Robert Y. Lin

Fatal anaphylaxis in the United States, 1999-2010: Temporal patterns and demographic associations

BACKGROUNDnAnaphylaxis-related deaths in the United States have not been well characterized in recent years.nnnOBJECTIVESnWe sought to define epidemiologic features and time trends of fatal anaphylaxis in the United States from 1999 to 2010.nnnMETHODSnAnaphylaxis-related deaths were identified by using the 10th clinical modification of the International Classification of Diseases system diagnostic codes on death certificates from the US National Mortality Database. Rates were calculated by using census population estimates.nnnRESULTSnThere were a total of 2458 anaphylaxis-related deaths in the United States from 1999 to 2010. Medications were the most common cause (58.8%), followed by unspecified (19.3%), venom (15.2%), and food (6.7%). There was a significant increase in fatal drug-induced anaphylaxis over 12xa0years: from 0.27 (95% CI, 0.23-0.30) per million in 1999 toxa02001 to 0.51 (95% CI, 0.47-0.56) per million in 2008 to 2010 (Pxa0< .001). Fatal anaphylaxis caused by medications, food, and unspecified allergens was significantly associated with African American race and older age (Pxa0< .001). Fatal anaphylaxis to venom was significantly associated with white race, older age, and male sex (Pxa0< .001). The rates of fatal anaphylaxis to foodsxa0in male African American subjects increased from 0.06xa0(95% CI, 0.01-0.17) per million in 1999 to 2001 to 0.21 (95% CI,xa00.11-0.37) per million in 2008 to 2010 (Pxa0< .001). Thexa0rates of unspecified fatal anaphylaxis decreased over timexa0from 0.30 (95% CI, 0.26-0.34) per million in 1999 to 2001xa0to 0.09 (95% CI, 0.07-0.11) per million in 2008 to 2010 (Pxa0<xa0.001).nnnCONCLUSIONnThere are strong and disparate associations between race and specific classes of anaphylaxis-related mortality in the United States. The increase in medication-related deaths causedxa0by anaphylaxis likely relates to increasedxa0medication andxa0radiocontrast use, enhanced diagnosis, and coding changes.

Fatal Anaphylaxis: Mortality Rate and Risk Factors

Up to 5% of the US population has suffered anaphylaxis. Fatal outcome is rare, such that even for people with known venom or food allergy, fatal anaphylaxis constitutes less than 1% of total mortality risk. The incidence of fatal anaphylaxis has not increased in line with hospital admissions for anaphylaxis. Fatal drug anaphylaxis may be increasing, but rates of fatal anaphylaxis to venom and food are stable. Risk factors for fatal anaphylaxis vary according to cause. For fatal drug anaphylaxis, previous cardiovascular morbidity and older age are risk factors, with beta-lactam antibiotics, general anesthetic agents, and radiocontrast injections the commonest triggers. Fatal food anaphylaxis most commonly occurs during the second and third decades. Delayed epinephrine administration is a risk factor; common triggers are nuts, seafood, and in children, milk. For fatal venom anaphylaxis, risk factors include middle age, male sex, white race, cardiovascular disease, and possibly mastocytosis; insect triggers vary by region. Upright posture is a feature of fatal anaphylaxis to both food and venom. The rarity of fatal anaphylaxis and the significant quality of life impact of allergic conditions suggest that quality of life impairment should be a key consideration when making treatment decisions in patients at risk for anaphylaxis.

Adverse drug effects and angioedema hospitalizations in the United States from 2000 to 2009.

Since angiotensin-converting enzyme (ACE) inhibitors became common treatments, there have been increasing reports of angioedema (AE). AE hospitalization (AEH) trend data in the new millennium are limited. This study calculates hospitalization rates for AEs and describes clinical characteristics of AEHs in the United States, especially as related to specific adverse drug effects (ADEs). The National Inpatient Samples 2000-2009 were queried for AEHs to calculate hospitalization rates and to examine for associations with specified ADEs, certain comorbidities, and demographic features. AEHs requiring intubation or tracheostomy were also examined for associations. There was a significant increase in the AEH rates (3.4 per 10(5) to 5.4 per 10(5)) over the study period (p < 0.0001) and the hospitalization rates for African Americans (AAs) were consistently higher. Throughout the study the proportions of AEH coding any ADEs, or an ADE due to a cardiovascular (CV) or antihypertensive (aHTN) drug increased over time. By 2009, 61.7% AEHs coded an ADE. Of these, 58.7% were caused by CV or aHTN drugs. In AEHs, having an ADE from a CV or aHTN medication had the strongest adjusted associations with hypertension and renal disease as well as with alcohol-related disorders. In AEHs, intubation/tracheostomy had the strongest ADE associations related to CV or aHTN medication (adjusted odds ratio, 1.4; 95% CI, 1.3, 1.6). AEHs continue to increase, but this can only be partially attributed to ACE inhibitor usage. Intubation/tracheostomy appears to be greater in AEHs with ADE due to CV/aHTN drugs. Alcohol-related disorders may have a role in ACE inhibitor-associated AEH.

Evolution of end-of-life care at United States hospitals in the new millennium.

OBJECTIVEnTo examine the characteristics of United States hospitalizations that result in hospice transfers including the clinical and demographic features, and to determine distinctive factors associated with discharges to hospice (DTH).nnnMETHODSnThe National Inpatient Sample (NIS) databases for 2000-2009 were queried for hospitalizations which resulted in transfers to hospice and expiration in the hospital. Yearly totals, as well as demographic and clinical features were tabulated for DTH hospitalizations. These characteristics were also compared with hospitalizations that ended with expiration using multivariate regression.nnnRESULTSnThe number of DTH per year increased 15 fold from 27,912 in 2000 to 420,882 in 2009. The median hospital stay decreased, while the median age, proportion of sepsis disease related groups (DRGs), and proportion of Medicare hospitalizations increased. Lung, gastrointestinal, hepato-biliary, and brain cancer were consistently the most prevalent malignancy DRGs. However, the initial preponderance of hospitalizations with any diagnosis of cancer was diminished by the end of the study. The adjusted odds ratio (95%CI) for the prediction of DTH (compared to hospital death) by any diagnosis of cancer decreased from 3.61 (3.52-3.71) to 2.02 (2.00-2.04) from the years 2000-2009. Female gender, age, and chronic obstructive pulmonary disease were predictors of discharge to hospice, while congestive heart failure was inversely associated.nnnCONCLUSIONSnHospital discharges to hospice have increased over the past ten years, with a concomitant shift in clinical and demographic characteristics. A growing trend toward offering and adopting hospice care upon discharge from US hospitals will likely impact health care finance and quality of care measures.

Patterns of Nasal Eosinophilia in Allergy Clinic Patients as Determined by Swab and Curette Sampling

The presence of eosinophils in nasal secretions often characterizes inflammatory disease in the nose and paranasal sinuses. This study analyzed differential associations between various clinical parameters and the presence of nasal eosinophilia in mucosal specimens obtained by two sampling methods (swab and curette-probe). Nasal mucosal secretions were obtained in patients attending an adult allergy clinic using both sampling methods for each patient. The presence of eosinophilia as determined by both methods had significant associations with 1) nasal mucosal pallor, 2) younger age, and 3) the presence of basophilic cells. To examine diagnostic characteristics of the two sampling methods of determining eosinophilia as a characteristic of allergic rhinitis, receiver operating characteristic (ROC) curves were evaluated for patients categorized as having allergic rhinitis on the basis of elevated aero-allergen specific IgE, and rhinitis based on either a) significant nasal mucosal appearance abnormalities, or b) a referring physicians diagnosis of rhinitis. The curette-probe determined nasal eosinophil quantitations had greater areas under the ROC curves when rhinitis was defined on the basis of mucosal appearance. On the other hand, the swab determined eosinophil quantitations had greater ROC curve areas when rhinitis was defined on the basis of referring diagnosis. In summary, nasal eosinophilia determined by curette or swab sampling has differences in strengths of their clinical associations.

Age dependent sex disproportion in US asthma hospitalization rates, 2000-2010

BACKGROUNDnAge-stratified sex differences in asthma hospitalizations rates have been reported to be most marked between the ages of 40 and 54 years in New York. It is not known whether age-dependent sex differences in asthma hospitalization rates also exist for the entire United States.nnnOBJECTIVESnTo compare sex-specific hospitalization rates for asthma in adults in the United States and to describe the adjusted associations between female sex and age in the fifth to sixth decades of life.nnnMETHODSnThe National Inpatient Sample databases for 2000-2010 were queried for a principal diagnosis of asthma to calculate the ratio of female to male hospitalization rates for different decades of adult life. Logistic regression modeling was used to determine whether age in the fifth to sixth decades of life had associations with female sex that remained significant after adjusting for comorbidities and demographic features.nnnRESULTSnFor all years of the study, there was a distinct peaking in female to male ratio most manifested in the fifth to sixth decades of life. This age grouping was significantly associated with female sex. Models revealed that female sex was significantly associated with this age grouping, even after adjustment for obesity, chronic obstructive pulmonary disease, race, insurance status, discharge year, and smoking. Excluding identifiable repeat admissions also did not abrogate the age grouping association.nnnCONCLUSIONnThere is a striking propensity of women in their fifth to sixth decades of life to be admitted for asthma, which appears to be independent of many known comorbidities.

The Epidemiology of Anaphylaxis

Anaphylaxis is a dramatic expression of systemic allergy. The lifetime prevalence of anaphylaxis is currently estimated at 0.05–2xa0% in the USA and ~3xa0% in Europe. Several population-specific studies have noted a rise in the incidence, particularly in the hospitalizations and ER visits due to anaphylaxis. The variable signs and symptoms that constitute the diagnostic criteria for anaphylaxis, the differences in diagnostic algorithms, and the limitations in the current coding systems have made summarizing epidemiologic data and comparing study results challenging. Nevertheless, across all studies, the most common triggers continue to be medications, food, and venom. Various risk factors for more severe reactions generally include older age, history of asthma, and having more comorbid diseases. Interesting seasonal, geographic, and latitude differences have been observed in anaphylaxis prevalence and incidence rates, suggesting a possible role of vitamin D and sun exposure in modifying anaphylaxis risk. While the incidence and prevalence of anaphylaxis appear to be increasing in certain populations, the overall fatality rate remains relatively low.

Disproportionate effects of dementia on hospital discharge disposition in common hospitalization categories.

BACKGROUNDnThe impact of dementia on hospitalization discharge dispositions (HDDs) in the United States has not been quantified, and dementia prevalence in various hospitalization categories has not been detailed in recent years.nnnOBJECTIVEnTo characterize hospitalizations prevalent with dementia, and to examine the relationship between dementia and HDDs.nnnDESIGNnA retrospective cross-sectional study.nnnSETTINGn2000 to 2012 National Inpatient Sample databases.nnnPATIENTSnHospitalizations in persons ≥65 years old assigned to 1 of 12 Diagnosis Related Groups (DRGs) with a high number of dementia patients.nnnINTERVENTIONnNone.nnnMEASUREMENTSnThe databases were queried for 12 DRGs (versions 18/24). Predictor effects for dementia on HDD categories were modeled adjusting for other defined comorbidities/covariates using logistic regression. Adjusted predictor effects of dementia on HDD in the DRG groupings were determined. Dementia prevalence and trends were assessed.nnnRESULTSnIncreasing proportions of dementia were noted in 4 DRGs studied. Dementia was strongly associated with being discharged to a nonhome setting. The most marked dementia effects were noted in DRGs 174 (gastrointestinal hemorrhage), 88 (chronic obstructive pulmonary disease), 182 (esophagitis/gastroenteritis), 138 (cardiac arrhythmias), 127 (congestive heart failure), and 89 (simple pneumonia and pleurisy), where there was at least a 76% reduction in the adjusted odds ratio (0.18-0.24) for home discharge. In contrast, DRGs 14 (stroke), 79 (respiratory infections/ inflammations), and 320 (kidney/urinary infections) had a smaller reduction in dementia-associated adjusted odds ratio (0.41-0.46) for home discharge. DRGs 79 and 320 had the highest proportions of dementia (>10%).nnnCONCLUSIONSnDementia proportions in many hospitalization categories have increased. The variable effect of dementia on home discharge suggests that dementia has a differential influence on hospital discharge disposition depending on the DRG. These findings have implications for healthcare allocation and long-term care planning.

Successful use of an older ionic contrast media in a patient with systemic hypersensitivity to ioxilan

Results A 78-year-old female with end stage renal disease on hemodialysis via arteriovenous fistula, diabetes mellitus, hypertension, and hyperlipidemia was evaluated for recurrent fever and rash after receiving CM for a fistulogram. She had received prednisone prophylactically for reactions associated with ioxilan administration on two prior fistulograms. These reactions consisted of diffuse erythematous rash preceded by fever that started 2-4 hours after contrast administration and lasted several days. After receiving pretreatment with prednisone and diphenhydramine, she received her most recent dose of ioxilan (70 mL) for a fistulogram and developed fever and diffuse erythematous rash (2 and 4 hours post injection, respectively). The fever lasted 3 days and the rash subsequently desquamated involving the arms, trunk, neck and face. Her skin fully re-epithelialized 2 weeks later. She had negative skin prick tests and negative patch tests to ioxilan, iothalamate, and iohexol. She subsequently underwent challenge with 10 mL of intravenous iothalamate and was observed for 4 hours without incident. Later, she underwent fistulogram with iothalamate and tolerated it without adverse reactions. Conclusions Hypersensitivity reactions are generally much less common with non-ionic CM compared to older ionic CM. However, for DHRs, reaction rates between ionic CM and non-ionic CM are similar. Successful administration of different CM selected based on skin tests has been reported for patients with previous DHRs to specific CM. In our case, skin testing was non-diagnostic, and we hypothesized that the distinct chemical structures of these agents would make immunological cross-reactivity unlikely. Indeed this patient who was repeatedly reactive to the non-ionic lowosmolal CM ioxilan, subsequently tolerated the ionic hyperosmolal CM iothalamate. We conclude that different epitopes involved in DHRs to CM may be suggested based on differing chemical structure and ionicity. Further research is needed regarding both the cross-reactivity and cross-tolerance of various CM in DHRs, especially in CM skin-test negative patients.

Protein-Losing Conditions

Protein-losing conditions can result from infectious, autoimmune, hypersensitivity, inflammatory, and mechanical etiologies. While various complications, such as edema, nutritional deficits, and end-organ disease, result from protein loss from the circulation, infectious complications that are noted in humoral immunodeficiency usually are not increased to the same extent, despite sometimes profound hypogammaglobulinemia. When properly diagnosed and managed, protein-losing conditions can be significantly ameliorated with both laboratory and clinical improvement.