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     

Dominant and diet-responsive groups of bacteria within the human colonic microbiota

The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resistant starch (RS) or non-starch polysaccharides (NSPs) and a reduced carbohydrate weight loss (WL) diet, over 10 weeks. Analysis of 16S rRNA sequences in stool samples of six volunteers detected 320 phylotypes (defined at >98% identity) of which 26, including 19 cultured species, each accounted for >1% of sequences. Although samples clustered more strongly by individual than by diet, time courses obtained by targeted qPCR revealed that ‘blooms'' in specific bacterial groups occurred rapidly after a dietary change. These were rapidly reversed by the subsequent diet. Relatives of Ruminococcus bromii (R-ruminococci) increased in most volunteers on the RS diet, accounting for a mean of 17% of total bacteria compared with 3.8% on the NSP diet, whereas the uncultured Oscillibacter group increased on the RS and WL diets. Relatives of Eubacterium rectale increased on RS (to mean 10.1%) but decreased, along with Collinsella aerofaciens, on WL. Inter-individual variation was marked, however, with >60% of RS remaining unfermented in two volunteers on the RS diet, compared to <4% in the other 12 volunteers; these two individuals also showed low numbers of R-ruminococci (<1%). Dietary non-digestible carbohydrate can produce marked changes in the gut microbiota, but these depend on the initial composition of an individual''s gut microbiota.     

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.     

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

     

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     

Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths

ObjectiveTo assess the hazards at an early phase of the growing epidemic of deaths from tobacco in China.DesignSmoking habits before 1980 (obtained from family or other informants) of 0.7 million adults who had died of neoplastic, respiratory, or vascular causes were compared with those of a reference group of 0.2 million who had died of other causes.Setting24 urban and 74 rural areas of China.SubjectsOne million people who had died during 1986-8 and whose families could be interviewed.ResultsAmong male smokers aged 35-69 there was a 51% (SE 2) excess of neoplastic deaths, a 31% (2) excess of respiratory deaths, and a 15% (2) excess of vascular deaths. All three excesses were significant (P<0.0001). Among male smokers aged ⩾70 there was a 39% (3) excess of neoplastic deaths, a 54% (2) excess of respiratory deaths, and a 6% (2) excess of vascular deaths. Fewer women smoked, but those who did had tobacco attributable risks of lung cancer and respiratory disease about the same as men. For both sexes, the lung cancer rates at ages 35-69 were about three times as great in smokers as in non-smokers, but because the rates among non-smokers in different parts of China varied widely the absolute excesses of lung cancer in smokers also varied. Of all deaths attributed to tobacco, 45% were due to chronic obstructive pulmonary disease and 15% to lung cancer; oesophageal cancer, stomach cancer, liver cancer, tuberculosis, stroke, and ischaemic heart disease each caused 5-8%. Tobacco caused about 0.6 million Chinese deaths in 1990 (0.5 million men). This will rise to 0.8 million in 2000 (0.4 million at ages 35-69) or to more if the tobacco attributed fractions increase.ConclusionsAt current age specific death rates in smokers and non-smokers one in four smokers would be killed by tobacco, but as the epidemic grows this proportion will roughly double. If current smoking uptake rates persist in China (where about two thirds of men but few women become smokers) tobacco will kill about 100 million of the 0.3 billion males now aged 0-29, with half these deaths in middle age and half in old age.

Key messages

• Of the Chinese deaths now being caused by tobacco, 45% are from chronic lung disease, 15% from lung cancer, and 5-8% from each of oesophageal cancer, stomach cancer, liver cancer, stroke, ischaemic heart disease, and tuberculosis
• Tobacco now causes 13% (and will probably eventually cause about 33%) of deaths in men but only 3% (and perhaps eventually about 1%) of deaths in women as the proportion of young women who smoke has become small
• Two thirds of men now become smokers before age 25; few give up, and about half of those who persist will be killed by tobacco in middle or old age
• If present smoking patterns continue about 100 million of the 0.3 billion Chinese males now aged 0-29 will eventually be killed by tobacco
• Tobacco caused 0.6 million deaths in 1990 and will cause at least 0.8 million in 2000 (0.7 million in men) and about 3 million a year by the middle of the century on the basis of current smoking patterns

     

Prawn Shell Chitosan Has Anti-Obesogenic Properties,Influencing Both Nutrient Digestibility and Microbial Populations in a Pig Model

The potential of natural products to prevent obesity have been investigated, with evidence to suggest that chitosan has anti-obesity effects. The current experiment investigated the anti-obesity potential of prawn shell derived chitosan on a range of variables relevant to obesity in a pig model. The two dietary treatment groups included in this 63 day study were: T1) basal diet and T2) basal diet plus 1000 ppm chitosan (n = 20 gilts per group (70 ± 0.90 kg). The parameter categories which were assessed included: performance, nutrient digestibility, serum leptin concentrations, nutrient transporter and digestive enzyme gene expression and gut microbial populations. Pigs offered chitosan had reduced feed intake and final body weight (P< 0.001), lower ileal digestibility of dry matter (DM), gross energy (GE) (P< 0.05) and reduced coefficient of apparent total tract digestibility (CATTD) of gross energy and nitrogen (P<0.05) when compared to the basal group. Fatty acid binding protein 2 (FABP2) gene expression was down-regulated in pigs offered chitosan (P = 0.05) relative to the basal diet. Serum leptin concentrations increased (P< 0.05) in animals offered the chitosan diet compared to pigs offered the basal diet. Fatness traits, back-fat depth (mm), fat content (kg), were significantly reduced while lean meat (%) was increased (P<0.05) in chitosan supplemented pigs. Pigs offered chitosan had decreased numbers of Firmicutes in the colon (P <0.05), and Lactobacillus spp. in both the caecum (P <0.05) and colon (P <0.001). Bifidobacteria populations were increased in the caecum of animals offered the chitosan diet (P <0.05). In conclusion, these findings suggest that prawn shell chitosan has potent anti-obesity/body weight control effects which are mediated through multiple biological systems in vivo.     

Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study

ObjectiveTo investigate the influence of weight reduction on obese patients with asthma.DesignOpen study, two randomised parallel groups.SettingPrivate outpatients centre, Helsinki, Finland.ParticipantsTwo groups of 19 obese patients with asthma (body mass index (kg/m²) 30 to 42) recruited through newspaper advertisements.InterventionSupervised weight reduction programme including 8 week very low energy diet.ResultsAt the end of the weight reducing programme, the participants in the treatment group had lost a mean of 14.5% of their pretreatment weight, the controls 0.3%. The corresponding figures after one year were 11.3% and a weight gain of 2.2%. After the 8 week dieting period the difference in changes in percentage of predicted FEV₁ from baseline in the treatment and control groups was 7.2% (95% confidence interval 1.9% to 12.5%, P=0.009). The corresponding difference in the changes in FVC was 8.6% (4.8% to 12.5%, P<0.0001). After one year the differences in the changes in the two groups were still significant: 7.6% for FEV₁ (1.5% to 13.8%, P=0.02) and 7.6% for FVC (3.5% to 11.8%, P=0.001). By the end of the weight reduction programme, reduction in dyspnoea was 13 mm (on a visual analogue scale 0 mm to 100 mm) in the treatment group and 1 mm in the control group (P=0.02). The reduction of rescue medication was 1.2 and 0.1 doses respectively (P=0.03). After one year the differences in the changes between the two groups were −12 for symptom scores (range −1 to −22, P=0.04) and −10 for total scores (−18 to −1, P=0.02). The median number of exacerbations in the treatment group was 1 (0-4) and in the controls 4 (0-7), P=0.001.ConclusionWeight reduction in obese patients with asthma improves lung function, symptoms, morbidity, and health status.     

Circulating MicroRNA Responses between ‘High’ and ‘Low’ Responders to a 16-Wk Diet and Exercise Weight Loss Intervention

BackgroundInteractions between diet, physical activity and genetic predisposition contribute to variable body mass changes observed in response to weight loss interventions. Circulating microRNAs (c-miRNAs) may act as ‘biomarkers’ that are associated with the rate of change in weight loss, and/or play a role in regulating the biological variation, in response to energy restriction.ObjectiveTo quantify targeted c-miRNAs with putative roles in energy metabolism and exercise adaptations following a 16 wk diet and exercise intervention in individuals with large (high responders; HiRes) versus small (low responders; LoRes) losses in body mass.MethodsFrom 89 male and female overweight/obese participants who completed the intervention (energy restriction from diet, 250 kcal/d, and exercise, 250 kcal/d), subgroups of HiRes (>10% body mass loss, n = 22) and LoRes (<5% body mass loss, n = 18) were identified. From resting plasma samples collected after an overnight fast pre and post intervention, RNA was extracted, quantified and reverse transcribed. Thirteen c-miRNA selected a priori were analysed using a customised 96-well miScript miRNA PCR Array.ResultsLoss of body mass (-11.0 ± 2.3 kg vs. -3.0 ± 1.3 kg; P<0.01) and fat mass (-11.1 ± 2.6 kg vs. -3.9 ± 1.6 kg; P<0.01) was greater for HiRes than LoRes (P<0.001). Expression of c-miR-935 was higher in LoRes compared to HiRes pre- (~47%; P = 0.025) and post- (~100%; P<0.01) intervention and was the only c-miRNA differentially expressed at baseline between groups. The abundance of c-miR-221-3p and -223-3p increased pre- to post-intervention in both groups (~57–69% and ~25–90%, P<0.05). There was a post-intervention increase in c-miR-140 only in LoRes compared to HiRes (~23%, P = 0.016).ConclusionThe differential expression and responses of selected c-miRNAs in overweight/obese individuals to an exercise and diet intervention suggests a putative role for these ‘biomarkers’ in the prediction or detection of individual variability to weight loss interventions.     

Contribution of Chronic Conditions to the Disability Burden across Smoking Categories in Middle-Aged Adults,Belgium

IntroductionSmoking is considered the single most important preventable cause of morbidity and mortality worldwide, contributing to increased incidence and severity of disabling conditions. The aim of this study was to assess the contribution of chronic conditions to the disability burden across smoking categories in middle-aged adults in Belgium.MethodsData from 10,224 individuals aged 40 to 60 years who participated in the 1997, 2001, 2004, or 2008 Health Interview Surveys in Belgium were used. Smoking status was defined as never, former (cessation ≥2 years), former (cessation <2 years), occasional light (<20 cigarettes/day), daily light, and daily heavy (≥20 cigarettes/day). To attribute disability to chronic conditions, binomial additive hazards models were fitted separately for each smoking category adjusted for gender, except for former (cessation <2 years) and occasional light smokers due to the small sample size.ResultsAn increasing trend in the disability prevalence was observed across smoking categories in men (never = 4.8%, former (cessation ≥2 years) = 5.8%, daily light = 7.8%, daily heavy = 10.7%) and women (never = 7.6%, former (cessation ≥2 years) = 8.0%, daily light = 10.2%, daily heavy = 12.0%). Musculoskeletal conditions showed a substantial contribution to the disability burden in men and women across all smoking categories. Other important contributors were depression and cardiovascular diseases in never smokers; depression, chronic respiratory diseases, and diabetes in former smokers (cessation ≥2 years); chronic respiratory diseases, cancer, and cardiovascular diseases in daily light smokers; cardiovascular diseases and chronic respiratory diseases in men and depression and diabetes in women daily heavy smokers.ConclusionsBeyond the well-known effect of smoking on mortality, our findings showed an increasing trend of the disability prevalence and different contributors to the disability burden across smoking categories. This information can be useful from a public health perspective to define strategies to reduce disability in Belgium.     

Determinants of Smoking and Quitting in HIV-Infected Individuals

BackgroundCigarette smoking is widespread among HIV-infected patients, who confront increased risk of smoking-related co-morbidities. The effects of HIV infection and HIV-related variables on smoking and smoking cessation are incompletely understood. We investigated the correlates of smoking and quitting in an HIV-infected cohort using a validated natural language processor to determine smoking status.MethodWe developed and validated an algorithm using natural language processing (NLP) to ascertain smoking status from electronic health record data. The algorithm was applied to records for a cohort of 3487 HIV-infected from a large health care system in Boston, USA, and 9446 uninfected control patients matched 3:1 on age, gender, race and clinical encounters. NLP was used to identify and classify smoking-related portions of free-text notes. These classifications were combined into patient-year smoking status and used to classify patients as ever versus never smokers and current smokers versus non-smokers. Generalized linear models were used to assess associations of HIV with 3 outcomes, ever smoking, current smoking, and current smoking in analyses limited to ever smokers (persistent smoking), while adjusting for demographics, cardiovascular risk factors, and psychiatric illness. Analyses were repeated within the HIV cohort, with the addition of CD4 cell count and HIV viral load to assess associations of these HIV-related factors with the smoking outcomes.ResultsUsing the natural language processing algorithm to assign annual smoking status yielded sensitivity of 92.4, specificity of 86.2, and AUC of 0.89 (95% confidence interval [CI] 0.88–0.91). Ever and current smoking were more common in HIV-infected patients than controls (54% vs. 44% and 42% vs. 30%, respectively, both P<0.001). In multivariate models HIV was independently associated with ever smoking (adjusted rate ratio [ARR] 1.18, 95% CI 1.13–1.24, P <0.001), current smoking (ARR 1.33, 95% CI 1.25–1.40, P<0.001), and persistent smoking (ARR 1.11, 95% CI 1.07–1.15, P<0.001). Within the HIV cohort, having a detectable HIV RNA was significantly associated with all three smoking outcomes.ConclusionsHIV was independently associated with both smoking and not quitting smoking, using a novel algorithm to ascertain smoking status from electronic health record data and accounting for multiple confounding clinical factors. Further research is needed to identify HIV-related barriers to smoking cessation and develop aggressive interventions specific to HIV-infected patients.     

Effects of Isoflavone-Enriched Feed on the Rumen Microbiota in Dairy Cows

In this study, we compared the effects of two diets containing different isoflavone concentrations on the isoflavone transfer from feed into milk and on the rumen microbiota in lactating dairy cows. The on-farm experiment was conducted on twelve lactating Czech Fleckvieh x Holstein cows divided into two groups, each with similar mean milk yield. Twice daily, cows were individually fed a diet based on maize silage, meadow hay and supplemental mixture. Control group (CTRL) received the basal diet while the experimental group (EXP) received the basal diet supplemented with 40% soybean isoflavone extract. The average daily isoflavone intake in the EXP group (16 g/day) was twice as high as that in the CTRL group (8.4 g/day, P<0.001). Total isoflavone concentrations in milk from the CTRL and EXP groups were 96.89 and 276.07 μg/L, respectively (P<0.001). Equol concentrations in milk increased from 77.78 μg/L in the CTRL group to 186.30 μg/L in the EXP group (P<0.001). The V3-4 region of bacterial 16S rRNA genes was used for metagenomic analysis of the rumen microbiome. The experimental cows exhibited fewer OTUs at a distance level of 0.03 compared to control cows (P<0.05) and reduced microbial richness compared to control cows based on the calculated Inverse Simpson and Shannon indices. Non-metric multidimensional scaling analysis showed that the major contributor to separation between the experimental and control groups were changes in the representation of bacteria belonging to the phyla Bacteroidetes, Proteobacteria, Firmicutes, and Planctomycetes. Surprisingly, a statistically significant positive correlation was found only between isoflavones and the phyla Burkholderiales (r = 0.65, P<0.05) and unclassified Betaproteobacteria (r = 0.58, P<0.05). Previous mouse and human studies of isoflavone effects on the composition of gastrointestinal microbial populations generally report similar findings.     

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     

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     

Protective Vascular and Cardiac Effects of Inducible Nitric Oxide Synthase in Mice with Hyperhomocysteinemia

Diet-induced hyperhomocysteinemia produces endothelial and cardiac dysfunction and promotes thrombosis through a mechanism proposed to involve oxidative stress. Inducible nitric oxide synthase (iNOS) is upregulated in hyperhomocysteinemia and can generate superoxide. We therefore tested the hypothesis that iNOS mediates the adverse oxidative, vascular, thrombotic, and cardiac effects of hyperhomocysteinemia. Mice deficient in iNOS (Nos2−/−) and their wild-type (Nos2+/+) littermates were fed a high methionine/low folate (HM/LF) diet to induce mild hyperhomocysteinemia, with a 2-fold increase in plasma total homocysteine (P<0.001 vs. control diet). Hyperhomocysteinemic Nos2+/+ mice exhibited endothelial dysfunction in cerebral arterioles, with impaired dilatation to acetylcholine but not nitroprusside, and enhanced susceptibility to carotid artery thrombosis, with shortened times to occlusion following photochemical injury (P<0.05 vs. control diet). Nos2−/− mice had decreased rather than increased dilatation responses to acetylcholine (P<0.05 vs. Nos2+/+ mice). Nos2−/− mice fed control diet also exhibited shortened times to thrombotic occlusion (P<0.05 vs. Nos2+/+ mice), and iNOS deficiency failed to protect from endothelial dysfunction or accelerated thrombosis in mice with hyperhomocysteinemia. Deficiency of iNOS did not alter myocardial infarct size in mice fed the control diet but significantly increased infarct size and cardiac superoxide production in mice fed the HM/LF diet (P<0.05 vs. Nos2+/+ mice). These findings suggest that endogenous iNOS protects from, rather than exacerbates, endothelial dysfunction, thrombosis, and hyperhomocysteinemia-associated myocardial ischemia-reperfusion injury. In the setting of mild hyperhomocysteinemia, iNOS functions to blunt cardiac oxidative stress rather than functioning as a source of superoxide.     

Clustering of Socioeconomic,Behavioural, and Neonatal Risk Factors for Infant Health in Pregnant Smokers

Background

Tobacco smoking is a major cause of morbidity and mortality, including during pregnancy. Although effective ways of promoting smoking cessation during pregnancy exist, the impact of these interventions has not been studied at a national level. We estimated the prevalence of smoking throughout pregnancy in the Netherlands and quantified associations of maternal smoking throughout pregnancy with socioeconomic, behavioural, and neonatal risk factors for infant health and development.

Methodology/Principal Findings

Data of five national surveys, containing records of 14,553 Dutch mothers and their offspring were analyzed. From 2001 to 2007, the overall rate of smoking throughout pregnancy fell by 42% (from 13.2% to 7.6%) mainly as a result of a decrease among highly educated women. In the lowest-educated group, the overall rate of smoking throughout pregnancy was six times as high as in the highest-educated group (18.7% versus 3.2%). Prenatal tobacco smoke exposure was associated with increased risk of extremely preterm (≤28 completed weeks) (OR 7.25; 95% CI 3.40 to 15.38) and small-for-gestational age (SGA) infants (OR 3.08; 95% CI 2.66 to 3.57). Smoking-attributable risk percents in the population (based on adjusted risk ratios) were estimated at 29% for extremely preterm births and at 17% for SGA outcomes. Infants of smokers were more likely to experience significant alcohol exposure in utero (OR 2.08; 95%CI 1.25 to 3.45) and formula feeding in early life (OR 1.91; 95% CI 1.69 to 2.16).

Conclusions

The rates of maternal smoking throughout pregnancy decreased significantly in the Netherlands from 2001 to 2007. If pregnant women were to cease tobacco use completely, an estimated 29% of extremely preterm births and 17% of SGA infants may be avoided annually.     

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 postal prompts to patients and general practitioners on the quality of primary care after a coronary event (POST): randomised controlled trial

ObjectivesTo determine whether postal prompts to patients who have survived an acute coronary event and to their general practitioners improve secondary prevention of coronary heart disease.DesignRandomised controlled trial.Setting52 general practices in east London, 44 of which had received facilitation of local guidelines for coronary heart disease.Participants328 patients admitted to hospital for myocardial infarction or unstable angina.InterventionsPostal prompts sent 2 weeks and 3 months after discharge from hospital. The prompts contained recommendations for lowering the risk of another coronary event, including changes to lifestyle, drug treatment, and making an appointment to discuss these issues with the general practitioner or practice nurse.ResultsPrescribing of β bockers (odds ratio 1.7, 95% confidence interval 0.8 to 3.0, P>0.05) and cholesterol lowering drugs (1.7, 0.8 to 3.4, P>0.05) did not differ between intervention and control groups. A higher proportion of patients in the intervention group (64%) than in the control group (38%) had their serum cholesterol concentrations measured (2.9, 1.5 to 5.5, P<0.001). Secondary outcomes were significantly improved for consultations for coronary heart disease, the recording of risk factors, and advice given. There were no significant differences in patients’ self reported changes to lifestyle or to the belief that it is possible to modify the risk of another coronary event.ConclusionsPostal prompts to patients who had had acute coronary events and to their general practitioners in a locality where guidelines for coronary heart disease had been disseminated did not improve prescribing of effective drugs for secondary prevention or self reported changes to lifestyle. The prompts did increase consultation rates related to coronary heart disease and the recording of risk factors in the practices. Effective secondary prevention of coronary heart disease requires more than postal prompts and the dissemination of guidelines.

Key messages

• Postal prompts to patients and their general practitioners about effective secondary prevention after a myocardial infarction did not improve the prescribing of cholesterol lowering drugs and β blockers
• The prompts did improve general practice recording of cardiovascular risk factors and lifestyle advice given to patients, but they made no difference to patients’ reports of changes to lifestyle
• Other methods are needed to improve the quality of secondary prevention of coronary heart disease in general practice

     

Clinical findings for the first 1000 Gulf war veterans in the Ministry of Defence’s medical assessment programme

ObjectiveTo review the clinical findings in the first 1000 veterans seen in the Ministry of Defence’s Gulf war medical assessment programme to examine whether there was a particular illness related to service in the Gulf.DesignCase series of 1000 veterans who presented to the programme between 11 October 1993 and 24 February 1997.SubjectsGulf war veterans.Results588 (59%) veterans had more than one diagnosed condition, 387 (39%) had at least one condition for which no firm somatic or psychological diagnosis could be given, and in 90 (9%) veterans no other main diagnosis was made. Conditions characterised by fatigue were found in 239 (24%) of patients. At least 190 (19%) patients had a psychiatric condition, which in over half was due to post-traumatic stress disorder. Musculoskeletal disorders and respiratory conditions were also found to be relatively common (in 182 (18%) and 155 (16%) patients respectively).ConclusionMany Gulf war veterans had a wide variety of symptoms. This initial review shows no evidence of a single illness, psychological or physical, to explain the pattern of symptoms seen in veterans in the assessment programme. As the veterans assessed by the programme were all self selected, the prevalence of illness in Gulf war veterans cannot be determined from this study. Furthermore, it is not known whether the veterans in this study were representative of sick veterans as a group.

Key messages

• Many Gulf war veterans present with a wide variety of symptoms
• No single cause has been found to explain these symptoms
• From a clinical standpoint the variety and multiplicity of symptoms makes it unlikely that any single cause will be found to underlie Gulf war illness
• Some of the illnesses may be an example of a postwar syndrome

     

Treatment of Cryptococcal Meningitis in KwaZulu-Natal,South Africa

Background

Cryptococcal meningitis (CM) remains a leading cause of death for HIV-infected individuals in sub-Saharan Africa. Improved treatment strategies are needed if individuals are to benefit from the increasing availability of antiretroviral therapy. We investigated the factors associated with mortality in routine care in KwaZulu-Natal, South Africa.

Methodology/Principal Findings

A prospective year long, single-center, consecutive case series of individuals diagnosed with cryptococcal meningitis 190 patients were diagnosed with culture positive cryptococcal meningitis, of whom 186 were included in the study. 52/186 (28.0%) patients died within 14 days of diagnosis and 60/186 (32.3%) had died by day 28. In multivariable cox regression analysis, focal neurology (aHR 11 95%C.I. 3.08–39.3, P<0.001), diastolic blood pressure <60 mmHg (aHR 2.37 95%C.I. 1.11–5.04, P = 0.025), concurrent treatment for tuberculosis (aHR 2.11 95%C.I. 1.02–4.35, P = 0.044) and use of fluconazole monotherapy (aHR 3.69 95% C.I. 1.74–7.85, P<0.001) were associated with increased mortality at 14 and 28 days.

Conclusions

Even in a setting where amphotericin B is available, mortality from cryptococcal meningitis in this setting is high, particularly in the immediate period after diagnosis. This highlights the still unmet need not only for earlier diagnosis of HIV and timely access to treatment of opportunistic infections, but for better treatment strategies of cryptococcal meningitis.