25 research outputs found
Estimated Worldwide Mortality Attributed to Secondhand Tobacco Smoke Exposure, 1990-2016
Importance: The World Health Organization estimates that the 1 billion individuals who smoke worldwide contribute to the 880 000 secondhand smoke (SHS)-related deaths among individuals who do not smoke each year. A better understanding of the scale of harm of SHS to those who do not smoke could increase awareness of the consequences of smoking and help to design measures to protect individuals who do not smoke, especially children. Objective: To calculate the number of individuals who smoke associated with the death of 1 individual who died of SHS exposure both on a global scale and in various World Bank regions. Design, Setting, and Participants: In this cross-sectional epidemiologic assessment, data from Our World in Data were used to tabulate the number of individuals who smoke in each country and number of premature deaths related to SHS in that country from 1990 to 2016. The mean number of cigarettes consumed in all countries was also included in analyses. Data were collected for the following World Bank regions: North America, Latin America and the Caribbean, Europe and Central Asia, the Middle East and North Africa, sub-Saharan Africa, South Asia, and East Asia and the Pacific from 1990 and 2016. Statistical analysis was conducted in July 2019. Exposure: Secondhand smoke. Main Outcomes and Measures: The pack-year index, calculated as the number of pack-years associated with the death of 1 individual who does not smoke but was exposed to SHS, and the SHS index, calculated as the number of individuals who smoked for 24 years (ie, the mean duration of smoking) associated with the death of 1 individual who does not smoke. Results: Globally, the SHS index changed favorably, from 31.3 (95% CI, 30.6-32.0) individuals who smoked associated with the death of 1 individual who did not smoke in 1990 to 52.3 (95% CI, 51.2-53.5) individuals who smoked in 2016. There was a wide regional variation in the 2016 secondhand smoke index, from 42.6 (95% CI, 41.6-43.5) individuals who smoked in the Middle East and North Africa to 85.7 (95% CI, 83.8-87.7) individuals who smoked in North America. Worldwide, the pack-year index also changed favorably from 751.9 (95% CI, 736.3-770.7) pack-years associated with 1 death in 1990 to 1255.9 (95% CI, 1227.2-1284.4) pack-years in 2016. Conclu
Screening for germline DND1 mutations in testicular cancer patients
Although several observations suggest that a strong genetic predisposition to developing testicular germ cell tumors (TGCT) exists, no associated, highly penetrant germline mutations have been identified so far. In the 129/Sv mouse strain, a germline mutation in the DND1 gene has been shown to strongly increase the TGCT risk. We screened 272 men with TGCT (89% sporadic cases, 11% familial) for germline mutations in the human homologue of DND1. A single nucleotide substitution c.657C > G (p.Asp219Glu) was observed in a non-familial case of testicular embryonal carcinoma. The variant was also present in the patient’s asymptomatic father and two brothers, but not observed in 210 control chromosomes. The wild type DND1 allele was not lost in the patient’s tumor. In silico analysis of the variant predicts it to be non-pathogenic. We conclude that germline DND1 mutations are unlikely to contribute significantly to human testicular germ cell tumor susceptibility. The role of human DND1 in normal physiology and disease, however, is still virtually unknown and it therefore warrants further research
Evaluating Comprehensibility of 157 Patient-Reported Outcome Measures (PROMs) in the Nationwide Dutch Outcome-Based Healthcare Program:More Attention for Comprehensibility of PROMs is Needed
IntroductionPatient-reported outcomes measures (PROMs) are increasingly prevalent in healthcare and used for shared decision-making and healthcare quality evaluation. However, the extent to which patients with varying health literacy levels can complete PROMs is often overlooked. This may lead to biased aggregated data and patients being excluded from studies or other PROM collection initiatives. This cross-sectional study evaluates the comprehensibility of 157 well-known and widely used PROM scales using a comprehensibility checklist.MethodsPairs of two independent raters scored 157 PROM scales designed for adults included in the 35 sets of outcome information developed as part of the Dutch Outcome-Based Healthcare Program. The PROM scales were scored on the eight comprehensibility domains of the Pharos Checklist for Questionnaires in Healthcare (PCQH). Interrater agreement of domain ratings was assessed using Intraclass Correlation Coefficients or Cohen's kappa. Subsequently, final ratings were established through discussion and used to evaluate the domain-specific comprehensibility rating for each PROM scale.ResultsComprehensibility of a large number of PROM scales (n = 157), which cover a wide range of diseases and conditions across Dutch medical specialist care, was assessed. While most PROM scales were written at an accessible language level, with minimal use of medical terms, instruction clarity, number of questions, and response options emerged as significant issues, affecting a substantial proportion of PROM scales. Interrater agreement was high for most domains of the PCQH.ConclusionThis study highlights the need for greater attention to the comprehensibility of PROMs to ensure their accessibility to all patients, including those with low health literacy. The PCQH can be a valuable tool in PROM development in addition to qualitative methods and in selection processes enabling comparison of comprehensibility between PROMs. However, the PCQH needs further development and validation for these purposes. Enhancing the comprehensibility of PROMs is essential for their effective incorporation in healthcare evaluation and decision-making processes
Association of a Public Health Campaign About Coronavirus Disease 2019 Promoted by News Media and a Social Influencer With Self-reported Personal Hygiene and Physical Distancing in the Netherlands
Importance: In the absence of a vaccine and therapeutic agent, personal hygiene and physical distancing are essential measures to contain the coronavirus disease 2019 pandemic. Objective: To determine whether a social media campaign, targeted at the gaps in behavior on personal hygiene and physical distancing and distributed nationwide via digital news media, may be an effective method to improve behavior and help to inhibit person-to-person transmission of severe acute respiratory syndrome coronavirus 2. Design, Setting, and Participants: This survey study was designed to uncover self-reported gaps in behavior regarding personal hygiene and physical distancing in the Netherlands. A diagnostic survey was distributed by a large national newspaper (De Telegraaf) and a popular social influencer (Govert Sweep) on March 17, 2020, and was completed by 16 072 participants. Analysis of these outcomes showed that coughing and sneezing in the elbow was done well, but that handwashing, face touching, and physical distancing showed serious gaps compared with advised behavior. This diagnostic information was used to design infographics and a video targeted at repairing these gaps in behavior. The video and infographics were distributed on a national level on March 21, 2020, followed by a postcampaign survey to measure the results on March 24, 2020. Data analysis was performed from March to April 2020. Exposure: Exposed participants were those who viewed the infographics and/or video. Main Outcomes and Measures: Improvement on the extent of handwashing in all areas, handwashing duration of 20 seconds or longer, awareness on face touching, and physical distancing were measured according to responses on the postcampaign survey. Results: A total of 17 189 participants (mean [SD] age, 47.61 [13.57] years; 9100 women [52.9%]) responded to the postcampaign survey. The news article in De Telegraaf was read more than 2 million times, and the influencer video was watched more than 80 000 times. Cross-sectional analysis of the postcampaign survey using logistic regression correcting for age, gender, and educational level showed that exposure to the video plus infographics (827 participants) (adjusted odds ratio [OR], 2.14; 95% CI, 1.83-2.50; P < .001) and to the infographics alone (11 348 participants) (adjusted OR, 1.31; 95% CI, 1.22-1.40; P < .001) were positively associated with washing hands in all areas compared with the unexposed group (4751 participants). In addition, exposure to the video plus infographics (adjusted OR, 1.86; 95% CI, 1.59-2.16; P < .001) and to the infographics alone (adjusted OR, 1.27; 95% CI, 1.19-1.36; P < .001) were positively associated with washing hands long enough compared with the unexposed group. Exposure to the video alone was not associated with improved handwashing. Compared with the unexposed group, exposure to the infographics alone and video plus infographics were associated with improvements in physical distancing when the participant had COVID-19 syptoms (infographics alone, adjusted OR, 1.10; 95% CI, 1.03-1.17; P = .006; video plus infographics, adjusted OR, 0.79; 95% CI, 0.69-0.91; P = .001) and face touching
Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum
Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.</p
Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum
Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions
RET and EDNRB mutation screening in patients with Hirschsprung disease: Functional studies and its implications for genetic counseling
Hirschsprung disease (HSCR) is a major cause of chronic constipation in children. HSCR can be caused by germline mutations in RET and EDNRB. Defining causality of the mutations identified is difficult and almost exclusively based on in silico predictions. Therefore, the reported frequency of pathogenic mutations might be overestimated. We combined mutation analysis with functional assays to determine the frequencies of proven pathogenic RET and EDNRB mutations in HSCR. We sequenced RET and EDNRB in 57 HSCR patients. The identified RET-coding variants were introduced into RET constructs and these were transfected into HEK293 cells to determine RET phosphorylation and activation via ERK. An exon trap experiment was performed to check a possible splice-site mutation. We identified eight rare RET-coding variants, one possible splice-site variant, but no rare EDNRB variants. Western blotting showed that three coding variants p.(Pr270Leu), p.(Ala756Val) an
Vitamin K-Antagonists Accelerate Atherosclerotic Calcification and Induce a Vulnerable Plaque Phenotype
Vitamin K-antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE(-/-) model of atherosclerosis.A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE(-/-) mice (10 weeks) received a Western type diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with vitamin K(1) (VK(1), 1.5 mg/g) or vitamin K(1) and warfarin (VK(1)&W; 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE(-/-) mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle
Genotype-phenotype correlations in L1 syndrome:a guide for genetic counselling and mutation analysis
Objectives To develop a comprehensive mutation analysis system with a high rate of detection, to develop a tool to predict the chance of detecting a mutation in the L1CAM gene, and to look for genotype-phenotype correlations in the X-linked recessive disorder, L1 syndrome.Methods DNA from 367 referred patients was analysed for mutations in the coding sequences of the gene. A subgroup of 100 patients was also investigated for mutations in regulatory sequences and for large duplications. Clinical data for 106 patients were collected and used for statistical analysis.Results 68 different mutations were detected in 73 patients. In patients with three or more clinical characteristics of L1 syndrome, the mutation detection rate was 66% compared with 16% in patients with fewer characteristics. The detection rate was 51% in families with more than one affected relative, and 18% in families with one affected male. A combination of these two factors resulted in an 85% detection rate (OR 10.4, 95% CI 3.6 to 30.1). The type of mutation affects the severity of L1 syndrome. Children with a truncating mutation were more likely to die before the age of 3 than those with a missense mutation (52% vs 8%; p=0.02).Conclusions We developed a comprehensive mutation detection system with a detection rate of almost 20% in unselected patients and up to 85% in a selected group. Using the patients' clinical characteristics and family history, clinicians can accurately predict the chance of finding a mutation. A genotype-phenotype correlation was confirmed. The occurrence of (maternal) germline mosaicism was proven.</p