A case series of recombinant platelet factor 4 for heparin reversal after cardiopulmonary bypass.

BACKGROUND: Platelet factor 4 (PF4) is released by activated platelets and has a strong affinity for heparin. Recombinant PF4 (rPF4) has been previously considered as an alternative to protamine for heparin reversal. However, it has been demonstrated that antibodies directed against the PF4/heparin moiety are important in the pathophysiologic development of heparin-induced thrombocytopenia, a prothrombotic complication for which cardiac bypass patients are at increased risk. METHODS: We retrospectively analyzed a case series from an open-label, comparative phase I-II study of rPF4 and protamine after cardiac surgery to determine the heparin-reversal activity of different doses of IV rPF4. Sixteen patients received rPF4, and 5 received protamine. Activated clotting time (ACT) was used to monitor heparin reversal, with reversal defined as ACT <150 seconds. Platelets, white blood cells, C3a, C5a, fibrinopeptide A, von Willebrand factor antigen, and prothrombin fragment 1.2 were monitored postoperatively as indicators of coagulation and inflammation. RESULTS: Heparin reversal was successful by 10 minutes after administration of rPF4 as measured by ACT in all 16 patients. Specifically, a dose of 5 mg/kg rPF4 resulted in ACT <150 seconds after 5 minutes in 10 of 10 patients. For both treatment groups, there were no bleeding or thrombotic complications, no clinical thrombocytopenia after day 5, and no deaths within the 30-day study period. CONCLUSIONS: Our case series demonstrates that heparin anticoagulation was effectively reversed by the administration of rPF4 without serious complications. Additional studies are needed to further validate the safety and efficacy of exogenous rPF4 administration.

A diagnosis of heparin-induced thrombocytopenia with combined clinical and laboratory methods in cardiothoracic surgical intensive care unit patients.

BACKGROUND: Diagnosing postoperative heparin-induced thrombocytopenia (HIT) in cardiothoracic surgical patients is complicated because of the profound thrombocytopenia that occurs with cardiopulmonary bypass (CPB). CPB predisposes patients to develop a frequent incidence of antibodies directed against platelet factor 4 (PF4)/heparin complexes and HIT. The sensitivity of readily available antibody immunoassays is high, but specificity is quite low. The use of both a clinical probability score and rapid laboratory immunoassay has been shown to increase specificity, which is of particular importance in the CPB setting. Prompt diagnosis is crucial because cessation of heparin and treatment with alternative anticoagulation can reduce the risk of thromboembolic events. METHODS: We retrospectively reviewed records from cardiothoracic surgical patients whose serum was tested with both the serotonin release assay (SRA) and the PF4/heparin immunoassay from January 2007 through December 2010. We assigned a high, intermediate, or low clinical "4Ts" probability score that quantifies thrombocytopenia, timing of platelet decrease, and thrombotic complications in each patient. We then compared the clinical score and the PF4/heparin immunoassay against the "gold standard" diagnostic test, the SRA. RESULTS: The sensitivity and specificity for PF4/heparin optical density >0.40 were 100% and 26%, respectively. Sensitivity and specificity for the diagnosis of HIT with a combination of PF4/heparin optical density >0.40 and high/intermediate 4Ts score were 100% and 70%, respectively. The negative predictive value was 100% for low 4Ts score. CONCLUSIONS: We demonstrated that the use of the 4Ts clinical score combined with the PF4/heparin immunoassay for HIT diagnosis increases the sensitivity and specificity of HIT testing compared with the PF4/heparin immunoassay alone. Furthermore, with an intermediate 4Ts score and positive PF4/heparin antibody test, a confirmatory platelet activation assay such as the SRA is necessary. Physicians treating patients after cardiothoracic surgery should recognize the need for an antibody test and confirmation with a platelet activation assay with even moderate clinical probability of HIT.

The divided dose approach to perioperative buprenorphine -management in patients with opioid use disorder.

There is limited evidence and no clear consensus suggesting best practices for perioperative buprenorphine management in patients with opioid use disorder. As such, we aimed to develop a standardized perioperative management approach with the goals of (1) optimizing perioperative analgesia, (2) minimizing relapse risk, (3) setting expectations for patients and clinicians, (4) achieving prescribing consistency and mitigating risk among clinicians not familiar with perioperative buprenorphine management, and (5) maintaining continuity throughout care transitions. An interprofessional expert focus group convened to develop a consensus algorithm based upon buprenorphine's unique pharmacologic features and published perioperative management recommendations. The resulting consensus algorithm continues the patient's home buprenorphine dose in order to minimize relapse risk, but utilizes a divided dose approach starting the day of surgery if moderate to severe post-operative pain is expected. This strategy leverages the analgesic effects of buprenorphine while allowing for additional opioid binding to optimize analgesia. A patient-centered multimodal perioperative approach including local and/or regional anesthetics and nonopioid adjuncts is employed. Post-operative care is optimized by preoperative planning, including standardized patient assessment, perioperative communication with the buprenorphine prescriber, and education for patients and clinicians. Overall, integrating an understanding of pharmacology and clinical impact through the use of a readily adaptable algorithm such as the divided dose approach is key to optimizing patient care in this high-risk population.

Hemolytic uremic syndrome and death in persons with Escherichia coli O157:H7 infection, foodborne diseases active surveillance network sites, 2000-2006.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a life-threatening illness usually caused by infection with Shiga toxin-producing Escherichia coli O157 (STEC O157). We evaluated the age-specific rate of HUS and death among persons with STEC O157 infection and the risk factors associated with developing HUS. METHODS: STEC O157 infections and HUS cases were reported from 8 sites participating in the Foodborne Diseases Active Surveillance Network during 2000-2006. For each case of STEC O157 infection and HUS, demographic and clinical outcomes were reported. The proportion of STEC O157 infections resulting in HUS was determined. RESULTS: A total of 3464 STEC O157 infections were ascertained; 218 persons (6.3%) developed HUS. The highest proportion of HUS cases (15.3%) occurred among children aged <5 years. Death occurred in 0.6% of all patients with STEC O157 infection and in 4.6% of those with HUS. With or without HUS, persons aged 60 years had the highest rate of death due to STEC O157 infection. Twelve (3.1%) of 390 persons aged 60 years died, including 5 (33.3%) of 15 persons with HUS and 7 (1.9%) of 375 without. Among children aged <5 years, death occurred in 4 (3.0%) of those with HUS and 2 (0.3%) of those without. CONCLUSIONS: Young children and females had an increased risk of HUS after STEC O157 infection. With or without HUS, elderly persons had the highest proportion of deaths associated with STEC O157 infection. These data support recommendations for aggressive supportive care of young children and the elderly early during illness due to STEC O157.

Predicting mortality in patients with disseminated intravascular coagulation after cardiopulmonary bypass surgery by utilizing two scoring systems.

: We evaluated clinical and laboratory biomarkers of disseminated intravascular coagulation (DIC) following cardiac surgery in the cardiothoracic surgical ICU (CTICU) to predict mortality. We retrospectively analyzed CTICU patients with suspected DIC identified from the hospital laboratory database, and calculated International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM) DIC scores to predict DIC-related mortality. The predictive accuracy of the JAAM and ISTH DIC scoring system were then assessed by logistic regression analysis and receiver operative characteristics analysis, and compared to other potential predictors of mortality (e.g., Acute Physiology and Chronic Health Evaluation II, systemic inflammatory response syndrome criteria, laboratory variables). Our study showed a 30-day mortality rate of 71% in CTICU patients with DIC. The JAAM DIC score offered the best predictive accuracy [area under the curve (AUC): 0.723, 95% % confidence interval (CI): 0.638-0.947, P = 0.021], when compared with ISTH DIC score (AUC: 0.707, 95% CI: 0.491-0.923, P = 0.066) and Acute Physiology and Chronic Health Evaluation II (AUC: 0.687, 95% CI: 0.483-0.891, P = 0.110). A JAAM DIC score at least 6 was reported in 89% of the nonsurvivors and 46% of survivors (P = 0.010), and predicted mortality [odds ratio: 9.33 (1.50-58.20)] with a 73% sensitivity and a 78% specificity. Our results also show a strong relationship between acid-base derangement and mortality. This initial evaluation of DIC-related mortality in the CTICU found the standardized JAAM DIC scoring system in combination with acid-base laboratory values were most useful to predict mortality in postcardiac surgery patients with DIC. Additional prospective studies are needed to further validate our findings.

Rocky Mountain spotted fever from an unexpected tick vector in Arizona.

BACKGROUND: Rocky Mountain spotted fever is a life-threatening, tick-borne disease caused by Rickettsia rickettsii. This disease is rarely reported in Arizona, and the principal vectors, Dermacentor species ticks, are uncommon in the state. From 2002 through 2004, a focus of Rocky Mountain spotted fever was investigated in rural eastern Arizona. METHODS: We obtained blood and tissue specimens from patients with suspected Rocky Mountain spotted fever and ticks from patients' homesites. Serologic, molecular, immunohistochemical, and culture assays were performed to identify the causative agent. On the basis of specific laboratory criteria, patients were classified as having confirmed or probable Rocky Mountain spotted fever infection. RESULTS: A total of 16 patients with Rocky Mountain spotted fever infection (11 with confirmed and 5 with probable infection) were identified. Of these patients, 13 (81 percent) were children 12 years of age or younger, 15 (94 percent) were hospitalized, and 2 (12 percent) died. Dense populations of Rhipicephalus sanguineus ticks were found on dogs and in the yards of patients' homesites. All patients with confirmed Rocky Mountain spotted fever had contact with tick-infested dogs, and four had a reported history of tick bite preceding the illness. R. rickettsii DNA was detected in nonengorged R. sanguineus ticks collected at one home, and R. rickettsii isolates were cultured from these ticks. CONCLUSIONS: This investigation documents the presence of Rocky Mountain spotted fever in eastern Arizona, with common brown dog ticks (R. sanguineus) implicated as a vector of R. rickettsii. The broad distribution of this common tick raises concern about its potential to transmit R. rickettsii in other settings.

Continued decline in the incidence of Campylobacter infections, FoodNet 1996-2006.

Campylobacter is a leading cause of foodborne illness worldwide. In the United States, changes in the incidence of culture-confirmed Campylobacter infections have been monitored by the Foodborne Diseases Active Surveillance Network (FoodNet) since 1996. In 2006, the incidence of culture-confirmed Campylobacter infection in the FoodNet sites was 12.7 per 100,000 persons. This represents a 30% decline (95% confidence = 35% to 24% decrease) compared to the 1996-1998 illness baseline; however, most of the decline occurred between 1996 and 1999 and the incidence still remains above the national health objective. Important declines were observed in four FoodNet sites (California, Connecticut, Georgia, and Maryland), all age groups, and both sexes. To promote continued progress towards achieving the national health objective, the epidemiology of Campylobacter infections in the United States, including geographic variation and higher incidence among the very young, warrants further study.

Occam's Razor Could Not Cut It: Tale of 2 Headaches in a Postpartum Patient: A Case Report.

Not all postpartum headaches are caused by dural puncture, and it is possible for postpartum patients to have >1 cause for headache. After neuraxial block with an incidental large-gauge dural puncture, our patient developed a severe, classic postdural puncture headache which initially responded to an epidural blood patch. The patient was readmitted 2 days after discharge complaining of recurrent headache less characteristic of a postdural puncture headache, now being bifrontal/retro-orbital and without clear positional component. Computerized tomography and magnetic resonance imaging revealed an enlarged pituitary gland with a possible hemorrhagic focus; all endocrine parameters were normal. The patient was ultimately diagnosed with lymphocytic adenohypophysitis, an autoimmune inflammation of the anterior pituitary gland.

Effect of basal insulin dosage on blood glucose concentration in ambulatory surgery patients with type 2 diabetes.

STUDY OBJECTIVE: Among patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery. DESIGN: Observational study. SETTING: Pre- and postoperative holding areas. PATIENTS: One hundred fifty patients with type 2 diabetes using a once daily, evening insulin glargine regimen undergoing ambulatory surgery were included. INTERVENTIONS: None. MEASUREMENTS: To conduct the analysis, patients were divided into four groups based on the percentage of normal evening glargine dose taken. Group 1 took no glargine. Group 2 took 33%-57%. Group 3 took 60%-87% and Group 4 took 100% of their normal dose. The primary outcome was the proportion of patients in each group with blood glucose in the target range (100-180 mg/dL), and the incidence of hypoglycemia (defined as BG <70 mg/dL or symptomatic, requiring glucose). MAIN RESULTS: Group 3 had the highest proportion (78%) of patients within target range (P<.001) and Group 4 had the highest proportion of patients with hypoglycemia (P=.01). Patients in Group 3 were significantly more likely to achieve target blood glucose than patients in either Group 1 (P=.001) or Group 4 (P=.002). CONCLUSIONS: Our study shows that the percent of normal insulin dose given the evening before surgery directly impacts perioperative glucose levels in ambulatory surgery patients. Patients taking 60%-87% of their usual dose the evening before surgery were likely to arrive in target blood glucose range with decreased risk for hypoglycemia. The mean and mode dose taken in Group 3 were 73% and 75%, respectively, suggesting that the optimal dose may be 75% of normal dose.

Outbreaks of enteric disease associated with animal contact: not just a foodborne problem anymore.

In the past 10 years, an increasing number of outbreaks of enteric disease associated with animals in public settings, such as fairs and petting zoos, have been reported. Fifty-five of these outbreaks that occurred in the United States during 1991-2005 are reviewed in this article. Lessons learned from these outbreaks and recommendations for prevention are also discussed. Physicians should be aware of this important public health problem and play an active role in prevention of human illness associated with animals in public settings.

Spotted fever group rickettsial infection in dogs from eastern Arizona: how long has it been there?

A serosurvey of free-roaming dogs for antibodies to spotted fever group rickettsiae was conducted using archival samples that had been collected in the White Mountain region of eastern Arizona during a plague study in 1996. Immunoglobulin G antibodies to Rickettsia rickettsii (5.1%) and to R. rhipicephali (3.6%) were demonstrated, and no cross-reactive samples were identified. This study indicates that R. rickettsii was likely present in the dog populations in this area prior to the recognition of human cases of Rocky Mountain spotted fever (RMSF). The role of dogs as short-term reservoirs and primary hosts for the vector tick, Rhipicephalus sanguineus, should receive closer attention.

Molecular typing of novel Rickettsia rickettsii isolates from Arizona.

Seven isolates of Rickettsia rickettsii were obtained from a skin biopsy, two whole-blood specimens, and from Rhipicephalus sanguineus ticks from eastern Arizona. Molecular typing of seven isolates of R. rickettsii and DNA samples from two other Rh. sanguineus ticks infected with R. rickettsii was conducted by PCR and DNA sequencing of rompA and 12 variable-number tandem repeat regions (VNTRs). All DNA specimens from Arizona were identical to each other and to reference human and Dermacentor andersoni isolates of R. rickettsii from Montana in their rOmpA gene sequences and 10 VNTRs. Two of the twelve VNTRs had differences in the number of repeat sequences in isolates from Arizona compared to those from Montana, thus conferring the novelty of the Rh. sanguineus-associated R. rickettsii.

Human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States, 2001-2002.

The epidemiologic features are described of cases of human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States.

Rocky mountain spotted fever in the United States, 1997-2002.

The increased incidence of Rocky Mountain spotted fever (RMSF) in 1997-2002 compared with previous years may be related to enhanced awareness and reporting of RMSF as well as changes in human-vector interaction. However, reports on RMSF mortality underscore the need for physician vigilance in considering a diagnosis of RMSF for febrile individuals potentially exposed to ticks and stress the importance of treating such persons regardless of the presence of a rash.

Rocky Mountain spotted fever in Arizona: documentation of heavy environmental infestations of Rhipicephalus sanguineus at an endemic site.

A recent epidemiologic investigation identified 16 cases and 2 deaths from Rocky Mountain spotted fever (RMSF) in two eastern Arizona communities. Prevalence studies were conducted by collecting free-living ticks (Acari: Ixodidae) from the home sites of RMSF patients and from other home sites within the community. Dry ice traps and flagging confirmed heavy infestations at many of the home sites. Only Rhipicephalus sanguineus ticks were identified and all developmental stages were detected. It is evident that under certain circumstances, this species does transmit Rickettsia rickettsii to humans and deserves reconsideration as a vector in other geographic areas.

An outbreak of Rocky Mountain Spotted Fever associated with a novel tick vector, Rhipicephalus sanguineus, in Arizona, 2004: preliminary report.

This study describes preliminary results of an investigation of RMSF in Arizona associated with the brown dog tick, Rhipicephalus sanguineus. High numbers of dogs and heavy infestations of ticks created a situation leading to human disease.

Rocky mountain spotted fever hospitalizations among American Indians.

To describe the epidemiology of Rocky Mountain spotted fever (RMSF) among American Indians/Alaska Natives (AI/ANs), we conducted a retrospective analysis of hospitalization records with an RMSF diagnosis using Indian Health Service (IHS) hospital discharge data for calendar years 1980-2003. A total of 261 RMSF hospitalizations were reported among AIs, for an average annual hospitalization rate of 1.21 per 100,000 persons; two deaths were reported (0.8%). Most hospitalizations (88.5%) occurred in the Southern Plains region, where the rate was 4.23 per 100,000 persons. Children 1-4 years of age had the highest age-specific hospitalization rate of 2.50 per 100,000 persons. The overall annual RMSF hospitalization rate declined during the study period. Understanding the epidemiology of RMSF among AI/ANs and educating IHS/tribal physicians on the diagnosis of tick-borne diseases remain important for the prompt treatment of RMSF and the reduction of the disease occurrence among AI/ANs, particularly in high-risk areas.

Rocky Mountain spotted fever in the United States, 1997-2002.

Rocky Mountain spotted fever (RMSF) is the most commonly reported fatal tick-borne disease in the United States. During 1997-2002, 3,649 cases of RMSF were reported to the Centers for Disease Control and Prevention via the National Electronic Telecommunications System for Surveillance; 2,589 case report forms, providing supplemental information, were also submitted. The average annual RMSF incidence during 1997-2002 was 2.2 cases/million persons. The annual incidence increased during 1997-2002 to a rate of 3.8 cases/million persons in 2002. The incidence was lowest among persons aged<5 and 10-29 years, and highest among adults aged 60-69 years. The overall case-fatality rate was 1.4%; the rate peaked in 1998 at 2.9% and declined to 0.7% in 2001 and 2002. Children<5 years of age had a case-fatality rate (5%) that was significantly greater than the rates for age groups<60 years of age, except for that for 40-49 years of age. Continued national surveillance is needed to assess the effectiveness of prevention efforts and early treatment in decreasing severe morbidity and mortality associated with RMSF.

Serologic evidence for exposure to Rickettsia rickettsii in eastern Arizona and recent emergence of Rocky Mountain spotted fever in this region.

During 2002 through 2004, 15 patients with Rocky Mountain spotted fever (RMSF) were identified in a rural community in Arizona where the disease had not been previously reported. The outbreak was associated with Rickettsia rickettsii in an unexpected tick vector, the brown dog tick (Rhipicephalus sanguineus), which had not been previously associated with RMSF transmission in the United States. We investigated the extent of exposure to R. rickettsii in the local area through serologic evaluations of children and dogs in 2003-2004, and in canine sera from 1996. Antibodies to R. rickettsii at titers > or = 32 were detected in 10% of children and 70% of dogs in the outbreak community and 16% of children and 57% of dogs in a neighboring community. In comparison, only 5% of canine samples from 1996 had anti-R. rickettsii antibodies at titers > or = 32. These results suggest that exposures to RMSF have increased over the past 9 years, and that RMSF may now be endemic in this region.