Personalized Cancer Monitoring Assay for the Detection of ctDNA in Patients with Solid Tumors.

BACKGROUND: Highly sensitive molecular assays have been developed to detect plasma-based circulating tumor DNA (ctDNA), and emerging evidence suggests their clinical utility for monitoring minimal residual disease and recurrent disease, providing prognostic information, and monitoring therapy responses in patients with solid tumors. The Invitae Personalized Cancer Monitoring™ assay uses a patient-specific, tumor-informed variant signature identified through whole exome sequencing to detect ctDNA in peripheral blood of patients with solid tumors. METHODS: The assay's tumor whole exome sequencing and ctDNA detection components were analytically validated using 250 unique human specimens and nine commercial reference samples that generated 1349 whole exome sequencing and cell-free DNA (cfDNA)-derived libraries. A comparison of tumor and germline whole exome sequencing was used to identify patient-specific tumor variant signatures and generate patient-specific panels, followed by targeted next-generation sequencing of plasma-derived cfDNA using the patient-specific panels with anchored multiplex polymerase chain reaction chemistry leveraging unique molecular identifiers. RESULTS: Whole exome sequencing resulted in overall sensitivity of 99.8% and specificity of > 99.9%. Patient-specific panels were successfully designed for all 63 samples (100%) with ≥ 20% tumor content and 24 (80%) of 30 samples with ≥ 10% tumor content. Limit of blank studies using 30 histologically normal, formalin-fixed paraffin-embedded specimens resulted in 100% expected panel design failure. The ctDNA detection component demonstrated specificity of > 99.9% and sensitivity of 96.3% for a combination of 10 ng of cfDNA input, 0.008% allele frequency, 50 variants on the patient-specific panels, and a baseline threshold. Limit of detection ranged from 0.008% allele frequency when utilizing 60 ng of cfDNA input with 18-50 variants in the patient-specific panels (> 99.9% sensitivity) with a baseline threshold, to 0.05% allele frequency when using 10 ng of cfDNA input with an 18-variant panel with a monitoring threshold (> 99.9% sensitivity). CONCLUSIONS: The Invitae Personalized Cancer Monitoring assay, featuring a flexible patient-specific panel design with 18-50 variants, demonstrated high sensitivity and specificity for detecting ctDNA at variant allele frequencies as low as 0.008%. This assay may support patient prognostic stratification, provide real-time data on therapy responses, and enable early detection of residual/recurrent disease.

Investigation of Presumptive HIV Transmission Associated with Hospitalization Using Nucleotide Sequence Analysis - New York, 2017.

Since implementation of Standard Precautions* for the prevention of bloodborne pathogen transmission in 1985, health care-associated transmission of human immunodeficiency virus (HIV) in the United States has been rare (1). In October 2017, the New York City Department of Health and Mental Hygiene (NYCDOHMH) and the New York State Department of Health (NYSDOH) were notified by a clinician of a diagnosis of acute HIV infection in a young adult male (patient A) without recognized risk factors (i.e., he was monogamous, had an HIV-negative partner, and had no injection drug use) who had recently been hospitalized for a chronic medical condition. The low risk coupled with the recent hospitalization and medical procedures prompted NYSDOH, NYCDOHMH, and CDC to investigate this case as possible health care-associated transmission of HIV. Among persons with known HIV infection who had hospitalization dates overlapping those of patient A, one person (patient B) had an HIV strain highly similar to patient A's strain by nucleotide sequence analysis. The sequence relatedness, combined with other investigation findings, indicated a likely health care-associated transmission. Nucleotide sequence analysis, which is increasingly used for detecting HIV clusters (i.e., persons with closely related HIV strains) and to inform public health response (2,3), might also be used to identify possible health care-associated transmission of HIV to someone with health care exposure and no known HIV risk factors (4).

Phylodynamic Analysis Complements Partner Services by Identifying Acute and Unreported HIV Transmission.

Tailoring public health responses to growing HIV transmission clusters depends on accurately mapping the risk network through which it spreads and identifying acute infections that represent the leading edge of cluster growth. HIV transmission links, especially those involving persons with acute HIV infection (AHI), can be difficult to uncover, or confirm during partner services investigations. We integrated molecular, epidemiologic, serologic and behavioral data to infer and evaluate transmission linkages between participants of a prospective study of AHI conducted in North Carolina, New York City and San Francisco from 2011-2013. Among the 547 participants with newly diagnosed HIV with polymerase sequences, 465 sex partners were reported, of whom only 35 (7.5%) had HIV sequences. Among these 35 contacts, 23 (65.7%) links were genetically supported and 12 (34.3%) were not. Only five links were reported between participants with AHI but none were genetically supported. In contrast, phylodynamic inference identified 102 unreported transmission links, including 12 between persons with AHI. Importantly, all putative transmission links between persons with AHI were found among large clusters with more than five members. Taken together, the presence of putative links between acute participants who did not name each other as contacts that are found only among large clusters underscores the potential for unobserved or undiagnosed intermediaries. Phylodynamics identified many more links than partner services alone and, if routinely and rapidly integrated, can illuminate transmission patterns not readily captured by partner services investigations.

Performance evaluation of the Bio-Rad Geenius HIV 1/2 supplemental assay.

BACKGROUND: In the US, the HIV diagnostic algorithm for laboratory settings recommends the use of an HIV-1/HIV-2 differentiation supplemental assay after an initial reactive antigen/antibody (Ag/Ab) assay result. Since the discontinuation of the Multispot HIV-1/HIV-2 Rapid Test (MS), the Geenius HIV-1/2 Supplemental assay (Geenius) is the only FDA-approved supplemental differentiation test. OBJECTIVE: We compared the performance of Geenius to MS and Western Blot (WB). STUDY DESIGN: The relative seroconversion plasma reactivity of Geenius and MS was assessed using a 50% cumulative frequency analysis from 17 HIV-1 seroconverters. In addition, previously characterized plasma specimens, 186 HIV-1 positive, 100 HIV-2 positive, and 93 Ag/Ab-positive/HIV-1 RNA-negative, were tested with Geenius v1.1 software. McNemar's test was used for paired comparison analysis. A subset of 48 specimens were retested with the upgraded Geenius v1.3 software. RESULTS: In HIV-1 seroconverters, the relative seroconversion reactivity was 2.5 and 2 days before the first positive HIV-1 WB for Geenius and MS, respectively. In HIV-1 positive samples, Geenius performed similarly to HIV-1 WB (p=0.1687) and MS (p=0.8312). In HIV-2 positive samples, Geenius underperformed compared to HIV-2 WB (p=0.0005) and MS (p=0.0012). When using the upgraded software among the HIV-1 positive and Ag/Ab-reactive/HIV-1 RNA-negative samples, gp140 reactivity decreased without affecting characterization of HIV-2 samples. CONCLUSIONS: With HIV-1 samples, Geenius, WB and MS performance was similar as supplemental tests. The updated Geenius software reduced false gp140 reactivity, but had no impact on identifying true HIV-2 infections. Further evaluation will assess the impact of the Geenius software update on final diagnostic interpretations.

Linking HIV and Viral Hepatitis Surveillance Data: Evaluating a Standard, Deterministic Matching Algorithm Using Data From 6 US Health Jurisdictions.

Accurate interpretations and comparisons of record linkage results across jurisdictions require valid and reliable matching methods. We compared existing matching methods used by 6 US state and local health departments (Houston, Texas; Louisiana; Michigan; New York, New York; North Dakota; and Wisconsin) to link human immunodeficiency virus and viral hepatitis surveillance data with a 14-key automated, hierarchical deterministic matching method. Applicable years of study varied by disease and jurisdiction, ranging from 1979 to 2016. We calculated percentage agreement and Cohen's κ coefficient to compare the matching methods used within each jurisdiction. We calculated sensitivity, specificity, and positive predictive value for each matching method, as compared with a new standard that included manual review of discrepant cases. Agreement between the existing matching method and the deterministic matching method was 99.6% or higher in all jurisdictions; Cohen's κ values ranged from 0.87 to 0.98. The sensitivity of the deterministic matching method ranged from 97.4% to 100% in the 6 jurisdictions; specificity ranged from 99.7% to 100%; and positive predictive value ranged from 97.4% to 100%. Although no gold standard exists, prior assessments of existing methods and review of discrepant classifications suggest good accuracy and reliability of our deterministic matching method, with the advantage that our method reduces the need for manual review and allows for standard comparisons across jurisdictions when linking human immunodeficiency virus and viral hepatitis data.

Frequency of Nucleic Acid Amplification Test Positivity Among Men Who Have Sex With Men Returning for a Test-of-Cure Visit 7 to 30 Days After Treatment of Laboratory-Confirmed Neisseria gonorrhoeae Infection at 2 Public Sexual Health Clinics, New York City, 2013 to 2016.

BACKGROUND: The Centers for Disease Control and Prevention 2015 Sexually Transmitted Disease Treatment Guidelines recommend that clinicians consider cephalosporin treatment failure in patients who deny interval sexual exposure and are nucleic acid amplification test (NAAT) positive for Neisseria gonorrhoeae (NG) at least 7 days after adequate treatment. We evaluate the real-world implications of the interval the Centers for Disease Control and Prevention recommends for a NAAT test-of-cure (TOC), by ascertaining the frequency of NG NAAT positivity at different anatomic sites among men who have sex with men (MSM) at TOC 7 to 30 days after treatment. METHODS: We analyzed data from the medical records of MSM with laboratory-confirmed NG who were presumptively treated for NG during the period from June 2013 to April 2016 and returned for a TOC visit within 30 days. Data examined included symptoms, site of NG specimen collection, treatment regimen, follow-up testing, and intervening sexual activity. RESULTS: There were 1027 NG-positive specimens obtained from 763 MSM patients at 889 presumptive treatment visits. Of these, 44% (337/763) MSM returned for 1 or more TOC visits, and 413 specimens were collected a median of 10 days after presumptive treatment. Three percent (14/413) of specimens collected were NG NAAT positive at TOC a median of 13 days after treatment: 5% (12/256) of urethral specimens, 1% (1/147) of anorectal specimens (P = 0.037, urethral vs. anorectal), and 10% (1/10) of oropharyngeal specimens (P = 0.40, urethral vs. oropharyngeal). CONCLUSIONS: A small percent of patients were NG NAAT positive at TOC. Compared with anorectal specimens, urethral specimens were more frequently still positive at TOC. A large proportion of MSM will return for a TOC visit as part of standard clinical care.

Persons living with diagnosed HIV in New York City: over 50% over 50 years old.

Using NYC HIV surveillance data, we estimated the annual median age of persons living with diagnosed HIV (PLWDH) and the proportion of PLWDH over 50 years old in NYC between 2008 and 2015, and described the characteristics, retention in care and viral suppression status among PLWDH in NYC in 2015, by age (<50 vs. ≥50 years old). The median age of PLWDH in NYC increased from 46.4 years (interquartile range [IQR]: 39.4, 53.2) in 2008 to 50.2 years (IQR: 39.8, 57.5) in 2015, and the proportion of PLWDH over 50 years old increased from 35.9% in 2008 to 50.6% in 2015. In 2015, by race/ethnicity, whites had the highest proportion over 50 years old (57.0%) and Asian/Pacific Islanders had the lowest (36.2%); by transmission risk, men who have sex with men were the lowest (40.0%) and injection drug users were the highest (76.1%). A large and increasing proportion of PLWDH over 50 years old presents challenges for HIV-infected individuals and healthcare system. Better social support services for HIV-infected individuals and additional training for medical and public health staff are needed.

Performance evaluation of the FDA-approved Determine™ HIV-1/2 Ag/Ab Combo assay using plasma and whole blood specimens.

BACKGROUND: The Determine™ HIV-1/2 Ag/Ab Combo (DC) rapid test can identify HIV-1 infection earlier than rapid antibody-only tests in plasma specimens. OBJECTIVES: We compared the performance of DC with a laboratory-based antigen/antibody (Ag/Ab) combo assay in plasma and evaluated antigen reactivity in whole blood specimens. STUDY DESIGN: We tested by DC 508 plasma specimens collected in a prospective study and 107 sequential plasma and simulated whole blood specimens from 20 seroconversion panels. Previous results using the ARCHITECT (ARC) Ag/Ab combo assay were compared to DC results. In seroconversion panels, the days from the first HIV1 RNA-positive test to first DC-reactive in plasma and whole blood was compared. McNemar's and Wilcoxon signed rank tests were used for statistical analysis. RESULTS: Of 415 HIV-positive samples, ARC detected 396 (95.4%) and DC 337 (81.2%) (p<0.0001). DC was reactive in 50.0% of ARC-reactive/MS-negative, 78.6% of ARC-reactive/MS-indeterminate, and 99.6% of ARC-reactive/MS-HIV-1-positive or -undifferentiated specimens. DC antigen reactivity was higher among ARC-reactive/MS-negative than MS-indeterminate samples. In 20 HIV-1 seroconversion panels, there was a significant difference between DC reactivity in plasma (91.1%) and whole blood (56.4%) (p<0.0001). DC with whole blood showed a significant delay in reactivity compared to plasma (p=0.008). CONCLUSIONS: In plasma, DC was significantly less sensitive than an instrumented laboratory-based Ag/Ab combo assay. DC in plasma was significantly more sensitive compared to whole blood in early HIV-1 infections. With the U.S. laboratory-based diagnostic algorithm, DC as the first step would likely miss a high proportion of HIV-1 infections in early stages of seroconversion.

Diagnosing acute HIV infection: The performance of quantitative HIV-1 RNA testing (viral load) in the 2014 laboratory testing algorithm.

New recommendations for laboratory diagnosis of HIV infection in the United States were published in 2014. The updated testing algorithm includes a qualitative HIV-1 RNA assay to resolve discordant immunoassay results and to identify acute HIV-1 infection (AHI). The qualitative HIV-1 RNA assay is not widely available; therefore, we evaluated the performance of a more widely available quantitative HIV-1 RNA assay, viral load, for diagnosing AHI. We determined that quantitative viral loads consistently distinguished AHI from a false-positive immunoassay result. Among 100 study participants with AHI and a viral load result, the estimated geometric mean viral load was 1,377,793copies/mL.

Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population.

IMPORTANCE: Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. OBJECTIVE: To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. DESIGN, SETTING, AND PARTICIPANTS: Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. EXPOSURES: All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. MAIN OUTCOMES AND MEASURES: Number and proportion with acute HIV infections detected. RESULTS: Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P < .001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% (95% CI, 8.8%-12.2%) and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4% (95% CI, 10.7%-14.3%). CONCLUSIONS AND RELEVANCE: In a high-prevalence population, HIV screening using an HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections detectable by pooled HIV RNA testing, with a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower-prevalence populations and in persons using preexposure prophylaxis for HIV prevention.

The Multispot rapid HIV-1/HIV-2 differentiation assay is comparable with the Western blot and an immunofluorescence assay at confirming HIV infection in a prospective study in three regions of the United States.

BACKGROUND: A new HIV diagnostic algorithm has been proposed which replaces the use of the HIV-1 Western blot and HIV-1 immunofluorescence assays (IFA) as the supplemental test with an HIV-1/HIV-2 antibody differentiation assay. OBJECTIVES: To compare an FDA-approved HIV-1/HIV-2 antibody differentiation test (Multispot) as a confirmatory test with the HIV-1 Western blot and IFA. STUDY DESIGN: Participants were screened with an HIV-1/HIV-2 combination Antigen/Antibody (Ag/Ab) screening assay. Specimens with repeatedly reactive results were tested with Multispot and either Western blot or IFA. Specimens with discordant screening and confirmatory results were resolved with HIV-1 RNA testing. RESULTS: Individuals (37,876) were screened for HIV infection and 654 (1.7%) had a repeatedly reactive Ag/Ab assay result. On Multispot, 554 (84.7%) were HIV-1 reactive, 0 (0%) were HIV-2 reactive, 1 (0.2%) was reactive for both HIV-1 and HIV-2 (undifferentiated), 9 (1.4%) were HIV-1 indeterminate, and 90 (13.8%) were non-reactive. HIV-1 RNA was detected in 47/90 Multispot non-reactive (52.2%) specimens. Among specimens confirmed to have HIV infection (true positives), Multispot and Western blot detected HIV-1 antibody in a similar proportion of cases (93.7% vs. 94.4% respectively) while Multispot and IFA also detected HIV-1 antibody in a similar proportion of cases (84.5% vs. 83.4% respectively). CONCLUSIONS: In this study, Multispot confirmed HIV infections at a similar proportion to Western blot and IFA. Multispot, Western blot, and IFA, however, did not confirm all of the reactive Ag/Ab assay results and underscores the importance of HIV NAT testing to resolve discordant screening and confirmatory results.

Disparities in the severity of influenza illness: a descriptive study of hospitalized and nonhospitalized novel H1N1 influenza-positive patients in New York City: 2009-2010 influenza season.

OBJECTIVE: To investigate the association between socioeconomic status (SES) and hospitalization for 2009 H1N1 influenza, independently of access to care and known risk factors for severe influenza illness, among New York City residents during the 2009-2010 influenza season. DESIGN: We used a 1:2 case-control study design, matching by age group and month of diagnosis. Cases were defined as laboratory-confirmed patients with 2009 H1N1 influenza who were hospitalized during their illness. Controls were defined as nonhospitalized laboratory-confirmed influenza A patients. Participants were contacted for a telephone interview to collect relevant clinical and demographic data. We used conditional logistic regression to analyze the association between SES and hospitalization. SETTING: New York City. PARTICIPANTS: Of the 171 hospitalized cases who were identified between October 2009 and February 2010, a total of 128 completed telephone interviews. A total of 640 nonhospitalized controls were contacted, and of these, 337 completed interviews. MAIN OUTCOME MEASURES: The main outcome of interest was whether or not a patient was hospitalized during his or her 2009 H1N1 influenza illness. Socioeconomic status was measured using education and neighborhood poverty. RESULTS: We identified a gradient in the odds of hospitalization for 2009 H1N1 influenza by education level among adults. This association could not be entirely explained by access to care and underlying risk factors. An inverse association between odds of hospitalization and neighborhood poverty was also identified among adults and children. CONCLUSIONS: This study suggests that individuals of lower SES were more vulnerable to severe illness during the 2009 H1N1 pandemic. Additional research is needed to help guide interventions to protect this population during future influenza pandemics.

Evaluating the New York City Emergency Department Syndromic Surveillance for Monitoring Influenza Activity during the 2009-10 Influenza Season.

OBJECTIVE: To use laboratory data to assess the specificity of syndromes used by the New York City emergency department (ED) syndromic surveillance system to monitor influenza activity. DESIGN: For the period from October 1, 2009 through March 31, 2010, we examined the correlation between citywide ED syndrome assignment and laboratory-confirmed influenza and respiratory syncytial virus (RSV). In addition, ED syndromic data from five select NYC hospitals were matched at the patient and visit level to corresponding laboratory reports of influenza and RSV. The matched dataset was used to evaluate syndrome assignment by disease and to calculate the sensitivity and specificity of the influenza-like illness (ILI) syndrome. RESULTS: Citywide ED visits for ILI correlated well with influenza laboratory diagnoses (R=0.92). From October 1, 2009, through March 31, 2010, there were 264,532 ED visits at the five select hospitals, from which the NYC Department of Health and Mental Hygiene (DOHMH) received confirmatory laboratory reports of 655 unique cases of influenza and 1348 cases of RSV. The ED visit of most (56%) influenza cases had been categorized in the fever/flu syndrome; only 15% were labeled ILI. Compared to other influenza-related syndromes, ILI had the lowest sensitivity (15%) but the highest specificity (90%) for laboratory-confirmed influenza. Sensitivity and specificity varied by age group and influenza activity level. CONCLUSIONS: The ILI syndrome in the NYC ED syndromic surveillance system served as a specific but not sensitive indicator for influenza during the 2009-2010 influenza season. Despite its limited sensitivity, the ILI syndrome can be more informative for tracking influenza trends than the fever/flu or respiratory syndromes because it is less likely to capture cases of other respiratory viruses. However, ED ILI among specific age groups should be interpreted alongside laboratory surveillance data. ILI remains a valuable tool for monitoring influenza activity and trends as it facilitates comparisons nationally and across jurisdictions and is easily communicated to the public.

Biostatistics.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Recognize the various terms used in biostatistics. 2. Describe the choices that are required in designing a particular research study. 3. Understand the different types of data that may be obtained in any given study. 4. Identify which statistical tools are appropriate for evaluating the different types of data. SUMMARY: Journals of medicine and surgery, such as Plastic and Reconstructive Surgery, are filled with statistics that readers may never have learned about or once understood but soon forgot. Unfortunately, critical review of any abstract requires a thorough understanding of the tools used to evaluate study results. It also requires an evaluation of whether the tools chosen were adequate or even proper, given the study design and the questions asked. This article was conceived to highlight the major topics in biostatistics. It includes a review of common definitions, an outline of the major tests used (correctly or not) in plastic surgery abstracts, and instruction as to their proper use in scientific studies.

Mifepristone followed in 24 hours to 48 hours by misoprostol for late first-trimester abortion.

OBJECTIVE: To investigate the efficacy of mifepristone and misoprostol for the termination of pregnancies in the late first trimester. METHODS: This was a prospective study of 321 women seeking termination of pregnancy with gestations from 64 days to 84 days (+/-3 days) by vaginal ultrasonography. Women were enrolled at three sites: University of Rochester Reproductive Health Program in Rochester, New York; Hung Vuong Hospital in Ho Chi Minh City, Vietnam; and K.E.M. Hospital in Pune, India. Eligible women received 800 mcg of misoprostol vaginally between 24 hours and 48 hours after administration of 200 mg mifepristone. Two additional doses of 400 mcg of misoprostol were administered either orally or vaginally as needed every 3 hours for a maximum of two additional doses (total 1,600 mcg). The primary study outcome measure was complete abortion without surgical intervention. RESULTS: Eighty-nine percent of women who completed the study successfully terminated their pregnancies. Most women were either satisfied (64.8%) or very satisfied (28.6%) with their experience. Ninety-four percent of women reported that they would recommend the procedure to a friend. Most women (90.4%) also agreed they would request a medical abortion if they required another abortion at this gestational age. CONCLUSION: Medical abortion is acceptable and effective in the late first trimester and offers women an acceptable alternative to surgical abortion. LEVEL OF EVIDENCE: II.

Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period.

OBJECTIVE: Mifepristone-misoprostol medical abortion has been approved in the United States since 2000. U.S. providers have preferred to use vaginal misoprostol because of evidence that such a regimen is more effective in later gestations. Buccal administration of misoprostol may be equally effective and more acceptable to some women. METHODS: This open-label, randomized trial was conducted at two sites in Rochester, NY, and involved healthy women with pregnancies through 56 days since the last menstrual period (LMP) as indicated by sonogram. Women received mifepristone 200 mg orally and were randomized to use 800 mug of misoprostol either buccally or vaginally 1 to 2 days later. They returned within 15 days for repeat sonogram. If the woman's pregnancy had not been completely aborted by day 36, a suction abortion was performed. The primary outcome was a complete abortion without surgical intervention. RESULTS: Four hundred forty-two women were enrolled in the study, and complete data were available on 429. The efficacy rate was 95% (205/216) in the buccal group and 93% (199/213) in the vaginal group (chi(2)=0.43, p=.51). Nausea was the most commonly reported side effect, affecting 70% in the buccal group and 62% in the vaginal group. There were no differences in the satisfaction with the overall procedure between the buccal (92%) and the vaginal groups (95%) (chi(2)=1.87, p=.17). CONCLUSION: Buccal administration of misoprostol after low-dose mifepristone for medical abortion appears to be a highly effective and acceptable alternative compared with vaginal administration for medical abortion in pregnancies through 56 days LMP.

Acceptance of HIV testing among pregnant women in Dar-es-Salaam, Tanzania.

BACKGROUND: Increased prevention of maternal-to-child transmission of HIV-1 has now become possible due to the availability of effective antiretroviral drugs in developing countries. It is necessary for pregnant women to know their HIV status in order to administer timely treatment to reduce transmission of the virus. This study assesses correlates of acceptance of testing for HIV infection in the antenatal setting in Dar-es-Salaam, Tanzania. METHODS: Between August 13, 2001 and November 27, 2002, 14,235 pregnant women were offered screening for HIV as part of routine prenatal care. Demographic information pertaining to the women and their partners, if applicable, was collected. Univariate and multiple logistic regression analyses were carried out. RESULTS: The majority of women were married monogamously (60.0%), had < or =7 years of education (75%), and were unemployed (70.4%). Of the 14,235 women offered screening for HIV, 10,991 (77.2%) accepted. Site of recruitment was significantly associated with screening acceptance (P for trend < 0.0001). Additionally, age, education, marital status, and partner's occupation were significant predictors of testing acceptance. CONCLUSION: The site at which recruitment occurs is a significant factor in determining a woman's odds of accepting HIV testing. The site covariate includes such factors as individual counselor effects, length of waiting time, and length of time the site has been operational.