Measuring inflammatory marker levels to determine risk of bone loss and fractures in older women
Barbour KE , Cauley JA . MLO Med Lab Obs 2013 45 (4) 8-12 Elevated levels of pro-inflammatory markers are associated with an increased risk of a number of chronic conditions1-6 and death7. Furthermore, there is evidence that high levels of inflammatory markers may contribute to faster rates of bone loss.8-10 More recently, we have demonstrated that greater inflammatory burden (measured primarily using cytokines and their soluble receptors) is associated with a greater fracture risk.11,12 Additionally, studies have found that high levels of high sensitivity C-reactive protein (hs-CRP) (a generic marker of systemic inflammation that increases in response to greater inflammation) also predict incident fractures.13-15 | Researchers have identified evidence of 2 biological mechanisms that may explain this increased bone loss and fracture risk among those with high levels of inflammatory markers.16-18 In the first, cytokines bind to mesenchymal stem cells and increase the expression of receptor-activator of NF-κβ ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) and decrease osteoprotegerin production, which effectively increases activation of osteoclasts (cells responsible for resorption of bone tissue).16 In the second, cytokine-mediated osteoclast activation is augmented in the presence of estrogen deficiency.17,18 | Extensive bone loss can result in the development of osteoporosis. Osteoporosis is defined as a systemic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a subsequent increase in bone fragility and susceptibility to fracture.19 The World Health Organization defines osteoporosis as having a sex-specific bone mineral density (BMD) of less than or equal to 2.5 standard deviations (SDs) below the mean BMD of a young adult.20 The burden of osteoporosis in women is high. In the US, the prevalence of osteoporosis is estimated to range from 17-20% among women ages 50 years or older.21 |
Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status
Ma H , Lu Y , Malone KE , Marchbanks PA , Deapen DM , Spirtas R , Burkman RT , Strom BL , McDonald JA , Folger SG , Simon MS , Sullivan-Halley J , Press MF , Bernstein L . BMC Cancer 2013 13 225 BACKGROUND: Black women are more likely than white women to have an aggressive subtype of breast cancer that is associated with higher mortality and this may contribute to the observed black-white difference in mortality. However, few studies have investigated the black-white disparity in mortality risk stratified by breast cancer subtype, defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Furthermore, it is not known whether additional consideration of p53 protein status influences black-white differences in mortality risk observed when considering subtypes defined by ER, PR and HER2 status. METHODS: Four biomarkers were assessed by immunohistochemistry in paraffin-embedded breast tumor tissue from 1,204 (523 black, 681 white) women with invasive breast cancer, aged 35-64 years at diagnosis, who accrued a median of 10 years' follow-up. Multivariable Cox proportional hazards regression models were fit to assess subtype-specific black-white differences in mortality risk. RESULTS: No black-white differences in mortality risk were observed for women with triple negative (ER-negative [ER-], PR-, and HER2-) subtype. However, older (50-64 years) black women had greater overall mortality risk than older white women if they had been diagnosed with luminal A (ER-positive [ER+] or PR+ plus HER2-) breast cancer (all-cause hazard ratio, HR, 1.88; 95% confidence interval, CI, 1.18 to 2.99; breast cancer-specific HR, 1.51; 95% CI, 0.83 to 2.74). This black-white difference among older women was further confined to those with luminal A/p53- tumors (all-cause HR, 2.22; 95% CI, 1.30 to 3.79; breast cancer-specific HR, 1.89; 95% CI, 0.93 to 3.86). Tests for homogeneity of race-specific HRs comparing luminal A to triple negative subtype and luminal A/p53- to luminal A/p53+ subtype did not achieve statistical significance, although statistical power was limited. CONCLUSIONS: Our findings suggest that the subtype-specific black-white difference in mortality risk occurs mainly among older women diagnosed with luminal A/p53- breast cancer, which is most likely treatable. These results further suggest that factors other than subtype may be relatively more important in explaining the increased mortality risk seen in older black women. |
Effect of urbanisation on the relationship between total serum IgE and asthma
Checkley W , Robinson CL , Baumann LM , Romero K , Combe JM , Gilman RH , Wise RA , Hamilton RG , Gonzalvez G , Cama V , Hansel NN . Eur Respir J 2013 41 (5) 1074-81 It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban versus a rural environment. We enrolled 1441 children aged 13-15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima versus Tumbes (262 versus 192 kU.L(-1); p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3-2.0) versus 1.4 (95% CI 0.9-2.1) per log unit increase in total serum IgE in Lima versus Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5-2.7) and 1.0 (95% CI 0.7-1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship. |
Association between depression and functional vision loss in persons 20 years of age or older in the United States, NHANES 2005-2008
Zhang X , Bullard KM , Cotch MF , Wilson MR , Rovner BW , McGwin Jr G , Owsley C , Barker L , Crews JE , Saaddine JB . JAMA Ophthalmol 2013 131 (5) 573-581 IMPORTANCE: This study provides further evidence from a national sample to generalize the relationship between depression and vision loss to adults across the age spectrum. Better recognition of depression among people reporting reduced ability to perform routine activities of daily living due to vision loss is warranted. OBJECTIVES: To estimate, in a national survey of US adults 20 years of age or older, the prevalence of depression among adults reporting visual function loss and among those with visual acuity impairment. The relationship between depression and vision loss has not been reported in a nationally representative sample of US adults. Previous studies have been limited to specific cohorts and predominantly focused on the older population. DESIGN: The National Health and Nutrition Examination Survey (NHANES) 2005-2008. SETTING: Across-sectional, nationally representative sample of adults, with prevalence estimates weighted to represent the civilian, noninstitutionalized US population. PARTICIPANTS: A total of 10,480 US adults 20 years of age or older. MAIN OUTCOME MEASURES: Depression, as measured by the 9-item Patient Health Questionnaire depression scale, and vision loss, as measured by visual function using a questionnaire and by visual acuity at examination. RESULTS: In 2005-2008, the estimated crude prevalence of depression (9-item Patient Health Questionnaire score of >=10) was 11.3% (95% CI, 9.7%-13.2%) among adults with self-reported visual function loss and 4.8% (95% CI, 4.0%-5.7%) among adults without. The estimated prevalence of depression was 10.7% (95% CI, 8.0%-14.3%) among adults with presenting visual acuity impairment (visual acuity worse than 20/40 in the better-seeing eye) compared with 6.8% (95% CI, 5.8%-7.8%) among adults with normal visual acuity. After controlling for age, sex, race/ethnicity, marital status, living alone or not, education, income, employment status, health insurance, body mass index, smoking, binge drinking, general health status, eyesight worry, and major chronic conditions, selfreported visual function loss remained significantly associated with depression (overall odds ratio, 1.9 [95% CI, 1.6-2.3]), whereas the association between presenting visual acuity impairment and depression was no longer statistically significant. CONCLUSIONS AND RELEVANCE: Self-reported visual function loss, rather than loss of visual acuity, is significantly associated with depression. Health professionals should be aware of the risk of depression among persons reporting visual function loss. (2013 American Medical Association. All rights reserved.) |
Risk factors for delayed initiation of combination antiretroviral therapy in rural north central Nigeria
Aliyu MH , Blevins M , Parrish DD , Megazzini KM , Gebi UI , Muhammad MY , Ahmed ML , Shepherd BE , Hassan A , Vermund SH , Wester CW . J Acquir Immune Defic Syndr 2013 65 (2) e41-9 BACKGROUND: Timely initiation of combination antiretroviral therapy (ART) in eligible HIV-infected patients is associated with substantial reduction in mortality and morbidity. Nigeria has the second largest number of persons living with HIV/AIDS in the world. We examined patient characteristics, time to ART initiation, retention and mortality at five rural facilities in Kwara and Niger states of Nigeria. METHODS: We analyzed program-level cohort data for HIV-infected, ART-naive clients (≥15 years) enrolled from June 2009-February 2011. We modeled the probability of ART initiation among clients meeting national ART eligibility criteria using logistic regression with splines. RESULTS: We enrolled 1,948 ART-naive adults/adolescents into care, of whom 1174 were ART eligible (62% female). Only 74% of eligible patients (n=869) initiated ART within 90 days post-enrollment. The median CD4+ count for eligible clients was 156 cells/microL [IQR: 81-257], with 67% in WHO stage III/IV disease. Adjusting for CD4+ count, WHO stage, functional status, hemoglobin, body mass index, sex, age, education, marital status, employment, clinic of attendance, and month of enrollment, we found that immunosuppression (CD4 350 vs. 200, odds ratio (OR)=2.10 [95%CI: 1.31, 3.35], functional status (bedridden vs. working, OR=4.17 [95%CI: 1.63-10.67]), clinic of attendance (Kuta hospital vs. referent: OR=5.70 [95%CI:2.99-10.89]), and date of enrollment (December 2010 vs. June 2009: OR=2.13 [95%CI:1.19-3.81]) were associated with delayed ART initiation. CONCLUSION: Delayed initiation of ART was associated with higher CD4+ counts, lower functional status, clinic of attendance, and later dates of enrollment among ART-eligible clients. Our findings provide targets for quality improvement efforts that may help reduce attrition and improve ART uptake in similar settings. |
Severe acute respiratory infections caused by 2009 pandemic influenza A (H1N1) among American Indians-southwestern United States, May 1-July 21, 2009
Suryaprasad A , Redd JT , Hancock K , Branch A , Steward-Clark E , Katz JM , Fry AM , Cheek JE . Influenza Other Respir Viruses 2013 7 (6) 1361-9 BACKGROUND: During April-July 2009, U.S. hospitalization rates for 2009 pandemic influenza A (H1N1) virus (H1N1pdm09) infection were estimated at 4.5/100 000 persons. We describe rates and risk factors for H1N1pdm09 infection among American Indians (AIs) in four isolated southwestern U.S. communities served by the Indian Health Service (IHS). METHODS: We reviewed clinical and demographic information from medical records of AIs hospitalized during May 1-July 21, 2009 with severe acute respiratory infection (SARI). Hospitalization rates were determined using denominator data provided by IHS. H1N1pdm09 infection was confirmed with polymerase chain reaction, rapid tests, or convalescent serology. Risk factors for more severe (SARI) versus milder [influenza-like illness (ILI)] illness were determined by comparing confirmed SARI patients with outpatients with ILI. RESULTS: Among 168 SARI-hospitalized patients, 52% had confirmed H1N1pdm09 infection and 93% had >1 high-risk condition for influenza complications. The H1N1pdm09 SARI hospitalization rate was 131/100 000 persons [95% confidence interval (CI), 102-160] and was highest among ages 0-4 years (353/100,000; 95% CI, 215-492). Among children, asthma (adjusted odds ratio [aOR] 3.2; 95% CI, 1.2-8.4) and age <2 years (aOR 3.8; 95% CI, 1.4-10.0) were associated with H1N1pdm09 SARI-associated hospitalization, compared with outpatient ILI. Among adults, diabetes (aOR 3.1; 95% CI, 1.5-6.4) was associated with hospitalization after controlling for obesity. CONCLUSIONS: H1N1pdm09 hospitalization rates among this isolated AI population were higher than reported for other U.S. populations. Almost all case patients had high-risk health conditions. Prevention strategies for future pandemics should prioritize AIs, particularly in isolated rural areas. |
A large community outbreak of blastomycosis in Wisconsin with geographic and ethnic clustering
Roy M , Benedict K , Deak E , Kirby MA , McNiel JT , Sickler CJ , Eckardt E , Marx RK , Heffernan RT , Meece JK , Klein BS , Archer JR , Theurer J , Davis JP , Park BJ . Clin Infect Dis 2013 57 (5) 655-62 BACKGROUND: Blastomycosis is a potentially life-threatening infection caused by the soil-based dimorphic fungus Blastomyces dermatitidis, which is endemic throughout much of the Midwestern United States. We investigated an increase in reported cases of blastomycosis that occurred during 2009-2010 in Marathon County, Wisconsin. METHODS: Case detection was conducted using the Wisconsin Electronic Disease Surveillance System (WEDSS). WEDSS data were used to compare demographic, clinical, and exposure characteristics between outbreak-related and historical case patients, and to calculate blastomycosis incidence rates. Because initial mapping of outbreak case patients' homes and recreational sites demonstrated unusual neighborhood and household case clustering, we conducted a 1:3 matched case-control study to identify factors associated with being in a geographic cluster. RESULTS: Among the 55 patients with outbreak-related cases, 33 (70%) were hospitalized, 2 (5%) died, 30 (55%) had cluster-related cases, and 20 (45%) were Hmong. The overall incidence increased significantly since 2005 (average 11% increase per year, P < .001), and incidence during 2005-2010 was significantly higher among Asians than non-Asians (2010 incidence: 168 vs 13 per 100,000 population). Thirty of the outbreak cases grouped into 5 residential clusters. Outdoor activities were not risk factors for blastomycosis among cluster case patients or when comparing outbreak cases to historical cases. CONCLUSIONS: This outbreak of blastomycosis, the largest ever reported, was characterized by unique household and neighborhood clustering likely related to multifocal environmental sources. The reasons for the large number of Hmong affected are unclear, but may involve genetic predisposition. |
Hepatocellular carcinoma and hepatitis B virus: family matters
McMahon BJ . Clin Gastroenterol Hepatol 2013 11 (12) 1646-7 In much of the world, hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, especially in men. In sub-Saharan Africa, most of eastern and southeast Asia, and the Pacific Islands, chronic hepatitis B virus (HBV) is the primary etiology for HCC, where the prevalence of chronic HBV infection ranges from 2% to more than 10% of the population.1 Several demographic, viral, and environmental factors have been found to increase the risk of HCC in HBV infection, which can help to identify those persons who should be targeted for regular surveillance to detect this tumor early, at a more treatable stage. More than 30 years ago, several case-control studies found family history of HCC to be a risk factor in relatives who were infected with HBV,2 but the magnitude of the risk previously was unknown. In this issue of Clinical Gastroenterology and Hepatology3 is an important article that takes advantage of a large population-based cohort study conducted in Taiwan, the REVEAL study, to better define and quantify the risk of family history of HCC. Briefly, the investigators screened more than 22,000 residents of 7 townships in Taiwan for HBV seromarkers and found almost 4000 to be positive for hepatitis B surface antigen (HBsAg). They then followed up those persons positive for HBsAg prospectively for 16 years and have written multiple publications regarding risk factors associated with HCC and cirrhosis that were found in this cohort.4, 5, 6 |
Incidence of diabetes mellitus in a population-based cohort of persons with chronic hepatitis B virus infection
Spradling PR , Simons B , Narayanan M , Xing J , Homan C , Bulkow L , Cagle H , Schraer CD , McMahon BJ . J Viral Hepat 2013 20 (7) 510-3 To investigate the effect of hepatitis B virus (HBV) infection on the development of diabetes mellitus (DM), we compared DM incidence and characteristics of Alaska Native persons with and without HBV infection. From 1990 to 2010, there were 52 incident DM cases among 1309 persons with infection vs 4557 DM cases among 85,698 persons without infection (log-rank test, P = 0.20). Compared to infected persons without DM, those with DM were significantly older (57.0 vs 47.4 years, P < 0.001) and had higher body mass index (34.5 vs 28.4 kg/m(2) , P < 0.001). Genotype, immune active disease and the presence of cirrhosis were not associated with DM. In this population-based cohort with over 20 years of follow-up, there was no effect of HBV infection on DM development. |
Investigation of a Chlamydia pneumoniae outbreak in a federal correctional facility in Texas
Conklin L , Adjemian J , Loo J , Mandal S , Davis C , Parks S , Parsons T , McDonough B , Partida J , Thurman K , Diaz MH , Benitez A , Pondo T , Whitney CG , Winchell JM , Kendig N , Van Beneden C . Clin Infect Dis 2013 57 (5) 639-47 BACKGROUND: Chlamydia pneumoniae illness is poorly characterized, particularly as a sole causative pathogen. We investigated a C. pneumoniae outbreak at a federal correctional facility. METHODS: We identified inmates with acute respiratory illness (ARI) from November 1, 2009 - February 24, 2010 through clinic self-referral and active case-finding. We tested oropharyngeal and/or nasopharyngeal swabs for C. pneumoniae by quantitative polymerase chain reaction (qPCR) and sera by microimmunofluorescence. Cases were inmates with ARI and radiologically-confirmed pneumonia, positive qPCR, or serological evidence of recent infection. Swabs from 7 acutely ill inmates were tested for 18 respiratory pathogens using qPCR TaqMan array cards (TAC). Follow-up swabs from case-patients were collected for up to 8 weeks. RESULTS: Among 33 self-referred and 226 randomly selected inmates, 52 (20.1%) met case definition; 4 were confirmed by radiologically-confirmed pneumonia only, 9 by qPCR only, 17 by serology only, and 22 by both qPCR and serology. The prison attack rate was 10.4% (95% CI: 7.0, 13.8%). White inmates and residents of housing unit Y were at highest risk. TAC testing detected C. pneumoniae in 4 (57%) inmates; no other causative pathogens were identified. Among 40 inmates followed prospectively, C. pneumoniae was detected for up to 8 weeks. Thirteen (52%) of 25 inmates treated with azithromycin continued to be qPCR positive >2 weeks after treatment. CONCLUSIONS: C. pneumoniae was the causative pathogen of this outbreak. Higher risk among certain groups suggests social interaction contributed to transmission. Persistence of C. pneumoniae in the oropharynx creates challenges for outbreak control measures. |
Burden of seasonal and pandemic influenza-associated hospitalization during and after 2009 A(H1N1)pdm09 pandemic in a rural community in India
Chadha MS , Hirve S , Dawood FS , Lele P , Deoshatwar A , Sambhudas S , Juvekar S , Lafond KE , Mott JA , Lal RB , Mishra AC . PLoS One 2013 8 (5) e55918 BACKGROUND: Influenza is vaccine-preventable; however, the burden of severe influenza in India remains unknown. We conducted a population-based study to estimate the incidence of laboratory confirmed influenza-associated hospitalizations in a rural community in western India. METHODS: We conducted active surveillance for hospitalized patients with acute medical illnesses or acute chronic disease exacerbations in Pune during pandemic and post pandemic periods (May 2009-April 2011). Nasal and throat swabs were tested for influenza viruses. A community health utilization survey estimated the proportion of residents hospitalized with respiratory illness at non-study facilities and was used to adjust incidence estimates from facility-based surveillance. RESULTS: Among 9,426 hospitalizations, 3,391 (36%) patients were enrolled; 665 of 3,179 (20.9%) tested positive for influenza. Of 665 influenza positives, 340 (51%) were pandemic A(H1N1)pdm09 and 327 (49%) were seasonal, including A/H3 (16%), A/H1 (3%) and influenza B (30%). The proportion of patients with influenza peaked during August 2009 (39%) and 2010 (42%). The adjusted annual incidence of influenza hospitalizations was 46.8/10,000 during pandemic and 40.5/10,000 during post-pandemic period with comparable incidence of A(H1N1)pdm09 during both periods (18.8 and 20.3, respectively). The incidence of both pH1N1 and seasonal hospitalized influenza disease was highest in the 5-29 year olds. CONCLUSIONS: We document the previously unrecognized burden of influenza hospitalization in a rural community following the emergence of influenza A(H1N1)pdm09 viruses in India. During peak periods of influenza activity circulation i.e during the monsoon period, 20% of all hospital admissions in the community had influenza positivity. These findings can inform development of influenza prevention and control strategies in India. |
Bats are a major natural reservoir for hepaciviruses and pegiviruses
Quan PL , Firth C , Conte JM , Williams SH , Zambrana-Torrelio CM , Anthony SJ , Ellison JA , Gilbert AT , Kuzmin IV , Niezgoda M , Osinubi MO , Recuenco S , Markotter W , Breiman RF , Kalemba L , Malekani J , Lindblade KA , Rostal MK , Ojeda-Flores R , Suzan G , Davis LB , Blau DM , Ogunkoya AB , Alvarez Castillo DA , Moran D , Ngam S , Akaibe D , Agwanda B , Briese T , Epstein JH , Daszak P , Rupprecht CE , Holmes EC , Lipkin WI . Proc Natl Acad Sci U S A 2013 110 (20) 8194-9 Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses. |
Public health surveillance in the dialysis setting: opportunities and challenges for using electronic health records
Wise ME , Lovell C . Semin Dial 2013 26 (4) 399-406 The US Centers for Disease Control and Prevention has conducted public health surveillance for healthcare-associated infections (HAIs) in dialysis facilities since the 1970s, evolving from facility-level surveys to patient-level surveillance systems. The Centers for Medicare and Medicaid Services (CMS) recently implemented incentives for all end-stage renal disease (ESRD) facilities to monitor and report patient-level quality indicators to the Centers for Disease Control and Prevention's (CDC's) National Healthcare Safety Network (NHSN) in accordance with the NHSN Dialysis Event Protocol. These CMS incentives have led to a rapid increase in dialysis facility NHSN enrollment during 2012. Ongoing challenges to HAI surveillance in this setting include variability in the surveillance process, assurance of data quality, and staff time and resource requirements. Use of existing electronic health records (EHR), especially in conjunction with detection algorithms, has increasingly been shown to produce valid and reliable estimates of HAI frequency in acute care hospitals. Given the large number of dialysis facilities that are now beginning to conduct surveillance using NHSN, the typical lack of dedicated infection prevention personnel in those facilities, and the widespread use of EHR in large dialysis provider organizations, the use of EHR will probably become a cornerstone of surveillance in these settings. Implemented properly, the use of EHR to support public health surveillance has enormous potential to focus and strengthen infection prevention activities in dialysis facilities. Systematic, ongoing validation efforts will be vital to ensure that reported data are accurate, permit valid comparisons of facility performance, and effectively support improved outcomes for dialysis patients. |
Multistate outbreak of Escherichia coli O145 infections associated with romaine lettuce consumption, 2010
Taylor EV , Nguyen TA , Machesky KD , Koch E , Sotir MJ , Bohm SR , Folster JP , Bokanyi R , Kupper A , Bidol SA , Emanuel A , Arends KD , Johnson SA , Dunn J , Stroika S , Patel MK , Williams I . J Food Prot 2013 76 (6) 939-44 Non-O157 Shiga toxin-producing Escherichia coli (STEC) can cause severe illness, including hemolytic uremic syndrome (HUS). STEC O145 is the sixth most commonly reported non-O157 STEC in the United States, although outbreaks have been infrequent. In April and May 2010, we investigated a multistate outbreak of STEC O145 infection. Confirmed cases were STEC O145 infections with isolate pulsed-field gel electrophoresis patterns indistinguishable from those of the outbreak strain. Probable cases were STEC O145 infections or HUS in persons who were epidemiologically linked. Case-control studies were conducted in Michigan and Ohio; food exposures were analyzed at the restaurant, menu, and ingredient level. Environmental inspections were conducted in implicated food establishments, and food samples were collected and tested. To characterize clinical findings associated with infections, we conducted a chart review for case patients who sought medical care. We identified 27 confirmed and 4 probable cases from five states. Of these, 14 (45%) were hospitalized, 3 (10%) developed HUS, and none died. Among two case-control studies conducted, illness was significantly associated with consumption of shredded romaine lettuce in Michigan (odds ratio [OR] = undefined; 95% confidence interval [CI] = 1.6 to undefined) and Ohio (OR = 10.9; 95% CI = 3.1 to 40.5). Samples from an unopened bag of shredded romaine lettuce yielded the predominant outbreak strain. Of 15 case patients included in the chart review, 14 (93%) had diarrhea and abdominal cramps and 11 (73%) developed bloody diarrhea. This report documents the first foodborne outbreak of STEC O145 infections in the United States. Current surveillance efforts focus primarily on E. coli O157 infections; however, non-O157 STEC can cause similar disease and outbreaks, and efforts should be made to identify both O157 and non-O157 STEC infections. Providers should test all patients with bloody diarrhea for both non-O157 and O157 STEC. |
The genome sequence of Lone Star virus, a highly divergent bunyavirus found in the Amblyomma americanum tick.
Swei A , Russell BJ , Naccache SN , Kabre B , Veeraraghavan N , Pilgard MA , Johnson BJ , Chiu CY . PLoS One 2013 8 (4) e62083 Viruses in the family Bunyaviridae infect a wide range of plant, insect, and animal hosts. Tick-borne bunyaviruses in the Phlebovirus genus, including Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) in China, Heartland virus (HRTV) in the United States, and Bhanja virus in Eurasia and Africa have been associated with acute febrile illness in humans. Here we sought to characterize the growth characteristics and genome of Lone Star virus (LSV), an unclassified bunyavirus originally isolated from the lone star tick Amblyomma americanum. LSV was able to infect both human (HeLa) and monkey (Vero) cells. Cytopathic effects were seen within 72 h in both cell lines; vacuolization was observed in infected Vero, but not HeLa, cells. Viral culture supernatants were examined by unbiased deep sequencing and analysis using an in-house developed rapid computational pipeline for viral discovery, which definitively identified LSV as a phlebovirus. De novo assembly of the full genome revealed that LSV is highly divergent, sharing <61% overall amino acid identity with any other bunyavirus. Despite this sequence diversity, LSV was found by phylogenetic analysis to be part of a well-supported clade that includes members of the Bhanja group viruses, which are most closely related to SFSTV/HRTV. The genome sequencing of LSV is a critical first step in developing diagnostic tools to determine the risk of arbovirus transmission by A. americanum, a tick of growing importance given its expanding geographic range and competence as a disease vector. This study also underscores the power of deep sequencing analysis in rapidly identifying and sequencing the genomes of viruses of potential clinical and public health significance. |
Evidence for the continued transmission of parvovirus B19 in patients with bleeding disorders treated with plasma-derived factor concentrates
Soucie JM , Monahan PE , Kulkarni R , De Staercke C , Recht M , Chitlur MB , Gruppo R , Hooper WC , Kessler C , Manco-Johnson MJ , Powell J , Pyle M , Riske B , Sabio H , Trimble S . Transfusion 2013 53 (5) 1143-4 Gajardo and colleagues1 contend that our finding of continued increased prevalence of parvovirus B19 (B19V) antibodies among users of plasma-derived factor concentrates relative to people with bleeding disorders unexposed to any blood or factor product2 may have been influenced by exposure to product not subjected to B19V nucleic acid test (NAT) screening or to exposure to low-purity products during the study period. The authors also disagree with our characterization of B19V as resistant to viral inactivation steps used in the manufacture of antihemophilic factor concentrates. | We understand and discuss in our article that B19V NAT screening was not initiated at the same time for all products. Nonetheless, we provided evidence, based on our finding of higher B19V prevalence in later years of the study period, that our findings were not likely due to transmissions that occurred solely in earlier years. For example, among 2- to 4-year-old children exposed to plasma-derived products, 77% of the specimens tested were drawn between 2006 and 2009—well after studies showed relatively complete adoption of screening.3 Others have reported the detection of B19V in products purchased in 2008.4 | The authors suggest that our study findings may also have been influenced by users of less highly purified products such as activated prothrombin complex concentrates. However, only 7% of subjects in our study were exposed to these products. |
Infection control assessment after an influenza outbreak in a residential care facility for children and young adults with neurologic and neurodevelopmental conditions
Azofeifa A , Yeung LF , Peacock G , Moore CA , Rodgers L , Diorio M , Page SL , Fowler B , Stone ND , Finelli L , Jhung MA . Infect Control Hosp Epidemiol 2013 34 (7) 717-22 OBJECTIVE: To assess the knowledge, attitudes, and practices of infection control among staff in a residential care facility for children and young adults with neurologic and neurodevelopmental conditions. DESIGN: Self-administered survey. SETTING: Residential care facility (facility A). PARTICIPANTS: Facility A staff ([Formula: see text]). METHODS: We distributed a survey to staff at facility A. We classified staff with direct care responsibilities as clinical (ie, physicians, nurses, and therapists) or nonclinical (ie, habilitation assistants, volunteers, and teachers) and used chi(2) tests to measure differences between staff agreement to questions. RESULTS: Of 248 surveys distributed, 200 (81%) were completed; median respondent age was 36 years; 85% were female; and 151 were direct care staff (50 clinical, 101 nonclinical). Among direct care staff respondents, 86% agreed they could identify residents with respiratory symptoms, 70% stayed home from work when ill with respiratory infection, 64% agreed that facility administration encouraged them to stay home when ill with respiratory infection, and 72% reported that ill residents with respiratory infections were separated from well residents. Clinical and nonclinical staff differed in agreement about using waterless hand gel as a substitute for handwashing (96% vs 78%; [Formula: see text]) and whether handwashing was done after touching residents (92% vs 75%; [Formula: see text]). CONCLUSIONS: Respondents' knowledge, attitudes, and practices regarding infection control could be improved, especially among nonclinical staff. Facilities caring for children and young adults with neurologic and neurodevelopmental conditions should encourage adherence to infection control best practices among all staff having direct contact with residents. |
Antimicrobial stewardship programs in Florida's acute care facilities
Abbo L , Lo K , Sinkowitz-Cochran R , Burke AC , Hopkins RS , Srinivasan A , Hooton TM . Infect Control Hosp Epidemiol 2013 34 (6) 634-7 We surveyed acute care facilities in Florida to assess components of and barriers to sustained antimicrobial stewardship programs (ASPs). Most respondents with and without ASPs are doing some stewardship-related activities to improve antimicrobial use. Collaborative efforts between facilities and health departments are important to providing better resources for ASPs. |
Attributable burden of hospital-onset Clostridium difficile infection: a propensity score matching study
Tabak YP , Zilberberg MD , Johannes RS , Sun X , McDonald LC . Infect Control Hosp Epidemiol 2013 34 (6) 588-96 OBJECTIVE: To determine the attributable in-hospital mortality, length of stay (LOS), and cost of hospital-onset Clostridium difficile infection (HO-CDI). DESIGN: Propensity score matching. SETTING: Six Pennsylvania hospitals (2 academic centers, 1 community teaching facility, and 3 community nonteaching facilities) contributing data to a clinical research database. Patients. Adult inpatients between 2007 and 2008. METHODS: We defined HO-CDI in adult inpatients as a positive C. difficile toxin assay result from a specimen collected more than 48 hours after admission and more than 8 weeks following any previous positive result. We developed an HO-CDI propensity model and matched cases with noncases by propensity score at a 1:3 ratio. We further restricted matching within the same hospital, within the same principal disease group, and within a similar length of lead time from admission to onset of HO-CDI. RESULTS: Among 77,257 discharges, 282 HO-CDI cases were identified. The propensity score-matched rate was 90%. Compared with matched noncases, HO-CDI patients had higher mortality (11.8% vs 7.3%; [Formula: see text]), longer LOS (median [interquartile range (IQR)], 12 [9-21] vs 11 [8-17] days; [Formula: see text]), and higher cost (median [IQR], $20,804 [$11,059-$38,429] vs $16,634 [$9,413-$30,319]; [Formula: see text]). The attributable effect of HO-CDI was 4.5% (95% confidence interval [CI], 0.2%-8.7%; [Formula: see text]) for mortality, 2.3 days (95% CI, 0.9-3.8; [Formula: see text]) for LOS, and $6,117 (95% CI, $1,659-$10,574; [Formula: see text]) for cost. CONCLUSIONS: Patients with HO-CDI incur additional attributable mortality, LOS, and cost burden compared with patients with similar primary clinical condition, exposure risk, lead time of hospitalization, and baseline characteristics. |
Genetic and phenotypic characterization of manufacturing seeds for a tetravalent dengue vaccine (DENVax).
Huang CY , Kinney RM , Livengood JA , Bolling B , Arguello JJ , Luy BE , Silengo SJ , Boroughs KL , Stovall JL , Kalanidhi AP , Brault AC , Osorio JE , Stinchcomb DT . PLoS Negl Trop Dis 2013 7 (5) e2243 BACKGROUND: We have developed a manufacturing strategy that can improve the safety and genetic stability of recombinant live-attenuated chimeric dengue vaccine (DENVax) viruses. These viruses, containing the pre-membrane (prM) and envelope (E) genes of dengue serotypes 1-4 in the replicative background of the attenuated dengue-2 PDK-53 vaccine virus candidate, were manufactured under cGMP. METHODOLOGY/PRINCIPAL FINDINGS: After deriving vaccine viruses from RNA-transfected Vero cells, six plaque-purified viruses for each serotype were produced. The plaque-purified strains were then analyzed to select one stock for generation of the master seed. Full genetic and phenotypic characterizations of the master virus seeds were conducted to ensure these viruses retained the previously identified attenuating determinants and phenotypes of the vaccine viruses. We also assessed vector competence of the vaccine viruses in sympatric (Thai) Aedes aegypti mosquito vectors. CONCLUSION/SIGNIFICANCE: All four serotypes of master vaccine seeds retained the previously defined safety features, including all three major genetic loci of attenuation, small plaques, temperature sensitivity in mammalian cells, reduced replication in mosquito cell cultures, and reduced neurovirulence in new-born mice. In addition, the candidate vaccine viruses demonstrated greatly reduced infection and dissemination in Aedes aegypti mosquitoes, and are not likely to be transmissible by these mosquitoes. This manufacturing strategy has successfully been used to produce the candidate tetravalent vaccine, which is currently being tested in human clinical trials in the United States, Central and South America, and Asia. |
Inactivated influenza vaccines for prevention of community-acquired pneumonia: the limits of using nonspecific outcomes in vaccine effectiveness studies
Ferdinands JM , Gargiullo P , Haber M , Moore M , Belongia EA , Shay DK . Epidemiology 2013 24 (4) 530-7 BACKGROUND: One to 4 million cases of community-acquired pneumonia (CAP) occur annually in the United States, resulting in 600,000 hospitalizations and 45,000 deaths. Influenza infection facilitates secondary bacterial infections, and influenza vaccination may prevent CAP directly by preventing influenza pneumonia or indirectly by preventing secondary bacterial CAP. METHODS: We investigated how influenza vaccination could affect incidence of CAP using deterministic probability and stochastic simulation models. The models included likely influential factors, including vaccine effectiveness (VE) against influenza, rates of influenza in the unvaccinated, vaccination coverage, and the relative risk (RR) of pneumonia, given influenza infection. To estimate effectiveness of influenza vaccine against CAP, we assumed mean VE against influenza of 55% and vaccine coverage of 38%. RESULTS: Given our baseline parameters, influenza vaccine had a mean effectiveness against CAP of 7% (95% confidence interval = 0-25%). Effectiveness of influenza vaccine against CAP increased as its effectiveness against influenza increased, as RR of pneumonia after influenza infection increased, and as rates of influenza among unvaccinated persons increased. CONCLUSIONS: No matter how effective vaccine may be in preventing influenza infection, it is only modestly effective at preventing CAP. Because of the large annual burden of CAP, a vaccine that is only moderately effective in preventing influenza infection has the potential to prevent a substantial number of CAP cases. This modeling approach may be useful for planning influenza vaccine-probe studies and evaluating the effectiveness of other interventions targeted against infections that manifest in nonspecific outcomes. |
Trends in driver licensing status and driving among high school seniors in the United States, 1996-2010
Shults RA , Williams AF . J Safety Res 2013 INTRODUCTION: Understanding the reasons for fluctuations in teenage driver crashes over time in the United States is clouded by the lack of information on licensure rates and driving exposure. METHODS: We examined results from the Monitoring the Future survey to estimate the proportion of high school seniors who possessed a driver's license and the proportion of seniors who did not drive "during an average week" during the 15-year period of 1996-2010. RESULTS: During 1996-2010, the proportion of high school seniors in United States who reported having a driver's license declined by 12 percentage points (14%) from 85% to 73%. Two-thirds of the decline (8 percentage points) occurred during 2006-2010. During the same 15-year period, the proportion of high school seniors who did not drive during an average week increased by 7 percentage points (47%) from 15% in 1996 to 22% in 2010, with essentially all of the increase occurring during 2006-2009. DISCUSSION: Findings in this report suggest that the economic recession in recent years has reduced rates of licensure and driving among high school seniors. |
A novel photoinduced electron transfer (PET) primer technique for rapid real-time PCR detection of Cryptosporidium spp.
Jothikumar N , Hill V . Biochem Biophys Res Commun 2013 436 (2) 134-9 We report the development of a fluorescently labeled oligonucleotide primer that can be used to monitor real-time PCR. The primer has two parts, the 3'-end of the primer is complimentary to the target and a universal 17-mer stem loop at the 5'-end forms a hairpin structure. A fluorescent dye is attached to 5' end of either the forward or reverse primer. The presence of guanosine residues at the first and second position of the 3'dangling end effectively quenches the fluorescence due to the photo electron transfer (PET) mechanism. During the synthesis of nucleic acid, the hairpin structure is linearized and the fluorescence of the incorporated primer increases several-fold due to release of the fluorescently labeled tail and the absence of guanosine quenching. As amplicons are synthesized during nucleic acid amplification, the fluorescence increase in the reaction mixture can be measured with commercially available real-time PCR instruments. In addition, a melting procedure can be performed to denature the double-stranded amplicons, thereby generating fluorescence peaks that can differentiate primer dimers and other non-specific amplicons if formed during the reaction. We demonstrated the application of PET-PCR for the rapid detection and quantification of Cryptosporidium parvum DNA. Comparison with a previously published TaqMan(R) assay demonstrated that the two real-time PCR assays exhibited similar sensitivity for a dynamic range of detection of 6000 to 0.6 oocysts per reaction. PET PCR primers are simple to design and less-expensive than dual-labeled probe PCR methods, and should be of interest for use by laboratories operating in resource-limited environments. |
Trichomonas vaginalis contact-dependent cytolysis of epithelial cells
Lustig G , Ryan CM , Secor WE , Johnson PJ . Infect Immun 2013 81 (5) 1411-9 Trichomonas vaginalis is an extracellular protozoan parasite that binds to the epithelium of the human urogenital tract during infection. In this study, we examined the propensities of 26 T. vaginalis strains to bind to and lyse prostate (BPH-1) and ectocervical (Ect1) epithelium and to lyse red blood cells (RBCs). We found that only three of the strains had a statistically significant preference for either BPH-1 (MSA1103) or Ect1 (LA1 and MSA1123). Overall, we observed that levels of adherence are highly variable among strains, with a 12-fold range of adherence on Ect1 cells and a 45-fold range on BPH-1 cells. Cytolysis levels displayed even greater variability, from no detectable cytolysis to 80% or 90% cytolysis of Ect1 and BPH-1, respectively. Levels of adherence and cytolysis correlate for weakly adherent/cytolytic strains, and a threshold of attachment was found to be necessary to trigger cytolysis; however, this threshold can be reached without inducing cytolysis. Furthermore, cytolysis was completely blocked when we prevented attachment of the parasites to host cells while allowing soluble factors complete access. We demonstrate that hemolysis was a rare trait, with only 4 of the 26 strains capable of lysing >20% RBCs with a 1:30 parasite/RBC ratio. Hemolysis also did not correlate with adherence to or cytolysis of either male (BPH-1)- or female (Ect1)-derived epithelial cell lines. Our results reveal that despite a broad range of pathogenic properties among different T. vaginalis strains, all strains show strict contact-dependent cytolysis. |
Lack of prophylactic efficacy of oral maraviroc in macaques despite high drug concentrations in rectal tissues
Massud I , Aung W , Martin A , Bachman S , Mitchell J , Aubert R , Tsegaye TS , Kersh E , Pau CP , Heneine W , Garcia-Lerma JG . J Virol 2013 87 (16) 8952-61 Maraviroc (MVC) is a potent CCR5 co-receptor antagonist that is in clinical testing for daily oral pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model consisting of weekly SHIV162p3 exposures to evaluate the efficacy of oral MVC in preventing rectal SHIV transmission. MVC dosing was informed by the pharmacokinetic profile seen in blood and rectal tissues, and consisted of a human-equivalent dose given 24h before virus exposure followed by a booster post-exposure dose. In rectal secretions, MVC peaked at 24h (10,242 ng/ml) with concentrations at 48h that were about 40 times those required to block SHIV infection of PBMCs in vitro. Median MVC concentrations in rectal tissues at 24h (1,404 ng/g) were 30 and 10 times those achieved in vaginal or lymphoid tissues, respectively. MVC significantly reduced MIP-1beta-induced CCR5 internalization in rectal mononuclear cells, an indication of efficient binding to CCR5 in rectal lymphocytes. The half-life of CCR5-bound MVC in PBMCs was 2.6 days. Despite this favorable profile, 5/6 treated macaques were infected during 5 rectal SHIV exposures as were 3/4 controls. MVC treatment was associated with a significant increase in the percentage of CD3+/CCR5+ cells in blood. We show that high and durable MVC concentrations in rectal tissues are not sufficient to prevent SHIV infection in macaques. The increases in CD3+/CCR5+ cells seen during MVC treatment point to unique immunological effects of CCR5 inhibition by MVC. The implications of these immunological effects on PrEP with MVC require further evaluation. |
Molecular modeling in structural nano-toxicology: interactions of nano-particles with nano-machinery of cells
Yanamala N , Kagan VE , Shvedova AA . Adv Drug Deliv Rev 2013 65 (15) 2070-7 Over the past two decades, nanotechnology has emerged as a key player in various disciplines of science and technology. Some of the most exciting applications are in the field of biomedicine - for theranostics (for combined diagnostic and therapeutic purposes) as well as for exploration of biological systems. A detailed understanding of the molecular details of interactions between nanoparticles and biological nano-machinery - macromolecules, membranes, and intracellular organelles - is crucial for obtaining adequate information on mechanisms of action of nanomaterials as well as a perspective on the long term effects of these materials and their possible toxicological outcomes. This review focuses on the use of structure-based computational molecular modeling as a tool to understand and to predict the interactions between nanomaterials and nano-biosystems. We review major approaches and provide examples of computational analysis of the structural principles behind such interactions. A rationale on how nanoparticles of different sizes, shape, structure and chemical properties can affect the organization and functions of nano-machinery of cells is also presented. |
N-linked glycosylation of the hemagglutinin protein influences virulence and antigenicity of the 1918 pandemic and seasonal H1N1 influenza A viruses
Sun X , Jayaraman A , Maniprasad P , Raman R , Houser KV , Pappas C , Zeng H , Sasisekharan R , Katz JM , Tumpey TM . J Virol 2013 87 (15) 8756-66 The hemagglutinin (HA) protein is a major virulence determinant for the 1918 pandemic virus, however it encodes no known virulence-associated determinants. In comparison to seasonal influenza viruses of lesser virulence, the 1918 H1N1 virus has fewer glycosylation sequons on the HA globular head region. Using site-directed mutagenesis we found that a 1918 HA recombinant virus, of high virulence, could be significantly attenuated in mice by adding two additional glycosylation sites (asparagine [Asn] 71 and Asn 286) on the side of the HA head. The 1918 HA recombinant virus was further attenuated by introducing two additional glycosylation sites on the top of the HA head at Asn 142 and Asn 172. In a reciprocal experimental approach, deletion of HA glycosylation sites (Asn 142 and Asn 177, but not Asn 71 and Asn 104) from a seasonal influenza H1N1 virus, A/Solomon Islands/2006 (SI/06) displayed increased virulence in mice. The addition of glycosylation sites to the 1918 HA and removal of glycosylation sites from SI/06 HA imposed constraints on the theoretical structure surrounding the glycan-receptor binding sites, which in turn led to distinct glycan receptor binding properties. The modification of glycosylation sites for the 1918 and SI/06 virus also caused changes in viral antigenicity based on cross hemagglutinin-inhibition antibody titers with antisera from mice infected with wild type or glycan mutant viruses. These results demonstrate that glycosylation patterns of the 1918 and seasonal H1N1 virus directly contributes to differences in virulence and is partially responsible for their distinct antigenicity. |
Plasmodium coatneyi in rhesus macaques replicates the multisystemic dysfunction of severe malaria in humans
Moreno A , Cabrera-Mora M , Garcia A , Orkin J , Strobert E , Barnwell JW , Galinski MR . Infect Immun 2013 81 (6) 1889-904 Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naive and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. |
Quantification of the adenylate cyclase toxin of Bordetella pertussis in vitro and during respiratory infection
Eby JC , Gray MC , Warfel JM , Paddock CD , Jones TF , Day SR , Bowden J , Poulter MD , Donato GM , Merkel TJ , Hewlett EL . Infect Immun 2013 81 (5) 1390-8 Whooping cough results from infection of the respiratory tract with Bordetella pertussis, and the secreted adenylate cyclase toxin (ACT) is essential for the bacterium to establish infection. Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrations in vitro, ACT has not been observed or quantified in vivo, and thus the concentration of ACT at the site of infection is unknown. The recently developed baboon model of infection mimics the prolonged cough and transmissibility of pertussis, and we hypothesized that measurement of ACT in nasopharyngeal washes (NPW) from baboons, combined with human and in vitro data, would provide an estimate of the ACT concentration in the airway during infection. NPW contained up to approximately 10(8) CFU/ml B. pertussis and 1 to 5 ng/ml ACT at the peak of infection. Nasal aspirate specimens from two human infants with pertussis contained bacterial concentrations similar to those in the baboons, with 12 to 20 ng/ml ACT. When approximately 10(8) CFU/ml of a laboratory strain of B. pertussis was cultured in vitro, ACT production was detected in 60 min and reached a plateau of approximately 60 ng/ml in 6 h. Furthermore, when bacteria were brought into close proximity to target cells by centrifugation, intoxication was increased 4-fold. Collectively, these data suggest that at the bacterium-target cell interface during infection of the respiratory tract, the concentration of ACT can exceed 100 ng/ml, providing a reference point for future studies of ACT and pertussis pathogenesis. |
Investigation of molluscum contagiosum virus, orf and other parapoxviruses in lymphomatoid papulosis
Fernandez KH , Bream M , Ali MA , Krogmann T , Zhao H , Li Y , Cohen JI , Damon I , Liu V . J Am Acad Dermatol 2013 68 (6) 1046-7 Lymphomatoid papulosis (LyP) is a primary cutaneous CD30+ lymphoproliferative disorder with large, atypical CD-30+ cells, which despite their ominous appearance, also occur in reactive processes, such as CD30+ cutaneous lymphoid hyperplasia. As most causes of CD30+ cutaneous lymphoid hyperplasia are viral,1 we explored the possibility that poxvirus or parapoxvirus could be detected in lesions of LyP. | Following University of Iowa Institutional Review Board approval, nine patients with a diagnosis of LyP that had available skin tissue blocks were included. For negative controls, two scar tissue samples were included. | DNA was extracted from formalin-fixed, paraffin-embedded slides. Tissue was dewaxed by addition of xylene, vortexing, and centrifuging; xylene was removed and the pellet was rehydrated in 100% ethanol. After vortexing, centrifugation, and air drying, the sample was resuspended in digestion buffer and was incubated at 55°C for 4–6 hrs. Chelex-100 (BioRad) was added to a final concentration of 5%. The mixture was boiled 8 min, chilled 2 min, and centrifuged for 5 min at 4°C. The supernatant was transferred to a fresh centrifuge tube as template. |
A randomized trial of the effect of centralized reminder/recall on immunizations and preventive care visits for adolescents
Szilagyi PG , Albertin C , Humiston SG , Rand CM , Schaffer S , Brill H , Stankaitis J , Yoo BK , Blumkin A , Stokley S . Acad Pediatr 2013 13 (3) 204-13 OBJECTIVE: To assess the impact of a managed care-based patient reminder/recall system on immunization rates and preventive care visits among low-income adolescents. METHODS: We conducted a randomized controlled trial between December 2009 and December 2010 that assigned adolescents aged 11-17 years to one of three groups: mailed letter, telephone reminders, or control. Publicly insured youths (n = 4115) were identified in 37 participating primary care practices. The main outcome measures were immunization rates for routine vaccines (meningococcus, pertussis, HPV) and preventive visit rates at study end. RESULTS: Intervention and control groups were similar at baseline for demographics, immunization rates, and preventive visits. Among adolescents who were behind at the start, immunization rates at study end increased by 21% for mailed (P < .01 vs control), 17% for telephone (P < .05), and 13% for control groups. The proportion of adolescents with a preventive visit (within 12 months) was: mailed (65%; P < .01), telephone (63%; P < .05), and controls (59%). The number needed to treat for an additional fully vaccinated adolescent was 14 for mailed and 25 for telephone reminders; for an additional preventive visit, it was 17 and 29. The intervention cost $18.78 (mailed) or $16.68 (phone) per adolescent per year to deliver. The cost per additional adolescent fully vaccinated was $463.99 for mailed and $714.98 for telephone; the cost per additional adolescent receiving a preventive visit was $324.75 and $487.03. CONCLUSIONS: Managed care-based mail or telephone reminder/recall improved adolescent immunizations and preventive visits, with modest costs and modest impact. |
Valproate prescriptions for nonepilepsy disorders in reproductive-age women
Adedinsewo DA , Thurman DJ , Luo YH , Williamson RS , Odewole OA , Oakley GP Jr . Birth Defects Res A Clin Mol Teratol 2013 97 (6) 403-8 BACKGROUND: Scientific evidence has consistently shown taking valproate during pregnancy increases risks of congenital malformations and cognitive impairment. As such, elimination of its use would be an important step in birth defects prevention. There are guidelines discouraging its use among women with epilepsy, but none exists for women without epilepsy, nor is the prevalence of valproate for nonepilepsy indications known. METHODS: Using de-identified data from the National Hospital and Ambulatory Medical Care Surveys (1996-2007), we examined individual prescriptions for reproductive-age adolescent girls and adult women ages 15 to 44 years in the United States, and estimated the number of antiepileptic drug and valproate prescriptions in the aggregate. We classified our study population using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, as women with epilepsy and women without epilepsy. The prevalence of antiepileptic drug and valproate prescriptions among women without epilepsy was estimated as prescriptions per 1000 patient visits for every 3-year time interval and the overall study period. RESULTS: We found 83% of valproate prescriptions were issued to women without epilepsy and 74% of these were for psychiatric diagnoses. The prevalence of antiepileptic drug prescriptions among women without epilepsy tripled during the study period (10.3 [1996-1998] vs. 34.9 [2005-2007] per 1000 patient visits), whereas valproate prescriptions remained relatively stable (3.1 [1996-1998] vs. 3.7 [2005-2007] per 1000 patient visits). CONCLUSION: Most women of reproductive age who receive a valproate prescription do not have epilepsy. Valproate prescriptions did not decline, despite increasing knowledge of its teratogenicity. Reducing valproate use among women of reproductive age, especially among those who use the drug for psychiatric indications, would prevent birth defects and cognitive deficits. (Birth Defects Research (Part A), 2013. (c) 2013 Wiley Periodicals, Inc.) |
The expanding role of the African nurse and midwife in paediatric HIV
Dziuban E . Afr J Midwifery Womens Health 2013 7 (2) 98-99 There are approximately 3.4 million infants and children in the world living with HIV, of which 91% are in Africa. Another 1.4 million African infants are born exposed to HIV every year (World Health Organization, 2013). Most are living in countries with severe shortages of all types of health-care workers. Previously, the management of paediatric HIV was considered the domain only of the medical doctor, and it was only they who were considered qualified to prescribe life-saving antiretroviral treatment (ART). | However, those days are now falling behind us. The extremely limited number of doctors in many parts of Africa means many patients, both children and adults, may not receive the medication they need for survival. Some countries adapted by permitting nurses and midwives with appropriate training to prescribe ART refills (Médecins Sans Frontières, 2012). Now, a number of ministries of health have taken the next important step in task-sharing—to permit nursing staff to initiate ART as well, thus breaking down a significant barrier in access for the millions of HIV-infected individuals living in districts where a doctor may be nearly impossible to find. |
Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants
Creek DJ , Bigira V , McCormack S , Arinaitwe E , Wanzira H , Kakuru A , Tappero JW , Sandison TG , Lindegardh N , Nosten F , Aweeka FT , Parikh S . J Infect Dis 2013 207 (11) 1646-54 BACKGROUND: Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking. METHODS: We conducted a prospective PK/PD study of piperaquine in 107 young children in Uganda. Samples were collected up to 28 days after 218 episodes of malaria treatment, which occurred during follow-up periods of up to 5 months. Malaria follow-up was conducted actively to day 28 and passively to day 63. RESULTS: The median capillary piperaquine concentration on day 7 after treatment was 41.9 ng/mL. Low piperaquine concentrations were associated with an increased risk of recurrent malaria for up to 42 days, primarily in those receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In children not receiving TMP-SMX, low piperaquine concentrations were only modestly associated with an increased risk of recurrent malaria. However, for children receiving TMP-SMX, associations were strong and evident for all sampling days, with PQ concentrations of ≤27.3 ng/mL on day 7 associated with a greatly increased risk of recurrent malaria. Notably, of 132 cases of recurrent malaria, 119 had detectable piperaquine concentrations at the time of presentation with recurrent malaria. CONCLUSIONS: These piperaquine PK/PD data represent the first in children <2 years of age. Piperaquine exposure on day 7 correlated with an increased risk of recurrent malaria after DP treatment in children receiving TMP-SMX prophylaxis. Interestingly, despite strong associations, infants remained at risk for malaria, even if they had residual levels of piperaquine. |
Trends in laboratory test volumes for Medicare Part B reimbursements, 2000-2010
Shahangian S , Alspach TD , Astles JR , Yesupriya A , Dettwyler WK . Arch Pathol Lab Med 2013 138 (2) 189-203 CONTEXT: Changes in reimbursements for clinical laboratory testing may help us assess the effect of various variables, such as testing recommendations, market forces, changes in testing technology, and changes in clinical or laboratory practices, and provide information that can influence health care and public health policy decisions. To date, however, there has been no report, to our knowledge, of longitudinal trends in national laboratory test use. OBJECTIVE: To evaluate Medicare Part B-reimbursed volumes of selected laboratory tests per 10,000 enrollees from 2000 through 2010. DESIGN: Laboratory test reimbursement volumes per 10,000 enrollees in Medicare Part B were obtained from the Centers for Medicare & Medicaid Services (Baltimore, Maryland). The ratio of the most recent (2010) reimbursed test volume per 10,000 Medicare enrollees, divided by the oldest data (usually 2000) during this decade, called the volume ratio, was used to measure trends in test reimbursement. Laboratory tests with a reimbursement claim frequency of at least 10 per 10,000 Medicare enrollees in 2010 were selected, provided there was more than a 50% change in test reimbursement volume during the 2000-2010 decade. We combined the reimbursed test volumes for the few tests that were listed under more than one code in the Current Procedural Terminology (American Medical Association, Chicago, Illinois). A 2-sided Poisson regression, adjusted for potential overdispersion, was used to determine P values for the trend; trends were considered significant at P < .05. RESULTS: Tests with the greatest decrease in reimbursement volumes were electrolytes, digoxin, carbamazepine, phenytoin, and lithium, with volume ratios ranging from 0.27 to 0.64 (P < .001). Tests with the greatest increase in reimbursement volumes were meprobamate, opiates, methadone, phencyclidine, amphetamines, cocaine, and vitamin D, with volume ratios ranging from 83 to 1510 (P < .001). CONCLUSIONS: Although reimbursement volumes increased for most of the selected tests, other tests exhibited statistically significant downward trends in annual reimbursement volumes. The observed changes in reimbursement volumes may be explained by disease prevalence and severity, patterns of drug use, clinical or laboratory practices, and testing recommendations and guidelines, among others. These data may be useful to policy makers, health systems researchers, laboratory directors, and industry scientists to understand, address, and anticipate trends in laboratory testing in the Medicare population. |
Classification of Leptospira genomospecies 1, 3, 4 and 5 as Leptospira alstonii sp. nov., Leptospira vanthielii sp. nov., Leptospira terpstrae sp. nov. and Leptospira yanagawae sp. nov., respectively
Smythe L , Adler B , Hartskeerl RA , Galloway RL , Turenne CY , Levett PN . Int J Syst Evol Microbiol 2013 63 1859-62 The genus Leptospira currently comprises 16 named species. In addition, four unnamed hybridization groups were designated Leptospira genomospecies 1, 3, 4 and 5. These groups represent valid species-level taxa, but were not assigned names in the original description by Brenner et al. [Int J Syst Bacteriol 49, 839-858 (1999)]. To rectify this situation, it is proposed that Leptospira genomospecies 1, genomospecies 3, genomospecies 4 and genomospecies 5 should be classified as Leptospira alstonii sp. nov., Leptospira vanthielii sp. nov., Leptospira terpstrae sp. nov. and Leptospira yanagawae sp. nov., respectively, with strains L. alstonii 79601(T) ( = ATCC BAA-2439(T)), L. vanthielii WaZ Holland(T) ( = ATCC 700522(T)), L. terpstrae LT 11-33(T) ( = ATCC 700639(T)) and L. yanagawae Sao Paulo(T) ( = ATCC 700523(T)) as the type strains. The type strains are also available from the culture collections of the WHO Collaborating Centres in Amsterdam, The Netherlands, and Brisbane, Australia. |
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