Validation of the surgical fear questionnaire in adult patients waiting for elective surgery

Objectives: Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. Methods: Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. Results: EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1-4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5-10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765-0.920 (SFQ-total), 0.766-0.877 (SFQ-s), and 0.628-0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. Discussion: The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.This study was conducted with departmental funding and supported by a grant from The Netherlands Organisation for Scientific Research (Zon-MW, http://www.zonmw.nl/en/), grant no. 110000007. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Pharmacogenomics in diabetes mellitus:insights into drug action and drug discovery

Genomic studies have greatly advanced our understanding of the multifactorial aetiology of type 2 diabetes mellitus (T2DM) as well as the multiple subtypes of monogenic diabetes mellitus. In this Review, we discuss the existing pharmacogenetic evidence in both monogenic diabetes mellitus and T2DM. We highlight mechanistic insights from the study of adverse effects and the efficacy of antidiabetic drugs. The identification of extreme sulfonylurea sensitivity in patients with diabetes mellitus owing to heterozygous mutations in HNF1A represents a clear example of how pharmacogenetics can direct patient care. However, pharmacogenomic studies of response to antidiabetic drugs in T2DM has yet to be translated into clinical practice, although some moderate genetic effects have now been described that merit follow-up in trials in which patients are selected according to genotype. We also discuss how future pharmacogenomic findings could provide insights into treatment response in diabetes mellitus that, in addition to other areas of human genetics, facilitates drug discovery and drug development for T2DM.</p

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

Background Studies have shown altered vitamin D metabolism in obesity. We assessed differences between obese and normal-weight subjects in total, free, and bioavailable 25-hydroxyvitamin D (25(OH) D, 25(OH) D-Free, and 25(OH) D-Bio, respectively), vitamin D binding protein (DBP), parathyroid hormone (PTH) and bone traits. Methods 595 37-47-year-old healthy Finnish men and women stratified by BMI were examined in this cross-sectional study. Background characteristic and intakes of vitamin D and calcium were collected. The concentrations of 25(OH) D, PTH, DBP, albumin and bone turnover markers were determined from blood. 25(OH) D-Free and 25(OH) D-Bio were calculated. pQCT was performed at radius and tibia. Results Mean +/- SE (ANCOVA) 25(OH) D-Free (10.8 +/- 0.6 vs 12.9 +/- 0.4 nmol/L; P = 0.008) and 25(OH) DBio (4.1 +/- 0.3 vs 5.1 +/- 0.1 nmol/L; P = 0.003) were lower in obese than in normal-weight women. In men, 25(OH) D (48.0 +/- 2.4 vs 56.4 +/- 2.0 nmol/L, P = 0.003), 25(OH) D-Free (10.3 +/- 0.7 vs 12.5 +/- 0.6 pmol/L; P = 0.044) and 25(OH) D-Bio (4.2 +/- 0.3 vs 5.1 +/- 0.2 nmol/L; P = 0.032) were lower in obese. Similarly in all subjects, 25(OH) D, 25(OH) D-Free and 25(OH) D-Bio were lower in obese (P Conclusions The associations between BMI and 25(OH) D, 25(OH) D-Free, and 25(OH) D-Bio, DBP, and PTH suggest that obese subjects may differ from normal-weight subjects in vitamin D metabolism. BMI associated positively with trabecular bone traits and CSI in our study, and slightly negatively with cortical bone traits. Surprisingly, there was a negative association of free and bioavailable 25(OH) D and some of the bone traits in obese women.Peer reviewe

Mycobacterium tuberculosis causing tuberculous lymphadenitis in Maputo, Mozambique

BACKGROUND: The zoonosis bovine tuberculosis (TB) is known to be responsible for a considerable proportion of extrapulmonary TB. In Mozambique, bovine TB is a recognised problem in cattle, but little has been done to evaluate how Mycobacterium bovis has contributed to human TB. We here explore the public health risk for bovine TB in Maputo, by characterizing the isolates from tuberculous lymphadenitis (TBLN) cases, a common manifestation of bovine TB in humans, in the Pathology Service of Maputo Central Hospital, in Mozambique, during one year. RESULTS: Among 110 patients suspected of having TBLN, 49 had a positive culture result. Of those, 48 (98 %) were positive for Mycobacterium tuberculosis complex and one for nontuberculous mycobacteria. Of the 45 isolates analysed by spoligotyping and Mycobacterial Interspersed Repetitive Unit - Variable Number Tandem Repeat (MIRU-VNTR), all were M. tuberculosis. No M. bovis was found. Cervical TBLN, corresponding to 39 (86.7 %) cases, was the main cause of TBLN and 66.7 % of those where from HIV positive patients. We found that TBLN in Maputo was caused by a variety of M. tuberculosis strains. The most prevalent lineage was the EAI (n?=?19; 43.2 %). Particular common spoligotypes were SIT 48 (EAI1_SOM sublineage), SIT 42 (LAM 9), SIT 1 (Beijing) and SIT53 (T1), similar to findings among pulmonary cases. CONCLUSIONS: M. tuberculosis was the main etiological agent of TBLN in Maputo. M. tuberculosis genotypes were similar to the ones causing pulmonary TB, suggesting that in Maputo, cases of TBLN arise from the same source as pulmonary TB, rather than from an external zoonotic source. Further research is needed on other forms of extrapulmonary TB and in rural areas where there is high prevalence of bovine TB in cattle, to evaluate the risk of transmission of M. bovis from cattle to humans.Swedish International Development Cooperation Agency / Department for Research Cooperation (Sida/SAREC) through Eduardo Mondlane University and Karolinska Institutet Research and Training (KIRT) collaboratio

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 &times; 10-11 to 5.0 &times; 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 &times; 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Bayesian network imputation methods applied to multi-omics data identify putative causal relationships in a type 2 diabetes dataset containing incomplete data: An IMI DIRECT Study

Here we report the results from exploratory analysis using a Bayesian network approach of data originally derived from a large North European study of type 2 diabetes (T2D) conducted by the IMI DIRECT consortium. 3029 individuals (795 with T2D and 2234 without) within 7 different study centres provided data comprising genotypes, proteins, metabolites, gene expression measurements and many different clinical variables. The main aim of the current study was to demonstrate the utility of our previously developed method to fit Bayesian networks by performing exploratory analysis of this dataset to identify possible causal relationships between these variables. The data was analysed using the BayesNetty software package, which can handle mixed discrete/continuous data with missing values. The original dataset consisted of over 16,000 variables, which were filtered down to 260 variables for analysis. Even with this reduction, no individual had complete data for all variables, making it impossible to analyse using standard Bayesian network methodology. However, using the recently proposed novel imputation method implemented in BayesNetty we computed a large average Bayesian network from which we could infer possible associations and causal relationships between variables of interest. Our results confirmed many previous findings in connection with T2D, including possible mediating proteins and genes, some of which have not been widely reported. We also confirmed potential causal relationships with liver fat that were identified in an earlier study that used the IMI DIRECT dataset but was limited to a smaller subset of individuals and variables (namely individuals with complete data at pre-defined variables of interest). In addition to providing valuable confirmation, our analyses thus demonstrate a proof-of-principle of the utility of the method implemented within BayesNetty. The full final average Bayesian network generated from our analysis is freely available and can be easily interrogated further to address specific focussed scientific questions of interest

DNA restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates from HIV-seropositive and HIV-seronegative patients in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>The identification and differentiation of strains of <it>Mycobacterium tuberculosis </it>by DNA fingerprinting has provided a better understanding of the epidemiology and tracing the transmission of tuberculosis. We set out to determine if there was a relationship between the risk of belonging to a group of tuberculosis patients with identical mycobacterial DNA fingerprint patterns and the HIV sero-status of the individuals in a high TB incidence peri-urban setting of Kampala, Uganda.</p> <p>Methods</p> <p>One hundred eighty three isolates of <it>Mycobacterium tuberculosis </it>from 80 HIV seropositive and 103 HIV seronegative patients were fingerprinted by standard IS<it>6110</it>-RFLP. Using the BioNumerics software, strains were considered to be clustered if at least one other patient had an isolate with identical RFLP pattern.</p> <p>Results</p> <p>One hundred and eighteen different fingerprint patterns were obtained from the 183 isolates. There were 34 clusters containing 54% (99/183) of the patients (average cluster size of 2.9), and a majority (96.2%) of the strains possessed a high copy number (≥ 5 copies) of the IS<it>6110 </it>element. When strains with <5 bands were excluded from the analysis, 50.3% (92/183) were clustered, and there was no difference in the level of diversity of DNA fingerprints observed in the two sero-groups (adjusted odds ratio [aOR] 0.85, 95%CI 0.46–1.56, <it>P </it>= 0.615), patients aged <40 years (aOR 0.53, 95%CI 0.25–1.12, <it>P </it>= 0.100), and sex (aOR 1.12, 95%CI 0.60–2.06, <it>P </it>= 0.715).</p> <p>Conclusion</p> <p>The sample showed evidence of a high prevalence of recent transmission with a high average cluster size, but infection with an isolate with a fingerprint found to be part of a cluster was not associated with any demographic or clinical characteristics, including HIV status.</p

Does socioeconomic status affect mortality subsequent to hospital admission for community acquired pneumonia among older persons?

BACKGROUND: Low socioeconomic status has been associated with increased morbidity and mortality for various health conditions. The purpose of this study was twofold: to examine the mortality experience of older persons admitted to hospital with community acquired pneumonia and to test the hypothesis of whether an association exists between socioeconomic status and mortality subsequent to hospital admission for community-acquired pneumonia. METHODS: A population based retrospective cohort study was conducted including all older persons patients admitted to Ontario hospitals with community acquired pneumonia between April 1995 and March 2001. The main outcome measures were 30 day and 1 year mortality subsequent to hospital admission for community-acquired pneumonia. RESULTS: Socioeconomic status for each patient was imputed from median neighbourhood income. Multivariate analyses were undertaken to adjust for age, sex, co-morbid illness, hospital and physician characteristics. The study sample consisted of 60,457 people. Increasing age, male gender and high co-morbidity increased the risk for mortality at 30 days and one year. Female gender and having a family physician as attending physician reduced mortality risk. The adjusted odds of death after 30-days for the quintiles compared to the lowest income quintile (quintile 1) were 1.02 (95% CI: 0.95–1.09) for quintile 2, 1.04 (95% CI: 0.97–1.12) for quintile 3, 1.01 (95% CI: 0.94–1.08) for quintile 4 and 1.03 (95% CI: 0.96–1.12) for the highest income quintile (quintile 5). For 1 year mortality, compared to the lowest income quintile the adjusted odds ratios were 1.01 (95% CI: 0.96–1.06) for quintile 2, 0.99 (95% CI: 0.94–1.04) for quintile 3, 0.99 (95% CI: 0.93–1.05) for quintile 4 and 1.03 (95% CI: 0.97–1.10) for the highest income quintile. CONCLUSION: Socioeconomic status is not associated with mortality in the older persons from community-acquired pneumonia in Ontario, Canada