The recent paper by Dobler et al. (2012) highlights the challenge of
variable selection and adjustment in multivariate analyses [1]. The
authors state that including the potentially confounding variable 'TB
incidence in the country of birth' was one of the major strengths of their
study. TB incidence in the country of birth is indeed an important
predictor of the risk of developing TB - but it may not be a true
confounde...
The recent paper by Dobler et al. (2012) highlights the challenge of
variable selection and adjustment in multivariate analyses [1]. The
authors state that including the potentially confounding variable 'TB
incidence in the country of birth' was one of the major strengths of their
study. TB incidence in the country of birth is indeed an important
predictor of the risk of developing TB - but it may not be a true
confounder.
The general rule for defining a confounding variable in
epidemiological research is the following: 1. The confounding variable is
causally associated with the outcome. 2. The confounding variable is non-
causally or causally associated with the exposure. 3. The confounding
variable is not an intermediate variable in the causal pathway between
exposure and outcome [2,3]. From the Dobler et al. paper, where diabetes
is the exposure variable and TB is the outcome, 'TB incidence in the
country of birth' is causally associated with the outcome, but it is not
associated with the exposure. Adjustment for a strong predictor of an
outcome that is not a confounder results in overadjustment [4], which
distorts the true relationship between the exposure and outcome [3]. As
the authors of the paper noticed, none of the previously published studies
conducted in the US or Canada, countries with a large number of
immigrants, have adjusted for TB incidence in the country of birth [5].
And this seems to be well justified due to the above reason.
A further concern relates to the measurement of the 'TB incidence in
the country of birth' variable. For example, was current or past TB
incidence used? What is 'current' and what is 'past'? Was TB incidence
obtained from the region of birth, or was it a national incidence
estimate? Was TB incidence available for all countries of origin? As TB
incidence greatly varies according to the time period and geographical
region - even within the same country - clarification on how this variable
was measured is important. Also, if a single estimate was used for
multiple individuals, the true heterogeneity in TB incidence rates
experienced by these individuals will be missed, leading to measurement
error [6]. This calls into question the validity of the measurement [7].
These concerns warrant a re-analysis of the data.
References:
1. Dobler CC, Flack JR, Marks GB. Risk of tuberculosis among people with
diabetes mellitus: an Australian nationwide cohort study. BMJ Open
2012;2:e00066. doi:10.1136/bmjopen-2011-000666.
2. Rothman KJ. Epidemiology: An Introduction. New York: Oxford University
Press; 2002.
3. Szklo M, Nieto J. Epidemiology: Beyond the Basics. 2nd ed.
Massachusetts: Jones and Bartlett Publishers; 2006.
4. Porta M. A Dictionary of Epidemiology. 5th edition. New York: Oxford
University Press; 2008.
5. Jeon CY, Murray MB. Diabetes mellitus increases the risk of active
tuberculosis: a systematic review of 13 observational studies. PLoS Med
2008;5:e152
6. Diez Roux AV. The study of group-level factors in epidemiology:
rethinking variables, study designs, and analytical approaches. Epidemiol
Rev 2004;26:104-11
7. Schsterman EF, Cole SR, Platt RW. Overadjustment bias and unnecessary
adjustment in epidemiologic studies. Epidemiology 2009;20(4):488-95
In response to the letter from ECOG we would to like highlight that
the criticisms levied against our research were already discussed
explicitly in our paper and the limitations, for example, of parental self
-report were mentioned up front in the article in the summary box. For
precisely the reasons mentioned by the ECOG group we generated a matched
sample from our total sample in which we controlled for age. The matched...
In response to the letter from ECOG we would to like highlight that
the criticisms levied against our research were already discussed
explicitly in our paper and the limitations, for example, of parental self
-report were mentioned up front in the article in the summary box. For
precisely the reasons mentioned by the ECOG group we generated a matched
sample from our total sample in which we controlled for age. The matched
sample did not differ on age, gender or SES. Despite employing such
conservative matching criteria our data showed significant differences in
the food preferences and BMI distribution of the two weaning groups.
Clearly these interesting findings warrant explanation. We hope that our
research generates further investigation into the effect that weaning
method may have on early developmental outcomes.
Thank you for you article entitled "Hypnotics' association with
mortality or cancer: a matched cohort study," I enjoyed reading it and
found it to be especially interesting. Nonetheless, I have a few comments
and questions related to your research area and your article.
Firstly, I thought the research design you choose was suitable for the
nature of the research. The matched cohort study was...
Thank you for you article entitled "Hypnotics' association with
mortality or cancer: a matched cohort study," I enjoyed reading it and
found it to be especially interesting. Nonetheless, I have a few comments
and questions related to your research area and your article.
Firstly, I thought the research design you choose was suitable for the
nature of the research. The matched cohort study was sufficient in
matching patients and controls based on age, gender, and smoking. However,
there is no mention of how non-prescription drugs that may have been
included within the sample population were accounted for. Also, how did
you account for the incidence of people using these hypnotic drugs without
a proper prescription? Additionally, I was wondering if the incidence of
cancer and mortality could have been a result of the use of multiple
medications by patients and their drug interactions. Furthermore, were any
adjustments made for patients that could have had prior forms of cancer
and how was it that the cancers studied developed within the 2.5 years.
Secondly, I am interested in why only temazepam and zolpidem were
presented in the data when any hypnotic user was noted in Table 1 of the
results. What other drugs were reported in this study and why was not
mention made of them and what were your inclusion criteria for which drugs
were classified to fit into this study. Furthermore, you comment on
temazepam being a benzodiazepine and the lethality being less severe than
the drug class barbiturates. In saying this, there is evidence of there
that supports that types of drugs in this class are not generally
associated with a increased risk of cancer and mortality. Therefore, how
can this increased risk of mortality and cancers be explained from your
research?
I also have a few concerns related to the statistical analyses of the
data. I feel the lack of inclusion of other drugs and possible
interactions warrant bias. I am also concerned the minimal information
provided on the other drugs that were included in this study and the lack
of cause of death that was reported. Finally, how were variables such as
the socioeconomic status of your particular population taken into account
and does this chosen group minimize the generalizaibility of this research
(or rather introduce any form of selection bias).
Overall, I found this article to be eye opening as these classes of drugs
are commonly used. I think the research is a relevant topic as society is
becoming increasing drug dependent ; however, I feel that more research
needs to confirm these high rates of cancer and mortality. Randomized
control trails would be ideal for this research in confirming these
studies results. As always, research is just one piece of the puzzle,
publicity and promotion of proper health practices are needed to ensure
research like this becomes available to the public.
Thanks for your article.
Sir,
we write you regarding the article "Baby knows best? The impact of weaning style on food preferences and
body mass index in early childhood in a case e controlled sample" by Ellen Townsend and Nicola J Pitchfordby, published on BMJ Open 2012;2:e000298. doi:10.1136/ bmjopen-2011-000298
We strongly disagree from the results shown by the authors, as we think that the article has strong bias which do not allow such conclusions....
Sir,
we write you regarding the article "Baby knows best? The impact of weaning style on food preferences and
body mass index in early childhood in a case e controlled sample" by Ellen Townsend and Nicola J Pitchfordby, published on BMJ Open 2012;2:e000298. doi:10.1136/ bmjopen-2011-000298
We strongly disagree from the results shown by the authors, as we think that the article has strong bias which do not allow such conclusions.
Our perplexities start from the introduction, where the authors state that "baby-led is suitable for most infants"; since, to our knowledge, no studies have been performed to show that the baby-led weaning style is safe from a nutritional point of view, this sentence is, at least, largely incomplete. Besides, "a maternal feeding style, which is low in control" is a well known determinant, in the long term, of childhood obesity; again, the sentence might be accepted, if referred to the period of weaning alone, but the life of a child does not end, hopefully, after weaning, and consequences of family life-styles, including control on the child's feeding patterns, quantities, and quality, must be taken into great consideration (1).
The problems continue with the sample composition. Since the start line, the two groups greatly differ for age, and for breastfeeding rate, and the gender rate is not considered, even though each one of these components can influence the nutritional status. Last, no information is provided regarding their parents' nutritional status.
Age difference can influence the results. Children composing the spoon-fed group are older than the baby-led one. This can imply that in some of them the adiposity rebound has already started, influencing the nutritional status' assessment.
Also the food preference changes along the years, and it has already been shown that 4 years old children actually prefer sweet foods when compared with 3 years old ones (2).
In addition, the different age can influence parents' memories for small details, such as when exactly the spoon was substituted by fingers and so on.
The breastfeeding rate is much higher in the baby-led group as compared with the other one. Even though the authors say that in the matched sample there is no difference between the two groups is hard to understand how the authors chose the single children composing the samples.
But the most important bias is that the anthropometric measurements have been taken using different procedures. The spoon-fed babies were measured by health professionals in an appropriate setting and using standardized procedures; for the baby-led weaning group, measurement's techniques are not specified, but from some passages in the article can be inferred that they had been measured by their own parents without any specific instruction and using "home-made" tools.
The different procedures can strongly influence the results and this makes the paper weak in its results and conclusions, especially when it declares that the baby-led weaning is a positive tool to prevent obesity development.
Faithful yours, Margherita Caroli, Marie Laure Frelut, Andrea Vania - (1) Wardle J, Sanderson S, Guthrie CA, Rapoport L, and Plomin R. Parental feeding style and the inter-generational transmission of obesity risk. Obes Res 2002; 10:453-62.
(2) Birch LL. Dimensions of preschool children's food preferences. J Nutr Ed. 1979;11:77-80.
We apologize if we created confusion by saying we "adjusted" for
prior cancer. Indeed, our method of adjustment was to exclude all
patients with any diagnosis of major cancer prior to the interval of
observation. Similarly, when examining non-melanoma skin cancers, we
excluded patients with prior skin cancers.
Unfortunately, only dichotomous responses concerning whether patients
used alcohol were available in...
We apologize if we created confusion by saying we "adjusted" for
prior cancer. Indeed, our method of adjustment was to exclude all
patients with any diagnosis of major cancer prior to the interval of
observation. Similarly, when examining non-melanoma skin cancers, we
excluded patients with prior skin cancers.
Unfortunately, only dichotomous responses concerning whether patients
used alcohol were available in the data files utilized. That is a
limitation of the study. A reliable quantitative history of alcohol use
is sometimes difficult to obtain, but if it were available, it could have
proven valuable in the analyses and could have reduced risks of residual
biases.
It might be surprising that cancers of the lung, prostate, or colon
would appear de novo within an average of 2.5 years, so the data may imply
that an effect of hypnotics was to disinhibit the growth of pre-existing
cancers, so that they were discovered. From a clinical point of view,
what is important is not when microscopic cancers originate, but whether
cancers reach a size and invasiveness that triggers clinical diagnosis and
concern. Experimental evidence for the carcinogenic potential of
hypnotics, which the manufacturers have not chosen to publish to my
knowledge, may be found in internet files of the U.S. Food and Drug
Administration New Drug Applications, and perhaps in similar European and
international data sources. Those animal data do not indicate if the
results reflect growth rates of cancers or their de novo neoplastic
transformation.
Our manuscript cited four studies finding no association of insomnia
with excess mortality, of which only one was authored by Dr. Kripke. The
literature is complex and perhaps lacking in consensus, but there is
consensus that the hazard ratio associated with insomnia is <2.0. Note
that in our study, not all patients prescribed hypnotics received their
prescriptions for a diagnosis of insomnia, and we have no reason to think
that patients in the control group were free of insomnia. Because the
contrast between those prescribed hypnotics vs. those not prescribed
hypnotics was not a contrast of those with and without insomnia, and
because the hazard ratio associated with insomnia is modest at best,
insomnia could not explain much of the hazard ratio of 4.6 associated with
hypnotic use.
We agree that cause of death data would be useful. However, that
information is not recorded in the electronic health records that formed
the basis for these analyses. We agree that osteoporosis should be
prevalent in the older women in this cohort. However, it was necessary to
restrict the classes of comorbidities which could be examined, and
osteoporosis was one of many kinds of comorbidity which were not extracted
from the electronic medical records.
With 18 previous studies showing an association of hypnotic use with
mortality in addition to ours, and no studies suggesting that hypnotics
prolong life or prevent cancer, the preponderance of evidence is now
sufficient for clinical decisions. More independent studies will be
valuable, but failing to act on available evidence now could cost lives.
As these distinguished authors write, efforts should be made to improve the accessibility of non-drug treatments for insomnia such as cognitive-behavioral approaches. By reducing the use of hypnotics, such treatments might be life-saving.
Insomnia is twice as common in the UK as anxiety or depressive
symptoms(1). Indeed, chronic insomnia is a risk factor for the development
of such mental health problems(2). Yet in a week when new research shows
that the prevalence of insomnia is increasing in England(3), and that even
occasional hypnotic drug use continues to be associated with excess
mortality(4), it is disappointing that after 21 months of waiting for a...
Insomnia is twice as common in the UK as anxiety or depressive
symptoms(1). Indeed, chronic insomnia is a risk factor for the development
of such mental health problems(2). Yet in a week when new research shows
that the prevalence of insomnia is increasing in England(3), and that even
occasional hypnotic drug use continues to be associated with excess
mortality(4), it is disappointing that after 21 months of waiting for a
response, NICE has said that a broadly based call for the development of
insomnia treatment guidance will not proceed through the topic selection
process(5).
We see a parallel here to the situation 30 years ago, when leading
researchers and clinicians denied the existence of obstructive sleep
apnoea (OSA) in Britain(6). Fortunately, OSA is now widely and effectively
treated in the NHS. What accounted for this remarkable transition?
First, the adoption of OSA by the medical speciality of respiratory
medicine; and second, the provision of NICE guidelines on treatment(7).
Insomnia likewise has lacked a clinical specialty to champion the
disorder, but surely the recent development of psychological therapy
services through the IAPT programme(8) offers the ideal opportunity for
rational integration of pharmacological and cognitive behavioural
treatments for insomnia in primary care? What is needed now is clear
direction, by means of national guidelines, to structure clinical
management and service provision in this neglected area. Otherwise, this
opportunity will almost certainly be lost, with consequences measureable
in degraded quality of life and amplified health risk among millions of
patients(9).
We estimate that, over the past 15 years, the British public has
supported over 5 million pounds worth of world-class research into the
nature and optimal treatment of chronic insomnia; research that has
greatly benefitted patients in other countries. To date, however, the
British public has received a poor return on this investment and we trail
far behind in the implementation of evidence-based practice. There can be
few conditions where the discrepancy between what should be done, and what
is being done, has been tolerated for so long.
References
1. Singleton N, Bumpstead R, O'Brien M, et al. Psychiatric morbidity
among adults living in private households, 2000. London: The Office for
National Statistics, HMSO;2001.
2. Baglioni C, Battagliese G, Feige B, et al. Insomnia as a
predictor of depression: A meta-analytic evaluation of longitudinal
epidemiological studies. J Affect Disord 2011;135:10-19.
3. Calem M et al. Increased Prevalence of Insomnia and Changes in
Hypnotics Use in England over 15 Years: Analysis of the 1993, 2000, and
2007 National Psychiatric Morbidity Surveys. Sleep 2012;35(3):377-384
4. Kripke DF, Langer RD, Kline LE. Hypnotics' association with
mortality or cancer: a matched cohort study. BMJ Open 2012;2:e000850.
doi:10.1136/bmjopen-2012-000850
5. NICE Topic Selection Team. Personal communication. 8 Feb 2012.
6. Shapiro CM, Catterrall JR, Oswald I, Flenley DC. Where are the
British sleep apnoea patients?. Lancet 1981; ii: 523.
7. National Institute for Health and Clinical Excellence (NICE).
Technology Appraisal Guidance 139: Sleep apnoea - continuous positive
airway pressure (CPAP), NICE, 2008.
8. Department of Health. IAPT Programme Review December 2011 v2.2.
http://www.iapt.nhs.uk/silo/files/iapt-programme-review-december.pdf
(accessed 3 March 2012)
9. Mental Health Foundation (MHF). Sleep Matters: The impact of
sleep on health and wellbeing. London, MHF 2011.
Authors
Colin Espie, Professor of Clinical Psychology, University of Glasgow;
Director, University of Glasgow Sleep Centre
Kevin Morgan, Professor of Gerontology, Loughborough University;
Director, Clinical Sleep Research Unit, Loughborough University
David Nutt, Professor of Neuropsychopharmacology, Imperial College
London
Niroshan Siriwardena, Professor of Primary and Prehospital Health
Care,
University of Lincoln
Derk-Jan Dijk, Professor of Sleep and Physiology, University of
Surrey; Director, Surrey Sleep Research Centre
Brian McKinstry, Professor of Primary Care E-Health, University of
Edinburgh
June Brown, Senior Lecturer in Clinical Psychology; Joint Head of
Mood, Anxiety and Personality (MAP) Clinical Academic Group (CAG), South
London & Maudsley NHS Foundation Trust
John Cape, Head of Clinical Psychology, Camden & Islington NHS
Foundation Trust, London
Sue Wilson, Senior Research Fellow, University of Bristol; President,
Sleep Section, Royal Society of Medicine
Maureen Tomeny, Consultant Clinical Psychologist, Clinical Director
of IAPT Services, Nottinghamshire Healthcare NHS Trust
Andrew McCulloch, Chief Executive, Mental Health Foundation, London
Neil Douglas, Professor of Sleep & Respiratory Medicine,
University of Edinburgh; Chairman, Academy of Medical Royal Colleges, UK
We have read with great interest the recent article by Kripke DF,
Langer RD and Kline LE that assessed the risk of all cause mortality and
cancer incidence in patients using benzodiazepines or zolpidem. The
article poses relevant questions about the use of these drugs and it is
likely to have a very large influence on the decisions that health care
practioners take, particularly because of the larg...
We have read with great interest the recent article by Kripke DF,
Langer RD and Kline LE that assessed the risk of all cause mortality and
cancer incidence in patients using benzodiazepines or zolpidem. The
article poses relevant questions about the use of these drugs and it is
likely to have a very large influence on the decisions that health care
practioners take, particularly because of the large number of patients
studied, the magnitude of the HR found and the fact that there are few
articles examining a possible relation between hypnotics and mortality.
However, our attention was drawn to some possible limitations that might
make the interpretation of the results difficult on a daily basis.
The first issue that we noticed was that in the abstract and in the
supplementary files Kripke DF et al state that the stratified models were
adjusted for prior cancer, while on the methods section it is explicitly
stated that patients with prior cancer (other that non-melanoma skin
cancer) were excluded from the study. We could not find any adjustement
for prior cancer in any table in the published article, or in
supplementary table 7. This might lead to some confusion as it is not
clear if the Cox proportional hazard model was indeed adjusted for prior
cancer, and it could pose a limitation to the external validity as
insomnia is more prevalent in cancer patients .
We also noticed some problems in the design regarding covariates used
for adjustement. Alcohol use was classified as a dichotomous variable,
depending on the patient's self response to alcohol use in a yes or no
question. This could pose an important limitation to the study, as alcohol
is a recognized dose dependant depressant in the central nervous system
acting as an agonist in GABA receptors and it might act synergistically
with benzodiazepines to induce sedation. The alcohol related central
nervous system depression is not equivalent between low alcohol
consumption and high alcohol consumption, and we believe that alcohol use
should have been an ordinal variable in the Cox proportional hazards model
used. According to supplementary table 3, there was a significant
prevalence (between 35-45%) of alcohol use in hypnotic users, and since
the quantity of alcohol was not taken into consideration there might have
been important differences between the hypnotic users and the control
group that could influence the results introducing selection bias.
Kripe et al analyzed the HR for incident cancers in hypnotic users
compared with non users, and it was statistically significant for some
important cancers like lymphoma, colon cancer and lung cancer. This is
very important for clinical practice, as doctors and patients might not
know about a possible carcinogenetic effect of hypnotics and might
consider alternative therapies if the results obtained by Kripke et al are
consistent with further studies. Nevertheless, we find the results
difficult to interpret in relation with lung, prostate and colon cancer.
The mean follow up of this cohort study was 2.5 years, and it is widely
known than lung, prostate and colon cancer take many years to develop. We
are skeptical as to whether the incident cancers are indeed related to
hypnotic use, as it is plausible that hypnotic users had an undiagnosed
cancer before hypnotic prescription, and developed cancer independently of
hypnotic use. Furthermore, since hypnotic users differed from the non
users on insomnia and sleep related problems they might have been more
carefully examined in hospital visits, leading to selective overdiagnosis.
This is particularly relevant to prostate cancer and to lung cancer . The
temporal sequence between hypnotics and cancer has not been assessed
robustly, and further studies should have a longer follow up of
participants to analyze this relation as it is possible that an
undiagnosed cancer lead to insomnia and hypnotic use and not the other way
around as Kripke et al discuss in their article. To our knowledge, there
is no experimental evidence for the carcinogenetic potential of hypnotics
except a previous study by Kripke DF. It would be more prudent to wait for
studies done by other researchers in order to see if the results are
consistent.
Perhaps the main factor that makes it difficult to interpret the
results is that the cause of death was not reported. This fact was taken
into consideration in the article's discussion, where Kripke et al cite
articles that suggest many pathways by which hypnotics may lead to excess
mortality. It is true that hypnotic use leads to impared balance and
cognition, and that there are numerous articles that find an association
between hypnotic use and adverse health outcomes but it is also true that
insomnia is associated with an increase in mortality , . Kripe et al
states that several large studies have found that insomnia is not a
significant mortality favor, but we could retrieve few articles by
independent researchers that support the statement. In fact, most of the
articles that support the statement are written by Kripe et al . We are
concerned that a confirmation bias might be present in this article, as
the relationship between insomnia and mortality was dismissed, but there
is sufficient evidence that insomnia is associated with an increase in
mortality. It could be that the increase in mortality was not due to
hypnotics but to insomnia, so the effect would be independent of hypnotic
use or even decreased by hypnotic use. Besides, there are other
comorbilities that ought to have been included as coviarates. We find that
osteoporosis and prior fracture history might be relevant in geriatric
patients, as there are various well designed studies that show an
increased mortality risk in geriatric patients after fractures . Since
more than 60% of the population in the cohort are women, osteoporosis
should have been taken into consideration and failure to account for
different prevalence between the hypnotic users and non users could limit
the applicability of the results.
In conclusion, the available evidence of an association between
hypnotics and mortality is not sufficiently vigorous. There are many
coviarates that might have introduced selection bias, so the specific
contribution of hypnotics to mortality is difficult to determine
objectively. The possibility of overdiagnosis of cancer, and of residual
confounding due to indication is still present in the study. More
independent studies are needed assessing the possible risks of
benzodiazepines in order to give health care recommendations. We consider
that it would be prudent to wait for more evidence before condemning
hypnotics.
References
1 Kripke DF, Langer RD, Kline LE. Hypnotics' association with
mortality or cancer: a matched cohort study. BMJ Open 2012;2:e000850.
doi:10.1136/bmjopen-2012-000850
2 Palesh OG, Roscoe JA, Mustian KM, Roth T, Savard J, Ancoli-Israel
S, Heckler C et al. Prevalence, Demographics, and Psychological
Associations of Sleep Disruption in Patients With Cancer: University of
Rochester Cancer Center-Community Clinical Oncology Program. Journal of
Clinical Oncology. 2010; 10;28(2):292-8.
3 Ashton H. Toxicity and adverse consequences of benzodiazepine
use. Psychiatric Annals. 1995;25:158-65.
4 Longo L, Johnson B. Addiction: Part I. Benzodiazepines- Side
effects, Abuse Risk and Alternatives. Am Fam Physician. 2000; 1.61(7):2121
-28
5 U.S. Preventive Services Task Force. Screening for Prostate Cancer:
U.S. Preventive Services Task Force Recommendation Statement. Annals of
Internal Medicine. 2008; 149.3: 185-91
6 Marcus PM, Bergstralh EJ, Fagerstrom RM, Williams DE, Fontana R,
Taylor WF, Prorok PC. Lung cancer mortality in the Mayo Lung Project:
impact of extended follow-up. J Natl Cancer Inst.2000; 92 (16): 1308-16
7 Vgontzas A, Liao D, Pejovic S, Calhoun S, Karataraki M, Basta M et
al. Insomnia with Short Sleep Duration and Mortality: The Penn State
Cohort. Sleep.2010; 33(9): 1159-1164
8 Prospective Study of the Association between Sleep-Disordered
Breathing and Hypertension
Peppard PE, Young T, Palta M, Skatrud J. Prospective Study of the
Association between Sleep- Disordered Breathing and Hypertension. New
England Journal of Medicine. 2000; 342: 1378-84
9 Kripke DF, Garfinkel L, Wingard D, Klauber M, Marler M. Mortality
associated with sleep duration and insomnia. Arch Gen Psychiatry. 2002;
59: 131-36
10 Bliuc D, Nguyen N, Milch V, Nguyen T, Einsman J, Jacqueline R.
Center. Mortality Risk Associated With Low-Trauma Osteoporotic Fracture
and Subsequent Fracture in Men and Women. JAMA. 2009; 301(5):513-21
Why weren't people with insomnia who didn't take hypnotics included
in the control group-could insomnia and not hypnotics be the factor
causing excess death???Is the dose relationship just an indication of the
severity of insomnia?
The recent paper by Dobler et al. (2012) highlights the challenge of variable selection and adjustment in multivariate analyses [1]. The authors state that including the potentially confounding variable 'TB incidence in the country of birth' was one of the major strengths of their study. TB incidence in the country of birth is indeed an important predictor of the risk of developing TB - but it may not be a true confounde...
In response to the letter from ECOG we would to like highlight that the criticisms levied against our research were already discussed explicitly in our paper and the limitations, for example, of parental self -report were mentioned up front in the article in the summary box. For precisely the reasons mentioned by the ECOG group we generated a matched sample from our total sample in which we controlled for age. The matched...
Dr. Daniel Kripke,
Thank you for you article entitled "Hypnotics' association with mortality or cancer: a matched cohort study," I enjoyed reading it and found it to be especially interesting. Nonetheless, I have a few comments and questions related to your research area and your article. Firstly, I thought the research design you choose was suitable for the nature of the research. The matched cohort study was...
We apologize if we created confusion by saying we "adjusted" for prior cancer. Indeed, our method of adjustment was to exclude all patients with any diagnosis of major cancer prior to the interval of observation. Similarly, when examining non-melanoma skin cancers, we excluded patients with prior skin cancers.
Unfortunately, only dichotomous responses concerning whether patients used alcohol were available in...
Conflict of Interest:
Please see our BMJ Open article
Insomnia is twice as common in the UK as anxiety or depressive symptoms(1). Indeed, chronic insomnia is a risk factor for the development of such mental health problems(2). Yet in a week when new research shows that the prevalence of insomnia is increasing in England(3), and that even occasional hypnotic drug use continues to be associated with excess mortality(4), it is disappointing that after 21 months of waiting for a...
Dear Editor:
We have read with great interest the recent article by Kripke DF, Langer RD and Kline LE that assessed the risk of all cause mortality and cancer incidence in patients using benzodiazepines or zolpidem. The article poses relevant questions about the use of these drugs and it is likely to have a very large influence on the decisions that health care practioners take, particularly because of the larg...
Why weren't people with insomnia who didn't take hypnotics included in the control group-could insomnia and not hypnotics be the factor causing excess death???Is the dose relationship just an indication of the severity of insomnia?
Conflict of Interest:
None declared
myalgc encephalomyelitis is viral damage to the brainstem. the rest is nhs garbage.
Pages