tive predictive value of provocation tests with beta-lactams. Allergy 2010; 65: 327-332.Provocation tests with beta-lactams play an important role in the diagnosis of hypersensitivity reactions to these antibiotics (1-3). In particular, drug provocation tests are included in both of the diagnostic algorithms of the European Network for Drug Allergy (ENDA) for evaluating immediate and nonimmediate hypersensitivity reactions to beta-lactams (2, 3). Immediate reactions are those occurring within the first hour after the last drug administration and are manifested clinically by urticaria, angioedema, rhinitis, bronchospasm and anaphylactic shock. Non-immediate reactions occur more than one hour after the last drug administration. The main non-immediate reactions are maculopapular eruptions and delayed-appearing urticaria/angioedema.Indications of provocation tests with beta-lactams are extensive for the European Academy of Allergology and Clinical Immunology -ENDA group (2-4) and more restricted for the American Academy of Allergy Asthma and Immunology (5). Recently, ENDA simplified the protocol of provocation tests in patients with immediate reactions to beta-lactams by reducing the number of doses (6). In addition, the ENDA questionnaire (7) allows patients with a potential beta-lactam allergy to be identified, and recommendations on drug provocation tests are available (4).Though not well established, the negative predictive value is important for both the patient and the physician. The patient has to know whether a reaction can occur after taking a drug, which was tested negatively. It is now well known that adverse drug reaction and especially drug allergy/ hypersensitivity are sources of anxiety and led to an avoidance of the drug. On the other hand, the physician has to Keywords allergy; beta-lactams; drug provocation tests; hypersensitivity; negative predictive value. Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). Conclusion: Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups.

The most important causes of anaphylaxis in our study were foods, and the most common symptoms were respiratory and cutaneous. The prevalence of anaphylaxis was higher in males and, in two thirds of patients there was a history of atopy. Despite being the primary and most important treatment for anaphylaxis, adrenaline is still used in only a minority of these cases.

IntroductionResults of systematic screening of healthcare workers (HCWs) for tuberculosis (TB) with the tuberculin skin test (TST) and interferon-γ release assays (IGRA) in a Portuguese hospital from 2007 to 2010 are reported.MethodsAll HCWs are offered screening for TB. Screening is repeated depending on risk assessment. TST and QuantiFERON Gold In-Tube (QFT) are used simultaneously. X-ray is performed when TST is > 10 mm, IGRA is positive or typical symptoms exist.ResultsThe cohort comprises 2,889 HCWs. TST and IGRA were positive in 29.5%, TST-positive but IGRA-negative results were apparent in 43.4%. Active TB was diagnosed in twelve HCWs - eight cases were detected during screening and four cases were predicted by IGRA as well as by TST. However, the progression rate in IGRA-positive was higher than in TST-positive HCWs (0.4% vs. 0.2%, p-value 0.06).ConclusionsThe TB burden in this cohort was high (129.8 per 100,000 HCWs). However, the progression to active TB after a positive TST or positive IGRA was considerably lower than that reported in literature for close contacts in low-incidence countries. This may indicate that old LTBI prevails in these HCWs.

The prevalence of latent tuberculosis (TB) infection (LTBI) and the incidence of active tuberculosis in healthcare workers (HCWs) in a Portuguese hospital were examined.This cross-sectional study comprises 4,735 hospital workers screened between May 2005 and September 2008. Tuberculin skin test (TST) and interferon-c release assay (IGRA) were used simultaneously in 1,219 HCWs (25.7%). Radiographs were taken in symptomatic HCWs or in testpositive HCWs. The tests were repeated annually or bi-annually depending on risk assessment.IGRA was positive in 32.6% and TST in 74.2% of the HCWs. Years spent in healthcare were a risk factor for a positive IGRA, but not for a positive TST. Repeated bacillus Calmette-Guérin vaccination increased the probability of TST+/IGRA-discordance (35.4% versus 54.4%, respectively). In those tested three times with TST during the study period (n559), the mean diameter of TST increased from 5 to 7 to 10 mm. Within 3 yrs, 31 HCWs were diagnosed with active TB (annual incidence rate 191 out of 100,000 people). In eight HCWs with active TB, TST and IGRA were performed at the time of diagnosis and each test was positive.TB burden in HCWs in Portugal is high. With IGRA, the number of radiographs needed to exclude active TB could have been reduced by about half without missing a case of active TB. Therefore IGRA should be introduced into TB screening programmes.

Purpose: To report on 2 cases of aggressive posterior retinopathy of prematurity (ROP) treated with intravitreal ranibizumab (Lucentis®) and laser photocoagulation. Methods: Two premature females, born at 25 and 26 weeks’ gestation with a birth weight of 530 and 550 g, respectively, with aggressive posterior ROP received combined treatment with laser photocoagulation and intravitreal ranibizumab (0.3 mg [30 µl]) to each eye. Structural outcomes were evaluated by indirect ophthalmoscopy and documented by retinography. Results: An intravitreal injection was made at 34 weeks of postmenstrual age in the first case, followed by laser photocoagulation 1 week later. There was a partial regression of ROP with treatment. Five weeks later, neovascularization regrowth with bleeding in both eyes (intraretinal and subhyaloid) occurred and retreatment with combined therapy was performed. In the second case, single therapy with laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the confluent photocoagulation in the avascular area, progression to 4A ROP stage occurred 1 week later. Both eyes were retreated 1 week later with intravitreal ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in both cases. There were no signs of systemic or ocular adverse side effects. Conclusion: The cases presented show that combination therapy of indirect laser photocoagulation and intravitreal ranibizumab can be effective in the management of aggressive posterior ROP. Further investigation on anti-VEGF safety in premature infants is necessary . Additional studies are needed to define the role of anti-VEGF in ROP treatment.

ObjectivesVaccination of healthcare workers (HCWs) was made a high priority during the phase six pandemic of the novel influenza A H1N1 (pH1N1) virus. We surveyed adherence to pH1N1 vaccination and the incidence of pH1N1 infection between vaccinated and unvaccinated HCWs.MethodsEmployees at the S. João Hospital in Porto, Portugal, were offered pH1N1 vaccinations free of charge. Pandemrix® was the vaccine administered. As part of the pandemic plan, employees with influenza-like symptoms (ILS) were called upon to take an RT-PCR H1N1 test. If the test results were positive, they had to stay off work for at least 7 days. Sociodemographic data, vaccination status, contact with infectious patients, ILS and pH1N1 test results were documented in a standardised manner.ResultsThe survey population comprised 5,592 employees. The vaccination rate was 30.8% (n = 1,720) for pH1N1 and 50.4% (n = 2,819) for the 2009/2010 seasonal trivalent inactivated influenza vaccine (TIV). One mild anaphylactic reaction occurred after pH1N1 vaccination. Minor local side effects occurred more often after pH1N1 vaccination than after 2009/2010 seasonal TIV (38.0% vs. 12.3%). Pandemic H1N1 infection was diagnosed in 97 HCWs (1.7%). Compared to employees with no regular patient contact, nurses (2.8%) had the highest risk of pH1N1 infection (adjusted OR 3.8; 95% CI 1.2–6.8). Vaccination reduced the pH1N1 infection risk (OR 0.12; 95% CI 0.05–0.29). Vaccine effectiveness was 90.4% (95% CI 73.5–97.3%).ConclusionVaccination reduced the pH1N1 infection risk considerably. The pandemic plan to contain the pH1N1 infection was successful. Nurses had the highest risk of pH1N1 infection and are therefore a target group for vaccination measures.

ObjectivesEvidence for the utility of the new Mycobacterium tuberculosis (MTB) specific IFN-γ release assays in diagnosing latent tuberculosis infection (LTBI) is growing. However, data concerning conversion and reversion rates in serial testing of healthcare workers (HCWs) with an interferon-γ release assay are sparse.MethodsBetween February 2007 and September 2009, 670 HCWs in the University Hospital of Porto, Portugal were tested at least twice with QuantiFERON-TB® Gold In-Tube (QFT) for LTBI. The tuberculin skin test (TST) was performed simultaneously. QFT was considered positive if INF-γ ≥0.35 IU/mL. TST conversion was defined as an increase ≥10 or ≥6 mm compared to a baseline TST <10 mm.ResultsThe second QFT was positive in 4.8% of the 376 HCWs with an INF-γ concentration at baseline below 0.1 IU/mL but in 48.8% of the 41 HCWs with an INF-γ concentration of 0.2 to <0.35 IU/mL. Out of 74 HCWs with a baseline INF-γ concentration ≥3.0 IU/mL, 4 (5.4%) reversed while 27 out of 55 HCWs (49%) with a baseline INF-γ concentration ≥0.35 to <0.7 IU/mL reversed to a negative QFT. Those 61 HCWs with TST conversion (increase ≥10 mm) were most often (78.7%) negative in both consecutive QFTs.ConclusionOur data suggests the use of an uncertainty zone between 0.2 and 0.7 IU/mL in serial testing with QFT. As long as the knowledge regarding disease progression in QFT-positive persons is limited, persons pertaining to this zone should be retested before being offered preventive chemotherapy.

Supplementary material Supplementary Figure 1. Data collection timeline Supplementary Figure 2. Scatter plot showing the relationship between days between assessments and difference in Control of Allergic Rhinitis and Asthma Test total scores (CARAT-T).