Care of patients with cancer can be enhanced by continued involvement of the primary care physician. The physician’s role may include informing the patient of the diagnosis, helping with decisions about treatment, providing psychological support, treating intercurrent disease, continuing patient-appropriate preventive care, and recognizing and managing or comanaging complications of cancer and cancer therapies. Adverse effects of therapy and cancer-related symptoms include nausea, febrile neutropenia, pain, fatigue, depression, and emotional distress. 5-Hydroxytryptamine antagonists are effective in controlling acute nausea associated with chemotherapy. Febrile neutropenia requires systematic evaluation and early empiric antibiotics while awaiting culture results. Cancer-related pain, depression, and fatigue often are underdiagnosed and undertreated. Use of brief screening tools for assessing fatigue and emotional distress can improve management of these symptoms. Exercise prescription, activity management, and psychosocial interventions are useful in treating cancer-related fatigue. The physician must be alert for signs and symptoms of cancer-related emergencies like spinal cord compression, hypercalcemia, tumor lysis syndrome, pericardial tamponade, and superior vena cava syndrome.

More than 1.3 million patients are diagnosed with cancer every year in the United States, and a typical family physician will have three or four patients each year who are given a new diagnosis of cancer. (1) These patients and their families face not only a life-threatening disease but a flurry of subspecialty consultations, medical tests, and treatments that may be difficult and disruptive. During the course of the patient’s cancer care, the family physician can remain an important resource for the patient and family, providing an empathetic and credible source of information, support, and advice as well as medical treatment for intercurrent illness, preoperative evaluation, postoperative care, and coordination of subspecialty care (Table 1 (2)).

Patients followed by an oncologist alone are less likely to receive preventive care, and care for noncancer chronic illness that is consistent with guidelines, than patients followed jointly by an oncologist and a primary care physician. (3) For patients with advanced disease, primary care continuity may reduce emergency department visits and make it more likely that the patient will be able to die at home. (4,5)

The responsibility to inform a patient about a cancer diagnosis may fall on the family physician. The SPIKES mnemonic, which was developed to guide this process, is provided in Table 2. (6) If cues indicate, touch may be beneficial in conveying concern and empathy, and the presence of significant others should be encouraged. (7) Most patients want full information about the extent of the disease, treatment options, adverse effects, symptoms, and prognosis, but want some control over the timing, mode, and extent of information they receive. (8,9) Regardless of the prognosis, some hope can and should be conveyed.

Adverse Effects of Chemotherapy and Radiation

Although chemotherapy and radiation treatments are usually directed by a subspecialist, the family physician must be aware of potential adverse effects and, in some practice settings, may be called on to manage them.

NAUSEA AND VOMITING

Approximately 70 to 80 percent of patients treated with chemotherapy experience nausea and vomiting, (10) which may be acute (occurring within a few hours after chemotherapy), delayed (occurring 24 or more hours after chemotherapy), breakthrough or refractory (occurring despite prophylactic treatment), or anticipatory (occurring before chemotherapy treatment). The emetogenic potential of chemotherapeutic agents varies from mild to severe. (11) Drug dose, schedule and route of administration, and patient variability also are factors.

Antiemetic therapy is most effective if given before chemotherapy and maintained while the emetic potential of the agent continues. Oral formulations are as effective as parenteral or rectal routes if the patient is able to swallow and digest tablets. Lorazepam (Ativan), metoclopramide (Reglan), and prochlorperazine (Compazine) often are used for moderate- to low-emetic-risk chemotherapy and for breakthrough nausea.

The introduction of 5-hydroxytryptamine (5-HT) receptor antagonists in the early 1990s represented a significant advance in antiemetic therapy. (12) Currently, 5-HT antagonists are most widely used in practice with high- to moderate-risk chemotherapy and include ondansetron (Zofran), granisetron (Kytril), dolasetron (Anzemet), and palonosetron (Aloxi). Trials with these agents indicate that they are highly effective in controlling acute nausea and vomiting associated with chemotherapy and have minimal adverse effects. (12-14) They are equally effective for acute nausea, (15) but palonosetron, which has a much higher affinity for the 5-HT receptor and a longer half-life than the other 5-HT antagonists, is more effective than dolasetron in preventing delayed emesis. (16) The coadministration of dexamethasone improves the effectiveness of 5-HT antagonists in controlling acute emesis. However, one study found that adding a 5-HT antagonist to dexamethasone for the treatment of delayed nausea and vomiting did not result in an improved antiemetic effect over dexamethasone alone. (17) Aprepitant (Emend) augments the activity of 5-HT antagonists and dexamethasone to inhibit acute and delayed emesis induced by cisplatin (Platinol).

Background: Irritable bowel syndrome (IBS) is a chronic disorder associated with altered bowel habits and abdominal pain and discomfort. To date, there is no accepted comprehensive pathologic explanation for IBS. Pimentel and colleagues conducted a randomized controlled trial to investigate whether administration of a nonabsorbed oral antibiotic (rifaximin [Xifaxan]) improves symptoms in patients with IBS.

The Study: The study population included 87 patients between 18 and 65 years of age. Eligible patients met Rome I criteria, a classification system for functional gastrointestinal disorders. Patients were excluded if they had underlying conditions known to produce overgrowth of intestinal bacterial flora, had taken oral antibiotics in the previous three months, or were currently taking tegaserod (Zelnorm) or antidepressants. Before beginning the study, patients completed a seven-day stool diary and a questionnaire assessing their symptoms during that period. Next, participants received a 10-day course of 400 mg rifaximin or placebo three times a day.

After completing the 10-day course, patients again recorded a seven-day stool diary and a follow-up questionnaire. In the follow-up phase of the study, patients completed questionnaires weekly for nine weeks. The questionnaires used throughout the study assessed the severity of the patients’ IBS symptoms. The symptoms chosen for treatment end point assessment were diarrhea, constipation, abdominal pain, and bloating. The patients reported their global improvement in overall IBS symptoms on a scale from 0 to 100 percent.

Results: Comparison of the global improvement scores of rifaximin versus placebo groups across the 10-week follow-up demonstrated an average increase of 36.4 versus 21.0 percent, respectively (see accompanying figure). Patient reports of symptom severity demonstrated a significant improvement in bloating but no significant differences in abdominal pain, diarrhea, or constipation. The most common adverse effects were abdominal pain, diarrhea, and a bad taste in the mouth; however, these were rare and the incidences reported were similar in both groups.

Conclusion: The authors conclude that the use of the antibiotic rifaximin resulted in a greater global improvement in IBS than placebo. The authors noted that improvements continued through 10 weeks of follow-up despite cessation of antibiotic treatment after 10 days. They feel that this new concept of IBS treatment warrants future studies that allow direct comparison of antibiotic treatment with other treatment strategies such as prokinetics and probiotics.

If this country’s cholesterol guidelines were fully implemented, most of the Western world’s adult population would be taking cholesterol-lowering statin drugs, according to research published in the British Medical Journal. Based on the latest figures available, Lipitor was the top-selling drug in the world for the five years leading up to 2005, with annual sales of $12.9 billion in that year. Yet lowering cholesterol may not be as healthy as we believe.

“Cholesterol is essential for life,” says Peter Langsjoen, MD, a cardiologist in Tyler, TX. “It has been extraordinarily vilified.”

Twenty-five years ago, experts didn’t know about lipoproteins and good and bad cholesterol, say Stephen T. Sinatra, MD, and James C. Roberts, MD, co-authors of Reverse Heart Disease Now. LDL (low-density lipoprotein) and HDL (high-density lipoprotein) were named by a researcher who spun blood plasma in a centrifuge. When they separated, LDL floated to the top while HDL sank.

Contrary to popular wisdom, cholesterol, with the exception of oxidized LDL (see p. 49), is a substance our bodies need to function normally. “Fifty percent of brain tissue is cholesterol,” says Langsjoen. The cholesterol in the brain doesn’t come from the blood but is made by brain cells, and statin drugs cross the blood-brain barrier and block the brain’s ability to make adequate cholesterol. Memory loss, insomnia, personality changes and road rage are some of the consequences, he explains, particularly among people over age 65 and even more so among those over age 80.

Many studies have shown that CoQIO is necessary for a healthy heart and can reverse heart disease. Every muscle in the body needs CoQ10 to produce energy, and the heart muscle, having the greatest energy requirement, has the greatest concentration of this nutrient. However, our natural production of CoQ10 peaks in our 20s and declines thereafter. With the main food sources of CoQ10 being organ meats, not usually a part of today’s diets, we are prone to a deficiency, especially from middle age onward.

Langsjoen has been studying CoQ 10 and heart disease since 1983. He points out that statins block production of CoQ10 in every cell, including the heart. “Fatigue is the most common symptom, in skeletal muscles as well as the heart,” he says.

Supplements are a practical source of the nutrient, but in order to be absorbed well, they should be taken with fatty food. Langsjoen recommends 100mg daily of CoQ10 with a fatty meal or, for maximum absorption, opening up a capsule, mixing the contents with a nut butter and chewing the combination. To determine individual needs, CoQ10 blood levels can be tested. (See “Your Heart Health Resource Guide,” p. 49.)

Skewed Research

Research that began in 1948 examined the correlation between cholesterol, diet and heart disease and formed the basis for today’s cholesterol guidelines. But now it seems that not all the data that was available supported the conclusions.

Sinatra and Roberts note that one of the key studies underlying today’s emphasis on lowering cholesterol was the Seven Countries Study. Although 20 countries had relevant data, only seven of these were used to “prove” the hypothesis that lowering cholesterol decreases risk for heart disease. When data from all 20 countries is included, the hypothesis fails.

Sinatra and Roberts also note that cholesterol protects us against bacterial infection, cancer and respiratory failure, and that higher cholesterol levels correlate with fewer car accidents and suicides. “Years of blaming cholesterol as the bad boy of heart disease have distorted the image of a totally necessary ingredient for the body’s normal functioning,” these authors say.

Lowering Cholesterol: Risk or Benefit?

Researchers at the University of California, San Diego, are examining the effects of statin drugs in the Statin Effects Study. Their observations about earlier research include:

* Healthy men who lower LDL cholesterol levels with statin drugs are less likely to die of heart disease but just as likely to die of other causes.

* Middle-aged men who are otherwise at high risk of heart disease probably receive more benefit than harm from statin drugs.

* There is no research to support the premise that statin drugs lower death rates among women, although they do reduce the rate of heart attacks.

* Among people over age 75, higher cholesterol seems to be protective against heart arrhythmias, atrial fibrillation and strokes.

The Real Culprits

Inflammation is the real risk factor we should be worried about, according to Sinatra and Roberts, and too much refined sugar and high-fructose corn syrup in our diets is a major contributing factor. Eliminating these sweeteners along with processed food and trans fat, while adding healthy fats, wholesome food and regular exercise, is all part of the solution, along with the fight supplements.

In mid-December 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the Kenya Ministry of Health (KMOH) from Garissa District in North Eastern Province (NEP). By December 20, a total of 11 deaths had been reported. Of serum samples collected from the first 19 patients, Rift Valley fever (RVF) virus RNA or immunoglobulin M (IgM) antibodies against RVF virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, Ebola, Crimean-Congo hemorrhagic fever, and dengue viruses. The outbreak was confirmed by isolation of RVF virus from six of the specimens. Humans can be infected with RVF virus from bites of mosquitoes or other arthropod vectors that have fed on animals infected with RVF virus, or through contact with viremic animals, particularly livestock. Reports of livestock deaths and unexplained animal abortions in NEP provided further evidence of an RVF outbreak. On December 20, an investigation was launched by KMOH, the Kenya Field Epidemiology and Laboratory Training Program (FELTP), the Kenya Medical Research Institute (KEMRI), the Walter Reed Project of the U.S. Army Medical Research Unit, CDC-Kenya’s Global Disease Detection Center, and other partners, including the World Health Organization (WHO) and Medecins Sans Frontieres (MSF). This report describes the findings from that initial investigation and the control measures taken in response to the RVF outbreak, which spread to multiple additional provinces and districts, resulting in 404 cases with 118 deaths as of January 25, 2007.

Teams of investigators conducted patient interviews and reviewed medical records from December 1 forward in major health-care facilities in the districts from which cases were first reported. The teams detected additional cases by meeting with elders, other leaders, and health-care providers in villages where cases had been reported and in adjacent villages. Blood samples from patients with suspected RVF were collected and maintained at 39.2[degrees]F (4.0[degrees]C). Samples from NEP and surrounding areas were transported to a field laboratory established at Garissa Provincial Hospital by CDC, KEMRI, and KMOH; samples from other areas were sent to KEMRI laboratories in Nairobi and to a laboratory in Malindi that was supported by a team from Health Canada.

A suspected case was defined as acute onset of fever (>99.5[degrees]F [>37.5[degrees]C]) with headache or muscle and joint pain since December 1 in a person who had no other known cause of acute febrile illness (e.g., malaria). A probable case was defined as acute onset of fever in a person with unexplained bleeding (i.e., in stool, vomit, or sputum or from gums, nose, vagina, skin, or eyes), vision deterioration, or altered consciousness. A confirmed case was defined as a suspected or probable case with laboratory confirmation of the presence in serum of anti-RVF virus IgM by enzyme-linked immunosorbent assay (ELISA) or RVF virus RNA by reverse transcription-polymerase chain reaction (RT-PCR).

The index case was reported in Garissa District in a patient who had symptom onset on November 30, 2006. Retrospective analysis of sera collected during July-November 2006 at Garissa Provincial Hospital revealed no evidence of earlier acute RVF infections. As of January 25, 2007, a total of 404 cases of RVF had been reported in Kenya with 118 deaths, a case-fatality rate of 29%. Of the reported cases, 115 (29%) were laboratory confirmed by anti-RVF virus IgM by ELISA (64 cases, 56%) or RT-PCR (79, 69%), including 28 cases (24%) confirmed by both. Of the remaining 289 cases, 109 were classified as probable.

Of the 230 patients with available demographic information, 140 (61%) were male (Figure 1). Patients ranged in age from 4 to 85 years, with a median age of 27 years (30 years for females and 25 years for males). RVF cases were reported from three districts in NEP (Garissa [175 cases], Ijara [125], and Wajir [26]); five districts in Coast Province (Kilifi [38], Tana River [16], Malindi [eight], Isiolo [eight], and Taita Taveta [one]); two districts in Central Province (Kirinyanga [two] and Maragua [one]); one district in Rift Valley Province (Kajiado [three]); and one from Nairobi Area (Figure 2). The patient from Nairobi had traveled to NEP during the week before illness onset but was hospitalized in Nairobi. Ijara (population 79,932) and Garissa (population 420,918) districts had the highest RVF incidence rates: 156 and 42 per 100,000 population, respectively.

[FIGURES 1-2 OMITTED]

Among the first 97 reported cases from Garissa and Wajir districts with detailed epidemiologic information available, 71 (73%) met the probable case definition; 38 of the 62 patients who provided blood samples tested positive by IgM ELISA, RT-PCR, or both. The most frequently reported symptoms among the 97 patients were fever (100%), headache (90%), bleeding (76%), malaise (70%), muscle pain (62%), back pain (60%), vomiting (56%), and joint pain (51%).

In this study, 102 patients with irritable bowel syndrome of over one year’s duration and unimproved with six months of conventional medical treatment were randomly assigned to a medical treatment group (high fiber diet and antispasmodic drugs) or to a psychological treatment group including an initial two-hour interview, followed by regular therapeutic interviews using the conversational model of Hobson. Each patient received a relaxation tape to use at home on a regular basis. No psychotropic medication was used. At three months, the psychotherapy group was significantly more improved than the medical-only group. Therapist-observed improvement was significant for discomfort (p<.01) and diarrhea (p<.05), and in subjective observations of decreased pain (p<.001), distension (p<.01), and diarrhea (p<.05). At three months, there was also significant correlation with improvement in the Psychiatric Assessment Schedule, the Hamilton Rating Scale, the Clinical Anxiety Scale, and the degree of decrease in abdominal symptoms (p<.001). Symptom scores, improved overall, were highly significantly improved in women (p<.01 to .001) but not significant in men. In the following year, clinic visits were reduced 75% vs. the previous year (p<.001), and the psychiatric improvement on HRS and CAS scores was much better than controls (p<.001 and p<.01, respectively).

COMMENT: As a whole, the psychological treatment group at three months and one year compared to the conventional medical treatment group. Men did not fare nearly as well as did women. Again, these gains were the result of group work. Physicians themselves can organize such groups or refer to psychologists and/or hospitals, many of whom do offer or at least should be encouraged to organize outpatient groups for patients with given diagnostic labels. The leadership of such groups is critical and must be facilitated by persons with the requisite skills. Many studies have shown improved diabetic self-care and management of low back pain following attendance at such groups with a psychological emphasis.

The purpose of this investigation was to evaluate the reduction in perceived pain in patients with myofascial pain (MFP) using a group cognitive behavior therapy (CBT) course. Twenty-six participants diagnosed as having MFP were enrolled. Each CBT session had a small-group format, where participants received instruction in habit reversal, stress management, and progressive relaxation. Participants served as their own control subjects and were surveyed for pain intensity, duration, and frequency at study enrollment, before attending the CBT course, and 2 to 3 weeks after course completion. Wilcoxon signedrank tests revealed that changes in intensity, frequency, and duration were significant

Myofascial pain (MFP) disorder is regional muscle pain referred from or emanating around active myofascial trigger points.1 It is the most common condition presenting to orofacial pain centers.2,3 Masticatory MFP has been described as a chronic condition with a cyclical nature.4 However, studies have demonstrated that MFP symptoms are often persistent over time without treatment.5,6 It has been recommended that the initial standard of care for the masticatory MFP patient include conservative treatment to facilitate musculoskeletal healing and symptom improvement. Common therapies of this nature include but are not limited to self-care modalities, cognitive behavioral modification, physical medicine therapies, medications, and oral appliances.1 Therapy varies with the provider’s training, expertise, and clinical experience.

Dentists commonly treat MFP patients with appliance therapy, often in combination with physical therapy and analgesics. This approach is effective for a limited number of MFP patients, but a sizable percentage (23%) may not respond to this type of therapy.7 One study demonstrated that 75% of 448 pain patients who were given patient education information, heat, massage, non-narcotic analgesics, and appliance therapy received satisfactory symptom relief, whereas the remaining 25% did not.8

Clinicians and researchers recognize the derived benefits of incorporating cognitive awareness and habit reversal instruction into MFP treatment protocols. Directing awareness to the consequences of parafunctional activities proves clinically useful in reducing negative behaviors and alleviating MFP symptoms.9 Current literature supports the interrelationship between chronic pain and behavioral, psychological, and psychosocial factors.10 In addition, the contributions of cognitive behavioral practices are well accepted among practitioners managing MFP with the interdisciplinary team concept.11,12

Clinical health psychologists, with their understanding of human behavior, are valuable in assisting dental practitioners in treating MFP patients. In particular, the management of maladaptive habits and behaviors, such as bruxism and clenching, is widely accepted as a standard therapy in reducing contributing factors in patients with orofacial pain.13 Clenching is defined as prolonged tooth contact, whereas bruxism implies grinding of the teeth.13 Other oral habits, such as jaw bracing, lip biting, gum chewing, and nail biting, may also contribute to MFP.

Early thinking embraced malocclusion as a major or sole etiological factor for bruxing and clenching, on the premise of it causing unstable occlusal relationships. The theory proposed that an individual bruxed and/or clenched because he or she could not occlude the teeth to form a stable relationship because of interferences.14 Subsequent studies found that occlusal contributions to MFP symptoms were minimal and, when present, typically represented more-advanced occlusal instabilities.15,16 Symptoms of temporomandibular disorders (TMD) occur in healthy individuals and appear to increase in frequency and severity particularly during adolescence.15

Psychophysiological causes are the basis for another theory, in which increased stress and anxiety lead to increases in physiological reactivity and adverse oral behaviors such as clenching. It is hypothesized that bruxers experience greater daily physiological reactivity to stress than do nonbruxers. The theory does not explain the cause of bruxing; rather, it suggests that increased stress increases bruxing. Although many studies show a correlational relationship between stress and bruxism, they suggest nothing about the cause of bruxing or clenching.13 Although emotional difficulties exist for many TMD sufferers and addressing emotional disturbances may be critical for treatment success for some individuals, there is no clear evidence that emotional difficulties are causally related to the development of TMD.17,18 There appears to be no greater Incidence of anxiety, depression, or major mental illness among initial TMD patients than among general medical patients.12

The learning theorists propose that TMD is the result of learned maladaptive oral habits. For example, a behavior may begin as relatively Innocuous (e.g., lip licking or biting because of chapped lips). The behavior then becomes a learned habit that is no longer in response to the original stimulus. According to learning theories, bruxlng is not necessarily related to greater stress or psychological disturbance.13 It is likely that TMD is a result of the relationship between patients’ stress, habits, and physical vulnerability.

Low-dose inhaled corticosteroids are the preferred treatment for children with mild persistent asthma because they demonstrate superior reduction in severity and frequency of asthma exacerbations compared with alternatives (strength of recommendation [SOR]: A, based on multiple randomized controlled trials). As add-on therapy, nedocromil, theophylline, and cromolyn have all demonstrated a modest benefit in symptom control; leukotriene receptor antagonists are also recommended based on data from older children (SOR: B, cohort study). Unlike treatment of moderate or severe asthma, long-acting beta-agonists are not recommended (SOR: A, randomized trials).

CLINICAL COMMENTARY

Clear medication choices for mild asthma are supported by good evidence Physicians who routinely treat children with asthma are fortunate to have the body of evidence outlined in this review. Clear medication choices are supported in most instances by relatively clear comparisons with alternatives. In my practice, where many children can be classified in the “mild persistent” category, I am always surprised at how many patients’ families lack a clear understanding of the factors that trigger a child’s asthma and how to avoid them.

Another common clinical scenario among children and adolescents is exercise-induced asthma. Depending on the sport, the asthma can be classified as “mild persistent” or “mild intermittent.” For true intermittent symptoms, my clinical experience (and often parental preference) argues for pre-activity treatment with short acting beta-agonists as the most practical therapy.

John Heintzman, MD

Oregon Health and Science University, Portland

* Evidence summary

Mild persistent asthma is defined as forced expiratory volume over 1 second (FEVI) [greater than or equal to] 80% predicted, with daytime symptoms more than twice per week but less than once daily, and nighttime symptoms more often than twice monthly. (1)

Low-dose inhaled corticosteroids

Two large randomized trials support using low-dose inhaled corticosteroids in these children. The Childhood Asthma Management Program (CAMP) study, which included 1041 children, evaluated treatment with either budesonide or nedocromil vs placebo. Patients taking budesonide had a lower rate of urgent care visits (absolute risk reduction [ARR] = 10%; number needed to treat [NNT] = 10; P = .02) compared with children taking nedocromil (ARR = 6%; NNT = 17; P=.02). The urgent care visits were reported as number of visits per 100 person-years.

In practical terms, this means that in order to decrease 1 urgent care visit, 1 patient would need to take budesonide for 10 years. However, because rates are not necessarily homogenous over time, the number of visits decreased during the first year may be different than the number of events decreased throughout the tenth year.

Children taking budesonide experienced 21.5% more episode-free days than those taking placebo (P=.01). No change was observed in the nedocromil group. (2) In the inhaled Steroid Treatment As Regular Therapy (START) in early asthma study, budesonide demonstrated a 44% relative reduction in time to first severe asthma related event, compared with placebo (95% confidence interval [CI], 0.45-0.71; NNT=44; P=.0001). (3)

Theophylline

Theophylline is considered an alternative to inhaled corticosteroids. One study compared beclomethasone with theophylline in 195 children. This study found near-equivalent efficacy in doctor visits, hospitalizations, monthly peak expiratory flow rates, and [FEV.sub.1]; however, beclomethasone was superior to theophylline in maintaining symptom control and decreasing the use of inhaled bronchodilators and systemic steroids.

When compared with beclomethasone, theophylline was linked to 14% more central nervous system adverse effects (P<.001) and 17% more gastrointestinal disturbances (P<.001). Although beclomethasone induced more oral candidiasis compared with theophylline (8.9% vs 2.4%; P<.001), the incidence of this infection can be reduced by using a spacer.

Long-term systemic effects

The potential long-term adverse systemic effects of inhaled corticosteroids on growth, bone metabolism, and pituitary-adrenal function call for longer-term studies. (4) A systematic review of 15 trials reported that the protective effect of leukotriene receptor antagonists is inferior to inhaled corticosteroids for adults (relative risk [RR]=1.71; 95% CI, 1.40-2.09); however, evidence is insufficient to extrapolate this to children. (5)

Beta-agonists

Evidence does not support use of long-acting beta-agonists as monotherapy or in combination with other medications for children with mild persistent asthma. Although 1 study showed an improvement in lung function for children taking budesonide plus formoterol compared with budesonide alone, the rate of severe exacerbations was lower for those taking budesonide alone (62% decrease vs 55.8% decrease; P=.001). Both groups had a 32% decrease in the number of rescue inhalations per day when compared with placebo (P=.0008). (6)

Restless legs syndrome is a problem plaguing many patients. It’s an unusual sensation (paresthesia) in the legs that typically occurs at bedtime and is a common cause of insomnia. The sensation has been described as uncomfortable, not painful, but more like “creepy crawly, tingling,” and temporarily is relieved by moving the legs.1 Most people with restless legs syndrome also move their legs once they are asleep. These movements can disrupt their sleep and further add to the daytime drowsiness the syndrome causes. With some people, it can be so extreme, it becomes like torture. They pace the floor in the middle of the night, only to have their symptoms return as soon as they collapse, exhausted, back to bed.1

Restless legs syndrome is surprisingly common. Various estimates have ranged from 2 percent to 15 percent of the adult population, with the real number likely to be about 6 percent.1 It is more common in women.2 The older you are, the more likely you are to suffer from restless legs. It is rare in young children, and for those older than 65 years, around 10 percent to 28 percent are affected.1

Despite its high occurrence, restless legs syndrome has been described as “the most common disorder you’ve never heard of,”1 but perhaps not any longer. In 2006, a new drug treatment was launched in the U.S., with all the associated media fanfare. This newly approved drug is ropinirole (Requip), which already was available as a treatment for Parkinson’s disease. It is now the first drug to be approved by the FDA for the treatment of restless legs syndrome.

The cause of restless legs syndrome is not known. However, it’s known to be associated with a number of medical conditions. For example, iron deficiency, even at levels that do not cause anemia, seems to predispose to restless legs. From 20 percent to 57 percent of people receiving kidney dialysis also are affected.1 The condition is much more common during pregnancy. One survey of 500 women found that 19 percent reported restless legs syndrome during pregnancy and 7 percent described their symptoms as “severe.” The condition abated in 96 percent of affected women within one month of giving birth.1 Increased symptoms also have been associated with decreased magnesium and folic acid.1 Magnesium therapy (12.4 mmol/day = 301 mg/day) has been shown to be beneficial.3 Obviously, these nutritional issues need to be addressed as part of any natural therapy for restless legs.

A number of lifestyle factors have been associated with restless legs syndrome. These include heavy smoking, advanced age, obesity, hypertension, loud snoring, use of antidepressant drugs,2 diabetes and lack of exercise.4 So obviously, the healthier the lifestyle, the less likely one is to suffer from this condition. Intake of alcohol, nicotine and caffeine should be minimized.1

Conventional medical treatment for restless legs syndrome focuses on drugs for the nervous system. Some of these drugs are quite powerful and dangerous, and should be reserved for more severe cases. They include opioid drugs such as apomorphine and tramadol, the benzodiazepine drugs such as clonazepam, drugs used to treat Parkinson’s disease such as levodopa and ropinirole, and even antiepileptic drugs like valproic acid. Most of this drug use is off-label, with the exception of ropinirole. To my thinking, the pharmaceutical approach seems like using a sledgehammer to crack a nut, and the evidence behind the value of many of these treatments is not strong for this disorder.

On the herbal side, herbs for the nervous system which also help improve sleep quality, such as valerian, skullcap and passion flower, all have a role in alleviating the nervous system imbalance that is part of restless legs syndrome. However, there is one approach I have found to work above all others with my patients: treating the circulation.

Circulation: The Neglected Factor in Restless Legs

If you think about the many factors associated with restless legs syndrome, such as heavy smoking, pregnancy, obesity, advanced age, diabetes and lack of exercise, they all link to one common factor - poor circulation. This factor has been recognized in some studies, but seems to be ignored on the treatment side in the rush to prescribe heavy-hitting drugs. For example, a study found that restless legs syndrome was very common in people with varicose veins (22 percent incidence).5 After treatment for superficial varicose veins (sclerotherapy or vein stripping), 98 percent reported an immediate improvement in their restless legs. This was just therapy for the superficial veins, whereas the deeper veins carry the bulk of the load of returning the blood from the extremities. When the blood is not circulating properly, the walls of the deeper veins can stretch, resulting in unpleasant sensations in the legs. The sluggish circulation can cause red blood cell aggregation that can further add to the paresthesia and restless legs. Flavonoids, which are found in many herbs, but notably in this context, ginkgo biloba and horsechestnut, have been found to be beneficial for restless legs.6

Background: Upper respiratory infections account for more than 30 million U.S. physician office visits each year; another 28 million visits are made for chronic sinusitis and allergic rhinitis. From a cost and convenience perspective, it is not practical to offer diagnostic imaging for patients with sinusitis who are not candidates for surgical intervention. A red streak resulting from nasal drainage often is visible on the oropharyngeal mucosa. Thomas and Aizin tried to determine whether this red streak in the lateral recess of the oropharynx could be helpful in diagnosing acute sinusitis.

The Study: Patients with nasal symptoms who visited an urgent care center were recruited for the study. Their symptoms included nasal drainage, congestion, obstruction, or facial pain. Patients with self-diagnosed sinusitis also were included. Participants’ medical histories and 10 physical examination findings, including sinus transillumination and presence of a red streak, were evaluated. All underwent coronal computed tomography (CT), and the findings were corroborated with a second evaluator. A neuroradiologist interpreted the CT images for air-fluid levels.

Results: Of the 73 patients included, 60 completed the study, and 27 patients were diagnosed with acute sinusitis. A red streak in the lateral recess of the oropharynx was identified in 30 patients. The red streak also was associated with acute sinusitis on CT with a positive likelihood ratio (LR) of 2.11 and a negative LR of 0.44 (see accompanying table).

Conclusion: The authors conclude that the red streak was positively associated with the diagnosis of acute sinusitis, which is a physical finding that has not been studied previously. They note that it is reproducible, simple to evaluate, and requires no special equipment. Transillumination also correlated with the diagnosis, but facial pain did not.

REFERENCES

(1.) Lindbaek M, Hjortdahl P, Johnson UL. Use of symptoms, signs, and blood tests to diagnose acute sinus infections in primary care: comparison with computed tomography. Fam Med 1996;28:183-8.

(2.) Agency for Healthcare Research and Quality. Diagnosis and treatment of acute bacterial rhinosinusitis. Summary. Rockville, M.D.: Agency for Healthcare Research and Quality, 1999. Accessed September 29, 2006, at: http://www.ahrq.gov/clinic/epcsums/sinussum.htm.

(3.) Williams JW Jr, Simel DL, Roberts L, Samsa GP. Clinical evaluation for sinusitis. Making the diagnosis by history and physical examination. Ann Intern Med 1992;117:705-10.

Source: Thomas C, Aizin V. Brief report: a red streak in the lateral recess of the oropharynx predicts acute sinusitis. J Gen Intern Med September 2006;21:986-8.

EDITOR’S NOTE: This study used CT as the comparison standard rather than radiography. In a previous study that used CT, it was found that a return of symptoms after a cold, purulent rhinorrhea and secretions, and an erythrocyte sedimentation rate greater than 10 mm per hour had independent associations with sinusitis. (1) Other studies have used radiography to establish reference criteria. According to a review by the Agency for Healthcare Research and Quality, the presence of three or four of four nasal symptoms–purulent rhinorrhea with unilateral predominance, local pain with unilateral predominance, bilateral purulent rhinorrhea, and pus in the nasal cavity–has an equivalent diagnostic accuracy to that of sinus radiography, which has been shown to have a sensitivity of 76 percent and a specificity of 79 percent. (2) In an earlier study, these criteria were developed into a prediction rule. (3) The oropharyngeal red streak may aid in the development of a more reliable predictive model.–C.W.

CAROLINE WELLBERY, M.D.

Likelihood Ratios for Selected History and Physical
Examination Findings in the Diagnosis of Sinusitis

Finding                                   LR+          LR-

Maxillary opacity on transillumination    1.89         0.56
Facial pain/percussion tenderness         0.59/0.42    1.88/1.88
Symptom duration > 10 days                1.89         0.46

LR = likelihood ratio.

Ranolazine (Ranexa) represents a new class of drugs known as metabolic modulators. It is labeled for use in combination with amlodipine (Norvasc), beta blockers, or nitrates in patients with chronic angina who have not had adequate antianginal responses. Although the exact mechanism of action is unknown, ranolazine seems to increase the efficiency of energy production in the heart, maintaining cardiac function without reducing heart rate or blood pressure. (1)

Ranolazine prolongs the QTc interval in a dose-related manner, particularly in persons with mild, moderate, or severe hepatic dysfunction. It is contraindicated in patients with preexisting QT prolongation, including congenital long QT syndrome, uncorrected hypokalemia, and hepatic impairment. The manufacturer does not state when the drug should be discontinued if QT interval prolongation occurs, only that modest QT prolongation (four to six milliseconds) is associated with torsades de pointes arrhythmia. Ranolazine also has been reported to increase blood pressure by approximately 15 mm hg in patients with severe renal impairment. (1,2)

Ranolazine should not be used in patients taking any medication that also prolongs the QT interval or inhibits the CYP3A enzyme system; this includes numerous medications. Potential drug-drug and drug-food interactions should be evaluated before starting ranolazine or when adding any therapy. Ranolazine is a U.S. Food and drug Administration pregnancy category c drug. It is not known whether it is distributed in breast milk. (1,2)

TOLERABILITY

In controlled studies of patients with angina, approximately 6 percent of those receiving ranolazine discontinued treatment because of side effects compared with 3 percent of those receiving placebo. (2) Dizziness, headache, and constipation were infrequently reported. Small, reversible elevations in serum creatinine and blood urea nitrogen levels have been reported, but no evidence of renal toxicity was observed. (1-4)

EFFECTIVENESS

Ranolazine primarily has been studied in patients who continue to be symptomatic despite pharmacotherapy with other anti-anginal medications, such as beta blockers or calcium antagonists. Patients with persistent angina who were given ranolazine in addition to another treatment experienced fewer episodes of angina attacks per week compared with patients given placebo (3.3 versus 4.3, respectively) and required fewer nitroglycerin doses per week (2.7 versus 3.6, respectively). (2,3) When added to a regimen of maximal dose amlodipine, ranolazine significantly reduced the frequency of angina episodes per week compared with placebo (2.9 versus 3.3, respectively) and weekly nitroglycerine uses (2.0 versus 2.7, respectively). (4)

Ranolazine therapy increased exercise tolerance, but the average increase was only 30 seconds longer than that seen with placebo (2.0 and 1.5 minutes, respectively). (2,5) Increases in exercise duration and decreases in exercise-induced ischemia and angina episodes were similar to those seen with atenolol (Tenormin) but without decreasing blood pressure or heart rate. (6) To date, no studies have been conducted to measure the effects of ranolazine on mortality or the progression of coronary heart disease.

PRICE

The addition of ranolazine to beta blockers, calcium antagonists, or nitrates would cost approximately $206 for a one-month supply (60 tablets, 500 mg each).

SIMPLICITY

The recommended starting dosage of ranolazine is one tablet (500 mg) twice daily. It can be increased to two tablets twice daily as needed based on clinical symptoms. Ranolazine can be taken with or without meals and should be swallowed whole and not crushed, broken, or chewed. Grapefruit juice or products should be avoided. If a dose is missed, it should be taken at the next scheduled time; no doses should be doubled. Baseline and follow-up electrocardiography should be performed to evaluate the QTc interval, and blood pressure should be monitored regularly in patients with severe renal failure. (1,2)

Bottom Line

Ranolazine will provide a small benefit in symptom control in patients with chronic angina and persistent symptoms despite medical therapy. It generally should be used in combination with amlodipine, beta blockers, or long-acting nitrates. Because ranolazine has the potential to induce arrhythmia, it should be reserved for use in patients who have not achieved adequate responses with other antianginal therapies.