- Email: [email protected]
Community treatment orders for patients with psychosis – Authors' reply
Correspondence
that no difference exists between two interventions, because the two groups become very similar. For this reason, Burns and colleagues did a per-protocol analysis (not included in the report), which gave much the same results as the ITT analysis. Nevertheless, per-protocol analysis results in a substantial loss of power with a type II error (ie, failure to reject a false null hypothesis) of 33% for the hypotheses stated in the Article. The obvious next step does not need new data acquisition. It is an equivalence meta-analysis, based on the three available randomised controlled trials.1–3 Since such an analysis would need to include both analysis sets (ITT and per protocol), it would be helpful for Burns and colleagues to provide the results of their per-protocol analysis. We declare that we have no conflicts of interest.
*Florian Naudet, Mohamed El Sanharawi fl[email protected] Centre d’Investigation Clinique CIC-P INSERM 0203, Hôpital de Pontchaillou, Centre Hospitalier Universitaire de Rennes et Université de Rennes 1, Rennes cedex 9, France (FN); and INSERM, UMRS 872, Centre de Recherche des Cordeliers, Team 17, Université Pierre et Marie Curie—Paris 6, Paris, France (MEL) 1
2
3
Burns T, Rugkåsa J, Molodynski A, et al. Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial. Lancet 2013; 381: 1627–33. Steadman HJ, Gounis K, Dennis D, et al. Assessing the New York City involuntary outpatient commitment pilot program. Psychiatr Serv 2001; 52: 330–36. Swartz MS, Swanson JW, Wagner HR, Burns BJ, Hiday VA, Borum R. Can involuntary outpatient commitment reduce hospital recidivism? findings from a randomized trial with severely mentally ill individuals. Am J Psychiatry 1999; 156: 1968–75.
The clinical efficacy and cost effectiveness of community treatment orders, known as assisted outpatient treatment in the USA, are of great interest worldwide to those who provide psychiatric services. The fundamental question is whether the trade-off of some coercion is associated with improved treatment, increased safety, and reduced expenditures. Do the outcomes merit the impingement on 502
civil rights? The study by Burns and colleagues1 might, unfortunately, be detrimental to understanding of this controversial topic, because of flaws in the methods and analysis. Orders for involuntary treatment in community settings in most countries are meant to address people with serious mental illness, who for whatever reasons—predominantly anosognosia—do not take medically indicated psychiatric medications, and by doing so, put themselves and others at risk. If we are to study the usefulness of community treatment imposed on an individual, we need to study the individuals for whom it is meant. To do otherwise is a waste of research time and money, since the outcome data can tell us nothing useful. Burns and colleagues’ methodology was flawed, such that the findings might not be applicable to most of the countries that have, or are contemplating, involuntary community psychiatric treatment. Burns and colleagues assessed 442 patients for the study. Of 106 who were excluded at the outset, 91 (21%) were eliminated because they refused to participate. Since involuntary community treatment in most of the world is focused on those who refuse to follow their treatment plans, there is a high likelihood that the refusers to participate and the refusers to take medication had a high overlap. Thus, the investigators excluded at the outset the population most likely to benefit from the intervention under study, substantially increasing the likelihood of finding no difference between the study and the control groups. A further 53 potential participants refused consent and were excluded from the study before the intervention was implemented. Thus, 144 (33%) patients were excluded because of refusal to participate. The actual target group for involuntary community treatment was on the sidelines, not in the study at all. Even if there had been no-one who refused to participate, the results
of this study would not be useful to most countries. The population that was randomised consisted of inpatients with psychosis. That is not the population for involuntary community treatment in most of the world. On the basis of the data provided, included in this study could have been an 18–22 year-old or a 60–65 year-old with three lifetime psychiatric admissions (two of which were involuntary) and no criminal involvement. The typical patient receiving a CTO would much more likely be an individual aged 25–55 years with several psychiatric admissions and criminal involvement secondary to untreated mental illness. For these reasons, the likelihood that Burns and colleagues could have shown a difference between the two groups was almost nil, independent of the potential effectiveness of the intervention under study. I declare that I have no conflicts of interest.
Jeffrey Geller jeff[email protected] University of Massachusetts Medical School, Department of Psychiatry, Worcester, MA 01655, USA 1
Burns T, Rugkåsa J, Molodynski A, et al. Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial. Lancet 2013; 381: 1627–33.
Authors’ reply Reporting a complex trial such as OCTET 1 in 3000 words is a challenge, so we are thankful to these correspondents for allowing us to clarify some important points. The two groups in our trial were very different indeed in the duration of community coercion. Perry and colleagues have confused the total time under coercion, which includes readmissions, with the time under coercion in the condition of randomisation (median 183 days for community treatment orders [CTOs] vs 8 days for Section 17). Section 17 leave is not best understood as the imposition of an alternative compulsory community regime. It is the use of a long-established and brief www.thelancet.com Vol 382 August 10, 2013
Correspondence
We declare that we have no conflicts of interest.
www.thelancet.com Vol 382 August 10, 2013
*Tom Burns, Joron Rugkåsa, Andrew Molodynski [email protected] Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK (TB, JR); Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway (JR); and Oxford Health NHS Foundation Trust, Oxford, UK (AM) 1
2
3
Burns T, Rugkåsa J, Molodynski A, et al. Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial. Lancet 2013; 381: 1627–33. Dawson J, Burns T, Rugkasa J. Lawfulness of a randomised trial of the new community treatment order regime for England and Wales. Med Law Rev 2011; 19: 1–26. Churchill R, Owen G, Singh S, Hotopf M. International experiences of using community treatment orders. London: Institute of Psychiatry, 2007.
Transmission of M abscessus in patients with cystic fibrosis I read with great interest Josephine Bryant and colleagues’ report (May 4, p 1551)1 on the use of wholegenome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis. Retrospectively, wholegenome sequencing and antimicrobial susceptibility testing were done on 168 consecutive isolates of M abscessus from 31 patients attending an adult cystic fibrosis centre in the UK between 2007 and 2011. In line with previous observations,2 there was no evidence for transmission within the 13 patients infected with M abscessus subspecies abscessus. However, for the 15 patients infected with M abscessus subspecies massiliense, isolates from 11 patients by phylogenetic analysis were found to represent two clustered outbreaks indicative of transmission. In epidemiological terms this is a classical example of a tardive epidemic spreading over several years, unlikely due to person-to-person spread but more probably involving contaminated hospital equipment. Most notably, all of the nine M abscessus subspecies massiliense isolates from cluster 1 showed high-level resistance
to both aminoglycosides and macrolides, with the corresponding and identical genetic mutations in 16S or 23S rRNA, respectively.3,4 Six out of nine patients had received long-term macrolide therapy and four out of nine patients had prior chronic aminoglycoside exposure, suggesting transmission of a primarily resistant strain rather than independent acquisition of resistance during therapy. I am concerned that this outbreak had remained unnoticed for 4 years. Antimicrobial susceptibility should be determined for M abscessus isolates from cystic fibrosis patients receiving antibiotic therapy, in particular for macrolide and aminoglycoside resistances, because in-vitro testing predicts clinical response to treatment.5 Apparently, this had not been done as part of a regular diagnostic workup for the patient isolates included in the study, although corresponding test procedures for microdilution are well established.5 A combined highlevel aminoglycoside and macrolide resistance in M abscessus is a rarity that should prompt thorough investigations, including patient history, genetic analyses to identify the corresponding resistance mutations, contact tracing, and molecular epidemiological studies.4
R A Longuehaye/Science Photo Library
clinical provision to ease the discharge to voluntary care used with many detained patients. We have reported the detailed legal considerations outlining its use in our study.2 We actively strove to keep the two groups similar in other respects to isolate and test the effect of the CTO. Our sample was drawn exclusively from patients who were judged by their treating psychiatrist to be poorly adherent to treatment and who needed to be subject to immediate recall to hospital (usually because of a high risk of rapid and severe relapse). These are the requirements for them to be considered for a CTO. Procedures for imposing CTOs vary in different jurisdictions, but the clinical features of those placed on them are very consistent and our sample closely matches international practice.3 We were disappointed by the number of protocol violations, although this occurrence is not uncommon in clinical effectiveness trials. They were exceptions rather than the rule, so an intention-to-treat analysis remains the appropriate approach to the data. A sensitivity analysis excluding the violators did not change our results. Since our results are in line with the only other two randomised controlled trials, we doubt that further metaanalyses (which we would welcome) would change the overall picture. We share the concern that such a powerful intervention has been in use for decades (assisted outpatient treatment has been in place in some states in the USA since the 1980s) without more attempts to test its effect to the same standards expected in other branches of medicine. More and better studies are certainly needed. There are great difficulties in providing high-quality evidence, but we believe we have made a contribution to understanding in this difficult discipline. Currently, the weight of evidence is that CTOs do not deliver the outcomes that they were introduced to achieve.
I declare that I have no conflicts of interest.
Erik C Böttger [email protected] Institut für Medizinische Mikrobiologie, Universität Zürich, 8006 Zürich, Switzerland 1
2
3
Bryant JM, Grogono DM, Greaves D, et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet 2013; 381: 1551–60. Bange FC, Brown BA, Smaczny C, Wallace Jr RJ, Böttger EC. Lack of transmission of Mycobacterium abscessus among patients with cystic fibrosis attending a single clinic. Clin Infect Dis 2001; 32: 1648–50. Prammananan T, Sander P, Brown BA, et al. A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae. J Infect Dis 1998; 177: 1573–81.
503
that no difference exists between two interventions, because the two groups become very similar. For this reason, Burns and colleagues did a per-protocol analysis (not included in the report), which gave much the same results as the ITT analysis. Nevertheless, per-protocol analysis results in a substantial loss of power with a type II error (ie, failure to reject a false null hypothesis) of 33% for the hypotheses stated in the Article. The obvious next step does not need new data acquisition. It is an equivalence meta-analysis, based on the three available randomised controlled trials.1–3 Since such an analysis would need to include both analysis sets (ITT and per protocol), it would be helpful for Burns and colleagues to provide the results of their per-protocol analysis. We declare that we have no conflicts of interest.
*Florian Naudet, Mohamed El Sanharawi fl[email protected] Centre d’Investigation Clinique CIC-P INSERM 0203, Hôpital de Pontchaillou, Centre Hospitalier Universitaire de Rennes et Université de Rennes 1, Rennes cedex 9, France (FN); and INSERM, UMRS 872, Centre de Recherche des Cordeliers, Team 17, Université Pierre et Marie Curie—Paris 6, Paris, France (MEL) 1
2
3
Burns T, Rugkåsa J, Molodynski A, et al. Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial. Lancet 2013; 381: 1627–33. Steadman HJ, Gounis K, Dennis D, et al. Assessing the New York City involuntary outpatient commitment pilot program. Psychiatr Serv 2001; 52: 330–36. Swartz MS, Swanson JW, Wagner HR, Burns BJ, Hiday VA, Borum R. Can involuntary outpatient commitment reduce hospital recidivism? findings from a randomized trial with severely mentally ill individuals. Am J Psychiatry 1999; 156: 1968–75.
The clinical efficacy and cost effectiveness of community treatment orders, known as assisted outpatient treatment in the USA, are of great interest worldwide to those who provide psychiatric services. The fundamental question is whether the trade-off of some coercion is associated with improved treatment, increased safety, and reduced expenditures. Do the outcomes merit the impingement on 502
civil rights? The study by Burns and colleagues1 might, unfortunately, be detrimental to understanding of this controversial topic, because of flaws in the methods and analysis. Orders for involuntary treatment in community settings in most countries are meant to address people with serious mental illness, who for whatever reasons—predominantly anosognosia—do not take medically indicated psychiatric medications, and by doing so, put themselves and others at risk. If we are to study the usefulness of community treatment imposed on an individual, we need to study the individuals for whom it is meant. To do otherwise is a waste of research time and money, since the outcome data can tell us nothing useful. Burns and colleagues’ methodology was flawed, such that the findings might not be applicable to most of the countries that have, or are contemplating, involuntary community psychiatric treatment. Burns and colleagues assessed 442 patients for the study. Of 106 who were excluded at the outset, 91 (21%) were eliminated because they refused to participate. Since involuntary community treatment in most of the world is focused on those who refuse to follow their treatment plans, there is a high likelihood that the refusers to participate and the refusers to take medication had a high overlap. Thus, the investigators excluded at the outset the population most likely to benefit from the intervention under study, substantially increasing the likelihood of finding no difference between the study and the control groups. A further 53 potential participants refused consent and were excluded from the study before the intervention was implemented. Thus, 144 (33%) patients were excluded because of refusal to participate. The actual target group for involuntary community treatment was on the sidelines, not in the study at all. Even if there had been no-one who refused to participate, the results
of this study would not be useful to most countries. The population that was randomised consisted of inpatients with psychosis. That is not the population for involuntary community treatment in most of the world. On the basis of the data provided, included in this study could have been an 18–22 year-old or a 60–65 year-old with three lifetime psychiatric admissions (two of which were involuntary) and no criminal involvement. The typical patient receiving a CTO would much more likely be an individual aged 25–55 years with several psychiatric admissions and criminal involvement secondary to untreated mental illness. For these reasons, the likelihood that Burns and colleagues could have shown a difference between the two groups was almost nil, independent of the potential effectiveness of the intervention under study. I declare that I have no conflicts of interest.
Jeffrey Geller jeff[email protected] University of Massachusetts Medical School, Department of Psychiatry, Worcester, MA 01655, USA 1
Burns T, Rugkåsa J, Molodynski A, et al. Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial. Lancet 2013; 381: 1627–33.
Authors’ reply Reporting a complex trial such as OCTET 1 in 3000 words is a challenge, so we are thankful to these correspondents for allowing us to clarify some important points. The two groups in our trial were very different indeed in the duration of community coercion. Perry and colleagues have confused the total time under coercion, which includes readmissions, with the time under coercion in the condition of randomisation (median 183 days for community treatment orders [CTOs] vs 8 days for Section 17). Section 17 leave is not best understood as the imposition of an alternative compulsory community regime. It is the use of a long-established and brief www.thelancet.com Vol 382 August 10, 2013
Correspondence
We declare that we have no conflicts of interest.
www.thelancet.com Vol 382 August 10, 2013
*Tom Burns, Joron Rugkåsa, Andrew Molodynski [email protected] Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK (TB, JR); Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway (JR); and Oxford Health NHS Foundation Trust, Oxford, UK (AM) 1
2
3
Burns T, Rugkåsa J, Molodynski A, et al. Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial. Lancet 2013; 381: 1627–33. Dawson J, Burns T, Rugkasa J. Lawfulness of a randomised trial of the new community treatment order regime for England and Wales. Med Law Rev 2011; 19: 1–26. Churchill R, Owen G, Singh S, Hotopf M. International experiences of using community treatment orders. London: Institute of Psychiatry, 2007.
Transmission of M abscessus in patients with cystic fibrosis I read with great interest Josephine Bryant and colleagues’ report (May 4, p 1551)1 on the use of wholegenome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis. Retrospectively, wholegenome sequencing and antimicrobial susceptibility testing were done on 168 consecutive isolates of M abscessus from 31 patients attending an adult cystic fibrosis centre in the UK between 2007 and 2011. In line with previous observations,2 there was no evidence for transmission within the 13 patients infected with M abscessus subspecies abscessus. However, for the 15 patients infected with M abscessus subspecies massiliense, isolates from 11 patients by phylogenetic analysis were found to represent two clustered outbreaks indicative of transmission. In epidemiological terms this is a classical example of a tardive epidemic spreading over several years, unlikely due to person-to-person spread but more probably involving contaminated hospital equipment. Most notably, all of the nine M abscessus subspecies massiliense isolates from cluster 1 showed high-level resistance
to both aminoglycosides and macrolides, with the corresponding and identical genetic mutations in 16S or 23S rRNA, respectively.3,4 Six out of nine patients had received long-term macrolide therapy and four out of nine patients had prior chronic aminoglycoside exposure, suggesting transmission of a primarily resistant strain rather than independent acquisition of resistance during therapy. I am concerned that this outbreak had remained unnoticed for 4 years. Antimicrobial susceptibility should be determined for M abscessus isolates from cystic fibrosis patients receiving antibiotic therapy, in particular for macrolide and aminoglycoside resistances, because in-vitro testing predicts clinical response to treatment.5 Apparently, this had not been done as part of a regular diagnostic workup for the patient isolates included in the study, although corresponding test procedures for microdilution are well established.5 A combined highlevel aminoglycoside and macrolide resistance in M abscessus is a rarity that should prompt thorough investigations, including patient history, genetic analyses to identify the corresponding resistance mutations, contact tracing, and molecular epidemiological studies.4
R A Longuehaye/Science Photo Library
clinical provision to ease the discharge to voluntary care used with many detained patients. We have reported the detailed legal considerations outlining its use in our study.2 We actively strove to keep the two groups similar in other respects to isolate and test the effect of the CTO. Our sample was drawn exclusively from patients who were judged by their treating psychiatrist to be poorly adherent to treatment and who needed to be subject to immediate recall to hospital (usually because of a high risk of rapid and severe relapse). These are the requirements for them to be considered for a CTO. Procedures for imposing CTOs vary in different jurisdictions, but the clinical features of those placed on them are very consistent and our sample closely matches international practice.3 We were disappointed by the number of protocol violations, although this occurrence is not uncommon in clinical effectiveness trials. They were exceptions rather than the rule, so an intention-to-treat analysis remains the appropriate approach to the data. A sensitivity analysis excluding the violators did not change our results. Since our results are in line with the only other two randomised controlled trials, we doubt that further metaanalyses (which we would welcome) would change the overall picture. We share the concern that such a powerful intervention has been in use for decades (assisted outpatient treatment has been in place in some states in the USA since the 1980s) without more attempts to test its effect to the same standards expected in other branches of medicine. More and better studies are certainly needed. There are great difficulties in providing high-quality evidence, but we believe we have made a contribution to understanding in this difficult discipline. Currently, the weight of evidence is that CTOs do not deliver the outcomes that they were introduced to achieve.
I declare that I have no conflicts of interest.
Erik C Böttger [email protected] Institut für Medizinische Mikrobiologie, Universität Zürich, 8006 Zürich, Switzerland 1
2
3
Bryant JM, Grogono DM, Greaves D, et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet 2013; 381: 1551–60. Bange FC, Brown BA, Smaczny C, Wallace Jr RJ, Böttger EC. Lack of transmission of Mycobacterium abscessus among patients with cystic fibrosis attending a single clinic. Clin Infect Dis 2001; 32: 1648–50. Prammananan T, Sander P, Brown BA, et al. A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae. J Infect Dis 1998; 177: 1573–81.
503