- Email: [email protected]
The point of point-of-care testing
Comment
that they had not recovered. So, further improvements are desirable. Hill and colleagues are to be applauded for showing that improvements in the management of low back pain in primary care are feasible. Clinicians and researchers now face the challenge of implementing and further optimising the new approach.
3
4
5
6
Bart Koes Department of General Practice, Erasmus University Medical Centre, 3000 CA Rotterdam, Netherlands [email protected]
7 8
I declare that I have no conflicts of interest. 1
2
Hill JC, Whitehurst DGT, Lewis M, et al. Comparison of stratified primary care management for low back pain with current best practice (STarT Back): a randomised controlled trial. Lancet 2011; published online Sept 29. DOI:10.1016/S0140-6736(11)60937-9. Koes BW, van Tulder M, Lin CW, Macedo LG, McAuley J, Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J 2010; 16: 2075–94.
9
van Tulder MW, Koes B, Malmivaara A. Outcome of non-invasive treatment modalities on back pain—an evidence-based review. Eur Spine J 2006; 15 (suppl 1): S64–S81. Kuijpers T, van Middelkoop M, Rubinstein SM, et al. A systematic review on the effectiveness of pharmacological interventions for chronic non-specific low-back pain. Eur Spine J 2011; 20: 40–50. van Middelkoop M, Rubinstein SM, Kuijpers T, et al. A systematic review on the effectiveness of physical and rehabilitation interventions for chronic non-specific low back pain. Eur Spine J 2011; 20: 19–39. Rubinstein SM, van Middelkoop M, Kuijpers T, et al. A systematic review on the effectiveness of complementary and alternative medicine for chronic non-specific low-back pain. Eur Spine J 2010; 19: 1213–28. Foster NE, Hill JC, Hay EM. Subgrouping patients with low back pain in primary care: are we getting any better at it? Man Ther 2011; 16: 3–8. Kamper SJ, Maher CG, Hancock MJ, Koes BW, Croft PR, Hay E. Treatment-based subgroups of low back pain: a guide to appraisal of research studies and a summary of current evidence. Best Pract Res Clin Rheumatol 2010; 24: 181–91. Stanton TR, Hancock MJ, Maher CG, Koes BW. Critical appraisal of clinical prediction rules that aim to optimize treatment selection for musculoskeletal conditions. Phys Ther 2010; 90: 843–54.
The point of point-of-care testing Ilesh Jani and colleagues’ study1 of point-of-care (POC) CD4 cell testing in The Lancet provides an example of effective operational research with routinely collected clinical data in a resource-limited setting. New durable, simple, and affordable cytometric CD4 testing devices aim to decrease the time to antiretroviral therapy initiation and loss to follow-up.2–4 Rapid testing with microfluidics meets the criteria for true POC testing, providing immediate results without needing laboratory personnel or infrastructure.5,6 These
Reuters
See Articles page 1572
Patients await treatment at an AIDS clinic outside Maputo, Mozambique
1532
tests will conserve diagnostic resources and provide convenience and savings for patients. Whether the availability of such technology will help to overcome the many obstacles to successful delivery and scale-up of antiretroviral therapy in resource-limited settings is still to be shown. CD4 staging establishes eligibility for antiretroviral therapy after HIV diagnosis. To obtain a CD4 cell count in resource-limited settings presents many challenges, and the scale of these challenges is often underestimated.1 The required two minimum clinic visits often span a month or longer, and associated transport costs can deter access to care. Pre-analysis infrastructure includes blood collection apparatus, a trained phlebotomist, and quick, reliable, and accountable transport and tracking of samples. Laboratories need functioning and calibrated instruments, trained and disciplined personnel, and quality assurance programmes.7 Finally, the return of CD4 results to a distant clinic is fraught with the difficulties of handwritten medical records and unique identifiers. POC testing offers a solution to many of these difficulties by dispensing with these multiple steps without compromising the accuracy of the result. The clinical settings in which POC CD4 testing might be most effective in treatment and retention have not been identified. Based on an observational study carried www.thelancet.com Vol 378 October 29, 2011
Comment
out in primary health clinics in Mozambique, Jani and colleagues report varied effects of POC CD4 testing on loss to follow-up at different points between enrolment and initiation of antiretroviral treatment. Decreased loss to follow-up was reported between enrolment and CD4 staging (21% vs 57% of patients, adjusted odds ratio 0·2, 95% CI 0·15–0·27), but not between CD4 staging and initiation of antiretroviral therapy in treatment-eligible patients (0·84, 0·49–1·45). Time from enrolment to CD4 testing also decreased with POC testing (a median 3 days vs 32 days), but this finding did not result in a difference in time to initiation of antiretroviral therapy after treatment eligibility was established. The largest loss, noted in many studies from Africa, occurs between rapid POC diagnosis of HIV infection and referral to a programme including CD4 testing.8,9 Efficiency could be improved through linkage of POC CD4 counts with HIV testing so that people who are HIV positive immediately receive CD4 testing, and targeted post-test counselling about risk of disease progression, transmission, and treatment eligibility. This approach might be particularly germane to programmes for the prevention of motherto-child transmission of HIV, in which the time to initiation of antiretroviral therapy needs to be short for maximum benefit. In resource-limited settings, where late attendance to antenatal clinics is common, the need for urgent initiation of antiretroviral therapy in treatment-eligible pregnant women is even greater. POC CD4 testing may not be ideal for every situation. In cities in Africa with well developed transportation and laboratory infrastructure, centralised, highthroughput flow-cytometry might be most efficient. At 20 min per sample, POC CD4 testing could rapidly overwhelm a busy clinic’s capacity for patient throughput and service delivery. Conversely, POC capacity in rural clinics and mobile diagnostic services depends on sufficient demand to justify the expense of services in dispersed communities. The costeffectiveness of placement of these units in voluntary counselling and testing for adults and antenatal clinics for prevention of mother-to-child transmission has not yet been tested, although the urgency of rapid initiation of antiretroviral treatment in eligible pregnant women is clearly of high importance for maternal health and transmission prevention. Feasibility and sustainability depend on the longterm durability of instruments; ease of maintenance, www.thelancet.com Vol 378 October 29, 2011
repairs, and replacements; availability of an adequate supply chain; and reasonable costs. POC testing is a promising advance in efficient service delivery and monitoring in resource-limited settings. However, persistent, albeit lower, loss to follow-up occurs despite the introduction of this technology, which emphasises the complexity of health-seeking behaviour especially for HIV and acceptance of lifelong antiretroviral therapy. Successful HIV programmes should efficiently identify people with HIV by rapid testing, engage HIV-positive patients in care with rapid provision of CD4 staging, provide appropriate counselling, and assess readiness, then initiate antiretroviral therapy and retain individuals in care and treatment with appropriate monitoring. Although technology such as POC CD4 testing might improve service efficiency, such advances must be accompanied by increased knowledge about the barriers to retention, and implementation of solutions to prevent loss to follow-up, and to realise the full potential of HIV treatment, care, and prevention. Seble G Kassaye, *David Katzenstein Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA (SGK); and Division of Infectious Diseases, Stanford University School of Medicine, CA 94305, USA (DK) [email protected] We declare that we have no conflicts of interest. 1
2
3
4
5
6
7 8
9
Jani IV, Sitoe NE, Alfai ER, et al. Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study. Lancet 2011; published online Sept 29. DOI:10.1016/S0140-6736(11)61052-0. Faal M, Naidoo N, Glencross DK, Venter WD, Osih R. Providing immediate CD4 count results at HIV testing improves ART initiation. J Acquir Immune Defic Syndr 2011; published online Aug 18. DOI:10.1097/ QAI.0b013e3182303921. Alassane DP, Geraldine D, Aziz CA, et al. Multi-site evaluation of a point-of-care instrument for CD4+ T cell enumeration using venous and finger prick blood: the PIMA CD4. J Acquir Immune Defic Syndr 2011; published online Sept 8. DOI:10.1097/QAI.0b013e318235b378. Zijenah LS, Kadzirange G, Madzime S, et al. Affordable flow cytometry for enumeration of absolute CD4+ T-lymphocytes to identify subtype C HIV-1 infected adults requiring antiretroviral therapy (ART) and monitoring response to ART in a resource-limited setting. J Transl Med 2006; 4: 33. Moon S, Gurkan UA, Blander J, et al. Enumeration of CD4+ T-cells using a portable microchip count platform in Tanzanian HIV-infected patients. PLoS One 2011; 6: e21409. Rodriguez WR, Christodoulides N, Floriano PN, et al. A microchip CD4 counting method for HIV monitoring in resource-poor settings. PLoS Med 2005; 2: e182. Thairu L, Katzenstein D, Israelski D. Operational challenges in delivering CD4 diagnostics in sub-Saharan Africa. AIDS Care 2011; 23: 814–21. Kranzer K, Zeinecker J, Ginsberg P, et al. Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa. PLoS One 2010; 5: e13801. Losina E, Bassett IV, Giddy J, et al. The “ART” of linkage: pre-treatment loss to care after HIV diagnosis at two PEPFAR sites in Durban, South Africa. PLoS One 2010; 5: e9538.
1533
that they had not recovered. So, further improvements are desirable. Hill and colleagues are to be applauded for showing that improvements in the management of low back pain in primary care are feasible. Clinicians and researchers now face the challenge of implementing and further optimising the new approach.
3
4
5
6
Bart Koes Department of General Practice, Erasmus University Medical Centre, 3000 CA Rotterdam, Netherlands [email protected]
7 8
I declare that I have no conflicts of interest. 1
2
Hill JC, Whitehurst DGT, Lewis M, et al. Comparison of stratified primary care management for low back pain with current best practice (STarT Back): a randomised controlled trial. Lancet 2011; published online Sept 29. DOI:10.1016/S0140-6736(11)60937-9. Koes BW, van Tulder M, Lin CW, Macedo LG, McAuley J, Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J 2010; 16: 2075–94.
9
van Tulder MW, Koes B, Malmivaara A. Outcome of non-invasive treatment modalities on back pain—an evidence-based review. Eur Spine J 2006; 15 (suppl 1): S64–S81. Kuijpers T, van Middelkoop M, Rubinstein SM, et al. A systematic review on the effectiveness of pharmacological interventions for chronic non-specific low-back pain. Eur Spine J 2011; 20: 40–50. van Middelkoop M, Rubinstein SM, Kuijpers T, et al. A systematic review on the effectiveness of physical and rehabilitation interventions for chronic non-specific low back pain. Eur Spine J 2011; 20: 19–39. Rubinstein SM, van Middelkoop M, Kuijpers T, et al. A systematic review on the effectiveness of complementary and alternative medicine for chronic non-specific low-back pain. Eur Spine J 2010; 19: 1213–28. Foster NE, Hill JC, Hay EM. Subgrouping patients with low back pain in primary care: are we getting any better at it? Man Ther 2011; 16: 3–8. Kamper SJ, Maher CG, Hancock MJ, Koes BW, Croft PR, Hay E. Treatment-based subgroups of low back pain: a guide to appraisal of research studies and a summary of current evidence. Best Pract Res Clin Rheumatol 2010; 24: 181–91. Stanton TR, Hancock MJ, Maher CG, Koes BW. Critical appraisal of clinical prediction rules that aim to optimize treatment selection for musculoskeletal conditions. Phys Ther 2010; 90: 843–54.
The point of point-of-care testing Ilesh Jani and colleagues’ study1 of point-of-care (POC) CD4 cell testing in The Lancet provides an example of effective operational research with routinely collected clinical data in a resource-limited setting. New durable, simple, and affordable cytometric CD4 testing devices aim to decrease the time to antiretroviral therapy initiation and loss to follow-up.2–4 Rapid testing with microfluidics meets the criteria for true POC testing, providing immediate results without needing laboratory personnel or infrastructure.5,6 These
Reuters
See Articles page 1572
Patients await treatment at an AIDS clinic outside Maputo, Mozambique
1532
tests will conserve diagnostic resources and provide convenience and savings for patients. Whether the availability of such technology will help to overcome the many obstacles to successful delivery and scale-up of antiretroviral therapy in resource-limited settings is still to be shown. CD4 staging establishes eligibility for antiretroviral therapy after HIV diagnosis. To obtain a CD4 cell count in resource-limited settings presents many challenges, and the scale of these challenges is often underestimated.1 The required two minimum clinic visits often span a month or longer, and associated transport costs can deter access to care. Pre-analysis infrastructure includes blood collection apparatus, a trained phlebotomist, and quick, reliable, and accountable transport and tracking of samples. Laboratories need functioning and calibrated instruments, trained and disciplined personnel, and quality assurance programmes.7 Finally, the return of CD4 results to a distant clinic is fraught with the difficulties of handwritten medical records and unique identifiers. POC testing offers a solution to many of these difficulties by dispensing with these multiple steps without compromising the accuracy of the result. The clinical settings in which POC CD4 testing might be most effective in treatment and retention have not been identified. Based on an observational study carried www.thelancet.com Vol 378 October 29, 2011
Comment
out in primary health clinics in Mozambique, Jani and colleagues report varied effects of POC CD4 testing on loss to follow-up at different points between enrolment and initiation of antiretroviral treatment. Decreased loss to follow-up was reported between enrolment and CD4 staging (21% vs 57% of patients, adjusted odds ratio 0·2, 95% CI 0·15–0·27), but not between CD4 staging and initiation of antiretroviral therapy in treatment-eligible patients (0·84, 0·49–1·45). Time from enrolment to CD4 testing also decreased with POC testing (a median 3 days vs 32 days), but this finding did not result in a difference in time to initiation of antiretroviral therapy after treatment eligibility was established. The largest loss, noted in many studies from Africa, occurs between rapid POC diagnosis of HIV infection and referral to a programme including CD4 testing.8,9 Efficiency could be improved through linkage of POC CD4 counts with HIV testing so that people who are HIV positive immediately receive CD4 testing, and targeted post-test counselling about risk of disease progression, transmission, and treatment eligibility. This approach might be particularly germane to programmes for the prevention of motherto-child transmission of HIV, in which the time to initiation of antiretroviral therapy needs to be short for maximum benefit. In resource-limited settings, where late attendance to antenatal clinics is common, the need for urgent initiation of antiretroviral therapy in treatment-eligible pregnant women is even greater. POC CD4 testing may not be ideal for every situation. In cities in Africa with well developed transportation and laboratory infrastructure, centralised, highthroughput flow-cytometry might be most efficient. At 20 min per sample, POC CD4 testing could rapidly overwhelm a busy clinic’s capacity for patient throughput and service delivery. Conversely, POC capacity in rural clinics and mobile diagnostic services depends on sufficient demand to justify the expense of services in dispersed communities. The costeffectiveness of placement of these units in voluntary counselling and testing for adults and antenatal clinics for prevention of mother-to-child transmission has not yet been tested, although the urgency of rapid initiation of antiretroviral treatment in eligible pregnant women is clearly of high importance for maternal health and transmission prevention. Feasibility and sustainability depend on the longterm durability of instruments; ease of maintenance, www.thelancet.com Vol 378 October 29, 2011
repairs, and replacements; availability of an adequate supply chain; and reasonable costs. POC testing is a promising advance in efficient service delivery and monitoring in resource-limited settings. However, persistent, albeit lower, loss to follow-up occurs despite the introduction of this technology, which emphasises the complexity of health-seeking behaviour especially for HIV and acceptance of lifelong antiretroviral therapy. Successful HIV programmes should efficiently identify people with HIV by rapid testing, engage HIV-positive patients in care with rapid provision of CD4 staging, provide appropriate counselling, and assess readiness, then initiate antiretroviral therapy and retain individuals in care and treatment with appropriate monitoring. Although technology such as POC CD4 testing might improve service efficiency, such advances must be accompanied by increased knowledge about the barriers to retention, and implementation of solutions to prevent loss to follow-up, and to realise the full potential of HIV treatment, care, and prevention. Seble G Kassaye, *David Katzenstein Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA (SGK); and Division of Infectious Diseases, Stanford University School of Medicine, CA 94305, USA (DK) [email protected] We declare that we have no conflicts of interest. 1
2
3
4
5
6
7 8
9
Jani IV, Sitoe NE, Alfai ER, et al. Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study. Lancet 2011; published online Sept 29. DOI:10.1016/S0140-6736(11)61052-0. Faal M, Naidoo N, Glencross DK, Venter WD, Osih R. Providing immediate CD4 count results at HIV testing improves ART initiation. J Acquir Immune Defic Syndr 2011; published online Aug 18. DOI:10.1097/ QAI.0b013e3182303921. Alassane DP, Geraldine D, Aziz CA, et al. Multi-site evaluation of a point-of-care instrument for CD4+ T cell enumeration using venous and finger prick blood: the PIMA CD4. J Acquir Immune Defic Syndr 2011; published online Sept 8. DOI:10.1097/QAI.0b013e318235b378. Zijenah LS, Kadzirange G, Madzime S, et al. Affordable flow cytometry for enumeration of absolute CD4+ T-lymphocytes to identify subtype C HIV-1 infected adults requiring antiretroviral therapy (ART) and monitoring response to ART in a resource-limited setting. J Transl Med 2006; 4: 33. Moon S, Gurkan UA, Blander J, et al. Enumeration of CD4+ T-cells using a portable microchip count platform in Tanzanian HIV-infected patients. PLoS One 2011; 6: e21409. Rodriguez WR, Christodoulides N, Floriano PN, et al. A microchip CD4 counting method for HIV monitoring in resource-poor settings. PLoS Med 2005; 2: e182. Thairu L, Katzenstein D, Israelski D. Operational challenges in delivering CD4 diagnostics in sub-Saharan Africa. AIDS Care 2011; 23: 814–21. Kranzer K, Zeinecker J, Ginsberg P, et al. Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa. PLoS One 2010; 5: e13801. Losina E, Bassett IV, Giddy J, et al. The “ART” of linkage: pre-treatment loss to care after HIV diagnosis at two PEPFAR sites in Durban, South Africa. PLoS One 2010; 5: e9538.
1533