Guidelines for health surveillance of health care workers exposed to biological risks set up by the Italian Society for Occupational Health and Industrial Hygiene: application in health facilities of the Regional Health Administration--District No. 7, Ancona

BACKGROUND: Evidence Based Medicine and the need to achieve better management of health budgets call for verification and, if necessary, revision of the criteria used in Occupational Health, in order to ensure appropriate measures as regards protection of health at the workplace. In December 2003, the Marche Region initiated a process of reform of the regional health service, which will be completed in two years, and will provide a new regional health organization that will improve the quality and appropriateness of health services available to the population. The reform also involves the Occupational Health Services responsible for prevention activities for 20,000 health care workers employed in regional public health facilities. The need was strongly felt to set up a network that would meet the health needs of health care workers, by adopting a common language among occupational health physicians, by eliminating reported criticism, which is due not only to lack of communication between different structures and profiles, but also to the different methods of approach, evaluation and management of occupational risks. OBJECTIVES AND METHODS: From a historical point of view, the health sector has the biggest as regards prevention of biological risk. Therefore, with a view to harmonizing actions and approach among occupational health physicians in the evaluation of this risk, the publication by the Italian Society for Occupational of Health and Industrial Hygiene of Guidelines for health surveillance of health care workers exposed to biological risks, produced by the working group under the leadership of Prof. Lorenzo Alessio, was considered to offer an interesting opportunity to verify the reproducibility of methods and the quality of results, as applied to health facilities under the Regional Health Administration in Ancona (District No. 7). RESULTS AND CONCLUSION: The Guidelines fully confirmed the need to plan activities, starting from analysis of epidemiological and occupational data, thus assuring good results both in terms of efficacy and efficiency of the health surveillance programme used. This method also assures a high level of appropriateness of medical measures as regards the "safety" target, at the same time avoiding waste and poor management of human and economic resources, which were till now caused by differences in methods used in assessment of biological risk.     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.     

Assessment of cardiovascular risk in shift healthcare workers.

BACKGROUND: Shift work has been associated with an increased risk of cardiovascular disease (CVD); in particular, night work affects the circadian rhythm. DESIGN AND METHODS: The study examines the effectiveness of three screening methods and plasma hyperhomocysteinemia, an independent risk factor, in assessing the risk of CVD in 147 healthcare providers doing daytime or rotational shift work. The methods applied were: (i) the method proposed by the European Cardiovascular Indicators Surveillance Set (EUROCISS); (ii) the metabolic syndrome (MS) criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) and (iii) the MS criteria of the International Diabetes Federation (IDF). RESULTS: EUROCISS was unable to distinguish between the CVD risk of daytime and rotational shift workers. Both the ATPIII and the IDF detected MS, which is strongly associated with CVD, but only the IDF evidenced a significantly greater prevalence of MS (P<0.05) among shift workers. Hyperhomocysteinemia was unable to discriminate the CVD risk between daytime and shift workers, as it was influenced by multiple confounding factors. CONCLUSIONS: The increased risk of CVD associated with shift work is related to the greater incidence of MS among these workers. In our study a high prevalence of MS was detected only with the IDF. The method is useful for CVD prevention and the promotion of health during any medical examination of shift workers.     

Discrepancies in reverse ABO typing due to prozone

Three group O sera manifesting prozone in reverse ABO tests are reported. All were implicated in erroneous blood typing results. One sample failed to react with A1 red cells (RBCs) in immediate-spin (IS) tests, had anti-A and -B titers of 8192 and 2048, respectively, by indirect antiglobulin technique (IAT), and was from a diabetic patient; the parenteral administration of A substance present in porcine insulin is a possible cause of hyperimmunity in this case. The second sample was from the recipient of a single unit of group B fresh-frozen plasma; the serum anti-A and -B titers were 10,240 by IAT, but only weak reactions with A1 and B RBCs were noted in routine IS reverse typing tests; the hyperimmunity in the patient concerned was likely due to crossreacting anti-A, B stimulated by B-active glycoproteins and/or glycolipids in the transfused plasma. The third serum also had anti-A and anti-B IAT titers of 10,240 but did not react with A1 and B RBCs by IS; the hyperimmunity in this case may be related to sepsis from intestinal flora carrying A- and/or B-like antigens. These antibodies lysed A1 and/or B RBCs in tests incubated at room temperature (RT) and strongly agglutinated those RBCs by IS when diluted 10-fold with saline. The absence of the prozone phenomenon in tests with RBCs suspended in diluents containing EDTA is consistent with the previously published mechanism for anti-A prozone: namely, the steric hindrance of agglutination by the C1 component of human complement.(ABSTRACT TRUNCATED AT 250 WORDS)