The wear and tear on health: What is the role of occupation?

Health is well known to show a clear gradient by occupation. Although it may appear evident that occupation can affect health, there are multiple possible sources of selection that can generate a strong association, other than simply a causal effect of occupation on health. We link job characteristics to German panel data spanning 29 years to characterize occupations by their physical and psychosocial burden. Employing a dynamic model to control for factors that simultaneously affect health and selection into occupation, we find that selection into occupation accounts for at least 60% of the association. The effects of occupational characteristics such as physical strain and low job control are negative and increase with age: late‐career exposure to 1 year of high physical strain and low job control is comparable to the average health decline from ageing 16 and 6 months, respectively.     

Occupational generalized urticaria and anaphylaxis after inhalation of cefuroxime in a nurse

We present the case of a 53 years old nonatopic female nurse who experienced repeated anaphylactic reactions at work without involvement in drug‐specific tasks such as crushing of tablets or preparation of injections. The causal allergen was not identified until a further severe anaphylactic reaction occurred after oral use of cefuroxime during a respiratory infection. Sensitization to cefuroxime was demonstrated by specific IgE, basophil activation test and skin prick test. An inhalation challenge with a dosimeter induced generalized urticaria after a cumulative dose of about 10 μg of the drug, but no asthmatic reaction. Complete exposure cessation was initiated and a 1‐year follow‐up was without further allergic reactions. We conclude that work‐related systemic allergic reactions to β‐lactam antibiotics may occur in nurses after inhalation of low doses and without perceived association with drug‐specific tasks like handling of antibiotics.

     

Reconstruction of the atrophic edentulous maxilla with free iliac crest grafts and implants: a 3-year report of a prospective clinical study

Purpose: The purpose of this study was to perform a longitudinal follow-up study of implant stability in grafted maxillae with the aid of clinical, radiological, and resonance frequency analysis (RFA) parameters. Materials and Methods: The atrophic edentulous maxillae in 29 patients were reconstructed with free iliac crest grafts using onlay/inlay or interpositional grafting techniques. The endpoint of the resorption pattern in the maxilla determined the grafting technique used. Endosteal implants were placed after 6 months of bone-graft healing. Implant stability was measured four times using RFA: when the implants were placed, after 6 to 8 months of healing, after 6 months and 3 years of bridge loading. Individual checkups were performed at the two later RFA registrations after removal of the supraconstructions (Procera® Implant Bridge, Nobel Biocare AB, Göteborg, Sweden). Radiological follow up of marginal bone level was performed annually. Results: Twenty-five patients remained for the follow-up period. A total of 192 implants were placed and with a survival rate of 90% at the 3-year follow up. Women and an implant position with a class 6 resorption prior to reconstruction were factors with significant increased risk for implant failure (multivariate logistic regression). Twelve of the 20 failed implants were lost before loading (early failures). The change in the marginal bone level was 0.3 ± 0.3 mm between baseline (bridge delivery) and the 3-year follow up. The implant stability quotient (ISQ) value for all implants differed significantly between abutment connection (60.2 ± 7.3) and after 6 months of bridge loading (62.5 ± 5.5) (Wilcoxon signed ranks test for paired data, p=.05) but were nonsignificant between 6 months of bridge loading and 3 years of bridge loading (61.8 ± 5.5). There was a significant difference between successful and failed implants when the ISQ values were compared for individual implants at placement (Mann-Whitney U test, p=.004). All 25 patients were provided with fixed implant bridges at the time of the 3-year follow up. Conclusion: This clinical follow up using radiological examinations and RFA measurements indicates a predictable and stable long-term result for patients with atrophic edentulous maxillae reconstructed with autogenous bone and with delayed placement of endosteal implants. The ISQ value at the time of placement can probably serve as an indicator of level of risk for implant failure.     

Professional burnout and work engagement among dentists

A recent development within burnout research is the shift to its conceptual opposite: work engagement. This study aimed to unravel the concepts of burnout and work engagement, and to determine their levels among dentists. A representative sample of 497 Dutch general dental practitioners was included (survey response rate of 59%), consisting of 372 men and 121 women (the gender of 4 dentists remained unknown). The hypothesized three-factor structure of work engagement (vigor, dedication, and absorption), as measured by the Utrecht Work Engagement Scale (UWES), was substantiated among dentists. It was also found that work engagement was related negatively to burnout, as measured by the Maslach Burnout Inventory (MBI). However, a model consisting of a reduced ('core') burnout factor and an 'enhanced' engagement factor (composed of the three original factors plus the burnout factor, personal accomplishment) showed the best fit. Overall burnout levels among dentists are low, and the levels of engagement indicate that dentists have a positive working attitude.     

Novel homogenous time-resolved fluorometric RT-PCR assays for quantification of PSA and hK2 mRNAs in blood

Objectives:The purpose of this study was to design, validate, and optimize internally standardized real-time quantitative RT-PCR assays and to identify and avoid problems with assay reliability and examine the impact of an exogenous internal standard.Design and methods:The model system consisted of internally standardized quantitative real-time RT-PCR assays specific for PSA and hK2 mRNA based on time-resolved fluorometric detection of lanthanide chelates.Results:Reproducibility was best when large copy numbers (> 5000 per milliliter blood) were analyzed. Addition of an exogenous target-mimicking internal standard had no significant effect on the reproducibility of the method, but increased the calculated copy numbers by an average of 2-fold.Conclusions:We developed an internally standardized, specific and reproducible real-time RT-PCR analysis method for PSA and hK2 mRNA in circulating cells in the bloodstream. Both PSA and hK2 assays are sufficiently sensitive to detect two LNCaP cells per milliliter whole blood.     

An approach to shortening the timeframe between the emergence of new compounds on the drugs market and the availability of reference standards: The microscale syntheses of nitrazolam and clonazolam for use as reference materials,utilizing polymer‐supported reagents

Nitrazolam and clonazolam are 2 designer benzodiazepines available from Internet retailers. There is growing evidence suggesting that such compounds have the potential to cause severe adverse events. Information about tolerability in humans is scarce but typically, low doses can be difficult to administer for users when handling bulk material. Variability of the active ingredient in tablet formulations can also be of a concern. Customs, toxicology and forensic laboratories are increasingly encountering designer benzodiazepines, both in tablet and powdered form. The unavailability of reference standards can impact on the ability to identify these compounds. Therefore, the need arises for exploring in‐house approaches to the preparation of new psychoactive substances (NPS) that can be carried out in a timely manner. The present study was triggered when samples of clonazolam were received in powdered and tablet form at a time when reference material for this drug was commercially unavailable. Therefore, microscale syntheses of clonazolam and its deschloro analog nitrazolam were developed utilizing polymer‐supported reagents starting from 2‐amino‐2'‐chloro‐5‐nitrobenzophenone (clonazolam) and 2‐amino‐5‐nitrobenzophenone (nitrazolam). The final reaction step forming the 1,2,4‐triazole ring moiety was performed within a gas chromatography–mass spectrometry (GC–MS) injector. A comparison with a preparative scale synthesis of both benzodiazepine derivatives showed that microscale synthesis might be an attractive option for a forensic laboratory in terms of time and cost savings when compared with traditional methods of synthesis and when qualitative identifications are needed to direct forensic casework. The reaction by‐product profiles for both the micro and the preparative scale syntheses are also presented.     

Different in vitro and in vivo tools for elucidating the human metabolism of alpha‐cathinone‐derived drugs of abuse

In vitro and in vivo experiments are widely used for studying the metabolism of new psychoactive substances (NPS). The availability of such data is required for toxicological risk assessments and development of urine screening approaches. This study investigated the in vitro metabolism of the 5 pyrrolidinophenone‐derived NPS alpha‐pyrrolidinobutyrophenone (alpha‐PBP), alpha‐pyrrolidinopentiothiophenone (alpha‐PVT), alpha‐pyrrolidinohexanophenone (alpha‐PHP), alpha‐pyrrolidinoenanthophenone (alpha‐PEP, PV8), and alpha‐pyrrolidinooctanophenone (alpha‐POP, PV9). First, they were incubated with pooled human liver microsomes (pHLM) or pooled human liver S9 fraction (pS9) for identification of the main phase I and II metabolites. All substances formed hydroxy metabolites and lactams. Longer alkyl chains resulted in keto group and carboxylic acid formation. Comparing these results with published data obtained using pHLM, primary human hepatocytes (PHH), and authentic human urine samples, PHH provided the most extensive metabolism. Second, enzyme kinetic studies showed that the initial metabolic steps were formed by cytochrome P450 isoforms (CYP) CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 resulting in pyrrolidine, thiophene or alkyl hydroxy metabolites depending on the length of the alkyl chain. The kinetic parameters indicated an increasing affinity of the CYP enzymes with increase of the length of the alkyl chain. These parameters were then used to calculate the contribution of a single CYP enzyme to the in vivo hepatic clearance. CYP2C19 and CYP2D6 were mainly involved in the case of alpha‐PBP and CYP1A2, CYP2C9 and CYP2C19 in the case of alpha‐PVT, alpha‐PHP, alpha‐PEP, and alpha‐POP.