- Email: [email protected]
Sure Start in England
Correspondence
We have received research support and honoraria for lectures from AstraZeneca, SPA, Pfizer, and SigmaTau.
*Luigi Tavazzi, Gianni Tognoni, on behalf of the GISSI-HF Steering Committee [email protected] GISSI-HF Coordinating Centre, ANMCO Research Centre, Via La Marmora 34, 50121 Florence, Italy 1
Tavazzi L, Tognoni G, Franzosi MG, et al. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Failure 2004; 6: 635–41.
www.thelancet.com Vol 373 January 31, 2009
2
3
Barzi F, Wood M, Marfisi RM, et al. Mediterranean diet and all-cause mortality after myocardial infarction: results from the GISSI-Prevenzione trial. Eur J Clin Nutr 2003; 57: 604–11. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007; 357: 2248–61.
Sure Start in England In her Comment (Nov 8, p 1610)1 on our second phase of evaluation of Sure Start local programmes in England,2 Penny Kane makes several points with which we could not agree more. Like her, we would have much preferred to see a randomised controlled trial done, since this would have afforded much stronger causal inferences than the quasiexperimental investigation we undertook. We also agree that the fact that we drew on data collected by two different research teams raises questions about the confidence that can be placed in conclusions drawn. Indeed, these were points we made in our original report. We remain agnostic as to whether the positive effects of Sure Start local programmes we detected were insufficient to be of policy importance or should have emerged on other child outcomes such as verbal ability, especially in so short a time frame (ie, when children are 3 years old). Open-minded scholars can have honest disagreements on this issue. We are continuing to follow up the children and families to determine whether, at age 5 years, the effects detected at age 3 years have been maintained, dissipated, or changed in some manner. We look forward to reporting on this matter in the nottoo-distant future. We declare that we have no conflict of interest.
*Jay Belsky, Alastair Leyland, Jacqueline Barnes, Edward Melhuish
1 2
Kane P. Sure Start Local Programmes in England. Lancet 2008; 372: 1610–12. Melhuish E, Belsky J, Leyland AH, Barnes J, for the National Evaluation of Sure Start Research Team. Effects of fully-established Sure Start Local Programmes on 3-year-old children and their families living in England: a quasi-experimental observational study. Lancet 2008; 372: 1641–47.
The UK’s system of general practice, based on the long-term registered population, is one of the most popular, successful, and efficient ways of delivering primary health care. It allows for continuity of care, a multidisciplinary approach, and a systematic integration of individual and family acute health care with risk management, preventive interventions, and care of long-term disorders. How tragic that the potential of this horizontal approach, so often shown to be successful, has been ignored by the vertical approach in relation to health care embodied in children’s centres and the Sure Start programme. I work in a large general-practice team that includes doctors, nurses, and child health visitors, in a health centre owned by the National Health Service. I walked 200 m down the street to discover a children’s centre under construction, of which none of us was aware. Although the additional support for families and children from psychology to baby massage is very welcome, it is no surprise that this separate programme is associated with lower child immunisation rates.1,2 Immunisation normally takes place in general practice, where Sure Start has no structural input. This has been a missed opportunity for strengthening children’s services through horizontal integration of social services with primary health care, and is ironic at a time when the UK government has been promoting polyclinics in the community. Development is always needed. I hope it is not too late to grow together.
Photolibrary
safety of the tested drugs were not different between patients with and without diabetes. We recorded the glycaemic and glycosylated haemoglobin values at baseline and during the 3·9 years of average follow-up. As for glitazones, their use is not extensive in Italy, but we did not specifically record this treatment. Christopher Florkowski and colleagues again bring up the hypothesis that a reduction in coenzyme Q10 induced by statins might mask the potential benefits of these drugs in patients with heart failure. Actually the Q10 argument was usually a safety concern, yet rosuvastatin seemed to be safe in GISSI-HF as well as in the CORONA trial.3 As for efficacy, although the possibility that a potential benefit from statins might be concealed by a decrease in Q10 production cannot be ruled out, the perspective of admistering two drugs, one to counteract the negative effect of the other, to elderly patients with heart failure, who are probably already on multiple drugs, does not seem too promising. Vincenzo Solfrizzi and coauthors seem to consider the GISSI-HF populations too heterogeneous, with frail elderly patients being over-represented. However, in the GISSI-HF population, two-thirds were of New York Heart Association (NYHA) class II and the remaining third were class III patients with a mean age of 67 years (the median age of patients with chronic heart failure being around 75 years). Accordingly, the criticism looks unfounded.
I declare that I have no conflict of interest.
[email protected]
Anna Eleri Livingstone
Institute for the Study of Children, Families and Social Issues, Birkbeck University of London, 7 Bedford Square, London WC1B 3RA, UK
[email protected] Limehouse Practice, London E14 8HQ, UK
381
Correspondence
1 2
Kane P. Sure Start Programmes in England. Lancet 2008; 372: 1610–11. Melhuish E, Belsky J, Leyland AH, Barnes J, for the National Evaluation of Sure Start Research Team. Effects of fully established Sure Start Local Programmes on children and their families living in England: a quasi-experimental observational study. Lancet 2008; 372: 1641–47.
NIOX MINO® from Aerocrine
Clinical use of exhaled nitric oxide measurements
See Correspondence page 378
382
Stanley Szefler and colleagues’ conclusion that measurement of exhaled nitric oxide (FENO) does not improve asthma outcomes compared with standard care (Sept 20, p 1065)1 could dissuade clinicians from using FENO. However, the study population and FENO management protocol substantially affected the conclusions. Intensive patient support is beneficial in asthma management, and this was shown by the striking improvements seen during the run-in phase, thus leaving little room for further benefit from using FENO. Further, Szefler and colleagues did not reduce inhaled corticosteroids when FENO was low in symptomatic patients. Why not? Their approach would be justified only if “asthma” symptoms were exclusively due to steroid-responsive airway inflammation. This is not true: there are many other causes—eg, anxiety-overlay. A low FENO permits steroid unresponsive symptoms to be differentiated from those due to steroid-responsive inflammation.2 Indeed, this point was made in post-hoc analyses of obese patients in whom symptoms and airway inflammation are more likely to be discordant. FENO measurements facilitated significantly improved outcomes for obese patients whose symptoms “might be difficult to interpret”. We agree. This also applies to other comorbidities—eg, severe rhinitis, anxiety-overlay, and gastrooesophageal reflux, which often make asthma management difficult.3
Cluster analysis indicates that, where symptoms and inflammation are concordant, a biomarker of inflammation is unlikely to help.4 This report confirms that NO measurements are for selected patients. Inflammometry is not for all, but for discordant phenotypes. Inclusion of the whole cohort reduced the study power and obscured the signal from asthma phenotypes that benefit from such assessment. We have received research funding from Aerocrine AB—a manufacturer of nitric oxide analysers.
*D Robin Taylor, Andrew Bush [email protected] Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (DRT); and Royal Brompton Hospital, London, UK (AB) 1
2
3
4
Szefler SJ, Mitchell H, Sorkness CA, et al. Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial. Lancet 2008; 372: 1065–72. Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med 2005; 18: 18. Taylor DR, Pijnenburg MW, Smith AD, De Jongste JC. Exhaled nitric oxide measurements: clinical application and interpretation. Thorax 2006; 61: 817–27. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178: 218–24.
Authors’ reply Robin Taylor and Andrew Bush indicate that our study design did not permit a reduction in steroid dose in the exhaled nitric oxide (NO) group when exhaled NO was low. As indicated in our report, the objective was to determine whether exhaled NO, when added to a guidelines-based approach, improved asthma control compared with the guidelines-based approach alone. We concluded that the addition of exhaled NO added little. Taylor and Bush also argue that a study by Smith and colleagues1 shows that exhaled NO helps differentiate steroid-responsive from steroid-unresponsive symptoms. The reduction in inhaled corticosteroids would probably result in no difference in the final steroid dose between the two treatment groups. Given the strong response to steroids in our population,
had we included this option in our study design, there is no reason to expect that the frequency of steroidunresponsiveness would be substantial enough to affect our result. Taylor and Bush point to our posthoc analyses as an indication that a subpopulation, such as obese patients, could benefit from exhaled NO application. Further, they suggest that exhaled NO measurements might prove useful for asthma phenotypes for which symptoms and inflammation are discordant, and suggest that our inclusion of the whole cohort obscures the value of inflammometry. Our results indicate that the population that might benefit in this way is probably very small, and the technique unlikely to prove cost effective. These are, however, all interesting notions and we would strongly support a well designed prospective study to assess the value of these suggestions. We declare that we have no conflict of interest.
*Stanley J Szefler, Peter J Gergen, Herman Mitchell, William W Busse, for the NIAID Inner City Asthma Consortium szefl[email protected] Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Room J313, Denver, CO 80206, USA (SJS); National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA (PJG); Rho, Chapel Hill, NC, USA (HM); and University of Wisconsin, Madison, WI, USA (WWB) 1
Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med 2005; 18: 18.
Department of Error GISSI-HF investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1223–30—In this Article (Oct 4), the first sentence of the Procedures section in the Methods should have read: “Between Aug 6, 2002, and Feb 28, 2005, patients were randomly assigned to receive one capsule per day of 1 g n-3 PUFA (850–882 mg eicosapentaenoic acid and docosahexaenoic acid as ethyl esters in the average ratio of 1·2:1) or to matching placebo.”
www.thelancet.com Vol 373 January 31, 2009
We have received research support and honoraria for lectures from AstraZeneca, SPA, Pfizer, and SigmaTau.
*Luigi Tavazzi, Gianni Tognoni, on behalf of the GISSI-HF Steering Committee [email protected] GISSI-HF Coordinating Centre, ANMCO Research Centre, Via La Marmora 34, 50121 Florence, Italy 1
Tavazzi L, Tognoni G, Franzosi MG, et al. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Failure 2004; 6: 635–41.
www.thelancet.com Vol 373 January 31, 2009
2
3
Barzi F, Wood M, Marfisi RM, et al. Mediterranean diet and all-cause mortality after myocardial infarction: results from the GISSI-Prevenzione trial. Eur J Clin Nutr 2003; 57: 604–11. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007; 357: 2248–61.
Sure Start in England In her Comment (Nov 8, p 1610)1 on our second phase of evaluation of Sure Start local programmes in England,2 Penny Kane makes several points with which we could not agree more. Like her, we would have much preferred to see a randomised controlled trial done, since this would have afforded much stronger causal inferences than the quasiexperimental investigation we undertook. We also agree that the fact that we drew on data collected by two different research teams raises questions about the confidence that can be placed in conclusions drawn. Indeed, these were points we made in our original report. We remain agnostic as to whether the positive effects of Sure Start local programmes we detected were insufficient to be of policy importance or should have emerged on other child outcomes such as verbal ability, especially in so short a time frame (ie, when children are 3 years old). Open-minded scholars can have honest disagreements on this issue. We are continuing to follow up the children and families to determine whether, at age 5 years, the effects detected at age 3 years have been maintained, dissipated, or changed in some manner. We look forward to reporting on this matter in the nottoo-distant future. We declare that we have no conflict of interest.
*Jay Belsky, Alastair Leyland, Jacqueline Barnes, Edward Melhuish
1 2
Kane P. Sure Start Local Programmes in England. Lancet 2008; 372: 1610–12. Melhuish E, Belsky J, Leyland AH, Barnes J, for the National Evaluation of Sure Start Research Team. Effects of fully-established Sure Start Local Programmes on 3-year-old children and their families living in England: a quasi-experimental observational study. Lancet 2008; 372: 1641–47.
The UK’s system of general practice, based on the long-term registered population, is one of the most popular, successful, and efficient ways of delivering primary health care. It allows for continuity of care, a multidisciplinary approach, and a systematic integration of individual and family acute health care with risk management, preventive interventions, and care of long-term disorders. How tragic that the potential of this horizontal approach, so often shown to be successful, has been ignored by the vertical approach in relation to health care embodied in children’s centres and the Sure Start programme. I work in a large general-practice team that includes doctors, nurses, and child health visitors, in a health centre owned by the National Health Service. I walked 200 m down the street to discover a children’s centre under construction, of which none of us was aware. Although the additional support for families and children from psychology to baby massage is very welcome, it is no surprise that this separate programme is associated with lower child immunisation rates.1,2 Immunisation normally takes place in general practice, where Sure Start has no structural input. This has been a missed opportunity for strengthening children’s services through horizontal integration of social services with primary health care, and is ironic at a time when the UK government has been promoting polyclinics in the community. Development is always needed. I hope it is not too late to grow together.
Photolibrary
safety of the tested drugs were not different between patients with and without diabetes. We recorded the glycaemic and glycosylated haemoglobin values at baseline and during the 3·9 years of average follow-up. As for glitazones, their use is not extensive in Italy, but we did not specifically record this treatment. Christopher Florkowski and colleagues again bring up the hypothesis that a reduction in coenzyme Q10 induced by statins might mask the potential benefits of these drugs in patients with heart failure. Actually the Q10 argument was usually a safety concern, yet rosuvastatin seemed to be safe in GISSI-HF as well as in the CORONA trial.3 As for efficacy, although the possibility that a potential benefit from statins might be concealed by a decrease in Q10 production cannot be ruled out, the perspective of admistering two drugs, one to counteract the negative effect of the other, to elderly patients with heart failure, who are probably already on multiple drugs, does not seem too promising. Vincenzo Solfrizzi and coauthors seem to consider the GISSI-HF populations too heterogeneous, with frail elderly patients being over-represented. However, in the GISSI-HF population, two-thirds were of New York Heart Association (NYHA) class II and the remaining third were class III patients with a mean age of 67 years (the median age of patients with chronic heart failure being around 75 years). Accordingly, the criticism looks unfounded.
I declare that I have no conflict of interest.
[email protected]
Anna Eleri Livingstone
Institute for the Study of Children, Families and Social Issues, Birkbeck University of London, 7 Bedford Square, London WC1B 3RA, UK
[email protected] Limehouse Practice, London E14 8HQ, UK
381
Correspondence
1 2
Kane P. Sure Start Programmes in England. Lancet 2008; 372: 1610–11. Melhuish E, Belsky J, Leyland AH, Barnes J, for the National Evaluation of Sure Start Research Team. Effects of fully established Sure Start Local Programmes on children and their families living in England: a quasi-experimental observational study. Lancet 2008; 372: 1641–47.
NIOX MINO® from Aerocrine
Clinical use of exhaled nitric oxide measurements
See Correspondence page 378
382
Stanley Szefler and colleagues’ conclusion that measurement of exhaled nitric oxide (FENO) does not improve asthma outcomes compared with standard care (Sept 20, p 1065)1 could dissuade clinicians from using FENO. However, the study population and FENO management protocol substantially affected the conclusions. Intensive patient support is beneficial in asthma management, and this was shown by the striking improvements seen during the run-in phase, thus leaving little room for further benefit from using FENO. Further, Szefler and colleagues did not reduce inhaled corticosteroids when FENO was low in symptomatic patients. Why not? Their approach would be justified only if “asthma” symptoms were exclusively due to steroid-responsive airway inflammation. This is not true: there are many other causes—eg, anxiety-overlay. A low FENO permits steroid unresponsive symptoms to be differentiated from those due to steroid-responsive inflammation.2 Indeed, this point was made in post-hoc analyses of obese patients in whom symptoms and airway inflammation are more likely to be discordant. FENO measurements facilitated significantly improved outcomes for obese patients whose symptoms “might be difficult to interpret”. We agree. This also applies to other comorbidities—eg, severe rhinitis, anxiety-overlay, and gastrooesophageal reflux, which often make asthma management difficult.3
Cluster analysis indicates that, where symptoms and inflammation are concordant, a biomarker of inflammation is unlikely to help.4 This report confirms that NO measurements are for selected patients. Inflammometry is not for all, but for discordant phenotypes. Inclusion of the whole cohort reduced the study power and obscured the signal from asthma phenotypes that benefit from such assessment. We have received research funding from Aerocrine AB—a manufacturer of nitric oxide analysers.
*D Robin Taylor, Andrew Bush [email protected] Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (DRT); and Royal Brompton Hospital, London, UK (AB) 1
2
3
4
Szefler SJ, Mitchell H, Sorkness CA, et al. Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial. Lancet 2008; 372: 1065–72. Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med 2005; 18: 18. Taylor DR, Pijnenburg MW, Smith AD, De Jongste JC. Exhaled nitric oxide measurements: clinical application and interpretation. Thorax 2006; 61: 817–27. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178: 218–24.
Authors’ reply Robin Taylor and Andrew Bush indicate that our study design did not permit a reduction in steroid dose in the exhaled nitric oxide (NO) group when exhaled NO was low. As indicated in our report, the objective was to determine whether exhaled NO, when added to a guidelines-based approach, improved asthma control compared with the guidelines-based approach alone. We concluded that the addition of exhaled NO added little. Taylor and Bush also argue that a study by Smith and colleagues1 shows that exhaled NO helps differentiate steroid-responsive from steroid-unresponsive symptoms. The reduction in inhaled corticosteroids would probably result in no difference in the final steroid dose between the two treatment groups. Given the strong response to steroids in our population,
had we included this option in our study design, there is no reason to expect that the frequency of steroidunresponsiveness would be substantial enough to affect our result. Taylor and Bush point to our posthoc analyses as an indication that a subpopulation, such as obese patients, could benefit from exhaled NO application. Further, they suggest that exhaled NO measurements might prove useful for asthma phenotypes for which symptoms and inflammation are discordant, and suggest that our inclusion of the whole cohort obscures the value of inflammometry. Our results indicate that the population that might benefit in this way is probably very small, and the technique unlikely to prove cost effective. These are, however, all interesting notions and we would strongly support a well designed prospective study to assess the value of these suggestions. We declare that we have no conflict of interest.
*Stanley J Szefler, Peter J Gergen, Herman Mitchell, William W Busse, for the NIAID Inner City Asthma Consortium szefl[email protected] Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Room J313, Denver, CO 80206, USA (SJS); National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA (PJG); Rho, Chapel Hill, NC, USA (HM); and University of Wisconsin, Madison, WI, USA (WWB) 1
Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med 2005; 18: 18.
Department of Error GISSI-HF investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1223–30—In this Article (Oct 4), the first sentence of the Procedures section in the Methods should have read: “Between Aug 6, 2002, and Feb 28, 2005, patients were randomly assigned to receive one capsule per day of 1 g n-3 PUFA (850–882 mg eicosapentaenoic acid and docosahexaenoic acid as ethyl esters in the average ratio of 1·2:1) or to matching placebo.”
www.thelancet.com Vol 373 January 31, 2009