• Increased Calcium intake doesn't reduce Fracture Risk in Older People
• Can Dextromethorphan plus Quinidine reduce Agitation in Patients with Alzheimer Disease Dementia?
• Increase in Self-Harm Emergencies noted after Bariatric Surgery
• Breast Cancer Stage at Diagnosis still affects Prognosis
• Do SSRIs Increase Violent Criminal Acts?
• Low-Dose Aspirin use and Colorectal Cancer risk
• Cardiometabolic Complications of Childhood Obesity appear early
• Reduce Nicotine Levels in Cigarettes, reduce Smoking?
MM: It is uncanny how we were duped to commit patients to consume high levels of Calcium and now we are told that it shows no benefit. It may be accurate that for older people the bone density benefits of increased calcium ingestion may be minimal. However, it is still a fact that increasing bone density earlier in life will translate to a decreased risk of thin or weak bones later in life. For that reason, amongst others, it is still wise to ingest some calcium and certainly at least 200-400mg of available magnesium such as Magnesium Glycinate daily for muscle, heart and bone health. Bones are not the only reason to consume these minerals in some quantity. Magnesium and calcium help with sleep and gastrointestinal regularity as well as muscle cramping, burning mouth syndrome, menopausal symptoms such as hot flashes and night sweats and other metabolic functions.
Increased Calcium Intake Doesn't Reduce Fracture Risk in Older People
By Joe Elia, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
Increased calcium intake, whether from dietary sources or supplements, is unlikely to have a substantive clinical effect on bone mineral density (BMD) or fracture risk, two analyses in The BMJ find.
Researchers, using data from randomized or cohort studies, examined whether calcium increased BMD or lowered fracture risk in people over age 50.
BMD, in trials comprising nearly 14,000 participants, showed small increases (1%–2%) with dietary calcium or supplements. The authors observe that such increases are "unlikely to translate into clinically meaningful reductions in fractures."
Similarly, fracture risk was not reduced with increased dietary calcium. Supplements initially showed a beneficial effect, which disappeared when the analysis was confined to trials at lowest risk for bias (those trials included some 45,000 people).
An editorialist finds "puzzling" the recommendations from various organizations for almost universal calcium supplementation in older adults. He writes that "it is surely time to reconsider" such an approach.
http://www.bmj.com/content/351/bmj.h4183
http://www.bmj.com/content/351/bmj.h4580
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MM: Dextromethorphan has historically been used as a non-prescription cough suppressant with its primary side effect being mild drowsiness. Quinidine has been used for centuries as an anti-malarial and an anti-arrhythmic drug. Both of these drugs have been virtually eliminated from general use by newer FDA guidelines requiring efficacy studies. Based on what has happened to some of the older drugs that have had to go through these studies for patient access (colchicine as an example), you can bet that these very old and very cheap chemicals will return to the market place as extremely expensive options in the future.
JAMA 2015 Sep 22/29; 314:1242
Can Dextromethorphan plus Quinidine Reduce Agitation in Patients with Alzheimer Disease Dementia?
Dextromethorphan-quinidine may be effective for the treatment of agitation in these patients.
Noncognitive neuropsychiatric symptoms (NPS) of dementia — including aggression, agitation, depression, anxiety, delusions, hallucinations, apathy, and disinhibition — appear nearly universally across dementia stages and etiologies. No FDA-approved treatments exist for NPS. Nonpharmacological interventions are considered first-line therapy, and psychotropic drugs are prescribed frequently for agitation, although safety concerns and lack of efficacy limit their use.
This study is a manufacturer-sponsored, parallel-group, phase II, double-blind, multicenter, randomized clinical trial evaluating the effect of dextromethorphan hydrobromide plus quinidine sulfate on clinically significant agitation in patients with mild to moderately severe Alzheimer disease. In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n=93) or placebo (n=127). In stage 2, patients receiving dextromethorphan-quinidine continued, and those receiving placebo in phase 1 were rerandomized in a 1:1 ratio to dextromethorphan-quinidine (n=59) or placebo (n=60), with placebo responders and nonresponders from phase 1 divided evenly between the treatment groups. The primary endpoint was change from baseline to week 10 (study end) on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain, which ranges from 0 (absence of symptoms) to 12 (daily symptoms with marked severity). The treatment was well tolerated.
The analysis combining stages 1 and 2 showed a reduction in NPI Agitation/Aggression domain scores for dextromethorphan-quinidine versus placebo. In stage 1, mean NPI Agitation/Aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo. In stage 2, NPI Agitation/Aggression scores were reduced from 5.8 to 3.8 with dextromethorphan-quinidine and from 6.7 to 5.8 with placebo. All treatment differences were significant.
Comment: Noncognitive neuropsychiatric symptoms are among the most frequent challenges in dementia care yet remain under- or mistreated. These findings suggest that dextromethorphan-quinidine is a good option for the treatment of agitation. Nevertheless, the study was too short to determine clinical improvement. Future studies are needed to confirm the finding.
Citation(s): Cummings JL et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: A randomized clinical trial. JAMA 2015 Sep 22/29; 314:1242.
(http://dx.doi.org/10.1001/jama.2015.10214)
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MM: Weight management tends to be trivialized by the medical community but it is a very dominating condition that effects a massive population in western society. An area that is typically failed to be managed are the psychological effects of rapid weight loss that does not include the patient taking an active part in that weight loss. Programs like Weight Watchers, Jenny Craig and the HCG protocol all involve patient support and patient intellectual involvement in the process. This could be part of the reason that these programs tend to have better long term results than bariatric procedures alone.
Increase in Self-Harm Emergencies Noted After Bariatric Surgery
By Joe Elia, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Patients undergoing bariatric surgery show a small but definite increase in self-harm emergencies after the procedure, researchers report inJAMA Surgery.
Using Ontario provincial health records, the researchers compared rates of self-harm incidents in the 3 years preceding surgery versus the 3 years following it in some 8800 patients. Self-harm was measured as emergency visits for medication overdose, physical trauma, alcohol, and toxic-chemical poisoning. The group had a 1.3% overall incidence for the 6 years of study.
The postoperative rate of self-harm, 3.63 events per 1000 patients annually, was some 50% higher than the preoperative rate of 2.33. The increase, according to the report, was "particularly evident" in people aged 35 and older, those with lower income, and those living in rural areas.
Commentators argue that it's time physicians treated bariatric surgery as "more than just an operation."
http://archsurg.jamanetwork.com/article.aspx?articleid=2448916
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Breast Cancer Stage at Diagnosis Still Affects Prognosis
By Kelly Young, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Breast tumor size and lymph node involvement still play a significant role — regardless of tumor biology — in breast cancer prognosis, according to a BMJ study.
Using Dutch cancer registries, researchers compared 80,000 women diagnosed with primary breast cancer in 1999–2005 to those from 2006–2012. Beginning in 2005, Dutch chemotherapy regimens changed, trastuzumab was introduced, and new guidelines recommended more liberal adjuvant therapy.
From 1999–2005 to 2006–2012, there was a 17% increase in breast cancer diagnoses. The 5-year relative survival rate improved from 91% to 96%. The recent group also had tumors that were smaller, lower grade, and had less lymph node involvement. In both cohorts, tumor stage and lymph node status were associated with mortality after multivariable adjustment.
Editorialists conclude that the study "strongly suggests that, even after accounting for biological variation in tumors and enhanced treatments, tumor stage at diagnosis still matters.
http://www.bmj.com/content/351/bmj.h4901
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PLoS Med 2015 Sep; 12:e1001875
Do SSRIs Increase Violent Criminal Acts?
Low doses are associated with violent crimes in 15- to 24-year-olds, according to a Swedish registry study.
Although it is well established that youth commit most crimes, whether use of selective serotonin reuptake inhibitors (SSRIs) are related to violence in this age group is less clear. To study this relationship, investigators analyzed registry data on 856,493 people in Sweden who received an SSRI prescription, 8377 of whom were convicted for a violent crime against a person.
Data analyses compared crimes when individuals were on or off SSRIs and controlled for other psychotropic medications and reverse causality (i.e., SSRI prescribed after the crime was committed). Subjects were placed into 10-year age groups, beginning with ages 15 to 24, until age 45 (due to low crime rates later in life). Conviction risk was significantly associated with SSRI treatment periods but only at low doses in the 15–24 age group. Arrests and nonviolent convictions also showed significant associations.
Comment : Increased violence in adolescents on low-dose SSRIs argues for increased vigilance during SSRI initiation, when doses are likely to be lowest and risk for suicide is highest (BMJ 2015; 350:h517). By contrast, other work suggests that using low doses during SSRI initiation should lower suicide risk by allowing neurons time to reset serotonin autoreceptors (NEJM JW Psychiatry Jul 2015and Transl Psychiatry 2015; 5:e563), although risk for teen self-harm increases only with high-dose antidepressants (JAMA Intern Med 2014; 174:899). Increased aggression in adolescents on SSRIs may also be due to switching to mania, a known risk factor for suicide/homicide. This is especially important in childhood because it cannot be known whether a first depressive episode is the start of a unipolar or bipolar course. Overall, young patients on SSRIs, regardless of dose, need monitoring for aggression, and those with bipolar family histories should not receive SSRIs.
Citation(s): Molero Y et al. Selective serotonin reuptake inhibitors and violent crime: A cohort study. PLoS Med2015 Sep; 12:e1001875.
(http://dx.doi.org/10.1371/journal.pmed.1001875)
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MM: I find it interesting that research continues to be aggressively performed to justify the use of low dose aspirin. It's almost like a dog with a bone. Low dose aspirin, regular dose aspirin and NSAIDs all have the risk of kidney dysfunction, gastric ulcer and cardiovascular disorders. Yet, we continue to seek justification for their chronic and regular use.
Ann Intern Med 2015 Sep 1; 163:347
Low-Dose Aspirin Use and Colorectal Cancer Risk
In a case-control study, continuous use of low-dose aspirin for ≥5 years was associated with a 27% reduction in colorectal cancer risk.
Many studies have demonstrated that long-term use of aspirin or of other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a substantial reduction in colorectal cancer risk. The benefits of low-dose aspirin are less certain.
To explore this issue, researchers conducted a case-control analysis of population-based registry data from northern Denmark. The study involved 10,280 case patients with first-time colorectal cancer between 1994 and 2011 and 102,800 matched controls.
Continuous use of low-dose aspirin (75–100 mg per tablet) for ≥5 years was associated with a 27% reduction in colorectal cancer risk. Long-term use of nonaspirin NSAIDs (≥2 prescriptions annually for ≥5 years) was associated with a 36% reduction in risk. There was no clear benefit from irregular use.
Comment: These findings support a benefit in colorectal cancer protection for the many patients on low-dose prophylactic aspirin and are consistent with previous data on nonaspirin NSAIDs.
Citation(s): Friis S et al. Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk: A population-based, case-control study. Ann Intern Med 2015 Sep 1; 163:347.
(http://dx.doi.org/10.7326/M15-0039)
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Cardiometabolic Complications of Childhood Obesity Appear Early
By F. Bruder Stapleton, MD, Dr. Stapleton is an associate editor with NEJM Journal Watch Pediatrics and Adolescent Medicine, from which this story was adapted. See full coverage at the link below.
Prevalence of cardiometabolic risk factors is associated with severity of obesity in children and young adults, especially in males, a New England Journal of Medicine study finds.
Using the National Health and Nutrition Examination Survey from 1999 to 2012, researchers analyzed data for roughly 8600 survey participants aged 3 to 19 years with body mass index >85% of normal.
The prevalence of abnormal levels of total cholesterol, HDL cholesterol, triglycerides, blood pressure, and glycated hemoglobin increased with increasing severity of obesity. In analyses adjusted for demographic factors, several abnormal risk factors — among males, but not females — were more prevalent in participants with class III obesity than in those with class I obesity (the reference). Among both males and females, several abnormal risk factors were more prevalent in participants with class I obesity than in those who were overweight.
As the risk for developing cardiovascular disease is potentially reversible, primary care providers should look to identify these risk factors and choose appropriate interventions in children and young adults.
http://www.nejm.org/doi/full/10.1056/NEJMoa1502821
http://www.jwatch.org/na39093/2015/09/30/complications-childhood-obesity-appear-early?query=pfw
http://www.jwatch.org/pa201111160000001/2011/11/16/reversing-adverse-cardiovascular-effects?query=pfw
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MM: Many attempts have been made to reduce smoking and its' ill effects but most are met with failure. This is another tool in the arsenal to eliminate hazardous habits or activities. The bottom line is that a person has to want to cease any hazardous activity and be highly motivated to do so. No one can do that for them no matter how well intentioned they may be.
Reduce Nicotine Levels in Cigarettes, Reduce Smoking?
By Kelly Young, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Substituting lower-nicotine cigarettes for regular cigarettes was associated with less smoking in a randomized trial in the New England Journal of Medicine.
Over 800 smokers who weren't planning to quit were assigned to smoke one of seven types of cigarettes for 6 weeks: their usual brand, a cigarette with standard nicotine content (primary control; 15.8 mg nicotine/g of tobacco), or one of five types of reduced-nicotine cigarettes (0.4–5.2 mg/g).
The primary outcome — the average number of cigarettes smoked daily at week 6 — was significantly higher among the regular cigarette groups than among some reduced-nicotine (up to 2.4 mg/g) groups (roughly 21 vs. 16); biochemical analyses confirmed lower nicotine exposure. Participants assigned to low-nicotine cigarettes were more likely to report smoking non-study cigarettes. Those who smoked cigarettes with the lowest nicotine level were more likely to make a quit attempt than the control group (35% vs. 17%).
In an accompanying perspective, writers conclude: "We recommend that additional attention be paid to low-nicotine cigarettes as a potential clinical smoking-cessation resource."
http://www.nejm.org/doi/full/10.1056/NEJMsa1502403
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