Effects of multiple applications of benzalkonium chloride and nonoxynol 9 on the vaginal epithelium in the pigtailed macaque (Macaca nemestrina).

OBJECTIVE: Safe and effective vaginally applied microbicides could help to control the continuing spread of sexually transmitted diseases. STUDY DESIGN: This study used nonhuman primates to test the effects of multiple applications of nonoxynol 9, benzalkonium chloride, or a combination on vaginal flora and lower reproductive tract tissues. Fourteen monkeys (Macaca nemestrina) received daily vaginal applications of nonoxynol 9, benzalkonium chloride, or both for 3 to 4 days. Vaginal microflora and colposcopic observations were made at baseline and during and after completion of treatments. Cervical biopsy specimens were collected from a subset of animals. RESULTS: Cervical erythema and vaginal erythema were observed in all 3 treatment groups. Cervical papillae and epithelial disruption were present in both the nonoxynol 9 and the nonoxynol 9 plus benzalkonium chloride groups. Vaginal epithelial disruption was noted in both the benzalkonium chloride and the nonoxynol 9 plus benzalkonium chloride groups. Cervical biopsy specimens from each group revealed acute inflammatory infiltrates with occasional plasma cells and lymphoid follicles. Detection of most microorganisms, including viridans streptococci, decreased in the benzalkonium chloride and the nonoxynol 9 plus benzalkonium chloride groups. Detection of Lactobacillus species decreased in the benzalkonium chloride group. All microflora levels recovered after several days without microbicide use. CONCLUSIONS: Although nonoxynol 9 is currently the only microbicide approved for use as a spermicide in the United States, its repeated use may be detrimental to the epithelial tissues of the female reproductive tract. Benzalkonium chloride, currently approved for use in other countries, not only may damage epithelial tissues but also appears to reduce the population of potentially protective Lactobacillus species in the vagina.     

Association between human recombinant EPO and peripheral vascular disease in diabetic patients receiving peritoneal dialysis

Peripheral vascular disease is a serious and frequent problem in diabetic patients. Since the beginning of the widespread use of erythropoietin (EPO), we have noted an increase in peripheral vascular disease in diabetic patients receiving peritoneal dialysis and erythropoietin. This prompted us to study the effects of erythropoietin on peripheral vascular disease in patients receiving peritoneal dialysis. We retrospectively reviewed medical records of all diabetic patients in our program who received peritoneal dialysis from 1990 to 1996. Demographic and laboratory data as well as EPO use data were collected. Hospital days and occurrence of vascular events (defined as peripheral vascular surgery, amputation, or recommendation of vascular surgery or amputation by a vascular surgeon) were determined for diabetic patients receiving peritoneal dialysis. Comparisons were made between those who received EPO and those who did not received EPO, as well as comparing vascular events in 28 patients who received peritoneal dialysis before and after beginning EPO. Patients who received erythropoietin were found to have a significantly shorter time to a first vascular event, a greater number of vascular events, and more hospital days associated with vascular disease than diabetic patients who did not receive erythropoietin. With multivariate analysis, significant risk factors for the development of peripheral vascular disease in these patients were erythropoietin use, erythropoietin dose, and smoking. Twenty-eight patients who initially performed peritoneal dialysis without receiving EPO, and later received EPO, had a significant increase in vascular events, including amputations only while receiving EPO. We found the use of erythropoietin to be associated with peripheral vascular events in diabetic patients who receive peritoneal dialysis. Further investigation is warranted.     

A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis

Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g -) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g - isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis.     

Health status, health care use, medication use, and medication adherence among homeless and housed people living with HIV/AIDS

Objectives. We sought to compare health status, health care use, HIV anti-retroviral medication use, and HIV medication adherence among homeless and housed people with HIV/AIDS.Methods. Data were obtained from a cross-sectional, multisite behavioral survey of adults (N=7925) recently reported to be HIV positive.Results. At the time interviews were conducted, 304 respondents (4%) were homeless. Self-ratings of mental, physical, and overall health revealed that the health status of homeless respondents was poorer than that of housed respondents. Also, homeless respondents were more likely to be uninsured, to have visited an emergency department, and to have been admitted to a hospital. Homeless respondents had lower CD4 counts, were less likely to have taken HIV anti-retroviral medications, and were less adherent to their medication regimen. Homeless respondents needed more HIV social and medical services, but nearly all respondents in both groups had received needed services. Housing status remained a significant predictor of health and medication outcomes after we controlled for potential confounding variables.Conclusions. Homeless people with HIV/AIDS are at increased risk of negative health outcomes, and housing is a potentially important mechanism for improving the health of this vulnerable group.Homeless people are at a disproportionate risk for negative health consequences. For instance, they typically have more chronic diseases and more physical and mental health problems than do the general population, and they are at greater risk for infectious diseases.1^–13 Homelessness is often coincident with poverty, mental illness, and alcohol and drug use, compounding the other health problems experienced by these individuals.14^–17Homeless people are also more likely than other groups to engage in behaviors that place them at risk for HIV infection, including risky sexual practices, injection drug use and needle sharing, and performing sexual acts in exchange for money, drugs, or a place to stay.18^–25 Perhaps not surprisingly, previous research has shown that HIV is 3 to 9 times more prevalent among homeless individuals than among individuals in stable housing situations.18^,20^,21^,26^–29It may be difficult for homeless people, who are often faced with immediate subsistence needs (e.g., finding adequate food and shelter), to obtain medical care and adhere to treatment regimens.30^,31 As a result, homeless individuals are less likely than are the general population to have stable sources of care, and they often rely on emergency departments or ambulatory care settings for their health care needs.32^,33 Delayed medical care or lack of care has negative effects such as delayed HIV diagnoses and higher rates of serious opportunistic infections.7^,31^,34People who are living with HIV/AIDS and are homeless face additional burdens not faced by homeless people without HIV/AIDS. For instance, individuals with HIV/AIDS need greater access to comprehensive health care, and barriers to care—including lack of financial resources, lack of transportation, and insufficient (or nonexistent) health insurance coverage—may be compounded among homeless people living with the disease.30^,34People with HIV/AIDS also may have difficulty adhering to prescribed HIV antiretroviral medication regimens.35^,36 These regimens can be complex and often involve restrictions on when and how the medications should be taken and stored.31^,34 In addition, these medications can have side effects, such as recurring diarrhea, that are especially problematic for homeless individuals. Medical providers may believe that homeless individuals will not be adherent, and thus they may be reluctant to prescribe antiretroviral medications for these individuals37 given that inadequate adherence can lead to drug resistance.34 Despite its importance, few studies have investigated the issue of adherence to antiretroviral medication regimens in this population.35^,36^,38^–42Overall, minimal research has been conducted on the health of homeless people living with HIV/AIDS.15^,43^,44 We used data from a large, multisite investigation to (1) assess differences between homeless and housed persons living with HIV/AIDS regarding sociodemographic, health care, and medication adherence variables and (2) examine associations between housing status and health, and medication adherence outcomes after controlling for potential confounding factors.     

Patient predictors of hospice choice. Hospital versus home care programs

Research findings indicate cost savings associated with home care hospices, while hospital-based hospices can be as expensive as conventional care. Based on National Hospice Study data, this article identifies the characteristics of patients admitted to hospital-based and home care hospices in those areas of the country where a choice of hospice model was possible. Multivariate logistic regression indicates that the significant discriminating factors between the two patient populations relate to the availability of supportive care at home and the severity of nursing care problems at the time of hospice entry. Reinforcing selected pre-existing differences, an examination of prehospice had longer episodes of care than was the case for home care hospice patients.     

Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA,factor H binding protein,Neisseria heparin-binding antigen and Neisseria adhesin A)

BACKGROUND:Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB.OBJECTIVE:To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine.METHODS:Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated.RESULTS:The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD.CONCLUSION:From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.     

Genetic and antigenic analysis of invasive serogroup C Neisseria meningitidis in Canada: A decrease in the electrophoretic type (ET)-15 clonal type and an increase in the proportion of isolates belonging to the ET-37 (but not ET-15) clonal type during the period from 2002 to 2009

BACKGROUND:

Serogroup C meningococcal disease has been endemic in Canada since the early 1990s, with periods of hyperendemic disease documented in the past two decades. The present study characterized invasive serogroup C meningococci in Canada during the period from 2002 to 2009.

METHODS:

Serogroup C meningococci were serotyped using monoclonal antibodies. Their clonal types were identified by either multilocus enzyme electrophoresis or multilocus sequence typing.

RESULTS:

The number of invasive serogroup C Neisseria meningitidis isolates received at the National Microbiology Laboratory (Winnipeg, Manitoba) for characterization has dropped from a high of 173 isolates in 2001 to just 17 in 2009, possibly related to the introduction of the serogroup C meningococcal conjugate vaccine. Before 2006, 80% to 95% of all invasive serogroup C meningococci belonged to the electrophoreic type (ET)-15 clonal type, and the ET-37 (but not ET-15) type only accounted for up to 5% of all isolates. However, beginning in 2006, the percentage of the ET-15 clonal type decreased while the ET-37 (but not ET-15) type increased from 27% in 2006 to 52% in 2009. The percentage of invasive serogroup C isolates not belonging to either ET-15 or ET-37 also increased. Most ET-15 isolates expressed the antigenic formula of C:2a:P1.7,1 or C:2a:P1.5. In contrast, the ET-37 (but not ET-15) isolates mostly expressed the antigens of C:2a:P1.5,2 or C:2a:P1.2.

CONCLUSION:

A shift in the antigenic and clonal type of invasive serogroup C meningococi was noted. This finding suggests vigilance in the surveillance of meningoccocal disease is warranted.