Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: Malcolm H[original query] |
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Investigation and successful control of a Candida auris outbreak at a tertiary health care facility in Kenya
Ombajo LA , Kanyua A , Ngugi R , Malcolm C , Berkow E , Gade L , Bancroft E , Osoro J , Njoroge R , Juma P , Ngirita M , Bore RC , Litvintseva A , Lyman M , Toda M . IJID Regions 2024 13 Objectives: This study aimed to conduct an epidemiological and genomic investigation of a hospital outbreak of Candida auris, and implement measures for its control. Methods: We collected demographic and clinical data from medical records of patients with C. auris from January 2017 to June 2019 after identifying increased cases in April 2019. Point-prevalence surveys for C. auris colonisation were conducted in the critical care units (CCU). Antifungal susceptibility testing and genomic sequencing of isolates were performed. A bundle of infection prevention and control measures was instituted. Results: Thirty-two patients with C. auris were identified. All patients had a history of CCU admission. A total of 283 screening swabs were obtained and 57 isolates of C. auris identified. Antifungal susceptibility testing was performed on 48 isolates. All but two isolates were resistant to fluconazole; one isolate was also resistant to amphotericin B. Forty-one of 46 isolate genomes were clonally related and formed a distinct genetic cluster in Clade III. C. auris colonisation reduced from 42% in June 2019 to 1% in August 2019, and no new hospital-acquired colonisation was identified in the subsequent 9 months. Conclusions: We identified a new genetic subcluster of Clade III C. auris. We also show that strict implementation of infection prevention measures can lead to substantial reductions in C. auris transmission. © 2024 The Authors |
Outbreak of postpartum group a Streptococcus infections on a labor and delivery unit
Haden M , Liscynesky C , Colburn N , Smyer J , Malcolm K , Gonsenhauser I , Rood KM , Schneider P , Hardgrow M , Pancholi P , Thomas K , Cygnor A , Aluko O , Koch E , Tucker N , Mowery J , Brandt E , Cibulskas K , Mohr M , Nanduri S , Chochua S , Day SR . Infect Control Hosp Epidemiol 2024 1-3 A healthcare-associated group A Streptococcus outbreak involving six patients, four healthcare workers, and one household contact occurred in the labor and delivery unit of an academic medical center. Isolates were highly related by whole genome sequencing. Infection prevention measures, healthcare worker screening, and chemoprophylaxis of those colonized halted further transmission. |
Correction: Opioid prescriptions among the World Trade Center Health Program population
Liu R , Calvert GM , Anderson KR , Malcolm H , Cimineri L , Dupont H , Martinez M . BMC Health Serv Res 2024 24 (1) 551 |
Opioid prescriptions among the World Trade Center Health Program population
Liu R , Calvert GM , Anderson KR , Malcolm H , Cimineri L , Dupont H , Martinez M . BMC Health Serv Res 2023 23 (1) 1323 BACKGROUND: The World Trade Center Health Program (Program) provides limited health care to those directly affected by the 9/11 terrorist attacks. Because of physical/mental trauma arising from the 9/11 attacks, Program members might be at high risk of opioid use. To prevent prescription opioid overuse, in 2018 the Program implemented various measures to improve opioid prescribing and expand access to non-opioid pain management among Program members. However, the characteristics of opioid prescriptions dispensed among this population has never been described. METHODS: Administrative and claims data from 07/01/2011 to 09/30/2022 were used to describe opioid prescriptions dispensed during 2013-2021. RESULTS: From 2013-2021, 108,285 members were Program-enrolled for ≥ 10 months, 4,053 (3.7%) had 22,938 outpatient opioid prescriptions, of which, 62.1% were for cancer-related pain, 11.1% for hospice/end of life care, 4.8% for surgery pain, and 9.8% for acute/chronic pain. Among members with Program-paid diagnostic/treatment claims (n = 70,721), the proportion with opioid prescriptions for cancer/hospice/end of life care increased from 0.5% in 2013 to 1.6% in 2018 (p = 0.010), then decreased to 1.1% in 2021 (p = 0.070), and the proportion for non-cancer surgery/acute/chronic pain decreased from 0.6% in 2013 to 0.23% in 2021 (p = 0.0005). Among members prescribed opioids without cancer/hospice/sickle cell disease, the proportion who started with long-acting opioids or had opioid prescriptions from ≥ 4 prescribers were below 6.5% annually; the proportion receiving a high-dose (≥ 90 morphine milligram equivalents per day [MED]), or with concurrent opioids and benzodiazepines use, or who started opioids with MED ≥ 50 or with long duration (≥ 7 days' supply) were above 10% annually, but decreased since 2017. CONCLUSIONS: Prevalence of outpatient opioid prescriptions paid by the Program was very low and prescriptions were primarily dispensed for cancer/hospice/end of life care. Although Program efforts to improve opioid prescribing coincided with improvements in outcomes, ongoing surveillance is needed. |
Survey of invasive mosquito surveillance and control capacity in Southeastern USA reveals training and resource needs
Nguyen V , Weaver-Romero AL , Wang X , Tavares Y , Bauer A , McDowell RC , Dorsainvil C , Eason MD , Malcolm AN , Raz CD , Byrd BD , Riegel C , Clark M , Ber J , Harrison RL , Evans CL , Zohdy S , Allen B , Campbell LP , Killingsworth D , Grey EW , Riles MT , Lee Y , Giordano BV . J Am Mosq Control Assoc 2023 39 (2) 108-121 Several invasive mosquito species that are nuisances or of medical and veterinary importance have been introduced into the Southeastern region of the USA, posing a threat to other species and the local ecosystems and/or increasing the risk of pathogen transmission to people, livestock, and domestic pets. Prompt and effective monitoring and control of invasive species is essential to prevent them from spreading and causing harmful effects. However, the capacity for invasive mosquito species surveillance is highly variable among mosquito control programs in the Southeast, depending on a combination of factors such as regional geography and climate, access to resources, and the ability to interact with other programs. To facilitate the development of invasive mosquito surveillance in the region, we, the Mosquito BEACONS (Biodiversity Enhancement and Control of Non-native Species) working group, conducted a survey on the capacities of various public health agencies and pest control agencies engaged in mosquito surveillance and control in seven Southeastern states (Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, and South Carolina). Ninety control programs completed the survey, representing an overall response rate of 25.8%. We report key findings from our survey, emphasizing the training and resource needs, and discuss their implications for future invasive mosquito surveillance and control capacity building. By increasing communication and collaboration opportunities (e.g., real-time sharing of collection records, coordinated multistate programs), the establishment of Mosquito BEACONS and the implementation of this survey can accelerate knowledge transfer and improve decision support capacity in response to or in preparation for invasive mosquito surveillance and can establish infrastructure that can be used to inform programs around the world. |
Monitoring and evaluation platform for HEARTS in the Americas: improving population-based hypertension control programs in primary health care
Prado P , Gamarra A , Rodriguez L , Brettler J , Farrell M , Girola ME , Malcolm T , Martinez R , Molina V , Moran AE , Neupane D , Rosende A , González YV , Mukhtar Q , Ordunez P . Rev Panam Salud Publica 2022 46 e161 HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization. The District Health Information Software 2 (DHIS2) web-based platform was chosen to implement aggregate data entry of CVD outcome, process, and structural risk factor indicators. In addition, PowerBI was chosen for data visualization and dashboarding for the analysis of performance and trends above the health care facility level. The development of this new information platform was focused on primary health care facility data entry, timely data reporting, visualizations, and ultimately active use of data to drive decision-making for equitable program implementation and improved quality of care. Additionally, lessons learnt and programmatic considerations were assessed through the experience of the M&E software development. Building political will and support is essential to developing and deploying a flexible platform in multiple countries which is contextually specific to the needs of various stakeholders and levels of the health care system. The HEARTS M&E platform supports program implementation and reveals structural and managerial limitations and care gaps. The HEARTS M&E platform will be central to monitoring and driving further population-level improvements in CVD and other noncommunicable disease-related health. |
Mapping stages, barriers and facilitators to the implementation of HEARTS in the Americas initiative in 12 countries: A qualitative study
Giraldo GP , Joseph KT , Angell SY , Campbell NRC , Connell K , DiPette DJ , Escobar MC , Valdés-Gonzalez Y , Jaffe MG , Malcolm T , Maldonado J , Lopez-Jaramillo P , Olsen MH , Ordunez P . J Clin Hypertens (Greenwich) 2021 23 (4) 755-765 The World Health Organization (WHO) Global Hearts Initiative offers technical packages to reduce the burden of cardiovascular diseases through population-wide and targeted health services interventions. The Pan American Health Organization (PAHO) has led implementation of the HEARTS in the Americas Initiative since 2016. The authors mapped the developmental stages, barriers, and facilitators to implementation among the 371 primary health care centers in the participating 12 countries. The authors used the qualitative method of document review to examine cumulative country reports, technical meeting notes, and reports to regional stakeholders. Common implementation barriers include segmentation of health systems, overcoming health care professionals' scope of practice legal restrictions, and lack of health information systems limiting operational evaluation and quality improvement mechanisms. Main implementation facilitators include political support from ministries of health and leading scientific societies, PAHO's role as a regional catalyst to implementation, stakeholder endorsement demonstrated by incorporating HEARTS into official documents, and having a health system oriented to primary health care. Key lessons include the need for political commitment and cultivating on-the-ground leadership to initiate a shift in hypertension care delivery, accompanied by specific progress in the development of standardized treatment protocols and a set of high-quality medicines. By systematizing an implementation strategy to ease integration of interventions into delivery processes, the program strengthened technical leadership and ensured sustainability. These study findings will aid the regional approach by providing a staged planning model that incorporates lessons learned. A systematic approach to implementation will enhance equity, efficiency, scale-up, and sustainability, and ultimately improve population hypertension control. |
COVID-19 Case Investigation and Contact Tracing in Central Washington State, June-July 2020.
Miller JS , Bonacci RA , Lash RR , Moonan PK , Houck P , Van Meter JJ , Butler M , Everson T , Morrison B , Sixberry M , Person A , Oeltmann JE . J Community Health 2021 46 (5) 1-4 OBJECTIVE: To evaluate participation in COVID-19 case investigation and contact tracing in central Washington State between June 15 and July 12, 2020. METHODS: In this retrospective observational evaluation we combined SARS-CoV-2 RT-PCR and antigen test reports from the Washington Disease Reporting System with community case investigation and contact tracing data for 3 health districts (comprising 5 counties) in central Washington State. All 3 health districts have large Hispanic communities disproportionately affected by COVID-19. RESULTS: Investigators attempted to call all referred individuals with COVID-19 (n = 4,987); 71% were interviewed. Of those asked about close contacts (n = 3,572), 68% reported having no close contacts, with similar proportions across ethnicity, sex, and age group. The 968 individuals with COVID-19 who named specific contacts (27% of those asked) reported a total of 2,293 contacts (mean of 2.4 contacts per individual with COVID-19); 85% of listed contacts participated in an interview. CONCLUSIONS: Most individuals with COVID-19 reported having no close contacts. Increasing community engagement and public messaging, as well as understanding and addressing barriers to participation, are crucial for CICT to contribute meaningfully to controlling the SARS-CoV-2 pandemic. |
Client preferences for contraceptive counseling: A systematic review
Fox E , Reyna A , Malcolm NM , Rosmarin RB , Zapata LB , Frederiksen BN , Moskosky SB , Dehlendorf C . Am J Prev Med 2018 55 (5) 691-702 CONTEXT: Providers can help clients achieve their personal reproductive goals by providing high-quality, client-centered contraceptive counseling. Given the individualized nature of contraceptive decision making, provider attention to clients' preferences for counseling interactions can enhance client centeredness. The objective of this systematic review was to summarize the evidence on what preferences clients have for the contraceptive counseling they receive. EVIDENCE ACQUISITION: This systematic review is part of an update to a prior review series to inform contraceptive counseling in clinical settings. Sixteen electronic bibliographic databases were searched for studies related to client preferences for contraceptive counseling published in the U.S. or similar settings from March 2011 through November 2016. Because studies on client preferences were not included in the prior review series, a limited search was conducted for earlier research published from October 1992 through February 2011. EVIDENCE SYNTHESIS: In total, 26 articles met inclusion criteria, including 17 from the search of literature published March 2011 or later and nine from the search of literature from October 1992 through February 2011. Nineteen articles included results about client preferences for information received during counseling, 13 articles included results about preferences for the decision-making process, 13 articles included results about preferences for the relationship between providers and clients, and 11 articles included results about preferences for the context in which contraceptive counseling is delivered. CONCLUSIONS: Evidence from the mostly small, qualitative studies included in this review describes preferences for the contraceptive counseling interaction. Provider attention to these preferences may improve the quality of family planning care; future research is needed to explore interventions designed to meet preferences. THEME INFORMATION: This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services. |
Clinic-based programs to prevent repeat teen pregnancy: A systematic review
Frederiksen BN , Rivera MI , Ahrens KA , Malcolm NM , Brittain AW , Rollison JM , Moskosky SB . Am J Prev Med 2018 55 (5) 736-746 CONTEXT: The purpose of this paper is to synthesize and evaluate the evidence on the effectiveness of repeat teen pregnancy prevention programs offered in clinical settings. EVIDENCE ACQUISITION: Multiple databases were searched for peer-reviewed articles published from January 1985 to April 2016 that included key terms related to adolescent reproductive health services. Analysis of these studies occurred in 2017. Studies were excluded if they focused solely on sexually transmitted disease/HIV prevention services, or occurred outside of a clinic setting or the U.S., Canada, Europe, Australia, or New Zealand. Inclusion and exclusion criteria further narrowed the studies to those that included information on at least one short-term (e.g., increased knowledge); medium-term (e.g., increased contraceptive use); or long-term (e.g., decreased repeat teen pregnancy) outcome, or identified contextual barriers or facilitators for providing adolescent-focused family planning services. Standardized abstraction methods and tools were used to synthesize the evidence and assess its quality. Only studies of clinic-based programs focused on repeat teen pregnancy prevention were included in this review. EVIDENCE SYNTHESIS: The search strategy identified 27,104 citations, 940 underwent full-text review, and 120 met the adolescent-focused family planning services inclusion criteria. Only five papers described clinic-based programs focused on repeat teen pregnancy prevention. Four studies found positive (n=2) or null (n=2) effects on repeat teen pregnancy prevention; an additional study described facilitators for helping teen mothers remain linked to services. CONCLUSIONS: This review identified clinic-based repeat teen pregnancy prevention programs and few positively affect factors that may reduce repeat teen pregnancy. Access to immediate postpartum contraception or home visiting programs may be opportunities to meet adolescents where they are and reduce repeat teen pregnancy. THEME INFORMATION: This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services. |
Community education and engagement in family planning: Updated systematic review
Sharma AE , Frederiksen BN , Malcolm NM , Rollison JM , Carter MW . Am J Prev Med 2018 55 (5) 747-758 CONTEXT: Community education and engagement are important for informing family planning projects. The objective of this study was to update two prior systematic reviews assessing the impact of community education and engagement interventions on family planning outcomes. EVIDENCE ACQUISITION: Sixteen electronic databases were searched for studies relevant to a priori determined inclusion/exclusion criteria in high development settings, published from March 2011 through April 2016, updating two reviews that included studies from 1985 through February 2011. EVIDENCE SYNTHESIS: Nine relevant studies were included in this updated review related to community education, in addition to 17 from the prior review. No new community engagement studies met inclusion criteria, as occurred in the prior review. Of new studies, community education modalities included mass media, print/mail, web-based, text messaging, and interpersonal interventions. One study on mass media intervention demonstrated a positive impact on reducing teen and unintended pregnancies. Three of four studies on interpersonal interventions demonstrated positive impacts on medium-term family planning outcomes, such as contraception and condom use. Three new studies demonstrated mostly positive, but inconsistent, results on short-term family planning outcomes. CONCLUSIONS: Findings from this systematic review update are in line with a previous review showing the positive impact of community education using traditional modalities on short-term family planning outcomes, identifying additional impacts on long-term outcomes, and highlighting new evidence for education using modern modalities, such as text messaging and web-based education. More research is necessary to provide a stronger evidence base for directing community education and engagement efforts in family planning contexts. THEME INFORMATION: This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services. |
Contraceptive counseling in clinical settings: An updated systematic review
Zapata LB , Pazol K , Dehlendorf C , Curtis KM , Malcolm NM , Rosmarin RB , Frederiksen BN . Am J Prev Med 2018 55 (5) 677-690 CONTEXT: The objective of this systematic review was to update a prior review and summarize the evidence (newly identified and cumulative) on the impact of contraceptive counseling provided in clinical settings. EVIDENCE ACQUISITION: Multiple databases, including PubMed, were searched during 2016-2017 for articles published from March 1, 2011, to November 30, 2016. EVIDENCE SYNTHESIS: The search strategy identified 24,953 articles; ten studies met inclusion criteria. Two of three new studies that examined contraceptive counseling interventions (i.e., enhanced models to standard of care) among adolescents and young adults found a statistically significant positive impact on at least one outcome of interest. Five of seven new studies that examined contraceptive counseling, in general, or specific counseling interventions or aspects of counseling (e.g., personalization) among adults or mixed populations (adults and adolescents) found a statistically significant positive impact on at least one outcome of interest. In combination with the initial review, six of nine studies among adolescents and young adults and 16 of 23 studies among adults or mixed populations found a statistically significant positive impact of counseling on at least one outcome of interest. CONCLUSIONS: Overall, evidence supports the utility of contraceptive counseling, in general, and specific interventions or aspects of counseling. Promising components of contraceptive counseling were identified. The following would strengthen the evidence base: improved documentation of counseling content and processes, increased attention to the relationships between client experiences and behavioral outcomes, and examining the comparative effectiveness of different counseling approaches to identify those that are most effective. THEME INFORMATION: This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services. |
Impact of contraceptive education on knowledge and decision making: An updated systematic review
Pazol K , Zapata LB , Dehlendorf C , Malcolm NM , Rosmarin RB , Frederiksen BN . Am J Prev Med 2018 55 (5) 703-715 CONTEXT: Educational interventions can help individuals increase their knowledge of available contraceptive methods, enabling them to make informed decisions and use contraception correctly. This review updates a previous review of contraceptive education. EVIDENCE ACQUISITION: Multiple databases were searched for articles published March 2011-November 2016. Primary outcomes were knowledge, participation in and satisfaction/comfort with decision making, attitudes toward contraception, and selection of more effective methods. Secondary outcomes included contraceptive behaviors and pregnancy. Excluded articles described interventions that had no comparison group, could not be conducted feasibly in a clinic setting, or were conducted outside the U.S. or similar country. EVIDENCE SYNTHESIS: A total of 24,953 articles were identified. Combined with the original review, 37 articles met inclusion criteria and described 31 studies implementing a range of educational approaches (interactive tools, written materials, audio/videotapes, and text messages), with and without healthcare provider feedback, for a total of 36 independent interventions. Of the 31 interventions for which knowledge was assessed, 28 had a positive effect. Fewer were assessed for their effect on attitudes toward contraception, selection of more effective methods, contraceptive behaviors, or pregnancy-although increased knowledge was found to mediate additional outcomes (positive attitudes toward contraception and contraceptive continuation). CONCLUSIONS: This systematic review is consistent with evidence from the broader healthcare field in suggesting that a range of interventions can increase knowledge. Future studies should assess what aspects are most effective, the benefits of including provider feedback, and the extent to which educational interventions can facilitate behavior change and attainment of reproductive health goals. THEME INFORMATION: This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services. |
Youth-friendly family planning services for young people: A systematic review update
Brittain AW , Loyola Briceno AC , Pazol K , Zapata LB , Decker E , Rollison JM , Malcolm NM , Romero LM , Koumans EH . Am J Prev Med 2018 55 (5) 725-735 CONTEXT: Youth-friendly family planning services may improve youth reproductive health outcomes. A systematic review conducted in 2011 was updated in 2016 to incorporate recent data examining the effects of youth-friendly family planning services on reproductive health outcomes and the facilitators and barriers facing young people in accessing family planning services. EVIDENCE ACQUISITION: PubMed, POPLINE, EMBASE, and other databases were used to identify relevant articles published from March 2011 through April 2016. EVIDENCE SYNTHESIS: Eighteen studies met inclusion criteria and were added to 19 studies from the review conducted in 2011. Of these, seven assessed the effect of youth-friendly services on outcomes: two showed a positive effect on reducing teen pregnancy, three on contraceptive use, and three on knowledge and patient satisfaction (not mutually exclusive). Facilitators or barriers were described in 32 studies. However, none were RCTs and most were at high risk for bias due to selection, self-report, and recall bias among others. CONCLUSIONS: The studies in this review suggest some positive effects of youth-friendly family planning services on reproductive health outcomes, but the need for more rigorous research persists. This review identified numerous factors relevant to young people's access to family planning services, reaffirming findings from the initial review: young people value confidentiality, supportive provider interaction, specialized provider training, and the removal of logistic barriers. Further, it illuminates the importance young people place on receiving comprehensive, client-centered family planning counseling. These findings should be considered when developing, implementing, and evaluating reproductive health services for young people. THEME INFORMATION: This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services. |
Lack of in vitro–in vivo correlation for a UC781-releasing vaginal ring in macaques
McConville C , Smith JM , McCoy CF , Srinivasan P , Mitchell J , Holder A , Otten RA , Butera S , Doncel GF , Friend DR , Malcolm RK . Drug Deliv Transl Res 2015 5 (1) 27-37 This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82–860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo–in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism. |
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. |
Increasing value and reducing waste in research design, conduct, and analysis.
Ioannidis JP , Greenland S , Hlatky MA , Khoury MJ , Macleod MR , Moher D , Schulz KF , Tibshirani R . Lancet 2014 383 (9912) 166-75 Correctable weaknesses in the design, conduct, and analysis of biomedical and public health research studies can produce misleading results and waste valuable resources. Small effects can be difficult to distinguish from bias introduced by study design and analyses. An absence of detailed written protocols and poor documentation of research is common. Information obtained might not be useful or important, and statistical precision or power is often too low or used in a misleading way. Insufficient consideration might be given to both previous and continuing studies. Arbitrary choice of analyses and an overemphasis on random extremes might affect the reported findings. Several problems relate to the research workforce, including failure to involve experienced statisticians and methodologists, failure to train clinical researchers and laboratory scientists in research methods and design, and the involvement of stakeholders with conflicts of interest. Inadequate emphasis is placed on recording of research decisions and on reproducibility of research. Finally, reward systems incentivise quantity more than quality, and novelty more than reliability. We propose potential solutions for these problems, including improvements in protocols and documentation, consideration of evidence from studies in progress, standardisation of research efforts, optimisation and training of an experienced and non-conflicted scientific workforce, and reconsideration of scientific reward systems. |
Development and evaluation of a vaginal ring device for sustained delivery of HIV microbicides to non-human primates
Promadej-Lanier Nattawan , Smith James M , Srinivasan Priya , McCoy Clare F , Butera Sal , Woolfson ADavid , Malcolm RKarl , Otten Ron A . J Med Primatol 2009 38 (4) 263-271 BACKGROUND: There is considerable interest in developing coitally independent, sustained release formulations for long-term administration of HIV microbicides. Vaginal ring devices are at the forefront of this formulation strategy. METHODS: Non-medicated silicone elastomer vaginal rings were prepared having a range of appropriate dimensions for testing vaginal fit in pig-tailed and Chinese rhesus macaques. Cervicovaginal proinflammatory markers were evaluated. Compression testing was performed to compare the relative flexibility of various macaque and commercial human rings. RESULTS: All rings remaine d in place during the study period and no tissue irritation or significant induction of cervicovaginal proinflammatory markers or signs of physical discomfort were observed during the 8-week study period. CONCLUSIONS: Qualitative evaluation suggests that the 25 x 5-mm ring provided optimal fit in both macaque species. Based on the results presented here, low-consistency silicone elastomers do not cause irritation in macaques and are proposed as suitable materials for the manufacture of microbicide-loaded vaginal rings. |
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