Thrombocytopenia is a common finding in several diseases but almost nothing is known about the prevalence of thrombocytopenia in the general population. We examined the prevalence of thrombocytopenia ...and determinants of platelet count in a healthy population with a wide age range.
We performed a cross-sectional study on 12,517 inhabitants of ten villages (80% of residents) in a secluded area of Sardinia (Ogliastra). Participants underwent a complete blood count evaluation and a structured questionnaire, used to collect epidemiological data.
We observed a platelet count lower than 150 × 10⁹/L in 3.2% (2.8%-3.6%) of females and 4.8% (4.3%-5.4%) of males, with a value of 3.9% (3.6%-4.3%) in the entire population. Thrombocytopenia was mild (platelet count: 100 × 10⁹/L-150 × 10⁹/L), asymptomatic and not associated with other cytopenias or overt disorders in most cases. Its standardized prevalence was quite different in different villages, with values ranging from 1.5% to 6.8%, and was negatively correlated with the prevalence of a mild form of thrombocytosis, which ranged from 0.9% to 4.5%. Analysis of platelet counts across classes of age revealed that platelet number decreased progressively with aging. As a consequence, thrombocytopenia was nearly absent in young people and its prevalence increased regularly during lifetime. The opposite occurred for thrombocytosis.
Given the high genetic differentiation among Ogliastra villages with "high" and "low" platelet counts and the substantial heritability of this quantitative trait (54%), we concluded that the propensity to present mild and transient thrombocytosis in youth and to acquire mild thrombocytopenia during aging are new genetic traits.
Cardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality ...risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data.
Clinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression.
From 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2-34.6) in 2010 to 20.9% (20.0-21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9-4.8) in 2017 to 3.4 (3.0-3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03-1.14) for all-cause mortality; 1.32 (1.09-1.59) for cardiovascular mortality).
Left-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors. Comorbid left-sided HF is also a poor prognostic marker. More substantial reduction in left-sided HF prevalence than incidence suggests persistently high IPF mortality. Given rising IPF incidence in the UK, this calls for better management of comorbidities such as left-sided HF to help optimise IPF survival.
Myopia is one of most common eye diseases in the world and affects 1 in 4 Americans. It is a complex disease caused by both environmental and genetics effects; the genetics effects are still not well ...understood. In this study, we performed genetic linkage analyses on Ashkenazi Jewish families with a strong familial history of myopia to elucidate any potential causal genes.
Sixty-four extended Ashkenazi Jewish families were previously collected from New Jersey. Genotypes from the Illumina ExomePlus array were merged with prior microsatellite linkage data from these families. Additional custom markers were added for candidate regions reported in literature for myopia or refractive error. Myopia was defined as mean spherical equivalent (MSE) of -1D or worse and parametric two-point linkage analyses (using TwoPointLods) and multi-point linkage analyses (using SimWalk2) were performed as well as collapsed haplotype pattern (CHP) analysis in SEQLinkage and association analyses performed with FBAT and rv-TDT.
Strongest evidence of linkage was on 1p36(two-point LOD = 4.47) a region previously linked to refractive error (MYP14) but not myopia. Another genome-wide significant locus was found on 8q24.22 with a maximum two-point LOD score of 3.75. CHP analysis also detected the signal on 1p36, localized to the LINC00339 gene with a maximum HLOD of 3.47, as well as genome-wide significant signals on 7q36.1 and 11p15, which overlaps with the MYP7 locus.
We identified 2 novel linkage peaks for myopia on chromosomes 7 and 8 in these Ashkenazi Jewish families and replicated 2 more loci on chromosomes 1 and 11, one previously reported in refractive error but not myopia in these families and the other locus previously reported in the literature. Strong candidate genes have been identified within these linkage peaks in our families. Targeted sequencing in these regions will be necessary to definitively identify causal variants under these linkage peaks.
Background: Determining the proportion of susceptible workers can represent a first step to the biological risk assessment related to measles, mumps, rubella and varicella exposure. This study aimed ...to assess the immunity against measles, mumps, rubella and varicella viruses in a cohort of female school workers. Methods: A cross-sectional seroepidemiological study in a sample of 263 school workers undergoing routine annual workplace health surveillance program was conducted. As part of the health surveillance program, serum samples were collected and tested for measles, mumps, rubella and varicella IgG antibodies. Results: Overall seropositivity was 90.5%, 85.2%, 94.7% and 97.3% for measles, mumps, rubella and varicella, respectively. In relation to mumps occupation-specific seropositivity, a statistically significant difference was observed, showing the lowest prevalence of protected individuals in other occupation groups. Moreover, in relation to rubella, school workers born in Centre Italy had the lowest seropositivity of protective antibodies and the difference between groups was statistically significant. Measles and rubella seropositivity showed a significant decrease after 2015. Conclusions: This study showed a relevant proportion of school workers susceptible to the aforementioned diseases. These results highlighted the need for proper health surveillance and immunological controls in school workers, especially for females, and provided useful insights to policymakers to select effective strategies aimed at containing the risk of vaccine-preventable diseases at schools.
Background and Aims
Communication of personalised disease risk can motivate smoking cessation. We assessed whether routine implementation of this intervention by general practitioners (GPs) in ...England is cost‐effective or whether we need further research to better establish its effectiveness.
Design
Cost‐effectiveness analysis (CEA) with value of information (VoI) analysis from the UK National Health Service perspective, using GP communication of personalised disease risk on smoking cessation versus usual care.
Setting
GP practices in England.
Study population
Healthy smokers aged 35–60 years attending the GP practice.
Measurements
Effectiveness of GP communication of personalised disease risk on smoking cessation was estimated through systematic review and meta‐analysis. A Bayesian CEA was then performed using a lifetime Markov model on smokers aged 35–60 years that measured lifetime costs and quality‐adjusted life‐years (QALYs) assigned to the four diseases contributing the most to smoking‐related morbidity, mortality and costs: chronic obstructive pulmonary disease, lung cancer, myocardial infarction and stroke. Costs and QALYs for each disease state were obtained from the literature. VoI analysis identified sources of uncertainty in the CEA and assessed how much would be worth investing in further research to reduce this uncertainty.
Findings
The meta‐analysis odds ratio for the effectiveness estimate of GP communication of personalised disease risk was 1.48 (95% credibility interval, 0.91–2.26), an absolute increase in smoking cessation rates of 3.84%. The probability of cost‐effectiveness ranged 89–94% depending on sex and age. VoI analysis indicated that: (i) uncertainty in the effectiveness of the intervention was the driver of the overall uncertainty in the CEA; and (ii) a research investment to reduce this uncertainty is justified if lower than £27.6 million (£7 per smoker).
Conclusions
Evidence to date shows that, in England, incorporating disease risk communication into general practitioners’ practices to motivate smoking cessation is likely to be cost‐effective compared with usual care.
This paper presents the results of the zooarchaeological analysis of the faunal materials brought to light during the excavations set up in the Nuragic village surrounding the Santu Antine Nuraghe, ...near Torralba (Sassari), Sardinia. Precisely, the remains come from the structure of the village named by archaeologists hut 12. They are 779 specimens out of thousands animal remains from the whole archaeological site. The majority of the rests belong to sheep (Ovis aries) or goats (Capra hircus), cattle (Bos taurus), pigs (Sus scrofa) and deers (Cervus elaphus). Such material may provide suggestions about the productive use of animals in the village and point out the importance of the economical management of animals in the Nuragic society. Indeed, many remains show signs with human origin, which testify that the hut may have been a workplace where bone fragments were processed to obtain different kind of tools.
During the underwater excavations carried out in the Santa Giusta Pond, near Oristano, Sardinia, a significant amount of Phoenician- Punic materials was brought to light including amphorae (dating ...back to 7th-2nd century BC) and vegetal and animal remains. All of these archaeological finds may come from Othoca, an important Phoenician- Punic city on the eastern shore of the pond, geographically corresponding with the modern-day town of Santa Giusta. Animal materials consist of more than 3000 very well-preserved remains, belonging to sheep (Ovis aries), goat (Capra hircus) and cattle (Bos taurus). Bone analyses allowed reconstructing the slaughtering methods, as well as manipulation procedures carried out to preserve meat in order to be exported overseas. Although pig (Sus scrofa) played an important economical role in other Sardinian Phoenician-Punic settlements, in this archaeological context this species is absent, suggesting that the meat contained in the amphorae was probably destined to other areas of the Mediterranean basin, where people did not eat pork.
Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a ..."triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings.
First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.
In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex.
Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
Lung Development Genes and Adult Lung Function Portas, Laura; Pereira, Miguel; Shaheen, Seif O ...
American journal of respiratory and critical care medicine,
09/2020, Letnik:
202, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Poor lung health in adult life may occur partly through suboptimal growth and development, as suggested by epidemiological evidence pointing to early life risk factors.
To systematically investigate ...the effects of lung development genes on adult lung function.
Using UK Biobank data, we tested the association of 391 genes known to influence lung development with FVC and FEV
/FVC. We split the dataset into two random subsets of 207,616 and 138,411 individuals, using the larger subset to select the most promising signals and the smaller subset for replication.
We identified 55 genes, of which 36 (16 for FVC, 19 for FEV
/FVC, and one for both) had not been identified in the largest, most recent genome-wide study of lung function. Most of these 36 signals were intronic variants; expression data from blood and lung tissue showed that the majority affect the expression of the genes they lie within. Further testing of 34 of these 36 signals in the CHARGE and SpiroMeta consortia showed that 16 replicated after Bonferroni correction and another 12 replicated at nominal significance level. Of the 55 genes, 53 fell into four biological categories whose function is to regulate organ size and cell integrity (growth factors; transcriptional regulators; cell-to-cell adhesion; extracellular matrix), suggesting that these specific processes are important for adult lung health.
Our study demonstrates the importance of lung development genes in regulating adult lung function and influencing both restrictive and obstructive patterns. Further investigation of these developmental pathways could lead to druggable targets.
Background: Symptoms, severity, and acuteness of peripheral artery disease (PAD) are major determinants of severe limb symptoms, subsequent risk of cardiovascular events, and mortality. ...Lower-extremity revascularization (LER) is a key option to relieve symptoms and to prevent limb loss in symptomatic patients with PAD. This study aimed to quantify the burden of disease among patients with PAD-LER in England. Methods: A retrospective population-based study of linked primary and secondary care electronic health records, included 13,869 adult patients (aged ⩾ 18 years) with PAD-LER from 2003 to 2018. The incidence of first ever PAD-LER was estimated both overall and by type of procedure (endovascular/surgical). Health resource utilization associated with PAD-related complications and treatment patterns were assessed. Results: A high annual incidence of lower-limb revascularization (41.2 per 1000 person years) and a nearly double incidence of endovascular first revascularization compared with open surgery were observed. More than 70% of patients with PAD-LER had a history of hyperlipidemia and hypertension and roughly one-third were diabetic and had a history of coronary artery disease. Cardiovascular mortality accounted for one-third (34.1 per 1000 person years) of all-cause mortality. Over 93% of patients were hospitalized for any reason and the commonest reasons for hospitalization were cardiovascular diseases and PAD with about one-third hospitalized for revascularization reoccurrence. Conclusion: There is a significant burden of PAD-LER to the individual and society with ongoing healthcare resource utilization, treatment, and increasing mortality.
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