Case fatality and population mortality associated with anaphylaxis in the United States.

BACKGROUND: Anaphylaxis is a serious allergic reaction that can cause death; however, the actual risk of death is unclear. OBJECTIVE: We sought to estimate the case fatality rate among hospitalizations or emergency department (ED) presentations for anaphylaxis and the mortality rate associated with anaphylaxis for the general population. METHODS: This was a population-based epidemiologic study using 3 national databases: the Nationwide Inpatient Sample (NIS; 1999-2009), the Nationwide Emergency Department Sample (NEDS; 2006-2009), and Multiple Cause of Death Data (MCDD; 1999-2009). Sources for these databases are hospital and ED discharge records and death certificates, respectively. RESULTS: Case fatality rates were between 0.25% and 0.33% among hospitalizations or ED presentations with anaphylaxis as the principal diagnosis (NIS+NEDS, 2006-2009). These rates represent 63 to 99 deaths per year in the United States, approximately 77% of which occurred in hospitalized patients. The rate of anaphylaxis-related hospitalizations increased from 21.0 to 25.1 per million population between 1999 and 2009 (annual percentage change, 2.23%; 95% CI, 1.52% to 2.94%), contrasting with a decreasing case fatality rate among hospitalizations (annual percentage change, -2.35%; 95% CI, -4.98% to 0.34%). Overall mortality rates ranged from 0.63 to 0.76 per million population (186-225 deaths per year, MCDD) and appeared stable in the last decade (annual percentage change, -0.31%; 95% CI, -1.54% to 0.93%). CONCLUSION: From 2006 to 2009, the overwhelming majority of hospitalizations or ED presentations for anaphylaxis did not result in death, with an average case fatality rate of 0.3%. Anaphylaxis-related hospitalizations increased steadily in the last decade (1999-2009), but this increase was offset by the decreasing case fatality rate among those hospitalized; both inpatient and overall mortality rates associated with anaphylaxis appeared stable and were well under 1 per million population. Although anaphylactic reactions are potentially life-threatening, the probability of dying is actually very low. With the prevalence of anaphylaxis on the increase, practitioners need to stay vigilant and follow the treatment guidelines to further reduce anaphylaxis-related deaths.

How can real-world evidence aid decision making during the life cycle of nonprescription medicines?

Real-world evidence (RWE) is an emerging scientific discipline which is being increasingly utilized for decision making on prescription-only medicines. However, there has been little focus to date on the application of RWE within the nonprescription sector. This paper reviews the existing and potential applications of RWE for nonprescription medicines, using the nonprescription medicine life cycle as a framework for discussion. Relevant sources of real-world data (RWD) are reviewed and compared with those available for prescribed medicines. Existing life-cycle data gaps are identified where RWE is required or where use of RWE can complement data from randomized controlled trials. Published RWE examples relating to nonprescription medicines are summarized, and potential relevant future sources of RWD discussed. Challenges and limitations to the use of RWE on nonprescription medicines are discussed, and recommendations made to promote optimal and appropriate use of RWE in this sector. Overall, RWE currently plays a key role in specific phases of the nonprescription medicine life cycle, including reclassification and postmarketing safety surveillance. The increasing availability of patient-generated health data is likely to further increase the utilization of RWE to aid decision making on nonprescription medicines.

Perception and management of fever in infants up to six months of age: a survey of US pediatricans.

BACKGROUND: A fever is an increase in the body's temperature above normal. This study examined how US pediatricians perceive and manage fever generally versus fever occurring after vaccination in infants up to six months of age. METHODS: A web-based survey of 400 US pediatricians subscribing to the Physician Desk Reference was conducted in December 2008. Data were collected on the respondents' socio-demographics, number of years in practice, type of practice, their definition of fever severity in infants, and their recommendations for managing fever. Generalized Estimating Equations were used to estimate the odds of a pediatrician recommending an emergency room visit (ER) or a hospital admission, office visits, or other treatment option, as a function of infant's age, temperature, whether the infant has recently received a vaccine, and whether the fever was reported during or after office hours, adjusting for practice type and socio-demographic variables. RESULTS: On average, the 400 responding pediatricians' (64% were female, average age of 49 years, years in practice = 20 years) threshold for extremely serious fever was ≥39.5°C and ≥ 40.0°C for infants 0-2 month and >2-6 month of age respectively. Infants were more likely to be referred to an ER or hospital admission if they were ≤ 2 months of age (Odds Ratio [OR], 29.13; 95% Confidence interval [95% CI], 23.69-35.82) or >2-4 months old (OR 3.37; 95% CI 2.99-3.81) versus > 4 to 6 months old or if they had a temperature ≥ 40.0°C (OR 21.06; 95% CI 17.20-25.79) versus a temperature of 38.0-38.5°C. Fever after vaccination (OR 0.29; 95% CI 0.25-0.33) or reported during office hours (OR 0.17; 95% CI 0.15-0.20) were less likely to result in referral to ER or hospital admission. CONCLUSION: Within this sample of US pediatricians, perception of the severity of fever in infants, as well as the response to infant fever are likely to depend on the infant's age. Recommendations for the management of fever in infants are likely to depend on fever severity level, the infant age, timing in relation to recent vaccination, and the time of day fever is reported. Our results indicate that US pediatricians are more concerned about general fever than fever following vaccination.

Acute migraine treatment with oral triptans and NSAIDs in a managed care population.

OBJECTIVE: To describe the use of oral triptans with or without nonsteroidal anti-inflammatory drugs (NSAIDs) for acute migraine treatment in a managed care population and its potential impact on functionality. BACKGROUND: Prescription or over-the-counter NSAIDs with or without oral triptans are commonly used for treatment of acute migraine pain. Little is known about patients' treatment strategy when they have had experiences using NSAIDs and oral triptan cotherapy and the relationship between treatment strategy and migraine symptoms and functionality. METHOD: Migraineurs identified from an administrative claims database were surveyed for their use of oral triptans and NSAIDs during their last attack in the screening phase and during the subsequent migraine attack in the follow-up phase of the study. Treatment regimens were classified into 6 categories: simultaneous coadministration of triptans and NSAIDs (T and N); triptans first followed by NSAIDs (T N); NSAIDs first followed by triptans (N T); triptans only (TRP only); NSAIDs only (NSAID only); and others. Headache experience, reasons for treatment regimens, and treatment satisfaction were cross-tabulated by treatment regimens. The log-rank test was used for the analysis of time-to-event data. RESULTS: Among 8440 oral triptan users surveyed during the screening phase, 2307 (27%) reported using triptans and NSAIDs combination therapy during their last migraine attack. Of those, 1502 experienced a subsequent migraine attack and completed the follow-up survey; 38% of these 1502 patients who used triptans and NSAIDs cotherapy during their last migraine attack continued to use combination therapy for their next attack. The most common treatment regimen, excluding "others" (n = 354, 24%), was TRP only (n = 403, 27%), followed by N T (n = 345, 23%), NSAID only (n = 170, 11%), T&N (n = 152, 10%), and T N (n = 75, 5.0%). More TRP only patients became nausea-free within 1 h after an initial dosing. TRP only, T&N, and N T had significantly shorter median hours of suffering from migraine and limited functioning, as compared with other treatment regimens. Substantially more patients taking TRP only (34.7%) were very satisfied with their current treatment regimen than other regimens. CONCLUSIONS: Migraine patients frequently change their treatment regimens in response to headache profiles. For patients with migraine associated nausea symptom, combination of therapy with triptan and NSAIDs appears to be less effective in relieving nausea than triptan monotherapy. Triptan montherapy remains a common and an effective migraine treatment strategy.

Cost analysis of five antimicrobial regimens for the treatment of intra-abdominal infection.

BACKGROUND: Cost of treatment is an important consideration in antimicrobial agent selection for intra-abdominal infection. We analyzed the relation between the total cost of inpatient stay and the initial selection of antimicrobial agent. METHODS: Actual costs of inpatient care were calculated for 1,234 patients treated at 22 hospitals with one of five antimicrobial regimens: Ampicillin/sulbactam (n = 428), ertapenem (n = 143), ceftriaxone (n = 101), levofloxacin (n = 245), or piperacillin/tazobactam (n = 317) for intra-abdominal infections. Length of stay (LOS), demographic data, diagnosis, disease severity index, intensive care unit (ICU) stay, and total and specific costs were obtained from a large hospital-based, service level, comparative database for five types of infection (appendicitis, cholecystitis, diverticulitis, pancreatitis, and postoperative infection). RESULTS: The LOS was shorter for appendicitis (3.8 days) and cholecystitis (4.6 days) than for diverticulitis (11.4 days), pancreatitis (8.1 days), or postoperative infection (8.4 days). Length of stay and total cost were most closely related to severity index (p < 0.01) and ICU days (p < 0.01). When patient and hospital characteristics and correlations within hospitals were accounted for in the model, piperacillin/tazobactam was associated with significantly higher cost than ertapenem, ampicillin/sulbactam, and levofloxacin. CONCLUSIONS: In assessing pharmacoeconomic outcomes in the treatment of intra-abdominal infection, cost of treatment, although lower with certain antimicrobial agents, is dependent on severity-of-illness indicators.

Estimating cholesterol treatment rates among individuals with multiple risk factors and without coronary heart disease.

This retrospective study examined lipid-lowering therapy treatment rates from 2000 to 2001 using the Ingenix LabRx Database. Patients with multiple risk factors without coronary heart disease were identified based on the presence of >/=2 of the following: men >/=45 years, women >/=55 years, hypertension, high-density lipoprotein cholesterol <40 mg/dl, total cholesterol >/=200 mg/dl, or obesity. Lipid treatment rates were estimated among those needing therapy (defined as low-density lipoprotein cholesterol >/=130 mg/dl or currently receiving lipid-lowering therapy). The overall lipid-lowering therapy treatment rate was 38% and the estimated lipid treatment gap (percent needing treatment who were not receiving it) was 62%.

Does initial choice of antimicrobial therapy affect length of stay for patients with complicated intra-abdominal infections?

Outcomes for complicated intra-abdominal infection are influenced by operation for source control, patient-related factors, and medical management, including antibiotic treatment. We analyzed length of stay (LOS) at 33 hospitals for 2,150 patients discharged between February 2002 and June 2003, who were > 18 years, had intra-abdominal infection, and received one of 6 first-line antimicrobials. A regression tree analysis selected important variables, their interactions, and their order of significance in explaining LOS. A linear mixed model evaluated the difference in LOS between treatment groups. Adjusted LOS was calculated by the least squares means from the model and was used to assess treatment differences. Mean LOS analyzed by initial antimicrobial therapy and stratified by diagnosis showed LOS for ampicillin/sulbactam and ertapenem to be significantly shorter from levofloxacin, ceftriaxone, and piperacillin/tazobactam (all P < 0.05). Adjusting for all other factors, the variables associated with severity (e.g., diagnosis, ICU stay, and comorbidities) had the greatest impact on adjusted LOS (all P < 0.001). Our findings indicate ampicillin/sulbactam and ertapenem were associated with shorter hospital stays, which may be explained by unaccounted for underlying severity of infection and/or by surgeons stratifying antimicrobial selection according to severity of illness.

Prediction model for penile prosthesis implantation for erectile dysfunction management.

OBJECTIVE: Penile prosthesis surgery is indicated based on undesirability, contraindication or ineffectiveness of non-surgical options for erectile dysfunction. This definitive treatment is often delayed after initial diagnosis. Our objective was to develop a prediction tool based on a patient's clinical history to determine likelihood of ultimately receiving a penile prosthesis. RESEARCH DESIGN AND METHODS: This retrospective analysis used claims data from Commercial and Medicare supplemental databases. Inclusion criteria were 18 years of age with 1 year of continuous enrollment at the first diagnosis of erectile dysfunction. Patients' demographics, co-morbidities and erectile dysfunction therapy were derived based on enrollment, medical and prescription histories. MAIN OUTCOME MEASURES: The Cox proportional hazards model with stepwise selection was used to identify and quantify (using relative risk) factors associated with a future penile prosthesis implant. Co-morbidities and therapies present prior to the index erectile dysfunction diagnosis were analyzed as fixed covariates. RESULTS: Approximately 1% of the dataset's population (N = 310,303 Commercial, N = 74,315 Medicare, respectively) underwent penile prosthesis implantation during the study period (3928 patients in the overall population: 2405 patients [0.78%] in the Commercial and 1523 patients [2.05%] in the Medicare population). Factors with the greatest predictive strength of penile prosthesis implantation included prostate cancer diagnosis (relative risk: 3.93, 2.29; 95% CI, 3.57-4.34, 2.03-2.6), diabetes mellitus (2.31, 1.23; 2.12-2.52, 1.1-1.37) and previous treatment with first-line therapy (1.39, 1.33; 1.28-1.5, 1.2-1.47) (all P < 0.01). CONCLUSION: The presence and extent of specific medical history factors at the time of erectile dysfunction diagnosis predict an individual's future likelihood of penile prosthesis. Calculating the likelihood of penile prosthesis implantation based on the weight of these factors may assist clinicians with the definition of a care plan and patient counseling. The precision of the model may be limited by factors beyond medical history information that possibly influence the decision to proceed to surgery.

The prevalence of opioid-related major potential drug-drug interactions and their impact on health care costs in chronic pain patients.

BACKGROUND: Literature has shown that chronic pain patients prescribed opioids are at an increased risk for experiencing drug-drug interactions as a result of polypharmacy. In addition, chronic, noncancer pain patients who experience drug-drug interactions have been shown to have greater health care utilization and costs. However, no study has focused on the health economics of major clinically significant drug-drug interactions associated with long-acting opioids. OBJECTIVES: To (a) estimate the prevalence of major drug-drug interactions among patients prescribed a long-acting opioid and (b) evaluate the potential impact of major drug-drug interactions on health care costs. METHODS: This study was a retrospective cohort analysis using claims data from the MarketScan Commercial Claims and Encounter Database between 2008 and 2010. Patients with at least 1 prescription for a long-acting opioid for ≥ 30 days were placed into cohorts according to the expected clinical impact of the potential drug-drug interaction: major versus none. Propensity score matching was used to mitigate differences in baseline characteristics between the cohorts. Health care costs were based on payments for all covered health care services, which consisted of inpatient and outpatient medical, emergency department, and outpatient prescription costs. RESULTS: Among 57,752 chronic, noncancer pain patients who met all inclusion and exclusion criteria, 5.7% (3,302) were exposed to a potential major drug-drug interaction. The costs associated with a potential interaction versus no potential interaction were significantly more after baseline characteristics of the cohorts were normalized by propensity score matching. Monthly health care costs in the 90-day post-index period were significantly greater ($3,366 vs. $2,757, a $609 difference) in patients exposed to a potential drug-drug interaction of major clinical significance, compared with those not exposed to a drug-drug interaction. The higher health care costs were mainly driven by outpatient and inpatient medical costs. CONCLUSIONS: Exposure to potential drug-drug interactions may result in unnecessary and unintended health care costs. Physicians should be made aware of commonly administered cytochrome P450 (CYP450) metabolized drugs in the chronic pain patient and consider prescribing non-CYP450 metabolized opioid and nonopioid analgesics. Managed care's use of utilization management tools to avoid these exposures may reduce costs.

Daily average consumption of 2 long-acting opioids: an interrupted time series analysis.

BACKGROUND: Oxycodone controlled release (CR) and oxymorphone extended release (ER) are frequently prescribed long-acting opioids, which are approved for twice-daily dosing. The US Food and Drug Administration approved a reformulated crush-resistant version of oxycodone CR in April 2010. OBJECTIVE: To compare the daily average consumption (DACON) for oxycodone CR and for oxymorphone ER before and after the introduction of the reformulated, crush-resistant version of oxycodone CR. METHODS: This was a retrospective claims database analysis using pharmacy claims from the MarketScan database for the period from January 2010 through March 2011. The interrupted time series analysis was used to evaluate the impact of the introduction of reformulated oxycodone CR on the DACON of the 2 drugs-oxycodone CR and oxymorphone ER. The source of the databases included private-sector health data from more than 150 medium and large employers. All prescription claims containing oxycodone CR and oxymorphone ER dispensed to members from January 1, 2010, to March 31, 2011, were included in the analysis. Prescription claims containing duplicate National Drug Codes, missing member identification, invalid quantities or inaccurate days supply of either drug, and DACON values of <1 and >500 were removed. RESULTS: The database yielded 483,063 prescription claims for oxycodone CR and oxymorphone ER from January 1, 2010, to March 31, 2011. The final sample consisted of 411,404 oxycodone CR prescriptions (traditional and reformulated) dispensed to 85,150 members and 62,656 oxymorphone ER prescriptions dispensed to 11,931 members. Before the introduction of reformulated oxycodone CR, DACON values for the highest strength available for each of the 2 drugs were 0.51 tablets higher for oxycodone CR than for oxymorphone ER, with mean DACON values of 3.5 for oxycodone CR and 3.0 for oxymorphone ER (P <.001). The differences of mean DACON between the 2 drugs for all lower strengths were 0.46 tablets, with mean DACON values of 2.7 for oxycodone CR and 2.3 for oxymorphone ER (P <.001). After the introduction of the new formulation, the difference in mean DACON between the 2 drugs was slightly lower: 0.45 tablets for the highest-strength and 0.40 tablets for the lower-strength pairs. Regression analyses showed that the immediate and overall impact of the reformulation of oxycodone CR on the DACON of oxycodone CR was minimal, whereas no changes were seen in the DACON of oxymorphone ER. The estimated DACON for oxycodone CR decreased by 0.1 tablets, or 3.7% (P <.001), 6 months after the new formulation was introduced. CONCLUSION: The mean DACON was 0.4 tablets per day higher for oxycodone CR compared with oxymorphone ER for all dosage strengths for the entire study period. After the introduction of the reformulated oxycodone CR, the DACON for this drug was slightly mitigated; however, there was a minimal impact on the mean differences between oxycodone CR and oxymorphone ER.

Clinical and economic outcomes associated with community-acquired intra-abdominal infections caused by extended spectrum beta-lactamase (ESBL) producing bacteria in China.

BACKGROUND: To compare clinical and economic outcomes in patients with community-acquired intra-abdominal infection (IAI) due to extended spectrum beta-lactamase (ESBL) producing (ESBL-positive) bacteria versus non-ESBL-producing (ESBL-negative) bacteria in China. METHODS: This was a retrospective chart review study of patients hospitalized with community-acquired IAI due to ESBL-positive or ESBL-negative infections caused by Escherichia coli or Klebsiella spp. Data were collected from six hospitals in China that participated in the Study for Monitoring Antibiotic Resistance Trends (SMART) during 2006-2007. Outcomes included clinical response at discharge and following first-line antibiotic, number of antibiotic agents and classes, duration of hospitalization, and overall hospitalization and intravenous antibiotic costs. RESULTS: Of the 85 patients included in the study, 32 (37.6%) had ESBL-positive and 53 (62.4%) had ESBL-negative infections; E. coli was responsible for 77.6% of infections. Infection resolved at discharge in 30 (93.8%) ESBL-positive and 48 (90.6%) ESBL-negative patients (P = NS). Fewer ESBL-positive patients achieved complete response following first-line antibiotics (56.3% versus 83.0%; P = 0.01). ESBL-positive patients required longer antibiotic treatment, more antibiotics, longer hospitalization (24.3 versus 14.6 days; 1.67-fold ratio; P = 0.001), and incurred higher hospitalization costs ( yen24,604 vs. yen13,788; $3604 vs. $2020; 1.78-fold ratio; P < 0.001). CONCLUSIONS: Patients with ESBL-positive infection had similar resolution rates at discharge compared to those with ESBL-negative infection, despite poorer first-line antibiotic response. However, ESBL-positive infection led to significantly greater hospitalization cost and intravenous antibiotic cost, and longer hospital stay.

Can migraineurs accurately identify their headaches as "migraine" at attack onset?

BACKGROUND: While treating migraine early when the headache is mild is believed to link to improved treatment outcomes, it is not clear whether patients can correctly self-identify a headache as a migraine at onset in real-world settings. OBJECTIVE: This study aims to assess the likelihood that patients can correctly self-identify a headache as a migraine at onset, and to evaluate cues that patients use to correctly identify migraine attacks. METHODS: Adult migraineurs were recruited from 14 headache clinics across the United States. Patients recorded their headache experiences via an electronic diary daily over a period of 30 days. On days when they experienced headaches, patients were asked to recall the types of headache they experienced at both onset and peak. Patients also identified cues for deciding whether the headache was a migraine or not. Using identification of migraine at headache peak as the criterion, we examined the sensitivity and specificity of migraine identification at onset. We employed generalized estimating equation (GEE) to evaluate factors identified at headache onset that predicted migraine identified at headache peak. RESULTS: Of the 192 enrolled patients, 182 patients recorded a total of 1197 headache episodes over 30 days. At headache onset, 888 episodes were deemed by patients as migraine and 309 episodes not migraine; a majority (92%) of these early migraine identifications were confirmed at headache peak. Sensitivity and specificity of self-identification of migraine at onset were 91% and 97%, respectively. A number of factors at headache onset were predictive of a migraine identified at peak: sensitivity to light (OR = 3.1, 95% CI: 1.9-5.0), headache severity (OR = 2.0, 95% CI: 1.4-2.8), nausea symptoms (OR = 2.6, 95% CI: 1.5-4.5), and visual disturbance (OR = 2.3, 95% CI: 1.1-4.9). Patients who ruled out tension-type headache at onset were twice (OR = 2.0, 95% CI: 1.5-2.8) as likely to conclude a migraine at peak. CONCLUSIONS: Most migraineurs in tertiary care settings can correctly self-identify a headache as a migraine at onset. Factors such as headache severity, presence of nausea, visual disturbance, sensitivity to light, and no tension-type headache, appeared to augment the correct identification.