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.

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.

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.

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.

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.

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.

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.

Assessment of patients who have experienced anaphylaxis: a 3-year survey.

DESIGN: A quality-control retrospective review of medical records was conducted for cases of anaphylaxis encountered at Mayo Clinic Rochester during a 3 1/2-year period. PATIENTS: For inclusion in the study, all patients had to manifest general symptoms of mediator release such as generalized pruritus, urticaria, angioedema, and flushing. Of the 179 patients with anaphylaxis (mean age, 36 years), 66% were female, 49% had atopy, and 37% had a previous history of immediate reactions to allergens. Of these study patients, 11 were receiving medications capable of exacerbating anaphylaxis (beta-blockers in 7 of them). RESULTS: Consultation with an allergist was obtained in 142 cases, and a probable diagnosis was made after review of the medical records. Causes of anaphylaxis included foods in 59 patients, idiopathic in 34, Hymenoptera in 25, medications in 23, and exercise in 12; false-positive diagnoses were recorded in 18. Allergy prick tests were done in 104 patients, 71 of whom had positive results; allergen-specific IgE tests were done in 44 patients, 23 of whom had positive results. In 19 patients, only allergen-specific IgE testing was done, and results were positive in 12. Normal test results included C1 esterase inhibitor in 33 patients, metabisulfite challenge in 15, and dye or preservative challenge in 10. Food skin tests were graded on a relative value scale and revealed 15 highly allergic, 24 moderately allergic, and 39 weakly allergic food groups. CONCLUSION: A standard protocol should be used for assessment of patients with anaphylaxis, and fresh food extracts should be used for prick skin testing. A national incidence study of anaphylaxis is needed. The public and school personnel should be educated about food anaphylaxis, and emergency treatment for anaphylaxis should be readily available for patients.

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.

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.

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.

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.

Biochemical parameters in evaluation of oligospermia.

In Pakistan, male infertility constitutes about 35% of all cases of infertility. The dysfunction can be at the level of the central nervous system or somewhere in the male genital tract. A study was conducted to screen cases of male infertility using various biochemical parameters. A total of 81 cases were screened. Oligospermia was seen in 13 (16%) patients. They were divided into severe and mild to moderate oligospermia. In severe oligospermia, there was an increase in serum FSH level with decrease in seminal transferrin and carnitine suggesting damage to sertoli cells. In mild to moderate oligospermia, serum FSH were normal with levels a slight decrease in the levels of transferrin and carnitine in semen indicating that sertoli cells were not significantly defective and the dysfunction could be somewhere else.

Demonstration of the site of obstruction in azoospermia by biochemical markers.

This study was carried out on 25 patients with azoospermia and normal serum FSH levels signifying obstruction as its cause. To determine the site of obstruction semen transferrin levels, carnitine and fructose were estimated. Patients with an obstruction at the testis-epididymal junction had low levels of transferrin but normal levels of carnitine and fructose. Patients who had lower levels of transferrin and carnitine, but normal levels of fructose had obstruction at the epididymal level, probably in the tail of the epididymis. Obstruction of the ejaculatory ducts was signified by lower levels of all parameters in the semen. Our study showed that levels of transferrin, carnitine and fructose when used in conjunction with each other could localize the site of obstruction in azoospermia.

Screening for chronic lead poisoning in lead factory workers.

One hundred and forty-nine lead factory workers comprising of 46 fume exposed, 78 handling lead materials and 25 controls were screened for chronic lead poisoning. Blood lead level was determined by atomic absorption spectrometery and urinary ALA by ion-exchange chromatography. Fume exposed workers had significantly higher (P < 0.01) blood lead (median 61.20 micrograms/dl, range 21.20-171.10 micrograms/dl) and urinary ALA levels (median 4.10 mg/l, range 01.0-22.9 mg/l) than workers handling lead materials and controls. Urinary ALA was found to be a more sensitive and specific test for lead poisoning than estimation of blood lead levels.

Blood lead levels and anemia in lead exposed workers.

The effects of lead on haematological parameters were studied in 51 occupationally exposed individuals comprising of 27 lead furnace workers, 24 lead pellet handlers and 20 healthy age and service matched controls. Blood lead levels were estimated by atomic absorption spectrometer AAS-180-80 and haematological parameters by Technicon H.1 system. The lead furnace workers had highest blood lead levels (median 71.20 ug/dl, range 21.2-171.10 ug/dl) and low Hb (median 106 g/l, range 73-144 g/l) as compared to healthy subjects (median lead levels 29.80 ug/dl, range 10.20-54.10 ug/dl and Hb median 135 g/l, range 101-153 g/l). The workers handling pellets had moderately increased blood lead levels (median 45.50 ug/dl, range 8.50-130.6 ug/l) and low Hb (median 114 g/l, range 74-158 g/l). The furnace exposed workers had higher blood lead levels and low Hb compared to the lead pellet handlers. TRBC, Hct, MCV, MCH and MCHC did not reveal any significant difference in all groups. It is concluded that chronic lead exposure causes normocytic normochromic anaemia and shows a dose response relationship between lead levels and severity of anemia.

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.

The role of the anti-sperm autoantibodies in the management of patients with primary infertility.

The role of antibody mediated infertility in patients with primary/secondary unexplained infertility is the subject of current interest worldwide. A prospective study was conducted to study the role of anti sperm antibodies in Pakistani patients with infertility. Patients reporting in the outpatient clinic of a local gynaecology department with problem of infertility were subjected to a detailed scrutiny by history and clinical examination including post-coital test and hysterosalpingography. Hormonal profile consisting of serum FSH, LH, Prolactin and Progesterone was assessed. Most of the ladies also underwent a pelviscopic examination. A total of 117 patients were selected where post-coital test was abnormal, semen analysis was not satisfactory or who had unexplained infertility. Tests were performed on the serum specimen from the husbands, wives and in some cases on the seminal plasma as well, for the measurement of the anti sperm agglutinating and anti-sperm immobilizing antibodies by the microagglutination technique. Fifteen of these patients were found positive for these antibodies, 7 were positive for the agglutinating antibody, 6 for the immobilizing antibody and two for both types. These results indicate that immunomodulation may be responsible for some cases of infertility in our population.

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.