Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

Approach to the diagnosis of drug hypersensitivity reactions: similarities and differences between Europe and North America.

Drug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. PERSPECTIVES: While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated.

International Consensus on drug allergy.

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.

Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial.

Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks.

Relationship between asthma and cognition: the Cooper Center Longitudinal Study.

BACKGROUND: Minimal data are available on the relationship between asthma and cognitive performance. In this report, we examine the relationship between asthma and cognitive performance in older adults, a subpopulation with elevated risk of cognitive impairment. METHODS: We conducted a cross-sectional, retrospective analysis of 1380 participants age ≥55 who completed preventive health examinations at the Cooper Clinic in Dallas, TX. Cognition was assessed using the Montreal Cognitive Assessment (MoCA), a brief test for mild cognitive impairment. Data were analyzed in a multiple logistic regression using MoCA scores suggestive of cognitive impairment as the dependent variable. RESULTS: When controlling for demographic characteristics, self-rated health status, inhaled corticosteroid use, and FEV1 /FVC, asthma were associated with 78% increased risk of cognitive impairment (P = 0.02) as defined by MoCA score. CONCLUSIONS: In the largest sample examined to date, we have identified a significant relationship between asthma and cognitive impairment in older people.

Therapeutic drug monitoring of amikacin in preterm and term infants.

INTRODUCTION: Amikacin is a commonly-prescribed drug used for the empirical treatment of bacterial infections in neonates. A marked change in the pharmacokinetics of amikacin has been reported during neonatal life. Amikacin has a very narrow therapeutic range and can cause very serious side effects such as nephrotoxicity and ototoxicity. The current therapeutic dose of amikacin, i.e. 15 mg/kg of body weight, may increase the risk of toxicity in preterm infants with immature renal functions. We aimed to determine the frequency of amikacin toxicity in preterm as compared to term infants by measuring its serum trough levels following the administration of the current therapeutic dose. METHODS: A comparative study was conducted at the neonatal intensive care unit of the Military Hospital, Rawalpindi, Pakistan. A total of 104 infants (52 term and 52 preterm) receiving amikacin at a dose of 15 mg/kg of their body weight, once daily for bacterial infection, were included. After clinical evaluation, serum creatinine levels were measured at admission and on the third day. Amikacin trough levels were taken after 72 hours of therapy and measured on the TDx Abbot Drug Analyser. RESULTS: The gestational age range was 37-40 weeks in term and 29-36 weeks in preterm infants. The term and preterm infants had a median weight of 2.8 kg and 2.1 kg, respectively. The preterm infants had significantly higher median (range) 11.33 (1.50-42.60) ug/ml levels of serum amikacin as compared to 8.5 (2.8-33.0) ug/ml in term infants (p-value is less than 0.01). The preterm infants had a high frequency of toxic 32 (62 percent) and subtherapeutic 12 (23 percent) levels, as compared to 11 (21 percent) and 5 (10 percent) in term infants, respectively. Serum amikacin levels revealed a positive correlation with post-dose serum creatinine (r equals 0.48; p-value is less than 0.05). CONCLUSION: This study demonstrated that the current practice of amikacin treatment for bacterial infection needs to be adjusted due to unique pharmacokinetic variability in preterm infants. There is a need for regular therapeutic drug monitoring and renal function assessment in all infants receiving amikacin therapy in order to avoid nephrotoxicity.

Safety and efficacy of treatment using interleukin-2 in a patient with idiopathic CD4(+) lymphopenia and Mycobacterium avium-intracellulare.

We present the case of a 39-year-old white man with a Myobacterium avium-intracellulare pulmonary infection found to have a CD4(+) count of 172 cells/mm(3) and diagnosed subsequently with idiopathic CD4(+) lymphopenia (ICL). After receiving clathromycin for 4 months with minimal improvement, the patient was started on pegylated subcutaneous interleukin (IL)-2 at 600,000 units daily. Later, he received incrementally higher pegylated IL-2 doses until he reached a maintenance dose 3 months later of 11 million units weekly divided into three equal doses. After 5 months of therapy, the patient's chronic cough resolved completely, sputum cultures became negative for Myobacterium avium-intracellulare and the CD4(+) T cell count increased to 553 cells/mm(3). After 35 months of well-tolerated IL-2 treatments and no recurrence of any opportunistic infections, IL-2 treatment was stopped. CD4(+) counts 6 and 9 months after discontinuing IL-2 treatment were 596 and 378 cells/mm(3) respectively, and he remains asymptomatic. This report supports IL-2 treatment for ICL-associated opportunistic infections as a safe and potentially efficacious treatment option, especially when combined with more traditional treatment regimens.

Lead-induced oxidative stress adversely affects health of the occupational workers.

Lead is a persistent toxic metal and associated with impairment of various body functions in occupational workers. The main objective was to determine the lead-induced oxidative stress and adverse health effects by biochemical markers in industrial workers. One hundred and forty-eight males consisting of 87 lead-exposed industrial workers and 61 controls were included. Blood lead level (BLL) was determined on a 3010B ESA lead analyzer. Blood complete counts were done on a hematology analyzer. Biochemical markers including serum uric acid, urea, creatinine, phosphate, alanine aminotransferase (ALT), and gamma glutamyltransferase (GGT) were measured on a Selectra E auto analyzer. Serum malondialdehyde (MDA) was measured spectrophotometrically and C-reactive protein (CRP) on Immulite-1000. Results revealed that lead-exposed workers had significantly high BLLs, median (range), 29.1 (9.0-61.1) microg/dL compared with controls, 8.3 (1.0-21.7) microg/dL. Oxidative stress (MDA, GGT) and inflammatory markers (high-sensitivity CRP) were significantly increased (P < or = 0.05). Blood pressure was raised, whereas hemoglobin was decreased in exposed group (P < or = 0.002). Serum urea, uric acid, phosphate, and ALT were significantly raised in lead-exposed workers (P < or = 0.001). Serum albumin, total proteins, and glomerular filtration rate (GFR) were decreased. Blood lead showed a significant positive correlation with serum GGT (r = 0.63), MDA (r = 0.71), CRP (r = 0.75), urea (r = 0.34), creatinine (r = 0.51), and uric acid (r = 0.29) (P < or = 0.01). It is concluded that lead exposure increases oxidative stress that correlates with adverse changes in hematological, renal, and hepatic function in the occupational workers. Elevated blood lead has positive correlation with oxidative stress, inflammatory and biochemical markers that might be used to detect impairment in the body function in lead exposed workers.

Prevalence of mood disorders and relationship to asthma severity in patients at an inner-city asthma clinic.

BACKGROUND: Depressive symptoms are associated with noncompliance and even sudden death in asthma patients. Some studies suggest that low-income, minority, inner-city asthma patients may be at high risk for asthma-related morbidity and mortality in which depression may be a risk factor. Minimal data are available on the prevalence of depression and other mood disorders in asthma patients. OBJECTIVE: In this pilot study, we examined the prevalence of depression and the association between depression and measures of asthma severity in patients at an inner-city asthma clinic. METHODS: Mood disorders were diagnosed using a diagnostic interview given to patients (N = 44) at asthma clinic visits. Inhaled steroid dose, FEV1 percentage, and asthma severity were also obtained. RESULTS: Eighteen patients (41%) had a lifetime mood disorder but only seven of these patients received pharmacotherapy. Patients with a past mood disorder had significantly higher FEV1 percentage predicted values (P = 0.03) than those without a mood disorder. Trends toward less severe asthma (P = 0.13) and lower inhaled steroid dose (P = 0.13) in patients with a mood disorder history were also found. CONCLUSIONS: The data suggest that mood disorders are common, but often unrecognized and untreated in asthma patients. The data also suggest that mood disorders are not necessarily associated with more severe asthma, at least in the population studied.

Allergic fungal sinusitis: an immunohistologic analysis.

BACKGROUND: Allergic fungal sinusitis is a noninvasive form of fungal sinusitis that has recently been delineated as a distinct clinicopathologic entity. It is increasingly recognized as a cause of chronic sinusitis, with the primary causative agents being members of the Dematiaceae fungus family. Although its immunopathogenesis has not been elucidated, the eosinophil is a prominent inflammatory cell on histologic examination. OBJECTIVE: We sought to characterize the involvement of eosinophils in sinus tissue and accompanying mucin from patients with allergic fungal sinusitis. As a comparison, neutrophil and mast cell involvement was also evaluated in the same group of patients. METHODS: Tissue specimens from 8 patients with allergic fungal sinusitis, along with 8 nasal polyp specimens from patients without allergic fungal sinusitis, were stained by using indirect immunofluorescence for eosinophil granule major basic protein (MBP). Neutrophil elastase and mast cell tryptase staining was also performed on the same allergic fungal sinusitis and nasal polyp tissues. RESULTS: MBP was diffusely localized within the mucin, showing intense staining at the periphery and variable staining of degenerated cell clusters throughout. Extracellular MBP in the mucin was strikingly greater than intact eosinophil staining. Diffuse extracellular neutrophil elastase was also present in the mucin. Mucinous areas showed no tryptase localization. Adjacent nonmucinous areas of respiratory mucosa showed predominantly cellular staining with eosinophil MBP, neutrophil elastase, and mast cell tryptase. MBP staining of nasal polyps showed a predominantly cellular pattern with focal areas of extracellular deposition. CONCLUSIONS: Given the known toxicities of eosinophil granule MBP and neutrophil elastase, their extracellular presence supports the contribution of these proteins in the pathogenesis of allergic fungal sinusitis and further indicates that eosinophil and neutrophil activation occurs in the disease.

Comparison of the internal state scale to clinician-administered scales in asthma patients receiving corticosteroid therapy.

Mood symptoms are reported frequently in asthma patients, particularly during corticosteroid therapy. This investigation compared the Internal State Scale (ISS), a self-report measure of symptoms of mania and depression, to the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS) in a group of asthma patients (n=60 at baseline) before, during, and after a 1-2 week burst of prednisone. The depression and well being subscales of the ISS correlated well with HDRS scores. The perceived conflict subscale correlated with the BPRS scores. However, none of the ISS subscales correlated consistently and specifically with the YMRS in this population. Possible explanations for differences observed in bipolar versus asthma patients given the ISS are discussed. These data suggest the ISS may be a useful tool for depression symptoms and overall psychopathology in asthma patients and in patients receiving corticosteroid therapy. However, its ability may be attenuated outside of the population for which it was designed.

Psychiatric diagnoses in inner city outpatients with moderate to severe asthma.

OBJECTIVE: Psychiatric symptoms may be associated with increased asthma morbidity and mortality. However, no investigations have identified syndromal psychiatric diagnoses in asthma patients using current diagnostic criteria or examined treatment received for mental illness. METHOD: We conducted structured clinical interviews on 32 patients with moderate to severe asthma to identify current and past psychiatric illness. RESULTS: Twenty-five percent of subjects had current major depressive disorder, but only 25 percent of these received antidepressants. Anxiety disorders, including panic disorder (16 percent), and social (13 percent) and specific phobias (28 percent) were also common. All subjects with panic disorder were receiving appropriate therapy. CONCLUSIONS: Asthma patients with moderate to severe asthma treated at community health facilities may have high rates of often untreated mood and anxiety disorders. Interventions aimed at identifying and treating psychiatric disorders in this population are needed.

Prevalence of macrovascular complications in diabetics of WAH, District Rawalpindi.

OBJECTIVE: To determine the prevalence of macrovascular complications in diabetic subjects with relation to age duration of diabetes and metabolic control. SETTING: Primary care centres of WAH, District Rawalpindi cross sectional population based study. METHODS: A total of 805 known diabetics (380 males and 425 females) were studied. Relevant history, detailed physician examination and ECG were done to assess the presence of ischaemic heart disease, stroke and diabetic foot complications. Their diabetic control was assessed by estimation of their plasma glucose and glycosylated haemoglobin. RESULTS: The prevalence of macrovascular complications was as follows: Ischaemic heart disease 19.8% (female 4.7%, males 7.8%), cerebrovascular disease 6.2% (females 4.7%, males 22.1%) and diabetic foot complications 2.1%. The macrovascular complications increased with age, duration of diabetes and were more prevalent in uncontrolled diabetics having glycosylated haemoglobin > 8.6%. CONCLUSION: Prevalence of macrovascular complication in our population is higher as compared to the West probably due to better management and diabetic care in those countries.

The psychiatric side effects of corticosteroids.

LEARNING OBJECTIVES: Readers will learn the importance of psychiatric symptomatology with corticosteroid drug therapy, especially when combined with other medications. DATA SOURCES: A brief history of corticosteroid use over the last five decades was complied utilizing MEDLINE and PSYCHOINFO as sources of information which include peer-reviewed research articles, case studies, and relevant reviews in English. CONCLUSION: Corticosteroids are routinely prescribed for a variety of allergic and immunologic illnesses. Psychiatric side effects from corticosteroids include mania, depression and mood disturbances. Psychiatric symptoms usually occur within the first two weeks of corticosteroid therapy and seem to be dose related. Treatment with lithium or antipsychotics may be helpful. Physicians should carefully monitor patients for psychiatric and cognitive side effects of corticosteroid use.

Reference values of common blood chemistry analytes in healthy population of Rawalpindi-Islamabad area.

The reference values of common blood chemistry analytes in healthy population, aged newborn to 80 years, of Rawalpindi Islamabad area were determined at AFIP, Rawalpindi. A total of 2115 healthy subjects, 1206 males and 909 females, were included in the study. Plasma glucose was analysed by GOD/POD, serum cholesterol by CHOD/PAP, triglycerides by GPO/PAP, urea by urease/GLDH, creatinine by Jaffe' rate reaction, uric acid by uricase, total bilirubin by Jendrassik and Grof, total protein by biuret, alanine transaminase (ALT) by optimized IFCC and alkaline phosphatase (AP) by optimized DGKC method. The between batch CVs of all the parameters were within acceptable quality goals. The reference values were calculated using 2.5 and 97.5 percentiles as lower and upper limits (95% CI). In healthy adult males the reference values were: fasting plasma glucose, 3.6-6.0 mmol/l; serum cholesterol; 3.2-6.6 mmol/l; triglycerides, 0.6-2.3 mmol/l; urea, 2.8-6.4 mmol/l; creatinine, 65-132 umol/l; uric acid, 164-430 umol/l; total bilirubin, 5-18 umol/l; total protein, 57-83 g/l; ALT, 15-45 U/l and AP, 185-620 U/l. The values in adult females, children and elderly subjects were slightly different than adult males. The reference values of our population show mild to moderate differences from the other Asian, European and American populations. It is recommended that reference values of different biochemical investigations should be established in various areas of Pakistan to make appropriate use of such investigations.

Evaluation of adrenal function in long standing pulmonary tuberculosis: a study of 100 cases.

Tuberculosis is a major public health problem in Pakistan and adrenal involvement in long-standing tuberculosis has been found to be common. A multi-center study was conducted to assess the adrenal function using short Synacthen test in one hundred patients with tuberculosis of more than 6 months duration at three hospitals of Rawalpindi and Islamabad. Forty patients demonstrated impaired response to Synacthen test. In 21 (52.5%) the increment from basal level was less than 300 nmol/L with a peak level increasing to over 600 mmol/L in 15 (37.5%) patients, the increment from basal level was less than 300 nmol/L as well as the peak level was also less than 600 nmol/L. In 4 (10%) patients the increment was more than 300 nmol/L but they were not able to obtain a peak level of 600 nmol/L. No significant difference was found between the patients with normal response and the impaired response with regards to their clinical features, duration of illness, body mass index (BMI), blood pressure variation and routine biochemical profile. It is concluded that adrenal dysfunction is common in patients with long-standing tuberculosis. Diagnosis of hypoadrenalism is not possible on clinical grounds and routine biochemical examinations. Synacthen stimulation test is necessary for its diagnosis.

Changes in plasma electrolytes during acclimatization at high altitude.

The effects on plasma electrolytes and related hormones were determined in non-acclimatized low lander males, exposed for 96 hours to an altitude of 4424 meters. Twenty healthy soldiers aged 18-34 years travelled by road from an altitude of 2303 meters to 4424 meters over a period of 10 hours. Plasma sodium levels (142.09 +/- 1.14 mmol/1) and aldosterone (16.61 +/- 5.70 ng/ml) decreased to 139.69 mmol/1 and 11.6 +/- 4.60 ug/ml respectively after 96 hours of acute exposure to high altitude (p < 0.05). The plasma potassium and chloride levels did not show significant change, while, plasma HCO3 decreased gradually from 21.06 +/- 1.38 mmol/1 to 18.55 +/- 0.82 mmol/1 after 96 hours exposure to this altitude (p < 0.01). The plasma ionized calcium and plasma phosphate concentration decreased from 1.32 +/- 0.11 mmol/1 and 1.58 +/- 1.3 mmol/1 to 1.20 +/- 0.05 mmol/1 and 1.47 +/- 0.99 mmol/1 respectively (p < 0.05). Plasma parathyroid hormone (PTH) level increased from 4.54 +/- 2.1 ng/ml to 11.19 +/- 4.31 ng/ml after 48 hours with subsequent decline to 2.52 +/- 1.7 ng/ml after 96 hours exposure to high altitude. It may be concluded that the process of acclimatization to sudden exposure to high altitude is characterised by fall in plasma aldosterone and PTH with subsequent decrease of related electrolytes.