Perinatal program evaluations: methods, impacts, and future goals.

The objective of this methodology note is to examine perinatal program evaluation methods as they relate to the life course health development model (LCHD) and risk reduction for poor birth outcomes. We searched PubMed, CDC, ERIC, and a list from the Association of Maternal and Child Health Programs (AMCHP) to identify sources. We included reports from theory, methodology, program reports, and instruments, as well as reviews of Healthy Start Programs and home visiting. Because our review focused upon evaluation methods we did not include reports that described the Healthy Start Program. The LCHD model demonstrates the non-linear relationships among epigenetic factors and environmental interactions, intentionality or worldview within a values framework, health practices, and observed outcomes in a lifelong developmental health trajectory. The maternal epigenetic and social environment during fetal development sets the stage for the infant's lifelong developmental arc. The LCHD model provides a framework to study challenging maternal child health problems. Research that tracks the long term maternal-infant health developmental trajectory is facilitated by multiple, linked public record systems. Two instruments, the life skills progression instrument and the prenatal risk overview are theoretically consistent with the LCHD and can be adapted for local or population-based use. A figure is included to demonstrate a method of reducing interaction among variables by sample definition. Both in-place local programs and tests of best practices in community-based research are needed to reduce unacceptably high infant mortality. Studies that follow published reporting standards strengthen evidence.

Maternal health literacy progression among rural perinatal women.

This research examined changes in maternal health literacy progression among 106 low income, high risk, rural perinatal African American and White women who received home visits by Registered Nurse Case Managers through the Enterprise Community Healthy Start Program. Maternal health literacy progression would enable women to better address intermediate factors in their lives that impacted birth outcomes, and ultimately infant mortality (Lu and Halfon in Mater Child Health J 7(1):13-30, 2003; Sharma et al. in J Natl Med Assoc 86(11):857-860, 1994). The Life Skills Progression Instrument (LSP) (Wollesen and Peifer, in Life skills progression. An outcome and intervention planning instrument for use with families at risk. Paul H. Brookes Publishing Co., Baltimore, 2006) measured changes in behaviors that represented intermediate factors in birth outcomes. Maternal Health Care Literacy (LSP/M-HCL) was a woman's use of information, critical thinking and health care services; Maternal Self Care Literacy (LSP/M-SCL) was a woman's management of personal and child health at home (Smith and Moore in Health literacy and depression in the context of home visitation. Mater Child Health J, 2011). Adequacy was set at a score of (≥4). Among 106 women in the study initial scores were inadequate (<4) on LSP/M-HCL (83 %), and on LSP/M-SCL (30 %). Significant positive changes were noted in maternal health literacy progression from the initial prenatal assessment to the first (p < .01) postpartum assessment and to the final (p < .01) postpartum assessment using McNemar's test of gain scores. Numeric comparison of first and last gain scores indicated women's scores progressed (LSP/M-HCL; p < .0001) and (LSP/M-SCL; p < .0001). Elevated depression scores were most frequent among women with <4 LSP/M-HCL and/or <4 LSP/M-SCL. Visit notes indicated lack or loss of relationship with the father of the baby and intimate partner discord contributed to higher depression scores.

Implementing early-warning indicators of HIV drug resistance in the Caribbean.

A key component of the World Health Organization's (WHO's) Global HIV Drug Resistance (HIVDR) prevention and assessment strategy is to monitor HIVDR early-warning indicators (EWIs), which provide strategic information for HIVDR containment. The Pan American Health Organization (PAHO)/WHO supported implementation of HIVDR EWI monitoring in 16 Caribbean countries. Results from 15 countries were analyzed by year of patient initiation of antiretroviral therapy for the period 2005-2009. This report demonstrates the need for capacity-building to standardize prescribing practices and to strengthen adherence strategies and antiretroviral drug procurement management systems.

Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study.

We performed a pilot surveillance study on transmitted HIV drug resistance (TDR) in Iran, with specimens collected and stored as dried blood spots (DBS). The protease region and relevant positions in the reverse transcriptase region of the pol gene were sequenced to detect mutations known to be associated with resistance to drugs in standard first-line regimens. Seventy-three specimens were collected, with 39 (53%) specimens yielding sequence from both protease and at least part of RT. Specimens were almost exclusively HIV-1 subtype CRF 35_A1D based on pol sequencing. Mutations were restricted to RT, with D67DG and V75AV each seen in a single specimen. An atypical protease inhibitor mutation, I47M, appeared at a resistance-associated position in protease from a single specimen. These preliminary data showed that the rate of transmitted drug resistance in Iran, within the areas sampled, was 5.1% (2/39). However, the small sample size makes this figure only an approximation. Due to the sampling strategy and resulting small sample size, we were unable to accurately calculate TDR rates for individual areas using the WHO HIV drug resistance threshold survey method. Increasing the sample size and improving the yield from DBS would improve the accuracy of drug resistance surveillance and facilitate wider application of this methodology in Iran.

The World Health Organization's global strategy for prevention and assessment of HIV drug resistance.

Antiretroviral treatment (ART) for HIV is being scaled up rapidly in resource-limited countries. Treatment options are simplified and standardized, generally with one potent first-line regimen and one potent alternate first-line regimen recommended. Widespread HIV drug resistance (HIVDR) was initially feared, but reports from resource-limited countries suggest that initial ART programmes are as effective as in resource-rich countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up. ART interruptions must be minimized to maintain viral suppression on the first-line regimen for as long as possible. Lack of availability of appropriate second-line drugs is a concern, as is the additional accumulation of resistance mutations in the absence of viral load testing to determine failure. The World Health Organization (WHO) recommends a minimum-resource strategy for prevention and assessment of HIVDR in resource-limited countries. The WHO's Global Network HIVResNet provides standardized tools, training, technical assistance, laboratory quality assurance, analysis of results and recommendations for guidelines and public health action. National strategies focus on assessments to guide immediate public health action to improve ART programme effectiveness in minimizing HIVDR and to guide regimen selection. Globally, WHO HIVResNet collects and analyses data to support evidence-based international policies and guidelines. Financial support is provided by major international organizations and technical support from HIVDR experts worldwide. As of December 2007, 25 countries were planning or implementing the strategy; seven countries report results in this supplement.

World Health Organization surveys to monitor HIV drug resistance prevention and associated factors in sentinel antiretroviral treatment sites.

The World Health Organization (WHO) estimates that >2 million people will have started antiretroviral therapy (ART) by the end of 2006. As the development of some HIV drug resistance (HIVDR) is inevitable in populations taking ART, the emergence of HIVDR must be balanced against the benefits of providing ART, including improved health outcomes and decreased HIV/AIDS-associated morbidity and mortality. ART programmes should operate to minimize the emergence of HIVDR in populations receiving therapy and HIVDR itself must be monitored to ensure ongoing regimen efficacy. ART regimens in resource-limited settings are usually selected at the national level following a public health approach: generally only one first-line regimen with alternate regimen(s) incorporating within-class drug substitutions are available in the public sector. The WHO has developed a population-based HIVDR assessment and prevention strategy, which includes standardized HIVDR monitoring surveys in populations receiving first-line ART at sentinel sites. The WHO surveys monitor HIVDR prevention in sentinel sites by utilizing a standardized, minimum-resource prospective survey methodology to assess the success of adult and paediatric ART sites in preventing HIVDR emergence during the first year of ART. The surveys also identify associated factors that can be addressed at the level of the ART site or programme. WHO HIVDR monitoring surveys are designed to be integrated easily into a country's ongoing, routine HIV-related evaluation activities. Performed regularly at representative sites, the data generated will inform evidence-based decision making regarding national and global ART regimen selection and minimize the emergence of HIVDR at a population level.

Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment.

BACKGROUND: The World Health Organization (WHO) HIV drug resistance (HIVDR) threshold survey method was developed for surveillance of transmitted HIVDR in resource-limited countries. The method is being implemented with minimal resources as a routine public health activity to produce comparable results in multiple countries and areas within countries. Transmitted drug resistant HIV strains will be seen first in cities or health districts where antiretroviral treatment (ART) has been widely available for years. WHO recommends countries begin surveillance in these areas. METHODS: Each survey requires < or =47 specimens from individuals consecutively diagnosed with HIV to categorize resistance to each relevant drug class as <5%, 5-15% or >15%. Use of routinely collected information and remnant specimens is recommended to minimize costs. Site and individual eligibility criteria are designed to minimize inclusion of ARV-experienced individuals and individuals infected before ART was available. RESULTS: Surveys have been implemented in 21 countries. In this supplement, seven countries report results of <5% transmitted HIVDR in areas where ART has been available for the longest time period. The main challenges in implementation are acquiring sufficient numbers of eligible specimens and optimizing specimen handling. CONCLUSION: The WHO HIVDR threshold survey method is feasible in resource-limited countries and produces information relevant to ART and drug resistance prevention planning.

HIV drug resistance transmission threshold survey in Bangkok, Thailand.

BACKGROUND: Antiretroviral therapy (ART) began in Thailand in the Bangkok Metropolitan Area (BMA) in 1988 and scale-up began in 2001. The national first-line regimen is stavudine, lamivudine and nevirapine in fixed-dose combination, which is a regimen with a low genetic barrier for resistance. Because viral load and resistance testing are not widely available, unidentified HIV drug resistance (HIVDR) may occur during treatment and could be transmitted. METHODS: We undertook a threshold survey to assess HIVDR transmission in two subsets of recently infected individuals in the BMA. The first group consisted of returning blood donors tested at the Thai Red Cross National Blood Centre who seroconverted within the past 12 months. The second group comprised recently infected (as defined by BED assay) clients of the Thai Red Cross voluntary counselling and testing centre (VCT). RESULTS: Genotyping of 50 consecutive specimens each from blood donors and VCT clients during 2005-2006 showed no mutations associated with HIVDR in the reverse transcriptase or protease regions of the HIV pol gene. These results are categorized by the WHO HIV drug resistance threshold survey method as representing a low prevalence (<5%) of transmitted HIV drug resistance. CONCLUSIONS: Every effort should be made to minimize the emergence of resistance in treated individuals and to prevent primary and secondary HIV transmission. To continue to monitor HIVDR transmission, Thailand has planned additional surveys--including longitudinal surveys--in these and additional groups of individuals.

World Health Organization/HIVResNet Drug Resistance Laboratory Strategy.

With rapidly increasing access to antiretroviral drugs globally, HIV drug resistance (HIVDR) has become a significant public health issue. This requires a coordinated and collaborative response from country level to international level to assess the extent of HIVDR and the establishment of efficient and evidence-based strategies to minimize its appearance and onward transmission. In parallel with the rollout of universal access to HIV treatment, countries are developing protocols based on the recommendations of the World Health Organization (WHO) to measure, at a population level, both transmitted HIVDR and HIVDR emerging during treatment. The WHO in collaboration with international experts (HIVResNet Laboratory Working Group), has developed a laboratory strategy, which has the overall goal of delivering quality-assured HIV genotypic results on specimens derived from the HIVDR surveys. The results will be used to help control the emergence and spread of drug resistance and to guide decision makers on antiretroviral therapy policy at national, regional and global level. The HIVDR Laboratory Strategy developed by the WHO includes several key aspects: the formation of a global network of national, regional and specialized laboratories accredited to perform HIVDR testing using a common set of WHO standard and performance indicators; recommendations of acceptable methods for collection, handling, shipment and storage of specimens in field conditions; and the provision of laboratory technical support, capacity building and quality assurance for network laboratories. The WHO/HIVResNet HIVDR Laboratory Network has been developed along the lines of other successful laboratory networks coordinated by the WHO. As of August 2007, assessment for accreditation has been conducted in 30 laboratories, covering the WHO's African, South-East Asia, Western Pacific, and the Caribbean Regions.

Conditions and Dynamics That Impact Maternal Health Literacy among High Risk Prenatal-Interconceptional Women.

The purpose of the study was to describe conditions and dynamics in the lives of high-risk, low-income, Southern United States prenatal-interconceptional women (n = 37) in a home visiting program that promoted maternal health literacy progression. In the Life Course Health Development (LCHD) Model, conditions were risk and protective factors that impacted health. Dynamics drove the complex, epigenetic relationships between risk and protective factors. Maternal health literacy promotion helped participants address conditions and dynamics to create positive life changes. This research was a retrospective, mixed methods study of women's service records documenting care from prenatal admission to 24 months post-delivery. The Life Skills Progression Instrument (LSP) was scored to measure maternal health literacy progression. Ethnographic content analysis of visit notes triangulated with quantitative data enabled specificity of critical data elements. Subsequently, a complementary focus group was conducted with the Registered Nurse Case Managers (RNCM). Severe social conditions included devastating poverty, low educational achievement, transient housing, unstable relationships, incarceration, lack of continuous health insurance, and shortage of health care providers. Dynamics included severe psycho-social stressors, domestic violence, lack of employment, low income, low self-esteem and self-expectations, and social/family restraints upon women's intended positive changes. An important protective factor was the consistent, stable, evidence-informed relationship with the RNCM. Findings from the focus group discussion supported content analysis results.

Surveillance methods to monitor the impact of HIV therapy programmes in resource-constrained countries.

To monitor the collective national impact of initiatives to expand the availability of HIV therapy including antiretroviral treatment (ART) countries need to monitor the proportion of HIV-infected individuals who are receiving HIV therapy, whether morbidity is decreasing, and HIV-infected individuals are experiencing increased survival, and if there is an overall decrease in the number of individuals dying of HIV. However, in many resource-constrained countries these data are limited or unavailable. Morbidity surveillance relies primarily on AIDS case reporting, but severe under-reporting limits the usefulness of these data. A variety of AIDS case definitions are in use and case definitions do not concur with clinical staging definitions. Harmonizing AIDS case definitions with clinical staging, providing resources and training to improve reporting, and using other surveillance systems, such as tuberculosis programme data to monitor morbidity are urgently needed. A cohort analysis of individuals in ART programmes to follow the progress and outcomes of these patients longitudinally is important to monitor quality of care and impact. Because the rapid scale-up of ART programmes may result in HIV drug resistance, surveillance for drug resistant viruses is also required. Very few resource-constrained countries have well-functioning vital registration systems to assess mortality trends and cause-specific mortality. Alternative approaches to measuring mortality trends, such as sample vital registration with verbal autopsy should be considered. Strong commitments from governments, international organizations and other partners are needed to establish and strengthen the HIV morbidity and mortality monitoring surveillance systems.

The combination of p53 mutation and neu/erbB-2 amplification is associated with poor survival in node-negative breast cancer.

PURPOSE: Increases in neu/erbB-2 have been implicated in breast cancer prognosis, but do not predict all recurrences. On the basis of evidence that p53 mutation is involved in the development of human neoplasia, we examined the prognostic value of p53 alterations in combination with neu/erbB-2 amplification. PATIENTS AND METHODS: A consecutive series of women were observed for recurrence and death (median follow-up of 85 months) and tumors from 543 individuals were analyzed for p53 mutation status and neu/erbB-2 amplification. Exons 4 through 10 of the p53 gene were analyzed by single-stranded conformational polymorphism and mutations were confirmed by DNA sequencing. The association of p53 mutation status and neu/erbB-2 amplification with risk of recurrence and death was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: p53 mutations occurred in 24.5% of the axillary node-negative breast carcinomas. Mutations were more frequent in carcinomas with neu/erbB-2 amplification: 38.9% compared with only 20.9% in those without neu/erbB-2 amplification. We found elevated risks of disease recurrence and overall mortality in patients with both p53 mutation and neu/erbB-2 amplification in their tumor compared with patients with neither or only one of the alterations. This increase persisted with adjustment for other prognostic factors (relative risk, 2.32; P =.002 for recurrence; relative risk, 2.22; P =.004 for death). CONCLUSION: Evaluation of tumors for p53 mutations may be beneficial to identify women at higher risk of disease recurrence and death when the tumor has neu/erbB-2 amplification, but in the absence of neu/erbB-2 amplification, the presence of p53 mutation may not provide additional independent prognostic information.

Prevalence and correlates of Chlamydia infection in Canadian street youth.

PURPOSE: To determine the prevalence and correlates of Chlamydia trachomatis in Canadian street youth. METHODS: A cross-sectional study of street youth between the ages of 15-24 years was conducted over a 9-month period in seven large urban centers across Canada. Youth were recruited through "drop-in" centers, outreach work, and mobile vans in each city. Information was collected through a nurse-administered questionnaire. Youth were asked to provide urine to test for chlamydia trachomatis by polymerase chain reaction. Separate logistic regression models were run for males and females controlling for age. RESULTS: The prevalence rate of chlamydia was 8.6% in 1355 youth (95% CI = (7.1%, 10.1%)). Higher prevalence rates were found in females than in males (10.9% vs. 7.3%, respectively) and in Aboriginal youth than in non-Aboriginal youth (13.7% vs. 6.6%, respectively). Four variables were associated with increased risk of chlamydia infection in females: Aboriginal status; self-perceived risk; having no permanent home; and having been in foster care. One predictor of chlamydia for males was having had a social worker. CONCLUSIONS: A high prevalence of chlamydia was found in this vulnerable population in comparison to other Canadian youth. Having been in foster care and having had a social worker were found to have a strong association with chlamydia.

HIV and hepatitis C virus testing and seropositivity rates in Canadian federal penitentiaries: A critical opportunity for care and prevention.

BACKGROUND: Incarcerated persons experience high rates of HIV and hepatitis C virus (HCV) infection, but little is known about the burden of these bloodborne viruses among federal penitentiary inmates in Canada. OBJECTIVE: The present study investigates rates of testing and seropositivity for HIV and HCV among inmates in all 53 Canadian federal penitentiaries. METHODS: A cross-sectional design using surveillance data on voluntary HIV and HCV antibody testing in 2002 were applied to estimate the rate of testing uptake and the rate of incident seropositive tests among new admissions to federal penitentiaries and resident inmates. Rates of testing and infection were further examined by sex and region. Seroprevalence of HIV and HCV was estimated from the number of cumulative positive tests to year-end. RESULTS: Of 7670 new admissions during 2002, 30% were tested for HIV and HCV. Test seropositivity rates in this group were 0.7% for HIV and 10% for HCV. Of the 12,426 resident inmates, 28% were tested for HIV and 27% for HCV. Seropositivity rates in this group were 0.3% for HIV and 7% for HCV. Seroprevalence rates at yearend for 2002 were 2.0% for HIV and 26% for HCV and were substantially higher among women offenders (HIV: 3.7% of women, 1.9% of men; HCV: 34% of women, 26% of men). Variations in testing uptake and test seropositivity were observed across regions. CONCLUSIONS: The present study underscores the value of continued monitoring and evaluation of trends in HIV and HCV infection, which remain prevalent in federal penitentiaries. Higher rates of testing are warranted for at-risk inmates to improve early detection of infection and provide infected inmates with timely care and treatment. For those who remain free of infection, testing can provide the additional benefits of exposing inmates to health counselling and for the reinforcement of prevention messages. The period of incarceration is also a critical opportunity to link inmates with outside resources in preparation for release to the community.

HIV drug resistance assessment in the Western Pacific region. A systematic review.

Antiretroviral therapy is being rapidly scaled-up in Western Pacific region countries. Prevention and assessment of HIV drug resistance is an essential component of successful global antiretroviral therapy scale-up. We performed a systematic review of public health surveys and HIV drug resistance studies conducted in the low- and middle-income countries in the Western Pacific region. A total of 38 publications assessing HIV drug resistance were reviewed. Studies assessing transmitted drug resistance in recently infected individuals or drug resistance among individuals starting antiretroviral therapy found low rates of HIV drug resistance. Assessments of HIV drug resistance emerging in populations receiving antiretroviral therapy demonstrated variable rates of drug resistance, but suggest an urgent need to support antiretroviral therapy adherence and retention in care, ensure the use of quality assured drugs, and guarantee continuous drug supplies. Additionally, programmatic assessment informed by routine standardized surveillance of transmitted and acquired HIV drug resistance is essential to optimize antiretroviral therapy delivery in the Western Pacific region.

Phase I/II trial of metronomic chemotherapy with daily dalteparin and cyclophosphamide, twice-weekly methotrexate, and daily prednisone as therapy for metastatic breast cancer using vascular endothelial growth factor and soluble vascular endothelial growth factor receptor levels as markers of response.

PURPOSE Preclinical studies indicate that metronomic chemotherapy is antiangiogenic and synergistic with other antiangiogenic agents. We designed a phase I/II study to evaluate the safety and activity of adding dalteparin and prednisone to metronomic cyclophosphamide and methotrexate in women with measurable metastatic breast cancer (MBC). PATIENTS AND METHODS Patients received daily dalteparin and oral cyclophosphamide, twice-weekly methotrexate, and daily prednisone (dalCMP). The primary study end point was clinical benefit rate (CBR), a combination of complete response (CR), partial response (PR), and prolonged stable disease for > or = 24 weeks (pSD). Secondary end points included time to progression (TTP), duration of response, and overall survival (OS). Biomarker response to treatment was assessed by using plasma vascular endothelial growth factor (VEGF) and soluble VEGF receptors (sVEGFRs) -1 and -2. Results Forty-one eligible patients were accrued. Sixteen (39%) had no prior chemotherapy for MBC; 15 (37%) had two or more chemotherapy regimens for MBC. Toxicities were minimal except for transient grade 3 elevation of liver transaminases in 11 patients (27%) and grade 3 vomiting in one patient (2%). One patient (2%) had CR, six (15%) had PR, and three (7%) had pSD, for a CBR of 10 (24%) of 41 patients. Median TTP was 10 weeks (95% CI, 8 to 17 weeks), and median OS was 48 weeks (95% CI, 32 to 79 weeks). VEGF levels decreased but not significantly, whereas sVEGFR-1 and -2 levels increased significantly after 2 weeks of therapy. There was no correlation between response and VEGF, sVEGFR-1, or sVEGFR-2 levels. CONCLUSION Metronomic dalCMP is safe, well tolerated, and clinically active in MBC.

Combining data sources to monitor the HIV epidemic in Canada.

This article describes the methods, results and future perspectives of four information sources used to monitor the HIV epidemic in Canada: AIDS case surveillance, HIV case surveillance, HIV sentinel serosurveillance, and behavioral surveillance. Synthesizing data from these multiple sources provides a more comprehensive picture of the HIV epidemic than any one source alone could provide. In Canada, there has been a shift over time from an epidemic dominated by men who have sex with men to one where more than half of new infections are attributed to other groups, such as injection drug users and non-injecting heterosexuals. The available evidence also suggests increasing HIV infections among Aboriginal persons and among women. Surveillance data have been used in Canada to guide prevention and care programs and to formulate policy. In particular, these data have been used to support the development of an HIV testing program in pregnancy, to re-direct community work toward injection drug users and the young, and to demonstrate the effectiveness of new treatments for HIV. The main challenge now is to continue to improve the monitoring of the shifting HIV epidemic with more accurate data and to use the resulting information to inform appropriate prevention and care responses.