Clinical Briefs in Primary Care
Gabapentin for Chronic Cough
Source: Ryan NM, et al. Gabapentin for refractory chronic cough: A randomised, double-blind, placebo-controlled trial. Lancet 2012;380:1583-1589.
Chronic undifferentiated cough — that is, cough without any readily visible explanation such as upper respiratory infection, lower respiratory infection, pulmonary lesion, heart failure, etc. — usually turns out to be one of three entities: post-nasal drip, asthma, or acid reflux. Indeed, empirically trying meds for such maladies usually resolves the cough. Nonetheless, despite exhaustive investigation, some patients remain with cough of undetermined etiology, at which point the treatment is problematic.
It has been suggested that chronic cough might reflect a central neural sensitization process that has some pathologic similarities to neuropathic pain. Since gabapentin works well for neuropathic pain, could it also have a positive effect on chronic cough?
Ryan et al studied a population of patients with chronic cough (n = 62) in whom secondary causes (e.g., infection, reflux, asthma) had been eliminated. Study subjects were randomized to gabapentin (up to 1800 mg/d) or placebo for 10 weeks.
At the end of the trial, gabapentin improved cough-related quality of life more than placebo and was well tolerated. Considering that in neuropathic pain trials the dose of gabapentin has been up to twice as high (3600 mg/d), it is reassuring to note that moderate gabapentin doses provide clinically relevant cough improvements. In an era of closer scrutiny applied to use of opioids, another alternative for chronic undifferentiated cough is welcome.
Can Statins Reduce Cancer-Related Mortality?
Source: Nielsen SF, et al. Statin use and reduced cancer-related mortality. N Engl J Med 2012;367:1792-1802.
It is generally believed that the primary mechanism of statin-related cardiovascular (CV) risk reduction is achieved through reductions in LDL. That statins might have other pleiotropic actions, such as plaque stabilization, is the subject of much controversy. Recently, recognition of the impact of statins on new-onset diabetes (a relative 9% greater risk than non-statin users) has given reason for pause. For secondary prevention, the risk-benefit ratio is prominently positive for statin therapy, but much less convincing for primary prevention. A similar picture is emerging in reference to aspirin in CV prophylaxis.
Reminiscent of the aspirin story (i.e., even though primary prevention with aspirin has never been shown to reduce mortality, the favorable effects on CV events — when combined with recently recognized cancer risk reduction — sweetens the deal), we are presented now with the suggestion that statins also reduce cancer-related mortality.
Nielsen et al report on a large dataset of Danish patients who had a diagnosis of cancer (n = 295,925) over the 1995-2007 interval. A comparison was made between statin never users (n = 277,204) and statin users (n = 18,721) with respect to overall and cancer-related mortality.
Statin users had a 15% relative risk reduction for cancer-related death when compared to non-users. Thirteen different cancer types were specified, each of which demonstrated similar benefit. The authors suggest that the cholesterol synthesis-limiting effects of statins may disrupt cancer cell membrane stability and cellular processes, leading to the beneficial observed effects.
Are All of Those Multivitamin Dollars Well Spent?
Source: Sesso HD, et al. Multivitamins in the prevention of cardiovascular disease in men: The Physicians' Health Study II randomized controlled trial. JAMA 2012; 308:1751-1760.
Americans have been depicted as an overly pill-happy lot, much more motivated to take a statin than incorporate dietary change for cholesterol, or take a sulfonylurea rather than exercise and lose weight to improve their diabetes, etc. For a while, the idea of multivitamins seemed like a no-lose proposition; after all, few of us were keeping track of the amounts of essential nutrients we ingest, so multivitamins appeared to provide, at worst, an innocent and inexpensive nutrient insurance policy.
In an era in which essential nutrient deficiency is a stark rarity, the use of vitamin and nutrient supplements is increasingly called into question.
The Physicians' Health Study II is a controlled trial of adult (age > 50 years) male U.S. physicians (n = 14,641) randomized to a daily multivitamin or placebo. Over a follow-up period of (median) 11.2 years, there was no discernible difference between placebo and a daily multivitamin on CV events, stroke, or mortality.
A parallel "sister study" from the Physicians' Health Study reported a week later in JAMA had slightly more encouraging news: Within the same population as mentioned above, the risk of total cancer was reduced by 8% in multivitamin users. Although the risk reduction for cancer was small, and the P value only marginally significant, for clinicians who would advocate for multivitamins in the face of failed CV data, the cancer outcomes are modestly more sanguine.
Relapsing Lyme Disease: Fact or Fiction?
Source: Nadelman RB, et al. Differentiation of reinfection from relapse in recurrent Lyme disease. N Engl J Med 2012;367:1883-1890.
A characteristic dermatologic manifestation of the acute phase of Lyme disease (LYME) is erythema migrans. With appropriate antibacterial treatment of LYME, the etiologic bacterium Borrelia burgdorferi is typically eradicated, and further disease progression is prevented. Untreated LYME can induce repetitive episodes of erythema migrans, as can LYME treated with antibiotics to which B. burgdorferi is not susceptible. In an individual patient, it may be difficult to differentiate disease relapse from new infection with a different strain of B. burgdorferi.
Genotyping of B. burgdorferi surface proteins allows determination of specific bacterial subtypes. Nadelman et al performed such analysis on patients (n = 17) who had experienced two episodes of erythema migrans. Each of the patients had received appropriate antibacterial treatment.
The second episode of erythema migrans was not caused by the same strain of B. burgdorferi in any of the patients, indicating that in each circumstance the patient had suffered reinfection rather than relapse. Whereas clinicians may have suspected relapse in patients with repeated episodes of LYME, it appears that reinfection with a new strain is more likely to be responsible.
Hypertension and Gout
Source: McAdams-DeMarco MA, et al. Hypertension and the risk of incident gout in a population-based study: The atherosclerosis risk in communities cohort. J Clin Hypertens 2012;14:675-679.
Gout and hypertension are often seen together. Indeed, there has been a substantial degree of discussion about the potential for elevated levels of uric acid to cause hypertension. The "storyline" remains incomplete, however, because of the observational nature of the data, confounders like thiazide diuretics (which of course elevate uric acid in treated hypertensives), and renal insufficiency, which is common in hypertension and is also associated with elevated uric acid. If uric acid is ultimately proven to increase the incidence of hypertension, it will still remain to be determined whether lowering urate can reduce hypertension safely and effectively.
The Atherosclerosis Risk in Communities study (ARIC) study population provides a dataset for evaluating the association between gout and hypertension. Adults (n = 15,792) from four different metropolitan areas were followed for approximately 10 years.
There was a strong relationship between gout and hypertension. Participants with hypertension were almost two to three times as likely to develop gout, even after adjustment for confounders. For instance, when results were evaluated only among persons not taking thiazide diuretics, a positive association between hypertension and gout was still found. The authors posit that the relationship between hypertension and gout is mediated through blood pressure-induced renal damage that leads to increased levels of uric acid.
Zoledronic Acid Treatment of Osteoporosis in Men
Source: Boonen S, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med 2012;367:1714-1723.
When hearing the word osteoporosis, most clinicians think "pink," as if the disorder only affected women. To the contrary, 30% of hip fractures occur in men, and the post hip-fracture mortality in men is higher than women. Although the dataset about preferred treatments is less robust for men than women, trials of oral bisphosphonates have been shown to provide meaningful fracture risk reduction for men and women.
Zoledronic acid (ZOL) is a parenterally administered bisphosphonate that has been previously demonstrated to provide significant reduction in osteoporotic fractures in women. For treatment of osteoporosis, ZOL is administered as a single intravenous dose, repeated in 1 year.
Boonen et al performed a placebo-controlled randomized trial in osteoporotic men (n = 1199). As in most osteoporosis trials, calcium (1000-1500 mg/d) and vitamin D (800-1200 IU/d) supplements were administered in both the treatment and placebo arms of the study. The primary outcome variable of the study was new vertebral fractures.
At the end of the 2-year study, men who had received ZOL enjoyed a 67% relative risk reduction in new vertebral fractures (1.6% vs 4.9%), as well as improved bone mineral density. There were no serious drug-related adverse events. Risk for osteoporotic vertebral fracture in men is promptly and effectively reduced by zoledronic acid.
Gabapentin for Chronic Cough; Can Statins Reduce Cancer-Related Mortality?; Are All of Those Multivitamin Dollars Well Spent?; Relapsing Lyme Disease: Fact or Fiction?; Hypertension and Gout;Zoledronic Acid Treatment of Osteoporosis in MenSubscribe Now for Access
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