Hospital admission after primary care consultation for community-onset lower urinary tract infection: a cohort study of risks and predictors using linked data

BACKGROUND: Urinary tract infections (UTIs) are a common indication for antibiotic prescriptions, reductions in which would reduce antimicrobial resistance (AMR). Risk stratification of patients allows reductions to be made safely. AIM: To identify risk factors for hospital admission following UTI, to inform targeted antibiotic stewardship. DESIGN AND SETTING: Retrospective cohort study of East London primary care patients. METHOD: Hospital admission outcomes following primary care consultation for UTI were analysed using linked data from primary care, secondary care, and microbiology, from 1 April 2012 to 31 March 2017. The outcomes analysed were urinary infection-related hospital admission (UHA) and all-cause hospital admission (AHA) within 30 days of UTI in primary care. Odds ratios between specific variables (demographic characteristics, prior antibiotic exposure, and comorbidities) and the outcomes were predicted using generalised estimating equations, and fitted to a final multivariable model including all variables with a P-value <0.1 on univariable analysis. RESULTS: Of the 169 524 episodes of UTI, UHA occurred in 1336 cases (0.8%, 95% confidence interval [CI] = 0.7 to 0.8) and AHA in 6516 cases (3.8%, 95% CI = 3.8 to 3.9). On multivariable analysis, increased odds of UHA were seen in patients aged 55-74 years (adjusted odds ratio [AOR] 1.49) and ≥75 years (AOR 3.24), relative to adults aged 16-34 years. Increased odds of UHA were also associated with chronic kidney disease (CKD; AOR 1.55), urinary catheters (AOR 2.01), prior antibiotics (AOR 1.38 for ≥3 courses), recurrent UTI (AOR 1.33), faecal incontinence (FI; AOR 1.47), and diabetes mellitus (DM; AOR 1.37). CONCLUSION: Urinary infection-related hospital admission after primary care consultation for community-onset lower UTI was rare; however, increased odds for UHA were observed for some patient groups. Efforts to reduce antibiotic prescribing for suspected UTI should focus on patients aged <55 years without risk factors for complicated UTI, recurrent UTI, DM, or FI

Recognition, telling and getting help with abuse and neglect: Young people's perspectives

An understanding of children's perspectives on telling about abuse and neglect has potential to boost children's access to services. The literature on disclosure has mostly focused on child sexual abuse with many studies based on adult survivors' accounts of their childhoods. However, disclosure is one part of a wider process which also includes how children recognise abuse and experience services. This paper presents findings from a thematic analysis of 30 interviews with children and young people who had experienced multiple types of abuse and neglect. A conceptual framework for understanding how children and young people recognise and tell about abuse and neglect and what they think of the help they receive is presented. The framework is used to present case studies tracing the processes of recognition, telling and help over time, in relation to multiple problems of abuse. Implications for professional practice are discussed

Thromboembolic and haemorrhagic events in patients with atrial fibrillation: a prospective cohort study in UK primary and secondary care

BACKGROUND: Strong evidence on the long-term safety and efficacy of different types of anticoagulants would help clinicians to prevent thromboembolic events among patients with atrial fibrillation (AF) while minimising the risk of haemorrhages. AIM: To estimate the risk of thromboembolic and haemorrhagic events for patients with AF on antiplatelets or anticoagulants. DESIGN AND SETTING: This was a cohort study using routinely collected UK primary and secondary care clinical data from patients with AF, aged ≥18 years, and with an indication to receive anticoagulation before April 2012. METHOD: The risk of ischaemic stroke or transient ischaemic attack (TIA), coronary heart disease (CHD), peripheral artery disease (PAD), or gastrointestinal (GI) haemorrhage, between 1 April 2012 and 1 April 2017, was estimated using multivariate Cox regression models for patients on antiplatelets only, a combination of antiplatelets and vitamin K antagonists (VKAs), or novel oral anticoagulants (NOACs), and compared with those on VKAs only. RESULTS: Compared with VKAs, antiplatelets were associated with a higher risk of stroke or TIA, hazard ratio (HR) 1.51, 95% confidence interval (CI) = 1.09 to 2.09, and GI haemorrhage, HR 1.79, 95% CI = 1.01 to 3.18. The risk of thromboembolic and haemorrhagic events was similar for those on a combination of antiplatelets and VKAs, or those on VKAs only. The risk was also similar for those on NOACs or VKAs, except for CHD, where it was higher for patients on NOACs, HR 2.07, 95% CI = 1.35 to 3.19. CONCLUSION: Anticoagulants are associated with lower risk of thromboembolic and haemorrhagic events among patients with AF than antiplatelets. More research is required on the risk associated with VKAs or NOACs

Common and Rare Variant Analysis in Early-Onset Bipolar Disorder Vulnerability

Bipolar disorder is one of the most common and devastating psychiatric disorders whose mechanisms remain largely unknown. Despite a strong genetic contribution demonstrated by twin and adoption studies, a polygenic background influences this multifactorial and heterogeneous psychiatric disorder. To identify susceptibility genes on a severe and more familial sub-form of the disease, we conducted a genome-wide association study focused on 211 patients of French origin with an early age at onset and 1,719 controls, and then replicated our data on a German sample of 159 patients with early-onset bipolar disorder and 998 controls. Replication study and subsequent meta-analysis revealed two genes encoding proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We performed additional replication studies in two datasets from the WTCCC (764 patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436 controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the WTCCC sample. In addition, we identified in the French cohort one affected individual with a deletion at the PLCXD3 locus and another one carrying a missense variation in PLCXD3 (p.R93H), both supporting a role of the phosphatidylinositol pathway in early-onset bipolar disorder vulnerability. Although the current nominally significant findings should be interpreted with caution and need replication in independent cohorts, this study supports the strategy to combine genetic approaches to determine the molecular mechanisms underlying bipolar disorder

Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 x 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 x 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 x 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies

Genome-wide association results and detailed peak association regions.

<p>(<b>A</b>) Manhattan plot of the meta-analysis performed on early-onset bipolar patients and controls from France and Germany. Physical position is shown along the <i>x</i> axis and –log10(<i>P</i>-value) is shown along the <i>y</i> axis. (<b>B</b>) Detail of the two most associated regions on chromosomes 5p13 and 12p12. Allele frequency differences are represented by –log10(<i>P</i>-values) for the French (open grey circles), the German (open grey squares) and the meta- (open red diamonds) analyses. Grey crosses represent –log10(<i>P</i>-value) for imputed ungenotyped SNPs. The most associated SNP for each region is shown with orange circle. On chromosome 12p12, the lowest <i>P</i>-value (<i>P</i> = 2.1×10⁻⁷) was observed for an imputed SNP (<i>rs10743315</i>). On chromosome 5p13, the lowest <i>P</i>-value (<i>P</i> = 2.6×10⁻⁷) was observed for a three-SNPs window haplotype (light blue line) located downstream to <i>OXCT1</i> and upstream to <i>PLCXD3</i> (<i>rs624097-rs316762-rs10512793</i>). The genome-wide significant threshold (<i>P</i> = 5×10⁻⁸) is indicated by the blue dash line and the dot black line shows a threshold at <i>P</i> = 5×10⁻⁵. The largest differences in allele frequencies are represented with filled diamonds. Gene position and annotation (<a href="http://genome.ucsc.edu/" target="_blank">http://genome.ucsc.edu/</a>) are symbolised by green arrows. Linkage disequilibrium (r²) estimated according to HapMap CEU population SNPs (release 3) is symbolised in the bottom part of each figure. Darker red indicates higher values.</p

Regions associated at <i>P</i><5×10⁻⁵ with early-onset BD in meta-analysis.

<p>OR, odds ratio; Q, <i>P</i>-value for Cochrane's Q statistic; I², heterogeneity index.</p>a<p>position from the short arm telomere based on Hg18.</p

Genome-wide Association Study Identifies Genetic Variation in Neurocan as a Susceptibility Factor for Bipolar Disorder

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies