Receipt of glucose testing and performance of two US diabetes screening guidelines, 2007-2012
Bullard KM , Ali MK , Imperatore G , Geiss LS , Saydah SH , Albu JB , Cowie CC , Sohler N , Albright A , Gregg EW . PLoS One 2015 10 (4) e0125249 BACKGROUND: Screening guidelines are used to help identify prediabetes and diabetes before implementing evidence-based prevention and treatment interventions. We examined screening practices benchmarking against two US guidelines, and the capacity of each guideline to identify dysglycemia. METHODS: Using 2007-2012 National Health and Nutrition Examination Surveys, we analyzed nationally-representative, cross-sectional data from 5,813 fasting non-pregnant adults aged ≥20 years without self-reported diabetes. We examined proportions of adults eligible for diagnostic glucose testing and those who self-reported receiving testing in the past three years, as recommended by the American Diabetes Association (ADA) and the US Preventive Services Task Force (USPSTF-2008) guidelines. For each screening guideline, we also assessed sensitivity, specificity, and positive (PPV) and negative predictive values in identifying dysglycemia (defined as fasting plasma glucose ≥100 mg/dl or hemoglobin A1c ≥5.7%). RESULTS: In 2007-2012, 73.0% and 23.7% of US adults without diagnosed diabetes met ADA and USPSTF-2008 criteria for screening, respectively; and 91.5% had at least one major risk factor for diabetes. Of those ADA- or USPSTF-eligible adults, about 51% reported being tested within the past three years. Eligible individuals not tested were more likely to be lower educated, poorer, uninsured, or have no usual place of care compared to tested eligible adults. Among adults with ≥1 major risk factor, 45.7% reported being tested, and dysglycemia yields (i.e., PPV) ranged from 45.8% (high-risk ethnicity) to 72.6% (self-reported prediabetes). ADA criteria and having any risk factor were more sensitive than the USPSTF-2008 guideline (88.8-97.7% vs. 31.0%) but less specific (13.5-39.7% vs. 82.1%) in recommending glucose testing, resulting in lower PPVs (47.7-54.4% vs. 58.4%). CONCLUSION: Diverging recommendations and variable performance of different guidelines may be impeding national diabetes prevention and treatment efforts. Efforts to align screening recommendations may result in earlier identification of adults at high risk for prediabetes and diabetes. |
Nutrition-related policy and environmental strategies to prevent obesity in rural communities: a systematic review of the literature, 2002-2013
Calancie L , Leeman J , Jilcott Pitts SB , Khan LK , Fleischhacker S , Evenson KR , Schreiner M , Byker C , Owens C , McGuirt J , Barnidge E , Dean W , Johnson D , Kolodinsky J , Piltch E , Pinard C , Quinn E , Whetstone L , Ammerman A . Prev Chronic Dis 2015 12 E57 INTRODUCTION: Residents of rural communities in the United States are at higher risk for obesity than their urban and suburban counterparts. Policy and environmental-change strategies supporting healthier dietary intake can prevent obesity and promote health equity. Evidence in support of these strategies is based largely on urban and suburban studies; little is known about use of these strategies in rural communities. The purpose of this review was to synthesize available evidence on the adaptation, implementation, and effectiveness of policy and environmental obesity-prevention strategies in rural settings. METHODS: The review was guided by a list of Centers for Disease Control and Prevention Recommended Community Strategies and Measurements to Prevent Obesity in the United States, commonly known as the "COCOMO" strategies. We searched PubMed, Cumulative Index of Nursing and Allied Health Literature, Public Affairs Information Service, and Cochrane databases for articles published from 2002 through 2013 that reported findings from research on nutrition-related policy and environmental strategies in rural communities in the United States and Canada. Two researchers independently abstracted data from each article, and resolved discrepancies by consensus. RESULTS: Of the 663 articles retrieved, 33 met inclusion criteria. The interventions most commonly focused on increasing access to more nutritious foods and beverages or decreasing access to less nutritious options. Rural adaptations included accommodating distance to food sources, tailoring to local food cultures, and building community partnerships. CONCLUSIONS: Findings from this literature review provide guidance on adapting and implementing policy and environmental strategies in rural communities. |
Examining adherence with recommendations for follow-up in the Prevention Among Colorectal Cancer Survivors study
Hawkins NA , Berkowitz Z , Rodriguez J , Miller JW , Sabatino SA , Pollack LA . Oncol Nurs Forum 2015 42 (3) 233-40 PURPOSE/OBJECTIVES: To explore the impact of health professionals' recommendations for medical follow-up among colorectal cancer (CRC) survivors. DESIGN: Cross-sectional survey. SETTING: Mailed surveys and telephone interviews with CRC survivors in California. SAMPLE: 593 adults diagnosed with a primary CRC six to seven years before the time of the study. METHODS: Participants were identified through California Cancer Registry records and invited to take part in a survey delivered via mail or through telephone interview. MAIN RESEARCH VARIABLES: The survey assessed cancer history, current preventive health practices, health status, demographics, and other cancer-related experiences. FINDINGS: More than 70% of CRC survivors received recommendations for routine checkups, surveillance colonoscopy, or other cancer screenings after completing CRC treatment, and 18%-22% received no such recommendations. Recommendations were sometimes given in writing. Receiving a recommendation for a specific type of follow-up was associated with greater adherence to corresponding guidelines for routine checkups, colonoscopy, mammography, and Papanicolaou testing. Receiving written (versus unwritten) recommendations led to greater adherence only for colonoscopy. CONCLUSIONS: Most CRC survivors reported receiving recommendations for long-term medical follow-up and largely adhered to guidelines for follow-up. Receiving a health professional's recommendation for follow-up was consistently associated with patient adherence, and limited evidence showed that recommendations in written form led to greater adherence than unwritten recommendations. IMPLICATIONS FOR NURSING: Given the increasingly important role of the oncology nurse in survivorship care, nurses can be instrumental in ensuring appropriate surveillance and follow-up care among CRC survivors. Conveying recommendations in written form, as is done in survivorship care plans, may be particularly effective. |
Gynecologic cancer information on YouTube: will women watch advertisements to learn more?
Cooper CP , Gelb CA , Chu J . J Cancer Educ 2015 31 (3) 602-4 The quality and accuracy of health content posted on YouTube varies widely. To increase dissemination of evidence-based gynecologic cancer information to US YouTube users, the Centers for Disease Control and Prevention (CDC) sponsored two types of advertisements: (1) pre-roll videos that users had to watch for at least 5 s before seeing a video they selected and (2) keyword-targeted listings that appeared in search results when users entered terms related to gynecologic cancer. From July 2012 to November 2013, pre-roll videos were shown 9.2 million times, viewed (watched longer than the mandatory 5 s) 1.6 million times (17.6 %), and cost $0.09 per view. Keyword-targeted listings were displayed 15.3 million times, viewed (activated by users) 59,766 times (0.4 %), and cost $0.31 per view. CDC videos in advertisements played completely in 17.0 % of pre-roll video views and 44.4 % of keyword-targeted listing views. Advertisements on YouTube can disseminate evidence-based cancer information broadly with minimal cost. |
Laboratory investigation and phylogenetic analysis of an imported Middle East respiratory syndrome coronavirus case in Greece.
Kossyvakis A , Tao Y , Lu X , Pogka V , Tsiodras S , Emmanouil M , Mentis AF , Tong S , Erdman DD , Antoniadis A . PLoS One 2015 10 (4) e0125809 Rapid and reliable laboratory diagnosis of persons suspected of Middle East respiratory syndrome coronavirus (MERS-CoV) infection is important for timely implementation of infection control practices and disease management. In addition, monitoring molecular changes in the virus can help elucidate chains of transmission and identify mutations that might influence virus transmission efficiency. This was illustrated by a recent laboratory investigation we conducted on an imported MERS-CoV case in Greece. Two oropharyngeal swab specimens were collected on the 1st and 2nd day of patient hospitalization and tested using two real-time RT-PCR (rRT-PCR) assays targeting the UpE and Orf-1a regions of the MERS-CoV genome and RT-PCR and partial sequencing of RNA-dependent RNA polymerase and nucleocapsid genes. Serum specimens were also collected and serological test were performed. Results from the first swab sample were inconclusive while the second swab was strongly positive for MERS-CoV RNA by rRT-PCR and confirmed positive by RT-PCR and partial gene sequencing. Positive serologic test results further confirmed MERS-CoV infection. Full-length nucleocapsid and spike gene coding sequences were later obtained from the positive swab sample. Phylogenetic analysis revealed that the virus was closely related to recent human-derived MERS-CoV strains obtained in Jeddah and Makkah, Saudi Arabia, in April 2014 and dromedary camels in Saudi Arabia and Qatar. These findings were consistent with the patient's history. We also identified a unique amino acid substitution in the spike receptor binding domain that may have implications for receptor binding efficiency. Our initial inconclusive rRT-PCR results highlight the importance of collecting multiple specimens from suspect MERS-CoV cases and particularly specimens from the lower respiratory tract. |
A reader's guide to the bactericidal activity of pyrazinamide and clofazimine alone and in combinations with pretomanid and bedaquiline
Grosset J , Vernon A . Am J Respir Crit Care Med 2015 191 (8) 871-3 In this issue of the Journal, Diacon and colleagues (pp. 943–953) assessed the 14-day extended early bactericidal activity (EBA) of pyrazinamide alone, clofazimine alone, and four combination regimens of bedaquiline in permutations with pyrazinamide, pretomanid (Pa824), and clofazimine (1). The positive treatment control was a standard regimen of rifampin, isoniazid, pyrazinamide, and ethambutol, delivered as a combination tablet (Rifafour; sanofi-aventis, Paris, France), and the study participants were treatment-naive patients with pulmonary tuberculosis with positive results from sputum-smear microscopy for acid-fast bacilli. On Day 14 of treatment, the pharmacokinetic (PK) parameters of the prescribed drugs alone and in combination were measured. | The results were clear-cut. First, each of the three experimental three-drug combinations (bedaquiline, pretomanid, and pyrazinamide; bedaquiline, pretomanid, and clofazimine; and bedaquiline, pyrazinamide, and clofazimine) and the one experimental four-drug combination (bedaquiline, pretomanid, pyrazinamide, and clofazimine) had extended EBA that was not significantly different from that of the Rifafour control regimen. Second, pyrazinamide alone had minimal EBA, as expected, and clofazimine alone provided no early activity at all. Third, the main PK parameters of each studied drug were apparently not affected by the other drugs given in combination; that is, drug–drug interactions were not apparent, and PK parameters were mostly within the expected range. For clofazimine, the peak plasma concentration after 14 days of daily administration was, on average, 0.2 μg/ml and close to its 0.25 μg/ml minimum inhibitory concentration for Mycobacterium tuberculosis. The peak plasma concentrations and 24-hour area under the concentration curve of bedaquiline, its M2 metabolite, and clofazimine varied six- to eightfold across regimens and among individuals, but the median exposures achieved were relatively similar across regimens; there was less variation in pretomanid and pyrazinamide exposures. |
Recent US case of variant Creutzfeldt-Jakob disease - global implications
Maheshwari A , Fischer M , Gambetti P , Parker A , Ram A , Soto C , Concha-Marambio L , Cohen Y , Belay ED , Maddox RA , Mead S , Goodman C , Kass JS , Schonberger LB , Hussein HM . Emerg Infect Dis 2015 21 (5) 750-9 Variant Creutzfeldt-Jakob disease (vCJD) is a rare, fatal prion disease resulting from transmission to humans of the infectious agent of bovine spongiform encephalopathy. We describe the clinical presentation of a recent case of vCJD in the United States and provide an update on diagnostic testing. The location of this patient's exposure is less clear than those in the 3 previously reported US cases, but strong evidence indicates that exposure to contaminated beef occurred outside the United States more than a decade before illness onset. This case exemplifies the persistent risk for vCJD acquired in unsuspected geographic locations and highlights the need for continued global surveillance and awareness to prevent further dissemination of vCJD. |
Tracking progress toward polio eradication - worldwide, 2013-2014
Porter KA , Diop OM , Burns CC , Tangermann RH , Wassilak SG . MMWR Morb Mortal Wkly Rep 2015 64 (15) 415-20 Global efforts to eradicate polio began in 1988 and have been successful in all but two of the six World Health Organization (WHO) regions. Within these two regions (African and Eastern Mediterranean), three countries (Afghanistan, Nigeria, and Pakistan) have never interrupted transmission of wild poliovirus (WPV). Outbreaks following importation of WPV from these countries occurred in the Horn of Africa, Central Africa, and in the Middle East during 2013-2014. The primary means of tracking polio is surveillance for cases of acute flaccid paralysis (AFP), the main symptom of polio, followed by testing of AFP patients' stool specimens for both WPV and vaccine-derived poliovirus (VDPV) in WHO-accredited laboratories within the Global Polio Laboratory Network (GPLN). This is supplemented with environmental surveillance (testing sewage for WPV and VDPV) (4). Both types of surveillance use genomic sequencing for characterization of poliovirus isolates to map poliovirus transmission and for identifying gaps in AFP surveillance by measuring genetic divergence between isolates. This report presents 2013 and 2014 poliovirus surveillance data, focusing primarily on the two WHO regions with endemic WPV transmission, and the 29 countries (African Region = 23; Eastern Mediterranean Region = six) with at least one case of WPV or circulating VDPV (cVDPV) reported during 2010-2014. In 2013, 20 of these 23 African region countries met both primary surveillance quality indicators; in 2014, the number decreased to 15. In 2013, five of the six Eastern Mediterranean Region countries met the primary indicators, and in 2014, all six did. To complete and certify polio eradication, surveillance gaps must be identified and surveillance activities, including supervision, monitoring, and specimen collection, further strengthened. |
Latent tuberculosis infection and associated factors among health care workers in Kigali, Rwanda
Rutanga C , Lowrance DW , Oeltmann JE , Mutembayire G , Willis M , Uwizeye CB , Hinda R , Bassirou C , Gutreuter S , Gasana M . PLoS One 2015 10 (4) e0124485 INTRODUCTION: Data are limited regarding tuberculosis (TB) and latent TB infection prevalence in Rwandan health facilities. METHODS: We conducted a cross-sectional survey among healthcare workers (HCWs) in Kigali during 2010. We purposively selected the public referral hospital, both district hospitals, and randomly selected 7 of 17 health centers. School workers (SWs) from the nearest willing public schools served as a local reference group. We tested for latent TB infection (LTBI) using tuberculin skin testing (TST) and asked about past TB disease. We assessed risk of LTBI and past history of TB disease associated with hospital employment. Among HCWs, we assessed risk associated with facility type (district hospital, referral hospital, health center), work setting (inpatient, outpatient), and occupation. RESULTS: Age, gender, and HIV status was similar between the enrolled 1,131 HCWs and 381 SWs. LTBI was more prevalent among HCWs (62%) than SWs (39%). Adjusted odds of a positive TST result were 2.71 (95% CI 2.01-3.67) times greater among HCWs than SWs. Among HCWs, there was no detectable difference between prevalence of LTBI according to facility type, work setting, or occupation. CONCLUSION: HCWs are at greater risk of LTBI, regardless of facility type, work setting, or occupation. The current status of TB infection control practices should be evaluated in the entire workforce in all Rwandan healthcare facilities. |
The East Jakarta Project: surveillance for highly pathogenic avian influenza A(H5N1) and seasonal influenza viruses in patients seeking care for respiratory disease, Jakarta, Indonesia, October 2011-September 2012
Storms AD , Kusriastuti R , Misriyah S , Praptiningsih CY , Amalya M , Lafond KE , Samaan G , Triada R , Iuliano AD , Ester M , Sidjabat R , Chittenden K , Vogel R , Widdowson MA , Mahoney F , Uyeki TM . Epidemiol Infect 2015 143 (16) 1-11 Indonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription-polymerase chain reaction. During October 2011-September 2012, 1131/3278 specimens from ILI cases (34.5%) and 276/1787 specimens from SARI cases (15.4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December-May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season. |
Ebola: the hidden toll
Hamel MJ , Slutsker L . Lancet Infect Dis 2015 15 (7) 756-7 The first anniversary of the west African Ebola epidemic has just passed. In Guinea, Liberia, and Sierra Leone, Ebola virus disease has resulted in more than 10 000 reported deaths while the virtual collapse of the countries’ health-care systems has contributed to countless more. In The Lancet Infectious Diseases, Patrick Walker and colleagues1 describe a mathematical model to estimate the effect of the ongoing Ebola disease epidemic on a less exotic and more familiar killer— malaria. The estimates are sobering, if not surprising: up to 10 900 additional malaria deaths in these three countries in 2014 can be attributed to the disruption of health-care services, with another 3900 attributed to lapses in the delivery of insecticide-treated bednets. The investigators predicted continued excess malaria mortality in 2015 and a rise in malaria transmission if immediate emergency strategies to control malaria are not implemented. | During the past decade, renewed commitment from donors, ministries of health, and international agencies has led to the scale-up of malaria interventions across sub-Saharan Africa, with a corresponding reduction in child malaria mortality of 50%.2 The continuous delivery of those life-saving interventions—prompt effective treatment, routine distribution of insecticide-treated bednets, indoor residual spraying, and intermittent preventive treatment of malaria in pregnancy—depends on a reliable, functioning health-care system. Large-scale challenges to already fragile health-care systems, as has occurred with Ebola virus disease, can result in disruption of programmes, which in turn could threaten or reverse the gains achieved in malaria control. Walker and colleagues have shown how quickly and extensively that reversal can occur. |
Effect of active case finding on prevalence and transmission of pulmonary tuberculosis in Dhaka central jail, Bangladesh
Banu S , Rahman MT , Uddin MK , Khatun R , Khan MS , Rahman MM , Uddin SI , Ahmed T , Heffelfinger JD . PLoS One 2015 10 (5) e0124976 BACKGROUND: Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. METHODS: The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). RESULTS: A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as 'modern' and 100 (30%) strains as 'ancestral'. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. CONCLUSIONS: Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh. |
The epidemiology of HIV and prevention needs of men who have sex with men in Abidjan, Cote d'Ivoire
Hakim AJ , Aho J , Semde G , Diarrassouba M , Ehoussou K , Vuylsteke B , Murrill CS , Thiam M , Wingate T . PLoS One 2015 10 (4) e0125218 To determine HIV prevalence and associated risk factors among men who have sex with men (MSM) in Abidjan, Cote d'Ivoire. We conducted a cross-sectional RDS survey of MSM in Abidjan from October 2011 to February 2012. Eligibility criteria included age ≥ 18 years and having had oral or anal sex with another man in the last 12 months. Weighted data analysis was conducted with RDSAT and SAS. We enrolled 603 participants, of whom 601 (99.7%) completed the questionnaire and 581 (96.7%) consented to HIV testing. HIV population prevalence was estimated as 18.0% (95% CI: 13.0-23.1); 86.4% (95% CI: 75.1-94.9) of HIV-positive MSM were unaware of their serostatus. In multivariable analysis, adjusting for age, education, and income, HIV infection was associated with unprotected sex at last sex with a woman, more than two male anal sex partners in last 12 months, inconsistent condom use during anal sex with a man, self-perceived risk of HIV, history of forced sex, history of physical abuse due to MSM status, and not receiving last HIV test result prior to study. HIV prevalence among MSM in Abidjan is more than four times as high as that of general population men. MSM engage in high-risk sexual behavior and most HIV-positive MSM are unaware of their serostatus. Greater access to HIV prevention, care, and treatment services targeted to MSM is necessary. |
Giardiasis surveillance - United States, 2011-2012
Painter JE , Gargano JW , Collier SA , Yoder JS . MMWR Suppl 2015 64 15-25 PROBLEM/CONDITION: Giardiasis is a nationally notifiable gastrointestinal illness caused by the protozoan parasite Giardia intestinalis. REPORTING PERIOD: 2011-2012. DESCRIPTION OF SYSTEM: Forty-four states, the District of Columbia, New York City, the Commonwealth of Puerto Rico, and Guam voluntarily reported cases of giardiasis to CDC through the National Notifiable Diseases Surveillance System (NNDSS). RESULTS: For 2011, a total of 16,868 giardiasis cases (98.8% confirmed and 1.2% nonconfirmed) were reported; for 2012, a total of 15,223 cases (98.8% confirmed and 1.3% nonconfirmed) were reported. In 2011 and 2012, 1.5% and 1.3% of cases, respectively, were associated with a detected outbreak. The incidence rates of all reported cases were 6.4 per 100,000 population in 2011 and 5.8 per 100,000 population in 2012. This represents a slight decline from the relatively steady rates observed during 2005-2010 (range: 7.1-7.9 cases per 100,000 population). In both 2011 and 2012, cases were most frequently reported in children aged 1-4 years, followed by those aged 5-9 years and adults aged 45-49 years. Incidence of giardiasis was highest in Northwest states. Peak onset of illness occurred annually during early summer through early fall. INTERPRETATION: For the first time since 2002, giardiasis rates appear to be decreasing. Possible reasons for the decrease in rates during 2011-2012 could include changes in transmission patterns, a recent change in surveillance case definition, increased uptake of strategies to reduce waterborne transmission, or a combination of these factors. Transmission of giardiasis occurs throughout the United States, with more frequent diagnosis or reporting occurring in northern states. Geographical differences might suggest actual regional differences in giardiasis transmission or variation in surveillance capacity across states. Six states did not report giardiasis cases in 2011-2012, representing the largest number of nonreporting states since giardiasis became nationally notifiable in 2002. Giardiasis is reported more frequently in young children, which might reflect increased contact with contaminated water or ill persons, or a lack of immunity. PUBLIC HEALTH ACTION: Educational efforts to decrease exposure to unsafe drinking and recreational water and prevent person-to-person transmission have the potential to reduce giardiasis transmission. The continual decrease in jurisdictions opting to report giardiasis cases could negatively impact the ability to interpret national surveillance data; thus, further investigation is needed to identify barriers to and facilitators of giardiasis case reporting. Existing state and local public health infrastructure supported through CDC (e.g., Epidemiology and Laboratory Capacity grants and CDC-sponsored Council of State and Territorial Epidemiologists Applied Epidemiology Fellows) could provide resources to enhance understanding of giardiasis epidemiology. |
Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand
Manosuthi W , Ongwandee S , Bhakeecheep S , Leechawengwongs M , Ruxrungtham K , Phanuphak P , Hiransuthikul N , Ratanasuwan W , Chetchotisakd P , Tantisiriwat W , Kiertiburanakul S , Avihingsanon A , Sukkul A , Anekthananon T . AIDS Res Ther 2015 12 12 New evidence has emerged regarding when to commence antiretroviral therapy (ART), optimal treatment regimens, management of HIV co-infection with opportunistic infections, and management of ART failure. The 2014 guidelines were developed by the collaborations of the Department of Disease Control, Ministry of Public Health (MOPH) and the Thai AIDS Society (TAS). One of the major changes in the guidelines included recommending to initiating ART irrespective of CD4 cell count. However, it is with an emphasis that commencing HAART at CD4 cell count above 500 cell/mm(3) is for public health, in term of preventing HIV transmission and personal benefit. In tuberculosis co-infected patients with CD4 cell counts ≤50 cells/mm(3) or with CD4 cell counts >50 cells/mm(3) who have severe clinical disease, ART should be initiated within 2 weeks of starting tuberculosis treatment. The preferred initial ART regimen in treatment naive patients is efavirenz combined with tenofovir and emtricitabine or lamivudine. Plasma HIV viral load assessment should be done twice a year until achieving undetectable results; and will then be monitored once a year. CD4 cell count should be monitored every 6 months until CD4 cell count ≥350 cells/mm(3) and with plasma HIV viral load <50 copies/mL; then it should be monitored once a year afterward. HIV drug resistance genotypic test is indicated when plasma HIV viral load >1,000 copies/mL while on ART. Ritonavir-boosted lopinavir or atazanavir in combination with optimized two nucleoside-analogue reverse transcriptase inhibitors is recommended after initial ART regimen failure. Long-term ART-related safety monitoring has also been included in the guidelines. |
Characteristics and outcomes of adult Ethiopian patients enrolled in HIV care and treatment: a multi-clinic observational study
Melaku Z , Lamb MR , Wang C , Lulseged S , Gadisa T , Ahmed S , Habtamu Z , Alemu H , Assefa T , Abrams EJ . BMC Public Health 2015 15 (1) 462 BACKGROUND: We describe trends in characteristics and outcomes among adults initiating HIV care and treatment in Ethiopia from 2006-2011. METHODS: We conducted a retrospective longitudinal analysis of HIV-positive adults (≥15 years) enrolling at 56 Ethiopian health facilities from 2006-2011. We investigated trends over time in the proportion enrolling through provider-initiated counseling and testing (PITC), baseline CD4+ cell counts and WHO stage. Additionally, we assessed outcomes (recorded death, loss to follow-up (LTF), transfer, and total attrition (recorded death plus LTF)) before and after ART initiation. Kaplan-Meier techniques estimated cumulative incidence of these outcomes through 36 months after ART initiation. Factors associated with LTF and death after ART initiation were estimated using Hazard Ratios accounting for within-clinic correlation. RESULTS: 93,418 adults enrolled into HIV care; 53,300 (57%) initiated ART. The proportion enrolled through PITC increased from 27.6% (2006-2007) to 44.8% (2010-2011) (p < .0001). Concurrently, median enrollment CD4+ cell count increased from 158 to 208 cells/mm3 (p < .0001), and patients initiating ART with advanced WHO stage decreased from 56.6% (stage III) and 15.0% (IV) in 2006-2007 to 47.6% (stage III) and 8.5% (IV) in 2010-2011. Median CD4+ cell count at ART initiation remained stable over time. 24% of patients were LTF before ART initiation. Among those initiating ART, attrition was 30% after 36 months, with most occurring within the first 6 months. Recorded death after ART initiation was 6.4% and 9.2% at 6 and 36 months, respectively, and decreased over time. Younger age, male gender, never being married, no formal education, low CD4+ cell count, and advanced WHO stage were associated with increased LTF. Recorded death was lower among younger adults, females, married individuals, those with higher CD4+ cell counts and lower WHO stage at ART initiation. CONCLUSIONS: Over time, enrollment in HIV care through outpatient PITC increased and patients enrolled into HIV care at earlier disease stages across all HIV testing points. However, median CD4+ cell count at ART initiation remained steady. Pre- and post-ART attrition (particularly in the first 6 months) have remained major challenges in ensuring prompt ART initiation and retention on ART. |
Community outbreak of HIV infection linked to injection drug use of oxymorphone - Indiana, 2015
Conrad C , Bradley HM , Broz D , Buddha S , Chapman EL , Galang RR , Hillman D , Hon J , Hoover KW , Patel MR , Perez A , Peters PJ , Pontones P , Roseberry JC , Sandoval M , Shields J , Walthall J , Waterhouse D , Weidle PJ , Wu H , Duwve JM . MMWR Morb Mortal Wkly Rep 2015 64 (16) 443-4 On January 23, 2015, the Indiana State Department of Health (ISDH) began an ongoing investigation of an outbreak of human immunodeficiency virus (HIV) infection, after Indiana disease intervention specialists reported 11 confirmed HIV cases traced to a rural county in southeastern Indiana. Historically, fewer than five cases of HIV infection have been reported annually in this county. The majority of cases were in residents of the same community and were linked to syringe-sharing partners injecting the prescription opioid oxymorphone (a powerful oral semi-synthetic opioid analgesic). As of April 21, ISDH had diagnosed HIV infection in 135 persons (129 with confirmed HIV infection and six with preliminarily positive results from rapid HIV testing that were pending confirmatory testing) in a community of 4,200 persons. |
Comparative mortality among people diagnosed with HIV infection or AIDS in the U.S., 2001-2010
Karch DL , Hall HI , Tang T , Hu X , Mermin J . Public Health Rep 2015 130 (3) 253-60 OBJECTIVE: The comparative mortality figure (CMF) is the expected number of deaths in the standard population compared with those observed. We assessed state-based CMFs for people with HIV infection to allow standardized assessment of mortality in all states. METHODS: We used National HIV Surveillance System data to compute CMFs for people diagnosed with HIV and AIDS from 2001 to 2010 who met the CDC HIV case definition; were alive on December 31, 2009; and died during 2010. RESULTS: In 33 U.S. states with name-based HIV reporting since 2001, the 2010 CMF for people with an HIV diagnosis was 2.8 compared with 4.5 for those with an AIDS diagnosis. CMFs for males were higher than for females (3.4 vs. 3.1) and black people had higher CMFs than white people for HIV (3.2 vs. 2.2) and AIDS (4.7 vs. 4.3). CMFs by state ranged from 0.9 to 4.2 for HIV and 1.9 to 9.7 for AIDS. In 50 states and the District of Columbia with AIDS reporting, CMFs for males and females were similar (4.5 and 4.6, respectively), CMFs for black people remained higher than for white people (5.0 and 3.9, respectively), and the range for states remained broad (1.2-9.4). CONCLUSION: State mortality figures varied based on population composition and disease stage at diagnosis, possibly indicating a need for state-specific testing, linkage to care, and viral suppression strategies to reduce mortality. |
Cryptosporidiosis surveillance - United States, 2011-2012
Painter JE , Hlavsa MC , Collier SA , Xiao L , Yoder JS . MMWR Suppl 2015 64 1-14 PROBLEM/CONDITION: Cryptosporidiosis is a nationally notifiable gastrointestinal illness caused by extremely chlorine-tolerant protozoa of the genus Cryptosporidium. REPORTING PERIOD: 2011-2012. DESCRIPTION OF SYSTEM: Fifty state and two metropolitan public health agencies voluntarily report cases of cryptosporidiosis through CDC's National Notifiable Diseases Surveillance System. RESULTS: For 2011, a total of 9,313 cryptosporidiosis cases (confirmed and nonconfirmed) were reported; for 2012, a total of 8,008 cases were reported; 5.8% and 5.3%, respectively, were associated with a detected outbreak. The rates of reported nonconfirmed cases were 1.0 and 0.9 per 100,000 population in 2011 and 2012, respectively, compared with an average of 0.0 during 1995-2004, and 0.3 during 2005-2010. The highest overall reporting rates were observed in the Midwest; 10 states reported >3.5 cases per 100,000 population in 2011 and in 2012. During 2011-2012, reported cases were highest among children aged 1-4 years (6.6 per 100,000 population), followed for the first time by elderly adults aged ≥80 years (3.4), and 75-79 years (3.3). Overall, cryptosporidiosis rates were higher among females than males during both years. For specific age groups, rates were higher among males than females aged <15 years and higher among females than males aged ≥15 years. Cryptosporidiosis symptom onset increased 4.4 fold during late summer. INTERPRETATION: Cryptosporidiosis incidence rates remain elevated nationally, and rates of nonconfirmed cases have increased. Rates remain highest in young children, although rates among elderly adults are increasing. Transmission of Cryptosporidium occurs throughout the United States, with increased reporting occurring in Midwestern states. Seasonal onset peaks coincide with the summer recreational water season and might reflect increased use of communal swimming venues. PUBLIC HEALTH ACTION: Future research is needed to address the evolving epidemiology of cryptosporidiosis cases, with a specific focus on the increase in nonconfirmed cases and increasing incidence rates among elderly adults. National systematic genotyping and subtyping of Cryptosporidium isolates could also help elucidate Cryptosporidium transmission and thus cryptosporidiosis epidemiology in the United States. |
Feasibility of conducting a longitudinal, transnational study of Filipino migrants to the United States: a dual-cohort design
Gee GC , de Castro AB , Wang MC , Crespi CM , Morey BN , Fujishiro K . J Health Care Poor Underserved 2015 26 (2) 488-504 Most studies of immigrant health are cross-sectional and fail to collect information prior to migration, leading to potential bias and confounding. The present pilot study examines the feasibility of studying migrants prospectively, with baseline data collected before migration. The study followed two cohorts of Filipinos for one year, a migrant cohort (n=27) that emigrated to the U.S. and a second non-migrant cohort (n=26) that remained in the Philippines. The one-year retention rate was 96%. The migrant cohort arrived in the U.S. within two months of their baseline assessment. Migrants and non-migrants did not differ with regard to body mass index, waist circumference, or waist to hip ratio at baseline or at follow-up. It is feasible to conduct a transnational, longitudinal study of two cohorts of Filipinos. This design provides important pre-migration information, is analogous to a natural experiment, can be upscaled, and allows for a rigorous examination of immigrant health. |
Exposure to select phthalates and phenols through use of personal care products among Californian adults and their children
Philippat C , Bennett D , Calafat AM , Picciotto IH . Environ Res 2015 140 369-376 INTRODUCTION: Certain phenols and phthalates are used in many consumer products including personal care products (PCPs). AIMS: We aimed to study the associations between the use of PCPs and urinary concentrations of biomarkers of select phenols and phthalates among Californian adults and their children. As an additional aim we compared phenols and phthalate metabolites concentrations measured in adults and children urine samples collected the same day. METHODS: Our study relied on a subsample of 90 adult-child pairs participating in the Study of Use of Products and Exposure Related Behavior (SUPERB). Each adult and child provided one to two urine samples in which we measured concentrations of selected phenols and phthalate metabolites. We computed Spearman correlation coefficients to compare concentrations measured in adults and children urine samples collected the same day. We used adjusted linear and Tobit regression models to study the associations between the use of PCPs in the past 24h and biomarker concentrations. RESULTS: Benzophenone-3 and parabens concentrations were higher in adults compared to their children. Conversely children had higher mono-n-butyl phthalate and mono-isobutyl phthalate concentrations. No significant difference was observed for the other compounds. The total number of different PCPs used was positively associated with urinary concentrations of methyl, propyl and butyl parabens and the main metabolite of diethyl phthalate in adults. Among children, the use of a few specific products including liquid soap, hair care products and sunscreen was positively associated with urinary concentrations of some phenols or phthalate metabolites. DISCUSSION: These results strengthen the body of evidence suggesting that use of PCPs is an important source of exposure to parabens and diethyl phthalate in adults and provide data on exposure to selected phenols and phthalates through use of PCPs in children. |
Ascaris and Escherichia coli inactivation in an ecological sanitation system in Port-au-Prince, Haiti
Berendes D , Levy K , Knee J , Handzel T , Hill VR . PLoS One 2015 10 (5) e0125336 The goal of this study was to evaluate the microbial die-off in a latrine waste composting system in Port-au-Prince, Haiti. Temperature data and samples were collected from compost aged 0 - 12+ months. Samples collected from compost bin centers and corners at two depths were assessed for moisture content, E. coli concentration, and Ascaris spp. viability. Center temperatures in compost bins were all above 58 degrees C, while corner temperatures were 10 - 20 degrees C lower. Moisture content was 67 +/- 10% in all except the oldest compost. A 4-log reduction in E. coli was observed over the first sixteen weeks of composting at both locations and depths, after which E. coli was undetectable (LOD: 142 MPN g-1 dry weight). In new compost, 10.4% and 8.3% of Ascaris eggs were viable and fully embryonated, respectively. Percent viability dropped to zero in samples older than six weeks. These findings indicate that the Haitian EcoSan composting process was effective in inactivating E. coli and Ascaris spp. in latrine waste within sixteen weeks. This study is one of the first to document efficacy of an ecological sanitation system under field conditions and provides insight into composting methods and monitoring for other international settings. |
Association between state assistance on the topic of indoor air quality and school district-level policies that promote indoor air quality in schools
Everett Jones S , Doroski B , Glick S . J Sch Nurs 2015 31 (6) 422-9 Nationally representative data from the 2012 School Health Policies and Practices Study examined whether state assistance on indoor air quality (IAQ) was associated with district-level policies and practices related to IAQ and integrated pest management (IPM). Districts in states that provided assistance on IAQ were more likely than districts not in such states to (1) have an IAQ management program (p < .001); (2) require schools to conduct periodic inspections of the heating, ventilation, and air conditioning system (p < .05); of the building for cracks, leaks, or past water damage (p < .01); for mold (p < .01); for clutter that prevents effective cleaning and maintenance (p < .05); of the plumbing system (p < .01); and for condensation in and around school facilities (p < .001); (3) have an engine idling reduction program ( < .001); (4) have a policy to purchase low-emitting products (p < .05); and (5) require IPM strategies (p < .05). Increasing the number of states that provide IAQ-related assistance to school districts and schools may improve school IAQ. |
Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin.
Bergeron E , Zivcec M , Chakrabarti AK , Nichol ST , Albarino CG , Spiropoulou CF . PLoS Pathog 2015 11 (5) e1004879 Crimean Congo hemorrhagic fever virus (CCHFV) is a negative-strand RNA virus of the family Bunyaviridae (genus: Nairovirus). In humans, CCHFV causes fever, hemorrhage, severe thrombocytopenia, and high fatality. A major impediment in precisely determining the basis of CCHFV's high pathogenicity has been the lack of methodology to produce recombinant CCHFV. We developed a reverse genetics system based on transfecting plasmids into BSR-T7/5 and Huh7 cells. In our system, bacteriophage T7 RNA polymerase produced complementary RNA copies of the viral S, M, and L segments that were encapsidated with the support, in trans, of CCHFV nucleoprotein and L polymerase. The system was optimized to systematically recover high yields of infectious CCHFV. Additionally, we tested the ability of the system to produce specifically designed CCHFV mutants. The M segment encodes a polyprotein that is processed by host proprotein convertases (PCs), including the site-1 protease (S1P) and furin-like PCs. S1P and furin cleavages are necessary for producing the non-structural glycoprotein GP38, while S1P cleavage yields structural Gn. We studied the role of furin cleavage by rescuing a recombinant CCHFV encoding a virus glycoprotein precursor lacking a functional furin cleavage motif (RSKR mutated to ASKA). The ASKA mutation blocked glycoprotein precursor's maturation to GP38, and Gn precursor's maturation to Gn was slightly diminished. Furin cleavage was not essential for replication, as blocking furin cleavage resulted only in transient reduction of CCHFV titers, suggesting that either GP38 and/or decreased Gn maturation accounted for the reduced virion production. Our data demonstrate that nairoviruses can be produced by reverse genetics, and the utility of our system uncovered a function for furin cleavage. This viral rescue system could be further used to study the CCHFV replication cycle and facilitate the development of efficacious vaccines to counter this biological and public health threat. |
A molecular phylogenetics-based approach for identifying recent hepatitis C virus transmission events.
Olmstead AD , Joy JB , Montoya V , Luo I , Poon AF , Jacka B , Lamoury F , Applegate T , Montaner J , Khudyakov Y , Grebely J , Cook D , Harrigan PR , Krajden M . Infect Genet Evol 2015 33 101-9 Improved surveillance methods are needed to better understand the current hepatitis C virus (HCV) disease burden and to monitor the impact of prevention and treatment interventions on HCV transmission dynamics. Sanger sequencing (HCV NS5B, HVR1 and Core-E1-HVR1) and phylogenetics were applied to samples from individuals diagnosed with HCV in British Columbia, Canada in 2011. This included individuals with two or three sequential samples collected <1year apart. Patristic distances between sequential samples were used to set cutoffs to identify recent transmission clusters. Factors associated with transmission clustering were analyzed using logistic regression. From 618 individuals, 646 sequences were obtained. Depending on the cutoff used, 63 (10%) to 92 (15%) unique individuals were identified within transmission clusters of predicted recent origin. Clustered individuals were more likely to be <40years old (Adjusted Odds Ratio (AOR) 2.12, 95% CI 1.21-3.73), infected with genotype 1a (AOR 6.60, 95% CI 1.98-41.0), and to be seroconverters with estimated infection duration of <1year (AOR 3.13, 95% CI 1.29-7.36) or >1year (AOR 2.19, 95% CI 1.22-3.97). CONCLUSION: Systematic application of molecular phylogenetics may be used to enhance traditional surveillance methods through identification of recent transmission clusters. |
Outbreak of Clostridium difficile infections at an outpatient hemodialysis facility - Michigan, 2012-2013
See I , Bagchi S , Booth S , Scholz D , Geller AI , Anderson L , Moulton-Meissner H , Finks JL , Kelley K , Gould CV , Patel PR . Infect Control Hosp Epidemiol 2015 36 (8) 1-3 Investigation of an outbreak of Clostridium difficile infection (CDI) at a hemodialysis facility revealed evidence that limited intrafacility transmission occurred despite adherence to published infection control standards for dialysis clinics. Outpatient dialysis facilities should consider CDI prevention, including environmental disinfection for C. difficile, when formulating their infection control plans. |
US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines
Saraiya M , Unger ER , Thompson TD , Lynch CF , Hernandez BY , Lyu CW , Steinau M , Watson M , Wilkinson EJ , Hopenhayn C , Copeland G , Cozen W , Peters ES , Huang Y , Saber MS , Altekruse S , Goodman MT . J Natl Cancer Inst 2015 107 (6) djv086 BACKGROUND: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. METHODS: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. RESULTS: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. CONCLUSIONS: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine. |
The Lao experience in deploying influenza A(H1N1)pdm09 vaccine: lessons made relevant in preparing for present day pandemic threats
Xeuatvongsa A , Mirza S , Winter C , Feldon K , Vongphrachanh P , Phonekeo D , Denny J , Khanthamaly V , Kounnavong B , Lylianou D , Phousavath S , Norasingh S , Boutta N , Olsen S , Bresee J , Moen A , Corwin A . PLoS One 2015 10 (4) e0121717 The Lao PDR, as did most countries of the Mekong Region, embarked on a pandemic vaccine initiative to counter the threat posed by influenza A(H1N1)pdm09. Overall, estimated vaccine coverage of the Lao population was 14%, with uptake in targeted health care workers and pregnant women 99% and 41%, respectively. Adverse Events Following Immunization accounted for only 6% of survey driven, reported vaccination experiences, with no severe consequences or deaths. Public acceptability of the vaccine campaign was high (98%). Challenges to vaccine deployment included: 1) no previous experience in fielding a seasonal influenza vaccine, 2) safety and efficacy concerns, and 3) late arrival of vaccine 10 months into the pandemic. The Lao success in surmounting these hurdles was in large measure attributed to the oversight assigned the National Immunization Program, and national sensitivities in responding to the avian influenza A(H5N1) crisis in the years leading up to the pandemic. The Lao "lessons learned" from pandemic vaccine deployment are made even more relevant four years on, given the many avian influenza strains circulating in the region, all with pandemic potential. |
Methods and challenges in measuring the impact of national pneumococcal and rotavirus vaccine introduction on morbidity and mortality in Malawi
Bar-Zeev N , Kapanda L , King C , Beard J , Phiri T , Mvula H , Crampin AC , Mwansambo C , Costello A , Parashar U , Tate JE , Verani JR , Whitney CG , Heyderman RS , Cunliffe NA , French N . Vaccine 2015 33 (23) 2637-45 BACKGROUND: Pneumonia and gastroenteritis are leading causes of vaccine-preventable childhood morbidity and mortality. Malawi introduced pneumococcal conjugate and rotavirus vaccines to the immunisation programme in 2011 and 2012, respectively. Evaluating their effectiveness is vital to ensure optimal implementation and justify sustained investment. METHODS/DESIGN: A national evaluation platform was established to determine vaccine effectiveness and impact in Malawi. Impact and effectiveness against vaccine-type invasive pneumococcal disease, radiological pneumonia and rotavirus gastroenteritis are investigated using before-after incidence comparisons and case-control designs, respectively. Mortality is assessed using a prospective population cohort. Cost-effectiveness evaluation is nested within the case-control studies. We describe platform characteristics including strengths and weaknesses for conducting vaccine evaluations. DISCUSSION: Integrating data from individual level and ecological methods across multiple sites provides comprehensive information for policymakers on programme impact and vaccine effectiveness including changes in serotype/genotype distribution over time. Challenges to robust vaccine evaluation in real-world conditions include: vaccination ascertainment; pre-existing rapid decline in mortality and pneumococcal disease in the context of non-vaccine interventions; and the maintenance of completeness and quality of reporting at scale and over time. In observational non-randomised designs ascertainment of vaccine status may be biased particularly in infants with fatal outcomes. In the context of multiple population level interventions targeting study endpoints attribution of reduced incidence to vaccine impact may be flawed. Providing evidence from several independent but complementary studies will provide the greatest confidence in assigning impact. Welcome declines in disease incidence and in child mortality make accrual of required sample sizes difficult, necessitating large studies to detect the relatively small but potentially significant contribution of vaccines to mortality prevention. Careful evaluation of vaccine effectiveness and impact in such settings is critical to sustaining support for vaccine programmes. Our evaluation platform covers a large population with a high prevalence of HIV and malnutrition and its findings will be relevant to other settings in sub-Saharan Africa. |
First use of a serogroup B meningococcal vaccine in the US in response to a university outbreak
McNamara LA , Shumate AM , Johnsen P , MacNeil JR , Patel M , Bhavsar T , Cohn AC , Dinitz-Sklar J , Duffy J , Finnie J , Garon D , Hary R , Hu F , Kamiya H , Kim HJ , Kolligian J Jr , Neglia J , Oakley J , Wagner J , Wagner K , Wang X , Yu Y , Montana B , Tan C , Izzo R , Clark TA . Pediatrics 2015 135 (5) 798-804 BACKGROUND: In 2013-2014, an outbreak of serogroup B meningococcal disease occurred among persons linked to a New Jersey university (University A). In the absence of a licensed serogroup B meningococcal (MenB) vaccine in the United States, the Food and Drug Administration authorized use of an investigational MenB vaccine to control the outbreak. An investigation of the outbreak and response was undertaken to determine the population at risk and assess vaccination coverage. METHODS: The epidemiologic investigation relied on compilation and review of case and population data, laboratory typing of meningococcal isolates, and unstructured interviews with university staff. Vaccination coverage data were collected during the vaccination campaign held under an expanded-access Investigational New Drug protocol. RESULTS: Between March 25, 2013, and March 10, 2014, 9 cases of serogroup B meningococcal disease occurred in persons linked to University A. Laboratory typing results were identical for all 8 isolates available. Through May 14, 2014, 89.1% coverage with the 2-dose vaccination series was achieved in the target population. From the initiation of MenB vaccination through February 1, 2015, no additional cases of serogroup B meningococcal disease occurred in University A students. However, the ninth case occurred in March 2014 in an unvaccinated close contact of University A students. CONCLUSIONS: No serogroup B meningococcal disease cases occurred in persons who received 1 or more doses of 4CMenB vaccine, suggesting 4CMenB may have protected vaccinated individuals from disease. However, the ninth case demonstrates that carriage of serogroup B Neisseria meningitidis among vaccinated persons was not eliminated. |
Immunogenicity of poliovirus vaccines in chronically malnourished infants: a randomized controlled trial in Pakistan
Saleem AF , Mach O , Quadri F , Khan A , Bhatti Z , Rehman NU , Zaidi S , Weldon WC , Oberste SM , Salama M , Sutter RW , Zaidi AK . Vaccine 2015 33 (24) 2757-63 Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9-12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV+IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n=386), 73.6% (n=332), and 70.7% (n=319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n=448), 87.0% (n=441) and 83.6% (n=397) in the normally nourished group (p<0.05). Children had previously received 9-10 doses of bOPV (80%) or tOPV (20%). One dose of IPV+bOPV given to malnourished children increased their serological protection (PV1, n=201, 97.6%; PV2, n=198, 96.1% and PV3, n=189, 91.7%) to parity with normally nourished children who had not received IPV (p=<0.001). Seroconversion and boosting for all three serotypes was significantly more frequent in children who received IPV+bOPV than in those with bOPV only (p<0.001) in both strata. Shedding of polioviruses in stool did not differ between study groups and ranged from 2.4% (n=5) to 7.1% (n=15). In malnourished children the shedding was reduced after bOPV+IPV compared to bOPV only. Chronically malnourished infants were more likely to be unprotected against polioviruses than normal infants. bOPV+IPV helped close the immunity gap better than bOPV alone. |
Concurrent and cross-season protection of inactivated influenza vaccine against A(H1N1)pdm09 illness among young children: 2012-2013 case-control evaluation of influenza vaccine effectiveness
Fu C , Xu J , Lin J , Wang M , Li K , Ge J , Thompson MG . Vaccine 2015 33 (25) 2917-21 In 2012-2013, we examined 1729 laboratory-confirmed A(H1N1)pdm09 influenza cases matched 1:1 with healthy controls and estimated influenza vaccine effectiveness (VE) for trivalent inactivated influenza vaccine (IIV3) to be 67% (95% confidence interval=58-74%) for ages 8 months to 6 years old. Among children aged 8-35 months old, VE for fully vaccinated children (73%, 60-81%) was significantly higher than VE for partially vaccinated children (55%, 33-70%). Significant cross-season protection from prior IIV3 was noted, including VE of 31% (8-48%) from IIV3 received in 2010-2011 against influenza illness in 2012--2013 without subsequent boosting doses. |
Using electronic clinical quality measure reporting for public health surveillance
Heisey-Grove D , Wall HK , Helwig A , Wright JS . MMWR Morb Mortal Wkly Rep 2015 64 (16) 439-42 By June 2013, three fourths of office-based practicing physicians in the United States had adopted some form of electronic health record (EHR) system. With greater EHR use, more health data are linked with available patient demographic information in a format that is easily retrievable and collected at the point of care. This highlights the potential of electronic clinical quality measure (CQM) reporting data for use in monitoring population health for those receiving health care services. To assess this possibility, electronic CQM data that were submitted to the Medicare EHR Incentive Program were analyzed to assess provider progress toward achieving blood pressure control among their patients with hypertension. Approximately 63,000 health care providers reported at least 1 time over 3 years, representing approximately 17 million patients with hypertension. On average, 62% of patients with hypertension had controlled blood pressure. Use of EHR data for public health surveillance could streamline reporting, facilitating more timely and possibly more complete data collection in key areas of public health concern. |
Monitoring HIV testing in the United States: consequences of methodology changes to national surveys
Van Handel MM , Branson BM . PLoS One 2015 10 (4) e0125637 OBJECTIVE: In 2011, the National Health Interview Survey (NHIS), an in-person household interview, revised the human immunodeficiency virus (HIV) section of the survey and the Behavioral Risk Factor Surveillance System (BRFSS), a telephone-based survey, added cellphone numbers to its sampling frame. We sought to determine how these changes might affect assessment of HIV testing trends. METHODS: We used linear regression with pairwise contrasts with 2003-2013 data from NHIS and BRFSS to compare percentages of persons aged 18-64 years who reported HIV testing in landline versus cellphone-only households before and after 2011, when NHIS revised its in-person questionnaire and BRFSS added cellphone numbers to its telephone-based sample. RESULTS: In NHIS, the percentage of persons in cellphone-only households increased 13-fold from 2003 to 2013. The percentage ever tested for HIV was 6%-10% higher among persons in cellphone-only than landline households. The percentage ever tested for HIV increased significantly from 40.2% in 2003 to 45.0% in 2010, but was significantly lower in 2011 (40.6%) and 2012 (39.7%). In BRFSS, the percentage ever tested decreased significantly from 45.9% in 2003 to 40.2% in 2010, but increased to 42.9% in 2011 and 43.5% in 2013. CONCLUSIONS: HIV testing estimates were lower after NHIS questionnaire changes but higher after BRFSS methodology changes. Data before and after 2011 are not comparable, complicating assessment of trends. |
Uncovering a missing demographic in trauma registries: epidemiology of trauma among American Indians and Alaska Natives in Washington State
Hoopes MJ , Dankovchik J , Weiser T , Cheng T , Bigback K , Knaster ES , Sugerman DE . Inj Prev 2015 21 (5) 335-43 BACKGROUND: The objectives of this study were to evaluate racial misclassification in a statewide trauma registry and to describe the epidemiology of trauma among the Washington American Indian and Alaska Native (AI/AN) population. METHODS: We performed probabilistic record linkage between the Washington Trauma Registry (2005-2009) and Northwest Tribal Registry, a dataset of known AI/AN. AI/AN patients were compared with caucasians on demographic, injury and clinical outcome factors. A multivariable model estimated odds of mortality. RESULTS: Record linkage increased ascertainment of AI/AN cases in the trauma registry 71%, from 1777 to 3039 cases. Compared with caucasians, AI/AN trauma patients were younger (mean age=36 vs 47 years, p<0.001) and more commonly male (66.5% vs 61.2%, p<0.001). AI/AN experienced more intentional injuries (suicide or homicide: 20.1% vs 6.7%, p<0.001), a higher proportion of severe traumatic brain injury (20.7% vs 16.8%, p=0.004) and were less likely than caucasians to use safety equipment such as seat belts/airbags (53.9% vs 76.7%, p<0.001). ISSs were similar (ISS >15: 21.4% vs 20.5%, p=0.63), and no difference was observed in mortality after adjustment for covariates (p=0.58). CONCLUSIONS: Linkage to a state trauma registry improved data quality by correcting racial misclassification, allowing for a comprehensive description of injury patterns for the AI/AN population. AI/AN sustained more severe injuries with similar postinjury outcomes to caucasians. Future efforts should focus on primary prevention for this population, including increased use of seat belts and child safety seats and reduction of interpersonal violence and suicide. |
Longitudinal mediators of relations between family violence and adolescent dating aggression perpetration
Reyes HLM , Foshee VA , Fortson BL , Valle LA , Breiding MJ , Merrick MT . J Marriage Fam 2015 77 (7) 1016-1030 Few longitudinal studies have examined the pathways through which family violence leads to dating aggression. In the current study the authors used 3 waves of data obtained from 8th- and 9th-grade adolescents (N=1,965) to examine the hypotheses that the prospective relationship between witnessing family violence and directly experiencing violence and physical dating aggression perpetration is mediated by 3 constructs: (a) normative beliefs about dating aggression (norms), (b) anger dysregulation, and (c) depression. Results from cross-lagged regression models suggest that the relationship between having been hit by an adult and dating aggression is mediated by changes in norms and anger dysregulation, but not depression. No evidence of indirect effects from witnessing family violence to dating aggression was found through any of the proposed mediators. Taken together, the findings suggest that anger dysregulation and normative beliefs are potential targets for dating abuse prevention efforts aimed at youth who have directly experienced violence. |
Tight junction disruption by cadmium in an in vitro human airway tissue model
Cao X , Lin H , Muskhelishvili L , Latendresse J , Richter P , Heflich RH . Respir Res 2015 16 (1) 30 BACKGROUND: The cadmium (Cd) present in air pollutants and cigarette smoke has the potential of causing multiple adverse health outcomes involving damage to pulmonary and cardiovascular tissue. Injury to pulmonary epithelium may include alterations in tight junction (TJ) integrity, resulting in impaired epithelial barrier function and enhanced penetration of chemicals and biomolecules. Herein, we investigated mechanisms involved in the disruption of TJ integrity by Cd exposure using an in vitro human air-liquid-interface (ALI) airway tissue model derived from normal primary human bronchial epithelial cells. METHODS: ALI cultures were exposed to noncytotoxic doses of CdCl2 basolaterally and TJ integrity was measured by Trans-Epithelial Electrical Resistance (TEER) and immunofluorescence staining with TJ markers. PCR array analysis was used to identify genes involved with TJ collapse. To explore the involvement of kinase signaling pathways, cultures were treated with CdCl2 in the presence of kinase inhibitors specific for cellular Src or Protein Kinase C (PKC). RESULTS: Noncytotoxic doses of CdCl2 resulted in the collapse of barrier function, as demonstrated by TEER measurements and Zonula occludens-1 (ZO-1) and occludin staining. CdCl2 exposure altered the expression of several groups of genes encoding proteins involved in TJ homeostasis. In particular, down-regulation of select junction-interacting proteins suggested that a possible mechanism for Cd toxicity involves disruption of the peripheral junctional complexes implicated in connecting membrane-bound TJ components to the actin cytoskeleton. Inhibition of kinase signaling using inhibitors specific for cellular Src or PKC preserved the integrity of TJs, possibly by preventing occludin tyrosine hyperphosphorylation, rather than reversing the down-regulation of the junction-interacting proteins. CONCLUSIONS: Our findings indicate that acute doses of Cd likely disrupt TJ integrity in human ALI airway cultures both through occludin hyperphosphorylation via kinase activation and by direct disruption of the junction-interacting complex. |
Tungsten carbide-cobalt nanoparticles induce reactive oxygen species, AKT, ERK, AP-1, NF-kappaB, VEGF, and angiogenesis
Liu LZ , Ding M , Zheng JZ , Zhu Y , Fenderson BA , Li B , Yu JJ , Jiang BH . Biol Trace Elem Res 2015 166 (1) 57-65 Powder mixtures of tungsten carbide and metallic cobalt (WC-Co) are widely used in various products. Nanoparticles are engineered structures with at least one dimension of 100 nm or smaller. WC-Co is known to be associated with lung injury and diseases. Angiogenesis is a key process during vasculature, carcinogenesis, recovery of injury, and inflammatory diseases. However, the cellular effects of WC-Co nanoparticles on angiogenesis remain to be elucidated. In this study, we investigated angiogenic response and relative mechanisms after exposure to WC-Co nanoparticles. Our results showed that WC-Co nanoparticles at 5 mug/cm2 induced ROS production which activated AKT and ERK1/2 signaling pathways in lung epithelial cells by reactive oxygen species (ROS) staining and immunoblotting; WC-Co treatment also increased transcriptional activation of AP-1, NF-kappaB, and VEGF by reporter assay. Further studies demonstrated that ROS are upstream molecules of AKT and ERK signaling pathways; the activation of AP-1, NF-kappaB, and VEGF was through ROS generation, AKT and ERK1/2 activation. In addition, WC-Co nanoparticles affected the cells to induce angiogenesis by chicken chorioallantoic membrane (CAM) assay. These results illustrate that exposure to WC-Co nanoparticles induces angiogenic response by activating ROS, AKT, and ERK1/2 signaling pathways and the downstream molecules and elucidate the potential molecular mechanisms during this process. This information may be useful for preventing potential damage from nanoparticle exposure in the future. |
Laboratory-acquired vaccinia virus infection in a recently immunized person - Massachusetts, 2013
Hsu CH , Farland J , Winters T , Gunn J , Caron D , Evans J , Osadebe L , Bethune L , McCollum AM , Patel N , Wilkins K , Davidson W , Petersen B , Barry MA . MMWR Morb Mortal Wkly Rep 2015 64 (16) 435-8 On November 26, 2013, the CDC poxvirus laboratory was notified by the Boston Public Health Commission (BPHC) of an inadvertent inoculation of a recently vaccinated (ACAM2000 smallpox vaccine) laboratory worker with wild type vaccinia virus (VACV) Western Reserve. A joint investigation by CDC and BPHC confirmed orthopoxvirus infection in the worker, who had reported a needle stick in his thumb while inoculating a mouse with VACV. He experienced a non-tender, red rash on his arm, diagnosed at a local emergency department as cellulitis. He subsequently developed a necrotic lesion on his thumb, diagnosed as VACV infection. Three weeks after the injury, the thumb lesion was surgically debrided and at 2 months post-injury, the skin lesion had resolved. The investigation confirmed that the infection was the first reported VACV infection in the United States in a laboratory worker vaccinated according to the Advisory Committee on Immunization Practices (ACIP) recommendations. The incident prompted the academic institution to outline biosafety measures for working with biologic agents, such as biosafety training of laboratory personnel, vaccination (if appropriate), and steps in incident reporting. Though vaccination has been shown to be an effective measure in protecting personnel in the laboratory setting, this case report underscores the importance of proper safety measures and incident reporting. |
Method for the determination of ammonium in cigarette tobacco using ion chromatography
Watson CV , Valentin-Blasini L , Damian M , Watson CH . Regul Toxicol Pharmacol 2015 72 (2) 266-70 Ammonia and other alkaline substances have been postulated to be important in cigarette design. The most significant potential contribution of ammonia is a possible interaction with the native, protonated nicotine in the smoke. Ammonia is more alkaline than nicotine and could facilitate a shift in the acid/base equilibrium where a fraction of the total nicotine converts to the more lipophilic, non-protonated form. This non-protonated, or free-base, form of nicotine absorbs more efficiently across membranes, resulting in more rapid delivery to the smoker's bloodstream. Ammonia and other potential ammonia sources, such as additives like diammonium phosphate, could influence the acid-base dynamics in cigarette smoke and ultimately the rate of nicotine delivery. To examine and characterize the ammonia content in modern cigarettes, we developed a fast, simple and reliable ion chromatography based method to measure extractable ammonia levels in cigarette filler. This approach has minimal sample preparation and short run times to achieve high sample throughput. We quantified ammonia levels in tobacco filler from 34 non-mentholated cigarette brands from 3 manufacturers to examine the ranges found across a convenience sampling of popular, commercially available domestic brands and present figures of analytical merit here. Ammonia levels ranged from approximately 0.9 to 2.4 mg per gram of cigarette filler between brands and statistically significance differences were observed between brands and manufacturers. Our findings suggest that ammonia levels vary by brand and manufacturer; thus in domestic cigarettes ammonia could be considered a significant design feature because of the potential influence on smoke chemistry. |
mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma after multi-walled carbon nanotube inhalation exposure in mice
Snyder-Talkington BN , Dong C , Sargent LM , Porter DW , Staska LM , Hubbs AF , Raese R , McKinney W , Chen BT , Battelli L , Lowry DT , Reynolds SH , Castranova V , Qian Y , Guo NL . J Appl Toxicol 2015 36 (1) 161-74 Inhalation exposure to multi-walled carbon nanotubes (MWCNT) in mice results in inflammation, fibrosis and the promotion of lung adenocarcinoma; however, the molecular basis behind these pathologies is unknown. This study determined global mRNA and miRNA profiles in whole blood from mice exposed by inhalation to MWCNT that correlated with the presence of lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma. Six-week-old, male, B6C3F1 mice received a single intraperitoneal injection of either the DNA-damaging agent methylcholanthrene (MCA, 10 microg g-1 body weight) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5 mg m-3 , 5 hours per day, 5 days per week) or filtered air (control) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for the development of pathological changes in the lung, and whole blood was collected and analyzed using microarray analysis for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up- or down-regulated in animals developing pathological changes in the lung after MCA/corn oil administration followed by MWCNT/air inhalation, including fcrl5 and miR-122-5p in the presence of hyperplasia, mthfd2 and miR-206-3p in the presence of fibrosis, fam178a and miR-130a-3p in the presence of bronchiolo-alveolar adenoma, and il7r and miR-210-3p in the presence of bronchiolo-alveolar adenocarcinoma, among others. The changes in miRNA and mRNA expression, and their respective regulatory networks, identified in this study may potentially serve as blood biomarkers for MWCNT-induced lung pathological changes. |
Optimization of LipL32 PCR assay for increased sensitivity in diagnosing leptospirosis
Galloway RL , Hoffmaster AR . Diagn Microbiol Infect Dis 2015 82 (3) 199-200 Early diagnosis of leptospirosis in humans is critical with regard to initiation of appropriate treatment; however, the gold standard serological test cannot detect antibodies until nearly a week after symptom onset. PCR has been shown to be sensitive and specific in the early phase of leptospirosis. Previously, we developed and validated a TaqMan PCR assay targeting lipL32. We reoptimized and validated this assay using PerfeCTa(R) qPCR ToughMix(R), Low ROX (Quanta Biosciences, Gaithersburg, MD, USA). For optimization with the new mix, the final primer concentrations were increased from 0.5mumol/L to 0.9mumol/L compared to our previous assay, and the probe concentration increased from 0.1mumol/L to 0.125mumol/L. This newly optimized assay resulted in a lower limit of detection and increased diagnostic sensitivity. Here, we present the performance data of the improved assay and describe several clinical cases that were initially negative but tested positive using the optimized assay. |
Potential explosion hazard of carbonaceous nanoparticles: explosion parameters of selected materials
Turkevich LA , Dastidar AG , Hachmeister Z , Lim M . J Hazard Mater 2015 295 97-103 Following a previous explosion screening study, we have conducted concentration and ignition energy scans on several carbonaceous nanopowders: fullerene, SWCNT, carbon black, MWCNT, graphene, CNF, and graphite. We have measured minimum explosive concentration (MEC), minimum ignition energy (MIE), and minimum ignition temperature (MITcloud) for these materials. The nanocarbons exhibit MEC ~101-102g/m3, comparable to the MEC for coals and for fine particle carbon blacks and graphites. The nanocarbons are confirmed mainly to be in the St-1 explosion class, with fullerene, at KSt~200bar-m/s, borderline St-1/St-2. We estimate MIE~102-103J, an order of magnitude higher than the MIE for coals but an order of magnitude lower than the MIE for fine particle graphites. While the explosion severity of the nanocarbons is comparable to that of the coals, their explosion susceptibility (ease of ignition) is significantly less (i.e., the nanocarbons have higher MIEs than do the coals); by contrast, the nanocarbons exhibit similar explosion severity to the graphites but enhanced explosion susceptibility (i.e., the nanocarbons have lower MIEs than do the graphites). MITcloud>550 degrees C, comparable to that of the coals and carbon blacks. |
Enhanced detection of type C botulinum neurotoxin by the Endopep-MS assay through optimization of peptide substrates
Wang D , Krilich J , Baudys J , Barr JR , Kalb SR . Bioorg Med Chem 2015 23 (13) 3667-73 It is essential to have a simple, quick and sensitive method for the detection and quantification of botulinum neurotoxins, the most toxic substances and the causative agents of botulism. Type C botulinum neurotoxin (BoNT/C) represents one of the seven members of distinctive BoNT serotypes (A to G) that cause botulism in animals and avians. Here we report the development of optimized peptide substrates for improving the detection of BoNT/C and /CD mosaic toxins using an Endopep-MS assay, a mass spectrometry-based method that is able to rapidly and sensitively detect and differentiate all types of BoNTs by extracting the toxin with specific antibodies and detecting the unique cleavage products of peptide substrates. Based on the sequence of a short SNAP-25 peptide, we conducted optimization through a comprehensive process including length determination, terminal modification, single and multiple amino acid residue substitution, and incorporation of unnatural amino acid residues. Our data demonstrate that an optimal peptide provides a more than 200-fold improvement over the substrate currently used in the Endopep-MS assay for the detection of BoNT/C1 and /CD mosaic. Using the new substrate in a four-hour cleavage reaction, the limit of detection for the BoNT/C1 complex spiked in buffer, serum and milk samples was determined to be 0.5, 0.5 and 1mouseLD50/mL, respectively, representing a similar or higher sensitivity than that obtained by traditional mouse bioassay. |
Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2
Pfeiffer CM , Sternberg MR , Fazili Z , Lacher DA , Zhang M , Johnson CL , Hamner HC , Bailey RL , Rader JI , Yamini S , Berry RJ , Yetley EA . Br J Nutr 2015 113 (12) 1-13 Serum and erythrocyte (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured the serum folate forms (5-methyltetrahydrofolate (5-methylTHF), unmetabolised folic acid (UMFA), non-methyl folate (sum of tetrahydrofolate (THF), 5-formyltetrahydrofolate (5-formylTHF), 5,10-methenyltetrahydrofolate (5,10-methenylTHF)) and MeFox (5-methylTHF oxidation product)) by HPLC-MS/MS and RBC total folate by microbiologic assay in US population ≥ 1 year (n approximately 7500) participating in the National Health and Nutrition Examination Survey 2011-2. Data analysis for serum total folate was conducted including and excluding MeFox. Concentrations (geometric mean; detection rate) of 5-methylTHF (37.5 nmol/l; 100 %), UMFA (1.21 nmol/l; 99.9 %), MeFox (1.53 nmol/l; 98.8 %), and THF (1.01 nmol/l; 85.2 %) were mostly detectable. 5-FormylTHF (3.6 %) and 5,10-methenylTHF (4.4 %) were rarely detected. The biggest contributor to serum total folate was 5-methylTHF (86.7 %); UMFA (4.0 %), non-methyl folate (4.7 %) and MeFox (4.5 %) contributed smaller amounts. Age was positively related to MeFox, but showed a U-shaped pattern for other folates. We generally noted sex and race/ethnic biomarker differences and weak (Spearman's r< 0.4) but significant (P< 0.05) correlations with physiological and lifestyle variables. Fasting, kidney function, smoking and alcohol intake showed negative associations. BMI and body surface area showed positive associations with MeFox but negative associations with other folates. All biomarkers showed significantly higher concentrations with recent folic acid-containing dietary supplement use. These first-time population data for serum folate forms generally show similar associations with demographic, physiological and lifestyle variables as serum total folate. Patterns observed for MeFox may suggest altered folate metabolism dependent on biological characteristics. |
Antimicrobial activity of bismuth subsalicylate on Clostridium difficile, Escherichia coli O157:H7, norovirus, and other common enteric pathogens
Pitz AM , Park GW , Lee D , Boissy YL , Vinje J . Gut Microbes 2015 6 (2) 93-100 Previous studies have shown bismuth subsalicylate (BSS) has antimicrobial properties, but few studies have addressed the mechanism of action. Furthermore, following BSS ingestion other bismuth salts form throughout the gastrointestinal tract including bismuth oxychloride (BiOCl) that also act upon enteric pathogens. To further understand the antimicrobial activity of bismuth in infectious diarrhea, the antimicrobial effect of BSS and BiOCl on Clostridium difficile, Salmonella, Shigella, Shiga toxin-producing Escherichia coli strains and norovirus (NoV) were measured. Bacterial enteric pathogens in pure culture or in human fecal material were exposed to 35mg/ml BSS or BiOCl with or without a vehicle suspension. BSS and BiOCl treated samples were quantified and visualized by transmission electron microscopy. To measure the effect on NoV, reduction of infectious murine NoV (MNV), a surrogate for human NoV, and Norwalk virus RNA levels were measured by viral plaque assay and RT-qPCR, respectively. BSS and BiOCl reduced bacterial growth by 3-9 logs in all strains with majority resulting in populations of <10 cfu/ml within 24 h. Similar results were found when fecal material was included. Microscopy images detected bismuth on bacterial membranes and within the bacterial organisms at 30 min post-treatment. At 8.8mg/ml BSS and BiOCl reduced infectivity of MNV significantly by 2.7 and 2.0 log after 24 h of exposure. In addition, both BSS and BiOCl slightly reduced the level of Norwalk replicon-bearing cells suggesting that bismuth may inhibit NoV in vivo. Collectively, our results confirm and build on existing data that BSS has antimicrobial properties against a wide-range of diarrhea-causing pathogens. |
Comment on "Concerns with amplitude variation in calibrated audiometer systems in clinical simulations"
Byrne DC , Themann CL , Stephenson MR . Noise Health 2015 17 (76) 172 Barlow and colleagues addressed the important question of variation in pure-tone audiometric thresholds within and across audiometers in their article entitled “Concerns with Amplitude Variation in Calibrated Audiometer Systems in Clinical Simulations.”[1] We agree that the reliability of thresholds obtained across test systems and individuals is a vital concern when monitoring hearing health. However, we believe that a few important details are missing, which limits the validity of this study. | The authors reported, “Each of the audiometers had recently undergone certified traceable calibration by its recommended laboratory, meaning that the tone presentation from each should theoretically be identical” [page 300]. Ideally, this would be the case; however, it is not necessarily true. An audiometer is considered “in calibration” when its output is within a certain tolerance range. The International Electrotechnical Commission (IEC) 60645-1 standard allows a deviation of ± 3.7 dB from the indicated value at test frequencies from 125 Hz through 4000 Hz, and ±6.2 dB up to and including 8000 Hz. This means, for example, that an audiometer set to generate a 50-dB HL tone at 6000 Hz could produce anywhere from 43.8 dB HL to 56.2 dB HL and be considered “in calibration.” In some cases, the ±3.7 dB calibration tolerance (i.e., 7.4 dB range) at frequencies below 6000 Hz is close to the range of variation reported for the audiometers in this study. Without verifying that all four audiometers actually produced identical outputs, the measured differences cannot be assumed to be solely due to earphone placement. (Note: The allowable deviation according to American National Standards Institute (ANSI) standard S3.6 is ±3 dB at test frequencies from 125 Hz through 5000 Hz, and ± 5 dB at 6000 Hz and higher.) |
Comprehensive chemical characterization of rape tobacco products: nicotine, un-ionized nicotine, tobacco-specific n'-nitrosamines, polycyclic aromatic hydrocarbons, and flavor constituents
Stanfill SB , da Silva AL , Lisko JG , Lawler TS , Kuklenyik P , Tyx RE , Peuchen EH , Richter P , Watson CH . Food Chem Toxicol 2015 82 50-8 Rape, a diverse group of smokeless tobacco products indigenous to South America, is generally used as a nasal snuff and contains substantial amount of plant material with or without tobacco. Previously uncharacterized, rape contains addictive and harmful chemicals that may have public health implications for users. Here we report % moisture, pH and the levels of total nicotine, un-ionized nicotine, flavor-related compounds, tobacco-specific N-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for manufactured and hand-made rape. Most rape products were mildly acidic (pH 5.17 - 6.23) with total nicotine ranging from 6.32 to 47.6 milligram per gram of sample (mg/g). Calculated un-ionized nicotine ranged from 0.03 to 18.5 mg/g with the highest values associated with hand-made rapes (pH 9.75 - 10.2), which contain alkaline ashes. In tobacco-containing rapes, minor alkaloid levels and Fourier transform infrared spectra were used to confirm the presence of Nicotiana rustica, a high nicotine tobacco species. There was a wide concentration range of TSNAs and PAHs among the rapes analyzed. Several TSNAs and PAHs identified in the products are known or probable carcinogens according to the International Agency for Research in Cancer. Milligram quantities of some non-tobacco constituents, such as camphor, coumarin, and eugenol, warrant additional evaluation. |
Dissolution and biodurability: Important parameters needed for risk assessment of nanomaterials
Utembe W , Potgieter K , Stefaniak AB , Gulumian M . Part Fibre Toxicol 2015 12 (1) 11 Biopersistence and biodurability have the potential to influence the long-term toxicity and hence pathogenicity of particles that deposit in the body. Therefore, biopersistence and biodurability are considered to be important parameters needed for the risk assessment of particles and fibres. Dissolution, as a measure of biodurability, is dependent on the chemical and physical properties (size, surface area, etc.) of particles and fibres and also of the suspension medium including its ionic strength, pH, and temperature. In vitro dissolution tests can provide useful insights as to how particles and fibres may react in biological environments; particles and fibres that release ions at a higher rate when suspended in vitro in a specific simulated biological fluid will be expected to do so when they exist in a similar biological environment in vivo. Dissolution of particles and fibres can follow different reaction kinetics. For example, the majority of micro-sized particles and fibres follow zero-order reaction kinetics. In this case, although it is possible to calculate the half-time of a particle or fibre, such calculation will be dependent on the initial concentration of the investigated particle or fibre. Such dependence was eliminated in the shrinking sphere and fibre models where it was possible to estimate the lifetimes of particles and fibres as a measure of their biodurability. The latter models can be adapted for the dissolution studies of nanomaterials. However, the models may apply only to nanomaterials where their dissolution follows zero-order kinetics. The dissolution of most nanomaterials follows first-order kinetics where dependence on their initial concentration of the investigated nanomaterials is not required and therefore it is possible to estimate their half-times as a measure of their biodurability. In dissolution kinetics for micro-sized and nano-sized particles and fibres, knowledge of dissolution rate constants is necessary to understand biodurability. Unfortunately, many studies on dissolution of nanoparticles and nanofibres do not determine the dissolution rates and dissolution rate constants. The recommendation is that these parameters should be considered as part of the important descriptors of particle and fibre physicochemical properties, which in turn, will enable the determination of their biodurability. |
Screening for human immunodeficiency virus and other sexually transmitted diseases among U.S. women with prenatal care
Ross CE , Tao G , Patton M , Hoover KW . Obstet Gynecol 2015 125 (5) 1211-6 OBJECTIVE: To estimate prenatal sexually transmitted disease-human immunodeficiency virus (HIV) screening rates among insured women with prenatal care and the association of chlamydia and gonorrhea screening with Pap testing. METHODS: We estimated prenatal screening rates for syphilis, hepatitis B, HIV, chlamydia, and gonorrhea among women aged 15-44 years using a 2009-2010 U.S. administrative claims database that captures information for health services provided for both Medicaid- and commercially insured persons. Procedural and diagnostic codes were used to identify pregnant women with a live birth in 2010 with continuous insurance coverage at least 210 days before delivery and at least one typical prenatal blood test. Strengths of association between chlamydia and gonorrhea screening and Pap testing were measured using a chi test of independence. RESULTS: Among 98,709 Medicaid-insured pregnant women, 95,064 (96.3%) were screened for syphilis, 95,082 (96.3%) for hepatitis B, 81,339 (82.4%) for HIV, 82,047 (83.1%) for chlamydia, and 73,799 (74.8%) for gonorrhea. Among 266,012 commercially insured women, 260,079 (97.8%) were screened for syphilis, 257,675 (96.8%) for hepatitis B, 227,276 (85.4%) for HIV, 187,071 (70.3%) for chlamydia, and 182,400 (68.6%) for gonorrhea. Prenatal screening for chlamydia and gonorrhea among both groups of women was more likely to be performed if a Pap test was also done (P<.001). CONCLUSION: Prenatal screening for syphilis and hepatitis B was nearly universal among Medicaid- and commercially insured women; HIV screening rates were much lower and varied by insurance type and demographic characteristics. Chlamydia screening was suboptimal and most often occurred with Pap testing. LEVEL OF EVIDENCE: III. |
Trends in the prevalence of autism spectrum disorder, cerebral palsy, hearing loss, intellectual disability, and vision impairment, metropolitan Atlanta, 1991-2010
Van Naarden Braun K , Christensen D , Doernberg N , Schieve L , Rice C , Wiggins L , Schendel D , Yeargin-Allsopp M . PLoS One 2015 10 (4) e0124120 This study examined the prevalence and characteristics of autism spectrum disorder (ASD), cerebral palsy (CP), hearing loss (HL), intellectual disability (ID), and vision impairment (VI) over a 15-20 year time period, with specific focus on concurrent changes in ASD and ID prevalence. We used data from a population-based developmental disabilities surveillance program for 8-year-olds in metropolitan Atlanta. From 1991-2010, prevalence estimates of ID and HL were stable with slight increases in VI prevalence. CP prevalence was constant from 1993-2010. The average annual increase in ASD prevalence was 9.3% per year from 1996-2010, with a 269% increase from 4.2 per 1,000 in 1996 to 15.5 per 1,000 in 2010. From 2000-2010, the prevalence of ID without ASD was stable; during the same time, the prevalence of ASD with and without co-occurring ID increased by an average of 6.6% and 9.6% per year, respectively. ASD prevalence increases were found among both males and females, and among nearly all racial/ethnic subgroups and levels of intellectual ability. Average annual prevalence estimates from 1991-2010 underscore the significant community resources needed to provide early intervention and ongoing supports for children with ID (13.0 per 1,000), CP, (3.5 per 1,000), HL (1.4 per 1,000) and VI (1.3 in 1,000), with a growing urgency for children with ASD. |
Maternal prepregnancy body mass index and child psychosocial development at 6 years of age
Jo H , Schieve LA , Sharma AJ , Hinkle SN , Li R , Lind JN . Pediatrics 2015 135 (5) e1198-209 BACKGROUND: Both obesity and developmental disabilities have increased in recent decades. Limited studies suggest associations between maternal prepregnancy obesity and child neurodevelopment. METHODS: The Infant Feeding Practices Study II, a US nationally distributed longitudinal study of maternal health and infant health and feeding practices, was conducted from 2005 to 2007. In 2012, mothers were recontacted for information on their children's health and development. We examined associations between maternal prepregnancy BMI and child psychosocial development in 1311 mother-child pairs included in this follow-up study. Children's development was assessed by maternal report of child psychosocial difficulties from the Strengths and Difficulties Questionnaire, past developmental diagnoses, and receipt of special needs services. RESULTS: Adjusting for sociodemographic factors, children of obese class II/III mothers (BMI >35.0) had increased odds of emotional symptoms (adjusted odds ratio [aOR] 2.24; 95% confidence interval [CI], 1.27-3.98), peer problems (aOR 2.07; 95% CI, 1.26-3.40), total psychosocial difficulties (aOR 2.17; 95% CI, 1.24-3.77), attention-deficit/hyperactivity disorder diagnosis (aOR 4.55; 95% CI, 1.80-11.46), autism or developmental delay diagnosis (aOR 3.13; 95% CI, 1.10-8.94), receipt of speech language therapy (aOR 1.93; 95% CI, 1.18-3.15), receipt of psychological services (aOR 2.27; 95% CI, 1.09-4.73), and receipt of any special needs service (aOR 1.99; 95% CI, 1.33-2.97) compared with children of normal weight mothers (BMI 18.5-24.9). Adjustment for potential causal pathway factors including pregnancy weight gain, gestational diabetes, breastfeeding duration, postpartum depression, and child's birth weight did not substantially affect most estimates. CONCLUSIONS: Children whose mothers were severely obese before pregnancy had increased risk for adverse developmental outcomes. |
Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines
Cordero AM , Crider KS , Rogers LM , Cannon MJ , Berry RJ . MMWR Morb Mortal Wkly Rep 2015 64 (15) 421-3 Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 microg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention. |
Impacts of a farmers' market incentive programme on fruit and vegetable access, purchase and consumption
Olsho LE , Payne GH , Walker DK , Baronberg S , Jernigan J , Abrami A . Public Health Nutr 2015 18 (15) 1-10 OBJECTIVE: The present study examines the impact of Health Bucks, a farmers market incentive programme, on awareness of and access to farmers markets, and fruit and vegetable purchase and consumption in low-income New York City neighbourhoods. DESIGN: The evaluation used two primary data collection methods: (i) an on-site point-of-purchase survey of farmers market shoppers; and (ii) a random-digit-dial telephone survey of residents in neighbourhoods where the programme operates. Additionally, we conducted a quasi-experimental analysis examining differential time trends in consumption before and after programme introduction using secondary Community Health Survey (CHS) data. SETTING: New York City farmers markets and communities. SUBJECTS: Farmers market shoppers (n 2287) completing point-of-purchase surveys in a representative sample of New York City farmers markets in 2010; residents (n 1025) completing random-digit-dial telephone survey interviews in 2010; and respondents (n 35 606) completing CHS interviews in 2002, 2004, 2008 and 2009. RESULTS: Greater Health Bucks exposure was associated with: (i) greater awareness of farmers markets; (ii) increased frequency and amount of farmers market purchases; and (iii) greater likelihood of a self-reported year-over-year increase in fruit and vegetable consumption. However, our CHS analysis did not detect impacts on consumption. CONCLUSIONS: While our study provides promising evidence that use of farmers market incentives is associated with increased awareness and use of farmers markets, additional research is needed to better understand impacts on fruit and vegetable consumption. |
Work-related asthma cluster at a syntactic foam manufacturing facility - Massachusetts 2008-2013
Casey M , Stanton ML , Cummings KJ , Pechter E , Fitzsimmons K , LeBouf RF , Schuler CR , Kreiss K . MMWR Morb Mortal Wkly Rep 2015 64 (15) 411-4 Work-related asthma is asthma that is caused or exacerbated by exposure to specific substances in the workplace. Approximately 10%-16% of adult-onset asthma cases are attributable to occupational factors, and estimates of asthma exacerbated by work range from 13% to 58%. During 2008-2012, the Massachusetts Department of Public Health received nine reports of work-related asthma among workers at a facility that manufactured syntactic foam used for flotation in the offshore oil and gas industry. These reports and a request from facility employees led to a CDC health hazard evaluation during 2012-2013 in which CDC reviewed records, toured the facility, and administered a questionnaire to current employees. Investigators found that workers' risk for asthma increased substantially after hire, possibly because of known asthma triggers (i.e., asthmagens) used in production. The company has since initiated efforts to reduce employee exposures to these substances. This cluster of work-related asthma was identified through CDC-funded, state-based surveillance and demonstrates complementary state and federal investigations. |
Occupational traumatic injuries among workers in health care facilities - United States, 2012-2014
Gomaa AE , Tapp LC , Luckhaupt SE , Vanoli K , Sarmiento RF , Raudabaugh WM , Nowlin S , Sprigg SM . MMWR Morb Mortal Wkly Rep 2015 64 (15) 405-10 In 2013, one in five reported nonfatal occupational injuries occurred among workers in the health care and social assistance industry, the highest number of such injuries reported for all private industries. In 2011, U.S. health care personnel experienced seven times the national rate of musculoskeletal disorders compared with all other private sector workers. To reduce the number of preventable injuries among health care personnel, CDC's National Institute for Occupational Safety and Health (NIOSH), with collaborating partners, created the Occupational Health Safety Network (OHSN) to collect detailed injury data to help target prevention efforts. OHSN, a free, voluntary surveillance system for health care facilities, enables prompt and secure tracking of occupational injuries by type, occupation, location, and risk factors. This report describes OHSN and reports on current findings for three types of injuries. A total of 112 U.S. facilities reported 10,680 OSHA-recordable* patient handling and movement (4,674 injuries); slips, trips, and falls (3,972 injuries); and workplace violence (2,034 injuries) injuries occurring from January 1, 2012-September 30, 2014. Incidence rates for patient handling; slips, trips, and falls; and workplace violence were 11.3, 9.6, and 4.9 incidents per 10,000 worker-months,dagger respectively. Nurse assistants and nurses had the highest injury rates of all occupations examined. Focused interventions could mitigate some injuries. Data analyzed through OHSN identify where resources, such as lifting equipment and training, can be directed to potentially reduce patient handling injuries. Using OHSN can guide institutional and national interventions to protect health care personnel from common, disabling, preventable injuries. |
Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010-2012.
Baldeviano GC , Okoth SA , Arrospide N , Gonzalez RV , Sanchez JF , Macedo S , Conde S , Tapia LL , Salas C , Gamboa D , Herrera Y , Edgel KA , Udhayakumar V , Lescano AG . Emerg Infect Dis 2015 21 (5) 797-803 During 2010-2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998-2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events. |
Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005-2013.
Morris U , Xu W , Msellem MI , Schwartz A , Abass A , Shakely D , Cook J , Bhattarai A , Petzold M , Greenhouse B , Ali AS , Bjorkman A , Froberg G , Martensson A . Infect Genet Evol 2015 33 110-7 BACKGROUND: Improved understanding of the asymptomatic malaria parasite reservoir is a prerequisite to pursue malaria elimination efforts. We therefore characterised temporal trends and transporter polymorphisms in asymptomatic Plasmodium infections during the transition from high to low transmission in Zanzibar. METHODS: Healthy individuals participating in cross-sectional surveys conducted 2005-2013 were screened for asymptomatic malaria by PCR. Complexity/diversity of infection and transporter polymorphisms were assessed in Plasmodium falciparum positive samples. Symptomatic samples were included for comparison of polymorphisms in 2013. RESULTS: PCR-determined parasite prevalence declined from 21.1% (CI95% 17.4-24.9) to 2.3% (CI95% 1.7-2.9) from 2005 to 2013. P. falciparum remained the predominant species; prevalence was highest in children and young adults aged 5-25years. Parasite densities and complexity of infection, but not population genetic diversity of P. falciparum, decreased from 2005-2009. pfcrt 76T (99.2-64.7%, p<0.001) and pfmdr1 86Y frequencies (89.4-66.7%, p=0.03) decreased over time. Pfmdr1 (a.a.86,184,1246) YYY and YYD haplotypes were more frequent in asymptomatic than symptomatic infections in 2013 (p<0.001). CONCLUSIONS: There is a declining, albeit persistent, reservoir of parasites present at low-densities in asymptomatic individuals in Zanzibar. This study revealed important characteristics of the remaining parasite population, including intriguing temporal trends in molecular markers associated with antimalarial resistance, which need to be further investigated. |
Canine infections with Onchocerca lupi nematodes, United States, 2011-2014
Otranto D , Giannelli A , Latrofa MS , Dantas-Torres F , Trumble NS , Chavkin M , Kennard G , Eberhard ML , Bowman DD . Emerg Infect Dis 2015 21 (5) 868-71 Infections with Onchocerca lupi nematodes are diagnosed sporadically in the United States. We report 8 cases of canine onchocercosis in Minnesota, New Mexico, Colorado, and Florida. Identification of 1 cytochrome c oxidase subunit 1 gene haplotype identical to 1 of 5 from Europe suggests recent introduction of this nematode into the United States. |
Bayesian modeling and analysis for gradients in spatiotemporal processes.
Quick H , Banerjee S , Carlin BP . Biometrics 2015 71 (3) 575-84 Stochastic process models are widely employed for analyzing spatiotemporal datasets in various scientific disciplines including, but not limited to, environmental monitoring, ecological systems, forestry, hydrology, meteorology, and public health. After inferring on a spatiotemporal process for a given dataset, inferential interest may turn to estimating rates of change, or gradients, over space and time. This manuscript develops fully model-based inference on spatiotemporal gradients under continuous space, continuous time settings. Our contribution is to offer, within a flexible spatiotemporal process model setting, a framework to estimate arbitrary directional gradients over space at any given timepoint, temporal derivatives at any given spatial location and, finally, mixed spatiotemporal gradients that reflect rapid change in spatial gradients over time and vice-versa. We achieve such inference without compromising on rich and flexible spatiotemporal process models and use nonseparable covariance structures. We illustrate our methodology using a simulated data example and subsequently apply it to a dataset of daily PM2.5 concentrations in California, where the spatiotemporal gradient process reveals the effects of California's unique topography on pollution and detects the aftermath of a devastating series of wildfires. |
Acetyl fentanyl, a novel fentanyl analog, causes 14 overdose deaths in Rhode Island, March-May 2013
Lozier MJ , Boyd M , Stanley C , Ogilvie L , King E , Martin C , Lewis L . J Med Toxicol 2015 11 (2) 208-17 From 2000 to 2011, the rate of death from unintentional drug poisoning in the USA more than doubled from 4.1 per 100,000 to 10.6 per 100,000, respectively [1]. Further, from 1999 to 2011, drug overdose deaths involving opioids quadrupled from 4030 to 16,917 [1]. Nationally, since 2009, more people have died each year from drug poisoning than from motor vehicle crashes [1]. In fact, overdose is the leading cause of adult unintentional injury death in Rhode Island, which is one of 30 states where overdose mortality exceeded motor vehicle collision mortality in 2010 [2]. | The major driver of the increase in drug overdose deaths is pharmaceutical opioids. In 2010, 60 % of the unintentional drug poisoning deaths in the USA were caused by pharmaceuticals, and 75 % of the fatal pharmaceutical overdoses were caused by opioids [3]. Nationally, heroin use doubled from 2003 to 2012, and from 2002 to 2011, drug poisoning deaths involving heroin more than doubled from 2089 to 4397, respectively [4, 5]. In Rhode Island, overdose deaths caused by illicit drugs increased so much during 2011–2013 that it overtook fatal pharmaceutical overdoses, which remained steady during the same time period [6]. | Fentanyl (N-(1-(2-phenethyl)-4-piperidinyl-N-phenyl-propanamide) is a synthetic opioid first synthesized by Janssen Pharmaceuticals in the 1960s and used medicinally since 1968. It is estimated to be between 80 and 100 times more potent than morphine [7, 8] and has over 200 chemical derivatives, some of which have been used recreationally or implicated in heroin adulteration in the past. The first fentanyl derivatives synthesized in the early 1970s showed similar pharmacokinetics but significantly different potencies. By the early 1980s, clandestinely produced synthetic fentanyl and fentanyl derivatives were becoming available on the black market [7, 9]. The speed of onset and potency of these drugs made them attractive to opioid users but also made them more dangerous. Fentanyl derivatives can be a few to hundreds of times more potent than heroin, and if users unknowingly obtain and administer packages sold as heroin but containing a more potent fentanyl derivative, this can lead to inadvertent overdose and death [10]. |
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