The impact of pharmacist intervention on prophylactic antibiotics use in orthopedic surgery at a hospital in China.

ABSTRACT: This study aimed to assess the impact of the pharmacist-led intervention on perioperative antibiotic prophylaxis by standardizing the cephalosporin intradermal skin test in the orthopedic department.A pre-and postintervention study was conducted among patients in the Orthopedics Department at the Beijing Chao-Yang Hospital in China. Use of intradermal skin test, perioperative antibacterial prophylaxis, and cost of care were compared between the preintervention population (admitted from 6/1/2018 to 8/31/2018) and postintervention population (admitted from 1/1/2019 to 3/31/2019). Logistic regression and generalized linear regression were used to assess the intervention impact.425 patients from the preintervention period and 448 patients from the postintervention period were included in the study. After the implementation of the pharmacist intervention program, there was a decrease in the utilization of intradermal skin tests, from 95.8% to 16.5% (P < .001). Patients were more likely to have cephalosporin as prophylactic antimicrobials (OR = 5.28, P < .001) after the implementation. The cost of antimicrobials was significantly reduced by $150.21 (P < .001) for each patient.Pharmacist-involved intervention can reduce the utilization of cephalosporins skin tests and decrease the prescription of unnecessary high-cost antimicrobials.

New strategy to improve quality control of Montenegro skin test at the production level

Abstract INTRODUCTION: The production of the Montenegro antigen for skin test poses difficulties regarding quality control. Here, we propose that certain animal models reproducing a similar immune response to humans may be used in the quality control of Montenegro antigen production. METHODS: Fifteen Cavia porcellus (guinea pigs) were immunized with Leishmania amazonensis or Leishmania braziliensis , and, after 30 days, they were skin tested with standard Montenegro antigen. To validate C. porcellus as an animal model for skin tests, eighteen Mesocricetus auratus (hamsters) were infected with L. amazonensis or L. braziliensis , and, after 45 days, they were skin tested with standard Montenegro antigen. RESULTS: Cavia porcellus immunized with L. amazonensis or L. braziliensis , and hamsters infected with the same species presented induration reactions when skin tested with standard Montenegro antigen 48-72h after the test. CONCLUSIONS: The comparison between immunization methods and immune response from the two animal species validated C. porcellus as a good model for Montenegro skin test, and the model showed strong potential as an in vivo model in the quality control of the production of Montenegro antigen.

Intradermal Skin Testing in Allergic Rhinitis and Asthma with Negative Skin Prick Tests.

Taking medical history, physical examination, and performing some in vivo and in vitro tests are necessary for the diagnosis of allergy. Skin prick test (SPT) is considered as the standard method and first-line approach for the detection of allergic sensitization. Although mainly SPT is used for the detection of allergic sensitization, intradermal skin test (IDST) may be necessary, especially in patients with a negative SPT result. IDST is quite safe; however, is nowadays seldom used for detection of inhalant allergy and its value remains controversial. We aimed to investigate whether IDST is useful and necessary in diagnosis of respiratory allergies or not. This study involved 4223 patients with allergic rhinitis (AR) and/or bronchial asthma (BA). SPT results were positive in 2419 patients (57%) and negative in 1804 (43%). IDST was applied to 344 patients with marked allergic symptoms and with negative SPT results. Out of 344 patients, 152 (44%) showed allergic sensitization to IDST. The most commonly encountered allergic response was against the house dust mite (HDM) (32.6%). Allergic response against fungal spores was also relatively high (22%), while the pollen allergy rate (4.3%) was quite low. In BA patients with negative prick test, IDST made a significant contribution to the diagnosis of HDM allergy (p=0.003). To avoid missed diagnosis of AR and BA, particularly regarding  the HDM allergy, application of IDST may be beneficial; therefore, IDST should be considered as the next step after SPT for diagnosis of allergy prior to in vitro or provocation tests.

New strategy to improve quality control of Montenegro skin test at the production level.

INTRODUCTION: The production of the Montenegro antigen for skin test poses difficulties regarding quality control. Here, we propose that certain animal models reproducing a similar immune response to humans may be used in the quality control of Montenegro antigen production. METHODS: Fifteen Cavia porcellus (guinea pigs) were immunized with Leishmania amazonensis or Leishmania braziliensis , and, after 30 days, they were skin tested with standard Montenegro antigen. To validate C. porcellus as an animal model for skin tests, eighteen Mesocricetus auratus (hamsters) were infected with L. amazonensis or L. braziliensis , and, after 45 days, they were skin tested with standard Montenegro antigen. RESULTS: Cavia porcellus immunized with L. amazonensis or L. braziliensis , and hamsters infected with the same species presented induration reactions when skin tested with standard Montenegro antigen 48-72h after the test. CONCLUSIONS: The comparison between immunization methods and immune response from the two animal species validated C. porcellus as a good model for Montenegro skin test, and the model showed strong potential as an in vivo model in the quality control of the production of Montenegro antigen.

Skin Testing for Allergic Rhinitis: A Health Technology Assessment.

BACKGROUND: Allergic rhinitis is the most common type of allergy worldwide. The accuracy of skin testing for allergic rhinitis is still debated. This health technology assessment had two objectives: to determine the diagnostic accuracy of skin-prick and intradermal testing in patients with suspected allergic rhinitis and to estimate the costs to the Ontario health system of skin testing for allergic rhinitis. METHODS: We searched All Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database for studies that evaluated the diagnostic accuracy of skin-prick and intradermal testing for allergic rhinitis using nasal provocation as the reference standard. For the clinical evidence review, data extraction and quality assessment were performed using the QUADAS-2 tool. We used the bivariate random-effects model for meta-analysis. For the economic evidence review, we assessed studies using a modified checklist developed by the (United Kingdom) National Institute for Health and Care Excellence. We estimated the annual cost of skin testing for allergic rhinitis in Ontario for 2015 to 2017 using provincial data on testing volumes and costs. RESULTS: We meta-analyzed seven studies with a total of 430 patients that assessed the accuracy of skin-prick testing. The pooled pair of sensitivity and specificity for skin-prick testing was 85% and 77%, respectively. We did not perform a meta-analysis for the diagnostic accuracy of intradermal testing due to the small number of studies (n = 4). Of these, two evaluated the accuracy of intradermal testing in confirming negative skin-prick testing results, with sensitivity ranging from 27% to 50% and specificity ranging from 60% to 100%. The other two studies evaluated the accuracy of intradermal testing as a stand-alone tool for diagnosing allergic rhinitis, with sensitivity ranging from 60% to 79% and specificity ranging from 68% to 69%. We estimated the budget impact of continuing to publicly fund skin testing for allergic rhinitis in Ontario to be between $2.5 million and $3.0 million per year. CONCLUSIONS: Skin-prick testing is moderately accurate in identifying subjects with or without allergic rhinitis. The diagnostic accuracy of intradermal testing could not be well established from this review. Our best estimate is that publicly funding skin testing for allergic rhinitis costs the Ontario government approximately $2.5 million to $3.0 million per year.

What we miss if standard panel is used for skin prick testing?

BACKGROUND: Although standard skin prick test (SPT) panels are crucial for routine investigation of sensitization in daily clinical practice, it has limitations in terms of missing allergens. OBJECTIVE: To find out sensitization rates (SR)s to additional panel of allergens and their relative contributions in allergic diseases. METHODS: SPTs with a battery of aeroallergens [tree pollen (A.glutinosa, C.arizonica, J.communis, T.platyphyllos, R.pseudoacacia), weed pollen (R.acetosa, U.dioica, A.artemisifolia), smut mix, yeast mix, storage mites (SM) (B.tropicalis, L.destructor, T.putrescentiae, A.siro), mouse and budgerigar epithelia], were performed to 318 participants (6-18 years) who were previously identified to be sensitized to at least one of the aeroallergens found in standard battery. RESULTS: Forty percent of participants were sensitized to at least one additional aerollergen. Three most frequent sensitizations were to B.tropicalis (11.3%), R.pseudoacacia (9.7%) and L.destructor (8.2%). SR for tree pollen increased from 6.9% to 19.8%, for mites increased from 26.3% to 31.6% and for moulds increased from 5.3% to 9.4% with addition of respective group of other allergens to battery. Furthermore, higher rates for additional tree pollen sensitization was found among patients with "only AR" (21%) compared to patients with "only asthma" (4.6%, p =0.006), contrarily higher rates for SM sensitization was found among patients with "only asthma" (20%) compared to patients with "only AR" (3.2%, p =0.003) CONCLUSIONS: Though some of sensitizations may occur due to cross-reactivity, almost 40% of sensitized children were also co-sensitized to the additional allergens tested. Physicians should consider further steps when a negative or inconsistent result is achieved through a standard skin test panel.

Is it possible to make a diagnosis of raw, heated, and baked egg allergy in children using cutoffs? A systematic review.

The diagnosis of IgE-mediated egg allergy lies both on a compatible clinical history and on the results of skin prick tests (SPTs) and IgEs levels. Both tests have good sensitivity but low specificity. For this reason, oral food challenge (OFC) is the ultimate gold standard for the diagnosis. The aim of this study was to systematically review the literature in order to identify, analyze, and synthesize the predictive value of SPT and specific IgEs both to egg white and to main egg allergens and to review the cutoffs suggested in the literature. A total of 37 articles were included in this systematic review. Studies were grouped according to the degree of cooking of the egg used for OFC, age, and type of allergen used to perform the allergy workup. In children <2 years, raw egg allergy seems very likely when SPTs with egg white extract are ≥4 mm or specific IgEs are ≥1.7 kUA /l. In children ≥2 years, OFC could be avoided when SPTs with egg white extract are ≥10 mm or prick by prick with egg white is ≥14 mm or specific IgE is ≥7.3 kUA /l. Likewise, heated egg allergy can be diagnosed if SPTs with egg white extract are >5 and >11 mm in children <2 and ≥2 years, respectively. Further and better-designed studies are needed to determine the remaining diagnostic cutoff of specific IgE and SPT for heated and baked egg allergy.

Improving the Effectiveness of Penicillin Allergy De-labeling.

BACKGROUND: Approximately 10-20% of hospitalized patients are labeled as penicillin allergic, and this is associated with significant health and economic costs. OBJECTIVES: We looked at the effectiveness of penicillin allergy de-labeling in clinical practice with the aim of deriving risk stratification models to guide testing strategies. METHODS: Consecutive patients aged 15 years or more, referred to a Western Australian public hospital drug allergy service between 2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and oral challenge (OC), and follow-up of post testing antibiotic usage were the main outcomes. RESULTS: SPT/IDT was performed in 401 consecutive patients with immediate (IMM) (≤ 1 hour) (n = 151) and nonimmediate (NIM) (>1 hour) (n = 250) reactions. Of 341 patients, 42 (12.3%) were SPT/IDT+ to ≥ 1 penicillin reagents, including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P < .0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious positive OC reactions to single dose penicillin VK (SPT/IDT negative predictive value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151 (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following the allergy label modifications (ALM) at the time of follow-up. CONCLUSIONS: Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and identifies selective beta-lactam allergies; however, incomplete adherence to ALM recommendations impairs effectiveness. Infrequent SPT/IDT+ and absent OC reactions in patients with NIM reactions suggest OC alone to be a safe and cost-effective de-labeling strategy that could improve the coverage of penicillin allergy de-labeling in lower risk populations.

Equine intradermal test threshold concentrations for house dust mite and storage mite allergens and identification of stable acari fauna.

BACKGROUND: House dust mite (HDM) and storage mite (SM) stable fauna and their associated equine intradermal test (IDT) threshold concentrations (TCs) for the midwestern region of the USA are unknown. HYPOTHESIS/OBJECTIVES: To determine IDT TCs and serum IgE concentrations for two HDM and three SM species in clinically normal horses over two seasons, and to identify the mite taxa and habitats in a stable. ANIMALS: Thirty-eight clinically normal horses. METHODS: Threshold concentrations for HDMs and SMs were determined using IDT subjective measurements and a statistical model. An enzyme-linked immunosorbent assay was used to quantify serum IgE concentrations for the same mite species. A modified flotation method was used to identify morphologically HDMs and SMs. RESULTS: Subjective IDT TCs were as follows: 1:80,000 w/v for Dermatophagoides farinae in both seasons; 1:80,000 w/v in spring and 1:160,000 w/v in late summer for Dermatophagoides pteronyssinus; 1:40,000 w/v in spring and 1:20,000 w/v in late summer for Acarus siro; 1:20,000 w/v for Lepidoglyphus destructor in both seasons; and 1:20,000 w/v in spring and 1:10,000 w/v in late summer for Tyrophagus putrescentiae. Statistically significant associations for increased serum IgE and a positive IDT reaction were evident for D. farinae in the spring and D. pteronyssinus in both seasons. One mite from all four genera specific to this study was identified; however,two HDM and A. siro species were not detected.Conclusions and clinical importance ­ This study established HDM and SM IDT dilution concentrations for the horses in this region. Exposure to diverse acaridae fauna may contribute to the pathogenesis of equine allergic disease.

[Quality to allegy testing and interpretation of its results]. / Laatua allergiatestaukseen ja tulosten tulkintaan.

Medication and immunotherapy for allergy and guidance for the avoidance of allergens are determined on the basis of a skin-prick test. The testing must be performed in a standardized manner of good quality. Testing quality is not in accord with the present-day requirements everywhere. Interpretation of the test result requires experience and knowledge of the test's nature. Testing should be concentrated into larger units and testing services rearranged. A testing service system for doctors within the Finnish capital region and test reaction reading keys to the aid of clinicians have been developed at the Helsinki University Central Hospital.

Diagnostic tests for food allergy.

The diagnosis of food allergy is still based primarily on a detailed medical history and comprehensive physical examination. Clinical or laboratory tests only serve as an add-on tool to confirm the diagnosis. The standard techniques include skin prick testing and in-vitro testing for specific IgE-antibodies, and oral food challenges. Properly done, oral food challenges continue to be the gold standard in the diagnostic workup. Recently, unconventional diagnostic methods are increasingly used. These include food specific IgG, antigen leucocyte antibody and sublingual/intradermal provocation tests, as well as cytotoxic food and applied kinesiology and electrodermal testings. These lack scientific rationale, standardisation and reproducibility. There have been no well-designed studies to support these tests, and in fact, several authors have disproved their utility. These tests, therefore, should not be advocated in the evaluation of patients with suspected food allergy because the results do not correlate with clinical allergy and may lead to misleading advice and treatment.

Comparison between an intradermal skin test and allergen-specific IgE-ELISA for canine atopic dermatitis.

The aim of this study was to compare the results of an intradermal skin test (IDST) with those of an allergen-specific IgE-ELISA in 210 dogs with atopic dermatitis. All the dogs had a clinical diagnosis of atopic dermatitis and underwent an IDST. The sera of all dogs were analysed for allergen-specific IgE by ELISA using the monoclonal antibody D9 against dog IgE. IDST was used as the standard assay. In both methods, the following antigens provided a positive test result: Dermatophagoides farinae, Acarus siro, Tyrophagus putrescentiae, ragweed, mugwort and Lepidoglyphus destructor. ELISA had an overall sensitivity of 82.4% and an overall specificity of 93.8%. The overall accuracy of the ELISA was 91.3%. The evaluated monoclonal D9 ELISA was found to be a reliable tool for the diagnosis of those allergens that cause clinical atopy, and can be recommended for use in dogs when immunotherapy is a therapeutic option.

[Value of intradermal skin test and serum sIgE detection in diagnosing artemisia pollinosis].

OBJECTIVE: To evaluate the value of intradermal skin test (IDT) and serum sIgE detection in diagnosing Artemisia sensitivity in Chinese patients with autumnal hay fever. METHODS: 1150 patients with autumnal rhinitis or asthma, 504 males and 646 females, aged 5 approximately 77, were evaluated by experienced physicians, then underwent IDT by using 20 kinds of aeroallergen extracts. The concentrations of Artemisia and Ragweed extracts employed in skin test were 1:1000 (W/V) and the concentrations of other aeroallergens were all 1:100 (W/V). Then all patients underwent detection of Artemisia sIgE. Diagnostic standards were established based on the results of IDT and sIgE results respectively. A reference standard was established according to the typical history, symptoms, and an wheal with a diameter >or= 5mm and a sIgE level >or= 0.35 kU(A)/L, an wheal with the diameter >or= 10 mm alone; or a sIgE level >or= 0.70 kUa/L alone. RESULTS: When using the reference standard as criteria, using IDT had better sensitivity (96.2%), specificity (74.2%), positive predictive value (+PV, 93.5%), negative predictive value (-PV, 85.7%), and efficiency (91.6%) than using sIgE >or= 0.35 kUa/L alone as the criteria of IDT; sIgE detection had better sensitivity (97.6%), specificity (94.9%), +PV (98.7%), -PV (91.1%), and efficiency (97.0%) than using wheal diameter >or= 5 mm alone as the criteria of sIgE detection. The false positive rate of IDT and sIgE detection decreased from 35% and 22.7% to 25.6% and 5.1% respectively when using the wheal diameter >or= 10 mm or sIgE >or= 0.70 kUa/L as a positive criteria. CONCLUSION: IDT and sIgE detection are correlated with each other well in diagnosing Artemisia pollinosis, both of them have the possibility of being false positive, but IDT has higher false positive rate than sIgE detection. The false positive rates of IDT and sIgE detection can be decreased by increasing the positive criteria to higher grading reaction.

Allergic contact dermatitis from corticosteroids: reproducibility of patch testing and correlation with intradermal testing.

BACKGROUND: Corticosteroid contact allergy is not uncommon. The diagnosis can be made with either patch testing or intradermal (ID) testing. In view of a few problems that have been encountered with patch testing, patch testing is considered inferior to ID testing. The reported reproducibility of positive patch-test results in the literature ranges from 47 to 98%. OBJECTIVES: This study was conducted to (1) determine the reproducibility of patch testing with topical steroid preparations and their clinical relevance, (2) correlate positive results with ID testing, (3) address the issue of cross-reactivity between different steroid groups, and (4) identify the percentage of positive reactions to preservatives and vehicles used in commercial topical steroids. METHODS: A total of 19 patients with positive patch-test reactions to steroids from 1995 to 2004 were identified. Atopic patients and patients with type I hypersensitivity were excluded. The patients were patch-tested with a steroid series, select commercial steroid products, and vehicles and preservatives used in these preparations. The same patients were subjected to ID testing with select steroids. Readings were done on days 2, 5, and 7. ID testing was also performed on 9 control patients. RESULTS: Tixocortol-21-pivalate is the most common steroid allergen (68%). The reproducibility of patch testing with topical steroid preparations ranged from 66 to 100%. Reactions to both ID testing and patch testing occurred in 16 patients (89%); 1 patient reacted to patch testing and 1 other reacted to ID testing. Formaldehyde and formaldehyde releasers accounted for the majority of reactions in the vehicles and preservatives group. CONCLUSION: Patch testing is sufficient in diagnosing allergic contact dermatitis from topical steroids. Testing with commercial products is not a good screen for steroid allergy. The most common cross-reactions were between group A (hydrocortisone-type) corticosteroids and group D2 corticosteroids (composed of labile esters, with a long-chain ester at C17 and possibly C21).

Leishmanin skin test in guinea pig with a single purified protein of Leishmania major.

A series of hybridomas was produced by fusion of SP2/0 myeloma cells with spleen cells of mice immunized with Leishmania major (L. major). The reactivity of secreted monoclonal antibodies (mAbs) was evaluated against available leishmanin antigen by enzyme linked immunosorbent assay. Only one hybridoma designated as 7F9 secreted IgG1 mAb which was shown to be reactive with leishmanin. This mAb was further tested against four species of Leishmania (L. donovani, L. tropica, L. infantum, L. major) and a recombinant gp63. Among the four species tested it was shown to be only reactive with promastigotes of L. major. The antigen recognized by this mAb was purified and analyzed from both sonicated and supernatant cultures of L. major by immunoaffinity chromatography and reverse phase high performance liquid chromatography. The purified antigen, which gave a single band of 56kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis elicited a strong delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized with L. major. It was almost of the same degree as that produced by leishmanin. These results suggest that an L. major-specific antigen is an alternative as a specific diagnostic skin test reagent, which could lead to a better understanding of the mechanism of DTH in L. major.

Evaluation of a point-of-care immunodot assay for predicting results of allergen-specific intradermal and immunoglobulin E serological tests.

Immunotherapy to prevent recurrence of clinical signs of atopic dermatitis (AD) is based on intradermal or serological tests that assist in identifying allergen-specific immunoglobulin E hypersensitivities. Unfortunately, the results of such tests can be negatively influenced by several factors, which include the age of the patients, the season of testing and the administration of anti-allergic drugs. Screening to predict when these expensive tests will be useful would benefit owners of dogs with AD. The objectives of this study were to determine whether a point-of-care allergen-specific immunodot assay (Allercept E-Screen, Heska Corp., Ft Collins, CO, USA) could predict results of either intradermal or Allercept full panel serological tests in atopic dogs. Thirty dogs living in the south-eastern USA were diagnosed with AD in accordance with current standards. Allergen-specific intradermal, serological and E-Screen tests were performed in all subjects. For flea, house dust mite and pollen allergens altogether, results of the E-Screen assay agreed with those of intradermal and serological tests in 26/30 dogs (87%) and 25/30 dogs (83%), respectively. In this group of dogs, the probabilities of obtaining intradermal or serological tests positive for these allergens were 70 and 67%, respectively. If either skin or serum tests were performed only in dogs with positive E-Screen tests, the probability of obtaining positive results would be increased from 70 to 95% and from 67 to 90%, respectively. In this population of dogs with AD, results of the E-Screen point-of-care immunodot assay was found to often agree with those of allergen-specific intradermal or Allercept tests for selected allergen groups.

Determination of threshold concentrations of allergens and evaluation of two different histamine concentrations in canine intradermal testing.

The purpose of this study was to determine the optimal histamine concentration and allergen threshold concentrations for canine intradermal testing. Thirty healthy dogs were tested using two different concentrations of histamine and four different concentrations of each allergen. The optimal histamine concentration was determined to be 1:10 000 w/v. The threshold concentration was at least 1750 PNU/mL for all tested grasses, weeds, trees, moulds and insects, except for fleas which was as least 1:500 w/v. For Dermatophagoides pteronyssinus, the optimal threshold concentration was 250 PNU/mL, whereas for Dermatophagoides farinae and Tyrophagus putrescentiae, it was 100 PNU/mL. Threshold concentration for all epidermals except human dander was at least 1250 PNU/mL. The optimal threshold concentration for human dander was 300 PNU/mL. Our results suggest that the currently used 1:100 000 w/v concentration of histamine and the 1000 PNU/mL concentration for most grasses, weeds, trees, moulds, epidermals and insects may not be appropriate for canine intradermal testing.