEarly diagnosis and surgical intervention for operable lesions is a crucial factor in determining patients'' outcomes

What this study adds

Older patients with acute intracranial haematomas were less likely to be transferred for specialist neurosurgical care than younger patients with similar severities of injuries, extracranial injuries, and physiological status at presentationSignificant differences in transfer rates related to age were still seen after pre-existing medical conditions were controlled for     

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     

Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome

Objective To investigate whether placebo effects can experimentally be separated into the response to three components—assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship—and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components.Design A six week single blind three arm randomised controlled trial.Setting Academic medical centre.Participants 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale.Interventions For three weeks either waiting list (observation), placebo acupuncture alone (“limited”), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence (“augmented”). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks.Main outcome measures Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life.Results At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus “limited” versus “augmented,” respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01).Results were similar at six week follow-up.Conclusion Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.Trial registration Clinical Trials NCT00065403.     

Referral for menstrual problems: cross sectional survey of symptoms,reasons for referral,and management

ObjectivesTo describe the menstrual experience of women referred for menstrual problems, in particular menorrhagia (excessive menstrual loss), and to assess associations with reasons for referral given by their general practitioners, the women''s understanding of the reasons for their attendance at the hospital clinics, and clinic outcome.DesignQuestionnaire survey, with partial review of case notes after 8 months.SettingThree hospital gynaecology clinics in Glasgow and Edinburgh.Participants952 women completed the questionnaire, and the first 665 were reviewed.ResultsOnly 38% (95% confidence interval 34% to 41%) of women reported excessive menstrual loss as a severe problem. However 60% (57-63%) gave it as reason for attending a clinic, and 76% (73-79%) of general practitioners gave it as reason for referral. Reason for referral was significantly biased towards bleeding (McNemar odds ratio 4.01, 3.0 to 5.3, P<0.001) and against pain (0.54, 0.4 to 0.7, P<0.001). Dysfunctional uterine bleeding was diagnosed in 37% (31-42%) of the 259 women who gave as reason for attendance something other than bleeding. Women who were economically disadvantaged differed in prevalence of the main diagnoses and were more likely to fail to reattend. Hysterectomy was associated with referral for bleeding (relative risk 4.9, 1.6 to 15.6, P<0.001) but not with the patient stating bleeding as the reason for clinic attendance.ConclusionsIntolerance of the volume of their bleeding is not a key feature among women attending clinics for bleeding problems. Broad menstrual complaint tends to be reframed as excessive bleeding at referral and during management. This may result in women receiving inappropriate care. Conceptualisation and assessment of menorrhagia requires reconsideration.

What is already known on this topic

Excessive menstrual loss (menorrhagia) is one of the commonest reasons for secondary referral of women, but there is no formalised clinical assessment in routine useManagement typically involves potent drugs or invasive surgery, with 60% of women having hysterectomy within 5 yearsMany women referred for menorrhagia have menstrual blood loss that is not excessive

What this study adds

Discordance exists between symptoms and both referral and diagnostic pathways, arising from a disproportionate focus on menstrual bleedingAmong women referred for menorrhagia, volume of bleeding is not a key symptomThis raises concerns about conceptualisation and assessment of menstrual complaint and the appropriateness of healthcare provision     

Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies

To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1×10⁻⁶. To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4×10⁻⁸³) and the phospholamban (PLN) gene (P = 1.9×10⁻²⁹). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death.     

Increase in blood glucose concentration during antihypertensive treatment as a predictor of myocardial infarction: population based cohort study

ObjectiveTo investigate the impact of an increase in blood glucose on the risk of developing myocardial infarction, with particular emphasis on people taking antihypertensive drugs.DesignProspective population based cohort study.SettingUppsala, Sweden.Participants1860 men who had participated in 1970-3 at age 50 in a health survey aimed at identifying risk factors for cardiovascular disease and were re-examined at age 60 and then followed for 17.4 years.ResultsThe incidence of myocardial infarction was significantly higher in men treated for hypertension than in those without such treatment (23% v 13.5%, P<0.0001). Participants who developed myocardial infarction after the age of 60 (n=253) showed a significantly larger increase in blood glucose between age 50 and 60 than did those without myocardial infarction. In multivariate Cox proportional hazard models increase in blood glucose was an independent risk factor for myocardial infarction (P=0.0001) in men receiving antihypertensive treatment at age 60 (n=291, mainly β blockers and thiazide diuretics) but not in those without such treatment. The impact of increase in blood glucose declined after inclusion of serum proinsulin concentrations at baseline but was still significant. A significant interaction existed between proinsulin concentration (a marker of insulin resistance) at baseline and antihypertensive treatment on increase in blood glucose.ConclusionsIncrease in blood glucose between the ages of 50 and 60 and baseline proinsulin concentration were important risk factors for myocardial infarction in men receiving antihypertensive treatment, indicating that both an insulin resistant state and the metabolic impact of β blockers and diuretics increase the risk of myocardial infarction.

What is already known on this topic

Patients with hypertension are resistant to insulin stimulated glucose uptake and are hyperinsulinaemic compared with normotensive controlsTreatment with β blockers and thiazide diuretics further increases insulin resistance, thereby increasing the risk of developing type 2 diabetes mellitus or impaired glucose toleranceThe influence of metabolic changes induced by antihypertensive treatment on the risk of myocardial infarction has been questioned

What this study adds

Men who received antihypertensive treatment showed a larger increase in blood glucose during a 10 year period than those without such treatmentIncrease in blood glucose during antihypertensive treatment was a significant, independent risk factor for myocardial infarction in men with an insulin resistant state at baseline