Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis.

Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying mechanisms are thought related to dysbiosis of the gut microbiome. We conducted a systematic review of the association between antibiotics and disruption of the pediatric gut microbiome. Searches used MEDLINE, EMBASE and Web of Science. Eligible studies: association between antibiotics and gut microbiome dysbiosis; children 0-18 years; molecular techniques of assessment; outcomes of microbiome richness, diversity or composition. Quality assessed by Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Meta-analysis where possible. A total of 4,668 publications identified: 12 in final analysis (5 randomized controlled trials (RCTs), 5 cohort studies, 2 cross-sectional studies). Microbiome richness was measured in 3 studies, species diversity in 6, and species composition in 10. Quality of evidence was good or fair. 5 studies found a significant reduction in diversity and 3 a significant reduction in richness. Macrolide exposure was associated with reduced richness for twice as long as penicillin. Significant reductions were seen in Bifidobacteria (5 studies) and Lactobacillus (2 studies), and significant increases in Proteobacteria such as E. coli (4 studies). A meta-analysis of RCTs of the effect of macrolide (azithromycin) exposure on the gut microbiome found a significant reduction in alpha-diversity (Shannon index: mean difference -0.86 (95% CI -1.59, -0.13). Antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. The potential for dysbiosis in the microbiome should be taken into account when prescribing antibiotics for children.Systematic review registration number: CRD42018094188.

Ethnic differences in smoking intensity and COPD risk: an observational study in primary care.

Chronic obstructive pulmonary disease risk is lower in black and south Asian people than white people, when adjusting for age, sex, deprivation and smoking status. The role of smoking intensity was assessed for its contribution to ethnic differences in chronic obstructive pulmonary disease risk, a relationship not previously investigated. This cross-sectional study included routinely collected primary care data from four multi-ethnic London boroughs. Smoking intensity (estimated by cigarettes per day) was compared between ethnic groups. Chronic obstructive pulmonary disease risk was compared between ethnic groups using multiple logistic regression, controlling for age, sex, deprivation, asthma and both smoking status and smoking intensity, examined independently. In all, 1,000,388 adults were included. Smoking prevalence and intensity were significantly higher in the white British/Irish groups than other ethnic groups. Higher smoking intensity was associated with higher chronic obstructive pulmonary disease risk. Chronic obstructive pulmonary disease risk was significantly lower in all ethnic groups compared with white British/Irish after adjustment for either smoking status or smoking intensity, with lowest risk in black Africans (odds ratio 0.33; confidence interval 0.28-0.38). Ethnic differences in chronic obstructive pulmonary disease risk were not explained in this study by ethnic differences in smoking prevalence or smoking intensity. Other causes of ethnic differences in chronic obstructive pulmonary disease risk should be sought, including ethnic differences in smoking behaviour, environmental factors, repeated respiratory infections, immigrant status, metabolism and addictiveness of nicotine and differential susceptibility to the noxious effects of cigarette smoke.COPD: SMOKING INTENSITY NOT BEHIND ETHNIC DIFFERENCES IN DISEASE RISK: Lower smoking intensity among blacks and south Asians does not explain their lower risk for chronic obstructive pulmonary disease (COPD). A UK team led by Alexander Gilkes from Kings College London analysed primary care data from more than a million people living in four multi-ethnic boroughs of the British capital. The researchers found that smoking status and intensity (as measured by number of cigarettes smoked per day) were both significantly higher in white British or Irish groups than in other ethnic populations. Even after statistically adjusting for smoking status or smoking intensity, however, the researchers couldn't account for the fact that people of south Asian or African descent had much lower prevalence rates of COPD, a lung disease linked to smoking. The findings suggest that other explanations of ethnic differences are still needed.

Is individual smoking behaviour influenced by area-level ethnic density? A cross-sectional electronic health database study of inner south-east London.

Tobacco smoking remains one of the greatest public health problems facing the UK today. It varies significantly by ethnic group. This study aimed to determine whether ethnic differences in smoking behaviour are related to neighbourhood-level, own-group ethnic density across south and east London. The association between ethnic density and individual smoking behaviour was assessed by multilevel logistic regression using the electronic health records of 688 397 general practitioner-registered patients. Restricted cubic splines were created to explore whether the effect of ethnic density on smoking behaviour was nonlinear. Increasing own-group ethnic density was found to be associated with a significant reduction in the odds of being a current smoker in all ethnic groups, except for Black Caribbean women. The relationship between ethnic density and current smoking was found to be nonlinear, with the strength of association varying significantly by sex and ethnic group. These novel findings point to a complex relationship between culture, neighbourhood-level experience of adversity or social support and smoking behaviour, and will allow us to target smoking cessation services differentially to individuals/groups living in relative ethnic isolation, who do not benefit from the potential cultural/social factors associated with reduced tobacco consumption.

Hospital readmissions for COPD: a retrospective longitudinal study.

Prevention of chronic obstructive pulmonary disease hospital readmissions is an international priority aimed to slow disease progression and limit costs. Evidence of the risk of readmission and of interventions that might prevent it is lacking. We aimed to determine readmission risk for chronic obstructive pulmonary disease, factors influencing that risk, and variation in readmission risk between hospitals across 7.5 million people in London. This retrospective longitudinal observational study included all chronic obstructive pulmonary disease admissions to any hospital in the United Kingdom among patients registered at London general practices who had emergency National Health Service chronic obstructive pulmonary disease hospital admissions between April 2006 and March 2010. Influence of patient characteristics, geographical deprivation score, length of stay, day of week of admission or of discharge, and admitting hospital, were assessed using multiple logistic regression. 38,894 chronic obstructive pulmonary disease admissions of 20,932 patients aged ≥ 45 years registered with London general practices were recorded. 6295 patients (32.2%) had at least one chronic obstructive pulmonary disease readmission within 1 year. 1993 patients (10.2%) were readmitted within 30 days and 3471 patients (17.8%) were readmitted within 90 days. Age and patient geographical deprivation score were very weak predictors of readmission. Rates of chronic obstructive pulmonary disease readmissions within 30 days and within 90 days did not vary among the majority of hospitals. The finding of lower chronic obstructive pulmonary disease readmission rates than was previously estimated and the limited variation in these rates between hospitals suggests that the opportunity to reduce chronic obstructive pulmonary disease readmission risk is small. CHRONIC LUNG DISEASE: LOWER RISK OF READMISSION FOR LONDON-BASED PATIENTS: A managed reduction of hospital readmissions for London-based chronic lung disease patients may not be needed. Preventing hospital readmissions for patients with chronic obstructive pulmonary disease (COPD) is a key priority to improve patient care and limit costs. However, few data are available to determine and ultimately reduce the risk of readmission. Timothy Harries at King's College, London, and co-workers conducted a longitudinal study incorporating all COPD admissions into UK hospitals for 20,932 patients registered at London general practitioners between 2006 and 2010. They found that 32% of patients were readmitted within a year, 17.8% within 90 days and 10% within 30 days. Neither age nor geographical deprivation were useful predictors of readmission. These represent lower than estimated levels of readmission, suggesting there may be fewer opportunities to reduce the risk of readmission further.

Long term condition morbidity in English general practice: a cross-sectional study using three composite morbidity measures.

BACKGROUND: The burden of morbidity represented by patients with long term conditions (LTCs) varies substantially between general practices. This study aimed to determine the characteristics of general practices with high morbidity burden. METHOD: Retrospective cross-sectional study; general practices in England, 2014/15. Three composite morbidity measures (MMs) were constructed to quantify LTC morbidity at practice level: a count of LTCs derived from the 20 LTCs included in the UK Quality and Outcomes Framework (QOF) disease registers, expressed as 'number of QOF LTCs per 100 registered patients'; the % of patients with one or more QOF LTCs; the % of patients with one or more of 15 broadly defined LTCs included in the GP Patient Survey (GPPS). Determinants of MM scores were analysed using multi-level regression models. Analysis was based on a national dataset of English general practices (n = 7779 practices); GPPS responses (n = 903,357); general practice characteristics (e.g. list size, list size per full time GP); patient demographic characteristics (age, deprivation status); secondary care utilisation (out-patient, emergency department, emergency admission rates). RESULTS: Mean MM scores (95% CIs) were: 57.7 (±22.3) QOF LTCs per 100 registered patients; 22.8% (±8.2) patients with a QOF LTC; 63.5% (±11.7) patients with a GPPS LTC. The proportion of elderly patients and social deprivation scores were the strongest predictors of each MM score; scores were largely independent of practice characteristics. MM scores were positive predictors of secondary care utilization and negative predictors' access, continuity of care and overall satisfaction. CONCLUSIONS: Wide variation in LTC morbidity burden was observed across English general practice. Variation was determined by demographic factors rather than practice characteristics. Higher rates of secondary care utilisation in practices with higher morbidity burden have implications for resource allocation and commissioning budgets; lower reported satisfaction in these practices suggests that practices may struggle with increased workload. There is a need for a readily available metric to define the burden of morbidity and multimorbidity in general practice.

Does COPD risk vary by ethnicity? A retrospective cross-sectional study.

BACKGROUND: Lower risk of COPD has been reported in black and Asian people, raising questions of poorer recognition or reduced susceptibility. We assessed prevalence and severity of COPD in ethnic groups, controlling for smoking. METHOD: A retrospective cross-sectional study using routinely collected primary care data in London. COPD prevalence, severity (% predicted forced expiratory volume in 1 second [FEV1]), smoking status, and treatment were compared between ethnic groups, adjusting for age, sex, smoking, deprivation, and practice clustering. RESULTS: Among 358,614 patients in 47 general practices, 47.6% were white, 20% black, and 5% Asian. Prevalence of COPD was 1.01% overall, 1.55% in whites, 0.58% in blacks, and 0.78% in Asians. COPD was less likely in blacks (adjusted odds ratio [OR], 0.44; 95% confidence interval [CI] 0.39-0.51) and Asians (0.82; CI, 0.68-0.98) than whites. Black COPD patients were less likely to be current smokers (OR, 0.56; CI, 0.44-0.71) and more likely to be never-smokers (OR, 4.9; CI, 3.4-7.1). Treatment of patients with similar disease severity was similar irrespective of ethnic origin, except that long-acting muscarinic antagonists were prescribed less in black COPD patients (OR, 0.53; CI, 0.42-0.68). Black ethnicity was a predictor of poorer lung function (% predicted FEV1: B coefficient, -7.6; P<0.0001), an effect not seen when ethnic-specific predicted FEV1 values were used. CONCLUSION: Black people in London were half as likely as whites to have COPD after adjusting for lower smoking rates in blacks. It seems likely that the differences observed were due either to ethnic differences in the way cigarettes were smoked or to ethnic differences in susceptibility to COPD.

Length of stay of COPD hospital admissions between 2006 and 2010: a retrospective longitudinal study.

BACKGROUND: Hospitalizations for COPD are associated with poor patient prognosis. Length of stay (LOS) of COPD admissions in a large urban area and patient and hospital factors associated with it are described. METHODS: Retrospective longitudinal study. All COPD patients registered with London general practitioners and admitted as an emergency with COPD (2006-2010), not having been admitted with COPD in the preceding 12 months were included. Association of patient and hospital characteristics with mean LOS of COPD admissions was assessed. Association between hospital and LOS was determined by negative binomial regression. RESULTS: The total number of admissions was 38,504, from 22,462 patients. The mean LOS for first admissions fell by 0.8 days (95% confidence interval [CI]: 0.7-1.5) from 8.2 to 7.0 days between 2006 and 2010. Seventy-nine percent of first admissions were ≤10 days, with a mean LOS of 3.7 days (2009-2010). The mean LOS of successive COPD admissions of the same patients was the same or less throughout the study period. The interval between successive admissions fell from a mean of 357 days between the first and second admission to a mean of 19 days after eight admissions. Age accounted for 2.3% of the variance in LOS. Socioeconomic deprivation did not predict LOS. Fewer discharges happened at the weekend (1,893/day) than on weekdays (5,218/day). The mean LOS varied between hospitals, from 4.9 days (95% CI: 3.8-5.9) to 9.5 days (95% CI: 8.6-10.3) when adjusting for clustering, age, sex, and socioeconomic deprivation. CONCLUSION: The fall in LOS of the first COPD admission between 2006 and 2010 reflects international trends. The stability of LOS in successive admissions suggests that increasing severity of disease does not affect recovery time from an exacerbation. Variations between hospitals of nearly 5 days in LOS for COPD admissions suggests that significant improvements in patient outcomes and in savings in health care utilization could be made in hospitals with longer LOS.