Risk of cancer in patients with thyroid disease and venous thromboembolism

Diana H Christensen,1 Katalin Veres,1 Anne G Ording,1 Jens Otto L Jørgensen,2 Suzanne C Cannegieter,3 Reimar W Thomsen,1 Henrik T Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands Objective: Risk of venous thromboembolism (VTE) is increased in patients with hypo/hyperthyroidism. It is unknown whether VTE may be a presenting symptom of occult cancer in these patients. Design: Nationwide population-based cohort study based on Danish medical registry data. Methods: We identified all patients diagnosed with VTE during 1978–2013 who had a previous or concurrent diagnosis of hypothyroidism (N=1481) or hyperthyroidism (N=1788). We followed them until a first-time cancer diagnosis, death, emigration, or study end, whichever came first. We calculated 1-year absolute cancer risk and standardized incidence ratios (SIRs) for cancer incidence in the study population compared with national cancer incidence in the general population. Results: During the first year after a VTE diagnosis, the 1-year absolute cancer risk was 3.0% among patients with hypothyroidism and 3.9% among those with hyperthyroidism. During the first year of follow-up, SIRs for cancer in the study population compared with the general population were 1.96 (95% CI: 1.42–2.64) among patients with hypothyroidism and 2.67 (95% CI: 2.07–3.39) among those with hyperthyroidism. SIRs declined substantially after 1 year but remained increased during the remainder of the follow-up period (up to 36 years) (SIR for hypothyroidism=1.16 [95% CI: 0.97–1.39]; SIR for hyperthyroidism=1.26 [95% CI: 1.08–1.46]). Conclusion: VTE may be a marker of underlying occult cancer in patients with hypothyroidism or hyperthyroidism. Keywords: hyperthyroidism, hypothyroidism, venous thromboembolism, cancer, cohort stud

Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo

Whether neurons can restore their original connectivity patterns during circuit repair is unclear. Taking advantage of the regenerative capacity of zebrafish retina, we show here the remarkable specificity by which surviving neurons reassemble their connectivity upon regeneration of their major input. H3 horizontal cells (HCs) normally avoid red and green cones, and prefer ultraviolet over blue cones. Upon ablation of the major (ultraviolet) input, H3 HCs do not immediately increase connectivity with other cone types. Instead, H3 dendrites retract and re-extend to contact new ultraviolet cones. But, if regeneration is delayed or absent, blue-cone synaptogenesis increases and ectopic synapses are made with red and green cones. Thus, cues directing synapse specificity can be maintained following input loss, but only within a limited time period. Further, we postulate that signals from the major input that shape the H3 HC's wiring pattern during development persist to restrict miswiring after damage

The incidence of interstitial lung disease 1995–2005: a Danish nationwide population-based study

<p>Abstract</p> <p>Background</p> <p>Current data on incidence of interstitial lung diseases (ILDs) are sparse and concerns about an increasing trend have been raised. We examined incidence rates (IRs) of ILDs and changes in IRs between 1995 and 2005.</p> <p>Methods</p> <p>All persons with a first-time hospital discharge or outpatient diagnosis of ILD were identified through the Danish National Registry of Patients, which covers all Danish hospitals. Crude and age-standardised IRs were computed for ILD overall, as well as stratified by ILD subcategories.</p> <p>Results</p> <p>A total of 21,765 patients with ILD were identified. Between 1995 and 1998 the overall standardised IR of ILD decreased from 27.14 (95% CI 25.82–28.46) per 100,000 person-years to 19.36 (95% CI 18.26–20.46) per 100,000 person-years. After 1998 the IR increased considerably, peaking at 34.34 (95% CI 32.84–35.85) per 100,000 person-years in 2002. Subsequently there was a slight decrease. The highest IR was observed in the non-specific category "Respiratory disorders in diseases classified elsewhere". By ILD subcategory, the greatest average increase during the study period was observed in "Respiratory disorders in diseases classified elsewhere".</p> <p>Conclusion</p> <p>The incidence rate of ILD in Denmark increased during the study period, most pronounced for ILDs associated with systemic diseases.</p

Single-tooth replacement: factors affecting different prosthetic treatment modalities

<p>Abstract</p> <p>Background</p> <p>The choice between several treatment options for replacing a single missing tooth is influenced by clinical, dentist- and patient-immanent factors. This study aimed to determine the patient factors that would affect the treatment decision to replace a single missing tooth and to assess the satisfaction with several options.</p> <p>Method</p> <p>200 volunteers involved (121 females and 79 males) divided into four groups, Group A: consisted of patients with conventional fixed partial dentures or patients with resin bonded fixed partial dentures. Group B: consisted of patients who received removable partial dentures while Group C: consisted of patients who received a single implant supported crown, and a control group D: consisted of patients who received no treatment. Data were collected using a questionnaire.</p> <p>Results</p> <p>The highest percentage of males within groups (58%) was within the removable prostheses category. The majority of the subjects in the study reported that the main reason for replacing a missing tooth was for esthetic and function. Most important factor affecting the choice between treatment modalities was damaging the neighboring teeth. Pain, post operative sensitivity and dental phobia were important factors in choosing the prosthesis type and affected the control group patients not to have any treatment. The highest satisfaction percentage among groups studied was recorded for dental implants then FPD groups, while the least percentage were in both the control and RPD groups, for all aspects of function, esthetic and speech efficiency.</p> <p>Conclusions</p> <p>The final choice between FPD, RPD and implant depended on several factors which affected the decision making; among these is cost and patients' awareness of the different treatment options.</p

Morbidity, Including Fatal Morbidity, throughout Life in Men Entering Adult Life as Obese

Background: The association between obesity in adults and excess morbidity and mortality is well established, but the health impact throughout adult life of being obese in early adulthood needs elucidation. We investigated somatic morbidity, including fatal morbidity, throughout adulthood in men starting adult life as obese. Methods: Among 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (defined as BMI$31.0 kg/m 2), and, as controls, a random 1 % sample of the others was identified. In the age range of 18–25 years, there were 1,862 obese, which encompass the men above the 99.5 percentile, and 3,476 controls. Information on morbidity was obtained via national registers. Cox regression models were used to estimate the relative morbidity assessed as first incidence of disease, occurrence of disease in the year preceding death and prevalent disease at time of death. Results: From age 18 through 80 years the obese had an increased risk of becoming diseased by or die from a broad range of diseases. Generally, the incidence of first event, occurrence in the year prior to death, and prevalence at time of death showed the same pattern. As an example, the relative hazard of type 2 diabetes was constant throughout life at 4.9 (95% confidence intervals [CI]: 4.1–5.9), 5.2 (95 % CI: 3.6–7.5), and 6.8 (95 % CI: 4.6–10.1), respectively. Conclusions: Our findings strongly support the continued need to avoid beginning adult life as obese, as obese young me

Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.Generalitat Valenciana in Spain (AP140/08) and the Biomedical Research Foundation from the Hospital of Elche, Spain (FIBElx0902). Conselleria de Educació (Generalitat Valenciana); Fundacion Juan Peran-Pikolinos; Fundacion Carolina-BBVA and Fondo Investigación Sanitaria (FI07/00303). Instituto de Salud Carlos III (INT09/208)

Can work ability explain the social gradient in sickness absence: a study of a general population in Sweden

<p>Abstract</p> <p>Background</p> <p>Understanding the reasons for the social gradient in sickness absence might provide an opportunity to reduce the general rates of sickness absence. The complete explanation for this social gradient still remains unclear and there is a need for studies using randomized working population samples. The main aim of the present study was to investigate if self-reported work ability could explain the association between low socioeconomic position and belonging to a sample of new cases of sick-listed employees.</p> <p>Methods</p> <p>The two study samples consisted of a randomized working population (n = 2,763) and a sample of new cases of sick-listed employees (n = 3,044), 19-64 years old. Both samples were drawn from the same randomized general population. Socioeconomic status was measured with occupational position and physical and mental work ability was measured with two items extracted from the work ability index.</p> <p>Results</p> <p>There was an association between lower socioeconomic status and belonging to the sick-listed sample among both women and men. In men the crude Odds ratios increased for each downwards step in socioeconomic status, OR 1.32 (95% CI 0.98-1.78), OR 1.53 (1.05-2.24), OR 2.80 (2.11-3.72), and OR 2.98 (2.27-3.90). Among women this gradient was not as pronounced. Physical work ability constituted the strongest explanatory factor explaining the total association between socioeconomic status and being sick-listed in women. However, among men, the association between skilled non-manual, OR 2.07 (1.54-2.78), and non-skilled manual, OR 2.03 (1.53-2.71) positions in relation to being sick-listed remained. The explanatory effect of mental work ability was small. Surprisingly, even in the sick-listed sample most respondents had high mental and physical work ability.</p> <p>Conclusions</p> <p>These results suggest that physical work ability may be an important key in explaining the social gradient in sickness absence, particularly in women. Hence, it is possible that the factors associated with the social gradient in sickness absence may differ, to some extent, between women and men.</p

Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir-2(dimen)(4)](2+), where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute-solvent pair distribution function, enabling the solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.1