Forecasting the global demand for HIV monitoring and diagnostic tests: A 2016-2021 analysis.

INTRODUCTION: Despite considerable progress, just over half of the 37 million people eligible to start antiretroviral therapy (ART) have accessed treatment and millions of HIV-positive people still do not know their status. With demand for ART continuing to grow, meeting the ambitious 90-90-90 HIV treatment targets will depend on improved access to high-quality diagnostics to both diagnose infection and monitor treatment adherence in low and middle-income countries (LMICs). Robust projections of future demand for CD4, viral load (VL), HIV early-infant-diagnosis (EID) tests and HIV rapid diagnostic tests (RDTs) are needed as scale-up continues. METHODS: We estimate the current coverage for HIV diagnostics and project future demand to 2021 using a consolidated forecast using data on past coverage and current demand from a number of sources, from 130 predominantly LMIC countries. RESULTS: We forecast that the overall number of CD4 tests is expected to decline between now and 2021 as more countries adopt test-and-treat and shift to VL testing for patient monitoring. Our consolidated forecast projects a gradual decline in demand for CD4 tests to 16.6 million by 2021. We anticipate that demand for VL tests will increase to 28.5 million by 2021, reflecting the increasing number of people who will receive ART and the adoption of VL testing for patient monitoring. We expect that the demand for EID tests will grow more rapidly than in past years, driven by the implementation of testing at birth in programmes globally, in line with WHO guideline recommendations, doubling to 2.1 million tests by 2021. Demand for rapid diagnostic tests is also likely to increase, reaching 509 million tests by 2021. DISCUSSION: In order to achieve the ambitious 90-90-90 targets, it will be essential to maintain and improve access to CD4, VL, EID tests and RDTs. These projections provide insight into the global demand we can expect to see for these HIV monitoring and diagnostic tests, both in relation to historical trends, and the 90-90-90 targets. Our projections will better enable producers to ensure adequate supply, and to support procurement organisations in planning future funding and purchase plans to meet the anticipated demand. The findings highlight the ongoing need for governments and international funding bodies to prioritise improving capacity and access to HIV diagnostic and monitoring technologies in line with demand.

Which factors determine the wear rate of large-diameter metal-on-metal hip replacements? Multivariate analysis of two hundred and seventy-six components.

BACKGROUND: Determining the relationship between clinical factors and engineering analysis of retrieved hip implants can help our understanding of the mechanism of device failure. This is particularly important for metal-on-metal hip arthroplasties because the most common cause of failure is unexplained. We sought to understand the variation in wear rates in a large series of retrieved metal-on-metal hip arthroplasty components. METHODS: We prospectively recorded preoperative, intraoperative, and postoperative data to study the effect on both head and cup wear rates of the following variables: patient sex, cause of failure, manufacturer type, resurfacing or modular design, blood cobalt and chromium levels, edge-loading, femoral head size, and cup inclination angle. We analyzed 276 components (138 femoral head and acetabular cup couples) retrieved from failed metal-on-metal hip replacements. RESULTS: We found a high rate of edge-loading (64%), but only forty-three (31%) of 138 hips had a cup inclination angle of >55°. Multivariate analysis showed that the most important factor responsible for the variation in wear rate was the presence or absence of edge-loading, even when adjusted for cup inclination angle. Strong positive correlations were found between acetabular cup and femoral head wear rates and between wear rates and both blood cobalt and chromium ion levels. CONCLUSIONS: Multivariate analysis of nine factors found that edge-loading was the most important predictor of wear rate and occurred in two-thirds of failed metal-on-metal hip replacements. The majority did not have excessive cup inclination angles: 68% had an inclination angle of ≤55°. This finding, together with the relatively low median wear rate of the components in our study, suggests that cup position and/or wear rate may not be the only outcome related to failure of metal-on-metal hip replacements.

Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement.

Blood metal ions have been widely used to investigate metal-on-metal hip replacements, but their ability to discriminate between well-functioning and failed hips is not known. The Medicines and Healthcare products Regulatory Agency (MHRA) has suggested a cut-off level of 7 parts per billion (ppb). We performed a pair-matched, case-control study to investigate the sensitivity and specificity of blood metal ion levels for diagnosing failure in 176 patients with a unilateral metal-on-metal hip replacement. We recruited 88 cases with a pre-revision, unexplained failed hip and an equal number of matching controls with a well-functioning hip. We investigated the 7 ppb cut-off level for the maximum of cobalt or chromium and determined optimal mathematical cut-off levels from receiver-operating characteristic curves. The 7 ppb cut-off level for the maximum of cobalt or chromium had a specificity of 89% and sensitivity 52% for detecting a pre-operative unexplained failed metal on metal hip replacement. The optimal cut-off level for the maximum of cobalt or chromium was 4.97 ppb and had sensitivity 63% and specificity 86%. Blood metal ions had good discriminant ability to separate failed from well-functioning hip replacements. The MHRA cut-off level of 7 ppb provides a specific test but has poor sensitivity.

Yield and nutrient content of milk in eight women breast-feeding twins and one woman breast-feeding triplets.

1. The milk yield of eight mothers each breast-feeding twins was determined by test weighing the mothers. Milk yield was determined at 2, 3, 6, 9, and 12 months post partum; however, only one mother was studied at all these times. 2. At 6 months post partum the milk yield for individual breasts of three mothers fully breast-feeding and four mothers partially breast-feeding their infants ranged from 0.84 to 2.16 kg/24 h and 0.42 to 1.39 kg/24 h respectively. The average frequency of breast-feeding for the mothers studied at 6 months post partum was 15.4 feeds/24 h. 3. The milk yield of one mother fully breast-feeding 2.5-month-old triplets was 3.08 kg/24 h and the infants were fed twenty-seven times in 24 h. 4. The concentration of lactose, protein and mixed fat in the milk from individual breasts of mothers fully breast-feeding their infants ranged from 65.6 to 82.2, 7.8 to 15.7 and 16.7 to 46.2 g/l respectively. For the three mothers partially breast-feeding 12-month-old infants the values ranged from 54.8 to 71.8, 14.2 to 19.9 and 4.7 to 40.5 g/l respectively. 5. At 6 and 12 months of age, the proportion of the total energy intake of the infants which was derived from breast milk ranged from 64 to 100% and 6 to 13% respectively. 6. It is concluded that the maximum potential milk yield for women may be higher than the often quoted value of 700-800 ml/24 h.