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Displaying 1-10 letters out of 2361 published
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Re:RISK/BENEFIT RATIO OF OPIOIDS FOR CHRONIC NONCANCER PAIN
Submit responseWhere is the evidence that opioid analgesics should be the first choice for drugs prescribed for chronic noncancer pain? Evidenced-based recommendations point to the opposite conclusion. These include: [1]a consensus panel recommendation for the management of neuropathic pain which considers opioids mainly as second-line agents,[2]a recent Cochrane systemic review on osteoarthritis of the knee or hip which concluded that the large increase in risks for adverse events of non-tramadol opioids outweigh any small to moderate benefits, and that they should not be used routinely,[3]a joint specialty clinical practice guideline for low back pain which placed opioids far down the list of treatment options, and [4] EULAR evidence-based recommendations which stated that strong opioids are not recommended for the pain of fibromyalgia syndrome.
It is apparent that even for tissue-derived chronic noncancer pain, opioids must be used very selectively, if at all, while for the large volume of people with central pain sensitivity states, the risks appear to far outweigh any perceived benefits. When the mounting toll of reported adverse events [including overdose and death] is factored in, it is clear that the nonselective long-term use of opioid therapy for chronic noncancer pain carries a significantly high risk/benefit ratio.
References:
[1]O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009;Oct;122[10 Suppl]:S22-32.
[2]Nuesch E et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009; Oct 7;[4]:CD003115.
[3]Chou R et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007;147[7]:478-491.
[4]Carville SF et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008;67:536-541.
Conflict of Interest:
None declared
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Is there an excess or lower diabetes risk in female cigarette smokers?
Submit responseAuthors examining prospectively the association of smoking status with the development of incident type-2 diabetes in the ARIC cohort (1) arrived at the conclusion that smoking predicts incident diabetes, and smoking cessation leads to higher short-term risk. The first part of the conclusion was not convincing for several reasons: Firstly, because excess risk did not emerge in one-third (mild smokers) of the smokers.
Secondly, the study does not clarify whether this risk is valid only for men or for both sexes, since sex-stratified analyses are totally missing. In the regression analyses, the referent never smokers and the top tertile were composed predominantly of different sexes differing substantially in risk. Sex adjustment may not disclose the situation for women who may well have been unaffected by the habit, though adjusted combined analyses have yielded excess risk.
Thirdly, adjustment for body mass index (BMI) may be biased depending on whether or not smoking led to a reduction in obesity in this cohort. If it did, which seems to be so from the significantly lower BMI values noted in increasing categories of smoking, this would conceal a possible beneficial BMI-mediated effect of the habit to the risk of diabetes. This adjustment might introduce bias to male smokers as well.
Finally, compared with never smokers, the adjusted hazard ratio persisted to be slightly raised at least a decade after discontinuance and was reported to be increased 1.54-fold among those who had quit 3-5 years previously.
Despite the statement in the introduction that cigarette smoking is consistently identified as a risk factor for incident diabetes, the issue is far from established, and several studies (2,3) indicate smoking may partly protect (women) against diabetes. Indeed, in a part of the ARIC cohort, adjusted subjects with isolated impaired glucose tolerance, a prediabetic state more prone to diabetes, were less likely to smoke than those with normal or impaired fasting glucose (4). In most studies concerned, the group which subsequently developed diabetes had fewer smokers than those who did not develop. The D.E.S.I.R. study cited in authors' article offers convincing findings to explain these observations. Authors were right in considering the effect of smoking on the pro-inflammatory state mediating the development of diabetes. Yet a large meta -analysis on circulating CRP in over 160,000 participants (5), noted same or marginally lower CRP concentrations compared to non-smokers in female current smokers, though male current smokers had higher CRP levels. Thus the reader would appreciate to learn the effect of smoking in this study on the risk of diabetes in each sex without the mediation by BMI.
References 1. Yeh H-C, Duncan BB, Schmidt MI, Wang N-Y, Brancati FL. Smoking, smoking cessation, and risk for type 2 diabetes. Ann Intern Med 2010:152:1-17
2. Onat A, Ozhan H, Esen AM, Albayrak S, Karabulut A, Can G, Hergenc, G. Prospective epidemiologic evidence of a "protective" effect of smoking on metabolic syndrome and diabetes among Turkish women -without associated overall health benefit. Atherosclerosis 2007; 193:380-9
3. Nagaya T, Yoshida H, Takahashi H, Kawai M. Heavy smoking raises risk for type 2 diabetes mellitus in obese men; but, light smoking reduces the risk in lean men: a follow-up study in Japan. Ann Epidemiol 2008; 18:113-8
4. Pankow JS, Kwan DK, Duncan BB, Schmidt MI, Couper DJ, Golden S, Ballantyne CM. Cardiometabolic risk in impaired fasting glucose and impaired glucose tolerance: the Atherosclerosis Risk in Communities Study. Diabetes Care 2007; 30:325-331.
5. The Emerging Risk Factors Collaboration: C-reactive protein concentration and the risk of coronary heart disease, stroke and mortality: an individual participant meta-analysis. Lancet 2009 Epub Dec 22
Conflict of Interest:
None declared
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2 of 282 extended patch users quit 1 year
Submit responseWhile benefit at 24 weeks, Schnoll and colleagues report nearly identical one-year point prevalence smoking cessation rates following 24 weeks of nicotine patch use versus the standard 8 weeks. They ignore long-term outcome in suggesting that their extended patch study "demonstrates the benefits of extended duration therapy with transdermal nicotine(1)." They arrive at this conclusion when only 2 of 282 extended patch quitters were able to stop smoking for the entire year, an appalling one-year continuous cessation rate of 0.7%. Contrary to suggesting extended use benefit, eight week patch users actually had a 30% higher rate of 1.0%, reflecting 3 of 286 participants able to quit smoking for a full year (1).
The authors ignore the fact that while historic one-year unaided continuous smoking cessation rates range from 3 to 11%[2], that the generally accepted rate is 5%, a minimum 7-fold advantage over this study's 0.7% finding.
This study exposes the reality that more than 200 placebo-controlled nicotine replacement studies were not about arresting chemical dependency upon nicotine but about ending a single form of delivery, smoking it. This study supports the contention that the human brain cannot down-regulate a4b2-type nicotinic receptor counts nor re-sensitize them while nicotine continues to arrive (3).
It evidences the neuro-chemical reality that using nicotine to aid nicotine addicts in quitting makes about as much sense as giving alcohol to alcoholics. Quality nicotine cessation research involves acceptance of three key factors: (1) that no placebo-controlled trial has yet been blind as claimed, that it is impossible to blind smokers with lengthy quitting histories as to the presence or absence of full-blown withdrawal, as that they are experts at recognizing it[4]; (2) teaching total respect for the "Law of Addiction," that just one puff or hit and up to 50% of the brain's a4b2-type receptors will become occupied by nicotine,(5) that while the smoker may walk away from relapse thinking they have gotten away with it, that their brain will soon be begging for more;(6) and, (3) that two weeks of intense abrupt cessation counseling and support (12-14 hours) are key to dramatically enhancing long-term nicotine cessation rates.
Schnoll and colleagues abandon the goal of nicotine cessation, impliedly suggesting that success can be claimed by keeping smokers dependent upon NRT for life. They propose this non-cessation solution knowing that even by their own data, which employs a quitting definition that's extremely forgiving of relapse, that roughly 70% of extended patch users had relapsed prior to 24 weeks.
Before abandoning nicotine cessation we need to design and execute studies where it's the sole objective. While smoking morbidity and mortality are compelling motivations, life isn't about how we eventually die but life's quality today. Nicotine addiction is about living a lie, that endless chemical servitude to nicotine's two-hour half-life is more important than life itself. It's time to destroy needless anxiety generating fears by attacking the lie itself. Smokers do not smoke because of flavor, boredom, aroma, pleasure or stress. They do so because they must, because a rising tide of insula routed anxieties begin to hurt when they don't.
References
[1] Schnoll RA et al, Effectiveness of Extended-Duration Transdermal Nicotine Therapy: A Randomized Trial, Ann Intern Med 2010 152:144-151.
[2] Gritz ER et al, Unaided Smoking Cessation, Great American Smokeout and New Year's Day Quitters, Journal of Psychosocial Oncology, Volume 6, Issue 3; 4 March 1989, pages 217-234.
[3] Ortells MO, Barrantes GE, Tobacco addiction: A biochemical model of nicotine dependence, Med Hypotheses, 2009 Dec 2. [Epub ahead of print].
[4] Polito JR, Smoking Cessation Trials, CMAJ, November 4, 2008; 179 (10); and Mooney M, et al, The blind spot in the nicotine replacement therapy literature: Assessment of the doubleblind in clinical trials, Addict Behav., 2004 June;29(4):673-684.
[5] Brody AL et al,Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors, Archives of General Psychiatry, August 2006, Volume 63(8), Pages 907-915.
[6] Brandon, TH et al, Postcessation cigarette use: the process of relapse, Addictive Behaviors, 1990; 15(2), pages 105-114; and Borland R, Slip-ups and relapse in attempts to quit smoking, Addictive Behaviors, 1990, Volume 15(3), Pages 235-245.
Conflict of Interest:
Director WhyQuit.com, an abrupt nicotine cessation forum and author of Freedom from Nicotine - The Journey Home.
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Re:OPIOID-RELATED MORTALITY AND RISK/BENEFIT RATIO
Submit responseWe disagree that "it is clear that non-opioid medications along with self-management multidiscplinary therapies are the treatments of choice." NSAIDs are deadlier than opioids, but there is no social stigma against these types of drugs nor towards patients that use them. In our experience, pain needs to be controlled first before patients can successfully complete a physical therapy program. We agree on a multidiscplinary approach, but opioids are often a necessary adjunt.
Conflict of Interest:
None declared
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Diabetes, Risky Behaviors and Stress: Those Pesky Confounding Factors.
Submit responseDiabetes, Risky Behaviors and Stress:
Those Pesky Confounding Factors.
Introduction - Background
Yeh et al report that smoking cessation slightly increases the risk for diabetes. They attribute this iatrogenic effect to the weight gain common after cessation(1). However, two important factors were not considered. Stress particularly during childhood(2) has strong graded effect on tobacco initiation and maintenance as well as obesity. Insular stroke(IS) was found to be related to smoking cessation(3). Because this relationship was observed in a convenience sample of the existing population, IS must play some role in the current tobacco cessation process.
Synthesis (Graphic)
Stress, through levels of cortisol, has an adverse effect on all major human sub-systems, but especially respiratory disorders and metabolic syndrome x (insulin resistance). Stress related depression is common to tobacco initiation(2), asthma(4), digestive disorders(5) and cardiovascular disease including stroke. Depressive symptoms are common in smoking cessation.
Nicotine a CNS and respiratory stimulant has been used to treat respiratory disorders including asthma. It increases respiratory drive, reducing hypoxia.
The insula translates internal and external senses into feelings to motivate action to achieve homeostatic balance. IS may disrupt the natural response to glucose and hypoxia levels, defeating self-medication efforts. However, in statistical studies, there would still be a correlation between reported smoking status and diabetes. We should not rule out the possibility that those who smoke are simply treating (self-medicating) stress related respiratory disorders.
Memories are malleable.
Studies of ACE's find that survivors of traumatic stress often lose autobiographic memory of details surrounding the event. The cessation process, often part of current mental health therapy entails changes in thought. Psychotherapy, group dynamics, hypnosis have been used to re-creating images and thoughts to foment a change in behavior. Imagine yourself as a nonsmoking (or thin) person. The population of interest, has had a high exposure to stress with an increased risk for tobacco use and obesity, and more likely exposed to memory changing influences. So, just how much credence can we give to self-reports of former or nonsmoking status?
Conclusion:
As exquisite as the Yeh, Naqvi and ACE studies are by current standards, this demonstrates the difficulty trying to establish causality in human adaptive behavior. If A correlates with B, A may cause B, or C may be caused by a yet undiscovered factor C. Only when close attention to the temporal and specificity issues can relationships be considered causal. And, even then, some new undiscovered confounding factor may come to light.
REFERENCES:
1. Yeh HC, Duncan BB, Schmidt MI, Wang NY, Brancati FL.
Smoking, smoking cessation, and risk for type 2 diabetes mellitus: a cohort study.
Ann Intern Med. 2010 Jan 5;152(1):10-7.
2. Anda RF, Croft JB, Felitti VJ, Nordenberg D, Giles WH, Williamson DF, Giovino GA.
Adverse childhood experiences and smoking during adolescence and adulthood.
JAMA. 1999 Nov 3;282(17):1652-8.
3. Naqvi NH, Rudrauf D, Damasio H, Bechara A.
Damage to the insula disrupts addiction to cigarette smoking.
Science. 2007 Jan 26;315(5811):531-4.
4. Scott KM, Von Korff M, Alonso J, Angermeyer MC, Benjet C, Bruffaerts R, de
Girolamo G, Haro JM, Kessler RC, Kovess V, Ono Y, Ormel J, Posada-Villa J.
Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.
Psychosom Med. 2008 Nov;70(9):1035-43.
5. Thomas C, Hyppönen E, Power C.
Obesity and type 2 diabetes risk in midadult life: the role of childhood adversity.
Pediatrics. 2008 May;121(5):e1240-9.
A graphic (flow chart) of the diabetes, smoking, & stress system can be viewed at:
http://home.earthlink.net/~schrand/ACEs%20Stress%20Insula%20-%20Feb%202010%20.htm
Conflict of Interest:
In 1994, the author requested an educational grant from the Council for Tobacco Research to study the relationship between tobacco use and sleep apnea. This request was denied. However the letter seems to have become part of the tobacco archives: http://tobaccodocuments.org/ctr/60024574 4574.html. Aside from this, the author has no financial interest in the tobacco, diet, or health industries other than as a consumer of their products and services.
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Opioid dose related to increased risk of overdose
Submit responseWe commend Dr. Dunn and colleagues on their findings of a dose- response relationship between opioid dose and overdose risk. Although some subjects partook in aberrant opioid use, most were not taking opioids for at least 6 months. The authors found that opioid doses of 20 mg daily were associated with lower potential for overdose than higher doses. The daily doses reported were reflective of the cumulative dose dispensed over 90 days, divided by 90 without indication of the prescribed duration of opioids. All subjects filled at least 3 opioid prescriptions, but the days supply was not reported. This may lead to misinterpretation of their finding. Consider the scenarios of Patients A and B, who have been opioid naive for at least 6 months and whose calculated average daily opioid dose was 20 mg over the 90-day period. Patient A took morphine 150 mg daily for a total of 12 days and Patient B took morphine 20 mg daily for 90 days. Both patients filled three morphine prescriptions and ingested a cumulative dose of 1800 mg over 90 days, with an average of 20 mg daily. It must be emphasized, however, that Patient A may be at a substantially higher risk of opioid-related overdoses than Patient B. Additional information, including the days supply of opioid prescriptions filled could have been useful, but clearly do not negate the value of the authors' findings, which offer guidance on safe initial doses of opioids for opioid-naive chronic nonmalignant pain.
Conflict of Interest:
None declared
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Failure to differentiate between men and women in primary prevention
Submit responseThis article's failure to distinguish between men and women is troublesome. Several meta-analyses of primary prevention statin results for women with elevated cholesterol show no statistically significant cardiac outcome benefits (1). And results for men and women statistically significantly differ (2). Some studies even suggest increased cardiovascular risk for women or for female age subgroups (1). One of the drugs emphasized in this article, atorvastatin, has no clinical trial showing cardiac benefits to women in a primary prevention context. The ASCOT trial showed increased heart attack risk to women and the CASHMERE trial, limited to post-menopausal women, showed no benefit to women in the IMT endpoint used. CASHMERE's results have not been published in a journal nor did PFizer's website alert physicians to their existence.
References
1. Eisenberg T, Wells MT. Statins, cholesterol, women and primary prevention: evidence-based medicine or wishful thinking? Future Cardiology 2009; 5: 1-4.
2. Eisenberg T, Wells MT. Statins and adverse cardiovascular events in moderate-risk females: a statistical and legal analysis with implications for FDA preemption claims. Journal of Empirical Legal Studies 2008; 5: 507-50.
Conflict of Interest:
None declared
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Value of Experience
Submit responseThis is a crucial issue and the responses you have thus far published seem unworthy of the importance. Medical practice depended traditionally on shared knowledge and experience yet experience is never examined for its quality. My experience is no more than the recollections ( highly selective) of the clinical encounters thus far in my practice. How accurately are they recalled. We do not know. Record keeping till now has been thoroughly inadequate. We tend to remember (and seek to replicate) our successes and I imagine suppress our failures. Only now with the entry of computers into clinical care can we begin to record and display what any individual's experience actually is and sharing this adds to a communal knowledge of how best to help our patient patients. The review while fragile highlights a key issue and needs better responses than have appeared thus far.
Conflict of Interest:
A Commitment to offering patients the best available information, advice and interventions in a humane manner.
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OPIOID-RELATED MORTALITY AND RISK/BENEFIT RATIO
Submit responseThe observation that pain is 'untreated and undertreated' does not mean that opioids are 'underutilized'; in fact they are overutilized which has contributed to the rising volume of overdose and death as brought out in this Annals article by Dunn et al.(1) and the accompanying editorial (2). Given the large volume of the population suffering from chronic pain syndromes, especially those related to central pain sensitivity states such as occurs with unattenuated stress associated with varying degrees of anxiety and depressive disorders,it is clear that non-opioid medications along with self-management multidiscplinary therapies are the treatments of choice, while opioids in these settings can increase the risk of addiction, overdose and death. Furthermore, good evidence is lacking for the long-term [e.g. over 6 months] effectiveness and safety of opioid therapy for chronic noncancer pain (3).
Any decision to start opioid therapy for chronic noncancer pain must consider the type of pain being treated and the significant risk/benefit ratio, which, in addition to addiction, should include awareness of the mounting toll of ER visits, overdose and death related to prescription opioids (4,5). It should be noted that in the state of Florida alone, there were 890 oxycodone-related deaths in the 6 months from January to June 2009, which was a 14.4% increase compared to the previous 6 months, and which was almost double the number of oxycodone-related deaths of 923 for the entire year of 2006. The highest percentage of deaths occurred in the 35 and above age groups which comprised 64% of all oxycodone-related mortality (6), the age groups which receive the vast majority of prescriptions for opioid painkillers, including OxyContin.
References:
1. Dunn KM et al. Opioid prescriptions for chronic pain and overdose. A cohort study. Ann Intern Med. 2010; 152:85-92.
2. McLellan AT, Turner BJ. Chronic noncancer pain management and opioid overdose: Time to change prescribing practices. Ann Intern Med. 2010; 152:123-124.
3. Trescot AM et al. Opioid guidelines in the management of chronic noncancer pain. Pain Phys. 2006; 9:1-39.
4. Paulozzi LJ et al. Increasing deaths from opioid analgesics in the United States. Pharmacoepidemiol Drug Saf. 2006; 15:618-627.
5. Dhalla IA et al. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone. CMAJ. 2009; 181[12]:891-896.
6. Florida Department of Law Enforcement. 2009 interim report of drugs identified in deceased persons by Florida Medical Examiners. Nov. 2009. [www.fdle.state.fl.us/publications/Examiners/2009DrugReport.pdf]
Conflict of Interest:
None declared
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Overdose can occur at a patient's usual opioid dose
Submit responseDunn and colleagues present sobering data on opioid overdose (1), showing a direct correlation between daily morphine equivalents and overdose rates. As echoed in the accompanying editorial by McLellan and Turner (2), these data provide every clinician prescribing opioids another forceful reminder to thoroughly review the indication, effectiveness and safety with patients.
One safe medication-taking practice that is often overlooked by clinicians and patients is asking patients on chronic opioids to contact the office when feeling unwell. Providers and patients, especially the elderly and those with multiple comorbidities, should understand that the effective opioid dose when feeling relatively well may be harmful when intercurrent illness is present. Volume depletion can increase plasma concentrations of opioids (3); decreases in glomerular filtration rate can promote accumulation of active opioid metabolites (4); and any co- occurring alteration in sensorium due to a variety of medical illnesses can be dramatically exacerbated by a patient's typical opioid dose. Most worrisome is that patients may increase opioid doses, or doses of other psychoactive medications, when feeling unwell in an attempt to treat symptoms.
Though adding another box to the checklist of safety reminders might make opioid prescribing even more onerous to clinicians, we believe strongly that common sense safety measures must be part of every prescriber's protocol to minimize adverse outcomes.
References:
1. Dunn KM, Saunders KW, Rutter CM, et al. Opioid Prescriptions for Chronic Pain and Overdose. Annals of Internal Medicine. 2010;152:85-92.
2. McLellan AT, Turner BJ. Chronic Noncancer Pain Management and Opioid Overdose: Time to Change Prescribing Practices. Annals of Internal Medicine. 2010;152:123-124.
3. Mercandante S. Opioid Rotation for Cancer Pain. Rationale and Clinical Aspects. Cancer. 1999;86(9):1856-1866.
4. Inturrisi CE. Clinical pharmacology of opioids for pain. Clinical Journal of Pain. 2002;18(4 Suppl):S3-13.
Conflict of Interest:
None declared