Last data update: Oct 28, 2024. (Total: 48004 publications since 2009)
Records 1-20 (of 20 Records) |
Query Trace: Bachman S[original query] |
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Defining blood hematology reference values in female pig-tailed macaques (Macaca nemestrina) using the Isolation Forest algorithm
Kim D , Derton A , Khalil G , Pan Y , Bachman S , Kelley K , Garcίa-Lerma G , Dobard CW , Daly MB . J Med Primatol 2024 53 (4) e12723 BACKGROUND: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. METHODS: Eighteen female PTMs were evaluated. Blood was collected 1-24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. RESULTS: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. CONCLUSIONS: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs. |
Successful child sexual violence prevention efforts start with data: how the Violence Against Children and Youth Survey helped curb the tide of child sexual violence in 20 countries
Chiang L , Miedema S , Saul J , Mercy J , Brooks A , Butchart A , Bachman G , Hegle J , Ligiero D , Logan J , Massetti G . BMJ Paediatr Open 2024 8 (1) |
Extended post-exposure protection against vaginal SHIV infection with tenofovir alafenamide fumarate/elvitegravir inserts in macaques
Makarova N , Singletary T , Peet MM , Mitchell J , Bachman S , Holder A , Dinh C , Lipscomb J , Agrahari V , Mendoza M , Pan Y , Heneine W , Clark MR , García-Lerma JG , Doncel GF , Smith JM . J Infect Dis 2023 Vaginal inserts that can be used on demand before or after sex may be a desirable HIV prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF/20mg) and elvitegravir (EVG/16mg) were highly protective against repeated SHIV vaginal exposures when administered to macaques 4h before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8h or 24h after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women. |
Orphanhood vulnerabilities for violence and HIV by education, sex, and orphan type among 18-24-year-old youth: findings from the 2018 Lesotho violence against children and youth survey
Lee N , Self-Brown SR , Bachman G , Howard AL , Gilbert LK , Hegle J , Perry EW , Saul J , Behl I , Massetti GM . Psychol Health Med 2023 1-15 HIV and violence among orphans are key measures of vulnerability in low-resource settings. Although Lesotho has the second highest HIV adult prevalence rate (21.1%) in the world, and the prevalence of orphanhood (44.2%) and violence exposure (67.0%) is high, little research exist on orphanhood vulnerabilities for violence and HIV in Lesotho. Using data from 4,408 youth (18-24 years old) from Lesotho's 2018 Violence Against Children and Youth survey, a nationally representative cross-sectional household survey, the study examined associations among orphan status, violence, and HIV and assessed how associations differed by education, sex, and orphan type, using logistic regression. Orphans had higher odds of violence (aOR, 1.21; 95% CI, 1.01-1.46) and HIV (aOR, 1.69; 95% CI, 1.24-2.29). Having primary education or less (aOR, 1.43; 95% CI, 1.02-2.02), male sex (aOR, 1.74; 95% CI, 1.27-2.36), and being a paternal orphan (aOR, 1.43; 95% CI, 1.14-1.80) were significant interaction terms for violence. Orphans who completed primary school or less (aOR, 1.61; 95% CI, 1.09-2.39), female (aOR, 3.08; 95% CI, 2.14-4.42) and double orphans (aOR, 2.54; 95% CI, 1.56-4.13) had higher odds of HIV. These relationships highlight the importance of comprehensive strategies to support education and family strengthening for orphans as core violence and HIV prevention efforts. |
Supporting parents of adolescents: a powerful and under-utilised opportunity to influence adolescent development
Skeen S , Ahmad JH , Bachman G , Cluver L , Gardner F , Madrid B , Miller K , Tomlinson M , Sherr L , Levy M . Vulnerable Child Youth Stud 2022 18 (1) 1-9 Throughout the rapid and intense changes that adolescents experience, their parents retain important influence over how they interact with the complex factors that shape their development. How parents care for their adolescent children has a deep and lasting impact on their well-being and development. Yet, parents often require support to meet their own and their adolescent children’s needs, which can be achieved through parenting support programmes. Parenting support programmes are delivered to parents of younger children across different contexts and populations, but the benefit of these programmes for parents of adolescents is not well-recognised or prioritised. Given the clear need for these interventions during adolescence and the substantial evidence for effectiveness in this age group, it is time to move the field forward. Increased resources to support parents of adolescents would maximise adolescents’ developmental potential and promote their well-being. We highlight four pressing areas for action: including parents of adolescents in parenting initiatives; involving parents in adolescent programming; strengthening efforts to address poverty and inequality, violence, and gender inequality; and engaging in strategic research to intensify the impact of programming. © 2022 Informa UK Limited, trading as Taylor & Francis Group. |
The evolution of DREAMS: using data for continuous program improvement
Saul J , Toiv N , Cooney C , Beamon T , Borgman M , Bachman G , Akom E , Benevides R , Limb A , Sato K , Achrekar A , Birx D . AIDS 2022 36 S5-s14 The DREAMS (Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe) Partnership, a public-private partnership launched by the United States President's Emergency Plan for AIDS Relief (PEPFAR), represents the largest investment in comprehensive HIV prevention for adolescent girls and young women (AGYW) ever made in a single global initiative. This paper describes the evolution of programming over time using the triangulation of multiple data sources to develop and refine an impactful program, as well as to improve efficacy and resource investment. Methods of analysis used to evolve this programming include reviews of literature on behavioral, biomedical and structural interventions, and HIV vulnerability; PEPFAR program data; external implementation science and impact studies;observations from site visits; in-depth reviews of program materials; and inputs from AGYW and other stakeholders. Key program improvements made in response to this real-time data use are described, including the rationale for programmatic changes and the evidence base for continual program refinements. This review emphasizes the importance and process of implementing the most effective combination of structural and biomedical HIV prevention programming, based on the best available science, while also adapting to local context in a way that does not compromise effectiveness or violate core implementation principles. Data from research and evaluation are critical to move the HIV prevention field toward more impactful and efficient programming responsive to the lived realities of AGYW. A central tenant to using these data sources effectively is the inclusion of AGYW in decision-making throughout the planning and implementation of programming. |
Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study.
Unwin HJT , Hillis S , Cluver L , Flaxman S , Goldman PS , Butchart A , Bachman G , Rawlings L , Donnelly CA , Ratmann O , Green P , Nelson CA , Blenkinsop A , Bhatt S , Desmond C , Villaveces A , Sherr L . Lancet Child Adolesc Health 2022 6 (4) 249-259 BACKGROUND: In the 6 months following our estimates from March 1, 2020, to April 30, 2021, the proliferation of new coronavirus variants, updated mortality data, and disparities in vaccine access increased the amount of children experiencing COVID-19-associated orphanhood. To inform responses, we aimed to model the increases in numbers of children affected by COVID-19-associated orphanhood and caregiver death, as well as the cumulative orphanhood age-group distribution and circumstance (maternal or paternal orphanhood). METHODS: We used updated excess mortality and fertility data to model increases in minimum estimates of COVID-19-associated orphanhood and caregiver deaths from our original study period of March 1, 2020-April 30, 2021, to include the new period of May 1-Oct 31, 2021, for 21 countries. Orphanhood was defined as the death of one or both parents; primary caregiver loss included parental death or the death of one or both custodial grandparents; and secondary caregiver loss included co-residing grandparents or kin. We used logistic regression and further incorporated a fixed effect for western European countries into our previous model to avoid over-predicting caregiver loss in that region. For the entire 20-month period, we grouped children by age (0-4 years, 5-9 years, and 10-17 years) and maternal or paternal orphanhood, using fertility contributions, and we modelled global and regional extrapolations of numbers of orphans. 95% credible intervals (CrIs) are given for all estimates. FINDINGS: The number of children affected by COVID-19-associated orphanhood and caregiver death is estimated to have increased by 90·0% (95% CrI 89·7-90·4) from April 30 to Oct 31, 2021, from 2 737 300 (95% CrI 1 976 100-2 987 000) to 5 200 300 (3 619 400-5 731 400). Between March 1, 2020, and Oct 31, 2021, 491 300 (95% CrI 485 100-497 900) children aged 0-4 years, 736 800 (726 900-746 500) children aged 5-9 years, and 2 146 700 (2 120 900-2 174 200) children aged 10-17 years are estimated to have experienced COVID-19-associated orphanhood. Globally, 76·5% (95% CrI 76·3-76·7) of children were paternal orphans, whereas 23·5% (23·3-23·7) were maternal orphans. In each age group and region, the prevalence of paternal orphanhood exceeded that of maternal orphanhood. INTERPRETATION: Our findings show that numbers of children affected by COVID-19-associated orphanhood and caregiver death almost doubled in 6 months compared with the amount after the first 14 months of the pandemic. Over the entire 20-month period, 5·0 million COVID-19 deaths meant that 5·2 million children lost a parent or caregiver. Our data on children's ages and circumstances should support pandemic response planning for children globally. FUNDING: UK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, and Medical Research Council), Oak Foundation, UK National Institute for Health Research, US National Institutes of Health, and Imperial College London. |
Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study.
Hillis SD , Unwin HJT , Chen Y , Cluver L , Sherr L , Goldman PS , Ratmann O , Donnelly CA , Bhatt S , Villaveces A , Butchart A , Bachman G , Rawlings L , Green P , Nelson CA3rd , Flaxman S . Lancet 2021 398 (10298) 391-402 BACKGROUND: The COVID-19 pandemic priorities have focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalisation. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation. METHODS: We used mortality and fertility data to model minimum estimates and rates of COVID-19-associated deaths of primary or secondary caregivers for children younger than 18 years in 21 countries. We considered parents and custodial grandparents as primary caregivers, and co-residing grandparents or older kin (aged 60-84 years) as secondary caregivers. To avoid overcounting, we adjusted for possible clustering of deaths using an estimated secondary attack rate and age-specific infection-fatality ratios for SARS-CoV-2. We used these estimates to model global extrapolations for the number of children who have experienced COVID-19-associated deaths of primary and secondary caregivers. FINDINGS: Globally, from March 1, 2020, to April 30, 2021, we estimate 1 134 000 children (95% credible interval 884 000-1 185 000) experienced the death of primary caregivers, including at least one parent or custodial grandparent. 1 562 000 children (1 299 000-1 683 000) experienced the death of at least one primary or secondary caregiver. Countries in our study set with primary caregiver death rates of at least one per 1000 children included Peru (10·2 per 1000 children), South Africa (5·1), Mexico (3·5), Brazil (2·4), Colombia (2·3), Iran (1·7), the USA (1·5), Argentina (1·1), and Russia (1·0). Numbers of children orphaned exceeded numbers of deaths among those aged 15-50 years. Between two and five times more children had deceased fathers than deceased mothers. INTERPRETATION: Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children. FUNDING: UK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, Medical Research Council), UK National Institute for Health Research, US National Institutes of Health, and Imperial College London. |
Vaccine Safety Datalink infrastructure enhancements for evaluating the safety of maternal vaccination
Naleway AL , Crane B , Irving SA , Bachman D , Vesco KK , Daley MF , Getahun D , Glenn SC , Hambidge SJ , Jackson LA , Klein NP , McCarthy NL , McClure DL , Panagiotakopoulos L , Panozzo CA , Vazquez-Benitez G , Weintraub ES , Zerbo O , Kharbanda EO . Ther Adv Drug Saf 2021 12 20420986211021233 Background: Identifying pregnancy episodes and accurately estimating their beginning and end dates are imperative for observational maternal vaccine safety studies using electronic health record (EHR) data. Methods: We modified the Vaccine Safety Datalink (VSD) Pregnancy Episode Algorithm (PEA) to include both the International Classification of Disease, ninth revision (ICD-9 system) and ICD-10 diagnosis codes, incorporated additional gestational age data, and validated this enhanced algorithm with manual medical record review. We also developed the new Dynamic Pregnancy Algorithm (DPA) to identify pregnancy episodes in real time. Results: Around 75% of the pregnancy episodes identified by the enhanced VSD PEA were live births, 12% were spontaneous abortions (SABs), 10% were induced abortions (IABs), and 0.4% were stillbirths (SBs). Gestational age was identified for 99% of live births, 89% of SBs, 69% of SABs, and 42% of IABs. Agreement between the PEA-assigned and abstractor-identified pregnancy outcome and outcome date was 100% for live births, but was lower for pregnancy losses. When gestational age was available in the medical record, the agreement was higher for live births (97%), but lower for pregnancy losses (75%). The DPA demonstrated strong concordance with the PEA and identified pregnancy episodes ⩾6 months prior to the outcome date for 89% of live births. Conclusion: The enhanced VSD PEA is a useful tool for identifying pregnancy episodes in EHR databases. The DPA improves the timeliness of pregnancy identification and can be used for near real-time maternal vaccine safety studies. Plain Language Summary: Improving identification of pregnancies in the Vaccine Safety Datalink electronic medical record databases to allow for better and faster monitoring of vaccination safety during pregnancy Introduction: It is important to monitor of the safety of vaccines after they have been approved and licensed by the Food and Drug Administration, especially among women vaccinated during pregnancy. The Vaccine Safety Datalink (VSD) monitors vaccine safety through observational studies within large databases of electronic medical records. Since 2012, VSD researchers have used an algorithm called the Pregnancy Episode Algorithm (PEA) to identify the medical records of women who have been pregnant. Researchers then use these medical records to study whether receiving a particular vaccine is linked to any negative outcomes for the woman or her child. Methods: The goal of this study was to update and enhance the PEA to include the full set of medical record diagnostic codes [both from the older International Classification of Disease, ninth revision (ICD-9 system) and the newer ICD-10 system] and to incorporate additional sources of data about gestational age. To ensure the validity of the PEA following these enhancements, we manually reviewed medical records and compared the results with the algorithm. We also developed a new algorithm, the Dynamic Pregnancy Algorithm (DPA), to identify women earlier in pregnancy, allowing us to conduct more timely vaccine safety assessments. Results: The new version of the PEA identified 2,485,410 pregnancies in the VSD database. The enhanced algorithm more precisely estimated the beginning of pregnancies, especially those that did not result in live births, due to the new sources of gestational age data. Conclusion: Our new algorithm, the DPA, was successful at identifying pregnancies earlier in gestation than the PEA. The enhanced PEA and the new DPA will allow us to better evaluate the safety of current and future vaccinations administered during or around the time of pregnancy. © The Author(s), 2021. |
Performance of a fully-automated system on a WHO malaria microscopy evaluation slide set.
Horning MP , Delahunt CB , Bachman CM , Luchavez J , Luna C , Hu L , Jaiswal MS , Thompson CM , Kulhare S , Janko S , Wilson BK , Ostbye T , Mehanian M , Gebrehiwot R , Yun G , Bell D , Proux S , Carter JY , Oyibo W , Gamboa D , Dhorda M , Vongpromek R , Chiodini PL , Ogutu B , Long EG , Tun K , Burkot TR , Lilley K , Mehanian C . Malar J 2021 20 (1) 110 BACKGROUND: Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. METHODS: The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. RESULTS: The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. CONCLUSIONS: EasyScan GO's expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings. |
The effect of blood glucose on quiet standing balance in young healthy individuals
Breloff SP , Bachman JL , Lugade VA , Stuka AD . Biomed Eng (Singapore) 2020 32 (2) Falling is one of the leading causes of accidental injury and death among elderly adults and construction workers, with costs exceeding US31 billion each year. Having good balance reduces the likelihood of falling - therefore it is important to determine which possible factors might influence balance. The purpose of this study was to determine if consuming three different types of breakfast altered blood glucose levels in such a way that young healthy individual's balance control was compromised. Balance was then measured while the subjects completed single- and dual-task standing trials with eyes open and closed. Although changing blood glucose did alter quiet standing balance - as measured by the separation distance between the COG and COP, the velocity of the COM, and the total distance traveled by the COG and COP along the anterior-posterior (AP) and medial-lateral (ML) axes - the results were contradictory to what was hypothesized. Subjects with lower blood glucose swayed less than those with higher blood glucose. This could potentially be due to the habitual skipping of breakfast in young adults. Though the changing of blood glucose did influence quiet standing balance of young healthy adults, it was not in a way which increased the risk of falling. |
Parenting in a time of COVID-19.
Cluver L , Lachman JM , Sherr L , Wessels I , Krug E , Rakotomalala S , Blight S , Hillis S , Bachman G , Green O , Butchart A , Tomlinson M , Ward CL , Doubt J , McDonald K . Lancet 2020 395 (10231) e64 Coronavirus disease 2019 (COVID-19) is changing family life. The United Nations Educational, Scientific and Cultural Organization estimates 1·38 billion children are out of school or child care, without access to group activities, team sports, or playgrounds. Parents and caregivers are attempting to work remotely or unable to work, while caring for children, with no clarity on how long the situation will last. For many people, just keeping children busy and safe at home is a daunting prospect. For those living in low-income and crowded households, these challenges are exacerbated. |
Hepatitis C virus testing and linkage to care in North Carolina and South Carolina jails, 2012-2014
Schoenbachler BT , Smith BD , Sena AC , Hilton A , Bachman S , Lunda M , Spaulding AC . Public Health Rep 2016 131 98-104 OBJECTIVE: We evaluated a hepatitis C virus (HCV) testing and linkage-to-care post-release program among detainees of small- to medium-sized jails in North Carolina and South Carolina as part of the Hepatitis Testing and Linkage to Care initiative. METHODS: An HCV testing and linkage-to-care program was implemented in selected jails in North Carolina and South Carolina from December 2012 to March 2014. Health-care workers not affiliated with the jails conducted HCV antibody (anti-HCV) and HCV ribonucleic acid (RNA) testing and linkage-to-care activities. The North Carolina jail provided universal opt-out testing for HCV; South Carolina jails initially targeted high-risk individuals before expanding to routine testing. RESULTS: Of 669 detainees tested for HCV in North Carolina, 88 (13.2%) tested anti-HCV positive, of whom 81 (92.0%) received an HCV RNA test, 66 (81.5%) of whom tested HCV RNA positive (i.e., currently infected). Of the 66 detainees with current HCV infection, 18 were referred to HCV medical care post-release and 10 attended their first appointment. Of 224 detainees tested for HCV in South Carolina, 18 (8.0%) tested anti-HCV positive, of whom 13 received an HCV RNA test. Nine of 13 detainees tested HCV RNA positive, seven detainees were referred to post-release medical care, and two detainees attended their first appointment. Overall, 106 of 893 (11.9%) detainees were anti-HCV positive. CONCLUSION: This study demonstrated that HCV testing, identification of infection, and linkage to care are feasible among jail populations. The rate of anti-HCV positivity was lower than that found in national studies of incarcerated populations, suggesting that HCV infection prevalence in jails may vary across U.S. states or regions. |
Lack of prophylactic efficacy of oral maraviroc in macaques despite high drug concentrations in rectal tissues
Massud I , Aung W , Martin A , Bachman S , Mitchell J , Aubert R , Tsegaye TS , Kersh E , Pau CP , Heneine W , Garcia-Lerma JG . J Virol 2013 87 (16) 8952-61 Maraviroc (MVC) is a potent CCR5 co-receptor antagonist that is in clinical testing for daily oral pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model consisting of weekly SHIV162p3 exposures to evaluate the efficacy of oral MVC in preventing rectal SHIV transmission. MVC dosing was informed by the pharmacokinetic profile seen in blood and rectal tissues, and consisted of a human-equivalent dose given 24h before virus exposure followed by a booster post-exposure dose. In rectal secretions, MVC peaked at 24h (10,242 ng/ml) with concentrations at 48h that were about 40 times those required to block SHIV infection of PBMCs in vitro. Median MVC concentrations in rectal tissues at 24h (1,404 ng/g) were 30 and 10 times those achieved in vaginal or lymphoid tissues, respectively. MVC significantly reduced MIP-1beta-induced CCR5 internalization in rectal mononuclear cells, an indication of efficient binding to CCR5 in rectal lymphocytes. The half-life of CCR5-bound MVC in PBMCs was 2.6 days. Despite this favorable profile, 5/6 treated macaques were infected during 5 rectal SHIV exposures as were 3/4 controls. MVC treatment was associated with a significant increase in the percentage of CD3+/CCR5+ cells in blood. We show that high and durable MVC concentrations in rectal tissues are not sufficient to prevent SHIV infection in macaques. The increases in CD3+/CCR5+ cells seen during MVC treatment point to unique immunological effects of CCR5 inhibition by MVC. The implications of these immunological effects on PrEP with MVC require further evaluation. |
Prophylactic effficacy of oral emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) combination against a tenofovir-resistant shiv containing the K65R mutation in macaques
Cong ME , Mitchell J , Sweeney E , Bachman S , Hanson DL , Heneine W , Garcia-Lerma JG . J Infect Dis 2013 208 (3) 463-7 Daily pre-exposure prophylaxis with FTC/TDF is a novel HIV prevention strategy. We investigated in macaques if FTC/TDF prevents transmission of a tenofovir-resistant SHIV containing the K65R mutation. Six macaques received weekly a dose of FTC/TDF 3 days before rectal SHIV exposures and a second dose 2h after. Six untreated animals were controls. Animals were exposed rectally to escalating virus doses weekly for up to 28 weeks. PrEP significantly delayed infection with SHIV(K65R) (p=0.028) although 4/6 FTC/TDF-treated macaques were infected at the end of the challenges. These findings highlight the need to closely monitor PrEP efficacy in areas with prevalent K65R. |
Evaluation of the lymphocyte trafficking drug FTY720 in vaginal tissues
Tsuiki A , Luo W , Henning T , Vishwanathan S , Dinh C , Adams D , Sweeney E , Mitchell J , Bachman S , Sharma P , Powell N , Hendry M , McNicholl J , Kersh E . J Med Primatol 2013 42 (2) 89-100 BACKGROUND: FTY720 is an immunomodulatory agent that reduces lymphocytes in peripheral tissues and circulation. Such agents may be effective as vaginal microbicides for HIV prevention. Systemic or vaginal application of FTY720 may reduce lymphocyte concentrations in genital tissues, reducing HIV target cell numbers. METHODS: Five female pigtail macaques received topical vaginal gel FTY720 (n = 2), intravenous (IV) FTY720 (n = 2), or placebo gel (n = 1) in this pilot study. Circulating and mucosal lymphocytes and genital mucosa, cytokines, and tissue histology were analyzed to document topical and IV FTY720 effects. RESULTS: Topical and IV FTY720 appeared to decrease the levels of cervicovaginal IL-8, IL-1ra, and genital inflammatory cells. Small sample size precluded statistical analysis. Topical administration had no overt adverse effects. CONCLUSIONS: This study introduces FTY720 as an immunomodulatory agent for the vaginal mucosa, compares topical effects to those of IV administration, and provides the basis for future studies involving FTY720 for HIV prevention. |
Prevention of vaginal SHIV transmission in macaques by a coitally-dependent Truvada regimen
Radzio J , Aung W , Holder A , Martin A , Sweeney E , Mitchell J , Bachman S , Pau CP , Heneine W , Garcia-Lerma JG . PLoS One 2012 7 (12) e50632 BACKGROUND: Daily pre-exposure prophylaxis (PrEP) with Truvada (a combination of emtricitabine (FTC) and tenofovir (TFV) disoproxil fumarate (TDF)) is a novel HIV prevention strategy recently found to prevent HIV transmission in men who have sex with men and heterosexual couples. We previously showed that a coitally-dependent Truvada regimen protected macaques against rectal SHIV transmission. Here we examined FTC and tenofovir TFV exposure in vaginal tissues after oral dosing and assessed if peri-coital Truvada also protects macaques against vaginal SHIV infection. METHODS: The pharmacokinetic profile of emtricitabine (FTC) and tenofovir (TFV) was evaluated at first dose. FTC and TFV levels were measured in blood plasma, rectal, and vaginal secretions. Intracellular concentrations of FTC-triphosphate (FTC-TP) and TFV-diphosphate (TFV-DP) were measured in PBMCs, rectal tissues, and vaginal tissues. Efficacy of Truvada in preventing vaginal SHIV infection was assessed using a repeat-exposure vaginal SHIV transmission model consisting of weekly exposures to low doses of SHIV162p3. Six pigtail macaques with normal menstrual cycles received Truvada 24 h before and 2 h after each weekly virus exposure and six received placebo. Infection was monitored by serology and PCR amplification of SHIV RNA and DNA. RESULTS: As in humans, the concentration of FTC was higher than the concentration of TFV in vaginal secretions. Also as in humans, TFV levels in vaginal secretions were lower than in rectal secretions. Intracellular TFV-DP concentrations were also lower in vaginal tissues than in rectal tissues. Despite the low vaginal TFV exposure, all six treated macaques were protected from infection after 18 exposures or 4 full menstrual cycles. In contrast, all 6 control animals were infected. CONCLUSIONS: We modeled a peri-coital regimen with two doses of Truvada and showed that it fully protected macaques from repeated SHIV exposures. Our results open the possibility for simplified PrEP regimens to prevent vaginal HIV transmission in women. |
Extent of maternal morbidity in a managed care population in Georgia
Bruce FC , Berg CJ , Joski PJ , Roblin DW , Callaghan WM , Bulkley JE , Bachman DJ , Hornbrook MC . Paediatr Perinat Epidemiol 2012 26 (6) 497-505 BACKGROUND: Although maternal deaths are among the most tragic events related to pregnancy, they are uncommon in the US and, therefore, inadequate indicators of a woman's pregnancy-related health. Maternal morbidity has become a more useful measure for surveillance and research. Traditional attempts to monitor maternal morbidity have used hospital discharge data, which include data only on complications that resulted in hospitalisation, underestimating the frequency and scope of complications. METHODS: To obtain a more accurate assessment of morbidity, we applied a validated computerised algorithm to identify pregnancies and pregnancy-related complications in a defined population enrolled in a health maintenance organisation in the south-eastern US. We examined the most common morbidities by pregnancy outcome and maternal characteristics. RESULTS: We identified 37,741 pregnancies; in half (50.7%), at least one complication occurred. The five most common were urinary tract infections, anaemia, mental health conditions, pelvic and perineal complications, and obstetrical infections. Complications were more likely in women with low socio-economic status (SES), and among non-Hispanic Black women compared with non-Hispanic White women. Multivariable models stratified by race/ethnicity indicated that in pregnancies among non-Hispanic White women, low SES had a modest effect on the odds of having preexisting medical conditions [adjusted odd ratio (AOR) 1.3 [95% confidence interval (CI) 1.2, 1.5]] or having any morbidity (AOR 1.3 [95% CI 1.2, 1.4]). Low SES had little effect on complications among non-Hispanic Black women. CONCLUSION: Our findings suggest that comprehensive health insurance coverage may lessen the unfavourable impact of socio-economic disadvantage on the risk of maternal morbidity. |
A system-based intervention to improve postpartum diabetes screening among women with gestational diabetes
Vesco KK , Dietz PM , Bulkley J , Bruce FC , Callaghan WM , England L , Kimes T , Bachman DJ , Hartinger KJ , Hornbrook MC . Am J Obstet Gynecol 2012 207 (4) 283 e1-6 OBJECTIVE: We sought to determine whether our process improvement program led to increased postpartum diabetes screening rates among women with gestational diabetes mellitus (GDM). STUDY DESIGN: In early 2009, we conducted obstetrics department staff education sessions, revised GDM patient care protocols, and developed an electronic system to trigger reminder calls to patients who had not completed diabetes mellitus screening by 3 months postpartum. We then evaluated the rates of postpartum glucose test order entry and completion for women with GDM delivering from July 2009 through June 2010 (n = 179) and July 2007 through June 2008 (n = 200). RESULTS: After the program's implementation, the proportion of women receiving an order for a postpartum glucose test within 3 months of delivery increased from 77.5-88.8% (P = .004), and test completion increased from 59.5-71.5% (hazard ratio, 1.37; 95% confidence interval, 1.07-1.75). CONCLUSION: Rates of postpartum diabetes testing can be improved with system changes and reminders. |
Newborn size among obese women with weight gain outside the 2009 Institute of Medicine recommendation
Vesco KK , Sharma AJ , Dietz PM , Rizzo JH , Callaghan WM , England L , Bruce FC , Bachman DJ , Stevens VJ , Hornbrook MC . Obstet Gynecol 2011 117 (4) 812-8 OBJECTIVE: To estimate risk of delivering macrosomic, large-for-gestational-age and small-for-gestational-age neonates in obese women with gestational weight gain outside the 2009 Institute of Medicine recommendation (11-20 pounds). METHODS: In a retrospective cohort study, we evaluated 2,080 obese women (body mass index 30 or higher) with singleton pregnancies that resulted in term live births within one health maintenance organization between 2000 and 2005; women with diabetes or hypertensive disorders were excluded. Gestational weight gain was categorized as less than 0, 0 to less than 11, 11-20 (referent), greater than 20-30, greater than 30-40, and greater than 40 pounds and as above, below, or within Institute of Medicine recommendations. We conducted multivariable logistic regression to estimate the odds of large for gestational age and small for gestational age (birth weights greater than the 90th percentile and less than the 10th percentile for gestational age, respectively) and macrosomia (greater than 4,500 g) adjusting for potential confounders. RESULTS: Eighteen percent gained below, 25% within, and 57% above Institute of Medicine recommendations. Prevalence of macrosomia, large for gestational age, and small for gestational age were 4.3%, 19.8%, and 4.3%, respectively. Compared with weight gain of 11-20 pounds, weight gain above recommendations did not significantly decrease small-for-gestational-age risk but was associated with increased odds of macrosomia (adjusted odds ratio [OR] 3.36; 95% confidence interval [CI] 1.74-6.51; 6.0% compared with 2.1%) and large for gestational age (adjusted OR 1.80; 95% CI 1.36-2.38; 23.8% compared with 16.6%). Weight gain below recommendations was associated with increased odds of small for gestational age (adjusted OR 3.94; 95% CI 2.04-7.61; 8.8% compared with 2.7%) and decreased odds of large for gestational age (adjusted OR 0.56; 95% CI 0.37-0.84; 11.2% compared with 16.6%). CONCLUSION: Regarding small for gestational age and large for gestational age, there is no benefit of weight gain above Institute of Medicine recommendations. Weight gain below recommendations decreases large for gestational age but increases small-for-gestational-age risk. LEVEL OF EVIDENCE: II. |
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