I wish to address the eLetter responding to our recently published
article in BMJ Open (Abouzeid M, Versace VL, Janus ED, et al. A population
-based observational study of diabetes during pregnancy in Victoria,
Australia, 1999-2008). Firstly, thank you to Wigdan Farah for taking the
time to read our article and providing positive feedback. Specifically
they suggest that we add the variable 'socio-eco...
I wish to address the eLetter responding to our recently published
article in BMJ Open (Abouzeid M, Versace VL, Janus ED, et al. A population
-based observational study of diabetes during pregnancy in Victoria,
Australia, 1999-2008). Firstly, thank you to Wigdan Farah for taking the
time to read our article and providing positive feedback. Specifically
they suggest that we add the variable 'socio-economic status' (SES) to our
analysis. They cite the paper by Nomura Y, Marks DJ, Grossman B, et al.
(2012) in Archives of Pediatrics & Adolescent Medicine as an example
of the influence of SES on health outcomes. We are pleased to advise that
we have just had an article accepted by PLoS One entitled 'Socio-cultural
disparities in GDM burden differ by maternal age at first delivery'
(accepted December 2nd, 2014, Abouzeid M, Versace V, Janus E, et al.). We
encourage Wigdan Farah to access this article once it appears online in
the near future.
Kind regards
Abouzeid M, Versace VL, Janus ED, M-A Davey M-A, Philpot B, Oats J,
and Dunbar JA
Articles cited
1. Abouzeid M, Versace VL, Janus ED, et al. A population-based
observational study of diabetes during pregnancy in Victoria, Australia,
1999-2008. BMJ Open. 2014;4(11):e005394.
2. Nomura Y, Marks DJ, Grossman B, et al. Exposure to gestational
diabetes mellitus and low socioeconomic status: effects on neurocognitive
development and risk of attention-deficit/hyperactivity disorder in
offspring. Arch Pediatr Adolesc Med. Apr 2012;166(4):337-343.
3. Abouzeid M, Versace VL, Janus ED, et al. Socio-cultural
disparities in GDM burden differ by maternal age at first
delivery.(Accepted December 2nd, 2014). PLoS One.
Landis et al. describe a temporal association between wartime
conflict, internal displacement, and Nodding syndrome (NS)(1). They raise
infectious, nutritional and neuropsychiatric elements as possible causal
factors. The authors, however, do not mention a key factor that may have
played a major role during the NS epidemic in northern Uganda: a lack of
ivermectin treatment in onchocerciasis endemic areas.
Landis et al. describe a temporal association between wartime
conflict, internal displacement, and Nodding syndrome (NS)(1). They raise
infectious, nutritional and neuropsychiatric elements as possible causal
factors. The authors, however, do not mention a key factor that may have
played a major role during the NS epidemic in northern Uganda: a lack of
ivermectin treatment in onchocerciasis endemic areas.
Mass-distribution of ivermectin is routinely used to interrupt
onchocerciasis transmission in endemic foci, and an association between NS
and onchocerciasis has repeatedly been reported (2). NS only occurs in
onchocerciasis hyperendemic areas, and other forms of epilepsy are also
thought to be highly prevalent in many of these regions(3).
During the civil war in northern Uganda (1986-2006/2008), there was
no access to ivermectin in districts affected by NS, and it was only after
the war that ivermectin treatment programmes were established. Ivermectin
has been distributed annually in NS-affected districts since 2008, and
biannually since 2012 (2). This has coincided with a dramatic drop in the
number of new NS cases, and no new cases were officially reported in 2013
(4). The ivermectin distribution programme in northern Uganda was
supplemented by control measures targeting blackflies (Simuliidae), the
vectors of onchocerciasis, in late-2012. The Achwa and Pager rivers were
initially treated with larvicides applied from boats and light aircraft,
and larval breeding sites are now being treated with the organophosphate,
temephos, at predefined points along the rivers (2). We believe that this
integrated approach, targeting both the vectors of onchocerciasis and the
parasite in the human population, has contributed to the reduction of NS
cases in northern Uganda.
The link between NS and onchocerciasis appears to be further
reinforced by a recent study which suggests that an antibody-mediated
autoimmune response to leiomodin-1 may be involved in the etiology of NS.
Johnson et al. have demonstrated that antibodies against leiomodin-1 are
more likely to be present in NS cases than in controls (5). These
antibodies are also present in the cerebrospinal fluid of certain patients
with NS, are neurotoxic in vitro, and cross-react with Onchocerca volvulus
-specific proteins.
We do not believe that NS can be explained by events only related to
war. In the Mahenge NS-focus in Tanzania, there is no recent history of
conflict or household internment. Hypotheses regarding NS etiology should
be based on information from all affected regions.
Further research is needed to explore whether NS is caused by an auto
-immune reaction in response to Onchocerca volvulus infection; whether the
species or strain of Onchocerca is unique in NS-affected areas, or whether
NS is caused by a currently unidentified agent transmitted by blackflies
(6).
R. Colebunders, K. Coudere, N. Van der Moeren, A Hendy
Reference List
(1) Landis JL, Palmer VS, Spencer PS. Nodding syndrome in Kitgum
District, Uganda: association with conflict and internal displacement. BMJ
Open 2014;4(11):e006195.
(2) Colebunders R, Post R, O'Neill S, Haesaert G, Opar B, Lakwo T et
al. Nodding syndrome since 2012: recent progress, challenges and
recommendations for future research. Trop Med Int Health 2014 October 28.
(3) Pion SD, Kaiser C, Boutros-Toni F, Cournil A, Taylor MM,
Meredith SE et al. Epilepsy in onchocerciasis endemic areas: systematic
review and meta-analysis of population-based surveys. PLoS Negl Trop Dis
2009;3(6):e461.
(4) Ministry of Health, Uganda. Weekly epidemiological bulletin. 2014.
(5) Johnson T, Tyagi R, Lee PR, Leea M-h, Johnson KR, Kowalak J,
Medynets M, Hategan A, Nutman TB, Sejvar J, Makumbi I, Aceng JR, Dowell
SF, Nath A. Detection of auto-antibodies to leiomodin-1 in patients with
nodding syndrome. j.jneuroim , 103. 2014.
(6) Colebunders R, Hendy A, Nanyunja M, Wamala JF, van OM. Nodding
syndrome-a new hypothesis and new direction for research. Int J Infect Dis
2014 August 23;27C:74-7.
Thanks to statistician Ole Olsen who again expresses his concern
about the validity of the data in the National Birth Registry, and the
inconsistent reporting of these data on the official on-line sites. This
time Ole Olsen, however, goes one step further. Now he demands the editors
of BMJ open to ensure "documentation of the validity of all variables for
all years in the study period".
Thanks to statistician Ole Olsen who again expresses his concern
about the validity of the data in the National Birth Registry, and the
inconsistent reporting of these data on the official on-line sites. This
time Ole Olsen, however, goes one step further. Now he demands the editors
of BMJ open to ensure "documentation of the validity of all variables for
all years in the study period".
To validate all recorded birth related diagnosis and procedural codes
over a time span of 13 years, during which more 829,000 women have
delivered, would require providing the clinical notes of a representative
sample of these deliveries to see first, if all the relevant codes were
recorded appropriately, and secondly, if any non-relevant codes had been
recorded. Fortunately such validation studies have been made,
demonstrating a general high validity of the recorded obstetrical
diagnosis and procedural codes in the National Health Registry, which
feeds the Danish Birth Registry (1).
The main variables used for our study were calendar years, the
gestational age of delivering women, and the codes assessing stillbirth.
As reported, the gestational age was recorded in 99.4 % of all deliveries,
and has been found to have a high validity (1). The same applies to the
codes for stillbirths, which is generally considered as a "hard" end
point. We have previously indicated how we assessed stillbirths (2).
So the remaining question is whether other circumstances than the
earlier induction practice could explain the encouraging substantial
decline in stillbirths - not whether such a decrease actually occurred.
Considering the dramatic increase in risk of stillbirth with increasing
gestational age, it is not surprising that moving deliveries from high-
risk post-term weeks to earlier weeks with substantial lower risk of
intrauterine death would decrease the overall stillbirth rate from 37
gestational weeks. This is possibly not a very welcome message for people
like Ole Olsen, who for many years has argued for home deliveries, but it
does not make the scientific evidence less valid. Ole Olsen indicates
specifically, that the recording of induction of labour may have had a
lower validity than ideal. However this variable was used only for
descriptive purposes in our study, to demonstrate the increasing
proportion of inductions of deliveries from 12.4% to 25.2% during the
study period. If some of the codes used to assess labour induction have
been prone to variation between departments, which is not unlikely, these
circumstance would not change anything in our analysis or in our
conclusion.
As Ole Olsen also demonstrates, there have been several attempts to
ensure the validity and standardisation of obstetrical coding in Denmark.
This has been done through national guidelines elaborated by the Danish
Society of Obstetrics and Gynaecology (DSOG)(3), and by annual meetings
where these registration rules are discussed and posted solid. These
attempts are expected generally to have improved the registration practice
in Denmark by time.
The experiences Ole Olsen and his midwife collaborators Rydahl and
Clausen have had by getting access to data in the Danish Birth Registry,
and the inconsistencies in the official online statistics are - again -
not our responsibility and should be addressed to the relevant bodies.
About data sharing, one of the strengths about Danish registry
research is that these registry data are available for all scientists,
including Ole Olsen, who want to investigate any obstetrical question.
Based on the high validity of the diagnosis codes used in our study,
we are still confident with our analyses, and with the conclusions drawn.
1) Langhoff-Roos J, Rasmussen S. [Validation of the National Health
Registry concerning obstetrical research and quality assurance][In
Danish]. National Health Board 2003. Page 1-193.
2) Lidegaard O. Reply to Rydahl and Clausen. BMJ open 2014, October
13, 2014.
3) https://dsog.squarespace.com/obstetrik/. Accessed December 4,
2014.
"Let food be thy medicine and medicine be thy food." Hippocrates
We read with interest the study by T.Sekhri,R.S.Kanwar et al(1).The
authors needs to be congratulated for such a meticulous and unique study
involving subjects from all over India.The study is first of its kind in
India and an eye-opener. However,the following issues we shall like to
share:
1.As it was a non-interventional and free-of-cos...
"Let food be thy medicine and medicine be thy food." Hippocrates
We read with interest the study by T.Sekhri,R.S.Kanwar et al(1).The
authors needs to be congratulated for such a meticulous and unique study
involving subjects from all over India.The study is first of its kind in
India and an eye-opener. However,the following issues we shall like to
share:
1.As it was a non-interventional and free-of-cost to the
participating subjects study.Why only 14,500 subjects( 55%) gave the
informed consent out of approximately 26,000.It may be worth mentioning
some important reasons of this rather less acceptance for the study.This
low level of participation compromises the external validity of the study.
2.The subjects with known coronary artery disease (CAD) were
excluded.It would have been interesting to know how many subjects with
newly discovered CAD were detected,including silent old MI pattern in ECG.
3.As mentioned in the introduction of the study(1),over 60% of CAD in
native Indians remain unexplained by conventional risk factors,why only
conventional risk factors were considered in the study.
4.Gainfully,in the protocol,disease history is included,it would have
been relevant to know about the other diseases and if any correlation with
the risk factors could have been made. Like patients with
depression/psychiatric morbidity (common diseases these-days)and
obstructive sleep apnea have much worse risk factor profile and are
increasing recognized as novel risk factors per se. Interestingly in
women( obstetric history was ascertained),any correlation with adverse
obstetric history and risk factor profile was observed?.The data is
rapidly accumulating between adverse obstetric history and development of
cardiovascular disease in future(2).
5.In the present study interestingly only 27% of hypertensives were
aware about their condition ( 73% were newly discovered).A rather lower
percentage particularly for civilian government employee,having free
access to the medical services.
6.78.6% of the subjects had two or more risk factors is a disturbing
fact.In Prabhakaran's study(3) in 2005 amongst industrial workers of north
India 47% subjects had atleast two risk factors.Is it a temporal trend or
the difference is due to the location of the subjects in the study,needs
to be explained.
The study emphasized the disturbing trend in the health status in
India and serious thoughts and actions are needed to contain this unabated
epidemic.What will be the peak of the epidemic is anybody's guess.
However, we have the following suggestions to offer:
1.When the epidemic reaches this gigantic proportion,secondary and
tertiary prevention have very limited impact at a community level.
2.The primordial and primary prevention assume huge importance. As
they are much more cost-effective and result yielding.
3.For Primordial prevention and primary prevention ,in a nutshell the
message is : to eat and try to assume the level of physical activity and
lifestyle ( may not be possible for everyone) similar to what our
grandparents used to have.
4.To counteract the adverse health consequences of modern life .We
advocate three levels of prevention: health education, health education
and health education of the entire world ( in particular developing
world), with emphasis upon educating health policy - makers.
References
1.T Sekhri, R S Kanwar, R Wilfred, P Chugh, M Chhillar, R Aggarwal, Y
K Sharma, J Sethi, J Sundriyal, K Bhadra, S Singh, N Rautela, Tek Chand, M
Singh, and S K Singh.Prevalence of risk factors for coronary artery
disease in an urban Indian population. BMJ Open 2014 4:e005346;
doi:10.1136/bmjopen-2014-005346
2.Bellamy L,Casas JP,Hingorani AD,Williams DJ.Pre-eclampsia and risk
of cardiovascular disease and cancer in later life:Systematic review and
meta-analysis.BMJ.2007;335:974
3.Prabhakaran D, Shah P, Chaturvedi V, et al. Cardiovascular risk
factor prevalence among men in a large industry of northern India. Natl
Med J India 2005;18:59-65.
CAM includes both complementary and alternative practices.
Alternative practices, by definition, either have not been proven to work,
or have been proven not to work. Complementary practices have always been
mainstream and many are evidence-based. There is no sound scientific or
medical justification for analysing the two together. Alternative
practitioners may prefer them to be considered together, as this may
provide...
CAM includes both complementary and alternative practices.
Alternative practices, by definition, either have not been proven to work,
or have been proven not to work. Complementary practices have always been
mainstream and many are evidence-based. There is no sound scientific or
medical justification for analysing the two together. Alternative
practitioners may prefer them to be considered together, as this may
provide a halo effect of legitimacy from being considered alongside
obviously valid concepts such as diet and exercise, but in analysing the
cost-effectiveness of these interventions it seems to me rather important
to unpick the two.
For example, any judgment of the validity of medical training in
nutrition cannot possibly shed light on the validity of training in a
refuted dogma such as homeopathy or reiki.
It is plausible that autohypnosis may be able to materially benefit
patients with anxiety disorders. It is wholly implausible that homeopathy
would deliver any objectively provable benefit at all. To consider the two
jointly, is to needlessly muddy the waters.
The authors reference the US National Center for Complementary and
Alternative Medicine (NCCAM), a body set up at the instigation of a pro-
CAM legislator to investigate and produce evidence around CAM
interventions.
Dr. David Gorski has been looking closely at NCCAM for some years,
along with several colleagues. They have noted that NCCAM has spent in
excess of one billion dollars since its inception in 1993. To date, they
have failed to validate a single alternative intervention. They have
produced supportive evidence for massage therapy (which is scarcely
controversial), but not for any of the alternative therapies tested - many
of which are by now considered refuted though still doggedly promoted by
believers.
I would suggest the authors do their best in future to unpick the
effects of legitimate and medically plausible complementary therapies,
from those of alternative therapies. This will reduce the risk of their
research being abused by advocates as support for therapies which, of
themselves, have little or no provable validity.
In the light of surveys showing that large numbers of doctors
knowingly prescribe placebos, it would also be valuable to understand how
many of the doctors using CAM therapies consider them to be valid
interventions and administer them on that basis.
I wish to address the eLetter responding to our recently published
article in BMJ Open (Joshi SR, et al. Results from a dietary survey in an
Indian T2DM population: a STARCH study. BMJ Open. 2014 Oct
31;4(10):e005138.) Firstly, thank you to Prof.Vishnupriya R Paturi for
taking the time to read our article and providing feedback. We believe
that the impact and relative importance that the type or sou...
I wish to address the eLetter responding to our recently published
article in BMJ Open (Joshi SR, et al. Results from a dietary survey in an
Indian T2DM population: a STARCH study. BMJ Open. 2014 Oct
31;4(10):e005138.) Firstly, thank you to Prof.Vishnupriya R Paturi for
taking the time to read our article and providing feedback. We believe
that the impact and relative importance that the type or source of
carbohydrate has on postprandial glucose level has continued to be an area
of debate. However, many studies highlights that the dietary carbohydrate
determines the postprandial blood glucose response. Garg A & Parillo M
reported that dietary carbohydrate increases blood glucose concentrations,
particularly in the postprandial period. Therefore, in diabetic patients,
particularly those treated with insulin or who have more severe forms of
type 2 diabetes, a carbohydrate-rich diet can have detrimental effects on
glycemic control, which plays a major role in the development of coronary
artery disease and other macrovascular and microvascular complications
(1,2). In parallel with the plasma glucose rise, plasma insulin and
triacylglycerol concentrations also tend to increase with a high-
carbohydrate diet, along with other cardiovascular disease risk
factors(3). Although, it is known that not all carbohydrate-rich foods are
equally hyperglycemic: differences in the postprandial blood glucose
response to various carbohydrate-containing foods have been shown in both
healthy subjects and diabetic patients, even when consumed in portion
sizes containing identical amounts of carbohydrate. It was observed that
carbohydrate-rich foods represent a heterogeneous category and, therefore,
may have a variable effect on energy and substrate metabolism in humans.
(4-6).
The American Diabetes Association reviewed the available scientific data
regarding the effect of the type or source of carbohydrate on the
prevention and management of diabetes and suggested the following
statements: [7]
* The component of the diet that has the greatest influence on blood
glucose is carbohydrate. However, other macronutrients in the diet, i.e.,
fat and protein, can influence the postprandial blood glucose level.
* Regulation of blood glucose to achieve near-normal levels is a primary
goal in the management of diabetes, and, thus, dietary techniques that
limit hyperglycemia following a meal are likely important in limiting the
complications of diabetes.
* Low-carbohydrate diets are not recommended in the management of
diabetes. Although dietary carbohydrate is the major contributor to
postprandial glucose concentration, it is an important source of energy,
water-soluble vitamins and minerals, and fiber.
* Both the amount (grams) of carbohydrate as well as the type of
carbohydrate in a food influence blood glucose level.
* The maintenance of a healthy body weight is strongly recommended as a
means of preventing this disease, because much of the risk of developing
type 2 diabetes is attributable to obesity,
Also most experts agree that the total carbohydrate intake from a
meal or snack is a relatively reliable predictor of postprandial blood
glucose. Thus in addition to advice fat proportions in diets, monitoring
total grams of carbohydrate, whether by use of exchanges or carbohydrate
counting, remains a key strategy in achieving glycemic control.In our
study, we suggested the need to investigate further the benefit of various
therapeutic interventions in high carbohydrate-consuming Indian type-2
diabetes mellitus participants in a prospective randomised controlled
study.
References:
1.Garg A, Bonanome A, Grundy SM, et al. Comparison of a high carbohydrate
diet with a high-monounsaturated-fat diet in patients with noninsulin-
dependent diabetes mellitus. N Engl J Med 1988;319:829 -34.
2.Parillo M, Giacco R, Ciardullo AV, et al. Does a high carbohydrate diet
have different effects in NIDDM patients treated with diet alone or
hypoglycemic drugs? Diabetes Care 1996;19:498 -500.
3.Rivellese A, Giacco R, Genovese S, et al. Effects of changing amount of
carbohydrate in diet on plasma lipoproteins and apolipoproteins in type II
diabetic patients. Diabetes Care 1990;13:446-8.
4.Coulston AM, Hoolenbeck CB. Swislocki AML, et al. Deleterious metabolic
effects of high carbohydrate, sucrose containing diets in patients with
NIDDM. Am J Med 1987;82:213-20.
5.O'Dea K, Nestel R, Autonoff L. Physical factors influencing postprandial
glucose and insulin responses to starch. Am J Clin Nutr 1980;33:760-5.
6.Liljeberg H, Granfeldt Y, Bjorck I. Metabolic responses to starch in
bread containing intact kernels versus milled flour. Eur J Clin Nutr
1992;46:561-5.
7.Nancy F. Sheard, et al. Dietary Carbohydrate (Amount and Type) in the
Prevention and Management of Diabetes. Diabetes Care 2004; 27(9):2266-
2271
Dear Editor:
We peruse with interest the interesting study by Meng Lee et al (1).
We would like to share the followings:
1.One of the strengths of any retrospective data analysis is the
acceptance/compliance with therapy in the real-life situation ( whatever
the compliance rate may be).The exclusion of 1632 patients ( 42% of the
total) because of medication possession ratio <80% has limited the
external vali...
Dear Editor:
We peruse with interest the interesting study by Meng Lee et al (1).
We would like to share the followings:
1.One of the strengths of any retrospective data analysis is the
acceptance/compliance with therapy in the real-life situation ( whatever
the compliance rate may be).The exclusion of 1632 patients ( 42% of the
total) because of medication possession ratio <80% has limited the
external validity of the study.
2.Excluding 355 patients (9% of the total) further because of Atrial
fibrillation, valvular heart diseases or coagulopathy may not be justified
( if they were put either on aspirin or clopidogrel ,they should have been
included).
3.During the follow-up period, statin and diuretics were used more
frequently ( statistically significant) in the clopidogrel group. It is
well known that statin and diuretics reduce ischemic strokes (2,3).Thus
tilting the balance in favor of clopidogrel.
4.Much less patients were put on clopidogrel (384 patients) versus
aspirin (1500 patients),even the best statistical model may not be able to
completely nullify the bias as the disparity is substantial.
As the above mentioned limitations are influential, the results of
the study may be biased and should be interpreted with caution.
References
1.Meng Lee, Yi-Ling Wu, Jeffrey L Saver, Hsuei-Chen Lee, Jiann-Der
Lee,Ku-Chou Chang, Chih-Ying Wu, Tsong-Hai Lee, Hui-Hsuan Wang, Neal M
Rao, and Bruce Ovbiagele.Is clopidogrel better than aspirin following
breakthrough strokes while on aspirin? A retrospective cohort study. BMJ
Open 2014 4:e006672; doi:10.1136/bmjopen-2014-006672
2.Pierre Amarenco, Julien Labreuche.Lipid management in prevention of
stroke:review and updated meta-analysis od statin for stroke
prevention.The Lancet Neurology. 2009;8(5):453-463.doi:1016/s1474-4422(09)
70058-4
3.PROGRESS Collaborative group. Randomised trial of a perindopril-
based blood pressure-lowering regimen among 6105 individuals with previous
stroke or transient ischemic attack.The Lancet. 2001;358:9287,1033-1041.
doi:10.1016/s014-6736(01)06178-5
We wish to highlight a number of inaccuracies noted in the protocol
for a proposed feasibility study of computerised cognitive behavioural
therapy (CCBT) in depressed adolescents (Wright et al, 2014). We believe
that the introduction to the study overplays concerns about the use of
antidepressants and the effectiveness of CBT in adolescents. The authors
fail to differentiate the level of severity of depression with respe...
We wish to highlight a number of inaccuracies noted in the protocol
for a proposed feasibility study of computerised cognitive behavioural
therapy (CCBT) in depressed adolescents (Wright et al, 2014). We believe
that the introduction to the study overplays concerns about the use of
antidepressants and the effectiveness of CBT in adolescents. The authors
fail to differentiate the level of severity of depression with respect to
the use of antidepressants, and only very briefly refer to the TADS data
(March et al, 2004). This remains the only trial in adolescents which
compares antidepressants and CBT, and demonstrated a lack of effect of CBT
over placebo at 12 weeks, but a substantial effect size of fluoxetine over
both placebo and CBT. In addition, fluoxetine has been demonstrated to be
superior to placebo in the treatment of acute depression (Emslie et al,
1997;2002), and has been shown to prevent relapse (Emslie et al, 2004). We
do think that our UK ADAPT trial has been misrepresented here. While our
Brief Initial Intervention did lead to improvement in a minority of
adolescents, we did move to antidepressants after 1-4 sessions for those
who did not respond; and those with severe depression would have been
offered antidepressants sooner. Also, ADAPT did not randomise between
medication and treatment as usual: all received medication and
psychosocial treatment as usual and half were randomly allocated to CBT.
The most important outcome of the ADAPT trial was that there was no
additional benefit in adding CBT to an antidepressant and routine care, a
finding that was replicated in the most impaired adolescents in TADS
(Curry et al, 2006). Based on the TADS data we would challenge the
statement that antidepressants show poor efficacy, particularly when
compared to CBT. Although the authors quote older studies in support of
CBT, more recent evidence challenges the extent of the effectiveness of
CBT both in adolescent and adult depression, particularly when studies
with sub-standard methodology are excluded (e.g. Weisz et al, 2006;
Cuijpers et al, 2013; Klein et al, 2007). While some small studies
suggested that CBT prevents depression, larger, more robust studies have
demonstrated no effect, and one of these demonstrated that CBT was
actually less effective at preventing depressive symptoms than standard
PHSE sessions from teachers (Challen et al, 2014; Sawyer et al, 2010;
Stallard et al, 2012). A Cochrane review of psychological treatment and
antidepressants (Cox et al, 2012) failed to come to any definitive
conclusions regarding the relative benefit of treatments, but did find
some superiority of antidepressants over CBT. Thus the assumption that
antidepressants are ineffective and CBT is more effective is not supported
by the research evidence. In addition, the authors describe the addictive
potential of antidepressants, however to our knowledge there is no
definitive evidence for this from any clinical trial in young people or
from clinical practice.
We do welcome this proposed study. Computerised CBT may be an
effective treatment for adolescents, and could be particularly helpful for
those who do not want to/are unable to attend clinics. It is also likely
to be cheaper than conventional CBT. We were surprised that the authors
have not referred to the large published trial of CCBT by Merry et al
(2012), which indicated that CCBT had similar effectiveness as routine
care in depressed adolescents. This is indeed a promising finding which
deserves replication in the UK. However, we believe the evidence is clear
in advocating the use of antidepressants within a stepped care approach
and await the results of IMPACT (Goodyer et al, 2011) which may provide
further information regarding the place of CBT in the treatment pathway.
References
Challen, A. R., S. J. Machin, et al. (2014). The UK Resilience Programme:
A school-based universal nonrandomized pragmatic controlled trial. Journal
of Consulting and Clinical Psychology 82(1): 75-89.
Cox, G. R., P. Callahan, et al. (2012). Psychological therapies versus
antidepressant medication, alone and in combination for depression in
children and adolescents. Cochrane Database of Systematic Reviews. 11.
Cuijpers, P., M. Berking, et al. (2013). A meta-analysis of cognitive-
behavioural therapy for adult depression, alone and in comparison with
other treatments. The Canadian Journal of Psychiatry / La Revue canadienne
de psychiatrie 58(7): 376-385.
Curry, J., Rodhe, P., Simons, A., Silva, S., Vitiello, B., Kratochvil, C.,
et al. (2006) Predictors and Moderators of Acute Outcome in the Treatment
for Adolescents With Depression Study (TADS). Journal American Academy
Child Adolescent Psychiatry, 45(12), 1427-1438.
Dimidjian, S. and S. D. Hollon (2010). How would we know if psychotherapy
were harmful? American Psychologist Vol.65(1): 21-33.
Emslie, G. J., A. J. Rush, et al. (1997). A double-blind, randomised,
placebo-controlled trial of fluoxetine in children and adolescents with
depression. Archives General Psychiatry 54: 1031-1037.
Emslie, G. J., J. H. Heiligenstein, et al. (2002). Fluoxetine for acute
treatment of depression in children and adolescents: a placebo-controlled,
randomized clinical trial. Journal of the American Academy of Child and
Adolescent Psychiatry 41(10): 1205-1215.
Emslie, G. J., J. H. Heiligenstein, et al. (2004). Fluoxetine treatment
for prevention of relapse of depression in children and adolescents: a
double-blind, placebo-controlled study. Journal American Academy Child
Adolescent Psychiatry 43(11): 1397-1405.
Goodyer, I., Tsancheva, S., et al. (2011). Improving mood with
psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness
superiority trial to investigate whether specialised psychological
treatment reduces the risk for relapse in adolescents with moderate to
severe unipolar depression: study protocol for a randomised controlled
trial. Trials 12:175.
Klein, J. B., R. H. Jacobs, et al. (2007). Cognitive-Behavioural Therapy
for Adolescent Depression: A meta-analytic investigation of changes in
effect-size estimates. Journal American Academy Child Adolescent
Psychiatry 46(11): 1403-1413.
March, J., Silva, S., et al. (2004). Fluoxetine, cognitive-behavioral
therapy, and their combination for adolescents with depression: Treatment
for Adolescents With Depression Study (TADS) randomized controlled trial.
JAMA, 292, 807 - 820.
Merry, S., K. Stasiak, et al. (2012). The effectiveness of SPARX, a
computerised self help intervention for adolescents seeking help for
depression: Randomised controlled non-inferiority trial. BMJ: British
Medical Journal 344(7857): 1-16.
Sawyer, M. G., T. F. Harchak, et al. (2010). School-based prevention of
depression: A 2-year follow-up of a randomized controlled trial of the
beyondblue schools research initiative. Journal of Adolescent Health
47(3): 297-304.
So, M., S. Yamaguchi, et al. (2013). Is computerised CBT really helpful
for adult depression?-A meta-analytic re-evaluation of CCBT for adult
depression in terms of clinical implementation and methodological
validity. BMC Psychiatry 13(ArtID 113).
Stallard, P., K. Sayal, et al. (2012). Classroom based cognitive
behavioural therapy in reducing symptoms of depression in high risk
adolescents: pragmatic cluster randomised controlled trial. BMJ 345.
Weisz, J. R., C. A. McCarty, et al. (2006). Effects of Psychotherapy for
Depression in Children and Adolescents: A Meta-Analysis. Psychological
Bulletin 132(1): 132-149.
Wright, B., L. Tindall, et al. (2014). Computerised cognitive behaviour
therapy for depression in adolescents: study protocol for a feasibility
randomised controlled trial. BMJ Open 4 (10).
Conflict of Interest:
PW, RK, IG have acted as consultants to Lundbeck.
PW is an interpersonal psychotherapy supervisor
BD, RK, IG are investigators on the HTA funded IMPACT study of psychological treatments in adolescent depression
I read the article by Marston et al
(http://bmjopen.bmj.com/content/4/12/e006135.full#ref-28) with keen
interest as my role in the crisis team involves assessment and management
of a majority of patients included in the cohort. However, I would urge
cautions on the author's interpretations on the following grounds.
1. I would like to point out the definition of Severe Mental Illness
has specifically excluded de...
I read the article by Marston et al
(http://bmjopen.bmj.com/content/4/12/e006135.full#ref-28) with keen
interest as my role in the crisis team involves assessment and management
of a majority of patients included in the cohort. However, I would urge
cautions on the author's interpretations on the following grounds.
1. I would like to point out the definition of Severe Mental Illness
has specifically excluded depression as a severe mental illness, despite
its devastating effects on an individual and family. This might be due to
a variety of factors, including recent negative publications (of wide
spread antidepressant prescriptions/ineffective antidepressants) and
potentially due to stigma.
2. A variety of antipsychotics mentioned have licenses for non-smi related
illness. Olanzapine has a license in the USA for treatment resistant
depression (http://pi.lilly.com/us/zyprexa-pi.pdf) and Quetiapine for
Major depressive disorder (licensed as add on in the UK but has a license
overseas as monotherapy for MDD), along with NICE (in generalised anxiety
disorder) advising "Moderate evidence suggests that quetiapine
monotherapy at most doses statistically significantly improved rates of
GAD response or remission compared with placebo (4 RCTs lasting 8-9 weeks)
but not compared with escitalopram or paroxetine (2 RCTs lasting 8
weeks)."
3. These drugs could have easily be commenced in secondary care (e.g.
while under the care of the crisis team) and continued in primary care
hence not being initiated there at all.
4. My thoughts on use of antipsychotic medication in the elderly have been
explored here
(http://bjp.rcpsych.org/content/205/1/44.abstract/reply#bjprcpsych_el_65158).
Even though I do not condone wide spread use of antipsychotic medication
in this population, it could clearly be initiated by a specialist and
dispensed in primary care, keeping all relevant national guidance in mind
and having a discussion with patient's family.
5. The authors quote Speilmans et al metaanalysis on atypical
antipsychotic use in major depressive disorder to suggest lack of
functional improvement in those patients
(http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001403).
However, despite including only 14 short term (4-12 weeks) trials, all
four drugs had statistically significant effects (effects unlikely to have
happened by chance) on remission (a much higher threshold), which was most
commonly defined as a score of less than eight at the study end point on
the Montgomery-Asberg Depression Rating Scale. The NNT was 9 for
Quetiapine, Risperidone and Aripiprazole. Arguably, the trials were too
short to effectively address functional recovery. It is however posited
with remission being the outcome measure; the functional recovery would
follow in time.
6. Ethically, "do no harm" seemingly applies to patients treated by
antipsychotics, including risks of sudden death and of deep vein
thrombosis, not mentioned by the authors. However, if a partially
treated/untreated patient with major depressive disorder chooses to end
their life, I would suggest that is a bigger harm. My comment on the
recent annual report by the National Confidential Enquiry into Suicide and
Homicide by People with Mental Illness, which was publicized for
highlighting that 72% of those who died by suicide between 2001 and 2011,
were not in contact with mental health services for the full year before
their death is available here
(http://bjp.rcpsych.org/content/205/2/120.abstract/reply#bjprcpsych_el_65324).
Hence to conclude, there are several ways to interpret the data and I
would urge readers to consider alternatives and not just draw similar
conclusions mentioned by the authors.
We agree with Dr Dubicka and colleagues (2015) that the study of
computerized CBT (cCBT) is to be welcomed especially to test treatments
for those unable or reluctant to attend clinics or face to face therapies.
Further research is also important to elucidate whether cCBT is a more
cost effective alternative and explore its contribution at different
points in the care pathway. We mistakenly described their study as
rando...
We agree with Dr Dubicka and colleagues (2015) that the study of
computerized CBT (cCBT) is to be welcomed especially to test treatments
for those unable or reluctant to attend clinics or face to face therapies.
Further research is also important to elucidate whether cCBT is a more
cost effective alternative and explore its contribution at different
points in the care pathway. We mistakenly described their study as
randomising between 'medication and treatment as usual' and not
'medication and medication + CBT' and we apologise for this. As is often
the case in studies of this nature clarity of treatment arms is often very
difficult to achieve. For example, those in the medication arm of their
study received psychosocial interventions including problem solving and
psychoeducation (Goodyer et al, 2007) both of which can be part of broad
based CBT packages. This issue is not specific to their study since in
many studies, treatment as usual is a mix of approaches and may
incorporate CBT techniques. They are right to point out that our protocol
was written at a time when there was greater concern over the efficacy of
anti-depressants in adolescents. Our cCBT study (Wright et al, 2014) is
nearly at completion and we did not feel it appropriate to change the
background narrative in the protocol at the point of publication since the
protocol defines the rationale for the study being undertaken at that
time.
There are in fact two RCTs comparing antidepressants and CBT in
adolescents (March et al, 2004; Melvin, 2006) and these are included in
the Cochrane systematic review by Cox and colleagues (2012). This meta-
analysis (Cox et al, 2012) shows mixed results with no statistically
significant difference between antidepressants and CBT for the majority of
outcomes. There is no difference between self-rated depression symptoms
post intervention or at 6-9 months follow up between the two groups in the
meta-analysis. At post-intervention there were significantly fewer
participants with suicidal ideation in the CBT group than the
antidepressant group and this was still the case at 6-9 months follow up.
There is 'limited' evidence of improved remission in the antidepressant
group but only in clinician rated remission ratings immediately post
intervention. As further research is emerging this picture may change and
clearly antidepressants have a place in the care pathway for adolescent
depression and studies such as the ones under discussion support this
(Goodyer et al, 2007; Byford et al, 2007).
It is relevant to note that CBT (or indeed cCBT) is not the same
treatment wherever it is delivered. CBT is a model of delivery that allows
exploration of interactions between cognitions, emotions, behaviours and
the environment. For depression packages may include a range of different
elements that incorporate activity scheduling, social problems solving
skill work, psychoeducation, coping strategy work, biofeedback,
relaxation, behavioural experiments, work on automatic negative thinking
(and other distortions of thinking) and so on. In this way SPARX (Merry et
al, 2012) is a very different cCBT programme from Stressbusters (Abeles et
al, 2009) and has different content, mode of delivery and number of
standard sessions. Issues such as these make it difficult to generalize
about CBT when comparing studies, or about the place of CBT or cCBT in the
care pathway given the very limited number of RCTs in this age group.
From a clinical perspective, we agree with Dubicka and colleagues
that antidepressants have an important place in a stepped care approach.
We welcomed Curry and colleagues' findings (2006) that suggest that there
is no apparent benefit from adding CBT to fluoxetine for those adolescents
with symptoms that are so severe that they cannot engage in CBT, and
indeed this makes clinical common sense and maps onto local clinical
practice. We agree with Cox and colleagues that 'there is very limited
evidence upon which to base conclusions about the relative effectiveness
of the psychological interventions, antidepressant medication and a
combination of these interventions'. We strongly suggest, and would be
hopeful that Dubicka and colleagues would agree, that further research in
this area is important and we look forward to the results of ongoing CBT
studies (Goodyer et al, 2011) and cCBT studies in London and Yorkshire
(Wright et al, 2015).
References
Abeles P, Verduyn C, Robinson A, Smith P, Yule W, Proudfoot J.
Computerized CBT for adolescent depression ("Stressbusters") and its
initial evaluation through an extended case series. Behav Cog
Psychotherapy 2009; 37: 151-165.
Byford S, Barrett B, Roberts C, Wilkinson P, Dubicka B, Kelvin RG,
White L, Ford C, Breen S, Goodyer I Cost-effectiveness of selective
serotonin reuptake inhibitors and routine specialist care with or without
cognitive behaviour therapy in adolescents with major depression. Brit J
Psych 2007; 191: 521-527.
Cox GR, Callahan P, Churchill R, Hunot V, Merry SN, Parker AG,
Hetrick SE. Psychological therapies versus antidepressant medication,
alone and in combination for depression in children and adolescents.
Cochrane Database of Systematic Reviews 2014, Issue 11. DOI:
10.1002/14651858.CD008324.pub3.
Curry J , Rohde P , Simons A , Silva S , Vitiello B , Kratochvil C ,
Reinecke M , Feeny N , Wells K , Pathak S , Weller E , Rosenberg D ,
Kennard B , Robins M , Ginsburg G , March J TADS Team : Predictors and
moderators of acute outcome in the Treatment for Adolescents with
Depression Study (TADS). J Am Acad Child Adolesc Psychiatry 2006; 45:1427-
1439
Dubicka B, Wilkinson P, Kelvin R, Goodyer I (2015) cCBT for
depression in adolescents. BMJ Open 4/10/e006488.full/reply
Goodyer I, Dubicka B, Wilkinson P, Kelvin R, Roberts C, Byford S,
Breen S, Ford C, barrett B, Leech A,Rothwell J, White L, Harrington R.
Selective serotonin reuptake inhibitors (SSRIs) and routine specialist
care with and without cognitive behaviour therapy in adolescents with
major depression: randomised controlled trial. BMJ 2007; 335: 142.
March J, Silva S, Petrycki S, et al. Fluoxetine, cognitive-behavioral
therapy, and their combination for adolescents with depression: Treatment
for Adolescents with Depression Study (TADS) randomized controlled trial.
JAMA 2004; 292: 807-20.
Melvin G, Tonge BJ, King NJ, Heyne D, Gordon MS, Klimkeit E. A
comparison of cognitive-behavioral therapy, sertraline, and their
combination for adolescent depression. J Acad Child Adol Psych 2006; 45:
1151-1161.
Merry SN, Stasiak K, Shepherd M, Frampton C, Fleming T, Lucassen MF.
The effectiveness of SPARX, a computerised self help intervention for
adolescents seeking help for depression: randomised controlled non-
inferiority trial. BMJ 2012; 344:e2598.
Wright, B., Tindall L., et al (2014) Computerised cognitive behaviour
therapy for depression in adolescents: study protocol for a feasibility
randomised controlled trial. BMJ Open 4 (10).
Dear Editor
I wish to address the eLetter responding to our recently published article in BMJ Open (Abouzeid M, Versace VL, Janus ED, et al. A population -based observational study of diabetes during pregnancy in Victoria, Australia, 1999-2008). Firstly, thank you to Wigdan Farah for taking the time to read our article and providing positive feedback. Specifically they suggest that we add the variable 'socio-eco...
Landis et al. describe a temporal association between wartime conflict, internal displacement, and Nodding syndrome (NS)(1). They raise infectious, nutritional and neuropsychiatric elements as possible causal factors. The authors, however, do not mention a key factor that may have played a major role during the NS epidemic in northern Uganda: a lack of ivermectin treatment in onchocerciasis endemic areas.
Mas...
Thanks to statistician Ole Olsen who again expresses his concern about the validity of the data in the National Birth Registry, and the inconsistent reporting of these data on the official on-line sites. This time Ole Olsen, however, goes one step further. Now he demands the editors of BMJ open to ensure "documentation of the validity of all variables for all years in the study period".
To validate all recorded...
"Let food be thy medicine and medicine be thy food." Hippocrates
We read with interest the study by T.Sekhri,R.S.Kanwar et al(1).The authors needs to be congratulated for such a meticulous and unique study involving subjects from all over India.The study is first of its kind in India and an eye-opener. However,the following issues we shall like to share:
1.As it was a non-interventional and free-of-cos...
CAM includes both complementary and alternative practices. Alternative practices, by definition, either have not been proven to work, or have been proven not to work. Complementary practices have always been mainstream and many are evidence-based. There is no sound scientific or medical justification for analysing the two together. Alternative practitioners may prefer them to be considered together, as this may provide...
Dear Editor
I wish to address the eLetter responding to our recently published article in BMJ Open (Joshi SR, et al. Results from a dietary survey in an Indian T2DM population: a STARCH study. BMJ Open. 2014 Oct 31;4(10):e005138.) Firstly, thank you to Prof.Vishnupriya R Paturi for taking the time to read our article and providing feedback. We believe that the impact and relative importance that the type or sou...
Dear Editor: We peruse with interest the interesting study by Meng Lee et al (1). We would like to share the followings:
1.One of the strengths of any retrospective data analysis is the acceptance/compliance with therapy in the real-life situation ( whatever the compliance rate may be).The exclusion of 1632 patients ( 42% of the total) because of medication possession ratio <80% has limited the external vali...
We wish to highlight a number of inaccuracies noted in the protocol for a proposed feasibility study of computerised cognitive behavioural therapy (CCBT) in depressed adolescents (Wright et al, 2014). We believe that the introduction to the study overplays concerns about the use of antidepressants and the effectiveness of CBT in adolescents. The authors fail to differentiate the level of severity of depression with respe...
I read the article by Marston et al (http://bmjopen.bmj.com/content/4/12/e006135.full#ref-28) with keen interest as my role in the crisis team involves assessment and management of a majority of patients included in the cohort. However, I would urge cautions on the author's interpretations on the following grounds.
1. I would like to point out the definition of Severe Mental Illness has specifically excluded de...
We agree with Dr Dubicka and colleagues (2015) that the study of computerized CBT (cCBT) is to be welcomed especially to test treatments for those unable or reluctant to attend clinics or face to face therapies. Further research is also important to elucidate whether cCBT is a more cost effective alternative and explore its contribution at different points in the care pathway. We mistakenly described their study as rando...
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