Systematic review and meta-analysis of rates of clozapine-associated myocarditis and cardiomyopathy.

BACKGROUND: Clozapine is the most effective medication for treatment refractory schizophrenia, but is associated with cardiac adverse drug reactions. Myocarditis and cardiomyopathy are the most serious cardiac adverse drug reactions although reported rates of these conditions vary in the literature. We systematically reviewed and meta-analysed the event rates, the absolute death rates and case fatality rates of myocarditis and cardiomyopathy associated with clozapine. METHODS: PubMed, EMBASE and PsycINFO were searched for studies that reported on the incidence of cardiomyopathy or myocarditis in people exposed to clozapine. Data were meta-analysed using a random effects model, with subgroup analysis on study size, time frame, region, quality, retrospective vs prospective, and diagnostic criteria of myocarditis or cardiomyopathy. RESULTS: 28 studies of 258,961 people exposed to clozapine were included. The event rate of myocarditis was 0.007 (95% confidence interval [CI] = [0.003, 0.016]), absolute death rate was 0.0004 (95% CI = [0.0002, 0.0009]) and case fatality rate was 0.127 (95% CI = [0.034, 0.377]). The cardiomyopathy event rate was 0.006 (95% CI = [0.002, 0.023]), absolute death rate was 0.0003 (95% CI = [0.0001, 0.0012]) and case fatality rate was 0.078 (95% CI = [0.018, 0.285]). Few included studies provided information on criteria for diagnosis of myocarditis and cardiomyopathy. Event rates of cardiomyopathy and myocarditis were higher in Australia. CONCLUSION: Clarity of diagnostic criteria for myocarditis remains a challenge. Observation bias may, in part, influence higher reported rates in Australia. Monitoring for myocarditis is warranted in the first 4 weeks, and treatment of comorbid metabolic syndrome and diabetes may reduce the risk of cardiomyopathy. The risks of myocarditis and cardiomyopathy are low and should not present a barrier to people with treatment refractory schizophrenia being offered a monitored trial of clozapine.

Acceptable interventions to reduce syphilis transmission among high-risk men who have sex with men in Los Angeles.

OBJECTIVES: We examined perceptions of and attitudes toward existing and potential syphilis interventions, including case management and Web-based programs, to increase syphilis testing among high-risk men who have sex with men (MSM). METHODS: Between October 2010 and June 2011, we conducted in-depth interviews with 19 MSM in Los Angeles, California, with repeat early syphilis infections (primary, secondary, and early latent syphilis) within the previous 5 years. We analyzed the interviews inductively to determine the most acceptable potential interventions. RESULTS: Experiences with health department and community-based standard of care case management were generally positive. The most popular interventions among respondents included a Web site providing information on syphilis and syphilis testing, automated Web reminders to test, being paid to test, free online home testing kits, and preexposure prophylactic medication. Respondents' beliefs that they would continue to practice high-risk sexual behaviors reinforced their reasons for wanting increased accessibility and convenient testing strategies. CONCLUSIONS: Public health officials should consider participant responses to potential interventions for syphilis, which suggest that high-risk MSM would consider testing more often or using other interventions.

Community-embedded disease intervention specialist program for syphilis partner notification in a clinic serving men who have sex with men.

BACKGROUND/OBJECTIVES: We evaluated the effectiveness of a Community-Embedded Disease Intervention Specialist (CEDIS) in providing partner notification (PN) for primary syphilis cases in a high STD morbidity, community-based clinic serving men who have sex with men in Los Angeles. METHODS: The CEDIS was trained by the same standards as the local health department Disease Investigator Specialists but was employed by and stationed at the clinic where the primary cases were diagnosed. We compared the CEDIS on specific PN outcomes before and after placement of the CEDIS and among countywide men who have sex with men primary syphilis cases, excluding the cases from the CEDIS clinic. RESULTS: In 2009-2010 after placement of the CEDIS, 100% (87) of primary cases assigned were interviewed; 28% (26) on the same day as their clinic visit and 64% (59) within 7 days. In 2006-2007 before placement of the CEDIS, 67% (43) of primary cases assigned were interviewed; only 2% (1) were interviewed within 7 days. In 2009-2010 countywide, 9% (21) of 252 primary cases assigned were interviewed on the same day as their clinic visit; 18% (45) within 7 days. After placement of the CEDIS, 15% (21) of 140 partners elicited were identified with early syphilis and brought to treatment compared with 0% of 13 partners elicited before placement of the CEDIS, and 15% (25) of 171 partners elicited countywide. CONCLUSION: The CEDIS program fosters key elements to a successful PN program, such as prompt interviewing of newly diagnosed cases and community trust.

Intragenomic sequence variation of the ITS-1 region within a single flow-cytometry-counted Cyclospora cayetanensis oocysts.

Cyclospora cayetanensis, a protozoan of emerging concern, causes self-limiting gastroenteritis in immune-competent hosts. It has been established that sequence variability exists in the first internal transcribed spacer region (ITS-1) of the ribosomal DNA operon from collections of oocysts obtained from individual or pooled fecal samples. To determine if single oocysts also exhibited ITS-1 sequence variability, DNA was extracted from individually flow-cytometry-counted oocysts. We determined that ITS-1 sequence variability exists at an individual-genome level for C. cayetanensis and approached or exceeded the variability exhibited among oocyst collections. ITS-1 variability, at the genome level, reduces this region's utility for inferring relationships between strains.

Enhanced concentration and isolation of Cyclospora cayetanensis oocysts from human fecal samples.

Cyclospora cayetanensis is the causative agent of cyclosporiasis, an emerging infectious disease. We present a new method for the purification of C. cayetanensis oocysts from feces using a modified detachment solution and Renocal-sucrose gradient sedimentation. This method yields oocysts free from adherent fecal debris and amenable to processing using flow cytometry.

Latent schistosomiasis in Portuguese soldiers.

Schistosomiasis was diagnosed in two Portuguese soldiers who had been deployed to Portuguese colonies in Africa. The first veteran was diagnosed as having schistosomiasis 34 years after returning from Angola, and the second veteran was found with Schistosoma haematobium infection 40 years after returning from Mozambique. The patient with Schistosoma mansoni had an active infection, because eggs were recovered with living miracidia. The second patient had developed urothelial cancer, but eggs recovered were calcified.

History of U.S. military contributions to the study of parasitic diseases.

U.S. military researchers have made major contributions to the discovery, diagnosis, treatment, and prevention of a number of parasitic diseases. We review the paramount U.S. military contributions to the understanding of leishmaniasis, filariasis, schistosomiasis, trypanosomiasis, gastrointestinal parasites, intestinal capillariasis, and angiostrongyliasis.

Detection of Cyclospora cayetanensis in animal fecal isolates from Nepal using an FTA filter-base polymerase chain reaction method.

Cyclospora cayetanensis is an emerging protozoan parasite capable of causing a protracted diarrheal illness in both immunocompromised and immunocompetent individuals. Ingestion of fresh produce and water sources contaminated with mature sporulated oocysts results in acquisition of cyclosporiasis. Currently, no animal model exists for the study of this pathogenic parasite and the only confirmed reservoir host for C. cayetanensis in nature is humans. Previously, Cyclospora-like oocysts had been detected by microscopy in several animals including non-human primates. However, their phylogenetic relationship to C. cayetanensis remained uncertain due to the limited availability of molecular techniques to differentiate and speciate these isolates. In the present study, we examined a series of fecal isolates obtained from dogs, chickens, and monkeys collected between May and September 2002 from several geographic regions of Nepal. All samples were examined by microscopy and a polymerase chain reaction (PCR) for the presence of C. cayetanensis. Both microscopic and conventional PCR/restriction fragment length polymorphism (RFLP) analysis demonstrated the presence of Cyclospora sp. in the fecal samples of two dogs, one chicken, and one monkey. Application of a species-specific multiplex PCR assay confirmed the presence of both Eimeria sp. and C. cayetanensis in the positive chicken sample and only C. cayetanensis in the dog and monkey samples. However, in the absence of tissue analysis, the assignment of these animals as a natural reservoir host for C. cayetanensis remains to be determined.

Reevaluation of the employment of Fick's law for diffusion dosimeters.

This paper reconsiders the means of applying Fick's first law to passive diffusion dosimeters. The performance of the organic vapor monitor (OVM), a commercially available dosimeter, is modeled in terms of gradients, which are generated by evaporating a compound from the dosimeter. The fluxes induced by the gradients are determined gravimetrically. The ratio of a flux and a gradient is reported as a Fick's law proportionality constant, the sampling rate. The sampling rate for the gradient across the OVM is calculated from a harmonic average of the sampling rates of two other gradients. The OVM sampling rates for nine compounds determined by the new methodology agree well with published values. Further analysis of the other two gradients provides a value for an apparent reduction in sampling rate in the absence of airflow across the dosimeter (a boundary-layer effect). Procedures are also described to validate measured air concentrations by determining the sampling rates before and after exposure and by correcting for the boundary-layer effect. Sampling rates were found to be stable during 2-4-day exposures in a variety of conditions. In contrast, the boundary-layer effect caused the measured air concentrations to be substantially lower than the estimated true air concentrations.

Diabetic demyelinating polyneuropathy responsive to intravenous immunoglobulin therapy.

BACKGROUND: There is growing evidence that idiopathic chronic inflammatory demyelinating polyneuropathy (CIDP) and polyneuropathy in patients with diabetes mellitus (DM) that meets the electrophysiological criteria for CIDP (DM-CIDP) have many similarities. OBJECTIVE: To evaluate whether DM-CIDP responds to intravenous immunoglobulin (IVIG) therapy. PATIENTS AND METHODS: Twenty-six patients (mean [SD] age, 64 [8.9] years; age range, 40-80 years) with type 2 DM (n = 25), who met the electrophysiological criteria for CIDP, were given IVIG therapy (400 mg/kg body weight per day for 5 days) in a prospective open-label pilot study. All patients had quantitative evaluation using the Neuropathy Impairment Score at baseline and at the end of 4 weeks from the initiation of IVIG therapy. RESULTS: The mean Neuropathy Impairment Score improved significantly from baseline (mean [SD], 61.5 [26.0] points) to the end of the fourth week (33 [29.6] points; P<.00l). This clinically significant improvement occurred in 21 (80.8%) of the 26 patients. Conduction block occurred in 11 (42.3%) of the 26 patients; improvement in the Neuropathy Impairment Score was more frequent in patients who had a conduction block (11 of 11 patients) than in those who did not (10/15 [66.7%]; P =.03). Adverse reactions to IVIG included reversible renal dysfunction in 3 patients, flulike symptoms in 5, headache in 5, and chest pain and shortness of breath in 1. CONCLUSION: Although IVIG therapy seemed to improve DM-CIDP in this uncontrolled trial, a controlled trial is required for confirmation of our findings.

Demyelinating neuropathy in diabetes mellitus.

BACKGROUND: Recent studies have reported that patients with diabetes mellitus (DM) have a predisposition to develop chronic inflammatory demyelinating polyneuropathy (CIDP). OBJECTIVES: To determine whether patients with DM have a polyneuropathy fulfilling electrophysiologic criteria for CIDP, and whether CIDP is more frequent in patients with type 1 than in patients with type 2 DM. METHODS: We prospectively studied the frequency of electrophysiologic changes meeting the criteria for CIDP in patients with DM seen in our electrophysiology laboratory during a 51-month period (period 1). To evaluate the relationship between DM and CIDP, we prospectively determined during a 14-month period (period 2) the frequency of DM in patients seen in our electrophysiology laboratory with other neuromuscular diseases, and the frequency of idiopathic CIDP. RESULTS: During period 1, 120 patients with DM met the electrophysiologic criteria for CIDP (DM-CIDP). The most frequent clinical features of DM-CIDP were those of a predominantly large-fiber sensorimotor neuropathy, with recent motor deterioration and a moderately increased cerebrospinal fluid protein concentration. Twenty-six of the 120 patients were given intravenous immunoglobulin (400 mg/kg per day for 5 days), and 21 patients (80.8%) had significant improvement in the neurologic deficit at the end of 4 weeks of therapy. The DM-CIDP occurred equally in type 1 and type 2 DM. During period 2, 1127 patients were seen. Of these, 189 (16.8%) had DM with various neurologic disorders, including 32 patients (16.9%) with DM-CIDP. Among the remaining 938 patients without DM, 17 (1.8%) had idiopathic CIDP. The odds of occurrence of DM-CIDP was 11 times higher among diabetic than nondiabetic patients (P<.001). CONCLUSIONS: Demyelinating neuropathy meeting the electrophysiologic criteria for CIDP occurred in both types of DM, and its occurrence was significantly higher in diabetic than in nondiabetic patients.

Flood hazard information disclosure by realtors

Research in California has show that mandatory disclosure of earthquake hazard information has had very little impact upon home purchases in danger areas. This study looks at a flood hazard area in the lower florida keys to see if there is a similar phenomenon. Questionnaires were sent to realtors, residential home buyers, and mobile home buyers within the study area (between Big Pine Key on the north and saddlebunch keys on the south) between january of 1980 and august of 1983. The response rate was 67

for realtors and residential real estate purchasers and 64

for mobile home buyers. The results are very similar to those in California: although the disclosures do have a positive influence upon the adquisition of flood insurance, they have not diminished the growth of population in flood hazard areas of the Florida keys. (AU)