Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

BACKGROUND Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. DESIGN Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. METHODS Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. RESULTS POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring. CONCLUSION The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Structural equation modeling of the medical outcome study: Short Form 36 (SF-36)

The factorial validity of the SF-36 was evaluated using confirmatory factor analysis (CFA) methods, structural equation modeling (SEM), and multigroup structural equation modeling (MSEM). First, the measurement and structural model of the hypothesized SF-36 was explicated. Second, the model was tested for the validity of a second-order factorial structure, upon evidence of model misfit, determined the best-fitting model, and tested the validity of the best-fitting model on a second random sample from the same population. Third, the best-fitting model was tested for invariance of the factorial structure across race, age, and educational subgroups using MSEM.^ The findings support the second-order factorial structure of the SF-36 as proposed by Ware and Sherbourne (1992). However, the results suggest that: (a) Mental Health and Physical Health covary; (b) general mental health cross-loads onto Physical Health; (c) general health perception loads onto Mental Health instead of Physical Health; (d) many of the error terms are correlated; and (e) the physical function scale is not reliable across these two samples. This hierarchical factor pattern was replicated across both samples of health care workers, suggesting that the post hoc model fitting was not data specific. Subgroup analysis suggests that the physical function scale is not reliable across the "age" or "education" subgroups and that the general mental health scale path from Mental Health is not reliable across the "white/nonwhite" or "education" subgroups.^ The importance of this study is in the use of SEM and MSEM in evaluating sample data from the use of the SF-36. These methods are uniquely suited to the analysis of latent variable structures and are widely used in other fields. The use of latent variable models for self reported outcome measures has become widespread, and should now be applied to medical outcomes research. Invariance testing is superior to mean scores or summary scores when evaluating differences between groups. From a practical, as well as, psychometric perspective, it seems imperative that construct validity research related to the SF-36 establish whether this same hierarchical structure and invariance holds for other populations.^ This project is presented as three articles to be submitted for publication. ^

Kaposi's Sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era

The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.

Regional Specialization in Communal Agriculture: The Shakers, 1850- 1880

When the Shakers established communal farms in the Ohio Valley, they encountered a new agricultural environment that was substantially different from the familiar soils, climates, and markets of New England and the Hudson Valley. The ways in which their response to these new conditions differed by region has not been well documented. We examine patterns of specialization among the Shakers using the manuscript schedules of the federal Agricultural Censuses from 1850 through 1880. For each Shaker unit, we also recorded a random sample of five farms in the same township (or all available farms if there were fewer than five). The sample of neighboring farms included 75 in 1850, 70 in the next two census years, and 66 in 1880. A Herfindahl-type index suggested that, although the level of specialization was less among the Shakers than their neighbors, trends in specialization by the Shakers and their neighbors were remarkably similar when considered by region. Both Eastern and Western Shakers were more heavily committed to dairy and produce than were their neighbors, while Western Shakers produced more grains than did Eastern Shakers, a pattern imitated in nearby family farms. Livestock and related production was far more important to the Eastern Shakers than to the Western Shakers, again similar to patterns in the census returns from other farms. We conclude that, despite the obvious scale and organizational differences, Shaker production decisions were based on the same comparative advantages that determined production decisions of family farms.

THE BACON CHOW STUDY: THE RELATIONSHIP BETWEEN INFECTIOUS ILLNESS AND GROWTH OF INFANTS

Multiple dietary deficiencies and high rates of infectious illness are major health problems leading to malnutrition and limitation of growth of children in developing countries. Longitudinal studies which provide information on illness incidence and growth velocity are needed in order to untangle the complex interrelationship between nutrition, illness and growth. From 1967 to 1973, researchers led by Dr. Bacon Chow of the Johns Hopkins University School of Hygiene undertook a quasi-experimental prospective study in Suilin Township, Taiwan to determine the effects of a nutritional supplement to the diets of pregnant and lactating women on the growth, development and resistance to disease of their offspring. This dissertation presents results from the analysis of infant morbidity and postnatal growth.^ Maternal nutritional supplementation has no apparent effect on the postnatal growth or morbidity of infants. Significant sex differences exist in growth response to illness and in illness susceptibility. Male infants have more diarrhea and upper respiratory illness. Respiratory illness is positively associated with growth rate in weight in the first semester of life. Diarrhea is significantly negatively associated with growth in length in the second semester. Small-for-date infants are more susceptible to illness in general and have a different pattern of growth response than large-for-date infants.^ Principal components analysis of illness data is shown to be an effective technique for making more precise use of ambiguous morbidity data. Multiple regression with component scores is an accurate method for estimating variance in growth rate predicted by indepenent illness variables. A model is advanced in which initial postnatal growth rate determines subsequent susceptibility to nutritional stress and infection. Initial growth rate is a function of prenatal nutrition, but is not significantly affected by maternal supplementation during gestation or lactation. Critical evaluation is made of nutritional supplementation programs which do not afford disease control.^

Migration as a rural development strategy and the migrants involved : an account of a migrants' hometown in Sichuan, China

This paper attempts to describe part of the history of Chinese rural migration to urban industrial areas. Using a case study of a township in Sichuan, the author examines a type of rural development which she defines as a "bottom-up" style strategy of regional development. Different types of social mobility are observed in the case study, and over its long history, migration in the township has offered diverse means of social mobility to the local peasants. The paper concludes by considering the diversity and limits of Chinese social mobility at this stage.

Fortification and Frontier: The Project Drawn up by Juan Martín Zermeño for Puebla de Sanabria in 1766

Following the death of engineer General Jorge Próspero de Verboom in 1744 and after a few years of transition in the management of Spanish fortifications, Juan Martín Zermeño took on the role, initially with a temporary mandate, but then definitively during a second period that ran from 1766 until his death in 1772. He began this second period with a certain amount of concern because of what had taken place during the last period of conflict. The Seven Years War (1756–1763) which had brought Spain into conflict with Portugal and England in the Caribbean had also lead to conflict episodes along the Spanish–Portuguese border. Zermeño’s efforts as a planner and general engineer gave priority to the northern part of the Spanish–Portuguese border. After studying the territory and the existing fortifications on both sides of the border, Zermeño drew up three important projects in 1766. The outposts that needed to be reinforced were located, from north to south, at Puebla de Sanabria, Zamora and Ciudad Rodrigo, which is where he is believed to have come from. This latter township already had a modern installation built immediately after the war of the Spanish Succession and reinforced with the Fort of La Concepción. However, Zamora and Puebla de Sanabria had some obsolete fortifications that needed modernising. Since the middle of the 15th century Puebla de Sanabria had had a modern castle with rounded turrets, that of the counts of benavente. During the 16th and 17th centuries it had also been equipped with a walled enclosure with small bastions. During the war of the Spanish Succession the Portuguese had enlarged the enclosure and had erected a tentative offshoot to the west. In order to draw up the ambitious Puebla de Sanabria project Zermeño had the aid of some previous reports and projects, such as those by the count of robelin in 1722, the one by Antonio de Gaver in 1752, and Pedro Moreau’s report dated June 1755. This study includes a technical analysis of Zermeño’s project and its strategic position within the system of fortifications along the Spanish–Portuguese border.

Cincinnati, Ohio, ca. 1840 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Cincinnati, Covington & Newport, drawn by B. Oertly. It was lithographed and published by Otto Onken, ca. 1840. Scale [ca. 1:10,500]. Covers also a portion of Northern Kentucky. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Ohio South State Plane NAD 1983 coordinate system (in Feet) (Fipszone 3402). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, drainage, selected buildings, city ward boundaries, cemeteries, canals, and more. Includes also indexes and inset map of Millcreek Township.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Denver, Colorado, 1890 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Rollandet's map of the city of Denver, compiled, drawn and published by Edward Rollandet. It was published by Edward Rollandet in 1890. Scale [ca. 1:21,250]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the HARN State Plane Colorado Central Zone NAD 1983 coordinate system (in Feet) (Fipszone 0502). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, drainage, selected buildings, selected names of landowners, additions, subdivisions, township and range, parks, and more. Includes index and views of buildings.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Madison, Wisconsin, 1855 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Madison and the Four Lake Country : Dane Co. Wis. It was published in 1855. Scale [ca. 1:53,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Wisconsin South NAD 1983 coordinate system (in Feet) (Fipszone 4803). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads (active and projected), drainage, selected points of interest, township and range boundaries, and more. Includes index and text.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

New England, 1862 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: G. Woolworth Colton's railroad, township & distance map of New England : with adjacent portions of New York, Canada & New Brunswick, drawn, engraved & published by G. Woolworth Colton. It was published in 1862. Scale 1:900,000. The image inside the map neatline is georeferenced to the surface of the earth and fit to the USA Contiguous Albers Equal Area Conic projection (Meters). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, state, county, and town boundaries, and more. Relief shown by hachures. Includes table of distances and inset: The eastern portion of Massachusetts on an enlarged scale. Scale 1:350,000. This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

New Hampshire, 1816 (Image 1 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New Hampshire by recent survey : made under the supreme authority and published according to law by Philip Carrigain ; J.J. Barralet, del. ; W. Harrison, sct., Philada. It was published by Philip Carrigain in 1816. Scale [ca. 1:200,000]. This layer is image 1 of 6 total images, representing the northeast portion of the six sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the New Hampshire State Plane coordinate system (NAD 1983 in Feet) (Fipszone 2800). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town boundaries, land grants, and more. Relief shown pictorially and by hachures. Includes area notes, text, and table of population. Also includes illustrations: View of the Great Boars Head and Hampton Beach -- The Cap of the White Mountains -- View of the White Mountains from Shelburne; inset maps: States of the Union east of the Hudson with the adjacent British colonies. Scale [ca. 1:1,920,000] -- The middle, southern and western sections of the United States with the territories. Scale [ca. 1:4,900,000]. Includes: ms. additions with updated county boundary & township names.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

New Hampshire, 1816 (Image 2 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New Hampshire by recent survey : made under the supreme authority and published according to law by Philip Carrigain ; J.J. Barralet, del. ; W. Harrison, sct., Philada. It was published by Philip Carrigain in 1816. Scale [ca. 1:200,000]. This layer is image 2 of 6 total images, representing the center east portion of the six sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the New Hampshire State Plane coordinate system (NAD 1983 in Feet) (Fipszone 2800). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town boundaries, land grants, and more. Relief shown pictorially and by hachures. Includes area notes, text, and table of population. Also includes illustrations: View of the Great Boars Head and Hampton Beach -- The Cap of the White Mountains -- View of the White Mountains from Shelburne; inset maps: States of the Union east of the Hudson with the adjacent British colonies. Scale [ca. 1:1,920,000] -- The middle, southern and western sections of the United States with the territories. Scale [ca. 1:4,900,000]. Includes: ms. additions with updated county boundary & township names.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

New Hampshire, 1816 (Image 3 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New Hampshire by recent survey : made under the supreme authority and published according to law by Philip Carrigain ; J.J. Barralet, del. ; W. Harrison, sct., Philada. It was published by Philip Carrigain in 1816. Scale [ca. 1:200,000]. This layer is image 3 of 6 total images, representing the southeast portion of the six sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the New Hampshire State Plane coordinate system (NAD 1983 in Feet) (Fipszone 2800). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town boundaries, land grants, and more. Relief shown pictorially and by hachures. Includes area notes, text, and table of population. Also includes illustrations: View of the Great Boars Head and Hampton Beach -- The Cap of the White Mountains -- View of the White Mountains from Shelburne; inset maps: States of the Union east of the Hudson with the adjacent British colonies. Scale [ca. 1:1,920,000] -- The middle, southern and western sections of the United States with the territories. Scale [ca. 1:4,900,000]. Includes: ms. additions with updated county boundary & township names.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.