Interventions to improve hand hygiene compliance in patient care

Four studies met the criteria for the review: two from the original review and two from the update. Two studies evaluated simple education initiatives, one using a randomized clinical trial design and the other a controlled before and after design. Both measured hand hygiene compliance by direct observation. The other two studies were both interrupted times series studies. One study presented three separate interventions within the same paper: simple substitutions of product and two multifaceted campaigns, one of which included involving practitioners in making decisions about choice of hand hygiene products and the components of the hand hygiene program. The other study also presented two separate multifaceted campaigns, one of which involved application of social marketing theory. In these two studies follow-up data collection continued beyond 12 months, and a proxy measure of hand hygiene compliance (product use) was recorded. Microbiological data were recorded in one study. Hand hygiene compliance increased for one of the studies where it was measured by direct observation, but the results from the other study were not conclusive. Product use increased in the two studies in which it was reported, with inconsistent results reported for one initiative. MRSA incidence decreased in the one study reporting microbiological data

Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI Direct study

Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n=403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n=458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariate regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred was associated with healthier diets high in wholegrain (β=0.004 g, p=0.02 and β=0.003 g, p=0.03) and lower energy intake (β=-0.0002 kcal, p=0.04 and β=-0.0002 kcal, p=0.003), and saturated fat (β=-0.03 g, p<.0001 and β=-0.03 g, p<.0001), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and improved lipid profiles HDL-cholesterol (β=0.07 mmol/L, p<.0001), (β=0.08 mmol/L, p=0.0002), and triglycerides (β=-0.1 mmol/L, p=0.003), (β=-0.2 mmol/L, p=0.0002), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat content (β=-0.74 %, p<.0001), and lower fasting concentrations of HbA1c (β=-0.9mmol/mol, p=0.02), glucose (β=-0.2 mmol/L, p=0.01) and insulin (β=-11.0 pmol/mol, p=0.01). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, p=0.03) and insulin (β=-9.2 pmol/mol, p=0.04) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health

Improving disease gene prioritization using the semantic similarity of Gene Ontology terms

Motivation: Many hereditary human diseases are polygenic, resulting from sequence alterations in multiple genes. Genomic linkage and association studies are commonly performed for identifying disease-related genes. Such studies often yield lists of up to several hundred candidate genes, which have to be prioritized and validated further. Recent studies discovered that genes involved in phenotypically similar diseases are often functionally related on the molecular level

Impact of observing hand hygiene in practice and research: a methodological reconsideration

The purpose of hand hygiene is to break the chain of healthcare-associated infection. In many countries hand hygiene is regularly audited as part of quality assurance based on recommendations from the World Health Organization. Direct observation is the recommended audit method but is associated with disadvantages, including potential for being observed to alter usual behaviour. The Hawthorne effect in relation to hand hygiene is analogous with productivity improvement by increasing the frequency with which hand hygiene is undertaken. Unobtrusive and/or frequent observation to accustom staff to the presence of observers is considered an acceptable way of reducing the Hawthorne effect, but few publications have discussed how to implement these techniques or examine their effectiveness. There is evidence that awareness of being watched can disrupt the usual behaviour of individuals in complex and unpredictable ways other than simple productivity effect. In the presence of auditors, health workers might defer or avoid activities that require hand hygiene, but these issues are not addressed in guidelines for practice or research studies. This oversight has implications for the validity of hand hygiene audit findings. Measuring hand hygiene product use overcomes avoidance tactics. It is cheaper and generates data continuously to assess the compliance of all clinicians without disrupting patient care. Disadvantages are the risk of overestimating uptake through spillage, wastage, or use by visitors and non-clinical staff entering patient care areas. Electronic devices may overcome the Hawthorne and avoidance effects but are costly and are not widely used outside research studies

Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments

Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments

Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium

Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10−26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10−10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10−8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10−5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusions In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histolog

Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta&lt;5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta&lt;5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites