Clinical Briefs in Primary Care

Fracture Risk Stratification in Diabetics

Source: Schwartz AV, et al. JAMA 2011; 305:2184-2192.

It has recently been recognized that type 2 diabetes (DM2) increases risk for osteoporotic fracture, even though it has been demonstrated that DM2 is associated with a paradoxical increase in bone mineral density (BMD) compared to age-matched control populations. With a burgeoning prevalence of DM2 in the United States, almost 20% of the at-risk population for osteoporotic fracture has DM2, hence, clarification of risk stratification for this group is highly relevant.

The World Health Organization (WHO) and the U.S. National Osteoporosis Foundation (NOF) suggest that clinicians assess patient risk for osteoporotic fracture by means of the fracture risk algorithm (FRAX) score. FRAX, an online risk assessment tool (available free of charge at, allows input of patient characteristics including gender, ethnicity, body mass index, risk factors for osteoporosis, history of fracture, family history of fracture, and BMD to calculate a 10-year risk of any osteoporotic fracture as well as 10-year risk of hip fracture. Similar to the structure of the ATPIII lipid guidance, intervention is threshold-based: Anyone with a 10-year risk of hip fracture > 3%, or total fracture risk > 20%, should be considered for pharmacotherapeutics intervention.

Gathering data from three prospective observational studies (n = 9449 women, 7346 men), Schwartz et al studied the relationship between FRAX scores, BMD, and subsequent osteoporotic fractures. Of concern, for any given T-score or FRAX score, the rate of osteoporotic fractures was higher in DM2 subjects than controls. DM2 appears to be a risk factor for osteoporotic fracture, above and beyond what is predicted by BMD or FRAX.

Amantadine for Dysphagia in the Elderly

Source: Gokula M, et al. Ann Long-Term Care 2011;19:37-40.

When amantadine (AMTD) was an appropriate first-line treatment for influenza, clinicians gained familiarity with its use. In the last decade, influenza resistance to the adamantanes (i.e., AMTD, rimantadine) has essentially eliminated their utility. The safety profile of AMTD is excellent however, heightening interest in clinical use for other syndromes.

Dysphagia in the elderly can be problematic, potentially leading to feeding difficulties and aspiration pneumonia. Probably the two most common scenarios in which we encounter dysphagia are Parkinson's disease and post-stroke, each of which is associated with reduced levels of dopamine. Since AMTD is a dopamine agonist, there is putative rationale for its potential use in dysphagia.

Gokula et al report their clinical experiences with AMTD in elderly patients with dysphagia. Based on positive responses in two test cases, they performed an uncontrolled case series (n = 12) among dysphagia subjects in a long-term care facility using an AMTD dose of either 50 mg or 100 mg/d orally. By 4 weeks, 11 of the 12 subjects demonstrated better swallowing, decreased cough, and weight gain. Additionally, fewer episodes of aspiration were seen.

Because AMTD is generally well tolerated, inexpensive, and there is little other resource for addressing dysphagia, clinicians may wish to consider a clinical trial.

Is Homocysteine a Culprit in Aging Skin?

Source: Namazi MR, Feily A. J Am Acad Derm 2011;64:1175-1178.

The Association of Homocysteine (HCST) with atherosclerosis is as strong and consistent as cholesterol, which prompted a flurry of clinical trials in the 1990s and early 2000s attempting to improve cardiovascular outcomes by lowering HCST levels (usually with pharmacologic doses of B vitamins). Unfortunately, HCST modulation did not result in cardiovascular risk reduction, to the point that interventions aimed at HCST have been largely abandoned.

HCST might also, however, be a culprit in aging skin. Photoaging is attributed to up-regulation of cutaneous matrix metalloproteinases and down-regulation of collagen synthesis. Homocystinuria, an inborn error of metabolism characterized by marked elevation of HCST, demonstrates thin, transparent skin.

HCST negatively impacts the three primary structural elements of healthy skin: collagen, elastin, and proteoglycans. Not only does elevated HCST increase degradation of these components, it also inhibits their regeneration.

There have not yet been any clinical trials to examine whether HCST reduction favorably impacts skin aging.

Hepatitis C Treatment by Primary Care Clinicians

Source: Arora S, et al. N Engl J Med 2011;364:2199-2207.

In most communities in the United States, hepatitis C (HEPc) treatment is provided by gastroenterologists. Because HEPc is now the most common cause of end-stage liver disease, and — unless trends reverse — will continue to be so for the foreseeable future, it is important that identification of HEPc infection be continued vigorously in the primary care community, since most at-risk persons see primary care clinicians as their point of initial contact with the health care system.

Treatment of HEPc offers the opportunity for cure of the disease more than 50% of the time, although persons infected with HEPc genotype I have a somewhat lower success rate. Ideally, treatment would be offered to as many infected persons as possible, yet limitations in specialist consultants who traditionally administer the treatment are an obstacle to access for some patients.

The ECHO program (Extension for Community Healthcare Outcomes) is intended to enhance opportunities for provision of health care to underserved populations through, for instance, video-conferencing technology that allows primary care clinicians to receive case-based education with specialist colleagues. Since 2003, ECHO has resulted in 800 HEPc patients being treated by primary care clinicians. The primary outcome of this ECHO-based trial was sustained virologic response, which is defined as undetectable HEPc RNA 6 months beyond the end of treatment. Encouragingly, analysis of outcomes for patients treated on-site at the University of New Mexico HEPc clinic were essentially identical with those of patients treated at distant sites by clinicians guided though case-based video conferencing. Hopefully, enlarging the spectrum of clinicians who can provide state-of-the-art care for HEPc patients will become a goal for other sites that have the capacity for video conferencing.

COPD Exacerbations: The EXACT Tool

Source: Jones PW, et al. Chest 2011;139: 1388-1394.

The impact and consequences of chronic obstructive pulmonary disease exacerbations (COPD-e) are underappreciated. This year, COPD has risen in prominence from the fourth most common cause of death to the third. COPD-e are problematic on multiple levels: as many as 10% of patients admitted for COPD-3 die in the hospital, and the mortality within the year of hospitalization is as much as 20%. Additionally, each COPD-e is associated with a further decline in FEV1 that is not restored once the exacerbation is resolved.

Jones et al have performed the first published formal analysis of COPD-e to derive an instrument known as EXACT (Exacerbations of Chronic Pulmonary Disease Tool).

Based on interviews with COPD patients (n = 410), the authors quantified items pertaining to dyspnea, cough, sputum production, chest discomfort, limitations of activity, fatigue, sleep disturbance, and anxiety associated with COPD symptoms.

Ultimately, 14 items were discerned that quantified COPD-e presence and severity. Hopefully, such a tool could be used in daily diaries of COPD patients to help identify exacerbations at the earliest possible stage so that abortive therapy could be instituted without delay. It remains to be determined whether enhanced early detection and intervention for COPD-e will favorably affect symptomatic control, hospitalizations, or mortality.

Are Diabetes Prevention Treatments Truly Disease Modifying?

Source: The DREAM Trial Investigators Diabetes Care 2011;34:1265-1269.

Prevention of Type 2 Diabetes (DM2) is possible by means of several different paths including diet, exercise, metformin, thiazolidinediones, orlistat, acarbose, and valsartan. Although reduced conversion from pre-diabetes to DM2 by as much as 60% has been seen in some DM2 prevention trials, critics point out that it is unclear whether any of the natural history of DM2 — that is, progressive decline in beta cell function — is impacted by currently available interventions. Animal studies have found incretin effects, such as beta cell proliferation and improved beta cell mass, but no persistence of such effects has been confirmed in humans, and most data suggest that none of these favorable effects persist once pharmacotherapy is discontinued. The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) Trial Investigators published an analysis of glycemic control 2-3 months after cessation of ramipril or rosiglitazone, the agents used in the DREAM trial.

Although the Heart Outcomes Prevention Evaluation trial supported a role for DM2 prevention by ramipril, this was not confirmed in the DREAM Trial, nor was there any beneficial "legacy effect." Although rosiglitazone was effective in DM2 prevention, once stopped, progression to DM2 was similar to placebo. Hence, although prevention of DM2 is achievable with thiazolidinediones, they do not appear to make a sustained impact upon underlying disease pathophysiology since drug cessation is followed by a resumption of declining beta-cell function similar to placebo.