Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-20 (of 20 Records) |
Query Trace: Sung J[original query] |
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Transition to enteral triazole antifungal therapy for pediatric invasive candidiasis: Secondary analysis of a multicenter cohort study conducted by the Pediatric Fungal Network
Bucayu RFT , Boge CLK , Yildirim I , Avilés-Robles M , Vora SB , Berman DM , Sharma TS , Sung L , Castagnola E , Palazzi DL , Danziger-Isakov L , Yin DE , Roilides E , Maron G , Tribble AC , Soler-Palacin P , López-Medina E , Romero J , Belani K , Arrieta AC , Carlesse F , Nolt D , Halasa N , Dulek D , Rajan S , Muller WJ , Ardura MI , Pong A , Gonzalez BE , Salvatore CM , Huppler AR , Aftandilian C , Abzug MJ , Chakrabarti A , Green M , Lutsar I , Knackstedt ED , Johnson SK , Steinbach WJ , Fisher BT , Wattier RL . J Pediatric Infect Dis Soc 2024 Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was success in 66 participants transitioned to enteral therapy. |
Effectiveness of bivalent mRNA COVID-19 vaccines in preventing COVID-19-related thromboembolic events among Medicare enrollees aged ≥65 years and those with end stage renal disease - United States, September 2022-March 2023
Payne AB , Novosad S , Wiegand RE , Najdowski M , Gomes DJ , Wallace M , Kelman JA , Sung HM , Zhang Y , Lufkin B , Chillarige Y , Link-Gelles R . MMWR Morb Mortal Wkly Rep 2024 73 (1) 16-23 COVID-19 has been associated with an increased risk for thromboembolic events, including ischemic stroke, venous thromboembolism, and myocardial infarction. Studies have reported lower rates of COVID-19-related thromboembolic events among persons who received the COVID-19 vaccine compared with persons who did not, but rigorous estimates of vaccine effectiveness (VE) in preventing COVID-19-related thromboembolic events are lacking. This analysis estimated the incremental benefit of receipt of a bivalent mRNA COVID-19 vaccine after receiving an original monovalent COVID-19 vaccine. To estimate VE of a bivalent mRNA COVID-19 dose in preventing thromboembolic events compared with original monovalent COVID-19 vaccine doses only, two retrospective cohort studies were conducted among Medicare fee-for-service enrollees during September 4, 2022-March 4, 2023. Effectiveness of a bivalent COVID-19 vaccine dose against COVID-19-related thromboembolic events compared with that of original vaccine alone was 47% (95% CI = 45%-49%) among Medicare enrollees aged ≥65 years and 51% (95% CI = 39%-60%) among adults aged ≥18 years with end stage renal disease receiving dialysis. VE was similar among Medicare beneficiaries with immunocompromise: 46% (95% CI = 42%-49%) among adults aged ≥65 years and 45% (95% CI = 24%-60%) among those aged ≥18 years with end stage renal disease. To help prevent complications of COVID-19, including thromboembolic events, adults should stay up to date with COVID-19 vaccination. |
Annual report to the nation on the status of cancer, part 2: Early assessment of the COVID-19 pandemic's impact on cancer diagnosis
Negoita S , Chen HS , Sanchez PV , Sherman RL , Henley SJ , Siegel RL , Sung H , Scott S , Benard VB , Kohler BA , Jemal A , Cronin KA . Cancer 2023 130 (1) 117-127 BACKGROUND: With access to cancer care services limited because of coronavirus disease 2019 control measures, cancer diagnosis and treatment have been delayed. The authors explored changes in the counts of US incident cases by cancer type, age, sex, race, and disease stage in 2020. METHODS: Data were extracted from selected US population-based cancer registries for diagnosis years 2015-2020 using first-submission data from the North American Association of Central Cancer Registries. After a quality assessment, the monthly numbers of newly diagnosed cancer cases were extracted for six cancer types: colorectal, female breast, lung, pancreas, prostate, and thyroid. The observed numbers of incident cancer cases in 2020 were compared with the estimated numbers by calculating observed-to-expected (O/E) ratios. The expected numbers of incident cases were extrapolated using Joinpoint trend models. RESULTS: The authors report an O/E ratio <1.0 for major screening-eligible cancer sites, indicating fewer newly diagnosed cases than expected in 2020. The O/E ratios were lowest in April 2020. For every cancer site except pancreas, Asians/Pacific Islanders had the lowest O/E ratio of any race group. O/E ratios were lower for cases diagnosed at localized stages than for cases diagnosed at advanced stages. CONCLUSIONS: The current analysis provides strong evidence for declines in cancer diagnoses, relative to the expected numbers, between March and May of 2020. The declines correlate with reductions in pathology reports and are greater for cases diagnosed at in situ and localized stage, triggering concerns about potential poor cancer outcomes in the coming years, especially in Asians/Pacific Islanders. PLAIN LANGUAGE SUMMARY: To help control the spread of coronavirus disease 2019 (COVID-19), health care organizations suspended nonessential medical procedures, including preventive cancer screening, during early 2020. Many individuals canceled or postponed cancer screening, potentially delaying cancer diagnosis. This study examines the impact of the COVID-19 pandemic on the number of newly diagnosed cancer cases in 2020 using first-submission, population-based cancer registry database. The monthly numbers of newly diagnosed cancer cases in 2020 were compared with the expected numbers based on past trends for six cancer sites. April 2020 had the sharpest decrease in cases compared with previous years, most likely because of the COVID-19 pandemic. |
Adjunctive diagnostic studies completed following detection of candidemia in children: Secondary analysis of observed practice from a multicenter cohort study conducted by The Pediatric Fungal Network
Wattier RL , Bucayu RFT , Boge CLK , Ross RK , Yildirim I , Zaoutis TE , Palazzi DL , Vora SB , Castagnola E , Avilés-Robles M , Danziger-Isakov L , Tribble AC , Sharma TS , Arrieta AC , Maron G , Berman DM , Yin DE , Sung L , Green M , Roilides E , Belani K , Romero J , Soler-Palacin P , López-Medina E , Nolt D , Bin Hussain IZ , Muller WJ , Hauger SB , Halasa N , Dulek D , Pong A , Gonzalez BE , Abzug MJ , Carlesse F , Huppler AR , Rajan S , Aftandilian C , Ardura MI , Chakrabarti A , Hanisch B , Salvatore CM , Klingspor L , Knackstedt ED , Lutsar I , Santolaya ME , Shuster S , Johnson SK , Steinbach WJ , Fisher BT . J Pediatric Infect Dis Soc 2023 12 (9) 487-495 BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days -17 years with invasive candidiasis (predominantly candidemia) from 2014-2017. Ophthalmologic examination, abdominal imaging, echocardiogram, neuroimaging, and lumbar puncture were performed per clinician discretion. aDS performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent abdominal imaging, 450 (68%) ophthalmologic examination, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) lumbar puncture; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing ophthalmologic examination, abdominal imaging, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing abdominal imaging (aOR 2.38; 95% CI 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive ophthalmologic examination was reported in 15 (3%), abdominal imaging in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%) and lumbar puncture in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted. |
Changes in sales of tobacco and nicotine replacement therapy products before and during the COVID-19 pandemic
Sung J , Shrestha SS , Kim Y , Emery S , Wang X . Prev Chronic Dis 2023 20 E71 INTRODUCTION: The COVID-19 pandemic and its associated social distancing policies such as lockdowns and quarantine influenced people's lives and health behaviors. We comprehensively assessed national trends in sales of cigarettes, cigars, e-cigarettes, and over-the-counter nicotine replacement therapy (NRT) products before and during the pandemic, allowing for cross-product comparisons. Stockpiling behavior was also assessed. METHODS: We used US national tobacco and over-the-counter NRT retail store scanner data (excluding internet, specialty/vape store, and prescription sales) collected at 4-week intervals by NielsenIQ from December 2018 to June 2021. We applied an interrupted time-series model to assess differences in tobacco product and NRT unit sales before and during the pandemic. We defined the prepandemic period as December 16, 2018, through April 4, 2020, pandemic as starting on April 5, 2020, through June 26, 2021, and the stockpiling period as one 4-week period before the pandemic started. RESULTS: Four-week cigarette, e-cigarette, and cigar unit sales on average increased by 11.5% (P = .006), 37.1% (P < .001), and 26.1% (P < .001) respectively, while 4-week NRT unit sales decreased on average by 13.1% (P < .001), during the pandemic compared with the prepandemic period. Stockpiling was associated with increases in sales of all tobacco products and NRT products. CONCLUSION: Unit sales of assessed tobacco products increased while NRT unit sales decreased during the COVID-19 pandemic, compared with the prepandemic period. These changes may suggest an increase in the intensity of tobacco product use or stockpiling of tobacco products among people who use tobacco. |
Annual report to the nation on the status of cancer, part 1: National cancer statistics
Cronin KA , Scott S , Firth AU , Sung H , Henley SJ , Sherman RL , Siegel RL , Anderson RN , Kohler BA , Benard VB , Negoita S , Wiggins C , Cance WG , Jemal A . Cancer 2022 128 (24) 4251-4284 BACKGROUND: The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States. METHODS: Data on new cancer diagnoses during 2001-2018 were obtained from the North American Association of Central Cancer Registries' Cancer in North America Incidence file, which is comprised of data from Centers for Disease Control and Prevention-funded and National Cancer Institute-funded, population-based cancer registry programs. Data on cancer deaths during 2001-2019 were obtained from the National Center for Health Statistics' National Vital Statistics System. Five-year average incidence and death rates along with trends for all cancers combined and for the leading cancer types are reported by sex, racial/ethnic group, and age. RESULTS: Overall cancer incidence rates were 497 per 100,000 among males (ranging from 306 among Asian/Pacific Islander males to 544 among Black males) and 431 per 100,000 among females (ranging from 309 among Asian/Pacific Islander females to 473 among American Indian/Alaska Native females) during 2014-2018. The trend during the corresponding period was stable among males and increased 0.2% on average per year among females, with differing trends by sex, racial/ethnic group, and cancer type. Among males, incidence rates increased for three cancers (including pancreas and kidney), were stable for seven cancers (including prostate), and decreased for eight (including lung and larynx) of the 18 most common cancers considered in this analysis. Among females, incidence rates increased for seven cancers (including melanoma, liver, and breast), were stable for four cancers (including uterus), and decreased for seven (including thyroid and ovary) of the 18 most common cancers. Overall cancer death rates decreased by 2.3% per year among males and by 1.9% per year among females during 2015-2019, with the sex-specific declining trend reflected in every major racial/ethnic group. During 2015-2019, death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, with the steepest declines (>4% per year) reported for lung cancer and melanoma. Five-year survival for adenocarcinoma and neuroendocrine pancreatic cancer improved between 2001 and 2018; however, overall incidence (2001-2018) and mortality (2001-2019) continued to increase for this site. Among children (younger than 15 years), recent trends were stable for incidence and decreased for mortality; and among, adolescents and young adults (aged 15-39 years), recent trends increased for incidence and declined for mortality. CONCLUSIONS: Cancer death rates continued to decline overall, for children, and for adolescents and young adults, and treatment advances have led to accelerated declines in death rates for several sites, such as lung and melanoma. The increases in incidence rates for several common cancers in part reflect changes in risk factors, screening test use, and diagnostic practice. Racial/ethnic differences exist in cancer incidence and mortality, highlighting the need to understand and address inequities. Population-based incidence and mortality data inform prevention, early detection, and treatment efforts to help reduce the cancer burden in the United States. |
Annual Report to the Nation on the Status of Cancer, Part 2: Patient Economic Burden Associated With Cancer Care
Yabroff KR , Mariotto A , Tangka F , Zhao J , Islami F , Sung H , Sherman RL , Henley SJ , Jemal A , Ward EM . J Natl Cancer Inst 2021 113 (12) 1670-1682 BACKGROUND: The American Cancer Society, National Cancer Institute, Centers for Disease Control and Prevention, and North American Association of Central Cancer Registries provide annual information about cancer occurrence and trends in the United States. Part 1 of this annual report focuses on national cancer statistics. This study is part 2, which quantifies patient economic burden associated with cancer care. METHODS: We used complementary data sources, linked Surveillance, Epidemiology, and End Results-Medicare, and the Medical Expenditure Panel Survey to develop comprehensive estimates of patient economic burden, including out-of-pocket and patient time costs, associated with cancer care. The 2000-2013 Surveillance, Epidemiology, and End Results-Medicare data were used to estimate net patient out-of-pocket costs among adults aged 65 years and older for the initial, continuing, and end-of-life phases of care for all cancer sites combined and separately for the 21 most common cancer sites. The 2008-2017 Medical Expenditure Panel Survey data were used to calculate out-of-pocket costs and time costs associated with cancer among adults aged 18-64 years and 65 years and older. RESULTS: Across all cancer sites, annualized net out-of-pocket costs for medical services and prescriptions drugs covered through a pharmacy benefit among adults aged 65 years and older were highest in the initial ($2200 and $243, respectively) and end-of-life phases ($3823 and $448, respectively) and lowest in the continuing phase ($466 and $127, respectively), with substantial variation by cancer site. Out-of-pocket costs were generally higher for patients diagnosed with later-stage disease. Net annual time costs associated with cancer were $304.3 (95% confidence interval = $257.9 to $350.9) and $279.1 (95% confidence interval = $215.1 to $343.3) for adults aged 18-64 years and ≥65 years, respectively, with higher time costs among more recently diagnosed survivors. National patient economic burden, including out-of-pocket and time costs, associated with cancer care was projected to be $21.1 billion in 2019. CONCLUSIONS: This comprehensive study found that the patient economic burden associated with cancer care is substantial in the United States at the national and patient levels. |
Annual Report to the Nation on the Status of Cancer, Part 1: National Cancer Statistics
Islami F , Ward EM , Sung H , Cronin KA , Tangka FKL , Sherman RL , Zhao J , Anderson RN , Henley SJ , Yabroff KR , Jemal A , Benard VB . J Natl Cancer Inst 2021 113 (12) 1648-1669 BACKGROUND: The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries collaborate to provide annual updates on cancer incidence and mortality and trends by cancer type, sex, age group, and racial/ethnic group in the United States. In this report, we also examine trends in stage-specific survival for melanoma of the skin (melanoma). METHODS: Incidence data for all cancers from 2001 through 2017 and survival data for melanoma cases diagnosed during 2001-2014 and followed up through 2016 were obtained from the Centers for Disease Control and Prevention- and National Cancer Institute-funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries. Data on cancer deaths from 2001 through 2018 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in age-standardized incidence and death rates and 2-year relative survival were estimated by joinpoint analysis, and trends in incidence and mortality were expressed as average annual percent change (AAPC) during the most recent 5 years (2013-2017 for incidence and 2014-2018 for mortality). RESULTS: Overall cancer incidence rates (per 100,000 population) for all ages during 2013-2017 were 487.4 among males and 422.4 among females. During this period, incidence rates remained stable among males but slightly increased in females (AAPC = 0.2%; 95% confidence interval [CI] = 0.1% to 0.2%). Overall cancer death rates (per 100,000 population) during 2014-2018 were 185.5 among males and 133.5 among females. During this period, overall death rates decreased in both males (AAPC = -2.2%; 95% CI = -2.5% to - 1.9%) and females (AAPC = -1.7%; 95% CI = -2.1% to - 1.4%); death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, but increased for 5 cancers in each sex. During 2014-2018, the declines in death rates accelerated for lung cancer and melanoma, slowed down for colorectal and female breast cancers, and leveled off for prostate cancer. Among children younger than age 15 years and adolescents and young adults aged 15-39 years, cancer death rates continued to decrease in contrast to the increasing incidence rates. Two-year relative survival for distant-stage skin melanoma was stable for those diagnosed during 2001-2009 but increased by 3.1% (95% CI = 2.8% to 3.5%) per year for those diagnosed during 2009-2014, with comparable trends among males and females. CONCLUSIONS: Cancer death rates in the United States continue to decline overall and for many cancer types, with the decline accelerated for lung cancer and melanoma. For several other major cancers, however, death rates continue to increase or previous declines in rates have slowed or ceased. Moreover, overall incidence rates continue to increase among females, children, and adolescents and young adults. These findings inform efforts related to prevention, early detection, and treatment and for broad and equitable implementation of effective interventions, especially among under-resourced populations. |
COVID-19 Response Efforts of Washington State Public Health Laboratory: Lessons Learned.
McLaughlin HP , Hiatt BC , Russell D , Carlson CM , Jacobs JR , Perez-Osorio AC , Holshue ML , Choi SW , Gautom RK . Am J Public Health 2021 111 (5) e1-e9 Laboratory diagnostics play an essential role in pandemic preparedness. In January 2020, the first US case of COVID-19 was confirmed in Washington State. At the same time, the Washington State Public Health Laboratory (WA PHL) was in the process of building upon and initiating innovative preparedness activities to strengthen laboratory testing capabilities, operations, and logistics. The response efforts of WA PHL, in conjunction with the Centers for Disease Control and Prevention, to the COVID-19 outbreak in Washington are described herein-from the initial detection of severe acute respiratory syndrome coronavirus 2 through the subsequent 2 months.Factors that contributed to an effective laboratory response are described, including preparing early to establish testing capacity, instituting dynamic workforce solutions, advancing information management systems, refining laboratory operations, and leveraging laboratory partnerships. We also report on the challenges faced, successful steps taken, and lessons learned by WA PHL to respond to COVID-19.The actions taken by WA PHL to mount an effective public health response may be useful for US laboratories as they continue to respond to the COVID-19 pandemic and may help inform current and future laboratory pandemic preparedness activities. (Am J Public Health. Published online ahead of print March 18, 2021: e1-e9. https://doi.org/10.2105/AJPH.2021.306212). |
Recombinant Zoster Vaccine (Shingrix) real-world effectiveness in the first two years post-licensure.
Izurieta HS , Wu X , Forshee R , Lu Y , Sung HM , Agger PE , Chillarige Y , Link-Gelles R , Lufkin B , Wernecke M , MaCurdy TE , Kelman J , Dooling K . Clin Infect Dis 2021 73 (6) 941-948 ![]() ![]() BACKGROUND: Shingrix™ (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as two doses given 2-6 months apart, among adults ages ≥50 years. Clinical trials yielded efficacy of >90% for confirmed herpes zoster,but post-market vaccine performance has not been evaluated. Efficacy of a single dose, delayed second dose, or among persons with autoimmune or general immunosuppressive conditions have also not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix. METHODS: We conducted a cohort study among vaccinated and unvaccinated Medicare Part D community dwelling beneficiaries ages >65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance, and marginal structural models to estimate hazard ratios. RESULTS: We found a vaccine effectiveness of 70.1% (95% CI, 68.6-71.5) and 56.9% (95% CI, 55.0-58.8) for two and one doses, respectively. The two-dose vaccine effectiveness was not significantly lower for beneficiaries 80+ years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8). CONCLUSIONS: This large real-world observational study of effectiveness of Shingrix demonstrates the benefit of completing the two-dose regimen. Second doses administered beyond the recommended 6 months did not impair vaccine effectiveness.Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity. |
Population-based Estimates of COVID-19-like Illness, COVID-19 Illness, and Rates of Case Ascertainment, Hospitalizations, and Deaths - Non-Institutionalized New York City Residents, March-April 2020.
Alroy KA , Crossa A , Dominianni C , Sell J , Bartley K , Sanderson M , Fernandez S , Levanon Seligson A , Lim SW , Wang SM , Dumas SE , Perlman SE , Konty K , Olson DR , Gould LH , Greene SK . Clin Infect Dis 2021 73 (9) 1707-1710 Using a population-based, representative telephone survey, ~930,000 New York City residents had COVID-19 illness beginning March 20-April 30, 2020, a period with limited testing. For every 1000 persons estimated with COVID-19 illness, 141.8 were tested and reported as cases, 36.8 were hospitalized, and 12.8 died, varying by demographic characteristics. |
Metagenomic sequencing generates the whole genomes of porcine rotavirus A, C, and H from the United States.
Hull JJA , Qi M , Montmayeur AM , Kumar D , Velasquez DE , Moon SS , Magaña LC , Betrapally N , Ng TFF , Jiang B , Marthaler D . PLoS One 2020 15 (12) e0244498 ![]() The genus Rotavirus comprises eight species, designated A to H, and two recently identified tentative species I in dogs and J in bats. Species Rotavirus A, B, C and H (RVA, RVB, RVC and RVH) have been detected in humans and animals. While human and animal RVA are well characterized and defined, complete porcine genome sequences in the GenBank are limited compared to human strains. Here, we used a metagenomic approach to sequence the 11 segments of RVA, RVC and RVH strains from piglets in the United States (US) and explore the evolutionary relations of these RV species. Metagenomics identified Astroviridae, Picornaviridae, Caliciviridae, Coronoviridae in samples MN9.65 and OK5.68 while Picobirnaviridae and Arteriviridae were only identified in sample OK5.68. Whole genome sequencing and phylogenetic analyses identified multiple genotypes with the RVA of strain MN9.65 and OK5.68, with the genome constellation of G5/G9-P[7]/P[13]-I5/I5- R1/R1-C1-M1-A8-N1-T7-E1/E1-H1 and G5/G9-P[6]/P[7]-I5-R1/R1-C1-M1-A8-N1-T1/T7-E1/E1-H1, respectively. The RVA strains had a complex evolutionary relationship with other mammalian strains. The RVC strain OK5.68 had a genome constellation of G9-P[6]-I1-R1-C5-M6-A5-N1-T1-E1-H1, and shared an evolutionary relationship with porcine strains from the US. The RVH strains MN9.65 and OK5.68 had the genome constellation of G5-P1-I1-R1-C1-M1-A5-N1-T1-E4-H1 and G5-P1-I1-R1-C1-M1-A5-N1-T1-E1-H1, indicating multiple RVH genome constellations are circulating in the US. These findings allow us to understand the complexity of the enteric virome, develop improved screening methods for RVC and RVH strains, facilitate expanded rotavirus surveillance in pigs, and increase our understanding of the origin and evolution of rotavirus species. |
Francisella-Like Endosymbiont Detected in Haemaphysalis Ticks (Acari: Ixodidae) From the Republic of Korea.
Takhampunya R , Kim HC , Chong ST , Korkusol A , Tippayachai B , Davidson SA , Petersen JM , Klein TA . J Med Entomol 2017 54 (6) 1735-1742 ![]() A total of 6,255 ticks belonging to three genera and six species (Haemaphysalis flava Neumann, Haemaphysalis longicornis Neumann, Haemaphysalis phasiana Saito, Ixodes nipponensis Kitaoka & Saito, Ixodes persulcatus Schulze, and Amblyomma testudinarium Koch) collected from May-August, 2013, at four southwestern provinces in the Republic of Korea (ROK) were submitted to the Armed Forces Research Institute of Medical Sciences and assayed for selected tick-borne pathogens. One pool each of H. flava and H. phasiana was positive by PCR and sequencing for a Francisella-like endosymbiont, while all pools were negative for Francisella tularensis, the causative agent of tularemia. |
A dose ranging pharmacokinetic evaluation of iQP-0528 released from intravaginal rings in non-human primates
Su JT , Teller RS , Srinivasan P , Zhang J , Martin A , Sung S , Smith JM , Kiser PF . Pharm Res 2017 34 (10) 2163-2171 PURPOSE: Design of intravaginal rings (IVRs) for delivery of antiretrovirals is often guided by in vitro release under sink conditions, based on the assumption that in vivo release will follow a similar release profile. METHODS: We conducted a dose-ranging study in the female reproductive tract of pigtail macaques using matrix IVRs containing IQP-0528, a poorly soluble but highly potent antiretroviral drug with an IC90 of 146 ng/mL. These IVRs consisted of drug-loaded segments, 15.6% IQP-0528 in Tecoflex 85A, comprising either all, half, or a quarter of the entire ring. RESULTS: In vitro release under sink conditions demonstrates loading-proportional release, with a cumulative 30-day release of 48.5 +/- 2.2 mg for our 100% loaded ring, 24.8 +/- .36 mg from our 50% loaded ring, and 13.99 +/- 1.58 mg from our 25% loaded ring. In vivo, while drug concentration in vaginal fluid is well in excess of IQP-0528's EC90, we find no statistical difference between the different ring loadings in either swab drug levels or drug released from our rings. CONCLUSIONS: We show that in vitro release may not accurately reflect in vivo release, particularly for poorly soluble drugs. All tested loadings of our IVRs are capable of delivering IQP-0528 well in excess of the IC90. |
Rotavirus antigen, cytokine, and neutralising antibody profiles in sera of children with and without HIV infection in Blantyre, Malawi
Hull JJ , Cunliffe N , Jere KC , Sung-Moon S , Wang Y , Parashar U , Jiang B . Malawi Med J 2017 29 (1) 24-28 Background Rotavirus and HIV infection are major causes of death among children in sub-Saharan Africa. A previous study reported no association between concomitant HIV infection and rotavirus disease severity among hospitalised children in Malawi. This study examined rotavirus antigenaemia and broader immune responses among HIV-infected and uninfected children. Methods Stored (-80°C), paired sera from acute and convalescent phases of Malawian children less than 5 years old, hospitalised for acute gastroenteritis in the primary study, collected from July 1997 to June 1999, were utilised. Among children older than 15 months, HIV infection was defined as the presence of HIV antibody in the blood, when confirmed by at least 2 established methods. For those younger than 15 months, nested polymerase chain reaction (PCR) amplification of proviral DNA was used for verification. All were followed for up to 4 weeks after hospital discharge. Rotavirus antigen levels in sera were measured with Premier™ Rotaclone® rotavirus enzyme immunoassay (EIA) kit. Acute-phase sera were examined for 17 cytokines, using Luminex fluorescent bead human cytokine immunoassay kit. Rotavirus-specific IgA and neutralising activity were determined by EIA and microneutralisation (MN) assay, respectively. Human strains and bovine-human reassortants were propagated in MA104 cells with serum-free Iscove’s Modified Dulbecco’s Medium (IMDM). Differences in results, from specimens with and without HIV infection, were analysed for statistical significance using the chi-square test. Results We detected rotavirus antigen in 30% of the HIV-infected and 21% HIV-uninfected, in the acute-phase sera. HIV-infected children developed slightly prolonged rotavirus antigenaemia compared to HIV-uninfected children. Conclusions Rotavirus-specific IgA seroconversion rates and neutralising titres were similar in HIV-infected and HIV-uninfected children, thus, HIV infection had no major effect on immune responses to rotavirus infection. |
Multiple-locus variable-number tandem repeat analysis for strain discrimination of non-O157 Shiga toxin-producing Escherichia coli.
Timmons C , Trees E , Ribot EM , Gerner-Smidt P , LaFon P , Im S , Ma LM . J Microbiol Methods 2016 125 70-80 ![]() Non-O157 Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens of growing concern worldwide that have been associated with several recent multistate and multinational outbreaks of foodborne illness. Rapid and sensitive molecular-based bacterial strain discrimination methods are critical for timely outbreak identification and contaminated food source traceback. One such method, multiple-locus variable-number tandem repeat analysis (MLVA), is being used with increasing frequency in foodborne illness outbreak investigations to augment the current gold standard bacterial subtyping technique, pulsed-field gel electrophoresis (PFGE). The objective of this study was to develop a MLVA assay for intra- and inter-serogroup discrimination of six major non-O157 STEC serogroups-O26, O111, O103, O121, O45, and O145-and perform a preliminary internal validation of the method on a limited number of clinical isolates. The resultant MLVA scheme consists of ten variable number tandem repeat (VNTR) loci amplified in three multiplex PCR reactions. Sixty-five unique MLVA types were obtained among 84 clinical non-O157 STEC strains comprised of geographically diverse sporadic and outbreak related isolates. Compared to PFGE, the developed MLVA scheme allowed similar discrimination among serogroups O26, O111, O103, and O121 but not among O145 and O45. To more fully compare the discriminatory power of this preliminary MLVA method to PFGE and to determine its epidemiological congruence, a thorough internal and external validation needs to be performed on a carefully selected large panel of strains, including multiple isolates from single outbreaks. |
Genomic Sequence of the First Porcine Rotavirus Group H Strain in the United States.
Hull JJ , Marthaler D , Rossow S , Ng TF , Montmayeur AM , Magana L , Moon SS , Jiang B . Genome Announc 2016 4 (2) ![]() The genomic sequence of a rotavirus group H was identified in the intestine of a diarrheal pig in the United States, designated RVH/Pig-wt/USA/MN9.65/2008/GxP[x]. |
Intestinal microbiome disruption in patients in a long-term acute care hospital: A case for development of microbiome disruption indices to improve infection prevention.
Halpin AL , de Man TJ , Kraft CS , Perry KA , Chan AW , Lieu S , Mikell J , Limbago BM , McDonald LC . Am J Infect Control 2016 44 (7) 830-6 ![]() BACKGROUND: Composition and diversity of intestinal microbial communities (microbiota) are generally accepted as a risk factor for poor outcomes; however, we cannot yet use this information to prevent adverse outcomes. METHODS: Stool was collected from 8 long-term acute care hospital patients experiencing diarrhea and 2 fecal microbiota transplant donors; 16S rDNA V1-V2 hypervariable regions were sequenced. Composition and diversity of each sample were described. Stool was also tested for Clostridium difficile, vancomycin-resistant enterococci (VRE), and carbapenem-resistant Enterobacteriaceae. Associations between microbiota diversity and demographic and clinical characteristics, including antibiotic use, were analyzed. RESULTS: Antibiotic exposure and Charlson Comorbidity Index were inversely correlated with diversity (Spearman = -0.7). Two patients were positive for VRE; both had microbiomes dominated by Enterococcus faecium, accounting for 67%-84% of their microbiome. CONCLUSIONS: Antibiotic exposure correlated with diversity; however, other environmental and host factors not easily obtainable in a clinical setting are also known to impact the microbiota. Therefore, direct measurement of microbiome disruption by sequencing, rather than reliance on surrogate markers, might be most predictive of adverse outcomes. If and when microbiome characterization becomes a standard diagnostic test, improving our understanding of microbiome dynamics will allow for interpretation of results to improve patient outcomes. |
Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.
Rhee SY , Blanco JL , Jordan MR , Taylor J , Lemey P , Varghese V , Hamers RL , Bertagnolio S , de Wit TF , Aghokeng AF , Albert J , Avi R , Avila-Rios S , Bessong PO , Brooks JI , Boucher CA , Brumme ZL , Busch MP , Bussmann H , Chaix ML , Chin BS , D'Aquin TT , De Gascun CF , Derache A , Descamps D , Deshpande AK , Djoko CF , Eshleman SH , Fleury H , Frange P , Fujisaki S , Harrigan PR , Hattori J , Holguin A , Hunt GM , Ichimura H , Kaleebu P , Katzenstein D , Kiertiburanakul S , Kim JH , Kim SS , Li Y , Lutsar I , Morris L , Ndembi N , Ng KP , Paranjape RS , Peeters M , Poljak M , Price MA , Ragonnet-Cronin ML , Reyes-Teran G , Rolland M , Sirivichayakul S , Smith DM , Soares MA , Soriano VV , Ssemwanga D , Stanojevic M , Stefani MA , Sugiura W , Sungkanuparph S , Tanuri A , Tee KK , Truong HH , van de Vijver DA , Vidal N , Yang C , Yang R , Yebra G , Ioannidis JP , Vandamme AM , Shafer RW . PLoS Med 2015 12 (4) e1001810 ![]() BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naive individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions-a proxy for recent infection-yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs-K101E, K103N, Y181C, and G190A-accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen. |
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Wang Z , Zhu B , Zhang M , Parikh H , Jia J , Chung CC , Sampson JN , Hoskins JW , Hutchinson A , Burdette L , Ibrahim A , Hautman C , Raj PS , Abnet CC , Adjei AA , Ahlbom A , Albanes D , Allen NE , Ambrosone CB , Aldrich M , Amiano P , Amos C , Andersson U , Andriole G Jr , Andrulis IL , Arici C , Arslan AA , Austin MA , Baris D , Barkauskas DA , Bassig BA , Beane Freeman LE , Berg CD , Berndt SI , Bertazzi PA , Biritwum RB , Black A , Blot W , Boeing H , Boffetta P , Bolton K , Boutron-Ruault MC , Bracci PM , Brennan P , Brinton LA , Brotzman M , Bueno-de-Mesquita HB , Buring JE , Butler MA , Cai Q , Cancel-Tassin G , Canzian F , Cao G , Caporaso NE , Carrato A , Carreon T , Carta A , Chang GC , Chang IS , Chang-Claude J , Che X , Chen CJ , Chen CY , Chen CH , Chen C , Chen KY , Chen YM , Chokkalingam AP , Chu LW , Clavel-Chapelon F , Colditz GA , Colt JS , Conti D , Cook MB , Cortessis VK , Crawford ED , Cussenot O , Davis FG , De Vivo I , Deng X , Ding T , Dinney CP , Di Stefano AL , Diver WR , Duell EJ , Elena JW , Fan JH , Feigelson HS , Feychting M , Figueroa JD , Flanagan AM , Fraumeni JF Jr , Freedman ND , Fridley BL , Fuchs CS , Gago-Dominguez M , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Garcia-Closas R , Gastier-Foster JM , Gaziano JM , Gerhard DS , Giffen CA , Giles GG , Gillanders EM , Giovannucci EL , Goggins M , Gokgoz N , Goldstein AM , Gonzalez C , Gorlick R , Greene MH , Gross M , Grossman HB , Grubb R 3rd , Gu J , Guan P , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Hartge P , Hattinger C , Hayes RB , He Q , Helman L , Henderson BE , Henriksson R , Hoffman-Bolton J , Hohensee C , Holly EA , Hong YC , Hoover RN , Hosgood HD 3rd , Hsiao CF , Hsing AW , Hsiung CA , Hu N , Hu W , Hu Z , Huang MS , Hunter DJ , Inskip PD , Ito H , Jacobs EJ , Jacobs KB , Jenab M , Ji BT , Johansen C , Johansson M , Johnson A , Kaaks R , Kamat AM , Kamineni A , Karagas M , Khanna C , Khaw KT , Kim C , Kim IS , Kim YH , Kim YC , Kim YT , Kang CH , Jung YJ , Kitahara CM , Klein AP , Klein R , Kogevinas M , Koh WP , Kohno T , Kolonel LN , Kooperberg C , Kratz CP , Krogh V , Kunitoh H , Kurtz RC , Kurucu N , Lan Q , Lathrop M , Lau CC , Lecanda F , Lee KM , Lee MP , Le Marchand L , Lerner SP , Li D , Liao LM , Lim WY , Lin D , Lin J , Lindstrom S , Linet MS , Lissowska J , Liu J , Ljungberg B , Lloreta J , Lu D , Ma J , Malats N , Mannisto S , Marina N , Mastrangelo G , Matsuo K , McGlynn KA , McKean-Cowdin R , McNeill LH , McWilliams RR , Melin BS , Meltzer PS , Mensah JE , Miao X , Michaud DS , Mondul AM , Moore LE , Muir K , Niwa S , Olson SH , Orr N , Panico S , Park JY , Patel AV , Patino-Garcia A , Pavanello S , Peeters PH , Peplonska B , Peters U , Petersen GM , Picci P , Pike MC , Porru S , Prescott J , Pu X , Purdue MP , Qiao YL , Rajaraman P , Riboli E , Risch HA , Rodabough RJ , Rothman N , Ruder AM , Ryu JS , Sanson M , Schned A , Schumacher FR , Schwartz AG , Schwartz KL , Schwenn M , Scotlandi K , Seow A , Serra C , Serra M , Sesso HD , Severi G , Shen H , Shen M , Shete S , Shiraishi K , Shu XO , Siddiq A , Sierrasesumaga L , Sierri S , Sihoe AD , Silverman DT , Simon M , Southey MC , Spector L , Spitz M , Stampfer M , Stattin P , Stern MC , Stevens VL , Stolzenberg-Solomon RZ , Stram DO , Strom SS , Su WC , Sund M , Sung SW , Swerdlow A , Tan W , Tanaka H , Tang W , Tang ZZ , Tardon A , Tay E , Taylor PR , Tettey Y , Thomas DM , Tirabosco R , Tjonneland A , Tobias GS , Toro JR , Travis RC , Trichopoulos D , Troisi R , Truelove A , Tsai YH , Tucker MA , Tumino R , Van Den Berg D , Van Den Eeden SK , Vermeulen R , Vineis P , Visvanathan K , Vogel U , Wang C , Wang C , Wang J , Wang SS , Weiderpass E , Weinstein SJ , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolk A , Wolpin BM , Wong MP , Wrensch M , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xiang YB , Xu J , Yang HP , Yang PC , Yatabe Y , Ye Y , Yeboah ED , Yin Z , Ying C , Yu CJ , Yu K , Yuan JM , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Mirabello L , Savage SA , Kraft P , Chanock SJ , Yeager M , Landi MT , Shi J , Chatterjee N , Amundadottir LT . Hum Mol Genet 2014 23 (24) 6616-33 ![]() Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. |
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